Highly sensitive glucose sensor based on pt nanoparticle/polyaniline hydrogel heterostructures.
Glucose enzyme biosensors have been shown useful for a range of applications from medical diagnosis, bioprocess monitoring, to beverage industry and environmental monitoring. We present here a highly sensitive glucose enzyme sensor based on Pt nanoparticles (PtNPs)-polyaniline (PAni) hydrogel heterostructures. High-density PtNPs were homogeneously loaded onto the three-dimensional (3D) nanostructured matrix of the PAni hydrogel. The PtNP/PAni hydrogel heterostructure-based glucose sensor synergizes the advantages of both the conducting hydrogel and the nanoparticle catalyst. The porous structure of the PAni hydrogel favored the high density immobilization of the enzyme and the penetration of water-soluble molecules, which helped efficiently catalyze the oxidation of glucose. In addition, the PtNPs catalyzed the decomposition of hydrogen peroxide that was generated during the enzymatic reaction. The transferred charges from these electrochemical processes were efficiently collected by the highly conducting PtNP/PAni hydrogel heterostructures. The glucose enzyme sensor based on this heterostructure exhibited unprecedented sensitivity, as high as 96.1 μA·mM(-1)·cm(-2), with a response time as fast as 3 s, a linear range of 0.01 to 8 mM, and a low detection limit of 0.7 μM.


Molecular Modeling, de novo Design and Synthesis of a Novel, Extracellular Binding Fibroblast Growth Factor Receptor 2 Inhibitor Alofanib (RPT835).
Fibroblast growth factor (FGF) receptors (FGFRs) play a key role in tumor growth and angiogenesis. The present report describes our search for an extracellularly binding FGFR inhibitor using a combined molecular modeling and de novo design strategy. Based upon crystal structures of the receptor with its native ligand and knowledge of inhibiting peptides, we have developed a computational protocol that predicts the putative binding of a molecule to the extracellular domains of the receptor. This protocol, or scoring function, was used in combination with the de novo synthesis program 'SYNOPSIS' to generate high scoring and synthetically accessible compounds. Eight compounds belonging to 3 separate chemical classes were synthesized. One of these compounds, alofanib (RPT835), was found to be an effective inhibitor of the FGF/FGFR2 pathway. The preclinical in vitro data support an allosteric inhibition mechanism of RPT835. RPT835 potently inhibited growth of KATO III gastric cancer cells expressing FGFR2, with GI50 value of 10 nmol/L. These results provide strong rationale for the evaluation of compound in advanced cancers.


Effects of headgear Herbst and mandibular step-by-step advancement versus conventional Herbst appliance and maximal jumping of the mandible.
The aims of this study were to compare dental and skeletal treatment changes in Class II division 1 malocclusions with two modes of maxillary control and two modes of bite-jumping. The subjects comprised Chinese children with severe Class II division 1 malocclusions, i.e. 21 consecutive subjects (13.4 +/- 1.4 years) treated with a headgear Herbst appliance and step-by-step advancement (HHSSA) of the mandible, and 24 consecutive subjects (13.2 +/- 1.4 years) treated with a 'conventional' Herbst appliance with maximal jumping (HMJ) of the mandible. Lateral cephalograms obtained at the start and end of treatment were analysed. The results showed that the improvement of the sagittal jaw relationship was significantly larger (2.9 mm; P < 0.001) in the HHSSA group than in the HMJ group due to the increased effect on the maxilla (-1.5 mm, P < 0.001) and the mandible (+1.4 mm, NS). There was no significant difference in the change in lower anterior face height, being 2.7 and 3.1 mm, respectively. The mandibular plane angle decreased significantly in the HHSSA group (-0.7 degree; P < 0.05) and increased insignificantly in the HMJ group (0.4 degree, NS), the difference being statistically significant (P < 0.01). The maxillary molars moved significantly more distally (1.1 mm, P < 0.05) and were intruded in the HHSSA group (-1.0 mm, P < 0.001) compared with a small extrusion in the HMJ group (+0.3 mm, NS), the difference being statistically significant (P < 0.001). There was no significant difference in the effect on the mandibular teeth. Treatment with HHSSA seems to result in a greater effect on the sagittal jaw relationship, improved vertical control and more maxillary molar movement. Mandibular anchorage loss was not reduced with step-by-step advancement of the mandible.


Human colostrum stimulates cytokine production.
The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.


Mechanical properties of NiTi and CuNiTi shape-memory wires used in orthodontic treatment. Part 1: stress-strain tests.
This research aimed to compare, through traction tests, eight types of superelastic and heat-activated NiTi archwires, by six trade companies (GAC, TP, Ormco, Masel, Morelli and Unitek) to those with addition of copper (CuNiTi 27°C and 35°C, Ormco). The tests were performed in an EMIC mechanical testing machine, model DL10000, capacity of 10 tons, at the Military Institute of Engineering (IME). The results showed that, generally, heat-activated NiTi archwires presented slighter deactivation loadings in relation to the superelastic ones. Among the archwires that presented deactivation loadings biologically more adequate are the heat-activated by GAC and by Unitek. Among the superelastic NiTi, the CuNiTi 27°C by Ormco were the ones that presented slighter deactivation loadings, being statistically (ANOVA) similar to the ones presented by the heat-activated NiTi archwires from Unitek. When compared the CuNiTi 27°C and 35°C archwires, it was observed that the 27°C presented deactivation forces of, nearly, ⅓ of the presented by the 35°C. It was concluded that the CuNiTi 35°C archwires presented deactivation loadings biologically less favorable in relation to the other heat-activated NiTi archwires, associated to lower percentage of deformation, on the constant baselines of deactivation, showing less adequate mechanical behavior under traction, in relation to the other archwires.


The cause of the artifact in 4-slice helical computed tomography.
The causes of the image artifacts in a 4-slice helical computed tomography have been discussed as follows: (1) changeover in pairs of data used in z interpolation, (2) sampling interval in z, and (3) the cone angle. This study analyzes the first two causes of the artifact and describes how the current algorithm [K. Taguchi and H. Aradate, Radiology 205P, 390 (1997); 205P, 618 (1997); Med. Phys. 25, 550-561 (1998); H. Hu, ibid. 26, 5-18 (1999); S. Schaller et al., IEEE Trans. Med. Imaging 19, 822-834 (2000); K. Taguchi, Ph.D. thesis, University of Tsukuba, 2002] solves the problem. An interpolated sinogram for a slice at the edge of a ball phantom shows discontinuity caused by the changeover. If we extend the streak artifact in the reconstructed image, it crosses the focus orbit at the corresponding projection angle. Applying z filtering can reduce such causes by its feathering effect and mixing data obtained by different cone angles; the best results are provided when z filtering is applied to densely sampled helical data.


Origin of espanola island and the age of terrestrial life on the galapagos islands.
Geological studies of Española (Hood) Island, Galápagos, Ecuador, indicate that the island had a subaerial rather than a submarine origin. Because the younger lava flows are dated at 3 million years, Española has apparently existed as an island for at least that long. Thus terrestrial life may have existed or arrived on the Galápagos Islands at least 3 million years ago, more than twice as long as had been assumed.


Efficacy of Ginger in Control of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients Receiving Doxorubicin-Based Chemotherapy.
Nausea and vomiting are among the most serious side effects of chemotherapy, in some cases leading to treatment interruption or chemotherapy dose reduction. Ginger has long been known as an antiemetic drug, used for conditions such as motion sickness, nausea-vomiting in pregnancy, and post-operation side effects. One hundred and fifty female patients with breast cancer entered this prospective study and were randomized to receive ginger (500 mg ginger powder, twice a day for 3 days) or placebo. One hundred and nineteen patients completed the study: 57 of them received ginger and 62 received ginger for the frst 3 chemotherapy cycles. Mean age in all patients was 48.6 (25-79) years. After 1st chemotherapy, mean nausea in the ginger and control arms were 1.36 (±1.31) and 1.46 (±1.28) with no statistically significant difference. After the 2nd chemotherapy session, nausea score was slightly more in the ginger group (1.36 versus 1.32). After 3rd chemotherapy, mean nausea severity in control group was less than ginger group [1.37 (±1.14), versus 1.42 (±1.30)]. Considering all patients, nausea was slightly more severe in ginger arm. In ginger arm mean nausea score was 1.42 (±0.96) and in control arm it was 1.40 (±0.92). Mean vomiting scores after chemotherapy in ginger arm were 0.719 (±1.03), 0.68 (±1.00) and 0.77 (±1.18). In control arm, mean vomiting was 0.983 (±1.23), 1.03 (±1.22) and 1.15 (±1.27). In all sessions, ginger decreased vomiting severity from 1.4 (±1.04) to 0.71 (±0.86). None of the differences were significant. In those patients who received the AC regimen, vomiting was less severe (0.64±0.87) compared to those who received placebo (1.13±1.12), which was statistically significant (p-value <0.05). Further and larger studies are needed to draw conclusions.


