The effect of 60-Hz magnetic fields on co-promotion of chemically induced skin tumors on SENCAR mice: a discussion of three studies.
Three independent experiments involving a total of 288 SENCAR mice were used to study the effects of 60-Hz magnetic fields on the growth and development of skin tumors. Given the constraints imposed by the experimental design, the results did not support a role for magnetic fields as a tumor co-promoter. This negative finding could also be interpreted to mean that the SENCAR mouse skin tumor model was not sensitive enough to detect the action of a weak co-promoter. The two-stage (initiation/promotion) model was used to assess the genotoxic potential of magnetic fields because it had been widely used to evaluate chemical carcinogens. This model, however, lacks the sensitivity to detect all but the most potent direct-acting carcinogens, and the tumor response to the action of low doses of promoter results in large random fluctuations in tumor incidence, yield, and multiplicity. The need to limit tumor incidence in the sham is a necessary condition to ensure that a magnetic field-induced effect on tumorigenesis would have a reasonable chance of being detected. This requirement, and the variability in tumor development between and within experiments, increases the level of uncertainty in the system and makes a weak response to the magnetic field difficult to detect and interpret.


Understanding how biologic and social determinants affect disparities in preterm birth and outcomes of preterm infants in the NICU.
To understand the disparities in spontaneous preterm birth (sPTB) and/or its outcomes, biologic and social determinants as well as healthcare practice (such as those in neonatal intensive care units) should be considered. Disparities in sPTB have been largely intractable and remain obscure in most cases, despite a myriad of identified risk factors for and causes of sPTB. We still do not know how they lead to the different outcomes at different gestational ages and if they are independent of NICU practices. Here we describe an integrated approach to study the interplay between the genome and exposome, which may drive biochemistry and physiology and lead to health disparities.


[Menopause and bone].
Osteoporosis is a diffuse disease of the skeleton characterized by a decrease and a change in bone microarchitecture, which causes excessive fragility of the bone exposing them to increased risk of fracture. It represents a major public health issue, with 200 million people suffering from this disease in the world. The therapeutic goal is to maintain bone mineral density while avoiding the risk of falling.


Dietary self-selection and intake of protein and energy is altered by the form of the diets.
The technique of dietary self-selection has been widely used to investigate proposed mechanisms of protein and carbohydrate regulation and to substantiate theories relating nutrients, brain chemistry and behaviour. These experiments have produced conflicting results which might be accounted for by differences in experimental variables or in the different techniques used to measure self-selection. The possibility that the sensory qualities of diets might alter dietary self-selection was examined in three groups of rats self-selecting protein and carbohydrate from pairs of isocaloric diets in which the physical form (finely-milled casein/corn starch powder, granular casein/corn starch powder and gelled finely-milled casein/corn starch), but not the nutrient composition of each pair was varied. In addition, since the serotonergic drug fenfluramine has been frequently used to influence dietary selection, the effects of this drug on the selection of protein and carbohydrate from the three diets were also examined. The selection of particular diets and consequently protein and carbohydrate intake was markedly altered by the form of the diet. Furthermore, the effects of fenfluramine on diet selection were also modified significantly by the form of the diet. These results suggest that intake of certain nutrients is not strictly regulated at a particular fixed value and that drug-induced changes of self-selection behaviour must be interpreted cautiously.


Genetic algorithm based ensemble system using MLR and MsetCCA methods for SSVEP frequency recognition.
BCI systems provide a direct communication channel between the human and the machine using brain signals. Among the various methods of steady-state visual evoked potential (SSVEP) stimulation frequency detection, multiple linear regression (MLR), and multiset canonical correlation analysis (MsetCCA) methods have achieved high accurate results in recent studies. The purpose of this study is to utilize both approaches and benefit from them using a genetic algorithm (GA). This algorithm leads to high-performance optimization due to its large number of regulatory parameters. Signal analysis was performed for the windows with 0.5 to 4 s duration length and with 0.5-second incremental steps. In this paper, we were able to achieve 100% accuracy of recognition for 2-second time-windows using the genetic algorithm to optimally ensemble SSVEP stimulation frequency detection methods. The accuracy of the proposed system indicates a significant improvement in detection compared to either MLR or MsetCCA alone and indicates that the ensemble system is correctly optimized using the genetic algorithm. Genetic algorithm is one of the most widely used algorithms because of its high regulatory parameters leading to its high flexibility. The improvement in detection of the proposed system is due to the use of the strengths of both two methods, and the optimal choice of the system response to visual stimuli.


Multiple odontogenic keratocysts in Ehlers-Danlos syndrome: a rare case report.
An odontogenic keratocyst is a lesion characterized by aggressive and infiltrative growth. The lesion is characterized by the existence of satellite microcysts (microtumours) and frequent recurrence (up to 30%). Ehlers-Danlos syndrome is a condition in which collagen production or its post-translational modifications are affected. Defects in connective tissues cause symptoms, which range from mild joint hypermobility to life-threatening complications. We present an extremely rare case of an 11-year old girl with Ehlers-Danlos syndrome and coexistence of multiple odontogenic keratocysts. This case shows mainly atypical or rare association between multiple odontogenic keratocysts and Ehlers-Danlos syndrome.


Cutaneous extrarenal rhabdoid tumor with myogenic differentiation.
The rhabdoid phenotype is characterized by large epithelioid cells with abundant eosinophilic cytoplasm and paranuclear inclusions of intermediate filaments. Although originally described in tumors from pediatric kidneys, the rhabdoid phenotype has since been described in a variety of patient ages and extrarenal sites. Extraordinarily, the rhabdoid phenotype has emerged in cutaneous neoplasms, either as a pure extrarenal rhabdoid tumor or a composite phenotype coupled with another malignancy. Regardless of the clinical setting, the rhabdoid phenotype is uniformly associated with aggressive biological behavior. We report the findings from a rare and very aggressive primary extrarenal rhabdoid tumor of the skin with myogenic differentiation. A 53-year-old woman presented with an ulcerated nodule on her right medial calf and ipsilateral inguinal lymphadenopathy. Histological examination of the skin nodule as well as cytologic examination of a lymph node disclosed the characteristic rhabdoid phenotype. Electron microscopy demonstrated paranuclear globules of intermediate filaments; special stains suggested an underlying myogenic histogenesis. The patient was aggressively treated with chemotherapy but ultimately died of her disease 8 months after presentation. The rhabdoid phenotype is rarely seen in cutaneous neoplasms, but when present, portends a poor prognosis adding particular importance to its recognition.


Vocal and physical phenotypes of calsyntenin2 knockout mouse pups model early-life symptoms of the autism spectrum disorder.
This study discovered a novel acoustic phenotype in Calsyntenin2 deficient knockout (Clstn2-KO) pups in the neurodevelopment period of 5-9 postnatal days (PND 5-9). The narrowband ultrasonic calls (nUSVs) were less complex (mostly one-note, shorter in duration and higher in peak frequency) in Clsnt2-KO than in wild-type (WT) C57BL/6 J pups. The wideband ultrasonic calls (wUSVs) were produced substantially more often by Clstn2-KO than WT pups. The clicks were longer in duration and higher in peak frequency and power quartiles in Clstn2-KO pups. The elevated discomfort due to additional two-minute maternal separation coupled with experimenter's touch, resulted in significantly higher call rates of both nUSVs and clicks in pups of both genotypes and sexes compared to the previous two-minute maternal separation, whereas the call rate of wUSVs was not affected. In Clstn2-KO pups, the prevalence of emission of wUSVs retained at both sex and both degrees of discomfort, thus providing a reliable quantitative acoustic indicator for this genetic line. Besides the acoustic differences, we also detected the increased head-to-body ratio in Clstn2-KO pups. Altogether, this study demonstrated that lack of such synaptic adhesion protein as calsyntenin2 affects neurodevelopment of vocalization in a mouse as a model organism.


Detection of polymerase chain reaction fragments using a conducting polymer-modified screen-printed electrode in a microfluidic device.
A simple and fast method for electrochemical detection of amplified fragments by PCR was successfully developed using CE in a microfluidic device with a modified screen-printed carbon electrode (SPCE). The surfaces of the SPCE were modified with poly-5,2'-5',2''-terthiophene-3'-carboxylic acid, which improves the analysis performance by lowering the detection potential, enhancing the S/N characteristics, and avoiding electrode poisoning. DNA fragments amplified by PCR were separated within 210 s in a 75.5 mm-long coated-separation channel at a separation field strength of -200 V/cm. To minimize the sample adsorption into the inner surface of the capillary wall, which disturbs the separation, a dynamically coated capillary with an acrylamide solution was used. Furthermore, the analysis procedure was simplified and rendered reproducible by using 0.50% w/v hydroxyethylcellulose as a separation matrix in a coated channel. The reproducibility of the analysis employing the coated channel yielded RSD of 4.3% for the peak areas and 1.4% for the migration times in eight repetitive measurements at a modified electrode, compared with 21.3 and 9.4% for a bare electrode. The sensitivity of the assay was 18.74 pAs/(pg/microL) with a detection limit of 584.31 +/- 1.3 fg/microL.


CT colonography training for radiographers--a formal evaluation.
To evaluate the efficacy of a new intensive "hands-on" course designed to train small teams of radiographers in computed tomography colonography (CTC) technique and initial interpretation for patient triage. The course comprised small-group lectures, active participation in the daily CTC service with practical technique and image interpretation training by experienced radiologists and radiographers. Evaluation was by assessment of knowledge using randomized sets of multiple choice questions (MCQ; pre/post-course), practical technique using checklists and expert global scores, and interpretation performance outcomes using randomized pre/post-course test datasets (five validated CTC examinations each). Paired t-tests were used to investigate change in performance for MCQ score and interpretation accuracy. Thirteen courses with 49 participants were evaluated over 2 years. Practical skills were high, with mean (SD) checklist scores of 14/15 (0.85) and global scores of 26/30 (2.3). MCQ scores increased significantly from a mean of 59% pre-course to 69% post-course, p<0.001. Correct classification of CTC examination improved significantly from a mean of 55% pre-course to 71% post-course, p<0.001. Cancer and large polyp (>10mm) detection rates also improved significantly from 49% to 60%, p=0.002. Structured training in CTC can significantly improve knowledge and interpretation skills of radiographers, while assessing safe procedural performance. Implementation of similar programmes nationally may help reduce performance gaps between centres.


