Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities.
Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.


Bridging the spatiotemporal scales of macromolecular transport in crowded biomimetic systems.
Crowding plays a key role in the transport and conformations of biological macromolecules. Gene therapy, viral infection, and transfection require DNA to traverse the crowded cytoplasm, including the cytoskeletal network of filamentous proteins. Given the complexity of cellular crowding, the dynamics of biological molecules can be highly dependent on the spatiotemporal scale probed. We present a powerful platform that spans molecular and cellular scales by coupling single-molecule conformational tracking (SMCT) and selective-plane illumination differential dynamic microscopy (SPIDDM). We elucidate the transport and conformational properties of large DNA, crowded by custom-designed networks of actin and microtubules, to link single-molecule conformations with ensemble DNA transport and cytoskeleton structure. We show that actin crowding leads to DNA compaction and suppression of fluctuations, combined with subdiffusion and heterogeneous transport, whereas microtubules have much more subdued impact across all scales. In composite networks of both filaments, scale-dependent effects emerge such that actin dictates ensemble DNA transport while microtubules influence single-molecule dynamics. We show that these intriguing results arise from a complex interplay between network rigidity, mesh size, filament concentration, and DNA size.


Doppler echocardiographic study of three different mechanical valves in the aortic position: the use of external nominal diameter indexed to body surface area.
Previous studies have demonstrated the benefit of indexing body surface area (BSA) with ventriculo-arterial orifice diameters (or calculated effective surface dynamics) and with nominal external diameters of valves in order to study hemodynamic profiles in vivo or determine the clinical influence of this parameter. This study analyzes the relationship between BSA and nominal external diameter of mechanical valves implanted in the aortic position. It also evaluates the potential interest of using these diameters indexed to BSA in an echo-Doppler study of valves. During 1994, a prospective echo-Doppler study of three models of mechanical valves in the aortic position was carried out. The echo-Doppler parameters of the aortic St. Jude Medical, Sorin Bicarbon and Dideco Monostrut prostheses have been studied with regard to nominal external diameters and were found identical to published data. There were no significant differences in these parameters between the three valves. In 128 patients, prosthetic external diameters were evenly distributed heterogeneously with regard to BSA. Indexing of nominal external diameter with BSA appeared a more reliable reference to study different echo-Doppler parameters, minimizing the effect of cardiac output. The in vivo echo-Doppler determination at rest of valve hemodynamic profiles should be carried out with reference to the nominal external diameter indexed to the BSA.


Biomass allocation to leaves, stems and roots: meta-analyses of interspecific variation and environmental control.
We quantified the biomass allocation patterns to leaves, stems and roots in vegetative plants, and how this is influenced by the growth environment, plant size, evolutionary history and competition. Dose-response curves of allocation were constructed by means of a meta-analysis from a wide array of experimental data. They show that the fraction of whole-plant mass represented by leaves (LMF) increases most strongly with nutrients and decreases most strongly with light. Correction for size-induced allocation patterns diminishes the LMF-response to light, but makes the effect of temperature on LMF more apparent. There is a clear phylogenetic effect on allocation, as eudicots invest relatively more than monocots in leaves, as do gymnosperms compared with woody angiosperms. Plants grown at high densities show a clear increase in the stem fraction. However, in most comparisons across species groups or environmental factors, the variation in LMF is smaller than the variation in one of the other components of the growth analysis equation: the leaf area : leaf mass ratio (SLA). In competitive situations, the stem mass fraction increases to a smaller extent than the specific stem length (stem length : stem mass). Thus, we conclude that plants generally are less able to adjust allocation than to alter organ morphology.


Vortex-ring-induced large bubble entrainment during drop impact.
For a limited set of impact conditions, a drop impacting onto a pool can entrap an air bubble as large as its own size. The subsequent rise and rupture of this large bubble plays an important role in aerosol formation and gas transport at the air-sea interface. The large bubble is formed when the impact crater closes up near the pool surface and is known to occur only for drops that are prolate at impact. Herein we use experiments and numerical simulations to show that a concentrated vortex ring, produced in the neck between the drop and the pool, controls the crater deformations and pinchoff. However, it is not the strongest vortex rings that are responsible for the large bubbles, as they interact too strongly with the pool surface and self-destruct. Rather, it is somewhat weaker vortices that can deform the deeper craters, which manage to pinch off the large bubbles. These observations also explain why the strongest and most penetrating vortex rings emerging from drop impacts are not produced by oblate drops but by more prolate drop shapes, as had been observed in previous experiments.


Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect.
H Syndrome is an autosomal recessive (AR) disease caused by defects in SLCA29A3 gene. This gene encodes the equilibrative nucleoside transporter, the protein which is highly expressed in spleen, lymph node and bone marrow. Autoinflammation and autoimmunity accompanies H Syndrome (HS). The aim was to further elucidate the mechanisms of disease by molecular studies in a patient with SLC29A3 gene defect. Mitochondrial dysfunction, lysosomal integrity, cytokine response in response to stimulation with different pattern recognition receptor ligands, and circulating cell-free mitochondrial-DNA(ccf-mtDNA) level in plasma were analyzed compared to controls to understand the cellular triggers of autoinflammation. RNA sequencing (RS) analyses were also performed in monocytes before/after culture with lipopolysaccharide. Patient had progressive destructive arthropathy in addition to clinical findings due to combined immunodeficiency. Pure red cell aplasia (PRCA), vitiligo, diabetes, multiple autoantibody positivity, lymphopenia, increased acute phase reactants were present. Recent thymic emigrants (RTE), naïve T cells were decreased, effector memory CD4 + T cells, nonclassical inflammatory monocytes were increased. Patient's peripheral blood mononuclear cells secreted more IL-1β and IL-6, showed lysosomal disruption and significant mitochondrial dysfunction compared to healthy controls. Plasma ccf-mtDNA level was significantly elevated compared to age-matched controls (p < 0.05). RNA sequencing studies revealed decreased expression of NLR Family Caspase Recrument-Domain Containing 4(NLRC4), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4(PFKFB4), serine dehydratase(SDS), heparan sulfate(Glucosamine) 3-O-sulfotransferase 1(HS3ST1), neutral cholesterol ester hydrolase 1 (NCEH1), and interleukin-8 (IL-8) in patient's monocytes compared to controls. Longstanding PRCA, which is possibly autoimmune, resolved after initiating monthly intravenous immunoglobulins (IVIG) and low dose steroids to the patient. Although autoinflammation and autoimmunity are reported in HS, by functional analyses we here show in the present patient that over-active inflammasome pathway in HS might be related with mitochondrial and lysosomal dysfunction. Increased plasma ccf-mtDNA may be used as a biomarker of inflammasomopathy in HS. HS should be included in the classification of primary immunodeficiency diseases.


Pop-up screening nested within routine community activities unmasks an addressed cardiovascular risk: A pilot study (Gippsland Healthy Heart Study).
To evaluate the benefits of a pop-up health screening for cardiovascular risk factors (CVRF) in the Gippsland region, and to assess the acceptability of the screening and to determine whether such a process results in attendance at a general practitioner (GP). Overall, 454 participants over the age of 18 who were residents of the Gippsland region were enrolled. This is a community-based, observational, prospective cohort study using pop-up screening sites at six retail locations or workplaces, where participants' blood pressure, body weight and lipid profile were measured. The primary outcome was to assess the proportion of participants with at least one unaddressed CVRF (hypertension [blood pressure >140/90 mmHg], overweight and obesity [body mass index >25 kg/m2 ] or hypercholesterolaemia [low-density lipoprotein cholesterol >2.5 mmol/L]). Email surveys were performed after 4 weeks of follow-up. Overall, 85.8% (95% confidence interval [CI], 82.1%-88.8%) of participants had at least one unaddressed CVRF. Among the 54 participants who responded to the email survey, 50 participants (92.6% [95% CI, 81.3%-97.6%]) found the screening approach acceptable, and 31 (57.4% [95% CI, 43.3%-70.5%]) considered a discussion with the GP. This study supported the feasibility and effectiveness of pop-up screening to detect CVRF in rural communities.


Using Coupled Energy, Airflow and IAQ Software (TRNSYS/CONTAM) to Evaluate Building Ventilation Strategies.
Building energy analysis tools are available in many forms that provide the ability to address a broad spectrum of energy-related issues in various combinations. Often these tools operate in isolation from one another, making it difficult to evaluate the interactions between related phenomena and interacting systems, forcing oversimplified assumptions to be made about various phenomena that could otherwise be addressed directly with another tool. One example of such interdependence is the interaction between heat transfer, inter-zone airflow and indoor contaminant transport. In order to better address these interdependencies, the National Institute of Standards and Technology (NIST) has developed an updated version of the multi-zone airflow and contaminant transport modelling tool, CONTAM, along with a set of utilities to enable coupling of the full CONTAM model with the TRNSYS simulation tool in a more seamless manner and with additional capabilities that were previously not available. This paper provides an overview of these new capabilities and applies them to simulating a medium-size office building. These simulations address the interaction between whole-building energy, airflow and contaminant transport in evaluating various ventilation strategies including natural and demand-controlled ventilation. CONTAM has been in practical use for many years allowing building designers, as well as IAQ and ventilation system analysts, to simulate the complex interactions between building physical layout and HVAC system configuration in determining building airflow and contaminant transport. It has been widely used to design and analyse smoke management systems and evaluate building performance in response to chemical, biological and radiological events. While CONTAM has been used to address design and performance of buildings implementing energy conserving ventilation systems, e.g., natural and hybrid, this new coupled simulation capability will enable users to apply the tool to couple CONTAM with existing energy analysis software to address the interaction between indoor air quality considerations and energy conservation measures in building design and analysis. This paper presents two practical case studies using the coupled modelling tool to evaluate IAQ performance of a CO2-based demand-controlled ventilation system under different levels of building envelope airtightness and the design and analysis of a natural ventilation system.