Chlamydia pneumoniae and age-related macular degeneration: a role in pathogenesis or merely a chance association?
The role of inflammation in the aetiology of age-related macular degeneration (AMD) has become very topical as the discovery that genetic variation in complement pathway genes influences the risk of developing AMD. Complement factor H gene, an inhibitor of the alternative complement activation pathway along with other complement pathway genes factor F (BF) and C2 show significant contribution to the risk of AMD. The alternative complement pathway is activated by a trigger, which is often microbial in nature. One current model of AMD aetiology implicates aberrant regulation of the alternative pathway of complement, in combination with some unknown infectious agents. Chlamydia pneumoniae could be one such potential trigger of the alternative complement pathway and several investigations have linked C. pneumoniae to AMD. However, there are only a few studies to date and numbers in most studies are small. Also there are many difficulties in verifying laboratory techniques for the detection of C. pneumoniae chronic infection. As such we need to be cautious not to over interpret the current results. However, the findings certainly give impetus for further work on C. pneumoniae and AMD. This paper provides an overview of work in this area.


Characterizing the distribution of sodium alkyl sulfate surfactant homologues in water-based, acrylic pressure-sensitive adhesive films.
The distributions of three sodium alkyl sulfate surfactants in dry adhesive films cast from water-based latexes were characterized using confocal Raman microscopy (CRM) and contact angle (CA) and tack measurements. Sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (STS), and sodium octadecyl sulfate (SODS) were added to dialyzed commercial adhesive latex at various concentrations. Uneven distributions were found for all three surfactants along with a tendency to enrich film-air interfaces and, to a much lesser extent, film-glass interfaces. SDS demonstrated the greatest tendency to concentrate near film surfaces followed by STS and SODS. For all three surfactants, water CA values for dried films decreased sharply with increasing concentrations in the latex, but significant differences were observed, with SDS again having the greatest impact followed by STS and SODS. Tack of dried polymer films was also found to decrease with increasing latex surfactant levels, with SDS producing the sharpest drop as well as the lowest plateau values. Results indicate that interfacial enrichment by surfactants is detectable via both CRM and CA measurements, and this enrichment can significantly affect the performance of films. Finally, surface enrichment levels are qualitatively related to measures of the surfactants' affinity for aqueous solutions, as characterized by the logarithm of their 1-octanol-water distribution coefficients (K(ow)).


The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells.
We previously demonstrated that human pericytes, which encircle capillaries and microvessels, give rise in culture to genuine mesenchymal stem cells (MSCs). This raised the question as to whether all MSC are derived from pericytes. Pericytes and other cells defined on differential expression of CD34, CD31, and CD146 were sorted from the stromal vascular fraction of human white adipose tissue. Besides pericytes, CD34+ CD31- CD146- CD45- cells, which reside in the outmost layer of blood vessels, the tunica adventitia, natively expressed MSC markers and gave rise in culture to clonogenic multipotent progenitors identical to standard bone marrow-derived MSC. Despite common MSC features and developmental properties, adventitial cells and pericytes retain distinct phenotypes and genotypes through culture. However, in the presence of growth factors involved in vascular remodeling, adventitial cells acquire a pericytes-like phenotype. In conclusion, we demonstrate the co-existence of 2 separate perivascular MSC progenitors: pericytes in capillaries and microvessels and adventitial cells around larger vessels.


Ribosomal protein L3 functions as a 'rocker switch' to aid in coordinating of large subunit-associated functions in eukaryotes and Archaea.
Although ribosomal RNAs (rRNAs) comprise the bulk of the ribosome and carry out its main functions, ribosomal proteins also appear to play important structural and functional roles. Many ribosomal proteins contain long, nonglobular domains that extend deep into the rRNA cores. In eukaryotes and Archaea, ribosomal protein L3 contains two such extended domains tethered to a common globular hub, thus providing an excellent model to address basic questions relating to ribosomal protein structure/function relationships. Previous work in our laboratory identified the central 'W-finger' extension of yeast L3 in helping to coordinate ribosomal functions. New studies on the 'N-terminal' extension in yeast suggest that it works with the W-finger to coordinate opening and closing of the corridor through which the 3' end of aa-tRNA moves during the process of accommodation. Additionally, the effect of one of the L3 N-terminal extension mutants on the interaction between C75 of the aa-tRNA and G2921 (Escherichia coli G2553) of 25S rRNA provides the first evidence of the effect of a ribosomal protein on aa-tRNA positioning and peptidyltransfer, possibly through the induced fit model. A model is presented describing how all three domains of L3 may function together as a 'rocker switch' to coordinate the stepwise processes of translation elongation.


Collaborative Care for Adolescents With Persistent Postconcussive Symptoms: A Randomized Trial.
Postconcussive and co-occurring psychological symptoms are not uncommon after sports-related concussion and are associated with functional impairment and societal costs. There is no evidence-based treatment targeting postconcussive symptoms in children and adolescents. The goal of this study was to test a collaborative care intervention model with embedded cognitive-behavioral therapy, care management, and psychopharmacological consultation. We hypothesized that patients in collaborative care would demonstrate greater reductions in postconcussive, depressive, and anxiety symptoms and improvement in functioning over the course of 6 months, compared with usual care control. Patients aged 11 to 17 years with persistent symptoms ≥1 month after sports-related concussion were randomly assigned to receive collaborative care (n = 25) or care as usual (n = 24). Patients were assessed before randomization and after 1, 3, and 6 months. Groups were compared over time via linear mixed effects regression models. Adolescents assigned to collaborative care experienced clinically and statistically significant improvements in postconcussive symptoms in addition to functional gains at 6 months compared with controls. Six months after the baseline assessment, 13.0% of intervention patients and 41.7% of control patients reported high levels of postconcussive symptoms (P = .03), and 78% of intervention patients and 45.8% of control patients reported ≥50% reduction in depression symptoms (P = .02). No changes between groups were demonstrated in anxiety symptoms. Orchestrated efforts to systematically implement collaborative care treatment approaches for slow-to-recover adolescents may be useful given the reductions in postconcussive and co-occurring psychological symptoms in addition to improved quality of life.


Measuring Marrow Density and Area Using Peripheral Quantitative Computed Tomography at the Tibia: Precision in Young and Older Adults and Individuals With Spinal Cord Injury.
The objective of this study was to compare the test-retest precision error for peripheral quantitative computed tomography (pQCT)-derived marrow density and marrow area segmentation at the tibia using 3 software packages. A secondary analysis of pQCT data in young adults (n = 18, mean ± standard deviation 25.4 ± 3.2 yr), older adults (n = 47, 71.8 ± 8.2 yr), and individuals with spinal cord injury (C1-T12 American Spinal Injury Association Impairment Scale, classes A-C; n = 19, 43.5 ± 8.6 yr) was conducted. Repeat scans of the tibial shaft (66%) were performed using pQCT (Stratec XCT2000). Test-retest precision errors (root mean square standard deviation and root mean square coefficient of variation [RMSCV%]) for marrow density (mg/cm3) and marrow area (mm2) were reported for the watershed-guided manual segmentation method (SliceOmatic version 4.3 [Sliceo-WS]) and the 2 threshold-based edge detection methods (Stratec version 6.0 [Stratec-TB] and BoneJ version 1.3.14 [BoneJ-TB]). Bland-Altman plots and 95% limits of agreement were computed to evaluate test-retest discrepancies within and between methods of analysis and subgroups. RMSCV% for marrow density segmentation was >5% for all methods across subgroups (Stratec-TB: 12.2%-28.5%, BoneJ-TB: 14.5%-25.2%, and Sliceo-WS: 10.9%-23.0%). RMSCV% for marrow area segmentation was within 5% for all methods across subgroups (Stratec-TB: 1.9%-4.4%, BoneJ-TB: 2.6%-5.1%, and Sliceo-WS: 2.4%-4.5%), except using BoneJ-TB in older adults. Intermethod discrepancies in marrow density appeared to be present across the range of marrow density values and did not differ by subgroup. Intermethod discrepancies varied to a greater extent for marrow area and were found to be more frequently at mid- to higher-range values for those with spinal cord injury. Precision error for pQCT-derived marrow density segmentation exceeded 5% for all methods of analysis across a range of bone mineral densities and fat infiltration, whereas precision error for marrow area segmentation ranged from 2% to 5%. Further investigation is necessary to determine alternative acquisition and analysis methods for pQCT-derived marrow segmentation.


Contrast-Enhanced Nanofocus X-Ray Computed Tomography Allows Virtual Three-Dimensional Histopathology and Morphometric Analysis of Osteoarthritis in Small Animal Models.
One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models. In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology. We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model. We have shown that CE-nanoCT is a tool that allows virtual histopathology and 3D morphological quantification of multitissue systems, such as the chondro-osseous junction. It provides faster and more quantitative data on cartilage structure and quality compared with standard histopathology while eliminating user bias. CE-nanoCT thus should allow capturing subtle differences in cartilage characteristics, carefully mapping OA progression and, ultimately, asses the beneficial changes when testing a candidate disease-modifying treatment.


