Microwave-assisted extraction and ultrasound-assisted extraction for recovering carotenoids from Gac peel and their effects on antioxidant capacity of the extracts.
The peel of Gac fruit (Momordica cochinchinensis Spreng.) contains high levels of bioactive compounds, especially carotenoids which possess significant antioxidant capacities. However, the peel of Gac is regarded as a waste from the production of carotenoid-rich oil from Gac fruit. In this study, carotenoids of Gac peel were extracted by microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) using ethyl acetate as extraction solvent. The effect of extraction time and different levels of microwave and ultrasonic powers on the yield of total carotenoid and antioxidant capacity of the extracts were investigated. The results showed that an extraction at 120 W for 25 min and an extraction at 200 W for 80 min were the most effective for MAE and UAE of the Gac peel samples, respectively. The maximum carotenoid and antioxidant capacity yields of UAE were significantly higher than those of the MAE. The antioxidant capacity of extract obtained by the UAE was also significantly higher that of the conventional extraction using the same ratio of solvent to material. The results showed that both MAE and UAE could be used to reduce the extraction time significantly in comparison with conventional extraction of Gac peel while still obtained good extraction efficiencies. Thus, MAE and UAE are recommended for the improvement of carotenoid and antioxidant capacity extraction from Gac peel.


Laboratory diagnosis of congenital von Willebrand disease.
Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).


The karyotypes and evolution of ZZ/ZW sex chromosomes in the genus Characidium (Characiformes, Crenuchidae).
Available data on cytotaxonomy of the genus Characidium Reinhardt, 1867, which contains the greatest number of species in the Characidiinae (Crenuchidae), with 64 species widely distributed throughout the Neotropical region, were summarized and reviewed. Most Characidium species have uniform diploid chromosome number (2n) = 50 and karyotype with 32 metacentric (m) and 18 submetacentric (sm) chromosomes. The maintenance of the 2n and karyotypic formula in Characidium implies that their genomes did not experience large chromosomal rearrangements during species diversification. In contrast, the internal chromosomal organization shows a dynamic differentiation among their genomes. Available data indicated the role of repeated DNA sequences in the chromosomal constitution of the Characidium species, particularly, in sex chromosome differentiation. Karyotypes of the most Characidium species exhibit a heteromorphic ZZ/ZW sex chromosome system. The W chromosome is characterized by high rates of repetitive DNA accumulation, including satellite, microsatellite, and transposable elements (TEs), with a varied degree of diversification among species. In the current review, the main Characidium cytogenetic data are presented, highlighting the major features of its karyotype and sex chromosome evolution. Despite the conserved karyotypic macrostructure with prevalent 2n = 50 chromosomes in Characidium, herein we grouped the main cytogenetic information which led to chromosomal diversification in this Neotropical fish group.


Body temperature, autonomic responses, and acute mountain sickness.
A few studies have reported increased body temperature (T(o)) associated with acute mountain sickness (AMS), but these usually include exercise, varying environmental conditions over days, and pulmonary edema. We wished to determine whether T(o) would increase with AMS during early exposure to simulated altitude at rest. Ninety-four exposures of 51 men and women to reduced P(B) (423 mmHg = 16,000 ft = 4850 m) were carried out for 8 to 12 h. AMS was evaluated by LL and AMS-C scores near end of exposure, and T(o) was measured by oral digital thermometer before altitude and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude. Other measurements included ventilation, O(2) consumption and autonomic indicators of plasma catecholamines, HR, and HR variability. Average T(o) increased by 0.5 degrees F from A1 to A12 in all subjects (p < 0.001). Comparison between 16 subjects with lowest AMS scores (mean LL = 1.0, range = 0 to 2.5) and 16 other subjects with highest AMS scores (mean LL = 7.4, range = 5 to 11) demonstrated a transient decline in T(o) from A1 to A6 in AMS, in contrast to a rise in non-AMS (p = 0.001). Catecholamines, HR, and HR variability (increased low F/high F ratio) indicated significant elevation of sympathetic activity in AMS, where T(o) fell, but no change in metabolic rate. The apparently greater heat loss during early AMS suggests increased hypoxic vasodilation in spite of enhanced sympathetic drive. Greater hypoxic vasodilation and elevated HR in AMS in the absence of other changes suggest that augmentation of beta-adrenergic tone may be involved in early AMS pathophysiology.


Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns.
Electrospun fibers of hydrophilic polymers meet challenges in a rapid degradation of fiber matrices and discharge of antibiotics to comply with requirements of infection control as a dermal regeneration template. In the current study, a pH conversion process is initially developed to ensure fluent electrospinning, an efficient in situ cross-linking of electrospun gelatin fibers with oxidized alginate and simultaneous loading of gentamicin sulfate (GS) and hydrophobic ciprofloxacin into fibers. The dual drug-loaded fibers indicate a complete release of GS during 6 d and a sustained release of ciprofloxacin for over three weeks, and the antibiotics release indicates significant growth inhibitions on Pseudomonas aeruginosa and Staphylococcus epidermidis. The wound healing efficacy is evaluated on a deep burn model infected with 10(8) CFU of P. aeruginosa. Compared with fibers with loaded individual drugs, the concomitant release of GS and ciprofloxacin significantly reduces the bacteria numbers in wound and livers, at around 2.30 × 10(5) and 1.25 × 10(3) CFU after 3 d, respectively. The wound re-epithelization, blood vessel formation, collagen deposition, and tissue remodeling process are accelerated with a complete healing observed after 21 d. This study provides a feasible strategy to design cross-linked hydrophilic fibers with an extended drug release for biomedical applications.