The prevalence of celiac disease in Europe: results of a centralized, international mass screening project.
Although the prevalence of celiac disease (CD) has been extensively investigated in recent years, an accurate estimate of CD frequency in the European population is still lacking. The aims of this study were: 1) to establish accurately the prevalence of CD in a large sample of the European population (Finland, Germany, Italy, and UK), including both children and adults; and 2) to investigate whether the prevalence of CD significantly varies between different areas of the European continent. Samples were drawn from the four populations. All 29,212 participants were tested for CD by tissue transglutaminase (tTG) antibody test. Positive and border-line findings were further tested for serum endomysial antibodies (EMA). All serological determinations were centrally performed. Small-bowel biopsies were recommended to autoantibody-positive individuals. Previously diagnosed cases were identified. The overall CD prevalence (previously diagnosed plus anti-tTG and EMA positives) was 1.0% (95% CI 0.9-1.1). In subjects aged 30-64 years CD prevalence was 2.4% in Finland (2.0-2.8), 0.3% in Germany (0.1-0.4), and 0.7% in Italy (0.4-1.0). Sixty-eight percent of antibody-positive individuals showed small-bowel mucosal changes typical for CD (Marsh II/III lesion). CD is common in Europe. CD prevalence shows large unexplained differences in adult age across different European countries.


Reactive oxygen species-evoked endoplasmic reticulum stress mediates 1-nitropyrene-induced epithelial-mesenchymal transition and pulmonary fibrosis.
1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 μg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-β wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.


The genome-associated, specific RNA binding proteins of avian and mammalian type C viruses.
A structural protein purified from the Rous sarcoma virus (RSV) can specificially bind in vitro to purified avian, but not mammalian, type C viral RNA. Following ultraviolet irradiation of viral particles under conditions which stabilize the polyploid 70S viral RNA, the same polypeptide can be directly purified from the RSV genome. Based on its electrophoretic mobility in polyacrylamide gels containing sodium dodecylsulfate, the RNA binding protein has been identified as the major phosphoprotein (p19) of avian type C viruses. Similar experiments show that the major phosphoproteins of mammalian type C viruses (p12 for murine viruses and p16 for endogenous primate viruses) are also the specific RNA binding proteins and, similarly, are found closely associated with the 70S RNA genomes in the intact viral particles.


Correlated NOS-Imu and myf5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment.
Satellite cells, muscle precursor cells in skeletal muscle, are normally quiescent and become activated by disease or injury. A lack of dystrophin and changes in the expression or activity of neuronal nitric oxide synthase (NOS-I) affect the timing of activation in vivo. Nitric oxide synthase inhibition delays muscle repair in normal mice, and worsens muscular dystrophy in the mdx mouse, a genetic homologue of Duchenne muscular dystrophy. However, the potential role of activation and repair events mediated by nitric oxide in determining the outcome of steroid or other treatments for muscular dystrophy is not clear. We tested the hypothesis that the extent of repair in dystrophic muscles of mdx mice is partly dependent on NOS-Imu expression and activity. Myotube formation in regenerating muscle was promoted by deflazacort treatment of mdx dystrophic mice (P<0.05), and improved by combination with the nitric oxide synthase substrate, L-arginine, especially in the diaphragm. NOS-Imu mRNA expression and activity were present in satellite cells and very new myotubes of regenerating and dystrophic muscle. Deflazacort treatment resulted in increased NOS-Imu expression in regenerating muscles in a strong and specific correlation with myf5 expression (r=0.95, P<0.01), a marker for muscle repair. Nitric oxide synthase inhibition prevented the deflazacort-induced rise in NOS-Imu and myf5 expression in the diaphragm without affecting the diameter of non-regenerating fibres. These in vivo studies suggest that gains in NOS-Imu expression and nitric oxide synthase activity in satellite cells can increase the extent and speed of repair, even in the absence of dystrophin in muscle fibres. NOS-Imu may be a useful therapeutic target to augment the effects of steroidal or other treatments of muscular dystrophy.


Pathologically confirmed port site metastasis after laparoscopic radical prostatectomy: case report and literature review.
Laparoscopic port site metastases remain exceedingly rare for urologic tumors, despite the increasingly widespread use of laparoscopic techniques in the management of urologic malignancy. We report a case of port site metastases after transperitoneal laparoscopic radical prostatectomy.


Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease.
Mutations in Vps13D cause defects in autophagy, clearance of mitochondria, and human movement disorders. Here, we discover that Vps13D functions in a pathway downstream of Vmp1 and upstream of Marf/Mfn2. Like vps13d, vmp1 mutant cells exhibit defects in autophagy, mitochondrial size, and clearance. Through the relationship between vmp1 and vps13d, we reveal a novel role for Vps13D in the regulation of mitochondria and endoplasmic reticulum (ER) contact. Significantly, the function of Vps13D in mitochondria and ER contact is conserved between fly and human cells, including fibroblasts derived from patients suffering from VPS13D mutation-associated neurological symptoms. vps13d mutants have increased levels of Marf/MFN2, a regulator of mitochondrial fusion. Importantly, loss of marf/MFN2 suppresses vps13d mutant phenotypes, including mitochondria and ER contact. These findings indicate that Vps13d functions at a regulatory point between mitochondria and ER contact, mitochondrial fusion and autophagy, and help to explain how Vps13D contributes to disease.


Neuropeptide α-Melanocyte-Stimulating Hormone Promotes Neurological Recovery and Repairs Cerebral Ischemia/Reperfusion Injury in Type 1 Diabetes.
Persons with type 1 diabetes have an increased risk of stroke compared with the general population. α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide that has protective effects against ischemia/reperfusion (I/R) induced organ damages. In this study, we aimed to investigate the neuroprotective role of this peptide on I/R induced brain damage after experimental stroke associated with hyperglycemia using C57BL/6J Ins2Akita/+ mice. Experimental stroke was induced by blocking the right middle cerebral artery for 2 h with reperfusion for 2 and 22 h, respectively using the intraluminal method. Animals were treated intraperitoneally with or without α-MSH at 1 h after ischemia and 1 h after reperfusion. Significantly higher survival rate and lower neurological scores were recorded in animals injected with α-MSH. Similarly, neuron death, glial cells activation as well as oxidative and nitrosative stress were significantly decreased in α-MSH treated group. Relative intensities of matrix metallopeptidases 9, cyclooxygenase 2 and nuclear factor-κB were significantly decreased while intensities of Akt, heme oxygenase (HO) 1, HO-2 and B-cell lymphoma 2 were significantly increased after α-MSH treatment. In addition, gene expressions of monocarboxylate transporter (MCT) 1, MCT-2 and activity-regulated cytoskeleton-associated protein were significantly higher in brain samples treated with α-MSH, suggesting this peptide may have role in neuron survival by an involvement of lactate metabolism. In conclusion, α-MSH is neuroprotective under hyperglycemic condition against I/R induced brain damage by its anti-inflammatory, anti-oxidative and anti-apoptotic properties. The use of α-MSH analogues may be potential therapeutic agents for diabetic stroke.


Local Delivery of Senolytic Drug Inhibits Intervertebral Disc Degeneration and Restores Intervertebral Disc Structure.
Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low back pain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.


Calcium Delivery System Assembled by a Nanostructured Peptide Derived from the Sea Cucumber Ovum.
In this study, the binding mechanism, morphological, and conformational analysis of the complex of a sea cucumber ovum derived octapeptide (EDLAALEK) with Ca2+ as well as its calcium delivery behavior via the gastrointestinal (GI) tract were investigated. The Ca2+ specifically bound to two carboxyl oxygen atoms of C-terminal Glu and Asp on the EDLAALEK peptide at a stoichiometric ratio of 1:1. Calcium coordination induced the self-assembly of the EDLAALEK peptide, resulting in the formation of a nanocomposite with a crystal structure. Furthermore, the formed nanocomposite went through dissociation and self-assembly during in vitro GI digestion, accompanied by the release and rechelation of Ca2+, which was related to changes in their secondary structure. Nevertheless, the GI digests of the EDLAALEK-calcium complex could significantly enhance Ca2+ absorption across Caco-2 cell monolayers. The findings suggest that the sea cucumber ovum derived peptide has the potential as an efficient nanocarrier to transport calcium through the GI system.


Allograft contamination during suture preparation for anterior cruciate ligament reconstruction: an ex vivo study.
Effects of suture preparation on graft contamination remain unknown in anterior cruciate ligament reconstruction (ACLR). This study aimed to evaluate the incidence of allograft contamination at different time points of graft preparation and investigate differences in contamination between different sites of the allografts. Fourteen hamstring tendon (HT), 9 quadriceps tendon (QT), and 9 bone-patellar tendon-bone (BTB) allografts were harvested, sterilised, and stored following routine procedures. Graft suture preparation was performed with baseball stitching for soft tissue and bone drilling for bone plug. The time was recorded simultaneously. The graft was kept moist in a standard operating room environment for 30 min after the initiation of preparation. The specimens were obtained from the middle and both ends of each graft for culture at three different time points: pre-suturing, post-suturing, and 30 min after the initiation of preparation. A total of 192 specimens were transferred to the microbiology laboratory for culture, identification, and semi-quantitative assessment. Culture results were classified as negative, poor, and abundant based on the extent of growth. Contamination level was recorded as low or high corresponding to culture results of poor or abundant. The duration of suture preparation was 348, 301, and 246 s for HT, QT, and BTB (P = 0.090). The specimens had a positive culture rate of 41/192 (21.4%), of which 21 were from the ends and 20 from the middle. More positive samples with abundant bacterial growth were detected from the ends than from the middles post-suturing (7/8 vs. 1/7, P = 0.010) and at 30 min (6/11 vs. 0/11, P = 0.012). The total graft contamination rate was significantly higher at 30 min (19/32, 59.4%) than pre-suturing (4/32, 15.6%) and post-suturing (9/32, 28.1%) (P < 0.001). The contamination rate with abundant bacterial growth was higher post-suturing (7/32, 21.9%) than pre-suturing (0%). No statistically significant differences were found among the three types of allografts. The contamination rate increases significantly at 30 min compared with pre-suturing and post-suturing. Suture preparation may have introduced the high-level contamination, to which the ends of the graft were more prone than the middle. Therefore, routine prophylactic decontamination after suture preparation should be considered, especially for the ends of the grafts.