Difficulties in Surgical Decision Making and Associated Factors Among Elective Surgical Patients in Taiwan.
Respect for the autonomy of patients is essential in life-threatening medical decisions such as surgery. Even if a patient has the competency to make decisions, many obstacles exist that may influence his or her willingness to participate in the surgical decision-making process. The aim of this study was to explore the perceived difficulties in surgical decision making and related factors among elective surgical patients. This was a cross-sectional correlational study. A convenience sampling method was used to recruit patients from a medical center in southern Taiwan. Patients who had received elective surgery, were older than 20 years old, and were competent to make medical decisions were invited to participate. A structured questionnaire was developed by the researchers to collect demographic data, decision patterns, and perceived difficulties in surgical decision making. Acceptable validity and reliability of the questionnaire were confirmed before data collection. Over 80% of the participants made the surgical decision by themselves or in collaboration with their family or physician. Less than 15% expected to make the surgical decision by themselves. Illness-related suffering was the greatest difficulty that participants faced. The patients who tended toward passive decision making faced greater difficulties in the dimensions of "do not understand information," "physician's lack of concern," and "difficulty in freely communicating with the physician" than their active decision-making peers. Male participants reported having more difficulty in communicating with their physician than their female peers. Age, education, and marital status were not significantly associated with perceived difficulties in surgical decision making. Family participation in the medical decision-making process is expected by most patients. Although less than 20% of the participants in this study were categorized as passive decision makers, this group reported more difficulties than the active decision-making group. Healthcare professionals should be more active in communicating with patients who are largely silent during the decision-making process to elicit their preferences and needs with regard to surgical decisions.


Essential roles of Sall family genes in kidney development.
We isolated a mouse Sall1, a mammalian homologue of the Drosophila region-specific homeotic gene spalt (sal), and found that mice deficient in Sall1 die in the perinatal period from kidney agenesis. Sall1 is expressed in the metanephric mesenchyme surrounding the ureteric bud, and the homozygous deletion of Sall1 results in an incomplete ureteric bud outgrowth. Therefore Sall1 is essential for ureteric bud invasion, the initial key step for metanephros development. We also set up an in vitro culture system, using NIH3T3 cells stably expressing Wnt4 as a feeder layer, to identify kidney progenitors in the metanephric mesenchyme. In this culture condition, a single renal progenitor in the mesenchyme forms colonies consisting of several types of epithelial cells that exist in glomeruli and renal tubules. We found that only cells strongly expressing Sall1 (Sall1-GFP(high) cells) form colonies and that they reconstitute a three-dimensional kidney structure in an organ culture setting. Thus our colony-forming assay, which identifies multipotent progenitors in the embryonic mouse kidney, can be used for examining mechanisms of renal progenitor differentiation.


Mechanical deformation promotes secretion of IL-1 alpha and IL-1 receptor antagonist.
Both IL-1 alpha and IL-1 beta lack an N terminus secretory sequence, and the mechanism of secretion of these pleiotropic cytokines is incompletely understood. The epidermis contains large quantities of IL-1 alpha in keratinocytes, which may play a role in inducing endothelial adhesion molecules and promoting extravasation of leukocytes. Here we report that mechanical deformation of human keratinocytes leads to rapid release of IL-1 alpha, possibly through transient disruptions in the plasma membrane. Using a device that precisely controls the amplitude of strain on the culture substrate, we found by pulse-chase analysis, Western analysis, and ELISA that the release of IL-1 alpha is dependent on the amplitude of the strain. A cyclic strain of 14% released a small but significant quantity of IL-1 alpha, while strains of 33% released 66 +/- 9% of cytoplasmic IL-1 alpha over 1 h (p < 0.001). Release of IL-1 alpha was accompanied by rapid release of large stores of IL-1R antagonist, approximately 25 to 30 times greater by mass than the quantity of IL-1 alpha released, but only a small fraction of cytoplasmic lactate dehydrogenase. Media conditioned by mechanically stimulated keratinocytes induced expression of E-selectin by human vascular endothelial cells; induction of E-selectin was completely inhibited by an Ab to IL-1 alpha. Therefore, mechanical strain promotes the secretion of IL-1 alpha, and deformation of keratinocytes in the epidermis may activate vascular endothelium through mechanically released IL-1 alpha. This pathophysiologic mechanism may play a role in the anatomic localization of some inflammatory skin diseases, such as psoriasis, which occurs more commonly in locations where the dermis is subjected to repetitive stretch or trauma.


Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage.
Angiopoietins (Angs) are endothelium-selective ligands that exert most of their actions through the Tie-2 receptor. It is widely accepted that Ang-1 promotes the structural integrity of blood vessels and exhibits anti-inflammatory properties. In contrast, the role of Ang-2 remains less clear because it has been shown to behave as a Tie-2 agonist or antagonist under different experimental conditions. To define the role of Ang-2 in acute inflammation, we studied the effects of recombinant Ang-2 administration in vivo. We show herein that Ang-2, but not Ang-1, induces edema formation in the mouse paw in a dose-dependent manner; the edema seems to be fast-peaking (maximum at 30 min) and resolves within 4 h. The effect of Ang-2 is blocked by the coadministration with a soluble form of the Tie-2 receptor or Ang-1. NO and prostaglandin E(2) levels in mouse paw following the injection of Ang-2 remained unaltered, suggesting that the action of Ang-2 does not involve these mediators. In addition, Ang-2 exerted a weak stimulatory effect on leukocyte migration in the mouse paw. Similarly, Ang-2 injected into the mouse air pouch produced only a modest effect on cell extravasation that peaked at 30 min. However, when cell migration was elicited using zymosan, Ang-2 significantly inhibited leukocyte migration. We conclude that Ang-2 by itself stimulates the extravasation of cell-poor fluid, but in the presence of ongoing inflammation it reduces cellular infiltration in tissues.


Dental caries trends among indigenous and non-indigenous Australian children.
To examine trends in dental caries among indigenous and non-indigenous children in an Australian territory. Routinely-collected data from a random selection of 6- and 12-year-old indigenous and non-indigenous children enrolled in the Northern Territory School Dental Service from 1989-2000 were obtained. The association of indigenous status with caries prevalence (percent dmft or DMFT>0 and percent dmft>3 or DMFT>1), caries severity (mean dmft or DMFT) and treatment need (percent d/dmft or D/DMFT) was examined. Results were obtained for 10,687 6- and 12-year old indigenous children and 21,777 6- and 12-year-old non-indigenous children from 1989-2000. Across all years, indigenous 6-year-olds had higher caries prevalence in the deciduous dentition, greater mean dmft and percent d/dmft, and indigenous 12-year-olds had greater percent D/DMFT than their non-indigenous counterparts (p<0.05). From 1996-2000 the mean dmft and percent d/dmft for indigenous 6-year-olds and mean DMFT and percent D/DMFT for indigenous 12-year-olds increased, yet remained relatively constant for their non-indigenous counterparts (p<0.05). From 1997-2000, the percent dmft>3 for 6-year-old indigenous children was more than double that of non-indigenous children, while across the period 1994-2000, indigenous 6-year-old mean dmft was more than double that of their non-indigenous counterparts (p<0.05). Indigenous children in our study experienced consistently poorer oral health than non-indigenous children. The severity of dental caries among indigenous children, particularly in the deciduous dentition, appears to be increasing while that of non-indigenous children has remained constant. Our findings suggest that indigenous children carry a disproportionate amount of the dental caries burden among Northern Territory 6- and 12-year-olds.


Emerging structural themes in large RNA molecules.
Extensive networks of tertiary interactions give rise to unique, highly organized domain architectures that characterize the three-dimensional structure of large RNA molecules. Formed by stacked layers of a near-planar arrangement of contiguous coaxial helices, large RNA molecules are relatively flat in overall shape. The functional core of these molecules is stabilized by a diverse set of tertiary interaction motifs that often bring together distant regions of conserved nucleotides. Although homologous RNAs from different organisms can be structurally diverse, they adopt a structurally conserved functional core that includes preassembled active and/or substrate binding sites. These findings broaden our understanding of RNA folding and tertiary structure stabilization, illustrating how large, complex RNAs assemble into unique structures to perform recognition and catalysis.