Gastrointestinal complications in patients with diabetes mellitus.
Diabetes mellitus is a systemic disease which affects patients of various age. Hyperglycemia induces damage of vascular endothelium, development of chronic inflammation, organic and functional lesions in several systems and organs. The principal gastroenterological complaints linked to the manifestation of the disease include abdominal pain, diarrhea, nausea, flatulence, and vomiting. However, complications in the alimentary system may manifest exclusively by difficulties in reaching normoglycemia and numerous persistent episodes of hypoglycemia. The most frequent complication of diabetes mellitus affecting the alimentary tract involves gastroparesis and disturbances in pancreatic function. Diabetes may also aggravate other coexisting diseases, such as gastroesophageal reflux or periodontitis. Subject-based references accentuate also a significantly more frequent manifestation together with diabetes of other autoimmune diseases, such as celiac disease or autoimmune gastritis. Also, a hepatic microangiopathy and increased incidence of certain tumors, linked to the manifestation of insulin resistance, may be regarded to represent complications of long-term diabetes. Rapid diagnosis and adequate treatment may significantly improve a patient's quality of life and influence the prolonged control of glycemia. Nevertheless, this requires a rigorous analysis of the signs and clinical condition of a patient as well as individualization of recommendations and therapy.


Accuracy of an electrochemical sensor for measuring capillary blood ketones by fingerstick samples during metabolic deterioration after continuous subcutaneous insulin infusion interruption in type 1 diabetic patients.
This study was designed to test the accuracy of capillary ketonemia for diagnosis of ketosis after interruption of insulin infusion. A total of 18 patients with type 1 diabetes treated by external pump were studied during pump stop for 5 h. Plasma and capillary ketonemia and ketonuria were determined every hour from 7:00 A.M. (time 0 min = T0) to 12:00 P.M. (time 300 min = T300). Plasma beta-hydroxybutyrate (beta-OHB) levels were measured by an enzymatic end point spectrophotometric method, and capillary beta-OHB levels were measured by an electrochemical method (MediSense Optium meter). Ketonuria was measured by a semiquantitative test (Ketodiastix). Positive ketosis was defined by a value of >/=0.5 mmol/l for ketonemia and >/=4 mmol/l (moderate) for ketonuria. After stopping the pump, concentrations of beta-OHB in both plasma and capillary blood increased significantly at time 60 min (T60) compared with T0 (P < 0.001), reaching maximum levels at T300 (1.30 +/- 0.49 and 1.23 +/- 0.78 mmol/l, respectively). Plasma and capillary beta-OHB values were highly correlated (r = 0.94, P < 0.0001). For diagnosis of ketosis, capillary ketonemia has a higher sensitivity and negative predictive value (80.4 and 82.5%, respectively) than ketonuria (63 and 71.8%, respectively). For plasma glucose levels >/=250 mg/dl, plasma and capillary ketonemia were found to be more frequently positive (85 and 78%, respectively) than ketonuria (59%) (P = 0.017). The time delay to diagnosis of ketosis was significantly higher for ketonuria than for plasma ketonemia (212 +/- 67 vs. 140 +/- 54 min, P = 0.0023), whereas no difference was noted between plasma and capillary ketonemia. The frequency of screening for ketosis and the efficiency of detection of ketosis definitely may be improved by the use of capillary blood ketone determination in clinical practice.


Unexplained proximal tibiofibular joint pain after high tibial osteotomy.
Problems of the proximal tibiofibular joint (pTFj) after high tibial osteotomy (HTO) are rare. With this case report, we strive to highlight the importance of investigating the pTFj in patients with unexplained knee pain after HTO. A 44 year old male patient presented with diffuse pain on his left knee 3 years after medial opening wedge HTO due to medial compartment overloading in a varus knee. Patient described persistent anterior tibial and lateral knee pain. 2 years after HTO, patient underwent implant removal but the knee pain persisted. As the reason for the persistent pain was not identified, further radiological evaluation was done. Single photon emission computerized tomography/computerized tomography (SPECT/CT) revealed that there was no increased uptake within the tibiofemoral joint, indicating a biologically well performed correction of the varus deformity. However, markedly increased tracer uptake was found at the pTFj. On the inherent axial CT scans, it was seen that the proximal screws were too long and placed within the pTFj. Along with this a severe osteoarthritis of the pTFj was identified. The cause of the patient's pain was then confirmed by a CT guided infiltration of local anesthetic. An arthrodesis of the pTFj was performed and at 12 months followup after the arthrodesis the patient was pain free. This case highlights how important it is to evaluate the pTFj in patients with unexplained pain after HTO. SPECT/CT was helpful in identifying the patient's problem in this challenging case.


Influence of calcium ion on the binding of fibrin amino terminal peptides to fibrinogen.
The affinity of the amino terminal tetrapeptide of the beta chain of fibrin, Gly-His-Arg-Pro, for fibrinogen dramatically increases in the presence of 2 millimolar calcium ion. In contrast, there is no significant increase in the affinity of peptides beginning with the amino terminal sequence of the fibrin alpha chain, Gly-Pro-Arg, in the presence of calcium ions, although the number of binding sites increases. In the latter case, the increased number of sites is due to the alpha chain analogs binding to the site ordinarily occupied by the beta chain analogs. These results indicate that structures at the amino terminus of the fibrin beta chain play a more important role in fibrin polymerization when calcium ions are present.


Robust Oil-Fouling Resistance of Amorphous Cellulose Surface Underwater: A Wetting Study and Application.
The antioil-fouling characteristic of an amorphous cellulose (a-cellulose) surface was elucidated using the sessile droplet method (static) and a modified Wilhelmy plate technique (dynamic). As compared to other hydrophilic surfaces (cellulose acetate, poly(vinyl alcohol), and glass), the oil (poly(dimethylsiloxane)) contact angle on the a-cellulose surface underwater shows the largest value (170.5 ± 5.0°), having the smallest deviation from its theoretical value (180.0°) as estimated by Young's equation. Also, the a-cellulose surface demonstrates the strongest affinity with water in an oil medium (stable hydrophilicity). Moreover, the work of adhesion between the receding oil phase and a-cellulose underwater is quantified to be 10.3 mN/m, approximately one-fourth of that in air (42.0 mN/m). The overall wetting study suggests a rather low oil/solid/water three-phase contact line (TPL) friction in the direction that water displaces oil. A proposed mechanism attributes these phenomena to the water-accessible rigid cellulose chains and supramolecular structure of a-cellulose. The former hinders molecular rearrangement during processing or upon exposure to oil, such that its polar hydroxyl groups are readily accessible to water, thereby retaining its hydrophilicity. The latter allows water to diffuse across the TPL, forming the hydration shells that weaken the van der Waals interactions between oil and cellulose chains. Such findings of the a-cellulose surface can be exploited to fabricate mesh membranes with high water permeation flux (375.4 ± 13.5 L m-2 h-1 Pa-1), high oil/water separation efficiency (93-98%), and long-lasting stability, which is suitable for offshore oil spill remediation.


The "wh" questions of visual phonics: what, who, where, when, and why.
Visual Phonics is a reading instructional tool that has been implemented in isolated classrooms for over 20 years. In the past 5 years, several experimental studies demonstrated its efficacy with students who are deaf or hard of hearing. Through a national survey with 200 participants, this study specifically addresses who, where, how, and why a sample of teachers use Visual Phonics in their everyday reading instruction. Through checklists of teaching practice, rating scales, and open-ended questions, teachers self-reported their use of Visual Phonics, reflected upon its efficacy, and what they think about using it with students with a diverse set of instructional needs. The majority reported that Visual Phonics was easy to use, engaging to students, and easy to integrate into a structured reading curriculum. The majority of respondents agreed that it helps increase phonemic awareness and decoding skills, build vocabulary, as well as increase reading comprehension. The implications of these findings in bridging the research-to-practice gap are discussed.


Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis.
Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain-like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level-dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve-ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain.


Analytical results for the interaction energy of a trapped, weakly interacting Bose-Einstein condensate.
We examine the problem of a repulsive, weakly interacting and harmonically trapped Bose-Einstein condensate under rotation. We derive a simple analytic expression for the energy incorporating the interactions when the angular momentum per particle is between zero and one and find that the interaction energy decreases linearly as a function of the angular momentum in agreement with previous numerical and limiting analytical studies.


Study of Thoracoscopic Repair of Diaphragmatic Eventration in Children: A Case Series.
Background: To present a case series of children with eventration of diaphragm who underwent thoracoscopic repair highlighting the technical points and surgical modifications to prevent a recurrence. Settings and Design: This is an observational study of patients with diaphragmatic eventration admitted to a tertiary care institute. The study was designed following CARE guidelines endorsed by EQUATOR Network. Pediatric patients who had undergone thoracoscopic repair between January 2010 and March 2019 were included in the study. Materials and Methods: Age at surgery, gender, weight, site of the lesion, operating time, need for postoperative drain, and complications were assessed. Results: Twenty-six patients had thoracoscopic repair of the eventration of diaphragm. The male-female ratio was 12:1 and mean weight at the time of surgery was 6.3 kg (2.2-22 kg) with most patients having left side congenital diaphragmatic eventration (n = 21) as compared with the right side (n = 5). The average operating time was 66 minutes (37-144 minutes). Conclusions: Diaphragm plication by a thoracoscopic approach is safe and feasible in neonates and pediatric patients.


