Extensive metabolic disorders are present in APC(min) tumorigenesis mice.
Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients.


An altered Bioheat model for persons with cervical spinal cord injury.
The objective of this work is to develop a Bioheat model to predict the thermal responses of people with tetraplegia (TP) under hot, cold and neutral ambient conditions as well as different physical activities suitable for their level of injury. The focus is on TP with impairment or loss of motor and/or sensory function in C1 to C7 segments of the spinal cord due to damage of neural elements within the spinal canal. Starting from transient multi-segmented Bioheat model of able-bodied (AB) people, specific modifications were performed reflecting the changes in physiology due to the injury affecting the blood circulation system, energy expenditure, and thermoregulatory functions in the body. The TP Bioheat model predicts the TP thermal responses under steady and transient thermal conditions, and different activity levels that are appropriate for the level of injury. The model was validated with published experimental data reporting physiological and thermal data measurements on cases of people with complete and incomplete tetraplegia under controlled environmental conditions and activity levels. In both transient and steady state environmental conditions, the predicted core and mean skin temperature values were compared against the experimental data with maximum error of 0.86 °C and 0.9 °C respectively. The TP Bioheat model can be used as a tool to propose appropriate personal cooling strategies for TP.


Measuring the diversity gap of cannabis clinical trial participants compared to people who report using cannabis.
Little is known about the demographics of people who use cannabis, including how use trends within population subgroups have evolved over time. It is therefore challenging to know if the demographics of participants enrolled in cannabis clinical trials are representative of those who use cannabis. To fill this knowledge gap, data from the National Survey on Drug Use and Health (NSDUH) on "past-month" cannabis use across various population subgroups in the United States was examined from 2002 to 2021. The most notable increases in "past-month" cannabis use prevalence occurred in those aged 65 and older (2,066.1%) and 50-64-year-olds (472.4%). In 2021, people reporting "past-month" cannabis use were 56.6% male and 43.4% female. Distribution across self-reported race and ethnicity was 64.1% White, 14.3% Black, 14.1% Hispanic, and 3.1% more than one race. And many ages were represented as 24.4% were 26-34, 24.1% were 35-49, 22.4% were 18-25, and 17.6% were 50-64 years old. To understand if these population subgroups are represented in cannabis clinical trials, participant demographics were extracted from peer-reviewed clinical trials reporting on pharmacokinetic and/or pharmacodynamic models of cannabis or cannabinoids. Literature was grouped by publication year (2000-2014 and 2015-2022) and participant prior exposure to cannabis. Results identified that cannabis clinical trial participants are skewed toward overrepresentation by White males in their 20s and 30s. This represents structural discrimination in the research landscape that perpetuates social and health inequities.


Ecological determinants of mould growth in stored grain.
Grain entering store carries a microflora of 'field' and 'storage' fungi. Field fungi require readily available water and therefore seldom develop in store. By contrast, storage fungi, especially Aspergillus spp., are able to grow at low water activities (aw, 0.70-0.75) enabling them to initiate grain spoilage. The ability of storage fungi to germinate, grow and sporulate in stored grain is dependent on the availability of water in the substrate, temperature and the intergranular gas composition. These factors may interact to have a profound influence on the initiation of spoilage of stored grain by fungi. An understanding of the ecological determinants of mould growth may help to develop improved and safer methods of grain storage.


Medical students in Russia evaluate the training during the COVID-19 pandemic: a student survey.
The aim of the study was to obtain feedback from medical students in Russia regarding their e-learning experience during COVID-19 Pandemic. Thirteen thousand forty students from 46 Medical Schools in Russia completed an original evaluation form validated by 6 experts. Criterion and construct validity were determined in a pilot study (n = 46). The study design was based on the use of Google Forms. Participants used the Visual Analog Scale from 1 to 10 to assess the level of knowledge acquired. 95.31% of medical schools in Russia switched to e-learning during the Pandemic. 39.8% of the students stated that the time to prepare for the class has doubled. For 19.9% of them, it increased by one third, while 26.6% did not report any changes. 38,4% of the participants are satisfied with particular elements of e-learning, 27.5% like such a format, 22.9% do not like it, and 11.2% could not answer the question. The average scores for the knowledge assessment were 5.9 for the humanities, 6.1 for fundamental science, and 6.0 for clinical training. The most important findings are increased self-instruction time, insufficient knowledge gained and territorial and socio-economic inequalities within the country. Meanwhile, most students favor distance learning or its particular elements. Consequently, medical education leaders in Russia should consider the implementation of blended training in medicine taking into account specific regional factors, ensuring its effectiveness at all stages.


Reasoning about knowledge: Children's evaluations of generality and verifiability.
In a series of experiments, we examined 3- to 8-year-old children's (N=223) and adults' (N=32) use of two properties of testimony to estimate a speaker's knowledge: generality and verifiability. Participants were presented with a "Generic speaker" who made a series of 4 general claims about "pangolins" (a novel animal kind), and a "Specific speaker" who made a series of 4 specific claims about "this pangolin" as an individual. To investigate the role of verifiability, we systematically varied whether the claim referred to a perceptually-obvious feature visible in a picture (e.g., "has a pointy nose") or a non-evident feature that was not visible (e.g., "sleeps in a hollow tree"). Three main findings emerged: (1) young children showed a pronounced reliance on verifiability that decreased with age. Three-year-old children were especially prone to credit knowledge to speakers who made verifiable claims, whereas 7- to 8-year-olds and adults credited knowledge to generic speakers regardless of whether the claims were verifiable; (2) children's attributions of knowledge to generic speakers was not detectable until age 5, and only when those claims were also verifiable; (3) children often generalized speakers' knowledge outside of the pangolin domain, indicating a belief that a person's knowledge about pangolins likely extends to new facts. Findings indicate that young children may be inclined to doubt speakers who make claims they cannot verify themselves, as well as a developmentally increasing appreciation for speakers who make general claims.


Capsular serotypes and antibiotic sensitivity of Streptococcus pneumoniae isolated from primary-school children.
A total of 1049 primary-school children in 18 schools were screened for carriage of Streptococcus pneumoniae. Data on family size, antibiotic use, travel and hospital admissions were collected. Pneumococcal serotyping and sensitivity tests were performed. One third of children were found to be pneumococcal carriers. Ten of 344 isolates were penicillin-resistant (2.9%). Apart from resistance to trimethoprim and ciprofloxacin, resistance rates in penicillin-sensitive strains were low. Among penicillin-resistant strains (PRP), co-resistance to trimethoprim, chloramphenicol and tetracycline was common. Cefotaxime-resistance was seen in 90% of PRP. Although 24 serotypes were represented, groups 6, 19 and 23 accounted for 55% of strains. Serogroup 23 strains were significantly more likely to be penicillin-resistant than other groups/types. Clustering of strains by serotype and antibiotic resistance was seen in several schools. No association with foreign travel, family size or age of siblings was seen and penicillin resistance was not associated with prior antibiotic use. However, hospital admission was significantly associated with carriage of PRP. The implications of detecting PRP in the community are discussed.


Studying the tidal-induced water circulation pattern within EL-Burullus fishing harbor, Egypt, using CMS-PTM numerical modeling.
Protection from waves and providing an appropriate calmness ratio are vital requirements in the designing phase of a harbor. Another crucial issue is guaranteeing sufficient water circulation as a key indicator for water quality and avoiding the associated environmental problems of poor water quality conditions. In a coastal harbor, the interior basin's water quality largely depends on the harbor's natural/self-ability to flush out different existing pollutants. El-Burullus fishing harbors is one of the Egyptian coastal fishing harbors that suffer from environmental issues such as accumulated pollutants, particularly in stagnant areas, and deterioration of water quality within the harbor's basin. Investigating water quality status within the coastal harbors necessitates knowledge about the mechanism of water circulation patterns within the harbor. The most common indicator for the water renewal and circulation pattern evaluation is the flushing time. Therefore, a coupled coastal hydrodynamic modeling system and particle tracking model (CMS-PTM) are utilized to investigate the tidal-induced circulation pattern within the El-Burullus fishing harbor, considering two tide scenarios (best and worst). Three locations (where most operational fishing facilities exist) were selected as point sources (instantaneous mass) for particle release. The results highlight the role of tidal actions on the water circulation within El-Burullus harbor and how the residence time varies based on the source release location.


First filter feeding in the Early Triassic: cranial morphological convergence between Hupehsuchus and baleen whales.
Modern baleen whales are unique as large-sized filter feeders, but their roles were replicated much earlier by diverse marine reptiles of the Mesozoic. Here, we investigate convergence in skull morphology between modern baleen whales and one of the earliest marine reptiles, the basal ichthyosauromorph Hupehsuchus nanchangensis, from the Early Triassic, a time of rapid recovery of life following profound mass extinction. Two new specimens reveal the skull morphology especially in dorsal view. The snout of Hupehsuchus is highly convergent with modern baleen whales, as shown in a morphometric analysis including 130 modern aquatic amniotes. Convergences in the snout include the unfused upper jaw, specialized intermediate space in the divided premaxilla and grooves around the labial margin. Hupehsuchus had enlarged its buccal cavity to enable efficient filter feeding and probably used soft tissues like baleen to expel the water from the oral cavity. Coordinated with the rigid trunk and pachyostotic ribs suggests low speeds of aquatic locomotion, Hupehsuchus probably employed continuous ram filter feeding as in extant bowhead and right whales. The Early Triassic palaeoenvironment of a restrictive lagoon with low productivity drove Hupehsuchus to feed on zooplankton, which facilitated ecosystem recovery in the Nanzhang-Yuan'an Fauna at the beginning of the Mesozoic.


Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production.
Mitochondrial dysfunctions and oxidative stress play important roles in the early pathogenesis of Alzheimer's disease (AD), which also involves the aberrant expression levels of mitochondrial proteins. However, the molecular mechanisms underlying the aberrant expression levels of these proteins in the pathogenesis of AD are still not completely understood. Tid1 (DnaJA3/mtHsp40), a mammalian homolog of the Drosophila tumor suppressor Tid56, is reported to induce mitochondrial fragmentation associated with an increase in reactive oxygen species (ROS) levels, resulting in cell death in some cancer cells. However, the involvement of Tid1 in AD pathogenesis is as yet unknown. In this study, we found that the Tid1 protein levels were upregulated in the hippocampus of AD patients and Tg2576 mice. Our in vitro studies showed that Aβ42 increased the expression levels of Tid1 in primary rat cortical neurons. The knockdown of Tid1 protected against neuronal cell death induced by Aβ42, and Tid1-mediated neuronal cell death, was dependent on the increased ROS generation and caspase-3 activity. The overexpression of Tid1 in HEK293-APP cells increased the BACE1 levels, resulting in increased Aβ production. Conversely, Tid1 knockdown in HEK293-APP cells and primary cultured neurons decreased Aβ production through the reduction in the BACE1 levels. We also found that the overexpression of Tid1 activated c-Jun N-terminal kinase (JNK) leading to increased Aβ production. Taken together, our results suggest that upregulated Tid1 levels in the hippocampus of patients with AD and Tg2576 mice induce apoptosis and increase Aβ production, and Tid1 may therefore be a suitable target in therapeutic interventions for AD.


Molecular characterization of NDM-1-producing Pseudomonas aeruginosa isolates from hospitalized patients in Iran.
The emergence of carbapenem-resistant Pseudomonas aeruginosa is one of the most important challenges in a healthcare setting. The aim of this study is double-locus sequence typing (DLST) typing of blaNDM-1 positive P. aeruginosa isolates. Twenty-nine blaNDM-1 positive isolates were collected during three years of study from different cities in Iran. Modified hodge test (MHT), double-disk synergy test (DDST) and double-disk potentiation test (DDPT) was performed for detection of carbapenemase and metallo-beta-lactamase (MBL) producing blaNDM-1 positive P. aeruginosa isolates. The antibiotic resistance genes were considered by PCR method. Clonal relationship of blaNDM-1 positive was also characterized using DLST method. Antibiotic susceptibility pattern showed that all isolates were resistant to imipenem and ertapenem. DDST and DDPT revealed that 15/29 (51.8%) and 26 (89.7%) of blaNDM-1 positive isolates were MBL producing isolates, respectively. The presence of blaOXA-10, blaVIM-2, blaIMP-1 and blaSPM genes were detected in 86.2%, 41.4%, 34.5% and 3.5% isolates, respectively. DLST typing results revealed the main cluster were DLST 25-11 with 13 infected or colonized patients. The presence of blaNDM-1 gene with other MBLs encoding genes in P. aeruginosa is a potential challenge in the treatment of microorganism infections. DLST showed partial diversity among 29 blaNDM-1 positive isolates.


Dissection of the stepwise mechanism to beta-lactam formation and elucidation of a rate-determining conformational change in beta-lactam synthetase.
Clavulanic acid is a widely used beta-lactamase inhibitor whose key beta-lactam core is formed by beta-lactam synthetase. beta-Lactam synthetase exhibits a Bi-Ter mechanism consisting of two chemical steps, acyl-adenylation followed by beta-lactam formation. 32PPi-ATP exchange assays showed the first irreversible step of catalysis is acyl-adenylation. From a small, normal solvent isotope effect (1.38 +/- 0.04), it was concluded that beta-lactam synthesis contributes at least partially to kcat. Site-specific mutation of Lys-443 identified this residue as the ionizable group at pKa approximately 8.1 apparent in the pH-kcat profile that stabilizes the beta-lactam-forming step. Viscosity studies demonstrated that a protein conformational change was also partially rate-limiting on kcat attenuating the observed solvent isotope effect on beta-lactam formation. Adherence to Kramers' theory gave a slope of 1.66 +/- 0.08 from a plot of log(o kcat/kcat) versus log(eta/eta(o)) consistent with opening of a structured loop visible in x-ray data preceding product release. Internal "friction" within the enzyme contributes to a slope of > 1 in this analysis. Correspondingly, earlier in the catalytic cycle ordering of a mobile active site loop upon substrate binding was manifested by an inverse solvent isotope effect (0.67 +/- 0.15) on kcat/Km. The increased second-order rate constant in heavy water was expected from ordering of this loop over the active site imposing torsional strain. Finally, an Eyring plot displayed a large enthalpic change accompanying loop movement (DeltaH approximately 20 kcal/mol) comparable to the chemical barrier of beta-lactam formation.


Fabrication of an auricular prosthesis: a case report.
The fabrication of ear prosthesis is considered by many prosthetists to be one of the more difficult replacements in maxillofacial reconstruction. The severe undercuts and pronounced convolutions of the ear's surface present a challenge in simulating a natural proportioned prosthesis. The mould for the ear is generally made by creating a three surface die to reproduce the unique configuration adequately and to allow retrieval of the finished prosthesis without damage. This article presents an outlined procedure in the basic fabrication of a prosthetic ear by a conventional technique where the wax pattern is fabricated from the impression of an individual with a similarly proportioned ear. Fabricating an auricular prosthesis may be part of the work of a maxillofacial department.


Adenohypophysial histophysiology of gonadectomized, fatectomized and steroid treated male frogs, Rana hexadactyla (Lesson).
Cytology of the pars distalis of unilaterally and bilaterally gonadectomized Rana hexadactyla kept for a period of 60, 75, 120, 150 and 180 days and those treated with testosterone (25 micrograms) and oestradiol (25 micrograms) was studied. Similarly adenohypophysial cytomorphology in unilaterally and bilaterally fatectomized animals and/or treated with aqueous fat body extract was also investigated. The results indicate the B2 and B3 cells of pars distalis are responsible for the gametogenetic activity. A1 and B2 cells may contain some fat mobilizing factor (FMF) for stimulating spermatogenesis.


Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 2. Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4).
A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. Fractionation by HPLC led to 35 smaller-size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). In this second part, we identified 19 oligosaccharide-alditols possessing core types 3 and 4. Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. J. Biochem. 143, 227-234]. The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch.


A novel alphaproteobacterial ectosymbiont promotes the growth of the hydrocarbon-rich green alga Botryococcus braunii.
Botryococcus braunii is a colony-forming green alga that accumulates large amounts of liquid hydrocarbons within the colony. The utilization of B. braunii for biofuel production is however hindered by its low biomass productivity. Here we describe a novel bacterial ectosymbiont (BOTRYCO-2) that confers higher biomass productivity to B. braunii. 16S rDNA analysis indicated that the sequence of BOTRYCO-2 shows low similarity (<90%) to cultured bacterial species and located BOTRYCO-2 within a phylogenetic lineage consisting of uncultured alphaproteobacterial clones. Fluorescence in situ hybridization (FISH) studies and transmission electric microscopy indicated that BOTRYCO-2 is closely associated with B. braunii colonies. Interestingly, FISH analysis of a water bloom sample also found BOTRYCO-2 bacteria in close association with cyanobacterium Microcystis aeruginosa colonies, suggesting that BOTRYCO-2 relatives have high affinity to phytoplankton colonies. A PCR survey of algal bloom samples revealed that the BOTRYCO-2 lineage is commonly found in Microcystis associated blooms. Growth experiments indicated that B. braunii Ba10 can grow faster and has a higher biomass (1.8-fold) and hydrocarbon (1.5-fold) yield in the presence of BOTRYCO-2. Additionally, BOTRYCO-2 conferred a higher biomass yield to BOT-22, one of the fastest growing strains of B. braunii. We propose the species name 'Candidatus Phycosocius bacilliformis' for BOTRYCO-2.


Use of codeine-containing medicines by Irish psychiatric inpatients before and after regulatory limitations on their supply.
In recent years, concerns have been highlighted in several jurisdictions, including Ireland, regarding abuse of over-the-counter codeine-containing medicines. On the 1st of August 2010, national regulatory guidelines aimed at limiting the supply of these medicines in Ireland came into force. Aims To study the effects of the new regulations on the use of non-prescribed codeine-containing medicines by psychiatric patients admitted to an Irish university teaching hospital before (n = 117) the regulations came into effect and 6 months afterwards (n = 126). Participants completed a brief self-administered survey questionnaire about their use of over-the-counter codeine-containing medicines in the preceding 3 months. Compared with before the introduction of the new regulations, there was a large decline in the reported 'often' or 'regular' use of codeine-containing medicines in the 3 months before admission (33.3% v. 17.4%, χ 2 = 6.354, p = 0.01) and there was a reduction in the proportion of patients for whom others had expressed concerns about their frequency of use of such medications (15.5% v. 4.8%, χ 2 = 7.29, p = 0.03). There was also a decline in the proportion of patients who stated that they would use codeine-containing medicines for either a 'feel-good' effect or to curb cravings (15.9% v. 1.9%, p < 0.01, two-tailed Fisher's exact test). We conclude that tight regulations on the supply of non-prescription codeine-containing medicines have the potential to reduce the use and abuse of such medicines in patient populations availing of admission to psychiatry hospitals.


Computed axial tomography-MIBI image fusion for preoperative localization in primary hyperparathyroidism.
An imaging-guided unilateral surgical approach in patients with primary hyperparathyroidism (HPTH) requires reliable preoperative localization procedures. Using present imaging techniques, 60% to 80% of patients with primary HPTH can be treated successfully with limited surgery. Thus, further improvement of diagnostic accuracy is required. Computed axial tomography (CAT)-MIBI image fusion was introduced as a new technique for localizing enlarged parathyroid glands. We describe the new method and present its first results. Six consecutive patients with primary HPTH underwent CAT-MIBI image fusion for preoperative parathyroid localization. CAT and technetium-99m-sestamibi scan were performed separately. The patient's head and neck were fixed with the noninvasive Vogele-Bale-Hohner Head Holder (VBH HeadFIX; Medical Intelligence, Schwabmünchen, Germany) and the BodyFIX (Medical Intelligence) vacuum cushion. Radiographic and scintigraphic markers were mounted at the head holder and the patient. CAT and MIBI images were fused by overlaying radiographic markers using a commercial software and workstation. In 5 patients, localization and dimension of the solitary adenomas were exactly predicted. In 1 patient with multiglandular disease (3 enlarged glands), CAT-MIBI image fusion was not able to predict multiple gland involvement. However, in a retrospective analysis of the localization study, the other two enlarged parathyroid glands could be correctly identified regarding their site and size. First results of CAT-MIBI image fusion are promising. The new technique provides a higher image resolution and better delimitation of enlarged parathyroid glands and adjacent anatomic structures than conventional scintigraphic methods.


