Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.
Histone deacetylases (HDACs) have been associated with tumor development and progression in several types of human malignancy and HDAC inhibitors are currently being explored as anti-cancer agents in clinical trials. The aim of the present study was to evaluate the clinical significance of HDAC-1 and -2 protein expression in mobile tongue squamous cell carcinoma (SCC). HDAC-1 and -2 protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. HDAC-1 overexpression was significantly associated with younger patients' age (P = 0.0381) and male gender (P = 0.0345), poor histopathological grade of differentiation (P = 0.0236) and the presence of lymph node metastases (P = 0.0104). Intense HDAC-1 staining intensity was significantly associated with male gender (P = 0.0127), increased stromal infiltration reaction (P = 0.0125) and well-defined shape of tumor invasion (P = 0.0396). HDAC-2 overexpression did not show significant correlations with any clinicopathological parameters, whereas intense HDAC-2 staining intensity was significantly associated with the presence of muscular invasion (P = 0.0466) and advanced depth of invasion (P = 0.0251). Mobile tongue SCC patients with HDAC-1 overexpression presented shorter overall and disease-free survival compared to those with no evidence of HDAC-1 overexpression (log-rank test, P = 0.0651 and 0.0247, respectively). The present study supported evidence that HDACs may participate in the formation and progression of mobile tongue SCC, reinforcing their possible use as biomarkers as also the therapeutic utility of HDAC inhibitors in mobile tongue SCC chemoprevention and treatment.


Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation: two unique but complementary strategies for the treatment of allergic diseases.
Despite a number of effective pharmaceutical options for the prevention and treatment of the pathophysiologic responses that occur in sensitized patients on allergen exposure, the termination of allergic hypersensitivities remains an elusive therapeutic goal. Traditional immunotherapy with allergen extracts is the only currently used intervention that has been shown to induce allergen tolerance, but it has a limited scope of efficacy. However, recent studies suggest that immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) -based interventions might offer an alternative and potentially more effective means for extinguishing T (H)2-biased hypersensitivities. Three basic ISS-ODN -based immunotherapeutic strategies have been studied to date. Immunization with allergen mixed with ISS- ODN, immunization with allergen -ISS- ODN conjugates, and immunomodulation with ISS- ODN alone all have proved efficacy in the attenuation of the allergic phenotype in mice. Preliminary results with allergen -ISS- ODN conjugate vaccines in allergic patients have also been encouraging. This article will provide our perspective on the application of ISS-ODN -based vaccination and immunomodulation to the treatment of atopic diseases and the immunologic basis for their antiallergic activities.


Cone beam computed tomography for percutaneous nephrolithotomy: initial evaluation of a new technology.
Cone beam CT (CBCT) is a novel imaging modality that combines the versatility of conventional C-arm imaging with the functionality of cross-sectional imaging. This is a pilot study to evaluate the capabilities of this new technology to obtain percutaneous access and for the immediate postoperative evaluation of residual fragments in percutaneous nephrolithotomy (PCNL). A retrospective analysis of all PCNL cases performed between April 2007 and November 2007 was performed. One urologist (NSS) and one radiologist (JFA) reviewed the studies postoperatively. Preoperative films were evaluated to see if CBCT influenced or improved percutaneous access. Postoperative films were evaluated that compared CBCT with conventional noncontrast CT to determine efficacy in finding postoperative stone fragments. Parameters of stone size, location, and quantity of fragments were compared. For preoperative access, CBCT was used in 52 cases of PCNL between April 2007 and November 2007. In eight of these cases, CBCT altered the percutaneous access. In postoperative evaluation, 26 cases had both CBCT and conventional CT for comparison. In 11 cases with residual stones, conventional CT identified a greater number of fragments, but these were less than 2 mm. The postoperative recommendation for a secondary procedure concurred in 22 of 26 studies. CBCT may provide advantages of improved preoperative imaging, which may result in better percutaneous access, and improved postoperative imaging, which allows surgeons to have "real-time" access to CT quality images. The intraoperative availability of these high quality tomographic images may obviate the need for other postoperative imaging and subsequent adjunctive procedures for residual fragments.


Smoke-Free Home Rules and Association with Child Secondhand Smoke Exposure among Mother-Child Dyad Relationships.
Smoke-free home rules restrict smoking in the home, but biomarkers of secondhand smoke exposure are needed to help understand the association between smoke-free homes and child secondhand smoke exposure. Participants (n = 346) were majority Black/African American mother-child dyads from a longitudinal study in North Carolina. Mothers completed questionnaires on household smoking behaviors and rules, and child saliva samples were assayed for secondhand smoke exposure. Regression models used smoke-free home rules to predict child risk for secondhand smoke exposure. Children in households with smoke-free home rules had less salivary cotinine and risk for secondhand smoke exposure. After controlling for smokers in the household, home smoking rules were not a significant predictor of secondhand smoke exposure. Compared to children in households with no smokers, children in households with at least one smoker but a non-smoking mother (OR 5.35, 95% CI: 2.22, 13.17) and households with at least one smoker including a smoking mother (OR 13.73, 95% CI: 6.06, 33.28) had greater risk for secondhand smoke exposure. Results suggest smoke-free home rules are not sufficient to fully protect children from secondhand smoke exposure, especially in homes with smokers. Future research should focus on how household members who smoke can facilitate the prevention of child secondhand smoke exposure.


A high dietary concentration of inulin is necessary to reduce the incidence of swine dysentery in pigs experimentally challenged with Brachyspira hyodysenteriae.
A total of sixty surgically castrated male pigs (Large White × Landrace) weighing 31·2 (sd 4·3) kg were used in a randomised block experiment to examine the effect of added dietary inulin (0, 20, 40 and 80 g/kg) on the occurrence of swine dysentery (SD) and on fermentation characteristics in the large intestine after experimental challenge with the causative spirochaete Brachyspira hyodysenteriae. The pigs were allowed to adapt to the diets for 2 weeks before each pig was challenged orally four times with a broth culture containing B. hyodysenteriae on consecutive days. Increasing dietary levels of inulin linearly (P = 0·001) reduced the risk of pigs developing SD; however, eight out of fifteen pigs fed the diet with 80 g/kg inulin still developed the disease. The pH values in the caecum (P = 0·072) tended to decrease, and in the upper colon, the pH values did decrease (P = 0·047) linearly with increasing inulin levels in the diets, most probably due to a linear increase in the concentration of total volatile fatty acids in the caecum (P = 0·018), upper colon (P = 0·001) and lower colon (P = 0·013). In addition, there was a linear reduction in the proportion of the branched-chain fatty acids isobutyric acid and isovaleric acid in the caecum (P = 0·015 and 0·026) and upper colon (P = 0·011 and 0·013) with increasing levels of dietary inulin. In conclusion, the present study showed that a diet supplemented with a high level of inulin (80 g/kg) but not lower levels reduced the risk of pigs developing SD, possibly acting through a modification of the microbial fermentation patterns in the large intestine.


Metabolic Reprogramming and Its Relationship to Survival in Hepatocellular Carcinoma.
Hepatocarcinogenesis is frequently accompanied by substantial metabolic reprogramming to maximize the growth and proliferation of cancer cells. In this study, we carried out a comprehensive study of metabolomics and lipidomics profiles combined with gene expression analysis to characterize the metabolic reprogramming in hepatocellular carcinoma (HCC). Compared with adjacent noncancerous liver tissue, the enhanced aerobic glycolysis and de novo lipogenesis (DNL) and the repressed urea cycle were underscored in HCC tissue. Furthermore, multiscale embedded correlation analysis was performed to construct differential correlation networks and reveal pathologically relevant molecule modules. The obtained hub nodes were further screened according to the maximum biochemical diversity and the least intraclass correlation. Finally, a panel of ornithine, FFA 18:1, PC O-32:1 and TG (18:1_17:1_18:2) was generated to achieve the prognostic risk stratification of HCC patients (p < 0.001 by log-rank test). Altogether, our findings suggest that the metabolic dysfunctions of HCC detected via metabolomics and lipidomics would contribute to a better understanding of clinical relevance of hepatic metabolic reprogramming and provide potential sources for the identification of therapeutic targets and the discovery of biomarkers.


Probing the chiroptical response of a single molecule.
Chirally sensitive measurement techniques have generally been restricted to bulk samples. Here, we report the observation of fluorescence-detected circular dichroism (FDCD) from single (bridgedtriarylamine) helicene molecules by using an excitation wavelength (457 nanometers) in the vicinity of an electronic transition that shows circular dichroism in bulk samples. The distributions of dissymmetry (g) parameters by analysis of signals from pure M- and P-type diastereomers are almost perfect mirror images of one another, each spanning a range of both positive and negative values. In addition, we observe a well-defined structure in the histogram of dissymmetry parameters suggestive of specific molecular orientations at the polymer interface. These single-molecule results highlight strong intrinsic circular dichroism responses that can be obscured by cancellation effects in ensemble measurements of a randomly oriented bulk sample.


Thematic minireview series on enzyme evolution in the post-genomic era.
The emergence of genomics; ongoing computational advances; and the development of large-scale sequence, structural, and functional databases have created important new interdisciplinary linkages between molecular evolution, molecular biology, and enzymology. The five minireviews in this series survey advances and challenges in this burgeoning field from complementary perspectives. The series has three major themes. The first is the evolution of enzyme superfamilies, in which members exhibit increasing sequence, structural, and functional divergence with increasing time of divergence from a common ancestor. The second is the evolutionary role of promiscuous enzymes, which, in addition to their primary function, have adventitious secondary activities that frequently provide the starting point for the evolution of new enzymes. The third is the importance of in silico approaches to the daunting challenge of assigning and predicting the functions of the many uncharacterized proteins in the large-scale sequence and structural databases that are now available. A recent computational advance, the use of protein similarity networks that map functional data onto proteins clustered by similarity, is presented as an approach that can improve functional insight and inference. The three themes are illustrated with several examples of enzyme superfamilies, including the amidohydrolase, metallo-β-lactamase, and enolase superfamilies.