Relationships between work-related factors and musculoskeletal health with current and future work ability among male workers.
The purpose was to increase job-specific knowledge about individual and work-related factors and their relationship with current and future work ability (WA). We studied cross-sectional relationships between mental demands, physical exertion during work, grip strength, musculoskeletal pain in the upper extremities and WA and the relationships between these variables and WA 11 years later. We used a dataset of a prospective cohort study (1997-2008) among employees of an engineering plant (n = 157). The cohort was surveyed by means of tests and written questions on work demands, musculoskeletal health, WA score (WAS; 0-10), and mental and physical WA. Spearman correlation coefficients and logistic regression analysis were used. Among manual workers, we found weak correlations between grip strength and current and future physical WA. We did not find predictors for future poor WA among the manual workers. Among the office workers, we found that musculoskeletal pain was moderately and negatively related to current WAS and physical WA. More handgrip strength related to better future WAS and physical WA. Musculoskeletal pain (OR 1.67 p < 0.01) and lower handgrip strength (OR 0.91 p < 0.05) predicted future poor WA among office workers. Our results showed cross-sectional and longitudinal relationships between musculoskeletal health and work ability depending on occupation. However, the present implies that predicting work ability in the far future based on health surveillance data is rather difficult. Testing the musculoskeletal system (grip strength) and asking workers' about their musculoskeletal health seems relevant when monitoring work ability.


Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity.
Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.


Indirect spinal canal decompression of vertebral burst fracture in calf model.
An experimental study of experimental burst fractures in bovine spinal specimens was conducted to analyze the effects of transpedicular short-segment posterior fixation followed by reduction on indirect spinal canal decompression. For this purpose, experimental burst fractures were created in 11 bovine specimens with a hydraulic materials-testing machine. The specimens were evaluated with plain radiographs and CT scans before reduction. Thereafter, they were instrumented with titanium transpedicular screws and rods (short-segment posterior fixation); and reduction was achieved which included distraction and kyphosis correction maneuvers. Each spinal specimen was evaluated with plain radiographs and CT scans after reduction by applying distraction and kyphosis correction maneuvers. Plain radiographic analysis showed that the kyphosis angle and segmental height values improved. Furthermore, CT scans revealed that the spinal canal diameter values improved compared with those before reduction. The differences between before and after reduction in kyphosis angle, segmental height, anterior body compression, and percentage of retropulsion were statistically significant. Short-segment posterior fixation followed by indirect spinal canal decompression led to an improvement over spinal canal retropulsion in experimental burst fractures. Furthermore, the kyphosis angle and segmental height values improved following the reduction compared with those before reduction.


StaR Child Health: developing evidence-based guidance for the design, conduct and reporting of paediatric trials.
There has been a huge upsurge in clinical research in children in the last decade, stimulated in England by dedicated research infrastructure and support through the National Institute for Health Research. This infrastructure offering research design, expert review, trial management, research nurse, data support and dedicated facilities enables paediatricians to conduct more and better research. The challenge is how to design and conduct trials that will make a real difference to children's health. Standards for Research (StaR) in Child Health was founded in 2009 to address the paucity and shortcomings of paediatric clinical trials. This global initiative involves methodologists, clinicians, patient advocacy groups and policy makers dedicated to developing practical, evidence-based standards for enhancing the reliability and relevance of paediatric clinical research. In this overview, we highlight the contribution of StaR to this agenda, describe the international context, and suggest how StaR's future plans could be integrated with new and existing support for research.


A novel cuproptosis-related lncRNA prognostic signature in thyroid cancer.
Aims: We aimed to investigate the value of cuproptosis-related lncRNA in screening out high-risk thyroid cancer patients. Materials & methods: RNA sequencing data of thyroid cancer were obtained from The Cancer Genome Atlas. A cuproptosis-related lncRNA signature was constructed by using Cox regression. Results: Four cuproptosis-related lncRNAs were used to construct a survival prognosis model for thyroid cancer. The receiver operating characteristic curve showed that the area under the curve reached 0.830 at 1 year, 0.790 at 3 years and 0.824 at 5 years. Conclusion: The model may help to screen out thyroid cancer patients at high risk, and thus develop more appropriate treatment strategies.


Association of autistic spectrum disorder with season of birth and conception in a UK cohort.
To examine the association between autistic spectrum disorder (ASD) and seasons of conception and birth in a UK birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC). Seasons of conception and birth were compared in children with and without ASD with season grouped as follows: spring (March-May); summer (June-August); autumn (September-November) and winter (December-February). A total of 86 children with ASD were identified in the ALSPAC cohort giving a prevalence of ASD of 61.9 per 10,000. There was some evidence for an excess of children with ASD being conceived during the summer months with a rate per 1,000 conceptions of 9.5 in summer compared to 5.1, 4.6, 5.7 in spring, autumn and winter, respectively. A doubling of the odds was suggested for summer compared to autumn (Odds ratio 2.08 [1.18, 3.70]). In agreement with previous research, there was a corresponding peak in spring births. Conception during the summer months was associated with an over-representation of children with ASD in this UK birth cohort. There was also an association between ASD and spring births. Further investigation of seasonal influences on the aetiology of autism is required to identify possible factors in the environment, and their mechanisms and timings.


Assessment of professionalism in Iranian pharmacists.
In the recent years, the role of a pharmacist has been significantly changed. Traditionally, in the late 20(th) century, a pharmacist's role was considered as merely dispensing medication to patients. This view however, has been significantly altered, and, today, a pharmacist is supposed to provide patients with information regarding the medication they are to take, as well as on different aspects of their disease. Therefore, one can suggest that some other factors have recently come into play in the daily tasks of a pharmacist such as accountability and authority. The current cross-sectional survey is conducted on a cohort of community pharmacists attending a continuing education program. A questionnaire comprised of 26 Likert-type scale questions was designed to assess pharmacists' attitude towards professionalism and its subscales which are defined later in detail. A total number of 1000 pharmacists were surveyed and 560 of them filled and returned the questionnaires. On a scale from 1-5 on which 1 was corresponded with strongly agree and 5 with strongly disagree, the total score of pharmacists professionalism was 92.9 ± 10.4 out of 130. As regards the subscales, in the subscale of accountability 46.8% of participants, in the subscale of altruism 90.1% of participants, in the theme of duty 85.7% of participants, and in the subscale of working relationship with physicians 84% of pharmacist achieved more than two third of the total score. Only in term of conflict of interest 67.9% of participants scored less than two third (17-25) of the total score. Women obtained significantly higher scores in altruism (P<0.05). Furthermore, there was a correlation between age and the score of accountability and working relationship with physicians; and, the same was observed in regards with work experience with the score of working relationship with physicians. The employment position affected neither our participants' response to the whole questionnaire nor any of subscales. Although the total score for professionalism was not dramatically decreased, the significantly low results are alarming and they should be considered more seriously. In order to enhance the level of pharmacists' professionalism, especially in some special aspects, it seems necessary to conduct similar surveys on pharmacy students and registered pharmacists with a more comprehensive questionnaire. Overall, it can be concluded that designing a proper teaching course in professionalism for pharmacy students is of paramount importance if we are to promote professionalism in future pharmacists.


Enhanced Methanol Synthesis over Self-Limited ZnO x Overlayers on Cu Nanoparticles Formed via Gas-Phase Migration Route.
Supported metal catalysts are widely used for chemical conversion, in which construction of high density metal-oxide or oxide-metal interface is an important means to improve their reaction performance. Here, Cu@ZnOx encapsulation structure has been in-situ constructed through gas-phase migration of Zn species from ZnO particles onto surface of Cu nanoparticles under CO2 hydrogenation atmosphere at 450 °C. The gas-phase deposition of Zn species onto the Cu surface and growth of ZnOx overlayer is self-limited under the high temperature and redox gas (CO2/H2) conditions. Accordingly, high density ZnOx-Cu interface sites can be effectively tailored to have an enhanced activity in CO2 hydrogenation to methanol. This work reveals a new route for the construction of active oxide-metal interface and classic strong metal-support interaction state through gas-phase migration of support species induced by high temperature redox reaction atmosphere.


The (paper) work of medicine: understanding international medical costs.
This paper draws on international evidence on medical spending to examine what the United States can learn about making its healthcare system more efficient. We focus primarily on understanding contemporaneous differences in the level of spending, generally from the 2000s. Medical spending differs across countries either because the price of services differs (for example, a coronary bypass surgery operation may cost more in the United States than in other countries) or because people receive more services in some countries than in others (for example, more bypass surgery operations). Within the price category, there are two further issues: whether factors earn different returns across countries and whether more clinical or administrative personnel are required to deliver the same care in different countries. We first present the results of a decomposition of healthcare spending along these lines in the United States and in Canada. We then delve into each component in more detail—administrative costs, factor prices, and the provision of care received—bringing in a broader range of international evidence when possible. Finally, we touch upon the organization of primary and chronic disease care and discuss possible gains in that area.