Effect of Thermostable α-Amylase Addition on Producing the Porous-Structured Noodles Using Extrusion Treatment.
Problems with rehydration and palatability are considered as unacceptable quality characteristics for the noodles produced using high-strength extrusion technique. Thus, the aim of this study was to solve these problems by designing a novel method to create a porous structure for the high-strength extruded noodles (HENs). The quality indices of HENs were significantly improved after adding to them thermostable α-amylase (TαA) at 0.05% to 0.10%. The microstructure graphs showed that a well-developed porous structures was successfully created throughout noodle strands. This indicated that the TαA has effectively worked on starch granules in spite of the high-strength performance of the extrusion process. MALLS-GFC, X-ray diffraction, and differential scanning calorimeter investigations showed that the appearance of a porous structure was mainly attributed to the internal collapse of α-1,4-glycosidic bonds and the dissolution of water-soluble degradation products, such as dextrin and oligosaccharides. Moreover, the slight inhibited effect of excess TαA on the starch gelatinization was because of the fact that the high enzyme concentration might cause TαA to adhere or overlay on it. The rehydration and palatability properties of HENs were greatly improved by creating a well-developed or honeycomb-like porous structure using TαA at low concentration. The findings of this study could be applied to enhance the quality characteristics of HENs and to encourage the research and development in the noodle industry.


Healthcare staff's views on the patients' prerequisites to be co-creator in preventing healthcare-associated infections.
Every year, patients are affected by suffering and death caused by adverse events in connection with health care and the most common adverse events are healthcare-associated infections (HAI). The Swedish Patient Act from 2015 strengthens the patient's position in health care; however, there is lack of knowledge of how healthcare staff experience the possibilities to make the patient involved in the preventive work of HAI. To describe healthcare professionals' views on the patient's prerequisites to be co-creator in preventing HAI in connection with hospital care. This study had a qualitative descriptive design with semi-structured individual interviews. Qualitative inductive content analysis was used to analyse the transcribed interview data. The study setting was a hospital in Sweden in 2015. Interviews were carried out among six healthcare professionals. In the analysis, 5 themes and 14 categories were identified in three different domains: Organisation, Healthcare staff and Patient. The result indicates an obstacle in each domain for the patient to become co-creator in preventing HAI. In Organisation domain, a lack of organizational structure such as elaborated working methods to involve the patient was pointed out. In the domain Healthcare staff, it showed that the professionals allocate the responsibility of preventing HAI to the patient but only if they had to or if they trusted the patient. In the Patient domain, the result states that the patient was perceived as passive; they did not take own initiatives to get involved. The patient has an important role in successful HAI prevention work and should be considered as an obvious co-creator. Nevertheless, this study shows that neither organisation nor healthcare staff are sufficiently prepared for this. The organisation must make an anchored, structured and systematic work centred on the patient's needs and give more support both to healthcare professionals and patients.


Standardized assessment of breast cancer surgical scars integrating the Vancouver Scar Scale, Short-Form McGill Pain Questionnaire, and patients' perspectives.
Currently, there is no standardized, comprehensive method to assess surgical scars after breast cancer surgery. This article evaluates the application of the Vancouver Scar Scale, in conjunction with patients' scar self-rating and scar-related pain, in a cohort of breast cancer patients. Data were prospectively collected in 59 women with breast cancer. Scar assessment comprised: 1. objective rating by pairs of independent observers using the Vancouver Scar Scale; 2. patient's ratings of the scar's physical parameters and overall satisfaction; and 3. pain assessment using the Short-Form McGill Pain Questionnaire. A total of 212 scar scores (59 pairs of breast/chest wall and 47 pairs of axillary scar scores) were generated by 13 observers: three physicians, five radiation therapists, and five nurses. Internal consistency was tested using Cronbach's alpha statistics. Interobserver reliability was evaluated with Spearman's rho and intraclass correlation coefficient computations. Convergent validity of the observer and patient ratings was examined with Spearman's correlation statistics. Linear regression analysis was performed to identify significant factors associated with Vancouver Scar Scale scores and patient satisfaction. The Vancouver Scar Scale, patient self-rating scale, and Short-Form McGill Pain Questionnaire had acceptable internal consistency (Cronbach's alpha 0.79, 0.64, and 0.72 respectively). Interobserver reliability using the Vancouver Scar Scale was significant with Spearman's correlation coefficients of 0.53 for pliability, 0.47 for scar height, 0.49 for vascularity, 0.54 for pigmentation, and 0.66 for overall score (all p values < 0.001). Significant agreement between observer and patient ratings of scar pliability (p = 0.01) and color (p = 0.001) was demonstrated. Mild to moderate pain was reported by more than 40 percent of patients. Patient satisfaction was significantly associated with self-rating of scar pliability and pain, but not Vancouver Scar Scale scores. The Vancouver Scar Scale is a reliable and valid tool to objectively evaluate scars after breast cancer surgery. Evaluation of scar-related pain and patients' scar rating and satisfaction provide additional information relevant to scar assessment. This integrated approach is feasible in a busy clinical setting to advance care and research in scar management for breast cancer patients.