Mo-Doped Zn, Co Zeolitic Imidazolate Framework-Derived Co9S8 Quantum Dots and MoS2 Embedded in Three-Dimensional Nitrogen-Doped Carbon Nanoflake Arrays as an Efficient Trifunctional Electrocatalysts for the Oxygen Reduction Reaction, Oxygen Evolution Reaction, and Hydrogen Evolution Reaction.
Herein, we first propose a facile strategy to synthesize Co9S8 and MoS2 nanocrystals embedded in porous carbon nanoflake arrays supported on carbon nanofibers (Co9S8-MoS2/N-CNAs@CNFs) by the pyrolysis of Mo-doped Zn, Co zeolitic imidazolate framework grown on carbon nanofibers and subsequent sulfuration. The electrocatalyst shows high and stable electrocatalytic performance, with a half-wave potential of 0.82 V for oxygen reduction reaction and an overpotential at 10 mA cm-2 for oxygen evolution reaction (0.34 V) and hydrogen evolution reaction (0.163 V), which outperform the metal-organic framework-derived transition metal sulfide catalysts reported so far. Furthermore, the Co9S8-MoS2@N-CNAs@CNFs are employed as an air cathode in a liquid-state and all-solid-state zinc-air battery, presenting high power densities of 222 and 96 mW cm-2, respectively. Such excellent catalytic activities are mainly owing to the unique three-dimensional structure and chemical compositions, optimal electronic conductivity, adequate surface area, and the abundance of active sites. Thus, this work provides an important method for designing other metal-organic framework-derived three-dimensional structural sulfide quantum dot multifunctional electrocatalysts for wider application in highly efficient catalysis and energy storage.


Later retinal degeneration following childhood surgical aphakia in a family with recessive CRYAB mutation (p.R56W).
To describe later retinal degeneration following childhood cataract surgery without intraocular lens implantation in a consanguineous family with developmental cataract from homozygous p.R56W mutation in CRYAB, a gene that encodes a heat-shock protein (alphaB-crystallin) in both retina and the lens. Prospective ophthalmologic examination and venous blood sampling for diagnostic CRYAB sequencing in the 12 available family members (7 siblings and their 2 parents, the siblings' maternal aunt and her son, and the siblings' maternal grandmother). Those who underwent childhood cataract surgery (2 siblings, their mother, their maternal aunt) or who had visually-insignificant lens opacities (2 siblings, their maternal grandmother) were homozygous for p.R56W CRYAB mutation. Among these 7 affected family members, clinically-obvious rod-cone degeneration was present only in the only 2 adults who were aphakic since childhood from cataract surgery. Recessive p.R56W CRYAB mutation shows variable expressivity for lens opacity. Decades of aphakia increases retinal light exposure and may be an environmental risk factor for significant retinal degeneration in patients homozygous for the mutation.


Calcium Pyrophosphate Dihydrate Crystal Deposition Disease Involving the Ligamentum Flavum of the Cervical Spine with Intense Enhancement on MRI: A Case Report.
Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is characterized by chondrocalcinosis, which mainly affects the knees, wrists, pelvis, and rarely, the spine. According to previous reports, CPPD crystal deposits display heterogeneous enhancement on MRI. When combined with inflammation of the surrounding soft tissue, strong enhancement by CPPD crystal deposition may appear similar to imaging features of other conditions such as infectious spondylitis. In these conditions, CT plays an important role in differential diagnosis. Here, we present a case of CPPD crystal deposition disease in the ligamentum flavum of the cervical spine that showed intense enhancement on MRI.


Dialysis dose and nutrition assessment by optical on-line dialysis adequacy monitor.
In light of the variability of dialysis sessions, on-line monitoring could improve hemodialysis (HD) adequacy. A new optical Dialysis Adequacy Monitor (DIAMON) prototype enables to estimate dialysis dose and protein nitrogen appearance (PNA) at every dialysis session. The aim of this study was to compare the adequacy of dialysis treatment and the patient's nutritional status by pre-and post-dialysis blood samples, the DIAMON prototype and Total Dialysate Collection (TDC). Ten patients were monitored during three consecutive hemodialysis sessions during one week. Blood samples were drawn before the start of dialysis and at the end of dialysis. The DIAMON prototype was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through during the on-line experiments, and TDC was performed for all dialysis treatments. Equilibrated Kt/V (eKt/V) values were estimated from blood-urea (eKt/Vb) and from DIAMON (eKt/Va), and normalized PNA (nPNA) values from TDC and DIAMON, respectively. The variable volume single pool urea kinetic modeling (VVSP UKM) was also utilized for single-pool Kt/V (spKt/V) and nPNA estimation. The mean +/- SD given by eKt/Vb was 1.08 +/- 0.22 (n = 30), and eKt/Va 1.05 +/- 0.21 (n = 28). The mean +/- SD of nPNA was 0.73 +/- 0.15 g/kg/day (n = 29) from TDC, and 0.73 +/- 0.14 g/kg/day (n = 28) using DIAMON prototype. The mean values of eKt/V from blood samples and nPNA from TDC were not statistically different from the corresponding values estimated by DIAMON (p < 0.05). Generally the delivered dialysis dose and dietary protein intake of the patients observed during the study using the DIAMON prototype was very similar to that obtained by TDC and VVSP UKM. The optical dialysis adequacy sensor, DIAMON, provides continuous, on-line measurements of dialysis adequacy and permits longitudinal analysis of the delivered dialysis dose and patient's nutritional status, and can immediately identify, and alert to, any deviations in dialysis treatment.


Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of (99m)Tc versus (188)Re.
Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of (188)Re-perrhenate and (99m)Tc-pertechnetate on cellular survival. Rat thyroid PC Cl3 cells in culture were incubated with (188)Re or (99m)Tc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified. Dose effect curves were established for (188)Re and (99m)Tc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and (188)Re reduced cell survival more efficiently than (99m)Tc. A(37), the activity that is necessary to yield 37% cell survival was 14 MBq/ml for (188)Re and 480 MBq/ml for (99m)Tc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A(37) was reduced by 30% for the beta-emitter and by 95% for (99m)Tc. The dose D(37) that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides. Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular (99m)Tc yielded a dose increase that was higher compared to (188)Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non-uniform lognormal radionuclide uptake.


Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells.
Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness.


[Proinflammatory cytokines in children with idiopathic headache].
The pathogenesis of primary headaches is differential, with a neurogenic inflammation participation. The aim of this research was to establish whether inflammation participates in the pathogenesis of migraine and tension-type headaches (ETTH). In order to establish this, the levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1beta), tumor necrosis factor (TNF) and soluble TNF receptor type I (sTNFRI) were detected in groups with headaches during headache-free interval and in controls and in the blood of children with idiopathic headaches to detect changes during headache attack. 30 children with migraine were included (16 with aura and 14 without aura), 17 boys and 13 girls aged 10-17 years (mean 13.5). The group with ETTH consisted of 31 patients, 24 girls and 7 boys, aged 6-17 years (mean 13.5). The control group, 28 children without headache, diagnosed with non-inflammatory orthopedic diseases, consisted of 15 boys and 13 girls, aged 7-17 years (mean 13.0). When the pain started during hospitalization, the blood was sampled in the first hour of the headache, then 3 hours and 6 hours since headache started (if headache persisted), and 6 hours after its termination. Two days after the pain termination, the blood samples were collected in children suffering from headaches, as the headache-free measurements and in controls under the same conditions at 7 a.m. after awakening. The cytokine level was established using Biosource kits, all 326 samples were processed. The statistical assessment was conducted. No differences were detected in cytokine levels between the groups with migraine and ETTH and with comparison to controls during headache-free interval and during headache attack as well. However, it was established that in 12/30 children with migraine there was a significant increase in IL-6 level in the first hour of the migraine attack. This group consisted of 12 children with TNF level higher and the tendency toward decrease in sTNFRI was established, 3 hours since headache started, as compared to 18/30 children with migraine but without increase in IL-6. The correlation between the level of cytokines and age and weight was not detected. Also no correlation was established between cytokine levels and leukocyte and thrombocyte count. 1. Changes of the level of IL-6, IL-1beta, TNF and sTNFRI in the blood of children with idiopathic headache do not indicate a significant role of inflammatory process in its pathogenesis. 2. Although the significant increase in IL-6 levels observed in several children in the first hour of the migraine attack may suggest that neurogenic inflammation participates in the pathogenesis of migraine.


Ultrasound Evaluation of the Effectiveness of the Use of Acitretin in the Treatment of Nail Psoriasis.
The study aimed to evaluate the effect of retinoid treatment on the morphological changes in the nail apparatus in patients with nail psoriasis. 41 patients aged 32 to 64 with nail psoriasis, without clinical signs of psoriatic arthritis, started on acitretin 0.6 to 0.8 mg kg b.w./d, for six months and 28 people in the control group were included in the study. Both groups had ultrasound examination of fingernails and digital extensor tendon in the distal interphalangeal joints. In psoriatic patients, US examination was conducted before starting the treatment and after six months. A total of 685 nails were examined. After six months of treatment, there was a reduction in the thickness of the nail bed and nail matrix (p = 0.046 and p = 0.031, respectively). The thickness of the nail plates decreased, although it was statistically insignificant (p = 0.059) and it was higher than in the control group (p = 0.034). The reduced severity of clinical nail changes after six months of retinoid treatment did not correlate with the reduction in extensor tendon thickness in any group of patients. In patients with nail psoriasis, acitretin treatment resulted in a rapid decrease in the thickness of the nail bed and matrix, but it did not affect the thickness of the nail plate after six months. There was no effect of acitretin on the digital extensor tendon thickness or the increased blood supply to the tendon area. The results of the study may indicate the usefulness of ultrasound nail examinations in patients with nail psoriasis not only to assess the advancement of morphological changes and response to treatment, but also to choose the potential treatment.