Antagonistic mechanism of iturin A and plipastatin A from Bacillus amyloliquefaciens S76-3 from wheat spikes against Fusarium graminearum.
Controlling toxigenic Fusarium graminearum (FG) is challenging. A bacterial strain (S76-3, identified as Bacillus amyloliquefaciens) that was isolated from diseased wheat spikes in the field displayed strong antifungal activity against FG. Reverse-phase high performance liquid chromatography and electrospray ionization mass spectrometry analyses revealed that S76-3 produced three classes of cyclic lipopeptides including iturin, plipastatin and surfactin. Each class consisted of several different molecules. The iturin and plipastatin fractions strongly inhibited FG; the surfactin fractions did not. The most abundant compound that had antagonistic activity from the iturin fraction was iturin A (m/z 1043.35); the most abundant active compound from the plipastatin fraction was plipastatin A (m/z 1463.90). These compounds were analyzed with collision-induced dissociation mass spectrometry. The two purified compounds displayed strong fungicidal activity, completely killing conidial spores at the minimal inhibitory concentration range of 50 µg/ml (iturin A) and 100 µg/ml (plipastatin A). Optical and fluorescence microscopy analyses revealed severe morphological changes in conidia and substantial distortions in FG hyphae treated with iturin A or plipastatin A. Iturin A caused leakage and/or inactivation of FG cellular contents and plipastatin A caused vacuolation. Time-lapse imaging of dynamic antagonistic processes illustrated that iturin A caused distortion and conglobation along hyphae and inhibited branch formation and growth, while plipastatin A caused conglobation in young hyphae and branch tips. Transmission electron microscopy analyses demonstrated that the cell walls of conidia and hyphae of iturin A and plipastatin A treated FG had large gaps and that their plasma membranes were severely damaged and separated from cell walls.


Osthole Reduces Mouse IOP Associated With Ameliorating Extracellular Matrix Expression of Trabecular Meshwork Cell.
Elevation of IOP in POAG is thought to involve excessive accumulation of extracellular matrix in the trabecular meshwork (TM), leading to an increase in outflow resistance of the aqueous humor. Osthole, a coumarin derivative extracted from the fruit of a variety of plants, such as Cnidium monnieri, is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-β in liver, kidney, and cardiac tissues. We tested if osthole can (1) inhibit TGF-β2-induced extracellular matrix expression in cultured human TM (HTM) cells, and (2) lower TGF-β2-induced ocular hypertension in the mouse. Cultured HTM cells were treated with 5 ng/mL TGF-β2 for 48 hours, then with osthole for 24 hours. The expressions of fibronectin, collagen type IV, and laminin were assessed by quantitative PCR, Western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGF-β2 (Ad.hTGF-β2226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eye serving as controls. Mice were then treated with a daily intraperitoneal injection of 30 mg/kg osthole. Conscious mouse IOP values were measured using a TonoLab rebound tonometer. In cultured HTM cells, stimulation with TGF-β2 increased expressions of fibronectin, collagen IV, and laminin. These in vitro changes were significantly and completely mitigated by osthole (10 µM). Daily intraperitoneal injections of 30 mg/kg osthole, starting either at day 0 (same day as Ad.hTGF-β2226/228 injection) or at day 14, significantly decreased TGF-β2-induced ocular hypertension in the mouse. In contrast, osthole did not affect IOP of control eyes. These results demonstrated that osthole is capable of reducing TGF-β2-induced extracellular matrix expression in cultured HTM cells. It also reduced TGF-β2-induced ocular hypertension in the mouse. These findings indicate that this natural product may be useful as a novel treatment for POAG.


Air and groundwater pollution in an agricultural region of the Turkish Mediterranean coast.
Air pollution and groundwater pollution in conjunction with agricultural activity were investigated in Antayla province on the Turkish Mediterranean coast. The air pollution was investigated in terms of gas-phase nitric acid (HNO3), sulfur dioxide (SO2), ammonia (NH3), and particulate matter for a 6-month period in the atmosphere using a "filter pack" system, which was developed and optimized in our laboratory. Ozone was measured by using an automated analyzer. Among all of the gas-phase pollutants, HNO3 had the lowest concentration (0.42 microg x m(-3)) followed by NH3. Agricultural activities seem to be the major source of observed NH3 in the air. The current state of water pollution was investigated in terms of organochlorine and organophosphorus pesticides around the greenhouses, in which mainly tomato, pepper, and eggplant are cultivated. Water samples were collected from 40 points, 28 of which were wells and 12 of which were surface water. The pesticide concentrations in water samples were determined by means of solid-phase extraction (SPE) followed by a gas chromatography (GC)-electron capture detector (ECD)/nitrogen phosphorus detector (NPD) system. In general, surface water samples were more polluted by the pesticides than groundwater samples. The most frequently observed pesticides were chlorpyriphos (57%) and aldrin (79%) in groundwater, and chlorpyriphos (75%), aldrin, and endosulfan sulfate (83%) in surface water samples. The highest concentrations were observed for fenamiphos (394.8 ng/L) and aldrin (68.51 ng/L) in groundwater, and dichlorvos (322.2 ng/L) and endosulfan sulfate (89.5 ng/L) in surface water samples. At least one pesticide had a concentration above the health limit in 38% of all the water samples analyzed.


Finite element modeling technique for predicting mechanical behaviors on mandible bone during mastication.
The purpose of this study was to propose finite element (FE) modeling methods for predicting stress distributions on teeth and mandible under chewing action. For FE model generation, CT images of skull were translated into 3D FE models, and static analysis was performed considering linear material behaviors and nonlinear geometrical effect. To find out proper boundary and loading conditions, parametric studies were performed with various areas and directions of restraints and loading. The loading directions are prescribed to be same as direction of masseter muscle, which was referred from anatomy chart and CT image. From the analysis, strain and stress distributions of teeth and mandible were obtained and compared with experimental data for model validation. As a result of FE analysis, the optimized boundary condition was chosen such that 8 teeth were fixed in all directions and condyloid process was fixed in all directions except for forward and backward directions. Also, fixing a part of mandible in a lateral direction, where medial pterygoid muscle was attached, gave the more proper analytical results. Loading was prescribed in a same direction as masseter muscle. The tendency of strain distributions between the teeth predicted from the proposed model were compared with experimental results and showed good agreements. This study proposes cost efficient FE modeling method for predicting stress distributions on teeth and mandible under chewing action. The proposed modeling method is validated with experimental data and can further be used to evaluate structural safety of dental prosthesis.


Rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder.
To investigate rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder (FDD). We segregated individuals diagnosed with FDD into two groups based on their defecation patterns: those with dyssynergic defecation and those with inadequate defecatory propulsion. We gathered general information through questionnaires and assessed rectal sensitivity using anorectal manometry. The rectal sensitivity performances of the two groups were compared; the factors related to rectal sensitivity were analyzed to determine the factors associated with rectal sensitivity, and the effect of biofeedback therapy on rectal sensitivity was clarified. Rectal sensitivity in different subtypes of FDD decreased, and the difference between the two groups was not statistically significant ( P > 0.05). There were no statistically significant differences in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume between the different subtypes of FDD ( P > 0.05). Multi-factor binary logistic regression analysis showed that age, constipation symptom score, and diabetes were all independent risk factors for decreased rectal sensitivity ( P < 0.05). There were no statistically significant differences between the prior- and post-biofeedback therapy in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume ( P > 0.05). Rectal sensitivity in different subtypes of FDD decreased. Age, constipation symptom score, and diabetes were independent risk factors for decreased rectal sensitivity. Short-term biofeedback therapy did not improve rectal hyposensitivity in patients with FDD.


[Evaluation of quality of Pacific Ocean squid by biotesting].
The influence of refrigerator storage on the quality of high-protein raw sea material and its products was studied by using squids as an example. The size of microorganisms in 1 g, the content of nitrogen of volatile bases, that of non-protein nitrogen, and the amount of free amino acids were estimated after cooling and freezing and during storage of frozen squids. In parallel, the relative food value of the cooled and frozen squids and their products were determined by biotesting by means of Tetrachymena pyriformis. Refrigerator storage of squids leads to its muscular tissue degradation whose depth determines the loss of their food value. The results of biotesting of squid meat with the infusoria Tetrachymena pyriformis completely correlate with the data of chemical analysis while assessing the quality.


Obstetrics and Gynaecology as career maze: Perceptions of medical students in Saudi Arabia.
This article was migrated. The article was marked as recommended. Background Over time, there has been a gradual decline in the selection of obstetrics and gynecology (OBGY) as a career choice worldwide, which is of great concern for the medical educators, stakeholders, and policymakers to optimize the demand of this specialty. Objective To explore the perceptions of medical students about the attractive and distracting factors to choose obstetrics and gynecology. Method The focused group discussion was conducted from September 2019 to December 2019 and thematic analysis was done based on grounded theory. Results In the study, a total of 49 students participated out of 75 expected participants, and the response rate was 65%. Few participants who agreed to continue their careers in this field supported their ideas because of female gender acceptance for this specialty in Saudi culture, opportunity to observe procedures, and family pressures. The main reason was the tough experience during OBGY clinical rotations, the clinician's attitude towards training at the hospital workplace, and work stress. Conclusion There is a profound influence on learning experience during the course and clinical training in hospital settings. The positive impact of teaching faculty, successful stories of patients, and teaching techniques supported by simulations can provoke the enthusiasm in the students. A mnemonic "BE SMART" is proposed to apply by medical educators to optimize the need of OBGY specialists in the future. It applies the abilities of true professionals indicated by doctors as beneficent, educators; enforces to augment the use of simulators as teaching modality; practices of meditation, and affectionate the mutual relationships.


[Origin of stromal mechanocytes in the bone marrow cell cultures].
The method of indirect immunofluorescence with the use of the isolinear antiserum was applied to the study of the linear reference of fibroblasts growing in the monolayer bone marrow cultures from the semisyngenous heterotropic transplants and radiochimerae. As shown, fibroblasts from the bone marrow of complete radiochimerae were of the recipient origin, whereas the histiocytes-macrophages (in the same cultures) - of donor origin. All the fibroblasts in the bone marrow cultures of the heterotropic transplant belonged to the initial donor, whereas 80% of the histiocytes were recipent's. This is a direct proof of the fact that stromal mechanocytes and hemopoietic cells, and also macrophages belonged to different cell lins.