Anthrax toxin delivers a one-two punch.
Although anthrax toxin was identified as a major Bacillus anthracis virulence factor over 50 years ago, defining the physiologically relevant targets has been challenging. Liu et al. demonstrate that intoxication of myeloid-derived cells contributes to establishing infection but is not required for mortality resulting from high toxin concentrations associated with end-stage disease.


Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension.
Dietary nitrite and nitrate are important sources of nitric oxide (NO). However, the use of nitrite as an antihypertensive drug may be limited by increased oxidative stress associated with hypertension. We evaluated the antihypertensive effects of sodium nitrite given in drinking water for 4 weeks in two-kidney one-clip (2K1C) hypertensive rats and the effects induced by nitrite on NO bioavailability and oxidative stress. We found that, even under the increased oxidative stress conditions present in 2K1C hypertension, nitrite reduced systolic blood pressure in a dose-dependent manner. Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats, it increased plasma nitrate levels significantly. Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats. A series of in vitro experiments was carried out to show that the antioxidant effects induced by nitrite do not involve direct antioxidant effects or xanthine oxidase activity inhibition. Conversely, nitrite decreased vascular NADPH oxidase activity. Taken together, our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats, which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition.


Laparoscopic demonstration of vena cava wall penetration by inferior vena cava filters in an ovine model.
To verify the penetration of struts and hooks of two inferior vena cava (IVC) filters (Günther tulip retrievable filter [GTF] and Celect filter) through the vena cava wall and to assess local or systemic complications resulting from this penetration. Eight IVC filters were placed in the IVC of four ewes for 30 days (1 GTF and 1 Celect filter in each ewe). Angiographic and laparoscopic examinations of the animals were performed to demonstrate the penetration through the vena cava wall, and the filters were removed under laparoscopic control. Specimens were extracted for anatomicopathological and histologic examination. Two-projection cavography showed a filter leg seemingly out of the vena cava in 19 of 32 legs (59.3%). Laparoscopy showed 7 real penetrating legs (5 Celect filters and 2 GTFs) out of the 14 legs that could be identified by laparoscopy owing to technique limitations. Neither laparoscopy nor necropsy showed any sign of wall hemorrhage or other injuries. Histologic examination showed intimal remodeling and slight thickening of adventitial tissue around filter legs. GTFs and Celect filters can produce a real penetration 1 month after implantation. This penetration did not lead to any complications in the IVC or surrounding tissues and did not compromise the subject's health in any of the studied cases.


Screening for Kidney Disease in Low- and Middle-Income Countries.
Kidney disease is the 10th leading cause of death worldwide and disproportionately increases morbidity and mortality for people residing in low- and middle-income countries (LMICs). Considering the high burden of chronic kidney disease (CKD) on patients, society, and health care systems, strategies to improve screening for CKD need to be prioritized. With appropriate interventions, screening could prevent progression of early stages of CKD and, ultimately, reduce the need for kidney replacement therapy. Unfortunately, few data exist to inform screening strategies for early detection and management of CKD in LMICs, where risk factors for CKD may differ from those in high-income countries. We review here the epidemiology of kidney disease in LMICs, current practices for screening for kidney disease, and challenges and opportunities available to LMICs. We also recommend ways in which screening could be improved for early identification and care for patients with kidney disease in LMICs and highlight critical gaps in knowledge.


Clinical experience of QuantiFERON(®) -TB Gold testing in patients with psoriasis treated with tumour necrosis factor blockers in Taiwan.
In Taiwan, an intermediate tuberculosis burden country, around 9·3% of patients with rheumatoid arthritis treated with adalimumab develop tuberculosis despite prescreening with the tuberculin skin test. Within the Asia-Pacific region, the tuberculosis risk in patients with psoriasis who use tumour necrosis factor (TNF) blockers is unknown. This study reports the use of QuantiFERON(®) -TB Gold (QFT-G) (Cellestis, Melbourne, Vic., Australia) as a screening method for latent tuberculosis infection (LTBI) in patients with psoriasis. This retrospective review evaluated 216 patients with psoriasis in whom TNF blockers were considered between 2004 and 2009 in a tertiary referral hospital in Taiwan. Beginning in 2007, QFT-G was performed on all patients who were candidates for TNF blockers. Seventeen patients who used TNF blockers for less than 4 weeks were excluded. Of the 147 assessed patients receiving TNF blockers, 110 (75%) underwent QFT-G tests. A total of 126 (86%) patients used etanercept and 40 (27%) patients used adalimumab. Nineteen patients switched between both. Overall, patients had a median of 24 weeks (range 4-307) exposure to TNF blockers. Twelve patients (11%) who were treated with TNF blockers and eight (15%) without TNF blockers had positive QFT-G results. Of all TNF blocker users, only one patient (0·68%) developed tuberculosis. QFT-G can be used to screen for LTBI in a tuberculosis endemic area where bacille Calmette-Guérin vaccination coverage is high. Isoniazid prophylaxis is recommended for those who have positive QFT-G test results.


Food Footprint as a Measure of Sustainability for Grazing Dairy Farms.
Livestock productions require significant resources allocation in the form of land, water, energy, air, and capital. Meanwhile, owing to increase in the global demand for livestock products, it is wise to consider sustainable livestock practices. In the past few decades, footprints have emerged as indicators for sustainability assessment. In this study, we are introducing a new footprint measure to assess sustainability of a grazing dairy farm while considering carbon, water, energy, and economic impacts of milk production. To achieve this goal, a representative farm was developed based on grazing dairy practices surveys in the State of Michigan, USA. This information was incorporated into the Integrated Farm System Model (IFSM) to estimate the farm carbon, water, energy, and economic impacts and associated footprints for ten different regions in Michigan. A multi-criterion decision-making method called VIKOR was used to determine the overall impacts of the representative farms. This new measure is called the food footprint. Using this new indicator, the most sustainable milk production level (8618 kg/cow/year) was identified that is 19.4% higher than the average milk production (7215 kg/cow/year) in the area of interest. In addition, the most sustainable pasture composition was identified as 90% tall fescue with 10% white clover. The methodology introduced here can be adopted in other regions to improve sustainability by reducing water, energy, and environmental impacts of grazing dairy farms, while maximizing the farm profit and productions.


60 Hz electric field parameters associated with the perturbation of a eukaryotic cell system.
Roots of Pisum sativum were exposed for seven days to 60 Hz electric fields ranging from 70--430 V/m in an aqueous medium whose conductivity was approximately 0.07 mho/m. (Corresponding current densities in the exposure medium associated with these field strengths ranged from 0.5--3.0 mA/cm2). Control and exposed roots were grown concomitantly in the same tank whose growth medium was continuously circulated. Temperature in the exposure medium was held at a constant 19 degrees C. All experiments were conducted "double blind." Root growth rates were determined daily. No perturbations in root growth were observed with electric fields of 150 V/m; there was a slight effect at 360 V/m, and a pronounced decrease in growth rate occurred at 430 V/m. Root conductivities are comparable to that of the growth medium. Under conditions in which growth inhibition occurs, it is estimated that induced 60 Hz cell membrane potentials would be of the order of 3--8 mV.


Alcohol-related victimization among young adult Canadian drinkers: the explanatory roles of hazardous drinking and illicit drug use.
Consistent evidence has shown that young people are significantly overrepresented among victims of violence due to another person's drinking. Yet little research has examined factors that explain alcohol-related victimization among young adults, particularly in Canada. The present study examines the influence of hazardous drinking and illicit drug use on the likelihood of experiencing alcohol-related physical victimization among young adult drinkers in a Canadian general population sample and determines whether gender differences exist in the roles of these explanatory variables. A secondary analysis of the 2004 Canadian Addiction Survey (CAS) was conducted, restricting analyses to young adult (ages 18 to 25) drinkers (785 females, 745 males). Logistic regression analyses were conducted to examine associations between explanatory variables and victimization. To assess gender differences in effects, interaction effects of gender by hazardous drinking and illicit drug use were tested. Alcohol-related victimization was more likely among men than among women, hazardous drinkers than non-hazardous drinkers, and illicit drug users than non-users. Multivariate analyses indicated that, among women, illicit drug use was associated with victimization whereas, among men, hazardous drinking was significant. An interaction effect between gender and hazardous drinking indicated that hazardous drinking was more strongly associated with victimization among men than among women. These results highlight the important role of substance use in explaining alcohol-related victimization among young adult Canadian drinkers and suggest that gender-specific prevention programs may be needed.


Effects of age and gender on the cytochrome P450 2D6 activity in a Korean population.
Age and gender have been reported to play a crucial role in modulating the disposition of pharmacological agents, and to influence the activities of cytochrome P450 (CYP) 2D6, a drug-metabolizing enzyme involved in the disposition of clinically used drugs. In the present study, the effects of age and gender on the CYP2D6 activity were evaluated using dextromethorphan as a probe drug in humans. Healthy young (20 < age < 30 years, n = 60) and old age (age >60 years, n = 60) subjects were enrolled and were given 15 mg dextromethorphan orally. Blood samples were collected before and 3 h after medication. Dextromethorphan and its metabolite dextrorphan were measured using HPLC-fluorescence, and dextromethorphan metabolic ratio (MR, log [dextromethorphan/dextrorphan]) was used to evaluate the CYP2D6 activity. Mean (±SD) dextromethorphan MR was -2.42 ± 0.46 for the young male group, -2.28 ± 0.56 for the young female group, -2.46 ± 0.55 for the older male group and -2.34 ± 0.65 for the old female group. Based on our findings, the effects of age and gender on CYP2D6 activity were not statistically significant. The results of the present study indicate that age and gender play a minor role in the modulation of CYP2D6 activity in the Korean population.