The Muscidae (Diptera) of Armenia.
A report is given on the Muscidae (Diptera) collected in Armenia during recent fieldwork. Locality data, Armenian distribution and general distribution are given for each species, including references to previously published records. 181 named species are listed, of which 93 are newly recorded from Armenia, and 15 are endemic (8%). Two new species are described: Thricops iliata sp. nov. and Phaonia gayaneae sp. nov.


The meaning of blood pressure.
Measurement of arterial pressure is one of the most basic elements of patient management. Arterial pressure is determined by the volume ejected by the heart into the arteries, the elastance of the walls of the arteries, and the rate at which the blood flows out of the arteries. This review will discuss the three forces that determine the pressure in a vessel: elastic, kinetic, and gravitational energy. Emphasis will be placed on the importance of the distribution of arterial resistances, the elastance of the walls of the large vessels, and critical closing pressures in small arteries and arterioles. Regulation of arterial pressure occurs through changes in cardiac output and changes in vascular resistance, but these two controlled variables can sometimes be in conflict.


Intra-operative applications of augmented reality in glioma surgery: a systematic review.
Augmented reality (AR) is increasingly being explored in neurosurgical practice. By visualizing patient-specific, three-dimensional (3D) models in real time, surgeons can improve their spatial understanding of complex anatomy and pathology, thereby optimizing intra-operative navigation, localization, and resection. Here, we aimed to capture applications of AR in glioma surgery, their current status and future potential. A systematic review of the literature was conducted. This adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, and Scopus electronic databases were queried from inception to October 10, 2022. Leveraging the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) framework, study eligibility was evaluated in the qualitative synthesis. Data regarding AR workflow, surgical application, and associated outcomes were then extracted. The quality of evidence was additionally examined, using hierarchical classes of evidence in neurosurgery. The search returned 77 articles. Forty were subject to title and abstract screening, while 25 proceeded to full text screening. Of these, 22 articles met eligibility criteria and were included in the final review. During abstraction, studies were classified as "development" or "intervention" based on primary aims. Overall, AR was qualitatively advantageous, due to enhanced visualization of gliomas and critical structures, frequently aiding in maximal safe resection. Non-rigid applications were also useful in disclosing and compensating for intra-operative brain shift. Irrespective, there was high variance in registration methods and measurements, which considerably impacted projection accuracy. Most studies were of low-level evidence, yielding heterogeneous results. AR has increasing potential for glioma surgery, with capacity to positively influence the onco-functional balance. However, technical and design limitations are readily apparent. The field must consider the importance of consistency and replicability, as well as the level of evidence, to effectively converge on standard approaches that maximize patient benefit.


Hybrid scatter correction applied to quantitative holmium-166 SPECT.
Ho-166 is a combined beta-gamma emitter of which the betas can be used therapeutically. From the 81 keV gammas of Ho-166, SPECT images can be obtained, which give opportunities to guide Ho-166 therapy. Accurate reconstruction of Ho-166 images is currently hampered by photopeak-scatter in the patient, down-scatter in the detector, collimator and patient caused by the 1.4 MeV photons and by bremsstrahlung. We developed and validated a method for quantitative SPECT of Ho-166 that involves correction for both types of scatter plus non-uniform attenuation correction using attenuation maps. Photopeak-scatter (S) is compensated for by a rapid 3D Monte Carlo (MC) method that is incorporated in ordered subset (OS) reconstruction of the emission data, together with simultaneous correction for attenuation (A) and detector response (D); this method is referred to as OS-ADS. Additionally, for correction of down-scatter, we use a 14 keV wide energy window centred at 118 keV (OS-ADSS). Due to a limited number of available energy windows, the same 118 keV energy window was used for down-scatter correction of the simultaneously acquired Gd-153 transmission data. Validations were performed using physical phantom experiments carried out on a dual-head SPECT system; Gd-153 transmission line sources were used for acquiring attenuation maps. For quantitative comparison of OS-ADS and OS-ADSS, bottles filled with Ho-166 were placed in both a cylindrical phantom and an anthropomorphic thorax phantom. Both OS-ADS and OS-ADSS were compared with an ordered subset reconstruction without any scatter correction (OS-AD). Underestimations of about 20% in the attenuation map were reduced to a few per cent after down-scatter correction. The average deviation from the true activity contained in the bottles was +72% with OS-AD. Using OS-ADS, this average overestimation was reduced to +28% and with OS-ADSS the deviation was further reduced to 16%. With OS-AD and OS-ADS, these numbers were more sensitive to the choice of volumes of interest than with OS-ADSS. For the reconstructed activity distributions, erroneous background activity found with OS-AD was reduced by a factor of approximately 2 by applying OS-ADS and reduced by a factor of approximately 4 by applying OS-ADSS. The combined attenuation, photopeak-scatter and down-scatter correction framework proposed here greatly enhanced the quantitative accuracy of Ho-166 imaging, which is of the uppermost importance for image-guided therapies. It is expected that the method, with adapted window settings, also can be applied to other isotopes with high energy peaks that contaminate the photopeak data, such as I-131 or In-111.