An intensive programme of passive stretch and motor training to manage severe knee contractures after traumatic brain injury: a case report.
While contemporary management of contractures (a common secondary problem of acquired brain injury that can be difficult to treat) includes passive stretch, recent evidence indicates that this intervention may not be effective. This may be because clinical trials have not provided a sufficient dose or have not combined passive stretch with other treatments. The purpose of this case report is to describe a programme of intensive passive stretch combined with motor training administered over a 1.5-year period to treat severe knee contractures. Five months after traumatic brain injury, an adolescent client with severe contractures in multiple joints underwent an intensive stretch programme for his knee contractures, including serial casting and splinting, which was administered for 10 months in conjunction with a motor training programme administered for 1.5 years. The client regained full extension range in his knees and progressed from being totally dependent to walking short distances with assistance; these effects were maintained at follow-up 5.5 years after injury. The use of a high dose of passive stretch in conjunction with motor training may be an option to consider for correcting severe contractures following acquired brain injury.


[Effects of dietary fibers on hepatocyte apoptosis in rats with alimentary polyhypovitaminosis].
The effect of dietary fibers (DF) of wheat bran on hepatocyte apoptosis in rats adequately provided with vitamins or insufficiently supplied with vitamins has been investigated. 48 male Wistar rats (initial body mass--58.1 +/- 0.5 g) were randomly divided into 6 groups and fed with semi-synthetic diet, containing 100% or 20% of vitamin mixture (Vit) with or without addition of DF in the dose corresponding to the upper allowable level of its consumption (5% of diet mass) for 4 weeks. The animals of the 1 group received 100% of vitamin mixture (100% Vit); 2 group--100% Vit + DF; 3 group--20% of vitamin mixture with full exclusion of vitamins E, B1 and B2 (20% Vit); 4 group--20% of vitamin mixture and DF (20% Vit + DF). The next 5 days rats from vitamin-deficient groups were fed with diets supplemented with 80% of vitamins from their content in control group: (5 group--20% Vit + 80% Vit; 6 group--20% Vit + DF + 80% Vit). The suspension of hepatocytes was received by Becton Dickinson Medimachine System (USA). Hepatocyte apoptosis was assessed by the method of flow cytometry using Beckman Coulter FC 500 (USA) cytometer by stained cells with Annexin V-FITC/ 7-Amino-Actinomycin D Kit (Beckman Coulter, USA). In rats fed complete semi-synthetic diet supplemented with DF (100% Vit + DF) the hepatocyte apoptosis was higher by 22% (p < 0.10) than that in rats of control group (4.99 +/- 1.82%). In rats fed diets with low vitamin content (groups: 20% Vit and 20% Vit + DF) the hepatocyte apoptosis was significantly higher (p < 0.05) than that in the control group and reached 7.03 +/- 1.74 and 7.26 +/- 1.13% accordingly. Normalization of vitamin content in the diets of rats from deficient groups during 5 days had no effect on the severity of apoptosis regardless from presence (8.02 +/- 2.18%) or absence of the DF (8.04 +/- 1.66%). Adding DF in dose corresponding to the upper allowable level of consumption, on the background of adequate vitamin content in the diet is accompanied by a tendency to develop hepatocyte apoptosis, which may be the result of a direct action of short chain fatty acids generated from the DF and the deterioration of vitamin sufficiency.


Reduced somatostatin in subgenual anterior cingulate cortex in major depression.
Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative Western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=-0.357, p=0.005) but not MDD (R=-0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches to the high female vulnerability to develop MDD.


Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells.
DNMT inhibitors are promising new drugs for cancer therapies. In this study, we have observed the antileukemic action of two diverse DNMT inhibitors, the nucleoside agent zebularine and the non-nucleoside agent RG108, in human promyelocytic leukemia (PML) HL-60 cells. Zebularine but not RG108 caused dose- and time-dependent cell growth inhibition and induction of apoptosis. However, co-treatment with either drug at a non-toxic dose and all trans retinoic acid (RA) reinforced differentiation to granulocytes, while 24 or 48 h-pretreatment with zebularine or RG108 followed by RA alone or in the presence of HDAC inhibitors (sodium phenyl butyrate or BML-210) significantly accelerated and enhanced cell maturation to granulocytes. This occurs in parallel with the expression of a surface biomarker, CD11b, and early changes in histone H4 acetylation and histone H3K4me3 methylation. The application of both drugs to HL-60 cells in continuous or sequential fashion decreased DNMT1 expression, and induced E-cadherin promoter demethylation and reactivation at both the mRNA and the protein levels in association with the induction of granulocytic differentiation. The results confirmed the utility of zebularine and RG108 in combinations with RA and HDAC inhibitors to reinforce differentiation effects in promyelocytic leukemia.


Compression of EMG Signals Using Deep Convolutional Autoencoders.
Efficient storage and transmission of electromyogram (EMG) data are important for emerging applications such as telemedicine and big data, as a vital tool for further advancement of the field. However, due to limitations in internet speed and hardware resources, transmission and storage of EMG data are challenging. As a solution, this work proposes a new method for EMG data compression using deep convolutional autoencoders (CAE). Eight-channel EMG data from 10 subjects, and high-density EMG data from 18 subjects, were investigated for compression. The CAE architecture was designed to extract an abstract data representation that is heavily compressed, but from which the salient information for classification can be effectively reconstructed. The proposed method attained efficient compression; for CR = 1600, the average PRDN (percentage RMS difference normalized) was 31.5% and the wrist motions classification accuracy (CA) reduced roughly 5%. The CAE substantially outperformed the state-of-the-art high-efficiency video coding and a well-known wavelet-thresholding compression technique. Moreover, by reducing the bit-resolution of the CAE's compressed data from 24 bits to 6 bits, an additional 4-fold compression was achieved without significant degradation of the reconstruction performance. Furthermore, the CAE's inter-subject performance was promising; e.g., for CR = 1600, the PRDN for the inter-subject case was only 2.6% less than that of the within-subject performance. The powerful EMG compression performance with remarkable reconstruction results reflects the CAEs potential as an automatic end-to-end approach with the ability to learn the complete encoding and decoding process. Furthermore, the excellent inter-subject performance demonstrates the generalizability and usability of the proposed approach.


AN INCREASED RISK OF HORMONAL DISORDERS, PRIMARILY DIABETES, IN INDIVIDUALS WITH Β -THALASSEMIA MAJOR: A RETROSPECTIVE ANALYSIS.
β-Thalassemia major is an inherited blood condition marked by a serious anemia and a lifetime need for blood transfusions. The effects of β-thalassemia major on endocrine health, notably the risk of diabetes, remain largely unstudied, despite the fact that its haematological components are established. The purpose of this systematic analysis was to examine the incidence of reduced metabolism of glucose in β--thalassemia major. The articles were under the inclusion requirements, after which the data was retrieved. The main outcome was determined to be every prevalence (P) of DM (diabetes mellitus) in β-thalassemia major. In order to examine the percentage of aberrant glucose metabolism (GM) with individuals among β-thalassemia major, the P with the 95% CI (Confidence Interval) was utilized. In this retrospective investigation, we looked at a cohort of people with β-thalassemia major diagnoses to determine the incidence and risk of hormonal diseases, particularly diabetes. A specialist thalassemia facility treated 315 individuals with β-thalassemia major, and their medical records were examined. Age, gender, age at which a main diagnosis of β-thalassemia was made, the length of transfusion treatment, and concomitant diseases were gathered as part of the demographic and clinical data. Our research, which included 17 studies and 1500 cases altogether, showed that with β -thalassemia major had a considerably greater frequency of diabetes than people in general. With a mean beginning age of 30 years, diabetes was identified in 28% of the research cohort's participants. The combined meta-analysis showed that each year had a rather stable level of DM P in β-thalassemia major. In people with major β-thalassemia, the P of impaired fasting glucose (IFG), DM, and impaired glucose tolerance (IGT) was 17.22% (95% CI: 8.44%-26.02%), (6.57 (95% CI: 5.31%- 7.79%) and 12.47 % (95% CI: 5.97%-18.95%), respectively. Our research suggests that people with β-thalassemia major have a high chance of acquiring diabetes, particularly if they get extended transfusion treatment. For prompt diagnosis and care, early detection of diabetes and other hormonal problems in this group is crucial. In β-thalassemia major, there is a high frequency of endocrine problems, including improper GM. To stop growth and endocrine issues, treatment and preventative measures can be required.