THE EFFECT OF TEMPERATURE ON BODY SIZE AND FECUNDITY IN FEMALE DROSOPHILA MELANOGASTER: EVIDENCE FOR ADAPTIVE PLASTICITY.
The reaction norm linking rearing temperature and size in Drosophila melanogaster results in progressively larger flies as the temperature is lowered from 30°C to 18°C, but it has remained unclear whether this phenotypic plasticity is part of an adaptive response to temperature. We found that female D. melanogaster reared to adulthood at 18°C versus 25°C showed a 12% increase in dry weight. Measurements of the fecundity of these two types of fly showed that the size change had no effect on lifetime fecundity, regardless of the adult test temperature. Thus the phenotypic plasticity breaks the usual positive correlation between body size and fecundity. However, at a given temperature, early fecundity (defined as productivity for days 5 through 12 after eclosion at 25°C and days 7 through 17 at 18°C) was highest when the rearing and test temperatures were the same. The early fecundity advantage due to rearing at the test temperature was 25% at 18°C and 16% at 25°C, a result consistent with the overall phenotypic response to temperature being adaptive. This conclusion is further supported by the finding that the temperature treatments resulted in a trade-off between early fecundity and longevity, a trade-off that parallels the known genetic correlation. Another parallel is that both the temperature-induced and genetic effects are independent of total fecundity. By contrast, within the temperature treatments, the phenotypic correlation between early fecundity and longevity was positive, illustrating the danger of assuming that phenotypic and genetic correlations are similar, or even of the same sign.


Effect of ultraviolet B radiation on activator protein 1 constituent proteins and modulation by dietary energy restriction in SKH-1 mouse skin.
The study examined the timing of modulation of activator protein 1(AP-1):DNA binding and production of AP-1 constituent proteins by ultraviolet B (UVB) radiation and effect of dietary energy restriction [DER, 40% calorie reduction from fat and carbohydrate compared to control ad libitum (AL) diet] in SKH-1 mouse epidermis. AP-1:DNA binding by electromobility shift assay (EMSA) was increased in a biphasic manner after treatment with a tumor-promoting suberythemal dose (750 mJ/cm(2)) of UVB light (311-313 nm) with peaks at 3 and 18 h postirradiation. DER overall reduced AP-1:DNA binding in mock-treated and UVB-treated skin at 3 and 18 h after UVB treatment. The timing of modulation of production of AP-1 constituent proteins by Western blot analysis was examined at 0 h (mock treatment), 3, 9, 18, and 24 h. We found that c-jun (9 h), jun-B (9 and 18 h), phosphorylated c-jun (3 h), and fra-1 (18 h) protein levels were increased after UVB treatment compared to mock controls. In a follow-up diet experiment, animals were placed on DER or AL diet for 10-12 wk and treated with UVB as before. DER was found to completely block the UVB-induced increase in phosphorylated c-jun protein levels and decrease in fra-2 protein levels at 18 h. In addition, DER enhanced UVB-induced increase in jun B levels and lowered basal levels of c-fos seen 18 h after UVB. These data suggest that DER may be able to assist in the prevention of UVB-induced skin carcinogenesis by modulating AP-1:DNA binding and AP-1 constituent protein levels.


The role of the nucleolus in regulating the cell cycle and the DNA damage response.
The nucleolus has long been perceived as the site for ribosome biogenesis, but numerous studies suggest that the nucleolus carefully sequesters crucial proteins involved in multiple cellular functions. Among these, the role of nucleolus in cell cycle regulation is the most evident. The nucleolus is the first responder of growth-related signals to mediate normal cell cycle progression. The nucleolus also senses different cellular stress insults by activating diverse pathways that arrest the cell cycle, promote DNA repair, or initiate apoptosis. Here, we review the emerging concepts on how the ribosomal and nonribosomal nucleolar proteins mediate such cellular effects.


Pulmonary Infection Caused by Mycobacterium malmoense in a Chronic HIV-Infected Individual Participating in a Therapeutic Vaccine Trial.
We report a case of Mycobacterium malmoense pulmonary infection and HIV-1 chronic co-infection in a 60-year-old man while participating in an HIV-1 therapeutic vaccine clinical trial and during the analytical treatment interruption. We present clinical and therapeutic features of a complicated M. malmoense pulmonary infection along with discussion of the possible relation to the HIV-1 cure-related interventions.


Non-compliance with the re-excision guidelines for cutaneous melanoma in The Netherlands does not influence survival.
To evaluate causes and consequences of not adhering to the clinical practice guideline for cutaneous malignant melanoma. We conducted a retrospective cohort study of the clinical records of 454 subjects whose pathological reports were obtained from a population-based cancer registry to assess determinants and effects of non-compliance of physicians with the excision policy and the related clinical practice guideline for patients with primary localized cutaneous malignant melanoma (CMM). A comparative analysis was performed of patients who did and did not undergo re-excision (compliance versus non-compliance with the guideline). Subjects diagnosed in 1988, 1993 and 1997, just 1 year after publication of the (adapted) guideline, were followed until death due to any cause or until July 1st 2003. Old age was the most important determinant of non-compliance. After adjusting for age at diagnosis, gender, subsite and Breslow thickness there was no significant difference in overall survival between the compliance group and the non-compliance group. Non-compliance to the guideline is more common in older patients and in patients with melanoma in the head and neck region. After adjusting for confounders, a significant effect of complying with the guidelines on overall survival could not be observed.


P-glycoprotein: so many ways to turn it on.
Expression of the ABC transporter P-glycoprotein (P-gp or ABCB1) is associated with resistance to chemotherapy in cancer. However, early investigations into the regulation of ABCB1 expression revealed that the process is not a classical induction as observed for certain metabolizing enzymes. The process involves the cellular stress response pathway initiated by either inflicted (e.g., chemotherapy damage) or endogenous (e.g., hypoxia) factors. However, ABCB1 is also expressed in a number of noncancerous tissues. In particular, the protein is found at tissues providing a barrier or secretory function. The localization of ABCB1 in normal tissues will impact significantly on drug pharmacokinetics, in particular the absorption and elimination processes. This review also describes the mechanism underlying ABCB1 expression in noncancerous tissue, a process that does not involve the stress response.


[Change in the structure of the lipid component of the plasma membrane during extraction of peripheral proteins].
Effect of peripheral proteins on the structure of lipids of thymocyte plasmic membranes was studied using the fluorescent probes 1-anilinonaphthalene-8 sulfonate, 3-methoxybenzanthrone, 4-dimethylaminochalcone and pyrene. It is shown that the extraction of peripheral proteins evokes the change of lipids structure and electrochemical properties of the membrane.


Study on laser-induced breakdown spectroscopy in high-pressure helium gas environment for deep ocean applications.
Laser-induced breakdown spectroscopy (LIBS) has gained wide acceptance as an in situ detection technique for elements. However, in deep-sea applications, the sensitivity of LIBS detection will be reduced due to the high-pressure environment and the nature of water. To address the negative effects of high-pressure water, this study used the method of draining the water from the sample surface by passing high-pressure helium gas, which allowed the plasma excitation environment to be converted from high-pressure water to high-pressure gas. The available spectral signals of solid samples at 60 MPa gas pressure were obtained for the first time, and the peak intensity and spectral broadening of the spectral lines at different pressures were analyzed for comparison. We found a nonlinear decrease in the spectral intensity and a gradual increase in the spectral broadening during the pressure increase. We also investigated the effect of laser energy on the intensity and width of the spectral lines in a high-pressure helium environment and found that increasing the laser energy in a high-pressure environment enhanced the spectral intensity and that the change in laser energy almost did not affect the line width. Finally, by observing the plasma images at different pressures with different energies, this study found that the laser penetrated the high-pressure helium gas in advance and leaved a column of light in the gas, and the plasma was slowly made smaller as the ambient pressure increases. This finding explained the cause of laser energy loss and demonstrated that the LIBS signal intensity can be improved by increasing the laser energy and shortening the laser transmission distance in a high-pressure gas environment.


Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis.
To determine whether duration of antibiotic exposure is an independent risk factor for necrotizing enterocolitis (NEC). A retrospective, 2:1 control-case analysis was conducted comparing neonates with NEC to those without from 2000 through 2008. Control subjects were matched on gestational age, birth weight, and birth year. In each matched triad, demographic and risk factor data were collected from birth until the diagnosis of NEC in the case subject. Bivariate and multivariate analyses were used to assess associations between risk factors and NEC. One hundred twenty-four cases of NEC were matched with 248 control subjects. Cases were less likely to have respiratory distress syndrome (P = .018) and more likely to reach full enteral feeding (P = .028) than control subjects. Cases were more likely to have culture-proven sepsis (P < .0001). Given the association between sepsis and antibiotic use, we tested for and found a significant interaction between the two variables (P = .001). When neonates with sepsis were removed from the cohort, the risk of NEC increased significantly with duration of antibiotic exposure. Exposure for >10 days resulted in a nearly threefold increase in the risk of developing NEC. Duration of antibiotic exposure is associated with an increased risk of NEC among neonates without prior sepsis.


An Antireflective Nanostructure Array Fabricated by Nanosilver Colloidal Lithography on a Silicon Substrate.
An alternative method is presented for fabricating an antireflective nanostructure array using nanosilver colloidal lithography. Spin coating was used to produce the multilayered silver nanoparticles, which grew by self-assembly and were transformed into randomly distributed nanosilver islands through the thermodynamic action of dewetting and Oswald ripening. The average size and coverage rate of the islands increased with concentration in the range of 50-90 nm and 40-65%, respectively. The nanosilver islands were critically affected by concentration and spin speed. The effects of these two parameters were investigated, after etching and wet removal of nanosilver residues. The reflection nearly disappeared in the ultraviolet wavelength range and was 17% of the reflection of a bare silicon wafer in the visible range.