Mental health in F-111 maintenance workers: the study of Health Outcomes in Aircraft Maintenance Personnel (SHOAMP) general health and medical study.
We sought to contrast mood disorder symptoms in F-111 aircraft Deseal/Reseal maintenance personnel with appropriate comparisons. Participants completed a comprehensive health assessment, including measures of mood disorder, self-reported mood symptom questionnaire items, and review of anxiolytic and depression medication. Multiple logistic regression was conducted for each outcome using exposure group and potential confounders as explanatory variables. There was high agreement between self-reported mood disturbance and objective tests. The exposed group was more likely to self-report previous diagnoses of depression/anxiety, had higher use of antidepressant medications, and had increased risk of diagnosis of depression/anxiety. Results were consistently strong against both comparison groups, with the exposed more likely to have mental distress and social dysfunction when compared with the Australian population. There is robust evidence for an association between F-111 Deseal/Reseal exposure and impaired mental health.


The healing potential of the periosteum molecular aspects.
The presence of pluripotential mesenchymal cells in the under surface of the periosteum in combination with growth factors regularly produced or released after injury, provide this unique tissue with an important role in the healing of bone and cartilage. The periosteum contributes in the secondary callus formation with cells and growth factors and should always be preserved and protected when surgery is performed for the management of a fracture. The current evidence about the cellular interactions, the stimulants and the signalling pathways related to osteogenesis and chondrogenesis is described. An essential knowledge of the basics related to the contribution of the periosteum in the healing of fractures, osteotomies, during the process of distraction osteogenesis and in some degree in the repair of cartilagenous defects, provides the surgeons with a better insight to understand the upcoming "biological" interventions in the management of skeletal injuries.


Assessment of Left Atrial Function in Patients with Celiac Disease.
There is some evidence suggesting increased risk of atrial fibrillation (AF) in patients with celiac disease (CD). Impaired left atrial function plays a significant role in the development of AF. This study aimed at assessing the electrical and mechanical functions of the left atrium in patients with CD. A total of 71 patients with biopsy-proven, antibody-positive CD and 52 age-matched healthy controls were included in this prospective study. P-wave dispersion (PWD) was measured to assess the electrical functions of the left atrium through the use of surface electrocardiography. A tissue Doppler echocardiography was performed to determine the atrial conduction and electromechanical delay (EMD) time. To evaluate the mechanical functions of the left atrium, maximum, minimum, and presystolic atrial volumes were estimated to calculate the contractile, conduit, and reservoir functions. In terms of transthoracic echocardiographic parameters, CD and control subjects were not significantly different. However, as compared to controls, patients with CD had significantly increased PWD (median 52 ms [interquartile range 46-58 ms] vs. 38 [36-40], P < 0.001). Also, significantly higher interatrial (49 ms [32-60] vs. 26 ms [22-28], P < 0.001), intra-left atrial (26 ms [17-44] vs. 14 ms [12-18], P < 0.001), and intra-right atrial (15 ms [8-22] vs. 10 ms [8-14], P < 0.001) EMD was found among CD subjects than controls. Despite an increase in the left atrial volume in patients with CD, conduit and reservoir functions were comparable. Although atrial mechanical functions are preserved in patients with CD, a slower electrical conduction was found, suggesting an increased risk of AF in this group of patients.


MicroRNA as a Biomarker in Gastroenterological Cancers.
This Special Issue aims to highlight the usefulness of microRNA (miRNA) as diagnostic and prognostic markers of gastroenterological cancer (GC) [...].


Benign non-traumatic inflammatory strictures of the extrahepatic biliary system.
Obstructive jaundice was the presenting feature in 12 patients with benign, non-traumatic strictures of the extrahepatic bile ducts. Ages at presentation ranged from 1.5 to 60 years and 11 were initially referred with diagnoses of malignant strictures. Histological examination, however, showed benign changes of chronic inflammation, with ulceration in seven, which were distinct from those of primary sclerosing cholangitis. All of the patients remain well from 3 to 14 years after surgery. The aetiology of the strictures is not known.


An assessment of the role of protein kinase and zymogen granule phosphorylation during secretion by the rat exocrine pancreas.
1. The levels of protein kinase activity and zymogen granule phosphorylation were studied in the adult rat during stimulus-coupled secretion in vitro. 2. The specific activity of protein kinase associated with intact zymogen granules was 11 pmol [32P]phosphate transferred to histone per min per mg protein. Most of this activity was recovered in purified granule membranes. 2. The addition of 10(-6) M cyclic AMP to a mixture of zymogen granules and the postmicrosomal supernatant resulted in a 5-fold increase in protein kinase activity associated with zymogen granules. The adsorbed activity was eluted from granules by 0.15 M NaCl. Cyclic GMP did not promote protein kinase binding to isolated granules. 4. Incubation of tissues with carbachol (10(-5) M), pancreozymin (0.1 unit/ml), caerulein (10(-8) M) or dibutyryl cyclic AMP (2.10(-4) M) between 2.5 and 60 min did not increase the levels of protein kinase activity in isolated zymogen granules above control values. 5. Protein phosphorylation of zymogen granule membranes and granule content was not detectable in tissues incubated with carbachol, pancreozymin-C-octapeptide, or caerulein. 6. These results suggest that neither the phosphorylation of zymogen granule membrane protein nor the adsorption of protein kinase activity to zymogen granules is an obligatory step in secretion.


Mitochondrial Dysfunction in Primary Open-Angle Glaucoma Characterized by Flavoprotein Fluorescence at the Optic Nerve Head.
To investigate the presence of flavoprotein fluorescence (FPF) at the optic nerve head (ONH) rim as a marker of mitochondrial dysfunction in primary open-angle glaucoma (POAG) and control eyes. Retrospective cross-sectional study of patients recruited from the New York Eye and Ear Infirmary of Mount Sinai. A total of 86 eyes (50 eyes of 30 patients with POAG and 36 eyes of 20 control participants) were enrolled. The presence of POAG was defined by circumpapillary retinal nerve fiber layer thickness (cpRNFLT) of less than the bottom fifth percentile of the normative database, glaucomatous ONH changes, and visual field defects on 24-2 tests. Primary open-angle glaucoma and control eyes were imaged using the OcuMet Beacon. A 23° × 23° infrared scan was obtained, and an FPF scan was performed within a capture field spanning 13° in diameter. The ONH margins on the infrared image were identified by software algorithms. Then, FPF was measured within an elliptical annulus around the ONH rim, with the inner and outer boundaries corresponding to 0.5 to 1.1 times the ONH rim size. Flavoprotein fluorescence at the OHN rim in POAG and control eyes. Differences in FPF between POAG and control eyes were characterized through mixed-effects logistic regression, adjusted for age and interocular pressure. Flavoprotein fluorescence was significantly higher in POAG versus control eyes, with a mean ± SD of 46.4 ± 27.9 versus 28.0 ± 11.7 (P < 0.001), respectively. Among POAG eyes, FPF showed correlation to visual field mean deviation (P < 0.001), visual field pattern standard deviation (P = 0.003), and cpRNFLT (P = 0.001) on linear mixed-effects models. Higher FPF in POAG versus control eyes suggests the presence of mitochondrial dysfunction at the ONH rim in eyes with glaucomatous damage. The degree of FPF corresponds to disease severity, as measured by visual field and nerve fiber layer thickness metrics. Thus, FPF may represent a metabolic indicator of disease status that reveals the extent of injury in glaucoma.


Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic beta-cells.
Using various biochemical, pharmacological and molecular biological approaches, we have recently reported regulatory roles for Rac1, a small G-protein, in glucose-stimulated insulin secretion (GSIS). However, little is understood with respect to localization of, and regulation by, specific regulatory factors of Rac1 in GSIS. Herein, we investigated regulatory roles for Tiam1, a specific nucleotide exchange factor (GEF) for Rac1, in GSIS in pancreatic beta-cells. Western blot analysis indicated that Tiam1 is predominantly cytosolic in distribution. NSC23766, a specific inhibitor of Tiam1-mediated activation of Rac1, markedly attenuated glucose-induced, but not KCl-induced insulin secretion in INS 832/13 cells and normal rat islets. Further, NSC23766 significantly reduced glucose-induced activation (i.e. GTP-bound form) and membrane association of Rac1 in INS 832/13 cells and rat islets. Moreover, siRNA-mediated knock-down of Tiam1 markedly inhibited glucose-induced membrane trafficking and activation of Rac1 in INS 832/13 cells. Interestingly, however, in contrast to the inhibitory effects of NSC23766, Tiam1 gene depletion potentiated GSIS in these cells; such a potentiation of GSIS was sensitive to extracellular calcium. Together, our studies present the first evidence for a regulatory role for Tiam1/Rac1-sensitive signaling step in GSIS. They also provide evidence for the existence of a potential Rac1/Tiam1-independent, but calcium-sensitive component for GSIS in these cells.


Daytime consumption of triazolam.
Six cases of daytime use of triazolam are reported. In all cases, daytime anxiety following the night-time use of this short-acting, high-potency hypnotic benzodiazepine led to the use of the drug during the day. Tolerance to the hypnotic and anxiolytic effects of the drug developed, as shown by a significant escalation of both the bedtime and daytime doses.