Model-Based Orthodontic Assessments for Dental Panoramic Radiographs.
For better treatment outcomes, dentists usually use a set of parameters for orthodontic evaluation. In this study, a new method is proposed to assist dentists in obtaining reliable assessment of these parameters. The proposed method is based on dental panoramic radiographs and can be divided into four stages: image preprocessing, model training, tooth segmentation, and assessment of orthodontic parameters. The image is first normalized and enhanced. Then, the model training stage consists of shape and image model training, energy function training, and weight training. Next, we automatically segment the tooth contours in an energy-minimized manner. Finally, the automatic assessment of orthodontic parameters is carried out. The experimental results show that the average of absolute distance, the Dice similarity coefficient, and the average qualitative score ranged between 4.17 and 6.03, 0.87 and 0.90, as well as 2.58 and 3.12, respectively. The orthodontic assessment also is close to the evaluation of orthodontists. It has been shown that the proposed method can obtain accurate and consistent measurement in helping dentists to obtain an objective treatment evaluation.


Forward chemical genetics: library scaffold design.
With the unraveling of the entire human genome, it has become imperative to understand the function of the gene products, proteins. Within the past several years, chemical genetics has gained recognition as a powerful approach to study protein function by using small molecules as gene knock-out or knock-in mimics. Forward chemical genetics is a three-step process; the design and synthesis of a small molecule library represents the first step followed secondly by the search for novel phenotypes and then by isolation and identification of target protein(s). This review will focus on the first step, the design of the scaffold for small molecule libraries. It will also examine the connection between the choice of a scaffold and the propensity of that library to demonstrate enhanced biological activity when tested in certain cellular systems.


Healthcare-associated infections in long-term care facilities (HALT) in Frankfurt am Main, Germany, January to March 2011.
Healthcare-associated infections (HAIs) are a potentially serious threat to elderly people living in longterm care facilities. Therefore, the European HALT (Healthcare-associated infections in long-term care facilities) project was launched in 2008. HAIs and the use of antibiotics were studied in all 40 nursing homes (100% response) in the city of Frankfurt am Main, Germany, from January to March 2011, using the HALT protocol. Of the 3,732 residents in the homes, 4.3% (n=161) had either signs or symptoms of infections and/or were on oral antibiotics. The most common infections were urinary tract infections (n=45; 1.2%), followed by infections of the respiratory tract (n=41; 1.1%) and skin except mycosis (n=25; 0.7%). The overall prevalence of oral antibiotic use was 2.4% (n=90). The most frequently prescribed oral antibiotics were quinolones (n=31), cephalosporins (n=19), penicillins (n=11) and co-trimoxazole (n=11). The prevalence of HAIs was about the same as that in a European pilot study carried out in November 2009 (5%), but was higher than in several national surveys carried out between May and September 2010 (1.6–3.6%).


Screening potential reference genes for quantitative real-time PCR analysis in the oriental armyworm, Mythimna separata.
The oriental armyworm, Mythimna separata, is a major insect pest in China and other Asian countries. Unfortunately, suitable reference genes for quantitative real-time PCR (qRT-PCR) have not been previously identified in M. separata for normalizing target gene expression. In this study, we evaluated the expression stability of eight candidate genes (18S, ACT, EF1-α, GAPDH, RPS7, RPS13, RPL32 and TUB) in M. separata using the comparative ΔCt method, BestKeeper, Normfinder geNorm and ReFinder, a comprehensive software platform. The results indicated that the appropriate reference gene varied depending on the experimental conditions. We found that ACTIN, EF1-α and TUB were optimal for different developmental stages; TUB, RPS13 and EF1-α showed the most stable expresssion in different tissues; RPS13 and 18S were the best reference genes for monitoring expression under high temperature conditions; TUB, RPS13 and RPS7 exhibited the most stable expression under larval-crowding conditions; RPS7, EF1-α, RPL32 and GAPDH were the best for pesticide exposure experiments. This study provides tools for reliable normalization of qRT-PCR data and forms a foundation for functional studies of target gene expression in M. separata.


Hand-assisted laparoscopic surgery with a Pfannenstiel incision in beta-thalassemia patients: initial experience.
beta-Thalassemia patients have splenomegaly significant enough to require splenectomy; furthermore, these patients also often require concurrent procedures. Between January and October 2005, seven patients with beta-thalassemia underwent hand-assisted laparoscopic splenectomy with cholecystectomy, appendectomy, and liver biopsy with the hand-port device introduced through a Pfannenstiel incision. The median age of the patients was 28 years, and the median spleen length was 23 cm. The median operating time was 210 minutes; there were no conversions to an open procedure; and the median spleen weight was 1072 g. One major postoperative complication occurred. The median hospital stay was 6 days. The proposed hand-assisted laparoscopic approach is safe and feasible. It provides a minimally invasive alternative that may become the treatment of choice in beta-thalassemia patients who require concurrent operations.


Thermotherapy for Harding-Passey melanoma: light and electron microscopic study.
The changes of implanted Harding-Passey melanoma in C57Bl/6J mice following treatment with wholebody hyperthermia were studied. The treated tumours showed a progressive growth delay, cellular and architectural irregularities as well as cell injury characteristics. The presence of distended and irregular blood vessels, the peripheral localization of the melanosomes and the melanosome complexes were constant.


The eukaryotic-type serine/threonine protein kinase Stk is required for biofilm formation and virulence in Staphylococcus epidermidis.
Serine/threonine kinases are involved in gene regulation and signal transduction in prokaryotes and eukaryotes. Here, we investigated the role of the serine/threonine kinase Stk in the opportunistic pathogen Staphylococcus epidermidis. We constructed an isogenic stk mutant of a biofilm-forming clinical S. epidermidis isolate. Presence of stk was important for biofilm formation in vitro and virulence in a murine subcutaneous foreign body infection model. Furthermore, the stk mutant exhibited phenotypes indicating an impact of stk on metabolic pathways. Using different constructs for the genetic complementation of the stk mutant strain with full-length Stk or specific Stk domains, we determined that the Stk intracellular kinase domain is important for biofilm formation and regulation of purine metabolism. Site-specific inactivation of the Stk kinase domain led to defective biofilm formation, in further support of the notion that the kinase activity of Stk regulates biofilm formation of S. epidermidis. According to immunological detection of the biofilm exopolysaccharide PIA and real-time PCR of the PIA biosynthesis genes, the impact of stk on biofilm formation is mediated, at least in part, by a strong influence on PIA expression. Our study identifies Stk as an important regulator of biofilm formation and virulence of S. epidermidis, with additional involvement in purine metabolism and the bacterial stress response.


Gripe water: what is it? Why is it given?
Large numbers of babies are given gripe water for no valid reason or for only trivial symptoms, write Cynthia Illingworth and John Timmins. When a health visitor survey of Sheffield mothers and babies showed how widespread was the practice of giving gripe water, they decided to seek information about the nature of gripe water, the conditions which it is supposed to treat and its use by a representative number of women.


Characteristics of participants enrolled in a Quit and Win smoking cessation program.
Quit and Win smoking cessation incentive programs have been used to promote community-based smoking cessation in the United States and internationally. The Quit and Win contest has been offered annually by the Lexington-Fayette County Health Department since 2001. In order to engage in continuous quality assessment of the Quit and Win program, demographic analysis of program participants is critical to better extend the marketing message to target audiences. The goal of this analysis is to report various baseline parameters of the 2003 Lexington-Fayette County Quit and Win contest cohort. Of the 876 participants, most were white, had at least a high school education, smoked cigarettes for more than 10 years, and had multiple previous quit attempts. Most anticipated using nicotine replacement products to aid the current quit attempt. The demographic information from this analysis can be used to design future programs that target a wider segment of the population.


Seated double-poling ergometer performance of individuals with spinal cord injury - a new ergometer concept for standardized upper body exercise.
This study aimed to evaluate biomechanics during seated double-poling exercises in individuals with spinal cord injury (SCI) and to compare these with those of able-bodied persons (AB). 26 participants volunteered for the study; 13 with SCI (injury levels C7-T12), and 13 AB. A seated double-poling ergometer (SDPE) was developed. 3-dimensional kinematics was measured and piezoelectric force sensors were used to register force in both poles for calculation of power during incremental intensities. Significantly lower power outputs, (143.2 ± 51.1 vs. 198.3 ± 74.9 W) and pole forces (137.1 ± 43.1 vs. 238.2 ± 81.2 N) were observed during maximal effort in SCI compared to AB. Sagittal upper trunk range of motion increased with intensity and ranged from 6.1-34.8° for SCI, and 6.9-31.3° for AB, with larger peak amplitudes in flexion for AB (31.4 ± 12.9°) compared to SCI (10.0 ± 8.0°). All subjects with SCI were able to exercise on the SDPE. Upper body kinematics, power and force outputs increased with intensity in both groups, but were in general, lower in SCI. In conclusion, the SDPE could be successfully used at low to high work intensities enabling both endurance and strength training for individuals with SCI.