Optimal Sparse Eigenspace and Low-Rank Density Matrix Estimation for Quantum Systems.
Quantum state tomography, which aims to estimate quantum states that are described by density matrices, plays an important role in quantum science and quantum technology. This paper examines the eigenspace estimation and the reconstruction of large low-rank density matrix based on Pauli measurements. Both ordinary principal component analysis (PCA) and iterative thresholding sparse PCA (ITSPCA) estimators of the eigenspace are studied, and their respective convergence rates are established. In particular, we show that the ITSPCA estimator is rate-optimal. We present the reconstruction of the large low-rank density matrix and obtain its optimal convergence rate by using the ITSPCA estimator. A numerical study is carried out to investigate the finite sample performance of the proposed estimators.


Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything.
Triple-negative breast cancer-defined by the absence of oestrogen/progesterone receptors and human epidermal growth factor receptor 2 expression-is a complex and heterogeneous type of tumour characterised by poor prognosis, aggressive behaviour and lack of effective therapeutic strategies. The identification of new biomarkers and molecular signatures is leading to development of new therapeutic strategies including immunotherapy, targeted therapy and antibody-drug conjugates (ADCs). Against a background where chemotherapy has always been considered the standard of care, evolution towards a precision medicine approach could improve TNBC clinical practice in a complex scenario, with many therapeutic options and new drugs. The aim of this review was to focus on emerging therapeutic targets and their related specific therapy, discussing available and emerging drugs, underlining differences in approval by American and European regulatory authorities and showing the future perspective in the large number of ongoing clinical trials.


An experimental and theoretical study on the interaction of DNA and BSA with novel Ni2+, Cu2+ and VO2+ complexes derived from vanillin bidentate Schiff base ligand.
In this investigation, the structure of bidentate N,N-Schiff base ligand of vanillin, (E)-4-(((2-amino-5-nitrophenyl)imino)methyl)-2-methoxyphenol (HL) was determined by single crystal X-ray diffraction. The interaction of new [CuL2], [NiL2] and [VOL2] complexes with DNA and BSA was explored through UV-Vis and fluorescence spectroscopy. The electronic spectra changes displayed an isosbestic point for the complexes upon titration with DNA. The Kb values for the complexes [CuL2], [NiL2] and [VOL2] were 2.4×105, 1.9×105 and 4.2×104, respectively. [CuL2] complex was bound more toughly than [NiL2] and [VOL2] complexes. These complexes had a significant interaction with Bovine Serum Albumin (BSA) and the results demonstrated that the quenching mechanism was a static procedure. Also, the complexes interacted with BSA by more than one binding site (n>1). Finally, the theoretical studies were performed using the docking method to calculate the binding constants and recognize the binding site of the DNA and BSA with the complexes. The ligand and complexes including Ni2+, Cu2+ and VO2+ ions were colonized by fungal growth.


On the transport of lipoplexes through cystic fibrosis sputum.
The aim of this study was to examine the extent to which plasmid DNA (pDNA) complexed to cationic liposomes diffuse through cystic fibrosis (CF) sputum. The influence of the physical and chemical properties of the sputa was evaluated. We further investigated whether degradation of the sputa by recombinant human DNase I (rhDNase I) enhances the transport. The transport of lipoplexes was studied through layers of CF sputa placed between the donor and acceptor compartment of vertical diffusion chambers. The content of the acceptor compartment was analyzed by confocal fluorescence microscopy, gel electrophoresis and Southern blotting. The influence of linear DNA present in the CF sputa on the size, surface charge and gene expression of the lipoplexes was evaluated by dynamic light scattering, particle electrophoresis and transfection experiments. Lipoplexes were observed in the acceptor compartments. However, the percent of diffused lipoplexes was low: 0.05/% +/- 0.01%. It was found that both steric obstruction by the sputa as well as the long" distance the lipoplexes have to travel were responsible for this low transport. Surprisingly, the transport occurred better through more viscoelastic sputa. The DNA in the CF sputa also retarded the transport, which was attributed to aggregation of the lipoplexes by the DNA. Finally, rhDNase I moderately enhanced the diffusion of lipoplexes. CF sputum drastically retards the diffusion of lipoplexes. DNA in the sputa aggregates the lipoplexes. This may lower the transport of lipoplexes through the sputa and gene expression. Pretreatment of CF patients with rhDNase I may enhance the efficiency of CF gene therapy, as it allows a better transport of the lipoplexes through the sputum and as it partly removes the sputum which will result in a thinner sputum layer on top of the epithelial cells.


The acute-phase protein serum amyloid A induces endothelial dysfunction that is inhibited by high-density lipoprotein.
The acute-phase protein serum amyloid A (SAA) is elevated during inflammation and may be deposited in atheroma where it promotes atherosclerosis. We investigated the proatherogenic effects of SAA on the vascular endothelium and their regulation by high-density lipoprotein (HDL). Exposure of human aortic endothelial cells (HAEC) to SAA (0.25-25μg/ml) decreased nitric oxide ((•)NO) synthesis/bioavailability, although the endothelial NO synthase monomer-to-dimer ratio was unaffected. SAA (10μg/ml) stimulated a Ca(2+) influx linked to apocynin-sensitive superoxide radical anion (O(2)(•-)) production. Gene expression for arginase-1, nuclear factor κB (NF-κB), interleukin-8, and tissue factor (TF) increased within 4h of SAA stimulation. Enzymatically active Arg-1/2 was detected in HAEC cultured with SAA for 24h. Therefore, in addition to modulating (•)NO bioavailability by stimulating O(2)(•-) production in the endothelium, SAA modulated vascular l-Arg bioavailability. SAA also diminished relaxation of preconstricted aortic rings induced by acetylcholine, and added superoxide dismutase restored the vascular response. Preincubation of HAEC with HDL (100 or 200, but not 50, μg/ml) before (not after) SAA treatment ameliorated the Ca(2+) influx and O(2)(•-) production; decreased TF, NF-κB, and Arg-1 gene expression; and preserved overall vascular function. Thus, SAA may promote endothelial dysfunction by modulating (•)NO and l-Arg bioavailability, and HDL pretreatment may be protective. The relative HDL to SAA concentrations may regulate the proatherogenic properties of SAA on the vascular endothelium.


Comparison of virtual wheelchair driving performance of people with traumatic brain injury using an isometric and a conventional joystick.
Cooper RA. Comparison of virtual wheelchair driving performance of people with traumatic brain injury using an isometric and a conventional joystick. To compare wheelchair driving performance in a driving simulator using a conventional joystick and an isometric joystick. Randomized, cohort study. A research facility based in a hospital or in an independent living center. Participants (N=20; 12 men, 8 women; mean age ± SD, 30.62±10.91 y) who were at least 1 year post-TBI. Driving performance using an isometric joystick compared with a conventional movement joystick. Average trial completion time, and trajectory-specific measures measured orthogonal to the center of driving tasks: root mean squared error, movement offset, movement error, and number of significant changes in heading. After statistically controlling for driving speed, participants were able to complete the driving tasks faster with an isometric joystick than while using a conventional movement joystick. Compared with the conventional joystick, an isometric joystick used for driving forward demonstrated fewer driving errors. During reverse driving the conventional joystick performed better. The customizable isometric joystick seems to be a promising interface for driving a powered wheelchair for individuals with TBI.


In-Hospital Bereavement Services as an Act of Care and a Challenge: An Integrative Review.
Globally, people most often die within hospitals. As such, healthcare providers in hospitals are frequently confronted with dying persons and their bereaved relatives. To provide an overview of the current role hospitals take in providing bereavement care. Furthermore, we want to present an operational definition of bereavement care, the way it is currently implemented, relatives' satisfaction of receiving these services, and finally barriers and facilitators regarding the provision of bereavement care. An integrative review was conducted by searching four electronic databases, from January 2011 to December 2020, resulting in 47 studies. Different study designs were included and results were reported in accordance with the theoretical framework of Whittemore and Knafl (2005). Only four articles defined bereavement care: two as services offered solely post loss and the other two as services offered pre and post loss. Although different bereavement services were delivered the time surrounding the death, the follow-up of bereaved relatives was less routinely offered. Relatives appreciated all bereavement services, which were rather informally and ad-hoc provided to them. Healthcare providers perceived bereavement care as important, but the provision was challenged by numerous factors (such as insufficient education and time). Current in-hospital bereavement care can be seen as an act of care that is provided ad-hoc, resulting from the good-will of individual staff members. A tiered or stepped approach based on needs is preferred, as it allocates funds towards individuals-at-risk. Effective partnerships between hospitals and the community can be a useful, sustainable and cost-effective strategy.


On the Mechanism of Cardioprotective Effect of Fabomotizole in Alcoholic Cardiomyopathy.
The molecular mechanisms underlying the cardioprotective effect of fabomotizole were studied using the translational rat model of alcoholic cardiomyopathy developed by us. It was shown that intraperitoneal administration of fabomotizole (15 mg/kg) for 28 days to animals with alcoholic cardiomyopathy contributes to normalization of the expression of mRNA of genes of regulatory proteins СаМ (p=0.00001), Ерас1 (p=0.021), and Ерас2 (p=0.018) and receptors RyR2 (p=0.0031) and IP3R2 (p=0.006) in the myocardium of the myocardium of the left ventricle that is enhanced in control animals (p<0.05). These changes were accompanied by echocardiographically documented decrease in the degree of left ventricle remodeling and improvement of its inotropic function.