Ram seminal plasma proteome and its impact on liquid preservation of spermatozoa.
Seminal plasma is composed of secretions from the epididymis and the accessory sex glands and plays a critical role in the fertilising ability of spermatozoa. In rams, analysis of seminal plasma by GeLC-MS/MS has allowed the identification of more than 700 proteins, including a high abundance of Binder of Sperm family proteins (BSP1, BSP5, SPADH1, SPADH2), the spermadhesin family (bodhesin2), lactoferrin and newly identified proteins like UPF0762 (C6orf58 gene). When spermatogenesis was stopped by scrotal insulation, changes in the proteome profile revealed the sperm origin of 40 seminal proteins, such as glycolysis pathway enzymes, the chaperonin containing TCP1 (CCT) complex and the 26S proteasome complex. Sperm mobility after liquid preservation (24h in milk at 15°C) is male dependent and can be correlated to differences in the seminal plasma proteome, detected by spectral counting. The negative association of zinc alpha-2 glycoprotein (ZAG) with semen preservation was confirmed by the use of recombinant human ZAG, which induced an increase in mobility of fresh sperm, but then decreased sperm mobility after 24h of incubation. Several sperm membrane proteins interacting with the cytoskeleton, glycolysis enzymes and sperm-associated proteins involved in capacitation correlated with better liquid storage and can be considered as seminal biomarkers of sperm preservation. Extensive analysis of the ram seminal plasma proteome reveals a complex and diverse protein composition. This composition varies between males with different sperm preservation abilities. Several proteins were shown to originate from the spermatozoa and positively correlate with sperm liquid preservation, indicating that these proteins can be traced as sperm biomarkers within the seminal plasma. The zinc alpha-2 glycoprotein (ZAG) was found to have a biphasic effect on sperm mobility, with a short-term stimulation followed by a long-term exhaustion of sperm mobility after a 24h preservation period.


Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance.
In Parkinson's disease (PD) and dementia with Lewy bodies (DLB) alpha-synuclein (alphaS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak's and McKeith's, currently in use for the assessment of alphaS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 alphaS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of alphaS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of alphaS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of alphaS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread alphaS pathology (Braak's PD stages 5-6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer's disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with alphaS pathology. However, finding that around half of the subjects with abundant alphaS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process.


Effectiveness of Serial Measurement of Differential Pressure in Closed Tibial Diaphyseal Fractures in Diagnosing Acute Compartment Syndrome using Whiteside's Technique.
Acute Compartment Syndrome is a limb-threatening emergency and it occurs most commonly after fractures. The aim of our study is to find out the effectiveness of serial measurement of differential pressure in closed tibial diaphyseal fractures, in diagnosing acute compartment syndrome, using Whiteside's technique. A total of 52 cases in the age group of 15 to 55 years admitted with closed fractures were studied for serial compartment pressure as well as serial differential pressure. Eight patients had persistent compartment pressure > 40mmHg, out of which only two patients had persistent differential pressure < 30mmHg and these two patients underwent fasciotomy. Thus, by measuring the compartment pressure serially and calculating differential pressure serially, acute compartment syndrome can be diagnosed or ruled out with higher precision, so that unnecessary fasciotomies can be avoided.


Understanding high- and low-quality URL Sharing on COVID-19 Twitter streams.
This article investigates the prevalence of high and low quality URLs shared on Twitter when users discuss COVID-19. We distinguish between high quality health sources, traditional news sources, and low quality misinformation sources. We find that misinformation, in terms of tweets containing URLs from low quality misinformation websites, is shared at a higher rate than tweets containing URLs on high quality health information websites. However, both are a relatively small proportion of the overall conversation. In contrast, news sources are shared at a much higher rate. These findings lead us to analyze the network created by the URLs referenced on the webpages shared by Twitter users. When looking at the combined network formed by all three of the source types, we find that the high quality health information network, the low quality misinformation network, and the news information network are all well connected with a clear community structure. While high and low quality sites do have connections to each other, the connections to and from news sources are more common, highlighting the central brokerage role news sources play in this information ecosystem. Our findings suggest that while low quality URLs are not extensively shared in the COVID-19 Twitter conversation, a well connected community of low quality COVID-19 related information has emerged on the web, and both health and news sources are connecting to this community.


[Significance of parameters of automated reticulocyte analysis in diagnosis and evaluation of treatment outcome in B12-deficient anemia].
The results of examinations of reticulocytes in blood samples of 12 patients with the confirmed diagnosis of B12-deficit anemia and of 20 virtually healthy subjects (control group) by means of the GEN-S hematological analyzer (Beckman-Coulter) are described in the paper. Typical changes of the reticulocyte parameters are defined and their dynamics (with treatment by Vitamin B12) is studied. It was established that the additional parameters of the reticulocyte analysis, characterizing the quantity of immature reticulocytes and the fraction of immature reticulocytes, increase by 3 days before the total quantity of erythrocytes increases, which means that the above parameters can be used earlier as criteria in evaluating the treatment efficiency.


Relationship between deep venous thrombosis and inflammatory cytokines in postoperative patients with malignant abdominal tumors.
Deep venous thrombosis (DVT) is a common surgical complication in cancer patients and evidence that inflammation plays a role in the occurrence of DVT is increasing. We studied a population of cancer patients with abdominal malignancies with the aim of investigating whether the levels of circulating inflammatory cytokines were associated with postoperative DVT, and to determine the levels in DVT diagnoses. The serum levels of C-reactive protein (CRP), interleukins (IL)-6 and IL-10, nuclear transcription factor-κB (NF-κB) and E-selectin (E-Sel) were determined in 120 individuals, who were divided into 3 groups: healthy controls, patients with and patients without DVT after surgery for an abdominal malignancy. Data were analyzed by ANOVA, Dunnet's T3 test, chi-square test, and univariate and multivariate logistic regression as needed. The CRP, IL-6, NF-κB, and E-Sel levels in patients with DVT were significantly higher than those in the other groups (P<0.05). The IL-10 level was higher in patients with DVT than in controls but lower than in patients without DVT. Univariate analysis revealed that CRP, IL-6, NF-κB, and E-Sel were statistically associated with the risk of DVT (OR=1.98, P=0.002; OR=1.17, P=0.000; OR=1.03, P=0.042; and OR=1.38, P=0.003; respectively), whereas IL-10 had a protective effect (OR=0.94, P=0.011). Multivariate analysis showed that E-Sel was an independent risk factor (OR=1.41, P=0.000). Thus, this study indicated that an increased serum level of E-Sel was associated with increased DVT risk in postoperative patients with abdominal malignancy, indicating that E-Sel may be a useful predictor of diagnosis of DVT.


Enzymatic production of galactooligosaccharides by beta-galactosidase from Bifidobacterium longum BCRC 15708.
The production of galactooligosaccharides (GOSs) by transgalactosylation using beta-galactosidase from Bifidobacterium longum BCRC 15708 was studied. Other than lactose, galactose, and glucose, two types of GOSs, tri- and tetrasaccharides, were formed after beta-galactosidase action on 40% lactose. Trisaccharides were the major type of GOS formed. Generally, an increase of the initial lactose concentration in the reaction mixture resulted in a higher GOS production. A maximum yield of 32.5% (w/w) GOSs could be achieved from 40% lactose solution at 45 degrees C, pH 6.8, when the lactose conversion was 59.4%. The corresponding productivity of GOSs was 13.0 g/(L.h). Transgalactosylation activity of beta-galactosidase from a test organism showed a relatively lower sensitivity toward glucose and galactose than that from other organisms. The addition of 5% or 10% glucose or galactose to the reaction mixture did not significantly (p>0.05) reduce the transgalactosylation reaction of beta-galactosidase.


The effects of heuristic rule training on operator performance in a simulated process control environment.
In complex work environments, the occurrence of novel system states represents a particular challenge for the design of training. This article is concerned with the use of heuristic rules to prepare operators for the management of unfamiliar fault states. An experiment was carried out to examine the effects of heuristic rule training on operator performance and system management behaviour. Thirty-nine trainee operators from the chemical industry took part in the study. They were trained for 4 h on a PC-based simulation of a process control task. Operators in the experimental group received training on heuristic rules while operators in the control group did not. One week later the operators participated in a 70-min testing session. While the results showed that heuristic rules training led to better diagnostic performance, it was also associated with increased operator fatigue and impaired secondary task performance. The implications of the findings for using heuristic rule training are discussed.


The properties of proteoglycan prepared from human articular cartilage by using associative caesium chloride gradients of high and low starting densities.
Proteoglycan was extracted from adult human articular cartilage from both the knee and the hip, and A1 preparations were prepared by CsCl-density-gradient centrifugation at starting densities of 1.69 and 1.5 g/ml. Irrespective of whether the cartilage was diced to 1 mm cubes or sectioned to 20 micron slices there was always a lower proportion of both protein and proteoglycan aggregate in the A1 preparation prepared at 1.69 g/ml. Furthermore, the addition of exogenous hyaluronic acid to the extracts before centrifugation did not improve the yield of aggregate at 1.69 g/ml. These results were not affected by the presence of proteinase inhibitors in the extraction medium. It appears that adult human articular cartilage contains a high proportion of low-density proteoglycan subunits and hyaluronic acid-binding proteins that make most of the re-formed proteoglycan aggregates of a lower density than is usually encountered with younger human and mammalian hyaline cartilages.