Preparation and evaluation of polycaprolactone/chitosan/Jaft biocompatible nanofibers as a burn wound dressing.
Tissue engineering is an emerging method for replacing damaged tissues. In this study, the potential application of electrospun polycaprolactone/chitosan/ the internal layer of oak fruit (Jaft) as skin scaffolds was investigated. A combination of Polycaprolactone (PCL), chitosan (CH), and the internal layer of oak fruit (Jaft) was used to incorporate mechanical properties of synthetic polymers, biological properties of natural polymers, and antibacterial activity of Jaft. Physical and morphological characteristics of prepared scaffolds were investigated using a scanning electron microscope (SEM), mechanical analysis, swelling ratio, and contact angle. Moreover, chemical and biological properties were evaluated by Fourier-transform infrared spectroscopy (FTIR), chromatography, flow cytometry, DAPI staining, MTT assay, and trypan blue exclusion assay. Obtained results demonstrated that the fabricated scaffolds have good mechanical properties. Moreover, the addition of chitosan and Jaft to the PCL scaffolds improved their water absorption capacity as well as surface hydrophilicity. MTT results showed the fabricated nanofibrous scaffolds have adequate cell viability, which is higher than the cell culture plate at each time point of culture. Furthermore, SEM images of cultured scaffolds, trypan blue exclusion assay, and DAPI staining confirmed that fibroblast cells could be well-attached and proliferate on the PCL/CH/Jaft scaffolds. Results have proven that this novel bioactive scaffold has promising mechanical properties, suitable biocompatibility in vitro, and in vivo. Consequently, it could be a promising candidate for skin tissue engineering applications.


Characteristics of 1-O-hexadecyl- and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine-stimulated granule enzyme release from human neutrophils.
1-O-Hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C16-AGEPC) and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C18-AGEPC) stimulated a time- and concentration-dependent release of granule-associated lysozyme and beta-glucuronidase from human neutrophils. Maximum discharge of granule enzymes occurred between 30 and 60 sec after neutrophil exposure to C16- or C18-AGEPC (0.01-10 microM). Less than 10% of total enzyme activity is released when cells are not preincubated with cytochalasin B prior to interaction with the AGEPC analogs. A time-dependent desensitization for granule exocytosis was observed in neutrophils which were stimulated with C18-AGEPC prior to contact with cytochalasin B. The rate and amount of enzyme released by C16- and C18-AGEPC activated neutrophils was significantly enhanced in the presence of extracellular calcium. Trifluoperazine, an inhibitor of calmodulin, caused a dose-related suppression of C18-AGEPC-induced degranulation. Granule enzyme extrusion from C18-AGEPC-treated neutrophils was inhibited by the sulfhydryl reagents, N-ethylmaleimide and iodoacetic acid, and by the glycolytic inhibitor, 2-deoxy-D-glucose. Sodium cyanide was inactive. Pretreatment of neutrophils with C16- or C18-AGEPC rendered the cells unresponsive to subsequent exposure to either AGEPC analog. C18-AGEPC-induced desensitization of neutrophil degranulation appears to be stimulus specific in that serum-treated zymosan and N-formyl-methionyl-leucyl-phenylalanine were capable of eliciting granule enzyme release from C18-AGEPC-pretreated cells.


Dynamic response of the ROSE damping device.
Methods used in clinical practice to increase the damping of a transducer hydraulically coupled to an intraarterial blood-pressure monitoring system often decrease the undamped natural frequency of the system. This leads to spuriously high systolic and low diastolic pressure readings. The ROSE damping device is being marketed as a possible solution to the problem. We tested the dynamic response of three different catheter systems, with various pressure-tubing lengths of 1 to 7 feet (30.5 to 213.4 cm), with and without the ROSE damping device. The device was able to substantially increase damping and at the same time maintain the undamped natural frequency. Typically it increased the damping coefficient from a minimum of 0.17 +/- 0.01 to a minimum of 0.33 +/- 0.01, while never significantly decreasing the undamped natural frequency. In testing a sample of 25 devices we did observe, however, a wide variability in damping characteristics among different devices. Damping coefficients ranged between 0.19 and 1.20.


Impact of altered venous hemodynamic conditions on the formation of platelet layers in thromboemboli.
Although it is generally believed that the structure of venous thromboemboli is a homogeneous red blood cell-fibrin clot, their structure may be heterogeneous, with non-uniformly distributed platelet layers, known as the lines of Zahn. We tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e. the lines of Zahn, and (b) whether, according to mathematical modeling, eddies can arise in the venous system, possibly contributing to platelet aggregation. The structure of venous thromboemboli ex vivo was determined by high-resolution magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High-resolution ultrasound (US) imaging was employed to determine the popliteal vein geometry and hemodynamics in healthy subjects and in subjects with previous venous thrombosis. The US data were then used as input for numerical simulations of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous thromboemboli were structurally heterogeneous with platelet layers. The peak venous flow velocity was higher in patients with partly recanalized deep vein thrombosis than in healthy subjects in the prone position (46±4cm/s vs. 16±3cm/s). Our numerical simulation showed that partial venous obstruction with stenosis or malfunctioning venous valves creates the conditions for eddy blood flow. Our experimental results and computer simulation confirmed that the heterogeneous structure of venous thromboemboli with twisted platelet layers may be associated with eddy flow at the sites of their formation.


A novel fluorinated erythromycin antibiotic.
A novel fluorinated erythromycin (16-fluoroerythromycin A) has been produced by Saccharopolyspora erythraea ERMD1, using precursor-directed biosynthesis.


Platelet DNA polymerase levels in CML: implications for oncogenesis.
Partially purified platelet DNA polymerase (PDP) was able to synthesize DNA transcripts of platelet polyadenylated RNA. PDP was elevated in the earliest stages of CML and PV. In PV, successful chemotherapy resulted in rapid return of PDP to normal levels while in CML this was not the case. An hypothesis is presented proposing that PDP contributes to oncogenesis by regulating the expression of oncogenes.


Knockdown of the astrocytic glucocorticoid receptor in the central nucleus of the amygdala diminishes conditioned fear expression and anxiety.
The amygdala is a key structure involved in both physiological and behavioural effects of fearful and stressful stimuli. The central stress response is controlled by the activity of the hypothalamic-pituitary-adrenal (HPA) axis via glucocorticoid hormones, acting mainly through glucocorticoid receptors (GR), widely expressed among different brain regions, including the central nucleus of the amygdala (CeA). Although to date, neuronal GR was postulated to be involved in the mediating stress effects, increasing evidence points to the vital role of glial GR. Here, we aimed to evaluate the role of astrocytic GR in CeA in various aspects of the stress response. We used a lentiviral vector to disrupt an astrocytic GR in the CeA of Aldh1l1-Cre transgenic mice. Astrocytic GR knockdown mice (GR KD) exhibited an attenuated expression of fear-related memory in the fear conditioning paradigm. Interestingly, the consolidation of non-stressful memory in the novel object recognition test remained unchanged. Moreover, GR KD group presented reduced anxiety, measured in the open field test. However, knockdown of astrocytic GR in the CeA did not affect an acute response to stress in the tail suspension test. Taken together, obtained results suggest that astrocytic GR in the CeA promotes aversive memory consolidation and some aspects of anxiety behaviour.


Wireless monitoring of reconstructed 12-lead ECG in atrial fibrillation patients enables differential diagnosis of recurrent arrhythmias.
Differential diagnosis of symptomatic events in post-ablation atrial fibrillation (AF) patients (pts) is important; in particular, accurate, reliable detection of AF or atrial flutter (AFL) is essential. However, existing remote monitoring devices usually require attached leads and are not suitable for prolonged monitoring; moreover, most do not provide sufficient information to assess atrial activity, since they generally monitor only 1-3 ECG leads and rely on RR interval variability for AF diagnosis. A new hand-held, wireless, symptom-activated event monitor (CardioBip; CB) does not require attached leads and hence can be conveniently used for extended periods. Moreover, CB provides data that enables remote reconstruction of full 12-lead ECG data including atrial signal information. We hypothesized that these CB features would enable accurate remote differential diagnosis of symptomatic arrhythmias in post-ablation AF pts. 21 pts who underwent catheter ablation for AF were instructed to make a CB transmission (TX) whenever palpitations, lightheadedness, or similar symptoms occurred, and at multiple times daily when asymptomatic, during a 60 day post-ablation time period. CB transmissions (TXs) were analyzed blindly by 2 expert readers, with differences adjudicated by consensus. 7 pts had no symptomatic episodes during the monitoring period. 14 of 21 pts had symptomatic events and made a total of 1699 TX, 164 of which were during symptoms. TX quality was acceptable for rhythm diagnosis and atrial activity in 96%. 118 TX from 10 symptomatic pts showed AF (96 TX from 10 pts) or AFL (22 TX from 3 pts), and 46 TX from 9 pts showed frequent PACs or PVCs. No other arrhythmias were detected. Five pts made symptomatic TX during AF/AFL and also during PACs/PVCs. Use of CB during symptomatic episodes enabled detection and differential diagnosis of symptomatic arrhythmias. The ability of CB to provide accurate reconstruction of 12 L ECGs including atrial activity, combined with its ease of use, makes it suitable for long-term surveillance for recurrent AF in post-ablation patients.


The peptide-catalyzed Maillard reaction: characterization of 13C reductones.
The reaction pathways of amino acids and reducing sugars are now fully understood. The focus in the last few years, however, has turned to the reaction of peptides and proteins with reducing sugars. We have investigated the reaction of gamma-aminobutanoic acid, the heptapeptide Nalpha-Acetyl-Lys-Lys-beta-Ala-Lys-beta-Ala-Lys-Gly, and the model protein beta-casein in Maillard reactions with 1-13C arabinose. Characterization of 13C-labeled acetic acid and norfuraneol by gas chromatography-mass spectrometry and nuclear magnetic resonance revealed new formation pathways. The results demonstrate significant differences in the labeling pattern of the products depending on the amine used, indicating different formation pathways of acetic acid and norfuraneol.


2.3THz radiation: Absence of genotoxicity/mutagenicity in Escherichia coli and Salmonella typhimurium.
The mutagenicity and genotoxicity in bacteria of 2.3THz radiation (THz) produced by a free-electron laser (NovoFEL) were evaluated; exposures were 5, 10, or 15min at average power 1.4W/cm(2). Two Ames mutagenicity test strains of Salmonella typhimurium, TA98 and TA102, were used. For the genotoxicity test, we measured SOS induction in Escherichia coli PQ37. No significant differences were found between exposed and control cells, indicating that THz radiation is neither mutagenic nor genotoxic under these conditions. Nevertheless, a small increase in total cell number of S. typhimurium after 15min exposure, and an increase in β-galactosidase and alkaline phosphatase activities in E.coli PQ37, were observed, indicating some effect of THz radiation on cell metabolism. We also examined the combined effect of 4-NQO (8μM; positive control) and THz exposure (5min) on genotoxicity in E.coli PQ37. Unexpectedly, THz radiation decreased 4-NQO genotoxicity.