Successful resolution of bowel obstruction in a patient with hereditary angioedema.
Hereditary angioedema (HAE), a rare genetic disorder caused by a deficiency of the C1 esterase inhibitor, leads to an episodic, self-limiting increase in vascular permeability. Related symptoms commonly include recurrent, intractable abdominal pain, vomiting, and/or diarrhea. DX-88 (ecallantide), a 60-amino acid recombinant protein discovered through phage display technology, is a highly specific, potent inhibitor of human plasma kallikrein that has been used successfully in the treatment of patients experiencing acute HAE attacks. This case study involves a 65-year-old woman who presented with severe abdominal pain, cramping, and nausea. The study describes the use of a video obtained by capsule endoscopy for the direct imaging of bowel occlusion in a patient with HAE that resolved upon treatment with DX-88. After administration of DX-88, 80 mg intravenously, abdominal pain and nausea resolved within 30 min. Capsule endoscopy demonstrated a coincident resolution of the bowel wall edema, with a return to normal within approximately 1.5 h of DX-88 administration. This case study demonstrates that DX-88 can produce dramatic clinical benefits in a patient with an acute abdominal HAE attack, resolving both symptoms and pathologic signs. Furthermore, it illustrates the usefulness of videos obtained from capsule endoscopy in identifying the presence of bowel occlusion and demonstrating its subsequent rapid resolution upon administration of DX-88.


A transcriptomic approach for evaluating the relative potency and mechanism of action of azoles in the rat Whole Embryo Culture.
We evaluated the effect of six azoles on embryonic development in the rat whole embryo culture (WEC). Using the total morphological scoring system (TMS), we calculated the ID10 concentration (effective dose for 10% decrease in TMS). For evaluating gene specific responses, we combined previously and newly collected transcriptomics data of rat WEC exposed to a total of twelve azoles at their ID10 for 4h. Results revealed shared expressions responses in genes involved in the retinoic acid (RA) and sterol biosynthesis pathways, which are respectively representatives of developmental toxicity and targeted fungicidal action of the azoles. Azoles with more pronounced effects on the regulation of RA-associated genes were generally characterized as more potent embryotoxicants. Overall, compounds with strong sterol biosynthesis related responses and low RA related responses were considered as more favourable candidates, as they specifically regulated genes related to a desired target response. Among the identified sterol associated genes, we detected that methylsterol monooxygenase 1 (Msmo1) was more sensitively induced compared to Cyp51, a classical biomarker of this pathway. Therefore, we suggest that Msmo1 could be a better biomarker for screening the fungicidal value of azoles. In summary, we conclude that the embryonic regulation of RA and sterol metabolic pathways could be indicators for ranking azoles as embryotoxicants and determining their drug efficacy.


Nanostructural effects on polymer and water dynamics in cellulose biocomposites: (2)h and (13)c NMR relaxometry.
Improved moisture stability is desired in cellulose biocomposites. In order to clarify nanostructural effects, a new approach is presented where water and polymer matrix mobilities are characterized separately. Nanocomposites from cellulose nanofibers (CNF) in the xyloglucan (XG) biopolymer matrix are investigated at different hydration states. Films of XG, CNF, and CNF/XG composites are subjected to detailed (2)H and (13)C NMR relaxation studies. Since the (2)H NMR signal arises from heavy water and the (13)C signal from the polysaccharides, molecular water and polymer dynamics is for the first time investigated separately. In the neat components, (2)H transverse relaxation (T2) data are consistent with water clustering at the CNF fibril surfaces, but bulk spread of moisture in XG. The new method results in a description of water interaction with the nanoscale phases. At low hydration, water molecules at the CNF/XG interface exhibit higher water mobility than in neat CNF or XG, due to locally high water concentration. At the same time, CNF-associated interphase segments of XG show slower NMR-dynamics than that in neat XG.


Phenotypic & genotypic characterization of vancomycin resistant Enterococcus isolates from clinical specimens.
Enterococci have emerged as important nosocomial pathogens and emergence of resistance to many of the antimicrobials used for Gram-positive organisms has made the management of infections due to Enterococcus species difficult. Resistance to glycopeptide antibiotics, especially vancomycin is of special concern. This study was undertaken to perform a phenotypic and genotypic characterization of vancomycin resistant Enterococcus (VRE) isolates obtained from clinical samples in a tertiary care hospital in southern India. Susceptibility testing was performed for Enterococcus isolates collected over a period of one year (November 2008-October 2009). Minimum inhibitory concentrations (MIC) of vancomycin and teicoplanin were determined for the isolates by the agar dilution method. Genotypic characterization of VRE isolates was done by performing multiplex polymerase chain reaction (PCR) for detecting the various vancomycin resistance genes. Of the 367 isolates of Enterococcus species isolated, 32 were found to be resistant to vancomycin after MIC testing. VanA was the commonest phenotype of vancomycin resistance and the commonest genotype was vanA. Among the other important findings of the study was the presence of heterogeneity in isolates of VRE with the vanA gene cluster with regards to resistance to teicoplanin and the coexistence of vanA and vanC1 gene clusters in an isolate of E. gallinarum which conferred high level glycopeptide resistance to the isolate. Enterococcus species have emerged as important nosocomial pathogens in our patients with a capacity to cause a variety of infections. The vancomycin resistance among Enterococcus isolates was 8.7 per cent in our study which was high compared to other Indian studies. VanA was the commonest phenotype of glycopeptide resistance and vanA was the commonest vancomycin resistance gene. The study also demonstrates phenotypic as well as genotypic heterogeneity among isolates of VRE from clinical specimens.


Lipid/peptide/nucleotide separation with MALDI-ion mobility-TOF MS.
Matrix-assisted laser desorption/ionization when combined with ion mobility-orthogonal time-of-flight mass spectrometry is a viable technique for fast separation and analysis of biomolecules in complex mixtures. Isobaric lipid, peptide, and oligonucleotide ions are preseparated before mass analysis by differences of up to 30% in mobility drift time. Ions of similar chemical type fall along well-defined "trend lines" (with deviations of approximately 3%) when plotted in two-dimensional representations of ion mobility as a function of m/z. Discussion of fundamental and technical limitations of the technique point to its potential for being most useful when applied to systems such as bodily fluids and intact tissue, where an alternative chemical or chromatographic preseparation step prior to mass analysis is either impractical or undesirable.


Aerospace Environmental Health: Considerations and Countermeasures to Sustain Crew Health Through Vastly Reduced Transit Time to/From Mars.
The concept of implementation of environmental health protection and sustainment in aerospace environments by definition implies a One Health systems approach. One Health indicates an inherently complex, contextually interrelated system with consideration of human, animal, plant, systems engineering, and environmental health, their interrelationships, and networks. One Health implies seamless integration of subsystem co-dependencies to achieve an outcome of overall health protection for the individual. One of the most challenging aspects of space travel involves prevention, mitigation and protection from radiation injuries. While avoidance altogether is the best approach, these authors will focus on minimized exposure through limiting time in the space radiation environment in the transit to Mars and back. Implementation of the pillars of time, distance and shielding comprise ALARA, "As Low as Reasonably Achievable" (www.cdc.gov/nceh/radiation/alara.html) and is stressed in this strategy. This general overview will briefly describe the critical components of space environmental health in anticipation of increasing duration and interaction of human, animal, and plant habitation of aerospace and extreme environments into the future. Of the many considerations that could be addressed, precision medicine, and bioinformatics are the most rapidly evolving. Complex interdependencies will emerge from macro- and micro-environmental ecosystems data analysis, not yet fully comprehended or understood in the context of space health. We will conclude this contribution with suggested new countermeasure strategies gleaned through big data analytics that may protect space crew through mitigation of radiation exposure in flight.


Macrophage migration inhibitory factor deficiency protects pancreatic islets from cytokine-induced apoptosis in vitro.
During pathogenesis of diabetes, pancreatic islets are exposed to high levels of cytokines and other inflammatory mediators that induce deterioration of insulin-producing beta cells. Macrophage migration inhibitory factor (MIF) plays a key role in the onset and development of several immunoinflammatory diseases and also controls apoptotic cell death. Because the occurrence of apoptosis plays a pathogenetic role in beta cell death during type 1 diabetes development and MIF is expressed in beta cells, we explored the influence of MIF deficiency on cytokine-induced apoptosis in pancreatic islets. The results indicated clearly that elevated MIF secretion preceded C57BL/6 pancreatic islets death induced by interferon (IFN)-γ + tumour necrosis factor (TNF)-α + interleukin (IL)-1β. Consequently, MIF-deficient [MIF-knock-out (KO)] pancreatic islets or islet cells showed significant resistance to cytokine-induced death than those isolated from C57BL/6 mice. Furthermore, upon exposure to cytokines pancreatic islets from MIF-KO mice maintained normal insulin expression and produced less cyclooxygenase-2 (COX-2) than those from wild-type C57BL6 mice. The final outcome of cytokine-induced islet apoptosis in islets from wild-type mice was the activation of mitochondrial membrane pore-forming protein Bcl-2-associated X protein and effector caspase 3. In contrast, these apoptotic mediators remained at normal levels in islets from MIF-KO mice suggesting that MIF absence prevented initiation of the mitochondrial apoptotic pathway. Additionally, the protection from apoptosis was also mediated by up-regulation of prosurvival kinase extracellular-regulated kinase 1/2 in MIF-KO islets. These data indicate that MIF is involved in the propagation of pancreatic islets apoptosis probably via nuclear factor-κB and mitochondria-related proteins.