Pioglitazone versus rosiglitazone treatment in patients with type 2 diabetes and dyslipidemia: cost-effectiveness in the US.
Pioglitazone hydrochloride (Actos † ) and rosiglitazone maleate (Avandia ‡ ) are members of the thiazolidinedione (TZD) class of oral anti-diabetic drugs (OADs) and are used to treat type 2 diabetes mellitus (T2DM). Greater beneficial effects on lipids have been demonstrated with pioglitazone, however. Study objectives were to evaluate the long-term cost-effectiveness of pioglitazone compared to rosiglitazone in treating patients with T2DM and dyslipidemia, and determine the extent to which reported beneficial lipid effects of pioglitazone would improve clinical and economic outcomes through reduced macrovascular complications. † Actos is a trade name of Takeda Pharmaceuticals Co. Ltd., Deerfield, IL, US ‡ Avandia is a trade name of GlaxoSmithKline, Research Triangle, NC, US. The validated CORE Diabetes Model (CDM) was used to simulate changes in glycosylated hemoglobin (HbA(1c)), complications, and direct medical costs. Baseline parameters came from a multi-center, double-blind trial comparing lipid and glycemic effects of pioglitazone (n = 400) and rosiglitazone (n = 402) among individuals with T2DM and untreated dyslipidemia. Sensitivity analyses examined the impact of cohort, clinical, and cost inputs on incremental cost effectiveness ratios (ICERs). In the base case, pioglitazone was associated with mean (standard deviation [SD]) quality-adjusted life years (QALYs) of 7.476 (0.123) vs. 7.326 (0.128) for rosiglitazone. Pioglitazone had $3038 higher total direct costs, but $580 lower complication costs. Risks of four cardiovascular complications were reduced with pioglitazone (relative risks 0.860-0.942), while risks of 17 other complications were slightly higher (relative risks 1.001-1.056). The ICER for pioglitazone treatment was $20 171/QALY. Results were most sensitive to the effects of HbA(1c), high-density lipoprotein-cholesterol, overall lipid effects, and pioglitazone acquisition costs. Study limitations include issues of generalizability of the trial patient population, as well as inability to capture non-adherence and variation in 'real-world' treatment patterns. Nevertheless, pioglitazone (when compared to rosiglitazone) was found to have long-term value as a treatment option for T2DM patients with dyslipidemia treated within the US payer setting.


Optimal reconstruction of concentrations, gradients and reaction rates from particle distributions.
Random walk particle tracking methodologies to simulate solute transport of conservative species constitute an attractive alternative for their computational efficiency and absence of numerical dispersion. Yet, problems stemming from the reconstruction of concentrations from particle distributions have typically prevented its use in reactive transport problems. The numerical problem mainly arises from the need to first reconstruct the concentrations of species/components from a discrete number of particles, which is an error prone process, and then computing a spatial functional of the concentrations and/or its derivatives (either spatial or temporal). Errors are then propagated, so that common strategies to reconstruct this functional require an unfeasible amount of particles when dealing with nonlinear reactive transport problems. In this context, this article presents a methodology to directly reconstruct this functional based on kernel density estimators. The methodology mitigates the error propagation in the evaluation of the functional by avoiding the prior estimation of the actual concentrations of species. The multivariate kernel associated with the corresponding functional depends on the size of the support volume, which defines the area over which a given particle can influence the functional. The shape of the kernel functions and the size of the support volume determines the degree of smoothing, which is optimized to obtain the best unbiased predictor of the functional using an iterative plug-in support volume selector. We applied the methodology to directly reconstruct the reaction rates of a precipitation/dissolution problem involving the mixing of two different waters carrying two aqueous species in chemical equilibrium and moving through a randomly heterogeneous porous medium.


Evaluating the Right Ventricle in Acute and Chronic Pulmonary Embolism: Current and Future Considerations.
The right ventricle (RV), due to its morphologic and physiologic differences, is susceptible to sudden increase in RV afterload, as noted in patients with acute pulmonary embolism (PE). Functional impairment of RV function is a stronger presage of adverse outcomes in acute PE than the location or burden of emboli. While current iterations of most clinical prognostic scores do not incorporate RV dysfunction, advancements in imaging have enabled more granular and accurate assessment of RV dysfunction in acute PE. RV enlargement and dysfunction on imaging is noted only in a subset of patients with acute PE and is dependent on underlying cardiopulmonary reserve and clot burden. Specific signs like McConnell's and "60/60" sign are noted in less than 20% of patients with acute PE. About 2% of patients with acute PE develop chronic thromboembolic pulmonary hypertension, characterized by continued deterioration in RV function in a subset of patients with a continuum of RV function from preserved to overt right heart failure. Advances in molecular and other imaging will help better characterize RV dysfunction in this population and evaluate the response to therapies.


Killing of cells by perforin. Resistance to killing is not due to diminished binding of perforin to the cell membrane.
Different cell types vary widely in their susceptibility to killing by the pore-forming cytolytic molecule perforin. In particular, the cells responsible for synthesis of perforin, i.e. cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, are very resistant to cytolysis by this molecule. It has previously been suggested that resistance is due, at least in part, to diminished binding of perforin to these cells. The purpose of the present study was to compare binding of perforin to sensitive and resistant cell types. To this end, perforin was biosynthetically labelled prior to purification. The purified labelled protein was then utilized to obtain a direct measure of the amount of perforin bound to cells during attack. Resistant cells (CTL, neutrophils) bound at least as much perforin as did sensitive cells (K562, HL60 etc.), indicating that resistance to perforin involves mechanisms operating after binding of the lytic molecule.


Lessons of the Israeli-Palestinian Conflict for Public Health: The Case of the COVID-19 Vaccination Gap.
In early 2020, the COVID-19 pandemic revealed a faceless, non-adversarial threat that endangered Israelis and Palestinians with the same ferocity. However, the capacities of the health systems to address it were not equal, with Israel more equipped for the outbreak with infrastructure, resources, manpower and later, vaccines. The pandemic demonstrated the life-saving benefits of cooperation and the self-defeating harms brought by non-cooperation. These trends are explored here by an international team of public health and environmental scholars, including those from different sides of the Israeli-Palestinian conflict. This article explores the importance of recognizing the Israeli and Palestinian jurisdictions as a single epidemiological unit, and illustrates how doing so is a pragmatic positioning that can serve self-interest. We demonstrate how despite political shocks precipitating non-cooperation, there has been a recurrent tendency towards limited cooperation. The paper concludes with lessons over the need for reframing public health as a potential bridge, the need for structural changes creating sustainable platforms for accelerated transboundary cooperation to enable the steady management of current and future public and environmental health crises regardless of dynamic political crises, and the importance of civil society and international organizations in forging collaboration in advance of governmental engagement.


Expression of alphasmooth muscle actin in lens epithelia from human donors and cataract patients.
In order to re-evaluate functional implications of alphasmooth muscle actin (alphaSMA) expression in lens epithelial cells (LECs), we assessed its presence in donor lenses without visible opacities (DON), lenses with mature cataract (CAT), and cataractous lenses with posterior subcapsular opacities (PSO) or anterior subcapsular fibrosis (ASF). The levels of alphaSMA and transforming growth factor-beta2 (TGFbeta2) mRNAs were measured by classical and real-time PCR. Expression and structural organisation of alphaSMA protein and beta-catenin were monitored by Western blotting and confocal microscopy. All DON analysed contained measurable amounts of alphaSMA mRNA. In CAT without and with PSO, mRNA expression was increased and, again more than doubled in ASF. TGFbeta2 mRNA expression varied widely between the individual samples but was slightly increased in ASF. No correlation existed between alphaSMA or TGFbeta2 expression and the age of the donors in any of the lens categories. Confocal microscopy revealed that, in DON and CAT, alphaSMA was preferentially expressed in a simple granular pattern in single or small clusters of LECs within a normally shaped cobblestone epithelium. Locally, the granules were merged into short stretches at the cell margin. In CAT, a few abnormally shaped cells contained polygonal alphaSMA structures and short stress fibres. In CAT with PSO and ASF, polygons and stress fibre bundles predominated in spindle-shaped cells. Expression patterns of different complexity were often present in the same epithelium. Apical polygons and basal stress fibres were detected within the same cell and may reflect instability of the interface between epithelium and cortical fibres and changes in adhesion to the capsule, respectively. High levels of betacatenin mRNA and protein were present in all lens types. However, with increasing complexity of alphaSMA organisation, betacatenin staining disappeared from the cell margin and basal infoldings and was shifted towards the cytoplasm and nucleus. The presence of alphaSMA in DON, the absence of any correlation between mRNA level and age, and the modest increase in complexity of alphaSMA-containing structures in CAT argue against an inevitable link between alphaSMA expression and the development of age-related cataract. Low levels of alphaSMA expression may reflect repair of normal wear and tear. In pathologic situations such as PSO and ASF, persisting stimulation and additional incentives may induce increased alphaSMA expression and more elaborate patterning, eventually leading to completion of EMT.


Congenital absence of the pericardium: a rare cause of right ventricular dilatation and levoposition of the heart.
Congenital absence of the pericardium is a rare cardiac defect with variable clinical presentations and is usually discovered incidentally. The pathology may lead to serious complications such as incarceration of cardiac tissue, myocardial ischemia, aortic dissection or valvular insufficiency. Diagnosis is not difficult so long as some tips are remembered. We present the cases of two patients with congenital absence of left pericardium.


Structural properties and foaming of plant cell wall polysaccharide dispersions.
Water suspensions of cellulose nanofibres with xylan, xyloglucan and pectin were studied for foaming and structural properties as a new means for food structuring. The dispersions were analysed with rheological measurements, microscopy and optical coherence tomography. A combination of xylan with TEMPO-oxidized nanocellulose produced a mixture with well-dispersed air bubbles, while the addition of pectin improved the elastic modulus, hardness and toughness of the structures. A similar structure was observed with native nanocellulose, but the elastic modulus was not as high. Shear flow caused cellulose nanofibres to form plate-like flocs in the suspension that accumulated near bubble interfaces. This tendency could be affected by adding laccase to the dispersion, but the effect was opposite for native and TEMPO-oxidized nanocellulose. Nanocellulose type also influenced the interactions between nanofibers and other polysaccharides. For example, xyloglucan interacted strongly with TEMPO-oxidized nanocellulose (high storage modulus) but not with native nanocellulose.