The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.
To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone. Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated. The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings. Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.


Microbial fuel cell powered by lipid extracted algae: A promising system for algal lipids and power generation.
In this study, a promising microbial fuel cell (MFC) system has been developed, wherein algae is cultivated in the cathode chamber, algae biomass is harvested and lipids are extracted. The lipid extracted algal (LEA) biomass was then used asan electron donor substrate. The performance of MFCs fed with LEA biomass was compared with that of fruit waste fed MFCs (FP-MFCs), wherein LEA-fed MFC was superior in all aspects. Power density of 2.7Wm-3 was obtained by LEA-fed MFCs which is 145% and 260% higher than FP MFC and control MFC respectively. The volumetric algae productivity of 0.028kgm-3day-1 in cathode chamber was achieved. The system was able to generate 0.0136kWhKg-1CODday-1 of electric energy and 0.0782kWhm-3day-1 of algal oil energy. The proposed system is a net energy producer which does not rely heavily on the external supply of electron donor substrates.


Synthesis and characterization of amidate bridged dimeric and oligomeric platinum complexes having short platinum-platinum interactions.
A number of pivalamidate bridged dinuclear [PtII2(RNH2)4(NHCOtBu)2]2+, [PtIII2LL (RNH2)4(NHCOtBu)2]n+ (2RNH2 = 2NH3, 1,2-ethylenediamine, 1,2-diaminocyclohexane; L, L' = NO3-, H2O, or ketonate), trinuclear [{PtII(dap)(NHCOtBu)2}2PdIII]3+ (dap = 1,2-diaminopropane), tetranuclear [{PtII2(NH3)2(DACH)(NHCOtBu)2}2]4+ (DACH = 1,2-diaminocyclohexane), pentanuclear [{Pt2(C5H7O)(NH3)2Cl2(NHCOtBu)2}2PtCl4], and hexanuclear [Pt2(NH3)2(en)(NHCOtBu)2Pt(NO2)4]2 platinum complexes containing Pt(II)-Pt(II), Pt(II)-Pt(III), Pt(II)-Pd(III), and Pt(III)-Pt(III) interactions have been prepared and structurally characterized. The Pt-Pt interactions are characteristic of covalent, dative, or orbital symmetric Pt-Pt bonds. The dimeric Pt(III) complexes are able to activate C-H bonds of ketones to afford ketonate platinum(III) complexes. The Pt-Pt bonds are either doubly amidate-bridged or ligand unsupported. Their distances are 2.99-3.22 A for Pt(II)-Pt(II), 2.59-2.72 A for Pt(III)-Pt(III), 2.98 A for Pt(II)-Pt(III), and 2.66 A for Pt(II)-Pd(III) bonds depending on the oxidation states of the two metals and the ancillary ligands.


Prevalence of occult nodal metastases in squamous cell carcinoma of the temporal bone: a systematic review and meta-analysis.
Primary: To determine the rate of occult cervical metastases in primary temporal bone squamous cell carcinomas (TBSSC). Secondary: to perform a subgroup meta-analysis of the risk of occult metastases based on the clinical stage of the tumour and its risk based on corresponding levels of the neck. A systematic review and meta-analysis of papers searched through Medline, Cochrane, Embase, Scopus and Web of Science up to November 2021 to determine the pooled rate of occult lymph node/parotid metastases. Quality assessment of the included studies was assessed through the Newcastle-Ottawa scale. Overall, 13 out of 3301 screened studies met the inclusion criteria, for a total of 1120 patients of which 550 had TBSCC. Out of the 267 patients who underwent a neck dissection, 33 had positive lymph nodes giving a pooled rate of occult metastases of 14% (95% CI 10-19%). Occult metastases rate varied according to Modified Pittsburg staging system, being 0% (0-16%) among 12 pT1, 7% (2-20%) among 43 pT2 cases, 21% (11-38%) among 45 pT3, and 18% (11-27%) among 102 pT4 cases. Data available showed that most of the positive nodes were in Level II. The rate of occult cervical metastases in TBSCC increases with pathological T category with majority of nodal disease found in level II of the neck.


In-hospital mortality among patients injured in motor vehicle crashes in a Saudi Arabian hospital relative to large U.S. trauma centers.
Traffic-related fatalities are a leading cause of premature death worldwide. According to the 2012 report the Global Burden of Disease 2010, traffic injuries ranked 8th as a cause of death in 2010, compared to 10th in 1990. Saudi Arabia is estimated to have an overall traffic fatality rate more than double that of the U.S., but it is unknown whether mortality differences also exist for injured patients seeking medical care. We aim to compare in-hospital mortality between Saudi Arabia and the United States, adjusting for severity and demographic variables. The analysis included 485,611 patients from the U.S. National Trauma Data Bank (NTDB) and 5,290 patients from a trauma registry at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. For comparability, we restricted our sample to NTDB data from level-I public trauma centers (≥400 beds) in the U.S. Multiple logistic regression analyses were performed to evaluate the effect of setting (KAMC vs. NTDB) on in-hospital mortality after adjusting for age, sex, Triage-Revised Scale (T-RTS), Injury Severity Score (ISS), mechanism of injury, hypotension, surgery and head injuries. Interactions between setting and ISS, and predictors were also evaluated. Injured patients in the Saudi registry were more likely to be males, and younger than those from the NTDB. Patients at the Saudi hospital were at higher risk of in-hospital death than their U.S. counterparts. In the highest severity group (ISSs, 25-75), the odds ratio of in-hospital death in KAMC versus NTDB was 5.0 (95% CI 4.3-5.8). There were no differences in mortality between KAMC and NTDB among patients from lower ISS groups (ISSs, 1-8, 9-15, and 16-24). Patients who are severely injured following traffic crash injuries in Saudi Arabia are significantly more likely to die in the hospital than comparable patients admitted to large U.S. trauma centers. Further research is needed to identify reasons for this disparity and strategies for improving the care of patients severely injured in traffic crashes in Saudi Arabia.


Effect of NKISK on tendon lengthening: an in vivo model for various clinically applicable dosing regimens.
One proposed mechanism of tendon lengthening is the "sliding fibril" hypothesis, in which tendons lengthen through the sliding of discontinuous fibrils after release of decorin-fibronectin interfibrillar bonds. The pentapeptide NKISK has been reported to inhibit the binding of decorin, a proteoglycan on the surface of collagen fibrils, to fibronectin, a tissue adhesion molecule, which are thought to play a role in interfibrillar binding. Prior investigations have demonstrated that NKISK produces in vivo tendon lengthening. This study investigates the effect of potential clinically applicable NKISK injection regimens in an in vivo model. One hundred and thirteen male Sprague-Dawley rats were divided into 15 different treatment groups, each receiving percutaneous patellar tendon injections of NKISK, QKTSK (a "nonsense" pentapeptide), or PBS of varying volumes, concentrations, and injection schedules. Following sacrifice, the patellar tendon lengths were measured in all groups, and biomechanical testing was performed with comparisons made to the contralateral, untreated control limbs. Tendon lengthening was significantly greater (p < or = 0.05) in nearly all NKISK-treated tendons as compared to PBS- and QKTSK-treated tendons and was dose-dependent. Measured lengthening was less in rats whose sacrifice was delayed following the final injection of NKISK, which likely indicates recontraction of lengthened tendons, but they remained significantly longer than the controls. Biomechanical testing did not reveal significant differences in ultimate load, modulus, stiffness, or displacement. This study demonstrates that NKISK given in clinically plausible dosing regimens produces dose-dependent tendon lengthening in an in vivo setting with minimal effects on the mechanical properties of the treated tendons.


Competitive nucleosome reconstitution of polydeoxynucleotides containing oligoguanosine tracts.
The ability of synthetic polydeoxynucleotides composed of oligoguanosine tracts of increasing length to form nucleosomes has been determined by several reconstitution procedures. When the presence of nucleosomes is determined by resistance to nuclease digestion, a protected band of approximately 150 base-pairs is detected only with difficulty for polymers containing long tracts of contiguous guanosines. However, when assayed by a shift in the electrophoretic mobility of radiolabeled polymers exchanged at 0.7 M-NaCl with authentic nucleosomes, all polymers tested are seen to form nucleosomes. Quantitative competitive reconstitution shows that the length of the tracts per se does not adversely affect their propensity to form nucleosomes, since even 150 base-pair poly(dG).poly(dC) forms nucleosomes as well as heterogeneous-sequence DNA. However, the ability to form nucleosomes does depend on the length of the polymer repeating unit.


Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide.
Schnitzler's syndrome is a rare clinical condition characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and monoclonal immunoglobulin M (IgM) gammopathy. Here we describe the case of a 48-year-old Italian female with a long history of arthralgia, leucocytosis, spiking fever, and chronic urticaria with severe pruritus. The IgM-kappa monoclonal component in the serum and bone densification on conventional X-ray with hyperfixation on bone technetium scanning at the distal part of the femurs and at the proximal part of the tibias were detected 4 years after the onset of the symptoms. After many ineffective treatments, the use of pulse cyclophosphamide (CPX) resulted in complete remission of the disease that is still lasting after a 2-year follow-up.