Glial cell line-derived neurotrophic factor alters lipid composition and protein distribution in MPP+-injured differentiated SH-SY5Y cells.
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and striatum. Glial cell line-derived neurotrophic factor (GDNF) can effectively promote the differentiation and survival of many types of neurons, especially dopaminergic neurons, suggesting it could be a treatment for PD. Lipid rafts are highly dynamic cell membrane domains that contain numerous signal protein receptors, providing an important platform for signal transduction. Compelling evidence indicates that alterations in lipid rafts are associated with PD, and some studies have reported that GDNF can regulate the expression of caveolin-1, a lipid raft-marker protein. However, the precise effects of GDNF on lipid rafts remain unknown. We developed a cellular PD model, purified detergent-resistant membranes (membrane rafts), and performed proteomic and lipid metabolomics analyses to examine changes in lipid rafts after GDNF treatment. The results showed considerable protein and lipid alterations in response to GDNF, especially altered levels of dopamine-β-hydroxylase, heat shock 70 kDa protein, neural cell adhesion molecule, cytoskeletal proteins, and long-chain polysaturated/unsaturated fatty acids. These findings reveal a new avenue to explore the relationships between GDNF, lipid rafts, and PD and support the hypothesis that GDNF may be a useful treatment for PD.


Dissolved thiolated arsenic formed by weathering of mine wastes.
Aqueous thiolated arsenic (As) species play an important role in the biogeochemical cycling of As in wetlands and hydrothermal systems. Although mine wastes such as tailings ponds and waste rock piles may harbor similarly sub-oxic and neutral to alkaline conditions that favor the formation and mobility of thio-As species, quantitative data on their existence in these systems is lacking. We conducted laboratory column experiments under contrasting redox conditions with waste rock from the Antamina mine, Peru, and processed tailings from Montague, Nova Scotia, Canada. Dissolved As concentrations between 1 and 7000 μg/L were recorded in drainages across these mine waste types, with up to 13 μg/L As present in thiolated form, predominantly monothioarsenate. Higher percentages of thio-As species (up to 5%) were observed in drainages from enargite-rich materials compared to arsenopyrite-bearing materials (<0.5%). The lower abundance of dissolved thio-As in the arsenopyrite-rich mine waste samples is attributed to their partially oxidized nature and reduced mineral reactivity under the experimental circumneutral drainage pH, the difference in S [-II/0]-to-As molar ratios compared to the enargite-rich mine waste samples, as well as the oxidation of di- and tri-thiolated As species by dissolved Fe. Overall, our results demonstrate that aqueous thiolated As species may occur in mine wastes with different As-bearing minerals and could play an important role in governing the mobility and fate of As in these systems.


Current Medication Practices and Preferences Among Patients With Psoriatic Arthritis.
The aim of this study was to evaluate real-world psoriatic arthritis (PsA) medication use and patient medication preferences. This is a cross-sectional survey of Classification for Psoriatic Arthritis criteria defined PsA patients recruited from a single-center PsA registry from June to September 2020. Preferences were ranked on a 5-point Likert scale ranging from "not at all important" to "extremely important." One hundred thirty-seven patients (29%) responded. The median duration (years) of PsA skin and joint symptoms was 19 (interquartile range, 10-34) and 12 (interquartile range, 8-21), respectively. The most common initial immunomodulatory medications were anti-tumor necrosis factor α (35%), methotrexate (19%), and anti-phosphodiesterase 4 (anti-PDE4) (12.4%). At survey administration, the most common immunomodulatory therapies were anti-tumor necrosis factor α (30%), anti-interleukin 17 (IL-17) (20.4%), and methotrexate (10.2%). After 2018, when updated guidelines from the American College of Rheumatology/National Psoriasis Foundation were published, a significantly higher percentage of patients' first medication was an anti-IL-17 compared with 2018 or earlier (30% vs 3.5%, p < 0.001), a pattern also seen with anti-PDE4 (40% vs 11.5%, p < 0.012). Medication preferences most ranked as "extremely" important were prevention of joint damage (80%), ability to perform daily activities (71%), prevention of pain (70.1%), rheumatologist recommendation (63%), and medication adverse effects (62%). The significant increase of anti-IL-17 and anti-PDE4 medications as initial treatment after 2018 may reflect their inclusion as potential initial therapy in updated guidelines, along with the importance placed by patients on medication adverse effects. Given the expanding armamentarium of PsA medications, it is increasingly important to align patient preferences and therapeutic options to ensure durable use of effective therapy.


Cardiopulmonary exercise testing to indicate increased ventilatory variability in subjects with dysfunctional breathing.
Dysfunctional breathing (DB) is a common, but largely underappreciated, cause of chronic dyspnoea. Under visual inspection, most subjects with DB present with larger sequential changes in ventilation (V̇E) and breathing pattern (tidal volume (VT) and breathing frequency (f)) before and/or during incremental cardiopulmonary exercise testing (CPET). Currently, however, there are no objective criteria to indicate increased ventilatory variability in these subjects. Twenty chronically dyspnoeic subjects with DB and 10 age- and sex-matched controls performed CPET on a cycle ergometer. Cut-offs to indicate increased V̇E, VT, f, and f/VT ratio variability (Δ = highest-lowest 20 s arithmetic mean) over the last resting minute (rest ), the 2sd min of unloaded exercise (unload ), and the 3rd min of loaded exercise (load ) were established by ROC curve analyses. Subjects with DB presented with increased V̇E, higher ventilatory variability, higher dyspnoea burden, and lower exercise capacity compared to controls (p < 0.05). ΔV̇Eload (>4.1 L/min), Δfrest (>5 breaths/min; bpm), Δfunload (>4 bpm), Δfload (>5 bpm), Δf/VTrest (>4.9 bpm/L), and Δf/VTload (>1.3 bpm/L) differentiated DB from a normal pattern (areas under the curve ranging from 0.729 to 0.845). High Δf, in particular, was associated with DB across all CPET phases. This study provides objective criteria to indicate increased ventilatory variability during incremental CPET in dyspnoeic subjects with DB. Large variability in breathing frequency seems particularly useful in this context, a finding that should be prospectively confirmed in larger studies.


Long versus short peroral endoscopic myotomy for the treatment of achalasia: results of a non-inferiority randomised controlled trial.
Peroral endoscopic myotomy (POEM) has become standard treatment for achalasia with comparable efficacy to surgery. In most of published series, the length of myotomy is 12-13 cm. Shorter cuts could have the advantage of shorter procedure time and possibly reduced gastro-oesophageal reflux disease (GORD) rate. This single-centre, patient-blinded, randomised, non-inferiority clinical trial included 200 patients, who were randomly allocated, to receive either a long-POEM (13 cm; 101 patients) or a short-POEM (8 cm; 99 patients). Primary outcome was defined as an Eckardt symptom score of ≤3 at 24 months after the procedure; a non-inferiority design was chosen with an accepted success range of 6% between the two treatments. Secondary outcomes included operating time, complication rate, postoperative manometry, GORD rate and quality of life. In the intention-to-treat analysis, clinical success rates were 89.1% in the long-POEM and 98.0% in the short-POEM group, resulting in an absolute between-group difference of -8.9% (90% CI -14.5 to -3.3).Procedure time was significantly reduced in the short-POEM as compared with the long-POEM group (40 vs 50 min, p<0.0001). Severe adverse events occurred in one patient in both groups.No differences were observed in postoperative GORD: acid exposure >6% on pH monitoring study at 6 months was seen in 34.3% (long-POEM) vs 31.1% (short-POEM), while endoscopic oesophagitis was diagnosed in 37.6% vs 51.5% at 6 months and in 21% vs 24.5% at 24 months. Regular proton pump inhibitor use was not different either (36.8% vs 37.5%). Our study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length. NCT03450928.


The appearance of a type of cortical vesicles subsequent to fertilization of the sea urchin egg, their character and possible function.
Three different types of vesicles present before fertilization in the sea urchin egg were examined. The "a-type" corresponds to rough endoplasmic vesicles; the vesicles of "b-type" are rather smooth but may have vestigial granules within their membranes; the "c-type" belongs to the multivesicular bodies. Upon fertilization, vesicles appear in the outer cortical zone (vesicles of "d-type"). The majority of them arises by budding from the vesicles ofb-type. The budding occurs mainly at the basis of or within ridges of the cell surface; they may also be present in broader microvilli. The distance between the ridges was varied by early transfer of the eggs to calcium-free sea water. An inducing effect of the ridges on location of theb-vesicles and on the formation ofd-vesicles by budding could thus be demonstrated.Thed-vesicles appearing upon fertilization resemble in size and structure Golgi vesicles formed by budding from Golgi bodies present in the interior cortex or below it. Also theb-vesicles have their counterpart in the Golgi bodies. Theb andd-vesicles are therefore regarded as a Golgi system in which theb-vesicles represent dispersed Golgi bodies and thed- vesicles Golgi vesicles. Thed-vesicles may be designated as cortical Golgi vesicles, (c.G.v.).In thec-vesicles i.e. the multivesicular bodies (m.v.b.), a nucleid was observed which may be subdivided. A compartmentation of m.v.b. was observed which may lead to a detachment of vesicles of about the same size as thed-vesicles (c.G.v.) but probably of a different character.The differentiation of the fertilization membrane of the sea urchin egg occurs in two stages: the assembly and the solidification stage. The tentative conclusion is drawn that a secretion from the c.G.v. functions as an agent in the solidification process. The c.G.v. may also act upon the hyaline layer, both in its early formation and its maintenance during the course of embryonic development.


Infective endocarditis in the adult with congenital heart disease.
Advances in the diagnosis and therapy of congenital heart disease in the past few decades have allowed the survival of young adults who are a fertile substrate for developing bacterial endocarditis. In addition to valvular involvement, young adults with congenital disease may develop infection on the ventricular septum, or in a vascular shunt, a patent ductus arteriosus, or coarctation of the aorta. The incidence of endocarditis in children and adults with congenital heart disease is higher than with rheumatic heart disease or mitral valve prolapse. Infecting organisms, diagnosis, and therapy are similar to acquired heart disease, but the physiologic variations and patient population often add a unique flavor to the management of this group.


Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.
Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.