TrapTech R-Octenol Lure Does Not Improve the Capture Rates of Aedes albopictus (Diptera: Culicidae) and Other Container-Inhabiting Species in Biogents Sentinel Traps.
Aedes albopictus (Skuse) and other container-inhabiting species have become important public health concerns due to the transmission of dengue, chikungunya, and Zika viruses. Effective surveillance is dependent on the ability to collect a sufficient number of mosquitoes for population monitoring and pathogen isolation. The Biogents Sentinel (BGS) trap supplied with a proprietary human skin lure has become the standard tool for container-inhabiting Aedes species collections worldwide. Recently, R-octenol, a single isomer of the well characterized mosquito attractant octenol, was shown to greatly improve the capture rate of some Aedes species when utilized with the Center for Disease Control and Prevention (CDC) light traps and Mosquito Magnet traps. This study evaluated the effectiveness of the TrapTech lure (TT lure), containing R-octenol, alone or in combination with the human skin lure in a BGS trap to capture Ae. albopictus and other species. BGS traps with human skin lures or a combination of the two lures collected approximately twice as many Ae. albopictus females compared to those with TT lures. Unlike previous studies, baiting BGS traps with TT lures did not result in increased diversity of mosquito species, or in higher numbers of other container-inhabiting Aedes species. Although human skin lures were clearly superior to TT R-octenol lures in BGS traps, R-octenol lures are more widely available and might still be used as an alternative lure, especially when Ae. albopictus populations are high.


[Use of new immunoglobulin isotype-specific ELISA-systems to detect Salmonella infections in pigs].
In Germany, the program for controlling salmonella infections in pigs is based on tests detecting salmonella-lipopolysaccharide (LPS) induced antibodies in meat-juice or blood. These conventional tests which are based on the technology of enzyme-linked immunosorbent assay (ELISA) detect exclusively or mainly immunoglobulin(lg)G antibodies. Meanwhile, novel ELISA systems (WCE-ELISA, 3-Isotype-Screening-ELISA) have been developed, which additionally detect the antibody classes IgM and IgA.This fact enables the registration of fresh salmonella infections (starting with day 5 p.i.) and thus, the distinction between early and older infections. The results show that animals with early salmonella infections appear significantly more often in herds with a high than with a low prevalence. With the newly developed tests this group of animals can be detected much more efficiently and precisely than with the tests used so far. Due to their clearly improved sensitivity the application of the WCE-ELISA and the 3-Isotype-Screening-ELISA in terms of the QS-Salmonella-Monitoring program can therefore significantly improve the selection of farms with potential salmonella excretors. Additionally, the WCE-ELISA can be applied very suitable for the examination of individual animals.


Quality of medical laboratory services in resource-limited settings.
This report endorses the author's own views on the subject after taking up a laboratory adviser mission in Africa. Taking the example of laboratory services practice in sub-Saharan countries, it is shown that diagnosis of diseases which require the use of laboratory suffer from lapses in the quality of case-detection and case-reporting. These services lack management and an information system that limits the set up of a laboratory network at national level. An efficient health program set in resource deprived countries would then yield improvements on systems and infrastructure.


[Anesthesia-induced changes in the preload-dependent circulatory reactions in patients with coronary heart disease].
The influence of preload changes (table tilt) on the hemodynamic regulation before and after induction of neuroleptanalgesia was studied in 31 patients with coronary heart disease. The induced preload changes are balanced in the awake patient for the maintenance of normal arterial pressure by regulation of stroke volume and peripheral vascular resistance. This regulation does not exist after induction of anaesthesia. Splitting the patients into sub-groups with good or poor left ventricular function, different ventricular function curves were obtained before and after the induction of anaesthesia. The pharmacologic and ventilatory reasons for the changed regulation of circulation are discussed. For investigations into hemodynamic changes produced by intervention in anaesthesia and intensive therapy, it is recommended to define more exactly the cardiovascular status of patients and the study conditions.


Deformity correction and limb lengthening with externally controlled motorized extendable intramedullary nails: Comparison of 2 different nails.
The aim of this study was to assess and compare the clinical, radiological, and functional results of patients treated with FITBONE or PRECICE nails due to deformity and length discrepancy in their lower extremities. This retrospective cohort study included 41 patients with length discrepancy and deformity in their lower extremities, who underwent limb lengthening surgery with either FITBONE (group F) or PRECICE (group P) nails between 2010 and 2020. The mean postoperative follow-up period was 15.95 ± 4.75 months in group F (20 patients) and 20.48 ± 7.57 months in group P (21 patients). Lower extremity mechanical and anatomical axes were measured on x-rays preoperatively and at the end of treatment. Consolidation and distraction indexes were also calculated to assess bone healing. Lower Extremity Functional Scale test was used to evaluate functional outcomes and quality of life. Neither of the treatment methods caused deviations in the mechanical axes and femoral distal angles (P > .05). No statistically significant difference in consolidation and distraction indexes was found between the groups (P > .05). Postoperative complications were seen in 3 of the patients in group F and 4 of the patients from group P. There was no significant difference in Lower Extremity Functional Scale scores between groups (P = .425). This study has demonstrated that treatment with both the FITBONE and PRECICE nails resulted in improved physical and emotional functional outcomes. Both nails had similar radiographic results, complication rates, high patient compliance, and good cosmesis. Level III, Therapeutic Study.