Flood control embankments contribute to the improvement of the health status of children in rural Bangladesh.
Every year, Bangladesh experiences major floods that inundate about one-third of the country. Therefore, flood control projects that comprise earthen dikes and irrigation/drainage systems are built along the major rivers to protect the people living in low-lying areas, stabilize the river banks and improve agricultural productivity. However, the adverse effects of these projects are regularly emphasized, such as environmental degradation and reduction of fishing supplies. The Demographic Surveillance System of the International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B) was used to assess the effect of a flood control programme on the mortality of 0-4-year-old children residing in the Matlab study area. Adjusted mortality rates were used in comparing four adjacent child populations residing either inside or outside a flood-control embankment and according to the type of health services provided in this area. Between the periods 1983-86 and 1989-92, the crude child mortality in the total study area decreased by 37%, from 185.9 per 1000 live births to 117.9 per 1000 live births. Following the construction of the embankment, death rates outside were up to 29% higher in 1-4-year-old children and 9% higher for 0-4-year age group compared to the flood-protected area (P < 0.001). Simultaneously, in the same study area, health interventions contributed to a 40% reduction in mortality among children less than 5 years of age in all causes of deaths (P < 0.001). Migration patterns and the effect of distances to the hospital are discussed.


Novel paramyxovirus associated with severe acute febrile disease, South Sudan and Uganda, 2012.
In 2012, a female wildlife biologist experienced fever, malaise, headache, generalized myalgia and arthralgia, neck stiffness, and a sore throat shortly after returning to the United States from a 6-week field expedition to South Sudan and Uganda. She was hospitalized, after which a maculopapular rash developed and became confluent. When the patient was discharged from the hospital on day 14, arthralgia and myalgia had improved, oropharynx ulcerations had healed, the rash had resolved without desquamation, and blood counts and hepatic enzyme levels were returning to reference levels. After several known suspect pathogens were ruled out as the cause of her illness, deep sequencing and metagenomics analysis revealed a novel paramyxovirus related to rubula-like viruses isolated from fruit bats.


Analysis by microcomputer of the effect of capsaicin on pulmonary mechanics in the rat and guinea-pig.
Analysis of airways resistance and lung compliance in anaesthetized rats and guinea-pigs was accomplished on-line by microcomputer. In spontaneously respiring guinea-pigs capsaicin (0.5-2.5 microgram/kg i.v.) increased both resistance by 0.33 +/- 0.13 cmH20/ml/sec and the end-expiratory lung volume and it decreased compliance by 0.24 +/- 0.09 ml/cmH2O. These effects of capsaicin were resistant to vagotomy. In the rat, doses of capsaicin (40-80 micrograms/kg i.v. and i.a.) which produced respiratory apnoea had no effect on resistance or compliance in artificially ventilated animals but it did cause a decrease of end-expiratory volume, an effect which was abolished by vagotomy. The results confirm that reduction in tidal volume seen in spontaneously respiring rats following capsaicin (Mitchell et al., 1984) appears to be due to an action other than one on the bronchial calibre.


Effect of PTH on blood pressure and response to vasoconstrictor agonists.
Parathyroid hormone (PTH) is known to be a vasodilator and to exert a hypotensive action. The present study examined the possible mechanisms involved, with special emphasis on the role of vasodilatory prostaglandins. The effects of the intact 1-84 PTH and that of its amino-terminal 1-34 fragment on mean arterial pressure (MAP) and on the vascular response to norepinephrine (NE) or angiotensin II (ANG II) were examined in rats before and after pretreatment with indomethacin. Bolus injections of 30 U of both 1-84 and 1-34 PTH produced a significant (P less than 0.01) decrease in MAP; however, the hypotensive response to 1-34 PTH (-28 +/- 4.6 mmHg) was more marked (P less than 0.01) than to 1-84 PTH (-9 +/- 1.8 mmHg). The infusion of 1-84 PTH (30 U/h) did not alter MAP, whereas the infusion of 1-34 PTH (30 U/h) led to a decrease in MAP from 124 +/- 2 to 103 +/- 4.0 mmHg (P less than 0.01) and to a rise in heart rate from 359 +/- 30 to 437 +/- 13 beats/min (P less than 0.02). Both 1-84 and 1-34 PTH antagonized the pressor effects produced by bolus injections of NE and ANG II. Pretreatment with indomethacin (5 mg/kg body wt) abolished the inhibitory effect of 1-84 and 1-34 PTH on the response of MAP to NE and ANG II and the hypotensive action of 1-34 PTH. Infusion of 1-84 and 1-34 PTH produced a significant rise in urinary excretion of 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)


What is commotio cordis?
Although thought to be rare, sudden deaths caused by nonpenetrating chest wall impact in the absence of structural injury to the ribs, sternum, and heart (commotio cordis) are reported with increasing frequency. This phenomenon is described in individuals when they are struck by relatively innocent blows to the chest wall. Young male athletes aged 5 to 18 years are particularly at risk for this catastrophe. It has been described after blows to the chest from baseballs, softballs, hockey pucks, and other objects. Death is usually instantaneous, and successful resuscitation is uncommon. A recently reported experimental model provides clues to the mechanisms and inferences for the prevention and treatment of this devastating condition. This swine model shows that a) ventricular fibrillation results from low-energy chest wall impacts during a vulnerable period of repolarization, b) the risk of this event can be decreased with softer-than-standard baseballs, and c) prompt defibrillation is crucial for resuscitation to be successful.


Non-surgical management of obstructive sleep apnoea: a review.
Obstructive sleep apnoea is common in children and, if untreated, can lead to multiple medical sequelae. The Childhood Adenotonsillectomy Trial demonstrated benefit from early surgical intervention, but rapid access to such treatment is not always available. To examine the recent literature on non-surgical aspects of the management of paediatric obstructive sleep apnoea (OSA). The English language literature was searched for articles on the conservative management of OSA. In mild cases of OSA, intra-nasal steroids and other anti-inflammatory medications may give relief in mild cases of OSA, but the long-term safety of these treatments has not been established. Weight loss in obese children has been shown to be effective in selected patients but is limited in practice. Non-invasive ventilation may be effective but compliance can be a major obstacle. Oral appliances are effective by stenting the pharyngeal airway, but research in this area is limited. There are number of potential, if not proven, alternative management strategies for children with OSA, which could be considered in the absence of early surgical intervention.


Galactose metabolism in regenerating rat liver.
1. Rats trained on a controlled lighting and feeding schedule were subjected to partial hepatectomy or sham operation. 2. After a large period of about 6h the activity of UDP-galactose 4-epimerase increased threefold, reaching a maximum 4 days after partial hepatectomy, and returned to normal values within a fortnight. 3. The enzyme pattern of the UDP-galactose-glycoprotein galactosyltransferase was biphasic, one peak appearing at 20 h, the second at 72 h after partial hepatectomy. 4. The rise in enzyme activities could be blocked by the injection of actinomycin D, and the Km values for UDP-glucose and UDP-galactose were nearly identical in regenerating and adult liver. It is therefore concluded that the increase in enzyme activity is due to synthesis de novo of enzyme protein.


The acylation of lysophosphoradylglycerocholines in guinea-pig heart mitochondria.
The importance of the deacylation-reacylation pathway for attaining the desired fatty acid composition in microsomal phospholipids has been well established. It is not clear, however, whether this mechanism is of equal importance in mitochondria. The absence of acyltransferase activity in mammalian heart mitochondria has been reported in a number of studies. In the present study we report the presence of acyltransferase activities for lysophosphoradylglycerocholines in guinea-pig heart mitochondria. This enzyme showed properties that were considerably different from those of the microsomal enzymes. Of all the acyl-CoAs tested (C18:0, C18:1, C18:2 and C20:4) the mitochondrial enzyme utilized only linoleoyl-CoA as fatty acyl donor and utilized both 1-acyl-sn-glycero-3-phosphocholine and 1-alkenyl-sn-glycero-3-phosphocholine as fatty acyl acceptors. The presence of significant quantities of fatty acids other than linoleate at the C-2 position of mitochondrial acylglycerophosphocholines, coupled with the specificity of the enzyme for linoleoyl-CoA, suggest that, in addition to reacylation, other mechanisms play a significant role in producing the molecular composition of these phospholipids found in the mitochondria.


Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?
The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.


Thermodynamics of the Coarse-Graining Master Equation.
We study the coarse-graining approach to derive a generator for the evolution of an open quantum system over a finite time interval. The approach does not require a secular approximation but nevertheless generally leads to a Lindblad-Gorini-Kossakowski-Sudarshan generator. By combining the formalism with full counting statistics, we can demonstrate a consistent thermodynamic framework, once the switching work required for the coupling and decoupling with the reservoir is included. Particularly, we can write the second law in standard form, with the only difference that heat currents must be defined with respect to the reservoir. We exemplify our findings with simple but pedagogical examples.