Comparison of sea snake (Hydrophiidae) neurotoxin to cobra (Naja) neurotoxin.
Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone.


Antimicrobial susceptibility and distribution of β-lactamase A (blaA) and β-lactamase B (blaB) genes in enteropathogenic Yersinia species.
One hundred eighty-six strains of enteropathogenic Yersinia (Y.) enterocolitica of bioserotypes 2/O:5,27, 2/O:9, 3/O:3, and 4/O:3 and 12 strains of Yersinia pseudotuberculosis of bioserotypes 1/O:1, 1/O:2, and 2/O:1 from different human (feces) and nonhuman (pig, pork, wild boar, monkey, chinchilla, mara, capybara, salad) sources collected in the years 1995-2009 were examined. Antimicrobial resistance patterns for 12 antimicrobial agents were generated using broth microdilution. The presence and characterization of the β-lactamase genes blaA and blaB were studied using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. The expression of β-lactamase BlaA and BlaB was detected using double-disc diffusion. Y. enterocolitica strains showed resistance to ampicillin (92%), streptomycin (13%), and sulfamethoxazole (2%). Intermediate susceptibility to tetracycline was shown by two Y. enterocolitica strains. All Y. pseudotuberculosis strains were susceptible to all tested antimicrobial agents. Most (99%) of the Y. enterocolitica strains carried both β-lactamase genes. One strain of bioserotype 3/O:3 lacked both genes. In contrast, all Y. pseudotuberculosis strains carried neither of the β-lactamase genes. Homogeneity was detected in all blaA and blaB genes of Y. enterocolitica using PCR-RFLP. The majority (89%) of Y. enterocolitica strains expressed both β-lactamase enzymes, whereas none of the Y. pseudotuberculosis strains showed expression of either enzyme. Also, it seems that the resistance of Y. enterocolitica has not changed during the last years.


Articulation and vocal tract acoustics at soprano subject's high fundamental frequencies.
The role of the vocal tract for phonation at very high soprano fundamental frequencies (F0s) is not yet understood in detail. In this investigation, two experiments were carried out with a single professional high soprano subject. First, using two dimensional (2D) dynamic real-time magnetic resonance imaging (MRI) (24 fps) midsagittal and coronal vocal tract shapes were analyzed while the subject sang a scale from Bb5 (932 Hz) to G6 (1568 Hz). In a second experiment, volumetric vocal tract MRI data were recorded from sustained phonations (13 s) for the pitches C6 (1047 Hz) and G6 (1568 Hz). Formant frequencies were measured in physical models created by 3D printing, and calculated from area functions obtained from the 3D vocal tract shapes. The data showed that there were only minor modifications of the vocal tract shape. These changes involved a decrease of the piriform sinus as well as small changes of tongue position. Formant frequencies did not exhibit major differences between C6 and G6 for F1 and F3, respectively. Only F2 was slightly raised for G6. For G6, however, F2 is not excited by any voice source partial. Therefore, this investigation was not able to confirm that the analyzed professional soprano subject adjusted formants to voice source partials for the analyzed F0s.


Isolation of a novel deoxyribonuclease with antifungal activity from Asparagus officinalis seeds.
A deoxyribonuclease distinct from the previously isolated asparagus ribosome-inactivating proteins, possessing a molecular weight of 30 kDa and requiring a pH of 7.5 for optimum hydrolytic activity toward herring sperm DNA, was isolated from Asparagus officinalis seeds. The isolation procedure involved extraction with saline, (NH(4))(2)SO(4) precipitation, ion-exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion-exchange chromatography on CM-Sepharose, and FPLC gel filtration on Superdex 75. The doxyribonuclease was unadsorbed onto DEAE-cellulose and Affi-gel blue gel and adsorbed onto CM-Sepharose. It exhibited the novel N-terminal sequence, GIEVIKIREL. The deoxyribonuclease was purified to a specific activity of 1584 units/mg. It was devoid of ribonuclease, protease, and HIV-1 reverse transcriptase-inhibitory activities. However, it inhibited cell-free translation in a rabbit reticulocyte lysate system with an IC(50) of 20 microM. It exhibited antifungal activity toward Botrytis cinerea but not toward Fusarium oxysporum and Mycosphaerella arachidicola.


Genetic polymorphism at miR-181a binding site contributes to gastric cancer susceptibility.
Recent evidences show that genetic polymorphisms falling in miRNA binding sites can alter the strength of miRNA binding and disturb miRNA-mediated posttranscriptional regulation. Our study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in putative miRNA binding sites in gastric cancer (GC). Based on microarray and quantitative reverse transcription PCR analyses, we found that miR-181a was significantly upregulated in GC tissues. Bioinformatics survey was used to explore SNPs within miR-181a binding sites. Three SNPs were genotyped in a case-control study (500 cases and 502 controls). The T allele genotypes (rs12537CT and TT) of MTMR3 were found associated with significantly increased GC risk [adjusted odds ratio 1.72, 95% confidence interval (CI) 1.36-2.16, P = 3.99×10(-5)] and poor overall survival [hazard ratio (HR) 1.38, 95% CI 1.03-1.83, P = 0.029], although they were not an independent prognostic factor in multivariate Cox regression analysis (HR 1.28, 95% CI 0.95-1.72, P = 0.11). We further demonstrated that the rs12537CT genotype carriers had lower MTMR3 mRNA expression levels than CC genotype carriers in GC tissues (P = 0.013), whereas no significant difference in miR-181a expression levels was found (P = 0.135). Luciferase assay revealed that miR-181a directly targeted MTMR3, and its suppressive effect was enhanced when the rs12537C allele was substituted by T variant, although the difference was not significant (P = 0.055). Our study suggested that rs12537 is associated with susceptibility and prognosis of GC in southern Han Chinese, and miR-181a and its target gene MTMR3 play important roles in GC.


Delayed diagnosis of splenic rupture following minor trauma: beware of comorbid conditions.
Although rare, spontaneous splenic rupture has been reported in cases of chronic lymphocytic leukemia (CLL). In contrast, there are no published reports of splenic injury resulting from minor trauma in CLL patients. We report the case of an 81-year-old woman with a history of CLL, who presented with minor trauma to her coccygeal region, and was found to have a splenic rupture. We briefly describe the incidence, pathogenesis, presentation, diagnosis, management and prognosis of splenic injury, especially in cases with a history of splenomegaly.


[Cerebral venous thrombosis: when etiology makes the difference].
To make a retrospective study of the clinical, etiological, diagnostic and prognostic features of cerebral vein and sinus thrombosis (CVST) diagnosed at our University Hospital. We performed a systematic research of the clinical records of our University Hospital's electronic database (1977-2009) using the key words <<cerebral vein or sinus thrombosis>>. Ninety-five possible cases were found, and 16 were excluded due to alternative or uncertain diagnosis. Seventy-nine patients (43 females), median age of 46 years (2-82), were studied. Hereditary or acquired thrombophilia was detected in 22 patients (27.8%): prothrombin G20210A mutation (10), factor V Leyden (3), protein C deficiency (2), homozygous MTHFR C677T mutation (1), antiphospholipid syndrome (7) and hematological conditions (3). CVST was associated with infection in 17 cases, intracranial neoplasm in 9, malignancy in 13, treatment with prothrombotic drugs in 20 (including substitutive/antineoplastic hormones and oral contraceptives) and other causes in 8. Thirteen cases were idiopathic. Clinical presentation was intracranial hypertension in 83.5%, focal deficits in 45.6% and seizures in 12.6 %. Transverse (57%) and superior sagittal sinus (49.4%) were the most commonly involved. Seizures occurred in 25.3%, venous infarction in 41% and severe intracranial hypertension in 22.8 %. Up to 31.6 % required surgical drainage, decompressive craniectomy or ventricular drainage. Nine cases associated peripheral venous thromboembolism and 4 CVST recurred. Evolution was favorable (modified Rankin scale 0-2 at 3 months) in 74.7%. Mortality rate was 13.9% (11 patients). Neoplastic and infectious origin was significantly associated with mortality and disability. We describe a large retrospective series of CVST where infectious and neoplastic etiologies were linked to an unfavorable outcome.


Photoinduced ligand transformations in a ruthenium complex of dimethoxytetrapyridotetraazapentacene.
The dinuclear ruthenium(II) complex [(phen)(2)Ru(tatpOMe)Ru(phen)(2)](4+) (2(4+); phen is 1,10-phenanthroline and tatpOMe is 10,21-dimethoxy-9,10,20,33-tetraazatetrapyrido[3,2-a:2'3'-c:3'',2''-l:2''',3'''-n]pentacene) has been synthesized and characterized by (1)H NMR, ESI mass spectroscopy and elemental analysis. Loss of methoxy group from bridging ligand of complex 2(4+) due to irradiation is observed by (1)H NMR and photochemistry. The interrelated electronic properties UV-Vis, electrochemistry, photochemistry and molecular orbital calculation are analyzed and discussed on the bridging ligand of the complex 2(4+).


[Structured electronic consultation letter for shoulder disorders].
Referral to a specialist has a significant influence on management of the patient and costs associated with the treatments. However, development and research of the process by which patients are referred has been almost neglected. Expectations considering the purpose, contents, and timing of the referral of the consulting physician and the consultant do not always meet. A structured, electronic consultation letter was developed to respond this need. Functionality and interactivity are the key elements of the referral, including (1) an electronic referral letter to a specialist, (2) interactive education in clinical examination and management of shoulder disorders, and (3) an instrument of clinical examination and documentation of shoulder disorders.


Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience.
Embryonal tumors with multilayered rosettes (ETMRs) are highly aggressive pediatric brain tumors with poor prognosis. No standard treatment strategy for them exists because of their rarity. This study aimed to share experiences on the clinical diagnosis and treatment of ETMRs at China Children's Medical Center (CCMC). Patients who received a diagnosis of an ETMR between January 2017 and June 2020 were included. Clinical characteristics, such as age of onset, tumor size, stage, tumor site, treatment strategy, and clinical outcome, were retrospectively analyzed. There were four boys and one girl within 4 years who received a diagnosis during this 4-year timeframe, and were thus included. The average age of morbidity was 29 months (range 16-66 months). The common clinical presentation was headaches and nausea caused by intracranial hypertension. All four patients were chromosome 19 microRNA cluster (C19MC) amplification positive. Two patients achieved complete remission, and one patient attained partial remission after multimodal treatment. Of the two deaths, one died from the rapid progression of the disease and another from tumor-related complications. ETMRs are extremely rare brain tumors with a high, early mortality in children. Surgery is the mainstream treatment for ETMRs. Some patients may also benefit from postoperative adjuvant chemotherapy and radiotherapy.


A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal localization in Chinese raccoon dog and Arctic fox.
Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are responsible for monogenic obesity, and some of them appear to be associated with predisposition or resistance to polygenic obesity. Thus, this gene is considered a functional candidate for fat tissue accumulation and body weight in domestic mammals. The aim of the study was comparative analysis of chromosome localization, nucleotide sequence, and polymorphism of the MC4R gene in two farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms. In the Chinese raccoon dog, only one silent substitution in the coding sequence was identified; whereas in the arctic fox, four InDels and two single-nucleotide polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9 (NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are discussed in terms of genome evolution of species belonging to the family Canidae and their potential use in animal breeding.


Pulmonary glomus tumour: a case initially diagnosed as carcinoid tumour.
Pulmonary glomus tumours are rare lesions, with few cases reported previously. Herein, we present the clinical and pathological features of a case of pulmonary glomus tumour. A 29-year-old female patient presented to our clinic complaining of cough, dyspnoea and left-sided chest pain. Computed tomography (CT) of the thorax revealed a nodular lesion causing obstruction of the left main bronchus. Fibreoptic bronchoscopy demonstrated a polypoid mass occluding the left main bronchus 10 mm distal to the main carina. Bronchoscopic biopsy was interpreted histologically as carcinoid tumour. Bronchotomy plus mass extirpation was performed with left thoracotomy. Microscopically, a tumoral structure composed of uniform cells with a round centrally located nucleolus and narrow eosinophilic cytoplasm was seen. Thin-walled vessels lined with endothelium were interspersed between tumoral structures. The cells were stained chromogranin and cytokeratin negative and strongly vimentin positive. The pathological diagnosis for the thoracotomy specimen was pulmonary glomus tumour. Follow-up chest CT was negative for recurrent tumour and the patient remains free of disease 17 months after surgery.


Effects of the Addition of Titanium Dioxide and Silaned Silica Nanoparticles on the Mechanical Properties of Maxillofacial Silicones.
Silicone-based elastomeric materials are commonly used to fabricate maxillofacial prostheses. The aim of this study was to evaluate the effect of different types of silica and nanosized titanium dioxide addition on the mechanical properties of two RTV silicone elastomers. A-2000 and A-2006 silicone elastomers were used, and each was divided into four subgroups (n = 5). The first group was the control without additives. Other groups were titanium dioxide, fumed silica, and silaned silica. Each specimen was prepared in compliance with the manufacturer's instructions for the tensile strength, percent elongation, tear resistance, and the hardness tests according to ISO and ASTM standards. A factorial ANOVA with pairwise interaction indicated that the pattern for all four outcomes of the materials was different for A-2000 and A-2006 (p < 0.05). Therefore, the average outcome values for the materials within silicone elastomers were then analyzed by Tukey HSD. For the hardness test results, Kruskal-Wallis and Mann-Whitney U test methods were used. The level of statistical significance was p < 0.05. There was a statistically significant interaction (p < 0.05) between materials and silicone type for all four tests (tensile strength, tear, hardness, percent elongation). The hydrophobic silica group had significantly higher tensile strength than TiO2 for A-2000. The fumed hydrophilic silica group had significantly higher tensile strength than TiO2 for A-2006. Most of silica specimens had higher tensile strength when compared with the control and TiO2 groups for A-2000 and A-2006 silicones. The TiO2 group had the highest hardness value for A-2000 while the lowest hardness value for A-2006 (p < 0.05). There was no significant difference of tear strength among the type of additives (p > 0.05) for A-2000. The fumed silica and TiO2 groups had significantly higher tear strength than the control group for A-2006. The fumed silica and the hydrophobic silica groups had significantly higher percent elongation than the control group (p < 0.05) for A-2000. The TiO2 group had the lowest percent elongation for A-2006. Results in this in vitro study may clarify future studies about the effect of different additives on the physical and mechanical properties of maxillofacial elastomers. There is a great interest in the effect of a new-generation hydrophobic silica incorporation into A-2000 silicone as well as the effect of fumed hydrophilic silica incorporation into A-2006 silicone. Future research should be supported with more in vitro trials in different percentages of such additives used in this study.


Abnormal renal and splanchnic arterial Doppler pattern in premature babies with symptomatic patent ductus arteriosus.
The flow velocity pattern in the descending aorta, renal arteries, and celiac and superior mesenteric arteries was studied with pulsed Doppler in eight premature babies with symptomatic ductus arteriosus before and after ductal closure, as compared to nine premature babies without ductus arteriosus. There was a decrease or reversal of flow in diastole in the above arteries in babies with ductus and diastolic flow reappeared after ductal closure. This diastolic steal phenomenon has not been previously demonstrated in the abdominal arteries. It may contribute to proneness to ischemic damage of abdominal organs in premature babies.


The effect of S-nitrosoglutathione and L-cysteine on chloride efflux from cystic fibrosis airway epithelial cells.
The endogenous bronchodilator, S-nitrosoglutathione (GSNO), has been proposed as a possible pharmacological remedy that reverses the ΔF508-CFTR (cystic fibrosis transmembrane conductance regulator) maturation defect and increases CFTR-mediated chloride efflux in cultured cystic fibrosis airway epithelial cells (CFBE41o(-)). It has also been reported that L-cysteine enhanced S-nitrosothiol uptake and increased the intracellular S-nitrosothiol levels, likely through transnitrosation chemistry. The present study investigated whether L-cysteine augmented the effect of GSNO on chloride efflux from CF airway epithelial cells. Treatment with 10 μM GSNO combined with 20 μM L-cysteine resulted in increased chloride efflux from CFBE41o(-) cells after 5 minutes exposure compared to the control efflux rate and to the efflux rate in the presence of L-cysteine alone as measured using the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE). Chloride efflux rates from these cells after 4h exposure to GSNO and L-cysteine were not different from control. Treatment with 10 μM GSNO alone increased chloride efflux from CFBE41o(-) cells after 4h but not at shorter incubation times. GSNO with or without L-cysteine did not alter epithelial tight junction integrity. In conclusion, a combination of GSNO with L-cysteine led to significant increase in chloride efflux in CFBE41o(-) cells but the effect was transient and not sustained beyond minutes.


Glycosylated VCAM-1 isoforms revealed in 2D western blots of HUVECs treated with tumoral soluble factors of breast cancer cells.
Several common aspects of endothelial phenotype, such as the expression of cell adhesion molecules, are shared between metastasis and inflammation. Here, we analyzed VCAM-1 variants as biological markers of these two types of endothelial cell activation. With the combination of 2-DE and western blot techniques and the aid of tunicamycin, we analyzed N-glycosylation variants of VCAM-1 in primary human endothelial cells stimulated with either TNF or tumoral soluble factors (TSF's) derived from the human breast cancer cell line ZR75.30. Treatments induced a pro-adhesive endothelial phenotype. 2D western blots analysis of cells subjected to both treatments revealed the expression of the two known VCAM-1 isoforms and of previously unknown isoforms. In particular TSFZR75.30 induced an isoform with a relative molecular mass (Mr) and isoelectric point (pI) of 75-77 kDa and 5.0, respectively. The unknown isoforms of VCAM-1 that were found to be overexpressed after treatment with TSF's compared with TNF, could serve as biomarkers to discriminate between inflammation and metastasis. 2D western blots revealed three new VCAM-1 isoforms expressed in primary human endothelial cells in response to TSF stimulation. Each of these isoforms varies in Mr and pI and could be the result of differential glycosylation states.


Polyamines and nucleic acids in gestational trophoblastic tumors.
To test the relationship between tumor malignancy and content and distribution of polyamines and nucleic acids, 2 forms of human gestational trophoblastic tumors were examined: the hydatidiform mole (self-limited form) and the human chorio-carcinoma (invasive form) xenografted into nude mice. The results indicate that there are 2 significant differences between the choriocarcinoma and the mole: 1) the choriocarcinoma is characterized by increased polyamine and nucleic acid levels, 2) tissues differ in their putrescine:spermidine and spermidine:spermine ratios. There is an increase in polyamines in the urine of mole-bearing patients over that of normal controls. The correlation between putrescine and spermidine with the chorionic gonadotropin indicates that these 2 polyamines reflect the biological activity of the mole.


Biosynthesis of polymyxin E by a cell-free enzyme system. II. Synthesis of enzyme-bound octanoyldiaminobutyric acid.
A partially purified enzyme of Aerobacillus polyaerogenes, which produces polymyxin E, activates L-2,4-diaminobutyric acid and binds it as a thioester. The incubation of the enzyme preparation with octanoyl coenzyme A and L-2,4-diaminobutyric acid in the presence of ATP and an ammonium sulfate fraction yields octanoyldiaminobutyric acid thioesterified to the enzyme.


Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria.
Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness. A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete. A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.


Digital mammography screening: weighing reduced mortality against increased overdiagnosis.
Digital mammography has been shown to increase the detection of ductal carcinoma in situ (DCIS) compared to screen-film mammography. The benefits and risks of such an increase were assessed. Breast cancer detection rates were compared between 502,574 screen-film and 83,976 digital mammograms performed between 2004 and 2006 among Dutch screening participants. The detection rates were then modeled using a baseline model and two extreme models that respectively assumed a high rate of progression and no progression of preclinical DCIS to invasive cancer. With these models, breast cancer mortality and overdiagnosis were predicted. The DCIS detection rate was significantly higher at digital mammography (1.2 per 1000 mammograms (95% C.I. 1.0-1.5)) than at screen-film mammography (0.7 per 1000 mammograms (95% C.I. 0.6-0.7)). Consequently, 287 (range progressive- non progressive model: 1-598) extra breast cancer deaths per 1,000,000 women (a 4.4% increase) were predicted to be prevented. An extra 401 (range: 165-2271) cancers would be overdiagnosed (a 21% increase). Modeling predicted that digital mammography screening would further reduce breast cancer mortality by 4.4%, at a 21% increased overdiagnosis rate. The consequences of digital screening, however, are sensitive to underlying assumptions on the natural history of DCIS.


Prevalence of gallstones in Finland: an autopsy study in the Helsinki area.
The prevalence of gallstones in Helsinki (Uusimaa county) was determined in an autopsy sample consisting of 1102 males and 768 females. The crude prevalence of gallstone disease in men was 15.3%, as compared with 34.5% in women. The age-adjusted rates for men and women were 8.7% and 15.9%, respectively. The prevalence of gallstone disease appears to be significantly lower in Finland than in Sweden. However, cholecystectomy rates appear to be higher in Finland than in reports from Sweden and Norway. No significant association with neoplastic disease was found.


Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus.
Alphavirus nsP3 phosphoprotein is essential for virus replication and functions initially within polyprotein P123 or P23 components of the short-lived minus-strand replicase, and upon polyprotein cleavage, mature nsP3 likely functions also in plus-strand synthesis. We report the identification of a second nsP3 mutant from among the A complementation group of Sindbis virus (SIN) heat-resistant strain, ts RNA-negative mutants. The ts138 mutant possessed a change of G4303 to C, predicting an Ala68-to-Gly alteration that altered a conserved His-Ala-Val tripeptide in the ancient (pre-eukaryotic), "X" or histone 2A phosphoesterase-like macrodomain that in SIN encompasses nsP3 residues 1 to 161 and whose role is unknown. We undertook comparative analysis of three nsP3 N-terminal region mutants and observed (i) that nsP3 and nsP2 functioned initially as a single unit as deduced from complementation analysis and in agreement with our previous studies, (ii) that the degree of phosphorylation varied among the nsP3 mutants, and (iii) that reduced phosphorylation of nsP3 correlated with reduced minus-strand synthesis. The most striking phenotype was exhibited by ts4 (Ala268 to Val), which after shift to 40 degrees C made significantly underphosphorylated P23/nsP3 and lost selectively the ability to make minus strands. After shift to 40 degrees C, mutant ts7 (Phe312 to Ser) made phosphorylated P23/nsP3 and minus strands but failed to increase plus-strand synthesis. Macrodomain mutant ts138 was intermediate, making at 40 degrees C partially phosphorylated P23/nsP3 and reduced amounts of minus strands. The mutants were able to assemble their nsPs at 40 degrees C into complexes that were membrane associated. Our analyses argue that P23/P123 phosphorylation is affected by macrodomain and Ala268 region sequences and in turn affects the efficient transcription of the alphavirus genome.


Effects of 9-cis retinoic acid on human homeobox gene NKX3.1 expression in prostate cancer cell line LNCaP.
To study the regulatory effects of 9-cis retinoic acid (RA) on the expression of human homeobox gene NKX3.1 in prostate cancer cell line LNCaP. Flow cytometry, reverse transcriptase polymerase chain reaction and Western blotting were performed to evaluate the effects of 9-cis RA on NKX3.1 expression and cell cycle of LNCaP cells. To identify a regulatory region within the NKX3.1 promoter contributing to the regulation induced by 9-cis RA, we have constructed an NKX3.1 promoter-reporter plasmid, pGL3-1040bp, and its 5'-deletion mutants, which were transfected into LNCaP cells with treatment of 9-cis RA in indicated concentrations. With the treatment of 9-cis RA, the NKX3.1 promoter activity was increased in reporter gene assay and NKX3.1 expression was enhanced at both mRNA and protein levels in LNCaP cells. We found that the region between -936 and -921 in the upstream of NKX3.1 gene involved the inducible regulation by 9-cis RA treatment. In flow cytometry, 9-cis RA treatment caused accumulation of cells in the G(1) phase of the cell cycle and a fewer cells pass through to G(2)/M. Our results demonstrated that 9-cis RA as a differentiating agent can arrest prostate cancer cells in G(1) phase and reduce cell mitosis, and upregulate the expression of human homeobox gene NKX3.1, which is thought to play an important role in prostate differentiation and to act as a tumor suppressor gene in the prostate.


The Effect of a Health Literacy Promotion Program on the Level of Health Literacy and Death Anxiety in Women with Breast Cancer.
With regard to the high rate of death anxiety in women with breast cancer and low levels of health literacy in these patients, this study aimed to investigate the effect of a health literacy promotion program on the level of health literacy and death anxiety in women with breast cancer. This is a clinical trial that was conducted in two groups of 30 women with breast cancer using a convenient sampling method in 2018. An educational program consisting of four sessions was arranged once every 2 weeks for the intervention group. The data collection tools were Templer Death Anxiety Scale and the Health Literacy For Women with Breast Cancer (HELBA) questionnaire with a demographic information record form. Mann-Whitney test showed that there were no significant differences in the level of death anxiety and health literacy before the intervention between the control and intervention groups (p ≥ 0.05). But there were significant differences in the level of death anxiety between the intervention and control groups immediately after the intervention (Z = 3.38, p = 0.001) and one month later (Z = 3.10, p = 0.002). Also, there was significant differences in the level of health literacy immediately after the intervention (Z = 4.74, p < 0.001) and 1 month later (Z = 4.92, p < 0.001). The findings of this study showed that the use of a health literacy promotion program for women with breast cancer might increase their health literacy while it might decrease their level of death anxiety.


Human papillomavirus, genital warts, and vaccines.
Human papillomavirus (HPV)-related diseases, including cancers, low-grade neoplasia, genital warts, and recurrent respiratory papillomatosis, have a substantial impact on public health. The increasing incidence of HPV infection and genital warts highlights the need for an effective strategy for the management of this disease. Immunization holds the promise of reducing the overall burden of clinical HPV-related diseases. A prophylactic quadrivalent HPV 6/11/16/18 vaccine is highly effective for reducing the risk of HPV 6-, 11-, 16-, and 18-associated cervical cancer, precancerous cervical lesions, and external genital lesions, including genital warts.


Afrocolombian Struggles for Food, Land, and Culture: The Case of El Tiple.
El Tiple is one of many marginalized Afrodescendant communities confined within a green desert located in the southwest region of Colombia. This green desert is most widely known as the second-largest sugarcane monoculture field in the Americas. Herein, we describe a transdisciplinary and participatory effort to understand agroindustrial expansion in the region through the lens of the El Tiple community. Using qualitative and quantitative methodologies, we characterized the socioenvironmental context of El Tiple in terms of ethnography, autoethnography, social cartography, and ethnobotany. We implemented a participatory approach to codevelop a technology-assisted strategy for strengthening the community's small-scale farming activities. Our contextual analysis results show systemic food dispossession, which arises from several factors, including dramatic land transformation, rapid depletion and contamination of natural assets, and biodiversity loss. All these factors are associated with the presence of bordering sugarcane plantations. In collaboration with community members, we designed, constructed, and analyzed a greenhouse hydroponic cultivation system as an actionable means to gradually restore local production of food and medicinal plants for the community. Our transdisciplinary and participatory approach demonstrates how academics can partner with vulnerable communities in the coproduction of knowledge and solutions to pressing social needs.


Sex differences in face gender recognition: an event-related potential study.
Multiple level neurocognitive processes are involved in face processing in humans. The present study examined whether the early face processing such as structural encoding is modulated by task demands that manipulate attention to perceptual or social features of faces and such an effect, if any, is different between men and women. Event-related brain potentials were recorded from male and female adults while they identified a low-level perceptual feature of faces (i.e., face orientation) and a high-level social feature of faces (i.e., gender). We found that task demands that required the processing of face orientations or face gender resulted in modulations of both the early occipital/temporal negativity (N170) and the late central/parietal positivity (P3). The N170 amplitude was smaller in the gender relative to the orientation identification task whereas the P3 amplitude was larger in the gender identification task relative to the orientation identification task. In addition, these effects were much stronger in women than in men. Our findings suggest that attention to social information in faces such as gender modulates both the early encoding of facial structures and late evaluative process of faces to a greater degree in women than in men.