Hepatocellular carcinoma and multiple myeloma with elevated globulin: a case report and literature review.
A 60-year-old male patient presented with a serum α-fetoprotein (AFP) level of 2940.5 ng/mL accompanied by a significant increase in serum globulin. Hepatitis B virus (HBV) DNA was 2.85 × 103 (normal value <1.0 × 103). B-mode ultrasound and magnetic resonance imaging showed characteristic manifestations and he was clinically diagnosed with hepatocellular carcinoma in January 2015. He received radiofrequency ablation and tenofovir disoproxil anti-HBV therapy and his serum AFP and globulin levels were significantly reduced. In March 2018, he presented at our Hematology Department with fatigue and a pale complexion. At that time, his serum AFP level was normal, with hemoglobin 61 g/L and globulin 64.7 g/L. He was diagnosed with multiple myeloma (MM) by bone marrow examination, and immunofixation electrophoresis. The patient received PCD chemotherapy (bortezomib 2.0 g/dL on days 1, 4, 8, and 11 plus cyclophosphamide 0.3 g/dL on days 1-4 plus dexamethasone 20 mg/dL on days 1-2, 4-5, 8-9, and 11-12). The patient finally died of MM complicated by disseminated intravascular coagulation.


Mechanisms of transjunctional transport of NaCl and water in proximal tubules of mammalian kidneys.
Tight junctions and the intercellular space of proximal tubules are not accessible to direct measurements of fluid composition and transport rates, but morphological and functional data permit analysis of diffusion and osmosis causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses through tight junctions along a chloride gradient, but against a sodium gradient. Calculation in terms of modified Nernst-Fick diffusion equation after eliminating electrical terms shows that transport rates (300-500 pmol min-1 mm-1 tubule length) and transepithelial voltage of +2 mV are in agreement with observations. Diffusion coefficients are Dtj=1500 microm2 s-1 in the S1 segment, and Dtj=90-100 microm2 s-1 in the S2 segment where apical intercellular NaCl concentration is 132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions with gap distance 6 A are impermeable to mannitol (effective molecular radius 4 A); reflection coefficients are sigma=0.92 for NaHCO3 and sigma=0.28 for NaCl, because of difference in anion size. The osmotic force is provided by a difference in effective transjunctional osmolality of 10 mOsm kg-1 in the S1 segment and 30 mOsm kg-1 in the S2 segment, where differences in transjunctional concentration contribute with 21 mOsm kg-1 for NaHCO3 and -4 mOsm kg-1 for NaCl. Transjunctional difference of 30 mOsm kg-1 causes a volume flow of 2 nL min-1 mm-1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow and diffusive and convective transport of NaCl. In conclusion, transjunctional diffusion and osmosis along gradients generated by transcellular transport of other solutes account for all NaCl transport in proximal tubules.


Reproducibility of Centric Relation Techniques by means of Condyle Position Analysis.
The aim of this study was to determine the reproducibility of clinical centric relation (CR) registration techniques (bimanual manipulation, chin point guidance and Roth's method) by means of condyle position analysis. Thirty two fully dentate asymptomatic subjects (16 female and 16 male) with normal occlusal relations (Angle class I) participated in the study (mean age, 22.6 ± 4.7 years). The mandibular position indicator (MPI) was used to analyze the three-dimensional (anteroposterior (ΔX), superoinferior (ΔZ), mediolateral (ΔY)) condylar shift generated by the difference between the centric relation position (CR) and the maximal intercuspation position (MI) observed in dental arches. The mean value and standard deviation of three-dimensional condylar shift of the tested clinical CR techniques was 0.19 ± 0.34 mm. Significant differences within the tested clinical CR registration techniques were found for anteroposterior condylar shift on the right side posterior (Δ Xrp; P ≤ 0.012); and superoinferior condylar shift on the left side inferior (Δ Zli; P ≤ 0.011), whereas between the tested CR registration techniques were found for anteroposterior shift on the right side posterior (ΔXrp, P ≤ 0.037) and superoinferior shift on the right side inferior (ΔZri, P ≤ 0.004), on the left side inferior (ΔZli, P ≤ 0.005) and on the left side superior (ΔZls, P ≤ 0.007). Bimanual manipulation, chin point guidance and Roth's method are clinical CR registration techniques of equal accuracy and reproducibility in asymptomatic subjects with normal occlusal relationship.


Opioid Prescribing After Discharge in a Previously Mechanically Ventilated, Opioid-Naïve Cohort.
Opioids are utilized for pain management during and after mechanical ventilation in the intensive care unit (ICU). The purpose of this study was to determine the percentage of potentially unnecessary opioid prescriptions on discharge in previously opioid-naïve patients. This retrospective cohort study included mechanically ventilated, opioid-naïve ICU patients who received opioids. The primary outcome of this study was the discrepancy between the amounts of opioids prescribed at discharge versus those likely required based on actual 24-hour prehospital discharge opioid requirements. A total of 71 patients were included. Of these, 63.3% (n = 45) of discharge prescriptions were in alignment with 24-hour predischarge requirements, and 36.7% (n = 26) of discharge prescriptions were in excess of calculated predischarge requirements. At discharge, 57.7% (n = 41) of patients received a nonopioid analgesic. Multivariable linear regression revealed that cardiothoracic ICU admission was associated with an increased risk of inappropriate discharge opioid prescribing, whereas a shorter duration of inpatient oral opioid therapy decreased risk of inappropriate discharge prescribing. Opioid prescribing for previously mechanically ventilated patients warrants improvement as a part of the discharge planning process. Application of these data may aid in the reduction of opioid overprescribing at discharge after an ICU stay.