Prevalence of Mycobacterium avium subspecies paratuberculosis (MAP) infection in suspected diarrhoeic buffaloes and cattle reporting at Veterinary University in India.
Murrah buffaloes, best breed for milk production are native of Haryana state. They contributes significantly to the farmer's income, livelihood and food (milk and meat) security, in the semi-tropical regions of North India. Johne's disease though endemic in the domestic livestock of the country, but reports are not available in the buffaloes suffering from morbidity due to progressive weakness and diarrhoea. We estimated the status of JD in diarrhoeic buffaloes and cattle reporting at Veterinary Clinical Complex of Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana, India, using conventional, serological and PCR assays.141 buffaloes suffering from chronic diarrhoea were screened to estimate sero-prevalence of MAP and 50.0 % young and 53.52 % adult animals were positive. Of 14 cattle screened, none of the young and 66.6 % adult cows were positive. In buffaloes, 66.1 and 6.77 %, fecal samples were positive in microscopy and IS900 PCR, respectively. Sero-prevalence of JD was very high in diarrhoeic buffaloes and cattle from Haryana state of India.Buffaloes positive for Mycobacterium avium subspecies paratuberculosis (MAP) infection had reduced total leukocyte count and lymphocytes.


Antifungal, antiradical and cytotoxic activities of extractives obtained from Tagetes patula L. (Asteraceae), a potential acaricide plant species.
Tagetes patula L. shows a complex chemical composition, ranging from glycosylated flavonoids and thiophenes in extracts until terpenoids in the essential oil. In the present study, due to this rich flavonoidic constitution, its antioxidant potential was determined, having shown values of antiradical percentage superior to reference compounds, mainly the extracts prepared with flowers. Previous studies performed emphasized the acaricide potential of T. patula and thus, the present study aimed to verify the action of extractives obtained from aerial parts on growth of entomopathogenic fungi related to biological control of brown dog tick Rhipicephalus sanguineus and the action against pathogenic fungi closely associated with pets. None of the samples inhibited the growth of strains of Beauveria bassiana or Metarhizium anisopliae, enabling feasible future studies of synergism on acaricide activity of formulations containing fungi and extracts. The antimicrobial activity of ethanolic extract of flowers (FlEtOH70%) against Microsporum canis and Trichophyton rubrum was significant (193.3 μg/mL and 253.9 μg/mL, respectively), as well as ethanolic extract from aerial parts (APEtOH70%) against T. rubrum (312.5 μg/mL). In order to ensure the safety of a topical formulation containing the extractives of T. patula, the cytotoxic potential of these samples were tested in murine macrophages cells. At higher concentrations all extracts were quite lethal, with IC50 ranging from 210.96 μg/mL to 468.75 μg/mL for APEtOH70% and FlEtOH70%, respectively. These results suggest that the application of a product containing T. patula extractives in the control of ticks could be used, at principle, only on the environment.


The influence of the conventional microflora on the body temperature of the chick.
1. Deep body temperature was measured daily in germ-free and conventional chicks from 1 to 16 of age. 2. The temperature of germ-free chicks rose rapidly during the first 4 d and thereafter only slowly, whereas that of conventional birds increased gradually throughout. 3. Body temperature attained by the germ-free birds was about 0.3 degrees C higher than that of conventional birds.


Comparison of complications secondary to cardiopulmonary resuscitation between out-of-hospital cardiac arrest and in-hospital cardiac arrest.
The aim of this study was to assess whether there was a significant difference in the complications of cardiopulmonary resuscitation (CPR) between out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) survivors using multidetector computed tomography (MDCT). We performed a retrospective analysis of prospective registry data. We enrolled both OHCA and IHCA patients who underwent successful CPR. We classified chest injuries secondary to chest compression into rib fractures, sternum fractures, and uncommon complications such as lung contusions and extrathoracic complications. We compared these complications according to CPR locations. We also analysed risk factors for CPR complications using multiple regression analysis and classification and regression tree analysis. During the study period, a total of 148 patients were included in the primary analysis. Rib fractures were detected more in OHCA survivors than in IHCA survivors (74 patients (83.2%) vs. 37 patients (62.7%), p=0.05), and frequency of multiple rib fractures was higher in OHCA survivors than IHCA survivors (69 patients (77.5%) vs. 34 patients (57.6%), p=0.01). Although other complications were not significantly different between the groups, there was a trend for OHCA survivors to sustain more serious and direct high-energy related complications. Older age, longer CPR, and OHCA were significantly associated with incidence of rib fractures, multiple rib fractures, and number of rib fractures. Rib fractures were more likely to occur in OHCA survivors, and serious complications tended to occur more often in OHCA compared to IHCA survivors.


Psychiatric screening for patients with faecal incontinence or chronic constipation referred for surgical treatment.
Fifty patients attending for surgical treatment of chronic constipation (n = 21) or faecal incontinence (n = 29) were studied using two psychiatric screening tests: the Hospital Anxiety and Depression (HAD) scale and the General Health Questionnaire (GHQ). Each patient was assessed preoperatively and 6-12 months postoperatively. Results were compared with age and sex-matched controls (n = 50). Constipated patients had significantly higher HAD depression scores compared with controls (median and range): 6 (2-12) versus 4 (0-8), P less than 0.05. Constipated patients who were improved by operation (n = 13) had significantly lower preoperative HAD anxiety scores compared with those who were not improved (n = 8): 8 (3-14) versus 15 (10-19), P less than 0.01; they also had significantly lower HAD depression scores: 4 (2-12) versus 7 (5-11), P less than 0.05. Using these parameters incontinent patients did not differ from controls, but patients who had a bad result after operation (n = 15) had significantly higher HAD anxiety scores than those who obtained clinical benefit (n = 14): 10 (2-15) versus 6 (2-12), P less than 0.05; HAD depression scores were also greater: 5 (2-15) versus 3 (0-9), P less than 0.05; and GHQ scores were greater: 12 (0-47) versus 4 (0-41), P less than 0.05.


Confirmatory factor analysis of the Cornell scale for depression in dementia among patient with dementia of various degrees.
Depression in dementia is difficult to diagnose. The psychometric qualities of the Cornell scale for depression in dementia and whether depression varies depending on the dementia severity are still controversial. Cross-sectional study of memory clinic and nursing-home patients. A sample of 1682 patients (750 from memory clinics and 932 from nursing homes) with Clinical dementia rating scale score of one or higher was evaluated with the Cornell scale. The sample was randomly divided into two groups. Exploratory factor analysis was performed on one-half of the patients and confirmatory factor analysis on the other half. It was further analysed whether the scores of the sub-scales differed across CDR score. A five-factor solution fitted the data best according to both the exploratory and confirmatory factor analysis: 'mood', 'physical', 'cyclic', 'retardation' and 'behaviour'. Further, it was found that the sum score of the Cornell scale differs significantly across dementia severity (p=0.018). The mood and the cyclic sub-scales scores did not vary across dementia severity, unlike the three remaining sub-scales scores. A five-factor solution of the Cornell scale best fitted the data according to both exploratory and confirmatory factor analysis. The mood and cyclic factors' scores did not vary across dementia severity, and this might suggest that they are the core symptoms of depression that are equally present regardless of dementia severity. The other factors scores were higher in severe dementia, which might suggest that these factors are related to the dementia.


Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1.
Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galectin-1, we show that galectin-1 induces a tumor-associated macrophage phenotype with increased expression of key immune checkpoint protein programmed cell death 1 ligand 1 (PD-L1/CD274) and immunomodulator indoleamine 2,3-dioxygenase-1 (IDO1). Galectin-1 induced IDO1 and its active metabolite kynurenine in a dose-dependent manner through JAK/STAT signaling. In a 3D organotypic tissue model system equipped with genetically engineered tumorigenic epithelial cells, we analyzed the cellular source of galectin-1 in the extracellular matrix and found that galectin-1 is derived from epithelial and stromal cells. Our results highlight the potential of targeting galectin-1 in immunotherapeutic treatment of human cancers.


Ostreopsis sp., a possible origin of palytoxin (PTX) in parrotfish Scarus ovifrons.
A clone of toxic dinoflagellate Ostreopsis sp. and six specimens of a parrotfish Scarus ovifrons were collected in October 1997 at Tokushima Prefecture, Japan. Ostreopsis sp. was cultured in ESM medium for 16 days, and after rearing the cell pellet (about 4.0x10(5) cells) was extracted with 50% methanol, partitioned between an aqueous layer and 1-butanol layer, and biochemically tested. Similarly, the crude toxin from S. ovifrons was extracted, and tested. The mice injected with each 1-butanol layer from Ostreopsis sp. and S. ovifrons showed the common symptoms of convulsion, drowsiness and collapse, and died within 48 h. The lethal potency of Ostreopsis sp. was calculated to be 1.0x10(-4) MU/cell. All specimens of S. ovifrons were found to be toxic, where the highest potency was determined as 2 MU/g in muscle of one specimen. After being injected with toxins, the serum creatine phosphokinase levels of mice were found to be elevated. Toxins from Ostreopsis sp. and S. ovifrons showed delayed haemolytic activity with mouse and human erythrocytes, which was inhibited by an anti-palytoxin (PTX) antibody antibody and ouabain. Toxins from Ostreopsis sp. and S. ovifrons thus resembled each other, and strongly suggested to be PTX or its akin substance. Additionally, a considerable number of adherent Ostreopsis sp. was found in the gut contents of S. ovifrons during the heavy occurrence of Ostreopsis sp. in October 1997 at Tokushima Prefecture. From the above results, it can be strongly postulated that the dinoflagellate Ostreopsis sp. is the origin of PTX which is sequestered by the parrotfish S. ovifrons through food chain.


Introducing a land use-based weight factor in regional health risk assessment of PAHs in soils of an urban agglomeration.
The high heterogeneity of land uses in urban areas has led to large spatial variations in the contents and health risks of polycyclic aromatic hydrocarbons (PAHs) in soils. A land use-based health risk assessment (LUHR) model was proposed for soil pollution on a regional scale by introducing a land use-based weight factor, which considered the differences in exposure levels of soil pollutants to receptor populations between land uses. The model was applied to assess the health risk posed by soil PAHs in the rapidly industrializing urban agglomeration of Changsha-Zhuzhou-Xiangtan Urban Agglomeration (CZTUA). The mean concentration of total PAHs (∑PAHs) in CZTUA was 493.2 μg/kg, and their spatial distribution was consistent with emissions from industry and vehicles. The LUHR model suggested the 90th percentile health risk value was 4.63 × 10-7, which was 4.13 and 1.08 times higher than those of traditional risk assessments that have adopted adults and children as default risk receptors, respectively. The risk maps of LUHRs showed that the ratios of the area exceeding the risk threshold (1 × 10-6) to the total area were 34.0 %, 5.0 %, 3.8 %, 2.1 %, and 0.2 % in the industrial area, urban green space, roadside, farmland, and forestland, respectively. The LUHR model back-calculated the soil critical values (SCVs) for ∑PAHs under different land uses, resulting in values of 6719, 4566, 3224, and 2750 μg/kg for forestland, farmland, urban green space, and roadside, respectively. Compared with the traditional health risk assessment models, this LUHR model identified high-risk areas and drew risk contours more accurately and precisely by considering both the spatial variances of soil pollution and their exposure levels to different risk receptors. This provides an advanced approach to assessing the health risks of soil pollution on a regional scale.