Anaphylaxis. The GP perspective.
Anaphylaxis is not uncommon in Australia, representing the most severe form of allergy. It is most likely to be triggered by food with the most common allergen being peanuts. It constitutes a medical emergency that requires a rapid medical response. This article aims to provide an overview of anaphylaxis--its prevalence, causes, diagnosis and treatment both acutely and in relation to long term management. It also aims to highlight the importance of having a protocol established for the management of this condition in the emergency situation. With the increased prevalence of allergy in the community, it is likely that at some stage most general practitioners will have to treat a case of acute anaphylaxis. It is imperative that GPs are prepared for such an event as failure to recognise the condition or to follow a validated protocol can have fatal consequences.


[Maturation of gonadotropin function during growth of the male rat: influence of neonatal castration (author's transl)].
Evolution during growth of plasma level gonadotropins, was studied in the normal or castrated rat at birth. In the control animals, the plasma level of gonadotropins increased from the 25th day to the 40th day, then declined to the 90th day. Neonatal castration induced a new phenomenon: the increase of plasma gonadotropins in the normal rat corresponded with a decrease in the castrated animals and inversely. Testis hormones affected gonadotropin function; however, an autonomous maturation of this function, independent of gonadal secretions, appeared to exist.


[Antimicrobial activity of nano-hydroxyapatite/polyamide 66 as a pulp capping agent in vitro].
OBJECTIVE To investigate the in vitro antimicrobial activity of nano-hydroxyapatite/polyamide 66 composites (nHA-PA66) as a pulp capping agent. The micro-organisims used in this study included Streptococcous mutans (S. mutans), Lactobacillus casei (L. casei) and Actinomyces viscosus (A. viscosus), three standard bacterial strains predominant in deep carious lesions. Agar diffusion test was used to determine the diameter of bacterial inhibition zones of nHA-PA66 compared with hydroxyapatite paste, calcium hydroxide paste and nHA-PA66 mixed with iodoform paste. It showed that the polymerized films and fresh paste of nHA-PA66 had no antimicrobial activity to S. mutans and very little to L. casei and A. viscosus. The antimicrobial activity of nHA-PA66 mixed with iodoform paste obviously increased, but no significant difference compared with calcium hydroxide paste. There, was no antimicrobial activity of hydroxyapatite paste to the three test bacterial strains. These findings suggest nHA-PA66 used as pulp capping agent alone almost has no antimicrobial effect to the three test bacteria, but the antimicrobial activity can be increased by combining with iodoform.


Sutureless biliodigestive anastomosis.
New modification of suture--free biliodigestive anastomosis was proposed. The suture--free anastomosis in our modification is performed by the help of Foley catheter. This technique was verified in dog experiments and than used for operation of four patients. Of these patients none died due to surgical intervention.


Directional Submicrofiber Hydrogel Composite Scaffolds Supporting Neuron Differentiation and Enabling Neurite Alignment.
Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel-fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber-hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber-hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord.


Does low acid orange juice equal low erosion?
This paper compares the erosive potential of standard Tropicana smooth orange juice with a new low acid orange juice. Three parameters are compared in the laboratory; pH, neutralizable acidity and the ability to erode enamel. The pH of the standard orange juice is 3.88 compared with the low acid orange juice which has a pH of 4.18. The neutralizable acidity of the low acid juice is lower (16.96 ml of 0.1 M NaOH) than the standard juice (28.46 ml of 0.1 M NaOH). The low acid orange juice produces less enamel erosion (2.49 microm) than the standard juice (5.23 pm). Ideally, these laboratory findings need to be confirmed in a randomized controlled clinical trial before this product could be recommended unreservedly for patients that are clinically susceptible to erosion. As dietary advice forms a cornerstone in the clinical management of erosion, the introduction of a commercially available low acid orange is most welcome.


Complete and safe resection of challenging retroperitoneal tumors: anticipation of multi-organ and major vascular resection and use of adjunct procedures.
Retroperitoneal tumors are often massive and can involve adjacent organs and/or vital structures, making them difficult to resect. Completeness of resection is within the surgeon's control and critical for long-term survival, particularly for malignant disease. Few studies directly address strategies for complete and safe resection of challenging retroperitoneal tumors. Fifty-six patients representing 63 cases of primary or recurrent retroperitoneal tumor resection between 2004-2009 were identified and a retrospective chart review was performed. Rates of complete resection, use of adjunct procedures, and perioperative complications were recorded. In 95% of cases, complete resection was achieved. Fifty-eight percent of these cases required en bloc multi-organ resection, and 8% required major vascular resection. Complete resection rates were higher for primary versus recurrent disease. Adjunct procedures (ureteral stents, femoral nerve monitoring, posterior laminotomy, etc.) were used in 54% of cases. Major postoperative complications occurred in 16% of cases, and one patient died (2% mortality). Complete resection of challenging retroperitoneal tumors is feasible and can be done safely with important pre- and intraoperative considerations in mind.


Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients.
Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation. The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control. COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 μg/day or FP/S 500/100 μg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index. Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S. BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation.


The phenotype of Hurthle and Warthin-like papillary thyroid carcinomas is distinct from classic papillary carcinoma as to the expression of retinoblastoma protein and E2F-1 transcription factor.
Retinoblastoma protein plays an important role in controlling cell cycle progression. The active form of retinoblastoma protein binds to E2F-1 and inhibits transcription of S phase genes. Overexpression of E2F-1 has been suggested as an important factor in carcinogenesis. The Hurthle cell (HPCA) and Warthin-like (WLPCA) variants of papillary carcinoma are two closely related entities that arise in association with Hashimoto's thyroiditis and share the presence of oxyphilic changes in the lining of epithelial cells and the presence of papillary nuclear features. The current study included formalin-fixed, paraffin-embedded tissues from 58 cases of thyroid papillary carcinoma: 20 HPCA, 6 WLPCA, 22 conventional papillary carcinomas (PCA), and 10 follicular variants of papillary carcinoma (FVPCA). The immunohistochemical studies were performed for retinoblastoma (Rb-1) and E2F-1, (KH95) after heat-induced epitope retrieval. None of the PCA or FVPCA cases were in the positive range for Rb-1. All cases of HPCA and WLPCA of the thyroid showed reactivity in 50% or more of the nuclei in the neoplastic cell population. As for E2F-1, all cases of HPCA and WLPCA showed positive reactivity, whereas none of the PCA or FVPCA cases were in the positive range. In conclusion, HPCA and WLPCA are Rb-positive and E2F-1-positive; PCA and FVPCA are Rb-negative and E2F1-negative. Hurthle metaplastic epithelium in Hashimoto's thyroiditis is Rb-positive and E2F-1-negative. This phenotypic difference is also helpful in distinguishing hyperplastic Hurthle cell proliferation in Hashimoto's thyroiditis from HPCA or WLPCA.


Effectiveness of different types and levels of social distancing measures: a scoping review of global evidence from earlier stage of COVID-19 pandemic.
Social distancing is one of the main non-pharmaceutical interventions used in the control of the COVID-19 pandemic. This scoping review aims to synthesise research findings on the effectiveness of different types and levels of social distancing measures in the earlier stage of COVID-19 pandemic without the confounding effect of mass vaccination. Scoping review. MEDLINE, Embase, Global Health and four other databases were searched for eligible studies on social distancing for COVID-19 published from inception of the databases to 30 September 2020. Effectiveness studies on social distancing between individuals, school closures, workplace/business closures, public transport restrictions and partial/full lockdown were included. Non-English articles, studies in healthcare settings or not based on empirical data were excluded. After screening 1638 abstracts and 8 additional articles from other sources, 41 studies were included for synthesis of findings. The review found that the outcomes of social distancing measures were mainly indicated by changes in Rt , incidence and mortality, along with indirect indicators such as daily contact frequency and travel distance. There was adequate empirical evidence for the effect of social distancing at the individual level, and for partial or full lockdown at the community level. However, at the level of social settings, the evidence was moderate for school closure, and was limited for workplace/business closures as single targeted interventions. There was no evidence for a separate effect of public transport restriction. In the community setting, there was stronger evidence for the combined effect of different social distancing interventions than for a single intervention. As fatigue of preventive behaviours is an issue in public health agenda, future studies should analyse the risks in specific settings such as eateries and entertainment to implement and evaluate measures which are proportionate to the risk.


Engineering a pH-Sensitive Liposomal MRI Agent by Modification of a Bacterial Channel.
MscL is a bacterial mechanosensitive channel that serves as a cellular emergency release valve, protecting the cell from lysis upon a drop in external osmolarity. The channel has an extremely large pore (30 Å) and can be purified and reconstituted into artificial membranes. Moreover, MscL is modified to open in response to alternative external stimuli including changes in pH. These properties suggest this channel's potential as a triggered "nanopore" for localized release of vesicular contents such as magnetic resonance imaging (MRI) contrast agents and drugs. Toward this end, several variants of pH-triggered MscL nanovalves are engineered. Stealth vesicles previously been shown to evade normal in vivo clearance and passively accumulate in inflamed and malignant tissues are reconstituted. These vesicles are loaded with 1,4,7,10-tetraazacyclododecane tetraacetic acid gadolinium complex (Gd-DOTA), an MRI contrast reagent, and the resulting nanodevices tested for their ability to release Gd-DOTA as evidenced by enhancement of the longitudinal relaxation rate (R1 ) of the bulk water proton spins. Nanovalves that are responsive to physiological pH changes are identified, but differ in sensitivity and efficacy, thus giving an array of nanovalves that could potentially be useful in different settings. These triggered nanodevices may be useful in delivering both diagnostic and therapeutic agents.