Protective capacity of an ice hockey goaltender helmet for three events associated with concussion.
The purpose of this study was to assess the protective capacity of an ice hockey goaltender helmet for three concussive impact events. A helmeted and unhelmeted headform was used to test three common impact events in ice hockey (fall, puck impacts and shoulder collisions). Peak linear acceleration, rotational acceleration and rotational velocity as well as maximum principal strain and von Mises stress were measured for each impact condition. The results demonstrated the tested ice hockey goaltender helmet was well designed to manage fall and puck impacts but does not consistently protect against shoulder collisions and an opportunity may exist to improve helmet designs to better protect goaltenders from shoulder collisions.


[Clinical study of interstitial lung disease in mixed connective tissue disease].
Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis/dermatomyositis, with a high anti-snRNP antibody titer. Respiratory manifestations, such as interstitial lung disease (ILD), are not well-described. Thirteen patients who met the diagnostic criteria for MCTD and showed ILD on high-resolution CT were analysed retrospectively. A restrictive pattern was found in 73% of cases and TLCO abnormalities in 90%. Exercise hypoxemia was observed in nine out of ten cases. The CT-scan pattern was compatible with non-specific interstitial pneumonia in seven cases and with usual interstitial pneumonia in five. Bronchoalveolar lavage showed lymphocytic alveolitis in two patients, neutrophil alveolitis in eight. Fifty percent ILD patients respond to steroids and immunosuppressive drugs. Progressive ILD (six in 13; 46%) compared with non-progressive ILD associated more systemic sclerosis manifestations (p<0.05). Progressive ILD tend to have more frequent pulmonary hypertension, neutrophilic alveolitis and honey combing pattern. MCTD-ILD characteristics are not specific. When systemic sclerosis manifestations are present, MCTD-ILD seems to associate more frequently pulmonary hypertension and progressive ILD.


Attentional bias modification facilitates attentional control mechanisms: evidence from eye tracking.
Social anxiety is thought to be maintained by biased attentional processing towards threatening information. Research has further shown that the experimental attenuation of this bias, through the implementation of attentional bias modification (ABM), may serve to reduce social anxiety vulnerability. However, the mechanisms underlying ABM remain unclear. The present study examined whether inhibitory attentional control was associated with ABM. A non-clinical sample of participants was randomly assigned to receive either ABM or a placebo task. To assess pre-post changes in attentional control, participants were additionally administered an emotional antisaccade task. ABM participants exhibited a subsequent shift in attentional bias away from threat as expected. ABM participants further showed a subsequent decrease in antisaccade cost, indicating a general facilitation of inhibitory attentional control. Mediational analysis revealed that the shift in attentional bias following ABM was independent to the change in attentional control. The findings suggest that the mechanisms of ABM are multifaceted.


Network-based integration of multi-omics data for prioritizing cancer genes.
Several molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression. We developed NetICS (Network-based Integration of Multi-omics Data), a new graph diffusion-based method for prioritizing cancer genes by integrating diverse molecular data types on a directed functional interaction network. NetICS prioritizes genes by their mediator effect, defined as the proximity of the gene to upstream aberration events and to downstream differentially expressed genes and proteins in an interaction network. Genes are prioritized for individual samples separately and integrated using a robust rank aggregation technique. NetICS provides a comprehensive computational framework that can aid in explaining the heterogeneity of aberration events by their functional convergence to common differentially expressed genes and proteins. We demonstrate NetICS' competitive performance in predicting known cancer genes and in generating robust gene lists using TCGA data from five cancer types. NetICS is available at https://github.com/cbg-ethz/netics. Supplementary data are available at Bioinformatics online.


Color stability of ten resin-based restorative materials.
Despite significant developments to improve the optical properties of composites, color stability remains a challenge with changes still observed immediately after polymerization and after some time of storage. This study aimed to evaluate the color change of ten commercially available resin composite systems immediately after polymerization, at 24 hours, and at 1 month of water storage. Five discs of two thicknesses (1 mm/3 mm) in two shades (A3/Bleach) were made from ten commercially available brands of resin composite. Color measurements were recorded with a colorimeter and expressed in terms of the CIE L*a*b* scale. Color change was calculated between baseline and immediate polymerization (ΔE*(1) ), between immediate polymerization and 24 hours (ΔE*(2) ), and between 24 hours and 1 month (ΔE*(3) ). Values ΔE* ≥ 3.3 were considered clinically unacceptable as color shifts over this threshold value may be noticeable. The results were analyzed using a three-way analysis of variance (ANOVA) and Student-Newman-Keuls's tests. A significance level of 0.05 was used for all tests. Color change was evidenced for all brands, shades, and thickness. The greatest color change was observed immediately after initial polymerization with ΔE* values ranging from 2.4 to 12.0. Color change after 24 hours and 1 month were significantly less than those observed after polymerization. Immediately after polymerization, only Tetric EvoCeram (Ivoclar-Vivadent, Amherst, NY, USA) showed changes below 3.3. At 24 hours, 20 out of the 40 groups including all materials in both shades and thicknesses showed changes above 3.3. At 1 month, color changes for all brands remained under 3.3. Overall, clinically relevant color changes (ΔE* ≥ 3.3) took place immediately after polymerization of current light-activated composites. These changes were predominantly attributed to shifts in the L* and b* parameters towards the dark and blue region, respectively. Color shifts continued at 24 hours with changes in the L* and b* parameters towards the light and yellow region, respectively. After 1 month, only minor changes under the 3.3 threshold took place. Ensuring an accurate color match of resin composite restorations to the surrounding tooth structure is a critical aspect of any esthetic restorative procedure. A better understanding of the changes taking place during the different stages of maturation and storage of composites may be of significant benefit to clinicians as this may help minimize shade mismatch issues.