Affinity of small-molecule solutes to hydrophobic, hydrophilic, and chemically patterned interfaces in aqueous solution.
Performance of membranes for water purification is highly influenced by the interactions of solvated species with membrane surfaces, including surface adsorption of solutes upon fouling. Current efforts toward fouling-resistant membranes often pursue surface hydrophilization, frequently motivated by macroscopic measures of hydrophilicity, because hydrophobicity is thought to increase solute-surface affinity. While this heuristic has driven diverse membrane functionalization strategies, here we build on advances in the theory of hydrophobicity to critically examine the relevance of macroscopic characterizations of solute-surface affinity. Specifically, we use molecular simulations to quantify the affinities to model hydroxyl- and methyl-functionalized surfaces of small, chemically diverse, charge-neutral solutes represented in produced water. We show that surface affinities correlate poorly with two conventional measures of solute hydrophobicity, gas-phase water solubility and oil-water partitioning. Moreover, we find that all solutes show attraction to the hydrophobic surface and most to the hydrophilic one, in contrast to macroscopically based hydrophobicity heuristics. We explain these results by decomposing affinities into direct solute interaction energies (which dominate on hydroxyl surfaces) and water restructuring penalties (which dominate on methyl surfaces). Finally, we use an inverse design algorithm to show how heterogeneous surfaces, with multiple functional groups, can be patterned to manipulate solute affinity and selectivity. These findings, importantly based on a range of solute and surface chemistries, illustrate that conventional macroscopic hydrophobicity metrics can fail to predict solute-surface affinity, and that molecular-scale surface chemical patterning significantly influences affinity-suggesting design opportunities for water purification membranes and other engineered interfaces involving aqueous solute-surface interactions.


Modelling the Ecological Suitability of the Chagas Disease Vector Triatoma rubrofasciata- China.
Triatoma rubrofasciata is a potential vector that can transmit American trypanosomiasis and was widely recorded in South of China. Because of the low density of the triatomines, more habitats have not been discovered. This study mainly focused on predicting the geographical distribution of T. rubrofasciata under current and future climatic conditions in China using the MaxEnt model. The result showed that the distribution of T. rubrofasciata was largely affected by annual mean temperature and possessed a high potential for expansion in southern China in the future. Our predictions are useful for targeting surveillance efforts in high-risk areas and increasing the efficiency and accuracy of public health investigations and vector control efforts in China.


Does perioperative blood transfusion influence long-term prognosis of gastric cancer?
We analyzed the influence of packed red blood cell (PRBC) transfusions on the prognosis of 163 patients with gastric adenocarcinoma undergoing subtotal gastrectomy with a curative intention. Over a period of 15 years, our department admitted 505 patients with gastric adenocarcinoma, with curative subtotal gastrectomy being performed in 167 cases. Mean age was 62.2 years (range: 30-87); there was a predominance of males (104 cases; 63.8%). Excluding the four patients who died in the immediate postoperative period (first 30 days), the remaining 163 were reviewed twice yearly in our department until either they died or the study ended. Follow-up averaged 49.5 months, with a median of 36 months. Sixty-nine (42.3%) of the 163 patients received transfusions of PRBC. On correlating the variables with the transfusion, we found a statistical significance only between the rate of transfusion and patient age over 63 years (P < 0.01), with an evolution time of less than three months (P < 0.05) and in tumors of >4 cm (P < 0.05). The five-year survival rate of the nontransfusion patients was 56.9% and of the transfusion patients 40%, with statistically significant differences (P = 0.0132). On studying patients according to tumor stage, we found that blood transfusion had a statistically significant influence on prognosis only in patients with tumor stage III (P = 0.0051). In the univariate analysis of the remaining variables collected, the existence of abdominal tumor (P = 0.0307), tumor size (P = 0.00001), degree of involvement of the gastric wall (P = 0.00001), lymph node involvement (P = 0.00001) and tumor stage (P = 0.00001) revealed a statistically significant influence on prognosis. If we apply Cox's regression model to the variables that in the univariate analysis had a statistically significant influence on prognosis, we found that only tumor size and stage were independent predictors of survival. In our experience, PRBC transfusion does not influence the long-term survival of patients with resected gastric adenocarcinoma.


5-Hydroxytryptamine induces endothelium-independent relaxations of sheep pulmonary vein: role of cyclic nucleotide.
5-Hydroxytryptamine produced concentration-dependent relaxations in isolated sheep pulmonary vein, which were insensitive to removal of the endothelium. 5-Hydroxytryptamine stimulated concentration-dependent increases of cyclic AMP levels in the pulmonary vein, and there was a significant linear correlation between relaxations elicited by 5-hydroxytryptamine and tissue cyclic AMP formations. The soluble guanylate cyclase inhibitor methylene blue (10 microM) failed to block 5-hydroxytryptamine-induced relaxations. The results suggest that 5-hydroxytryptamine-induced relaxations of sheep pulmonary vein are mediated, at least in part, by increases of tissue cyclic AMP levels.


Cell surface markers in cord blood leucocytes after stimulation with lipopolysaccharide B.
T- and B-lymphocyte markers were studied in cord blood cells cultured with lipopolysaccharide B (LPS). Cells cultured with leucoagglutinin (LA) and pokeweed mitogen (PWM) were used as controls. LPS-induced lymphoblasts were negative for surface Ig, positive for intracellular Ig and did not form rosettes with sheep red blood cells (SRBC). LA-activated cells formed rosettes with SRBC, while PWM cultures showed a varying proportion of surface Ig-positive or SRBC rosetting cells, dependent on the time of culture. About 50% of both LA- and LPS-activated lymphoblasts formed EA rosettes (specific for Fc receptors) and EAC rosettes (specific for complement receptors). The response of foetal cells to LPS was reduced when lymphocytes obtained from Isopaque-Ficoll gradients were passed through nylon wool columns, whereas this procedure led to an increased response to LA. Thus LPS-activated foetal leucocytes are B lymphocytes expressing intracellular but not surface Ig.


Effect on hypothalamic self-stimulation of the novel beta-carbolines ZK 93 426 (a benzodiazepine receptor antagonist) and ZK 91 296 (a putative partial agonist).
Low doses (300 micrograms/kg-1.0 mg/kg) of the novel beta-carboline, ZK 91 296, a putative agonist at the benzodiazepine receptor, produced a significant increase in the rate of variable-interval self-stimulation responding, similar to that found with typical benzodiazepines. This effect was blocked by simultaneous administration of the specific benzodiazepine-receptor antagonists Ro 15-1788 (2.0 mg/kg), and ZK 93 426 (10 mg/kg). Neither antagonist, ZK 93 426 (100 micrograms/kg-10 mg/kg) or Ro 15-1788 (2.0 mg/kg), had any effect on self-stimulation when given alone. Unlike all benzodiazepine-receptor agonists previously tested, higher doses of ZK 91 296 did not depress self-stimulation response rates, even at a dose-level 100 times greater than the maximally stimulant dose. It is uncertain why ZK 91 296 lacks depressant effects: available evidence does not conclusively favour any single current explanation, but is consistent with it acting as a "partial" agonist.


[Pain Management in Palliative Care].
Patients in the palliative phase of a disease often suffer from pain, which leads to a significant reduction in quality of life. Since in most cases there is a progression rather than an improvement of the disease over time, pain therapy must also be dynamically adapted. Due to accompanying symptoms and the physical burden of the disease, treatment of pain is often difficult. In the palliative situation, pain should not only be understood as an excitation of nociceptors but is rather also an expression of mental stress. In this article, we would like to give an overview of the available drugs, application methods and alternative treatment options. Specifically, the article is divided into the following subsections: non-opioid analgesics, opioids, co-analgesics, patient-controlled analgesia procedures, neuraxial and peripheral regional anesthesia procedures, neurolysis, supportive therapies and palliative sedation. Thus, when treating palliative patients, the focus should not only be on the one symptom of pain, but, in the sense of the bio-psycho-social model, a multimodal oriented treatment of the patient with all his symptoms, also including his relatives, must be carried out.


The Development and Effectiveness of Combining Case-Based Online Lecture and Simulation Programs to Facilitate Interprofessional Function Care Training in Nursing Homes.
The aim of this study was to (1) develop a case-based combination of online lectures and simulations for function-focused care by nursing home interdisciplinary caregivers and (2) evaluate participants' increasing shared team and task knowledge by surrogate measures of team process and team performance. The study comprised the following steps: (1) the design of a learning module using a shared understanding of function-focused care as a shared mental model; (2) the establishment of two computer programs for online lectures and simulations using cases involving older adults with disabilities; and (3) testing the educational programs using a repeated-measures design. Participants were 61 interdisciplinary caregivers from seven nursing homes in four regions. Data from participants' team process and team performance were collected pre test, post online lecture, and post simulation. Repeated-measures analysis of variance showed that the mean scores for scales of "transactive memory system," "knowledge sharing and utilization," "team outcomes," "motivation for learning transfer," "self-efficacy," "interpersonal understanding," "proactivity in problem solving," and "function-focused care knowledge" differed significantly between the time points. The results indicate that a case-based program of a combination of online lectures and simulations elicits significant improvements in participants' team process and team performance.