Changing long-term outcomes for infants 500-999 g birth weight in Victoria, 1979-2005.
To determine the survival and neurological outcome at 2 years of age of extremely low birthweight (ELBW, birth weight 500-999 g) infants born in the state of Victoria compared with term controls, and contrasted with ELBW cohorts from previous eras. A population-based cohort study of consecutive ELBW infants born during 2005 in the state of Victoria, and also in 1979-1980, 1985-1987, 1991-1992 and 1997. All 257 live births free of lethal malformations weighing 500-999 g in 2005, 220 randomly selected term, normal birthweight (birth weight >2499 g) controls, and equivalent cohorts born in earlier eras. Survival rates and quality-adjusted survival rates at 2 years of age, contrasted between cohorts. Of 257 ELBW live births in 2005, 66.9% survived to 2 years of age, significantly lower than the survival rate of 75.2% for 1997 (odds ratio (OR) 0.67, 95% CI 0.45 to 0.99, p=0.046), but not after adjustment for confounders of birth weight, gestational age and gender (adjusted OR 0.73, 95% CI 0.46 to 1.16, p=0.18). This was a reversal of the steady increase in survival rates up to 1997. Rates of blindness, severe developmental delay and severe disability were significantly lower in 2005 than in ELBW survivors from previous eras. Consequently the difference in the quality-adjusted survival rates between 2005 and 1997 was only -3.8% (95% CI -11.4% to 3.7%, p=0.32). Regional survival rates for ELBW infants have plateaued since the late 1990s, but the neurosensory outcome in survivors has improved in 2005.


Probing potassium channel function in vivo by intracellular delivery of antibodies in a rat model of retinal neurodegeneration.
Inward rectifying potassium (Kir) channels participate in regulating potassium concentration (K(+)) in the central nervous system (CNS), including in the retina. We explored the contribution of Kir channels to retinal function by delivering Kir antibodies (Kir-Abs) into the rat eye in vivo to interrupt channel activity. Kir-Abs were coupled to a peptide carrier to reach intracellular epitopes. Functional effects were evaluated by recording the scotopic threshold response (STR) and photopic negative response (PhNR) of the electroretinogram (ERG) noninvasively with an electrode on the cornea to determine activity of the rod and cone pathways, respectively. Intravitreal delivery of Kir2.1-Ab coupled to the peptide carrier diminished these ERG responses equivalent to dimming the stimulus 10- to 100-fold. Immunohistochemistry (IHC) showed Kir2.1 immunostaining of retinal bipolar cells (BCs) matching the labeling pattern obtained with conventional IHC of applying Kir2.1-Ab to fixed retinal sections postmortem. Whole-cell voltage-clamp BC recordings in rat acute retinal slices showed suppression of barium-sensitive Kir2.1 currents upon inclusion of Kir2.1-Ab in the patch pipette. The in vivo functional and structural results implicate a contribution of Kir2.1 channel activity in these electronegative ERG potentials. Studies with Kir4.1-Ab administered in vivo also suppressed the ERG components and showed immunostaining of Müller cells. The strategy of administering Kir antibodies in vivo, coupled to a peptide carrier to facilitate intracellular delivery, identifies roles for Kir2.1 and Kir4.1 in ERG components arising in the proximal retina and suggests this approach could be of further value in research.


Necessity and concerns about lipid-lowering medical treatments and risk factors for non-adherence: A cross-sectional study in Palestine.
Strong evidence indicates that drugs reduce blood lipids and improve cardiovascular end-points, leading to their wide usage. However, the success of these drugs can be affected by poor patient's adherence to prescribed medication. This study aimed to evaluate medication adherence in patients with dyslipidaemia in association with patient beliefs about medicines. The study was conducted from January 2019 to July 2019 at the middle governmental primary healthcare clinics in Ramallah and Bethlehem cities, and used a cross-sectional design. Adherence was determined using the 4-item Morisky medication adherence scale, while beliefs were determined using the Beliefs about Medicines Questionnaire. Of 220 patients, 185 agreed to participate in the study, resulting in a response rate of 84.1%. Of the participants, 106 (57.3%) were men, and almost half (88, 46.5%) were ≥56 years. Medication non-adherence was high (47.6%), but a majority (65.5%) reported believing their treatment to be necessary for their continued good health. Accordingly, the mean necessity score (17.3, SD 3.7) significantly outweighed (P < .001) the mean concerns score (14.0, SD 3.5). Multivariate regression demonstrated four variables to be significantly correlated with non-adherence: illiterate (OR = 2.52; CI: 0.9-4.3; P = .03), polypharmacy (OR = 3.18; CI: 1.9-5.7; P = .007), having comorbidity (OR = 3.10; CI: 2.2-4.6; P = .005) and having concerns about side effects (OR = 2.89; CI: 1.1-4.6, P = .04). Non-adherence among patients taking lipid-lowering agents was high despite most holding positive beliefs regarding medication necessity. This may be due to concern also being high. Physicians should identify and target high-risk patients and individualise their treatment plans in order to achieve adequate control of dyslipidaemia.


Saxitoxin binding in nerves from walking legs of the lobster Homarus americanus. Two classes of receptors.
The binding of exchange-labeled saxitoxin (STX) to sodium channels has been investigated in the nonmyelinated fibers of the walking leg nerves of the lobster. The properties of the STX binding site differed systematically among the nerves from different walking legs. The equilibrium dissociation constant for STX binding (KSTX) to the front legs is approximately twice that for the binding to the rear legs; the average ratio of KSTX (front): KSTX (rear) from five separate experiments was 1.80 +/- 0.21 (mean +/- SE). The actual KSTX values ranged from 124.0 to 22.7 nM for the front leg nerves and from 8.6 to 12.7 nM for the rear leg nerves. KSTX values for the middle two walking leg nerves fell between those for the front and rear legs. The inhibitory dissociation constant for tetrodotoxin (KTTX), calculated from tetrodotoxin's inhibition of labeled STX binding, was 3.02 +/- 0.27 nM for the front legs and 2.20 +/- 0.33 nM for the rear legs. The ratio KSTX: KTTX was different in the front and rear leg nerves, being 5.5 and 4.2, respectively. The apparent P pKa of the STX receptor also differed between the two legs, being 4.6 +/- 0.3 for the front legs and 5.1 +/- 0.1 for the rear legs. These results demonstrate that one tissue type in one organism can contain different toxin binding sites. The difference in the receptors can be qualitatively accounted for by the location of an additional negative charge near the receptor site of the rear walking leg.


A Video-Enhanced, Electronic Modality for Preparticipation Examination of Young Athletes.
We developed a video-enhanced preparticipation evaluation symptom questionnaire (the V-PPE), intended to help screen athletes for heart disease. We now report results of a pilot quality improvement study evaluating V-PPE's performance. In a prospective before-and-after study, approximately 5700 high-school athletes were prompted to voluntarily fill out the V-PPE questionnaire. We compared symptom frequencies on standard PPE to those on V-PPE. Of 5700 athletes, 46 (0.8%), 117 (2.0%), 33 (0.6%), and 101 (1.8%) reported syncope, angina, palpitations, and dyspnea, respectively on routine screening. Four hundred and ninety-two (8.6%) voluntarily filled out the V-PPE. Athletes were more likely to report palpitations on V-PPE than PPE, but not angina, dyspnea, syncope, or at least one symptom. Symptom frequencies on electronic PPE questionnaires are lower than recent reports suggest. Embedded videos can alter screening yield. More research is necessary to evaluate the predictive value of the V-PPE for clinically relevant cardiac pathology.


[The orbitofrotal cortex I: anatomy and memory procesing].
The orbitofrontal cortex has extensive tight connections with the medial temporal tobe and medial thalamic structures, which are responsible for memory processing and consolidation. What is more, this cortex is constantly activated in the memory encoding processes. This makes the orbitofrontal cortex a critical region for memory formation. This cortex is also connected with the motor and hetero- and uni- modal association sensory cortices, the limbic cortices, and subcortical structures responsible for functions related with these systems. All these facts convert the orbitofrontal cortex into a nodal region within the neural networks responsible of selecting, assembling and analyzing, based on our memory, present and pass experiences, so that we can organize and decide the most appropriate behaviour in a given situation.


Proton pump inhibitor therapy improves symptoms in postnasal drainage.
Gastroesophageal reflux is common among patients with postnasal drainage. We investigated whether proton pump inhibitor therapy improved symptoms in patients with postnasal drainage without sinusitis or allergies. In a parallel-group, double-blind, multi-specialty trial, we randomly assigned 75 participants with continued symptoms of chronic postnasal drainage to groups that were given 30 mg of lansoprazole twice daily or placebo. Participants were followed up for 16 weeks. Symptoms were assessed at baseline and after 8 and 16 weeks. Ambulatory pH and impedance monitoring assessed presence of baseline reflux. The primary objective of the study was to determine if acid suppressive therapy improved postnasal drainage symptoms. The secondary objective was to assess if pH and impedance monitoring at baseline predicted response to treatment. Postnasal drainage symptoms improved significantly among patients given lansoprazole compared with placebo. After 8 and 16 weeks, participants given lansoprazole were 3.12-fold (1.28-7.59) and 3.50-fold (1.41-8.67) more likely to respond, respectively, than participants given placebo. After 16 weeks, median (interquartile) percent symptom improvements were 50.0% (10.0%-72.0%) for participants given lansoprazole and 5.0% (0.0%-40.0%) for participants given placebo (P = .006). Neither baseline presence of typical reflux symptoms nor esophageal physiologic parameters predicted response to therapy. Among participants with chronic postnasal drainage without evidence of sinusitis and allergies, twice-daily therapy with proton pump inhibitors significantly improved symptoms after 8 and 16 weeks. The presence of heartburn, regurgitation, abnormal levels of esophageal acid, or nonacid reflux did not predict response to therapy.