[Patients' Rights Act - Relevance for surgical disciplines].
The new Patients' Rights Act does not reflect rights of patients as professional obligations of physicians for the first time. It adopted common longtime jurisdiction, but in some respects it is going beyond. This law clearly extends the documentation requirements of physicians, especially concerning the extent of documentation. In surgical fields the requirements for enlightening physicians were more strongly worded than in previous jurisdiction. In medical facilities it is now mandatory to establish an internal quality management system.


Development of Diamond and Silicon MEMS Sensor Arrays with Integrated Readout for Vapor Detection.
This paper reports on the development of an autonomous instrument based on an array of eight resonant microcantilevers for vapor detection. The fabricated sensors are label-free devices, allowing chemical and biological functionalization. In this work, sensors based on an array of silicon and synthetic diamond microcantilevers are sensitized with polymeric films for the detection of analytes. The main advantage of the proposed system is that sensors can be easily changed for another application or for cleaning since the developed gas cell presents removable electrical connections. We report the successful application of our electronic nose approach to detect 12 volatile organic compounds. Moreover, the response pattern of the cantilever arrays is interpreted via principal component analysis (PCA) techniques in order to identify samples.


[Vascular calcification and anti-aging].
Vascular calcification encountered in atherosclerotic lesions is a common consequence of aging. We suggested that apoptosis plays an important role in vascular smooth muscle cells (VSMC) calcification which is dependent on downregulation of the growth arrest-specific gene 6 (Gas6) -mediated survival pathway. Recently, we demonstrated that adiponectin antagonizes the stimulatory effect of TNF-alpha on vascular calcification by restoration of the AMP-activated protein kinase (AMPK) -dependent Gas6-mediated survival pathway. These results provide evidences of the effect of metabolic syndrome on vascular diseases including calcification.


Low, but Not High, Doses of Cisplatin Damage Cochlear Hair Cells in C57 Mouse Organotypic Cultures.
The purpose of this study was to investigate the characteristics of cisplatin-induced C57 mouse cochlear hair cell damage in vitro. Forty-seven cochleae harvested from 2- to 4-day-old C57 mice were used. Forty specimens were treated with different concentrations of cisplatin (10, 25, 50, 100, 400, and 1,000 μmol/l) for 48 h. The remaining seven specimens were used as a control group. The rate of hair cell loss increased from 14.5 to 78.4% over cisplatin concentrations of 10 to 100 μmol/l, whereas hair cell loss decreased to 48.8 and 8.77% at concentrations of 400 and 1,000 μmol/l, respectively. Apoptosis was detected by DAPI staining in the areas of hair cell damage. Hair cell loss rates differed significantly among the cisplatin-treated groups. Linear regression analysis of cisplatin dose versus hair cell number showed a significant negative correlation for cisplatin doses up to 100 μmol/l and a positive correlation with further increases up to 1,000 μmol/l. We conclude that cisplatin-induced hair cell damage was concentration dependent only up to a certain dose and that injury resistance may occur in cochlear cells treated with higher doses of cisplatin.


Synthesis and enhanced photoluminescence of surface-modified barium borate nanorods.
Well-dispersed barium borate nanorods with uniform diameters were synthesized successfully, using Na2B4O7 x 10H2O and Ba(NO3)2 as raw materials and oleic acid as a modifying agent. Oleic acid was used to modify the surface property of nanorods prepared from the precipitation reaction. TEM images confirmed that the synthesized sample presented nanorod morphology with a length of about 200-400 nm and an average diameter of 20 nm. Moreover, the photoluminescence properties of both pure and modified BaB2O4 nanorods were tested. After the surfaces of the nanorods were modified with oleic acid, the visible light emission of the sample centered at 380 and 400 nm became more intensive. It was discussed that the enhancement of the luminescence intensity was attributed to the formation of surface BaB2O4/oleic acid complexes.


The beta-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells.
Asthma is a disease characterized by reversible airway obstruction. An additional hallmark of chronic asthma is altered wound healing that leads to airway remodeling. Although beta-agonists are effective in treating the bronchospasm associated with asthma, their effects on airway wound healing, which are related to airway remodeling, are unknown. It has been demonstrated that beta-agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the beta-agonist isoproterenol would affect wound healing. Using an in vitro scrape wound assay, we demonstrated that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing beta2-adrenergic receptor-yellow fluorescent protein, we show that attenuation is due to the accumulation of cAMP and the involvement of at least one additional pathway. Furthermore, attenuation is not due to a direct effect on the EGF receptor or to an alteration of the ERK/MAPK signaling cascade. Based on these results, we propose that isoproterenol may exert its effects through other MAPK signaling pathways (JNK and/or p38) or through parallel mechanisms. These results also demonstrate a problem of potential therapeutic relevance in which a commonly prescribed medication may alter wound healing and contribute to the remodeling of asthmatic airways.