Risk of Early Infection in Idiopathic Inflammatory Myopathies: Cluster Analysis Based on Clinical Features and Biomarkers.
Patients with idiopathic inflammatory myopathies (IIMs), referred to as myositis, are prone to infectious complications, which hinder the treatment of the disease and worsen the outcome of patients. The purpose of this study was to explore the different types of infectious complications in patients with myositis and to determine the predisposing factors for clinical reference. A retrospective study was conducted on 66 patients with IIM who were divided into different subpopulations by an unsupervised analysis of their clinical manifestations, laboratory features, and autoantibody characteristics. Combined with the incidence of infectious complications, the types of infectious pathogens and the sites of infection, the characteristics of infection, and susceptibility factors were explored. Three clusters with significantly different clinical characteristics and coinfection rates were identified (76.2% vs. 41.6% vs. 36.4%, p = 0.0139). Cluster 1 (n = 12) had a moderate risk of infection, with an infection rate of 41.6%. The patients in cluster 1 had a high probability of positive mechanic's hands, periungual erythema, anti-Ro52 antibody, and anti-Jo1 antibody. CD3 and CD4 were the highest among the three groups. Cluster 2 (n = 21) had a high risk of infection, and the incidence of infection was 76.2%. Almost all patients in this cluster had a rash, prominent clinical symptoms, and decreased WBC, PMN, LYM, CD3, and CD4 counts. Cluster 3 (n = 33) had a low risk of infection, with an infection rate of 36.4%. Compared with the other two clusters, cluster 3 (n = 33) lacked a typical rash but had a high ANA-positive rate. The patients in cluster 1 and cluster 3 were mainly infected by viruses, followed by bacterial infections. In cluster 2 patients, bacterial infections were the most prevalent. Fungal and Pneumocystis carinii were common causes of cluster 2 and 3 infections. In addition, the patients within a cluster often have a single infection, and pulmonary infections are the most common. We clustered the patients with IIM complicated with infection into three different types by their clinical symptoms and found that there were differences in the infection risk and infection types among the different cluster groups.


Anchorage effects of ligation and direct occlusion in orthodontics: A finite element analysis.
During orthodontic treatment, the figure-of-eight ligature and the physiological occlusion play an important role in providing anchorage effects. However, their effects on reaction forces of tooth and stress state in periodontal ligament (PDL) have not been quantitatively evaluated yet. In this study, we presented a finite element analysis process for simulating posterior molar ligature and direct occlusion during orthodontics in order to quantitatively assess their anchorage effects. A high precision 3D biomechanical model containing upper and lower teeth, PDL, brackets and archwire was generated from the images of computed tomographic scan and sophisticated modelling procedures. The orthodontic treatment of closing the extraction gap was simulated via the finite element method to evaluate the biomechanical response of the molars under the conditions with or without ligation. The simulations were divided into experimental and control groups. In the experimental group, orthodontic force of 1 N was first applied, then direct occlusal forces of 3 and 10 N were applied on each opposite tooth. While in the control group, occlusal forces were applied without orthodontic treatment. The tooth displacement, the stress state in the PDL and the directions of the resultant forces on each tooth were evaluated. In the case of molars ligated, the maximum hydrostatic stress in the molars' PDL decreases by 60%. When an initial tooth displacement of several microns occurs in response to an orthodontic force, the direction of the occlusal force changes simultaneously. Even a moderate occlusal force (3 N per tooth) can almost completely offset the mesial forces on the maxillary teeth, thus to provide effective anchorage effect for the orthodontics. The proposed method is effective for simulating ligation and direct occlusion. Figure-of-eight ligature can effectively disperse orthodontic forces on the posterior teeth, while a good original occlusal relationship provides considerable anchorage effects in orthodontics.


Salmonellosis in garden birds in Scotland, 1995 to 2008: geographic region, Salmonella enterica phage type and bird species.
Salmonellosis was diagnosed in garden birds from 198 incidents in Scotland between September 1995 and August 2008. Salmonellosis was essentially a disease of finches in the north of Scotland, but in the south of Scotland it was also a problem in house sparrows. Almost all of the incidents were caused by Salmonella Typhimurium phage types 40 or 56/variant, but regional variation in phage types was observed. In the north of Scotland, one phage type (DT 40) predominated, but in the south of Scotland two phage types were commonly isolated (DTs 40 and 56/variant, with the latter the more common of the two phage types). This regional difference was statistically significant for salmonellosis in greenfinches, chaffinches and 'other garden birds', but not for house sparrows. Different temporal patterns for different species of bird and different phage types were also observed within regions. These findings suggest that the epidemiology of salmonellosis in garden birds varies depending on the phage type of Salmonella and the species of garden bird, with additional regional differences depending on the wild bird populations and the phage types of Salmonella in circulation. An awareness of these differences will help when formulating guidelines aimed at reducing the impact of salmonellosis in garden birds.


Corneal injury from a metallic foreign body: an occupational hazard.
To describe a patient with a corneal injury from a metallic foreign body caused by negligence, and to highlight the importance of measures that must be taken to prevent corneal injuries. A 21-year-old man experienced a foreign body sensation, pain, and redness in his left eye after he cut some iron material without using any eye protection. Slitlamp examination showed a thin, curled piece of iron material stuck into the cornea horizontally. The nasal part had penetrated the nasal tarsal conjunctiva below the upper lid. After removal of the foreign body, the cornea healed without scarring after a short follow-up. A corneal foreign body is a common cause of ocular morbidity and loss of working hours. Most workers do not use protective eyewear during work. By consistently wearing proper safety eyewear, which is the easiest and most effective preventive measure, loss of sight can easily be prevented after an eye injury.


Hereditary protein C deficiency caused by novel compound heterozygous mutants in a Chinese pedigree: A case report.
Purpura fulminans (PF) is a neonatal presentation of homozygous or compound heterozygous protein C (PC) deficiency; infants who are diagnosed with it are determined to have a major defect in coagulation regulation which is associated with undetectable levels of PC. We report a pedigree who suffered from the hereditary PC deficiency with compound heterozygous mutants; genetic analysis revealed compound heterozygous mutations of 262 G > T(Asp88Tyr) and 400 + 5G > A that were identified in the proband; moreover, Asp88Tyr and 400 + 5G > A were also detected in the father and the mother, respectively. A bioinformatics analysis revealed 262 G > T is probably damaging, and structural analysis indicated a possible mechanism for the functional impairment of PC in this pedigree.


Auto-ignition and upper explosion limit of rich propane-air mixtures at elevated pressures.
The auto-ignition limits of propane-air mixtures at elevated pressures up to 15 bar and for concentrations from 10 mol% up to 70 mol% are investigated. The experiments are performed in a closed spherical vessel with a volume of 8 dm3. The auto-ignition temperatures decrease from 300 degrees C to 250 degrees C when increasing the pressure from 1 bar to 14.5 bar. It is shown that the fuel concentration most sensitive to auto-ignition depends on initial pressure. A second series of experiments investigates the upper flammability limit of propane-air mixtures at initial temperatures up to 250 degrees C and pressures up to 30 bar near the auto-ignition area. Finally the propane auto-oxidation is modelled using several detailed kinetic reaction mechanisms and these numerical calculations are compared with the experimental results.


The relationship between the variants in the 5'-untranslated regions of equine chorionic gonadotropin genes and serum equine chorionic gonadotropin levels.
An experiment was conducted to study the association between the single nucleotide polymorphisms (SNPs) in 5'-untranslated regions (5'-UTR) of equine chorionic gonadotropin (eCG) genes and the serum eCG levels. SNPs in 5'-UTR of eCG genes were screened across 10 horse breeds, including 7 Chinese indigenous breeds and 3 imported breeds using iPLEX chemistry, and the association between the serum eCG levels of 174 pregnant Da'an mares and their serum eCG levels (determined with ELISA) was analyzed. Four SNPs were identified in the 5'-UTR of the eCGα gene, and one of them was unique in the indigenous breeds. There were 2 SNPs detected at the 5' end of the eCGβ subunit gene, and one of them was only found in the Chinese breeds. The SNP g.39948246T>C at the 5'-UTR of eCGα was associated significantly with eCG levels of 75-day pregnant mare serum (p<0.05) in Da'an mares. Prediction analysis on binding sites of transcription factors showed that the g.39948246T>C mutation causes appearance of the specific binding site of hepatocyte nuclear factor 3 forkhead homolog 2 (HFH-2), which is a transcriptional repressor belonging to the forkhead protein family of transcription factors. The SNP g.39948246T>C at the 5'-UTR of eCGα is associated with eCG levels of 75-day pregnant mare serum (p<0.05).


Microfabrication procedure of PDMS microbeam array using photolithography for laminin printing and piconewton force transduction on axons.
The purpose of this paper is to introduce our design for transducing forces on the order of tens of piconewtons by optically measuring deflection of a microfabricated beam tip as it pulls on an array of flexible structures such as axons in an array of laminin-printed neurons. To achieve this we have designed polymeric beams with spring constants on the order of 10 pN/microm. We have fabricated circular microbeams with Sylgard polydimethylsiloxane (PDMS). The elastic modulus of PDMS was determined experimentally using a microscale and a micrometer at different concentrations of curing agent and base agent and found to be on the order of 100 kPa. The designed geometry is a 100x100 tapered microcone array with each beam having a length of 100 microm, and a base diameter of 10 microm. A SU-8 negative photoresist is etched using photolithography and used as a mold for PDMS soft lithography. PDMS was injected into the mold and the array peeled from the mold.


Electrophysiological and sleep alterations in experimental mouse rabies.
Changes in the spontaneous brain electrical activity and sleep organization were investigated in 5 mice strains during the evolution of experimental fixed rabies infection. Cortical electrodes were chronically implanted for continuous EEG recording and spectral analysis until death. Three evolutionary phases were individualized. The initial phase exhibited alterations of sleep stages, REM sleep disappearance, pseudoperiodic facial myoclonus and first clinical signs. The mature phase was characterized by a generalized EEG slowing (2-4 cycles/s). The terminal phase occurring with extinction of hippocampal rhythmic slow activity showed a flattening of cortical activity. The brain electrical activity ceased about 30 min before the cardiac arrest. Paroxysmal activities appeared during the course of the disease as bursts of rhythmic slow waves, pseudoperiodic spikes or occasionally ictal epileptic discharges. Spectral analysis revealed a progressive and characteristic clustering of the EEG frequency band power values. The spread of infection in the CNS was monitored by specific immunofluorescence studies which revealed the presence of rabies virus antigen in the pons, the cerebellum, the thalamus and the cortex during the initial phase. The pyramidal field of the hippocampus was infected during the mature phase but the gyrus dentatus was never infected even at the terminal phase. These studies show that particular neuronal functions are impaired during rabies virus infection suggesting that neuronal alterations may be involved in the pathogenic mechanisms leading to lethality.