Effects of experimental calcium availability and anthropogenic metal pollution on eggshell characteristics and yolk carotenoid and vitamin levels in two passerine birds.
The maternal investment into egg quality depends on the condition of the female, the quality of the mate, and the quality of the environment. In that sense, availability of nutrients and exposure to pollutants are essential parameters to consider. The main aim of this study is to assess the effects of calcium (Ca) availability and anthropogenic metal pollution on early-stage reproduction in two passerine species, great tits (Parus major) and pied flycatchers (Ficedula hypoleuca), inhabiting a Ca-poor and metal-polluted area in SW Finland. Both species were able to obtain sufficient Ca for eggshell formation, and metal pollution was below the level of having negative effects in the egg size and eggshell characteristics. However, metal polluted environment negatively affected yolk lutein and vitamin D3 levels in both species, probably because of a lower access to carotenoid-rich diet and higher metal interference with vitamin D3 metabolism. The higher levels of vitamin D3 in yolks in the unpolluted zone could also be due to upregulated D3 levels as a response to the lower natural Ca availability. Yolk carotenoids and vitamin D3 were positively associated with nestling growth and size, supporting their importance for the appropriate chick development. The interspecific differences in yolk nutrient concentrations possibly reflect the different growth rate of these species. Pied flycatchers are likely adapted to low Ca availability through an efficient vitamin D3 metabolism, but their Ca intake could be close to a deficient level.


Lectin cytochemical characterization of the N- and O-linked oligosaccharides in the human rectum.
The oligosaccharides of the mucus glycoproteins of the human rectum are important for the lubricant and protective role suggested for the rectal mucus. Changes in oligosaccharide composition are observed in several colon diseases, and some of these changes could be used as diagnostic and prognostic indicators. Thus, a previous knowledge of the normal mucus glycoproteins is necessary. The aim of the present study is the characterization of the oligosaccharides of the goblet cells and enterocytes of the human rectum. For this, a battery of 15 lectins, in combination with chemical and enzymatic deglycosylation procedures, was used. Our results suggest the presence of N-acetylglucosamine (GlcNAc), Man, Glc, N-acetylneuraminic acid (Neu5Ac)(alpha2-6)- and Neu5Ac(alpha2-3)-linked, N-acetylgalactosamine (GalNAc) and Gal(beta1-3)GalNAc in the oligosaccharides of the goblet cells. Moreover, N-linked oligosaccharides specifically contained Gal(beta1-4)GlcNAc, while AAA-positive Fuc was only detected in O-linked oligosaccharides. Some of these carbohydrates were only visualized after removal of N- or O-linked oligosaccharides, suggesting a high level of approximation between the oligosaccharide chains, that render the carbohydrate inaccessible to the lectins. Differences in the labelling pattern between the goblet cells of the surface epithelium and the upper half of the crypts, and those of the lower half of the crypts suggests a maturation process for the goblet cells, which modifies the oligosaccharide composition of the secreted glycoproteins, as they ascend throughout the crypts. This maturation process includes the incorporation of new carbohydrates (GlcNAc), and the masking (Neu5Ac(alpha2-3)-linked) or unmasking (Glc and GalNAc) of others.


Immunohistochemical localization of Trk receptor protein in pediatric small round blue cell tumors.
Expression of Trk protein has been documented by Northern analysis in neuroblastomas with good prognosis. To localize the expression of this protein at the cellular level within individual tumors, we adapted a recently characterized pan-Trk antibody for use in formalin fixed, paraffin-embedded tissue. We have examined a group of small round blue cell tumors occurring in children, including both high and low stage neuroblastomas, to assess the presence or absence of Trk expression and its cellular localization. Positive staining for Trk protein was observed in four of four low stage (good prognosis) neuroblastomas, five of five primitive neuroectodermal tumors/Ewing's sarcoma, five of five rhabdomyosarcomas, and no lymphomas. Within the neuroblastomas, expression of Trk protein was most striking in ganglion cells, in which positive cytoplasmic staining was demonstrated regardless of tumor stage. The latter observation may lend further insight into the pathobiology of this malignant childhood tumor.


Hypothalamic-pituitary-testicular function in 70 patients with myotonic dystrophy.
Hypothalamic-pituitary-testicular function was studied in 70 patients with myotonic dystrophy (MD). The diagnosis was confirmed by electromyography. The mean age of the patients was 36.2 +/- 13.2 yr and the duration of the disease was 11.17 +/- 8.01 yr. Testicular atrophy (testes less than or equal to 12 ml on a Prader orchidometer) was present in 65.5% of patients. Fertility among married patients was 66.6%. Mean testosterone plasma levels were 438 +/- 298 ng/dl vs 520 +/- 185 ng/dl in the control group (P = NS). Basal plasma FSH and LH levels, and their response after the administration of 100 mcg of LH-RH were significantly increased although a wide dispersion was observed. Sperm count was carried out in 27 cases, showing a normal count in 7, oligospermia in 12, and azoospermia in 8 patients. Testicular biopsy was performed in 45 patients being normal in 2, showing mild testicular damage in 8, moderate in 14, and severe in 18; it was nule in 3 of them. A significant relationship between testicular atrophy and the sperm count (p less than 0.01), testicular damage and testicular atrophy (p less than 0.025), and sperm count and testicular damage (p = 0.017) was found. Basal plasma FSH and LH level were significantly related to the degree of damage in the testicular biopsy. All these findings indicate a primary testicular pathology, prevailing tubular over interstitial damage. We have not found any association between the duration of the disease and gonadal dysfunction.


Randomized clinical trial of intrapartum clindamycin cream for reduction of group B streptococcal maternal and neonatal colonization.
In a randomized trial, we sought to determine whether 2% clindamycin cream administered intravaginally during labor to group B streptococcal-colonized pregnant women without risk factors would decrease maternal and neonatal colonization. The eligible women were randomized to receive either cream or no treatment. Two hours after treatment or admission, the patients were tested with rectal and vaginal cultures. The neonates of the study patients were also tested. Of women randomized to cream, 5 of 5 remained positive and 2 (33%) of their 6 neonates were positive. Of 4 randomized to no treatment, 3 (75%) remained positive and 1 (25%) of 4 neonates was positive. Intravaginal 2% clindamycin cream was ineffective in reducing colonization with group B streptococci.


Combined treatment of impacted ureteral stones: Holmium laser and pneumatic ballistic.
The treatment of impacted stones remains a challenging issue for urologists, and is usually treated clinically by a single surgical procedure. In this paper, we report a case of combined holmium laser and pneumatic ballistics for the treatment of an impacted ureteral stone. The postoperative examination showed that the stone was cleared and no complications occurred.


Radiation therapy of pancreatic cancers.
We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of pancreatic tumors. Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In the adjuvant setting, the standard treatment is six months of chemotherapy with 5-fluorouracile, irinotecan and oxaliplatin. Chemoradiation may improve the survival of patients with incompletely resected tumours (R1). This remains to be confirmed by a prospective trial. Neoadjuvant chemoradiation is a promising treatment especially for patients with borderline resectable tumours. For patients with locally advanced tumours, there is no standard. An induction chemotherapy followed by chemoradiation for non progressive patients reduces the rate of local relapse. Whereas in the first trials of chemoradiation large fields were used, the treated volumes have been reduced to improve tolerance. Tumour movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique has poor evidence-based recommendation. Stereotactic body radiation therapy is also being studied, as a neoadjuvant or exclusive treatment.


Multiple myeloma treated with high dose intravenous melphalan.
High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).


Balloon dilation of the eustachian tube in a cadaver model: technical considerations, learning curve, and potential barriers.
The surgical management options for eustachian tube dysfunction have historically been limited. The goal of the current study was to evaluate the technical considerations, learning curve, and potential barriers for balloon dilation of the eustachian tube (BDET) as an alternative treatment modality. Prospective preclinical trial of BDET in a cadaver model. A novel balloon catheter device was used for eustachian tube dilation. Twenty-four BDET procedures were performed by three independent rhinologists with no prior experience with the procedure (eight procedures per surgeon). The duration and number of attempts of the individual steps and overall procedure were recorded. Endoscopic examination of the eustachian tube was performed after each procedure, and the surgeon was asked to rate the subjective difficulty on a five-point scale. Successful completion of the procedure occurred in each case. The overall mean duration of the procedure was 284 seconds, and a mean number of 1.15 attempts were necessary to perform the individual steps. The mean subjective procedure difficulty was noted as somewhat easy. Statistically shorter duration and subjectively easier procedure were noted in the second compared to the first half of the series, indicating a favorable learning curve. Linear fissuring within the eustachian tube lumen without submucosal disruption (nine procedures, 37%) and with submucosal disruption (five procedures, 21%) were noted. The significance of these physical findings is unclear. Preclinical testing of BDET is associated with favorable duration, learning curve, and overall ease of completion. Clinical trials are necessary to evaluate safety and efficacy.