Diagnosis of acute coronary syndrome.
The term "acute coronary syndrome" encompasses a range of thrombotic coronary artery diseases, including unstable angina and both ST-segment elevation and non-ST-segment elevation myocardial infarction. Diagnosis requires an electrocardiogram and a careful review for signs and symptoms of cardiac ischemia. In acute coronary syndrome, common electrocardiographic abnormalities include T-wave tenting or inversion, ST-segment elevation or depression (including J-point elevation in multiple leads), and pathologic Q waves. Risk stratification allows appropriate referral of patients to a chest pain center or emergency department, where cardiac enzyme levels can be assessed. Most high-risk patients should be hospitalized. Intermediate-risk patients should undergo a structured evaluation, often in a chest pain unit. Many low-risk patients can be discharged with appropriate follow-up. Troponin T or I generally is the most sensitive determinant of acute coronary syndrome, although the MB isoenzyme of creatine kinase also is used. Early markers of acute ischemia include myoglobin and creatine kinase-MB subforms (or isoforms), when available. In the future, advanced diagnostic modalities, such as myocardial perfusion imaging, may have a role in reducing unnecessary hospitalizations.


Carbon utilization profiles of Fusarium virguliforme isolates.
Fusarium virguliforme is the cause of sudden death syndrome in soybean. Physiological variability among isolates of the fungus is unknown. One way to measure physiologic variability is to analyze growth on different carbon sources. The carbon source utilization profiles of 18 F. virguliforme isolates were examined using the Biolog FF 96-well microplate, which contains 95 different carbon sources. The utilization of dextrin,D-mannitol, maltotriose,D-lactic acid methyl ester, N-acetyl-D-galactosamine, salicin, D-trehalose, and L-alanine differed significantly among isolates (P = 0.05). Carbon sources were grouped into 3 clusters based on their ability to promote growth of F. virguliforme, after calculating Euclidean distances among them. About 12% of the carbon sources promoted a high amount of mycelial growth, 39% promoted a medium amount of growth, and 49% promoted a low amount of mycelial growth; the latter was not significantly different from the water blank control. A hierarchical tree diagram was produced for the 18 isolates based on their carbon source utilization profiles using Ward's hierarchical analysis method. Two main clusters of isolates were formed. One cluster represented greater average mycelial growth on all of the carbon sources than the other cluster. In this study, variability in carbon source utilization among F. virguliforme isolates was evident, but the results were not associated with geographic origin of the isolates, year collected, or published data on aggressiveness. Additional research is needed to determine if these carbon utilization profiles are associated with other biological characteristics, like spore germination, propagule formation, and saprophytic competitiveness.


Evidence of biomechanical and collagen heterogeneity in uterine fibroids.
Uterine fibroids (leiomyomas) are common benign tumors of the myometrium but their molecular pathobiology remains elusive. These stiff and often large tumors contain abundant extracellular matrix (ECM), including large amounts of collagen, and can lead to significant morbidities. After observing structural multiformities of uterine fibroids, we aimed to explore this heterogeneity by focusing on collagen and tissue stiffness. For 19 fibroids, ranging in size from 3 to 11 centimeters, from eight women we documented gross appearance and evaluated collagen content by Masson trichrome staining. Collagen types were determined in additional samples by serial extraction and gel electrophoresis. Biomechanical stiffness was evaluated by rheometry. Fibroid slices displayed different gross morphology and some fibroids had characteristics of two or more patterns: classical whorled (n = 8); nodular (n = 9); interweaving trabecular (n = 9); other (n = 1). All examined fibroids contained at least 37% collagen. Tested samples included type I, III, and V collagen of different proportions. Fibroid stiffness was not correlated with the overall collagen content (correlation coefficient 0.22). Neither stiffness nor collagen content was correlated with fibroid size. Stiffness among fibroids ranged from 3028 to 14180 Pa (CV 36.7%; p<0.001, one-way ANOVA). Stiffness within individual fibroids was also not uniform and variability ranged from CV 1.6 to 42.9%. The observed heterogeneity in structure, collagen content, and stiffness highlights that fibroid regions differ in architectural status. These differences might be associated with variations in local pressure, biomechanical signaling, and altered growth. We conclude the design of all fibroid studies should account for such heterogeneity because samples from different regions have different characteristics. Our understanding of fibroid pathophysiology will greatly increase through the investigation of the complexity of the chemical and biochemical signaling in fibroid development, the correlation of collagen content and mechanical properties in uterine fibroids, and the mechanical forces involved in fibroid development as affected by the various components of the ECM.


Evidence of mast cell activity in the middle ears of children with otitis media with effusion.
This is the first study to report the presence of tryptase, a reflection of mast cell activity, in chronic middle ear effusion of patients whose atopic status was characterized. Mediator activity of mast cells and eosinophils was measured prospectively from effusion of 33 randomly selected patients and 5 control subjects with chronic otitis media with effusion (OME). Atopy was determined by enzyme-linked immunosorbent assay. Middle ear biopsies from a second group of 8 OME patients and 4 controls were fixed in plastic and stained immunohistochemically for mast cells. Sixty-one percent of patients had extensive activation of mast cells in their middle ears. Among those with elevated tryptase in their effusion, 95.6% were atopic and 94.7% also had elevated levels of effusion eosinophilic cationic protein (ECP). Tryptase levels were elevated only in the effusion of atopic patients, as compared with 5 controls (P < .01). Mast cells were present in 6 of 8 OME ears and absent in all 4 normal ears. Mast cells and its mediator tryptase, both indicators of a Th2-driven immune response, are present in a majority of ears that have chronic effusion. These findings support the hypothesis that middle ear mucosa is capable of an allergic response and that the inflammation within the middle ear of most OME patients is allergic in nature.


Decreased neuroplasticity in minor burn injury survivors compared to non-injured adults: A pilot study in burn injury survivors aged 45 years and older.
Neuroplasticity is the capacity of the brain to change or adapt with experience: brain changes occur with use, disuse, and injury. Repetitive transcranial magnetic stimulation (rTMS) can be used to induce neuroplasticity in the human brain. Here, we examined rTMS-induced neuroplasticity in the primary motor cortex in burns survivors and controls without injury, and whether neuroplasticity is associated with functional recovery in burns survivors. Sixteen burn injury survivors (total body surface area of burn injury <15%) and 13 non-injured control participants were tested. Repetitive TMS (specifically, spaced continuous theta-burst stimulation[cTBS]) was applied to induce neuroplasticity 6 and 12 weeks after injury in burn survivors and in two sessions separated by 6 weeks in controls. Motor evoked potentials (MEPs) elicited by single-pulse TMS were measured before and after rTMS to measure neuroplasticity. Burns survivors completed a functional assessment 12 weeks after injury. Non-injured controls showed decreased MEP amplitude 15-30 min after spaced cTBS in both experimental sessions. Burn survivors showed a smaller change in MEP amplitude after spaced cTBS compared to controls 6 weeks after burn injury but no difference compared to controls 12 weeks after burn injury. In burn survivors, there was a significant positive association between general health outcome (Short-Form Health Survey) and the change in MEP amplitude after spaced cTBS 12 weeks after injury (r=.73, p = .01). The current findings suggest that burn survivors have a reduced capacity for neuroplasticity early in the recovery period (6 weeks after injury), which normalizes later in the recovery period (12 weeks after injury). Furthermore, the results provide preliminary evidence to suggest that burn survivors with normalized neuroplasticity 12 weeks after injury recover faster after burn injury.


Prebiotics for the prevention of allergies: A systematic review and meta-analysis of randomized controlled trials.
Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics are selectively fermented food ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies. To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines. We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies. Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results. Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.


Evoked potentials in the diagnosis of multiple sclerosis: a follow up study.
Visual, somatosensory and brain stem auditory evoked potentials were recorded in 84 patients in whom the diagnosis of multiple sclerosis was under consideration. The patients were followed up for a maximum of 38 months or until a definite diagnosis of multiple sclerosis or of some other condition was established. Seven patients were found not to have multiple sclerosis. Abnormal evoked potentials indicating clinically silent lesions were found at the initial investigation in fourteen of the twenty-eight patients in whom a diagnosis of clinically definite multiple sclerosis was accepted during the period of follow up. In the thirty-seven patients in whom no change in clinical category occurred during the period such abnormalities were found in five. The visual evoked potential was found to be of greatest predictive value.


Detection of Caries Around Resin-Modified Glass Ionomer and Compomer Restorations Using Four Different Modalities In Vitro.
The aim of this study was to evaluate the ability of visual examination (International Caries Detection and Assessment System-ICDAS II), light-emitting diodes (LED) fluorescence (SPECTRA), laser fluorescence (DIAGNODent, DD), photothermal radiometry and modulated luminescence (PTR-LUM, The Canary System, CS) to detect natural decay beneath resin-modified glass ionomer (RMGIC) and compomer restorations in vitro. Twenty-seven extracted human molars and premolars, consisting of 2 control teeth, 10 visually healthy/sound and 15 teeth with natural cavitated lesions, were selected. For the carious teeth, caries was removed leaving some carious tissue on one wall of the preparation. For the sound teeth, 3 mm deep cavity preparations were made. All cavities were restored with RMGIC or compomer restorative materials. Sixty-eight sites (4 sites on sound unrestored teeth, 21 sound sites and 43 carious sites with restorations) were selected. CS and DD triplicate measurements were done at 2, 1.5, 0.5, and 0 mm away from the margin of the restoration (MOR). SPECTRA images were taken, and two dentists provided ICDAS II scoring for the restored surfaces. The SPECTRA data and images were inconclusive due to signal interference from the restorations. Visual examinations of the restored tooth surfaces were able to identify 5 of the 15 teeth with caries. In these situations, the teeth were ranked as having ICDAS II 1 or 2 rankings, but they could not identify the location of the caries or depth of the lesion. CS and DD were able to differentiate between sound and carious tissue at the MOR, but larger variation in measurement, and poorer accuracy, was observed for DD. It was concluded that the CS has the potential to detect secondary caries around RMGIC and compomer restorations more accurately than the other modalities used in this study.