Degree of basal cisterns compression predicting mortality and functional outcome after craniotomy and primary decompressive craniectomy in acute subdural hematoma population.
The compression of basal cisterns on CT is one of the signs of intracranial hypertension in TBI population. This study evaluates the relationship between the degree of basal cisterns effacement and outcomes in aSDH population. The study includes prospectively collected data from 290 patients who underwent osteoplastic craniotomy (OC) or primary decompressive craniectomy (pDC) for aSDH from 2016 to 2021. Univariate and multivariate regression analyses were performed to evaluate the association of baseline characteristics and extent of basal cisterns compression on pre-operative and post-operative CT scans with the outcomes at the time of discharge. Outcomes were dichotomized into mortality (and unfavourable (GOS 1-3 vs GOS 4-5). The degree of cisternal compression was evaluated using the cisternal effacement score of perimesencephalic and quadrigeminal cisternal components. Critical thresholds associated with the outcomes were calculated. Age and pre-/post-operative degree of cisternal compression were the strongest independent predictors of intrahospital mortality in a whole sample and separately in OC and pDC subgroups. The unfavourable outcome was independently predicted by age, pre-/post-operative status of cisternal compression and initial GCS. Critical thresholds associated with the mortality and poor functional outcome were, respectively, age ≥ 70 (OR 3.14 [CI 95% 1.82-5.46], p < 0.001) and ≥ 67 (OR 3.87 [CI 95% 2.33-6.54], p < 0.001), pre-operative cisternal effacement score ≥ 9 (OR 6.39 [CI 95% 3.62-11.53], p < 0.001) and ≥ 7 (OR 4.93 [CI 95% 2.96-8.38], p < 0.001), post-operative cisternal effacement score ≥ 6 (OR 20.6 [CI 95% 10.08-45.10], p < 0.001) and ≥ 3 (OR 7.47 [CI 95% 3.87-15.73], p < 0.001) and initial GCS ≤ 8 (OR 0.24 [CI 95% 0.13-0.43], p < 0.001 and OR 0.12 [CI 95% 0.07-0.21], p < 0.001). After adjusting for baseline characteristics, age and degree of cisternal compression remained the independent predictors of mortality, whereas unfavourable outcomes were associated with age, cisternal obliteration and GCS on presentation.


Depression in Parkinson's disease: a quantitative and qualitative analysis.
Depression is a common feature of Parkinson's disease, a fact of both clinical and theoretical significance. Assessment of depression in Parkinson's disease is complicated by overlapping symptomatology in the two conditions, making global assessments based on observer or self-ratings of doubtful validity. The present study aimed to provide both a quantitative and qualitative description of the nature of the depressive changes found in Parkinson's disease as compared with normal elderly subjects and arthritis patients. As with previous studies, the patients with Parkinson's disease scored significantly higher than normal controls on various self-ratings of depression and anxiety but, in this study, did not differ from those with arthritis. Qualitatively, both the Parkinson's disease and the arthritis groups had depression characterised by pessimism and hopelessness, decreased motivation and drive, and increased concern with health. In contrast, the negative affective feelings of guilt, self-blame and worthlessness were absent in both patient groups. This pattern of depression was significantly associated with severity of illness and functional disability. However, these factors account for only a modest proportion of the variability in test scores. Probable unexplored factors are individual differences in coping style and availability of support.


Chasing cardiac physiology and pathology down the CaMKII cascade.
Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca(2+) in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca(2+) signaling explains the subtle and critical control of important events of ECC and relaxation, such as Ca(2+) influx and SR Ca(2+) release and uptake. The multifunctional Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation but also in cell death, transcriptional activation of hypertrophy, inflammation, and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca(2+) levels. This activity can be sustained, creating molecular memory after the decline in Ca(2+) concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation, and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca(2+) regulation and dysregulation in cardiac health and disease.


Generation of CCR5-ablated Human Induced Pluripotent Stem Cells as a Therapeutic Approach for Immune-mediated Diseases.
C-C chemokine receptor type 5 (CCR5) is a receptor for some pro-inflammatory chemokines which plays important roles in immunological disorder and host responses to infectious agents. Additionally, the prognosis of some immune-mediated diseases in the people who are naturally carrying the CCR5 32bp deletions is optimistic. However, the clinical application of CCR5 32bp mutant cells is very limited due to the rare availability of donors who are homozygous for CCR5 D32. The transfection efficiency of nucleofected placental mesenchymal stem cells derived - human induced pluripotent stem cells (PMSC-hiPSCs) was examined through the evaluation of green fluorescent protein (GFP) expression using flow cytometry. The nucleofected clonal populations were selected using colony picking. The CCR5 gene disrupted clonal populations were evaluated and confirmed by PCR and Sanger sequencing methods. Also, off-target sites were evaluated by the "Loss of a primer binding site" technique. The results of the flow cytometry revealed that among the six applied nucleofection programs for PMSC-iPSCs, the program of A-033 has achieved the best transfection efficiency (27.7%). PCR and then sequencing results confirmed the CCR5 gene was disrupted in two clonal populations of 16 (D6) and 62 (D20) by the Clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease 9 (CRISPR/Cas9) system. The "Loss of a primer binding site" technique showed that no exonic off-target mutations were induced in both CCR5 gene disrupted clonal populations. We establish a CRISPR/Cas9 mediated CCR5 ablated PMSC-hiPSCs without detectable off-target damage. This approach can provide a stable supply of autologous/allogeneic CCR5-disrupted PMSC-hiPSCs that might be a feasible approach for the treatment of immune-mediated diseases.


Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application.


Identification of polcyclic aromatic hydrocarbons in semi-reinforcing furnance carbon black.
A weighed amount of a "special" semi-reinforcing (SRF) carbon black, made in 1964 and not considered to be typical for furnace blacks, was extracted with triple distilled benzene for 24 hours. The separation of carcinogens from the benzene extract was achieved by gas chromatography on a 5 ft x 0.25 inch stainless steel column packed with 3% OV-1 on chromosorb W. The chromatogram yielded 20 peaks. These peaks were collected, eluted and identified by (a) comparison of retention times, (b) peak enhancement technique, and (c) comparison of their excitation and fluorescence spectra with those of known polycyclic aromatic hydrocarbons (PCAH) standards. The PCAH's identified in SRF-carbon black were: anthracene, phenanthrene, fluoranthene, pyrene, benzo(mno)fluoranthene, chrysene, 1,2-benzanthracene, 9,10-dimethyl-1,2-benzanthracene, 1,2-benzopyrene, 3,4-benzopyrene, perylene, o-phenylene pyrene 1,2-benzoperylene, anthanthrene, and coronene. Of these, 1,1-benzanthracene, 9,10-dimethyl-1,2-benzanthracene, 3,4-benzopyrene and o-phenylene pyrene are known carcinogens. These and others have also been quantitated.


Mental disorder and violence: is there a relationship beyond substance use?
A general consensus exists that severe mental illness (SMI) increases violence risk. However, a recent report claimed that SMI "alone was not statistically related to future violence in bivariate or multivariate analyses." We reanalyze the data used to make this claim with a focus on causal relationships between SMI and violence, rather than the statistical prediction of violence. Data are from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a two-wave study (N = 34,653: Wave 1: 2001-2003; Wave 2: 2004-2005). Indicators of mental disorder in the year prior to Wave 1 were used to examine violence between Waves 1 and 2. Those with SMI, irrespective of substance abuse status, were significantly more likely to be violent than those with no mental or substance use disorders. This finding held in both bivariate and multivariable models. Those with comorbid mental and substance use disorders had the highest risk of violence. Historical and current conditions were also associated with violence, including childhood abuse and neglect, household antisocial behavior, binge drinking and stressful life events. These results, in contrast to a recently published report, show that the NESARC data are consistent with the consensus view on mental disorder and violence: there is a statistically significant, yet modest relationship between SMI (within 12 months) and violence, and a stronger relationship between SMI with substance use disorder and violence. These results also highlight the importance of premorbid conditions, and other contemporaneous clinical factors, in violent behavior.


Perinatal outcome and financial impact of Eritrean and Sudanese refugees delivered in a tertiary hospital in Tel Aviv, Israel.
A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent. To compare the perinatal outcome of refugees and Israeli parturients. The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls. During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250). The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.


Processing of ribosomal precursor RNAs in Physarum polycephalum.
The processing of intermediates of Physarum rRNA has been investigated using two cloned rDNA restriction fragments as sequence specific probes. The size of the largest stable pre-rRNA detected is 11.8 Kb, as determined by denaturing gel electrophoresis. R-loop analysis revealed that this pre-rRNA fraction mainly consists of transcripts which do not contain the two insertion sequences present in the 26 S gene. However, a small number of molecules are found which still contain one or the other, or both, of these introns. These observations suggest that the two introns are transcribed but spliced out in a random order before RNA synthesis has reached the 3-end of the primary transcript. Transcription starts at about 17.7 Kb and stops at 4.4 Kb as measured from the ends of the linear palindromic rDNA molecule. Besides the 11.8 Kb transcript several further ribosomal RNA precursors have been identified, ranging in size from 2.5 to 8.8 Kb. In addition, the genes for 5.8 S RNA have been located by R-loop mapping.