Effectiveness of two distraction strategies in reducing preoperative anxiety in children in China: A randomized controlled trial.
Music and animation are the most common and affordable distraction strategies to reduce preoperative anxiety in children; however, their effects are inconsistent. This study aimed to examine the effectiveness of two distraction strategies (music or animation) in reducing preoperative anxiety in children. In this randomized controlled trial, 183 children who underwent surgery were divided into music, animation, and control groups using a single-blind block randomized design. Children in the control group underwent routine preoperative visits. Meanwhile, the children in the intervention groups could choose their favorite music and cartoons as intervention content. Study outcomes included anxiety levels, degree of cooperation, heart rate, and blood pressure. Data were collected before entering the operating room, entering the operating room, and before the induction of anesthesia; only the degree of cooperation was collected before the induction of anesthesia. Only animation significantly reduced preoperative anxiety in the children (P < 0.05) upon entering the operating room. Both music and animation reduced the level of preoperative anxiety before induction of anesthesia; however, there was no significant difference between them (P > 0.05). The induction compliance score was significantly lower in the music and animation groups than in the control group (P < 0.05). Heart rates differed significantly between the three groups from before entering the operating room to before induction of anesthesia. Children in the control group had the highest systolic blood pressure upon entering the operating room (P < 0.05). Music and animation strategies can significantly reduce preoperative anxiety in children and improve surgical cooperation during anesthesia induction. Clinical. gov NCT05285995.


Calculations predict rapid tunneling by carbon from the vibrational ground state in the ring opening of cyclopropylcarbinyl radical at cryogenic temperatures.
B3LYP/6-31G(d) calculations have been performed on the ring opening of cyclopropylcarbinyl radical 1 to 3-buten-1-yl radical 2. The dynamics of the reaction have been computed with canonical variational transition state theory (CVT), both with and without inclusion of small-curvature tunneling (SCT). The CVT + SCT calculations predict that 1 should undergo rapid and temperature-independent ring opening to 2 at cryogenic temperatures, by tunneling from the lowest vibrational level of 1.


Chromatographic Techniques for Assessment of Bisoprolol Fumarate and Perindopril Arginine in Solid Formulations under Various Stress Conditions and Application to Six Sigma, Content Uniformity, and Comparative Dissolution Approaches.
Antihypertensives bisoprolol fumarate (BIS) and perindopril arginine (PER) were simultaneously determined in their pure, bulk, and combined tablet dosage form. This study develops a novel, reproducible, and accurate Reversed phase high-performance liquid chromatography (RP-HPLC) and Reversed phase ultra-performance liquid chromatography (RP-UPLC) with photodiode array detection techniques, which were then applied to in vitro dissolution studies. The first RP-HPLC method relied on isocratic elution using a mobile phase of methanol-0.05 M phosphate buffer pH 2.6 (1 + 1, by volume), and separation was performed using a Thermo Hypersil C8 column (150 mm × 4.6 mm, 5 μm). Ion-pair UPLC was the second method. An acceptable resolution was achieved using an RP-C18 chromatographic column, Agilent Eclipse (100 × 2.1 mm, 1.7 μm), with a mobile phase containing 0.005 M sodium 1-heptane sulfonate-triethylamine (64 + 1 + 35, by volume), adjusted with phosphoric acid to a pH of 2.0. RP-HPLC used a 1.0 mL/min flow rate, while UPLC used 0.5 mL/min, and the two methods used detection at 210 nm. Calibration curves of BIS and PER were linear for RP-HPLC and RP-UPLC methods at 0.5-15 and 0.5-40 μg/mL, respectively. BIS and PER had RP-UPLC LODs of 0.22 and 0.10 μg/mL, respectively, and LOQs of 0.68 and 0.31 μg/mL, respectively. As a result, the approach has been effectively applied to in vitro dissolution testing for drugs in generic and reference products, showing that the two products are comparable. The Six Sigma approach was implemented to compare the recommended and United States Pharmacopeia (USP) procedures, which both exhibited process capability index (Cpk) >1.33. A content uniformity test demonstrated that the drugs in their dosage form met the acceptance limit (85-115%). The degradation products were reliably distinguished from pure drugs for a range of retention times. In their commercial drug product, the proposed method could be used in QC laboratories for concurrent testing, content uniformity, and in vitro dissolution investigations of BIS and PER. The methods were successfully validated per International Council for Harmonisation (ICH) guidelines. This study is innovative since it is the first to establish and validate specific and reproducible UPLC and HPLC methods for the concurrent quantitation of the studied drugs in their binary mixture and application to lean Six Sigma, content uniformity, and comparative dissolution approaches.


Morphological evidence for synaptic junctions between substance P-containing neurons in the arcuate nucleus of the rat.
The presence of synaptic junctions between substance P-containing neurons (SP neurons) was shown in the hypothalamic arcuate nucleus of rats by pre-embedding electron microscopic immunohistochemistry. The immunoreactive perikarya were synapsed by immunoreactive fiber terminals as well as immunonegative fiber terminals. The functional implication of the synapses between SP neurons is discussed in relation to autoregulatory mechanisms of the neurons.


Determination of shelf heat transfer coefficients along the shelf flow path of a freeze dryer using the shelf fluid temperature perturbation approach.
The spatial distribution of local shelf heat transfer coefficients, Ks, was determined by mapping the transient temperature response of the shelf surface along the serpentine internal channels of the shelf while the temperature of the heat transfer fluid was ramped from -40 degrees to 40 degrees C. The solution of a first-order non-steady-state differential equation resulted in a predicted shelf surface temperature as a function of the shelf fluid temperature at any point along the flow path. During the study, the shelf surfaces were maintained under a thermally insulated condition so that the heat transfers by gas conduction and radiation were negligible. To minimize heat conduction by gas, the chamber was evacuated to a low pressure, such as 100 mTorr. To minimize heat transfers between shelves, shelves were moved close together, with a gap of approximately 3 mm between any two shelves, because the shelf surface temperatures at corresponding vertical locations of two shelves are virtually equal. In addition, this also provides a shielding from radiation heat transfer from shelf to walls. Local heat transfer coefficients at the probed locations h(x) ( approximately Ks) were calculated by fitting the experimental shelf temperature response to the theoretical value. While the resulting values of K(s) are in general agreement with previously reported values, the values of Ks close to the inlet are significantly higher than those of other locations of the shelf channel. This observation is most likely attributed to the variation of the flow pattern of heat transfer fluid within the channels.


Osteoarthritis: A problematic disease in past human populations. A dependence between entheseal changes, body size, age, sex, and osteoarthritic changes development.
Osteoarthritis is a problematic trait in terms of etiology and interpretation in past human populations. The relationships between osteoarthritic changes (osteophytes, porosity, and eburnation) and entheseal changes, body mass, stature, bone massiveness, sex, and age on the basis of skeletal material from Łekno (Poland) are analyzed here. Entheses were the strongest contributor to the prediction of osteophyte expression and when all types of changes and all joints were taken together. Stature demonstrates a negative dependence on porosity. When each joint was analyzed separately, entheses were the strongest contributor to the prediction of arthritis expression in the wrist and hip. Age was the strongest contributor to the prediction of arthritis expression in the elbow. Body mass, stature, bone massiveness, and sex had no effect on osteoarthritic changes in any of the examined joints. The results of the present study suggest an important dependence between entheses and osteoarthritic changes. Other factors had little to no effect on differences in OA severity. These results do not dispel all doubts but enrich knowledge about the effect of etiological factors on osteoarthritic change formation. This knowledge is essential for proper, reliable interpretation of osteoarthritic changes in the context of past human biology, ecology, and behavior.


Arctic adaptation in reindeer. The energy saving of a hemoglobin.
Previous results [(1988) Arct. Med. Res. 47, 83-88] have shown that hemoglobin from reindeer is characterized by a low overall heat of oxygenation. This particular aspect has been investigated further in a series of precise oxygen equilibrium experiments. The results obtained show a peculiar dependence of the temperature effect on the fractional saturation of hemoglobin with oxygen, which could be regarded as a very interesting case of molecular adaptation to extreme environmental conditions.


The effects of yoga practice on balance, strength, coordination and flexibility in healthy children aged 10-12 years.
The purpose of this study was to investigate the effects of yoga practice on balance, strength, coordination, and flexibility in healthy children aged 10-12 years. Quasi-experimental, nonrandomized. Research on the effects of yoga in children has focused on the benefits seen in non-healthy children or on the effects on hand grip strength and motor performance. The studies on the effects of yoga on balance, strength, coordination, and flexibility have been limited. A convenience sample of 26 children, aged 10-12 years was obtained. The children participated in 40 min yoga sessions, led by a registered yoga teacher, 1-3 times per week for 8 weeks. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), the sit and reach test, and the 90/90 hamstring flexibility test were administered at baseline and at the end of the 8 weeks. Descriptive statistics were calculated for all measurements. A Shapiro-Wilk test was used to test normality. A Wilcoxin signed-rank test was used to analyze pre- and post-test measurements for all variables. There was a statistically significant within-subject difference from pre-test to post-test for balance (p = 0.026), sit and reach (p = 0.000), popliteal angle right (p = 0.005), and popliteal angle left (p = 0.018). There were no statistically significant differences in strength and bilateral coordination from pre-to post-test measurements. Yoga may be a beneficial form of exercise in the school-based setting for improving balance and flexibility in healthy children.


Childhood trauma exposure and personality traits in schizophrenia patients.
Childhood trauma in schizophrenia (SCZ) is associated with aberrant neurobiological downstream effects and cognitive deficits that markedly hinder patient outcome and functioning. However, the relationship between specific forms of childhood abuse and the tendency for certain personality traits in patients with SCZ has not been comprehensively studied yet. We recruited 374 SCZ patients and screened for history of physical abuse (PA), emotional abuse (EA), sexual abuse (SA), physical neglect (PN) and emotional neglect (EN) using the Childhood Trauma Questionnaire and measured personality traits using the NEO Five-Factor inventory. Using CTQ cut-off scores, the prevalence of EA, PA, SA, EN and PN was 60.7%, 42.0%, 37.7%, 64.2% and 54.3% respectively. Exposure to any form of childhood abuse was associated with increased neuroticism. Exposure to EA, SA, PN and EN was correlated with decreased agreeableness and conscientiousness scores. PN, EN and PA exposure was associated with decreased openness while EA, PN and EN exposure was associated with decreased extraversion. Furthermore, a positive correlation was found between all forms of childhood abuse and trait neuroticism whereas negative correlations were found between certain forms of childhood abuse and all other personality traits. Exposure to specific forms of childhood abuse was associated with specific personality traits in patients with SCZ.