Interaction between the marine sponge cyclic peptide theonellamide A and sterols in lipid bilayers as viewed by surface plasmon resonance and solid-state (2)H nuclear magnetic resonance.
Theonellamides (TNMs) are members of a distinctive family of antifungal and cytotoxic bicyclic dodecapeptides isolated from the marine sponge Theonella sp. Recently, it has been shown that TNMs recognize 3β-hydroxysterol-containing membranes, induce glucan overproduction, and damage cellular membranes. However, to date, the detailed mode of sterol binding at a molecular level has not been determined. In this study, to gain insight into the mechanism of sterol recognition of TNM in lipid bilayers, surface plasmon resonance (SPR) experiments and solid-state deuterium nuclear magnetic resonance ((2)H NMR) measurements were performed on theonellamide A (TNM-A). SPR results revealed that the incorporation of 10 mol % cholesterol or ergosterol into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes significantly enhances the affinity of the peptide for the membrane, particularly in the initial binding to the membrane surface. These findings, together with the fact that binding of TNM-A to epicholesterol (3α-cholesterol)-containing liposomes and pure POPC liposomes was comparably weak, confirmed the preference of the peptide for the 3β-hydroxysterol-containing membranes. To further establish the formation of the complex of TNM-A with 3β-hydroxysterols in lipid bilayers, solid-state (2)H NMR measurements were conducted using deuterium-labeled cholesterol, ergosterol, or epicholesterol. The (2)H NMR spectra showed that TNM-A significantly inhibits the fast rotational motion of cholesterol and ergosterol, but not epicholesterol, therefore verifying the direct complexation between TNM-A and 3β-hydroxysterols in lipid bilayers. This study demonstrates that TNM-A directly recognizes the 3β-OH moiety of sterols, which greatly facilitates its binding to bilayer membranes.


Differential localization of N-acetylated indolealkylamines in CNS and the Harderian gland using immunohistology.
Using two different antisera, one binding only melatonin (M) and the other binding both M and N-acetylserotonin (NAS), brain tissue and the Harderian gland were investigated using fluorescence and peroxidase labeled double antibody immunohistology. M has been identified in the outer nuclear layer of the retina, in the optic nerves, chiasma and the tracts, suprachiasmatic nucleus and the Harderian gland. NAS, but not M, was found in the granule layer of the cerebellum, spinal tract of the trigeminal roots and the pontal and spinal reticular formation. The possible relationship of cerebellar and brain stem NAS to brain excitability as well as localization of M in the visual pathway, suprachiasmatic nucleus and the Harderian gland in the relation to the regulation of light dependent circadian periodicity is discussed.


Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain protein CAL.
We have previously identified the cystic fibrosis transmembrane regulator (CFTR)-interacting protein CAL and demonstrated that CAL modulates CFTR plasma membrane expression by retaining CFTR within the cell. Here, we report that in addition to regulating membrane expression, CAL also regulates the expression of mature CFTR. The co-expression of hemagglutinin-tagged or Myc-tagged CAL with green fluorescent protein (GFP)-CFTR in COS-7 cells causes a dose-dependent reduction in mature GFP-CFTR, independent of its tags. Bafilomycin A1, a lysosomal proton pump inhibitor, increases mature GFP-CFTR, confirming previous reports of lysosomal degradation of mature CFTR. Importantly, bafilomycin A1 reverses CAL-mediated CFTR degradation. The proteasome inhibitor, MG132, on the other hand, does not reverse the effect of CAL. CAL has no effect on CFTR maturation, suggesting that it exerts its effects on mature CFTR. Co-expression of CAL enhances the degradation of CFTR. We showed previously that CAL reduces the half-life of CFTR at the cell surface. Here we show that expression of dominant-negative dynamin 2 K44A, a large GTPase inhibitor that is known to inhibit clathrin-mediated endocytosis and vesicle formation in the Golgi, increases cell surface CFTR as measured by surface biotinylation. More importantly, dynamin 2 K44A also restores cell surface CFTR in CAL-overexpressing cells and partially blocks the CAL-mediated degradation of mature CFTR. These data suggest a model in which CAL retains CFTR in the cell and targets CFTR for degradation.


Chyle leak following biliary pancreatitis.
Chylous ascites is a rare clinical entity that historically has been accompanied by high mortality due to the association with malignancy. Here we present a case of chylous ascites as a complication of mild pancreatitis in a young woman. We review the literature of similar cases, which revealed four similar cases with a range of outcomes. Treatment options vary from dietary restriction of medium chain fatty acids, total parental nutrition, radiological intervention and surgery.


An evaluation of traumatic deaths associated with animal attacks: A 10-year autopsy study.
Just as throughout the world in general, deaths related to animal attacks continue to be a public health problem in Turkey. A decrease in areas of natural habitat because of human invasion, and the use of these areas for hunting, wood-cutting, recreational and sporting activities has increased the possibility of humans encountering wild animals. A physical retrospective screening was made of the forensic records of a total of 8944 autopsy cases in the Forensic Medicine Institute of the Trabzon Group Directorate in the 10-year period between Januarry 2007 and December 2016. When the types of animals causing the traumatic death were examined, the most frequent was cattle in 15 cases followed by horses in 7 cases, bears in 4 cases, wolves in 2 cases, and wild boars in 2 cases. According to the autopsy results, the cause of death was most often intrathoracic bleeding and intrathoracic organ damage, the regions of the body injured were seen to be most often the chest and back, and the most common form of injury was blunt/crush trauma. From these records, cases were identified where the cause of death was traumatic animal attack, and examination was made of the sociodemographic characteristics, the type of animal that caused the injuries, information about the location of the incident, witness statements, information about the healthcare centre, findings of external examination and autopsy, and the cause.


NMDA receptor-mediated activation of NADPH oxidase and glomerulosclerosis in hyperhomocysteinemic rats.
This study investigated the role of NMDA receptor in hyperhomocyteinemia (hHcys)-induced NADPH oxidase (Nox) activation and glomerulosclerosis. Sprague-Dawley rats were fed a folate-free (FF) diet to produce hHcys, and a NMDA receptor antagonist, MK-801, was administrated. Rats fed the FF diet exhibited significantly increased plasma homocysteine levels, upregulated NMDA receptor expression, enhanced Nox activity and Nox-dependent O(2)(.-) production in the glomeruli, which were accompanied by remarkable glomerulosclerosis. MK-801 treatment significantly inhibited Nox-dependent O(2)(.-) production induced by hHcys and reduced glomerular damage index as compared with vehicle-treated hHcys rats. Correspondingly, glomerular deposition of extracellular matrix components in hHcys rats was ameliorated by the administration of MK-801. Additionally, hHcys induced an increase in tissue inhibitor of metalloproteinase-1 (TIMP-1) expression and a decrease in matrix metalloproteinase (MMP)-1 and MMP-9 activities, all of which were abolished by MK-801 treatment. In vitro studies showed that homocysteine increased Nox-dependent O(2)(.-) generation in rat mesangial cells, which was blocked by MK-801. Pretreatment with MK-801 also reversed homocysteine-induced decrease in MMP-1 activity and increase in TIMP-1 expression. These results support the view that the NMDA receptor may mediate Nox activation in the kidney during hHcys and thereby play a critical role in the development of hHcys-induced glomerulosclerosis.


Pituitary tumor transforming gene binding factor: a new gene in breast cancer.
Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17beta-estradiol in estrogen receptor alpha (ERalpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ERalpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ERalpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects.


Translating Research into Practice: How Confident Are Allied Health Clinicians?
Knowledge translation (KT) is a multistage process of implementing practice change to align with evidence-based practice. This study aimed to determine the confidence of allied health professionals (AHPs) to undertake KT. A quantitative questionnaire was disseminated to AHPs over a 4-week period. Awareness of and confidence with KT was assessed using a 100-mm visual analogue scale. 374 AHPs responded from 12 metropolitan hospitals in Queensland, Australia. Moderate confidence was reported for identifying an evidence-practice gap (median 70 mm, interquartile range [IQR] 50-80 mm), finding relevant literature/evidence (67 mm, 40-84 mm), and sharing evidence with colleagues (70 mm, 50-85 mm). Clinicians were less confident in choosing a KT framework (20 mm, 3-50 mm), implementing a practice change (40 mm, 15-61 mm), assessing barriers and enablers (50 mm, 25-70 mm) and supporting less experienced clinicians undertaking KT (42 mm, 14-68 mm). There was a weak positive correlation between years of experience and confidence in implementing practice change (rho=0.127, p=0.017). A majority of respondents (89%, n=333) reported an interest in learning more about KT. AHPs were interested in KT but had low confidence in implementing research into practice. These findings identify opportunities to support the training and education needs of AHPs in KT.