[Exercise tolerance in evaluating the efficacy of continuous electrocardiostimulation in patients with atrioventricular block].
Fifty-three patients with brady-cardia were examined prior to and 1 year after the implantation of the cardiostimulator. It was found that the bicycle ergometric test was not contraindicated in examining the function of the respiration and circulation in patients with stable forms of bradyarrhythmia. Three types of the body's response to exercise were identified. It was shown that in patients with the third type of response the compensatory possibilities of the respiratory and cardiovascular systems were at the breaking point. The authors believe that electrocardiostimulation in them is of a doubtful value in terms of improving the quality of life and restoring the capacity for work. Implantation of cardiostimulators in such patients is mostly necessary in the presence of Morgagni-Edems-Stokes attacks.


The influence of voluntary muscle contractions upon the onset and modulation of tinnitus.
To evaluate the frequency of tinnitus onset (in normal subjects) and modulation (in tinnitus patients) during muscle contractions, estimating possible risk factors. This case-control study enrolled 121 tinnitus patients and 100 healthy volunteers who underwent medical history, ENT examination and 16 maneuvers of muscular contraction (head, neck and limbs). Modulation data were compared between patients with and without normal audiometry, well-defined diagnosis and symptoms of craniomandibular disorders. The ability to modulate tinnitus (65.3%) was significantly higher than that to originate tinnitus (14.0%). The head and neck musculature was significantly more efficient than that of the limbs. Audiometric pattern, well-defined etiology and symptoms of craniomandibular disorders showed no relation to tinnitus modulation. Somatic modulation is a characteristic aspect of tinnitus.


A Quantitative Framework Classifying the Palliative Care Workforce into Specialist and Generalist Components.
Early referral to palliative care (PC) services has been shown to improve quality of life in advanced cancer. However, limitations in trained PC workforce raise issues with the sustainability of delivering PC with early PC referral. Classifying PC into generalist and specialist components could be one approach to sustainable PC delivery models but a quantitative guide for this classification is presently lacking in the literature. To undertake a retrospective examination of clinical data obtained from a PC benchmarking project to develop a quantitative framework guiding classification of PC services into specialist and generalist components. A descriptive retrospective study of data from 2726 hospitalized inpatients under the care of a tertiary consultative PC service over a 2-year period was conducted. Daily categorical symptom, overall psychological and social distress scores at the start and end of 3392 palliative care episodes as well as the number of visits made by the PC team to patients were extracted for analysis. More than 50% of patients had symptom, overall psychological or social distress scores of nil or mild severity at episode start and end. Approximately 20% of all 2726 patients accounted for approximately half of all visits made by the team regardless of the reasons for review. This patient percentage minority had more PC episodes starting with moderate or severe pain. These findings suggest a Pareto-like distribution in the occurrence of moderate/severe PC problems and the intensity of PC input. Large-scale clinical data supports the use of a Pareto-based quantitative framework for a workforce comprising of mainly generalist PC staff supported by smaller numbers of PC specialists.


Evaluating ChatGPT's Ability to Solve Higher-Order Questions on the Competency-Based Medical Education Curriculum in Medical Biochemistry.
Background Healthcare-related artificial intelligence (AI) is developing. The capacity of the system to carry out sophisticated cognitive processes, such as problem-solving, decision-making, reasoning, and perceiving, is referred to as higher cognitive thinking in AI. This kind of thinking requires more than just processing facts; it also entails comprehending and working with abstract ideas, evaluating and applying data relevant to the context, and producing new insights based on prior learning and experience. ChatGPT is an artificial intelligence-based conversational software that can engage with people to answer questions and uses natural language processing models. The platform has created a worldwide buzz and keeps setting an ongoing trend in solving many complex problems in various dimensions. Nevertheless, ChatGPT's capacity to correctly respond to queries requiring higher-level thinking in medical biochemistry has not yet been investigated. So, this research aimed to evaluate ChatGPT's aptitude for responding to higher-order questions on medical biochemistry. Objective In this study, our objective was to determine whether ChatGPT can address higher-order problems related to medical biochemistry. Methods This cross-sectional study was done online by conversing with the current version of ChatGPT (14 March 2023, which is presently free for registered users). It was presented with 200 medical biochemistry reasoning questions that require higher-order thinking. These questions were randomly picked from the institution's question bank and classified according to the Competency-Based Medical Education (CBME) curriculum's competency modules. The responses were collected and archived for subsequent research. Two expert biochemistry academicians examined the replies on a zero to five scale. The score's accuracy was determined by a one-sample Wilcoxon signed rank test using hypothetical values. Result The AI software answered 200 questions requiring higher-order thinking with a median score of 4.0 (Q1=3.50, Q3=4.50). Using a single sample Wilcoxon signed rank test, the result was less than the hypothetical maximum of five (p=0.001) and comparable to four (p=0.16). There was no difference in the replies to questions from different CBME modules in medical biochemistry (Kruskal-Wallis p=0.39). The inter-rater reliability of the scores scored by two biochemistry faculty members was outstanding (ICC=0.926 (95% CI: 0.814-0.971); F=19; p=0.001) Conclusion The results of this research indicate that ChatGPT has the potential to be a successful tool for answering questions requiring higher-order thinking in medical biochemistry, with a median score of four out of five. However, continuous training and development with data of recent advances are essential to improve performance and make it functional for the ever-growing field of academic medical usage.


Computed tomographic localization for fine needle aspiration biopsy of orbital tumors.
Fine needle aspiration biopsy techniques have recently been applied to the evaluation of orbital masses. Ultrasound and CT examination have been useful in accurately localizing and characterizing such lesions prior to biopsy. Small retrobulbar tumors may be difficult to biopsy using blind needling, despite accurate localization. Preliminary studies on cadaver orbits confirmed that successful biopsy of the normal optic nerve could be accomplished using direct CT guidance. The technique was applied to 2 patients with monocular blindness due to small infiltrating optic nerve tumors and a histologic diagnosis was obtained in each case. This low morbidity procedure though applicable to only a small group of patients may spare them the morbidity of an orbitiotomy or craniotomy.


Changes in flavor compounds of dry-cured Chinese Jinhua ham during processing.
Sixty experimental Jinhua hams were processed by a traditional method using green hams from local Liangtouwu cross-bred pigs. Samples of Biceps femoris were taken from five hams randomly at each of the key stages of production, i.e., green ham, end of salting, end of sun-drying, middle of loft-aging, end of loft-aging, post-aging-1 and post-aging-2. Analysis of flavor compounds showed 89 compounds at the green ham stage and at the end of salting, 90 at the end of sun-drying, 91 at the middle of loft-aging, 96 at the end of loft-aging, 93 at the post-age-1 and 94 at the post-age-2. The flavor compounds could be clustered in the following chemical families: alkanes and alkenes, aromatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids, esters, oxygenous heterocycle compounds, nitrogenous compounds, sulphur compounds, chloride compounds, amides, and terpenes. During processing, the concentrations of aldehydes and carboxylic acids increased; while the concentrations of alcohols, ketones, alkanes, alkenes, aromatic and cyclic hydrocarbons decreased. Sulphur compounds and pyrazines were formed and increased continuously during processing. In the final Jinhua ham, the contents of aldehydes, carboxylic acids, alcohols and ketones were 45.07%, 18.39%, 13.93% and 9.00% of the total flavor substances, respectively. The first principal component was a group dominated by five unbranched aldehydes; the second principal component was a group dominated by five branched and unbranched alcohols, two branched ketones, toluene, hexane and 4-nitrophthalamide. The two principal components explained 90.6% of the total flavor variance in Jinhua ham.


Friction-Induced Skin Disorders-A Review.
Friction is unavoidable in activites of daily life and is associated with various dermatological disorders. A comprehensive literature review showed friction can induce epidermal changes, dermatitis, alteration of the dermis, diseases of abnormal deposition, alteration of the hair and follicles, nail diseases, pigmentary disorders, and skin tumors. Cultural, religious, and occupational factors may predispose to the development friction-related skin disorders. However, friction often occurs together with other external stimuli, such as pressure and occlusion. Careful observation and investigation are required to establish the exact role of friction in the development of various dermatoses.


Intra- and inter-rater reliability of joint range of motion tests using tape measure, digital inclinometer and inertial motion capturing.
In clinical practice range of motion (RoM) is usually assessed with low-cost devices such as a tape measure (TM) or a digital inclinometer (DI). However, the intra- and inter-rater reliability of typical RoM tests differ, which impairs the evaluation of therapy progress. More objective and reliable kinematic data can be obtained with the inertial motion capture system (IMC) by Xsens. The aim of this study was to obtain the intra- and inter-rater reliability of the TM, DI and IMC methods in five RoM tests: modified Thomas test (DI), shoulder test modified after Janda (DI), retroflexion of the trunk modified after Janda (DI), lateral inclination (TM) and fingertip-to-floor test (TM). Two raters executed the RoM tests (TM or DI) in a randomized order on 22 healthy individuals while, simultaneously, the IMC data (Xsens MVN) was collected. After 15 warm-up repetitions, each rater recorded five measurements. Intra-rater reliabilities were (almost) perfect for tests in all three devices (ICCs 0.886-0.996). Inter-rater reliability was substantial to (almost) perfect in the DI (ICCs 0.71-0.87) and the IMC methods (ICCs 0.61-0.993) and (almost) perfect in the TM methods (ICCs 0.923-0.961). The measurement error (ME) for the tests measured in degree (°) was 0.9-3.3° for the DI methods and 0.5-1.2° for the IMC approaches. In the tests measured in centimeters the ME was 0.5-1.3cm for the TM methods and 0.6-2.7cm for the IMC methods. Pearson correlations between the results of the DI or the TM respectively with the IMC results were significant in all tests except for the shoulder test on the right body side (r = 0.41-0.81). Measurement repetitions of either one or multiple trained raters can be considered reliable in all three devices.