Analysis on Characteristics of ZnO Surface Acoustic Wave with and without Micro-Structures.
In this paper, we fabricate a surface acoustic wave (SAW) device with micro-structures on a zinc oxide (ZnO) thin film and measure its signal response. The manufacturing processes of the SAW device include the fabrication of micro-structures of a SAW element and its interdigital transducer by silicon micro-machining and the fabrication of a thin film of ZnO by RF magnetron sputtering. We, then, measure the SAW properties. This research investigates the properties of sputtered thin films for various amounts of O2/(Ar + O2) using Zn and ZnO targets. Regardless of target, the growth rate of the ZnO thin film decreases as the oxygen content increases. When the SAW is sputtered ZnO thin film using 30% oxygen, the digital signal of the SAW has better performance. The measurement signal of the SAW with micro-structures is similar to that without micro-structures.


The Trembley Effect or the birth of marine zoology.
At a time when Europe was engaged in the War of Austrian succession, an unknown scholar, Abraham Trembley, managed to dramatically influence the course of the Natural Sciences. He focused his interest not only on the properties of a new organism, the polyp later named Hydra, and its freshwater environment, but also on the communication of his discoveries to the most estimable scholarly circles of his time. Under the patronage of influential scholars, Réaumur in Paris and Folkes in London, he forged a new perspective on a common object – water. Everyone had seen a glass of water and through it he could project the concept of a wet laboratory and hence reshape the experimental practices of naturalists. His research propelled a surge of interest for investigation of the aquatic environment, a new line of investigative force that can be called the Trembley Effect. This effect pushed scholars to explore the shallow areas of water, to test the properties of tiny aquatic bodies, to examine the frontiers between organisms. Thanks to Trembley, it was the first time that, in a fully artificial setting, man could give life to an animal species, a practice that created for all of those who tried it, an enigmatic feeling of power that stirred passions for decades. Indeed this experimental approach that emerged in parallel to Linnaean classifications, inaugurated a new phase of Natural Sciences.


What's wrong with the debate on mesh surgery?
There is an increasingly acrimonious debate surrounding the use of anchored mesh in prolapse surgery. It is evident that clinicians and researchers working with this technology are under pressure from the public, from lawyers, regulators and colleagues. There is a risk that rapidly changing societal standards, championed by colleagues, lawyers and bureaucrats, will interfere with professional independence to such a degree that an entire new technology is lost before there has been time for clinical research to assess risks and benefits properly, before we learn which patients stand to benefit most, and before we get a chance to optimise implant design.


Metabolic shifts in immunity and inflammation.
Sites of ongoing inflammation and triggered immune responses are characterized by significant changes in metabolic activity. Recent studies have indicated that such shifts in tissue metabolism result from a combination of profound recruitment of inflammatory cells (neutrophils and monocytes) and high proliferation rates among lymphocyte populations. The resultant shifts in energy supply and demand can result in metabolic acidosis and diminished delivery and/or availability of oxygen, leading to hypoxia extensive enough to trigger transcriptional and translation changes in tissue phenotype. Such phenotypic shifts can imprint fundamental changes to tissue metabolism. In this study, we review recent work addressing metabolic changes and metabolic control of inflammation and immunity.


Can E-selectin be a reliable marker of inflammation in lumbar disc disease?
The cause of sciatica and low back pain associating with lumbar disc herniation has not been clearly identified until now. Inflammation has been shown to occur via immunohistochemical and biochemical methods in herniated disc tissues. The important prognostic role of E-selectin has recently been substantiated by other studies in early rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). The important role of adhesion molecules in the initiation and progression of the inflammatory response is well known for infectious diseases and autoimmune disorders. In our study, we aimed to show the role of E-selectin as an inflammatory marker and the correlation of inflammation with straight-leg raise (SLR) test findings and subtype of disc herniation. We found that the cases with positive SLR test had higher rates of immunostaining with E-selectin. This led us to think that E-selectin might play an important role in the activity status of the disease, meaning patients with more limited movement capacity might benefit from E-selectin antagonist therapy. Among the many studies performed to identify the relationship between the inflammation markers and activity of lumbar disc herniation, this is the first investigation held with E-selectin.


Polyethylene Glycol Crowder's Effect on Enzyme Aggregation, Thermal Stability, and Residual Catalytic Activity.
Protein stability and performance in various natural and artificial systems incorporating many other macromolecules for therapeutic, diagnostic, sensor, and biotechnological applications attract increasing interest with the expansion of these technologies. Here we address the catalytic activity of lysozyme protein (LYZ) in the presence of a polyethylene glycol (PEG) crowder in a broad range of concentrations and temperatures in aqueous solutions of two different molecular mass PEG samples (Mw = 3350 and 10000 g/mol). The phase behavior of PEG-protein solutions is examined by using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), while the enzyme denaturing is monitored by using an activity assay (AS) and circular dichroism (CD) spectroscopy. Molecular dynamic (MD) simulations are used to illustrate the effect of PEG concentration on protein stability at high temperatures. The results demonstrate that LYZ residual activity after 1 h incubation at 80 °C is improved from 15% up to 55% with the addition of PEG. The improvement is attributed to two underlying mechanisms. (i) Primarily, the stabilizing effect is due to the suppression of the enzyme aggregation because of the stronger PEG-protein interactions caused by the increased hydrophobicity of PEG and lysozyme at elevated temperatures. (ii) The MD simulations showed that the addition of PEG to some degree stabilizes the secondary structures of the enzyme by delaying unfolding at elevated temperatures. The more pronounced effect is observed with an increase in PEG concentration. This trend is consistent with CD and AS experimental results, where the thermal stability is strengthened with increasing of PEG concentration and molecular mass. The results show that the highest stabilizing effect is approached at the critical overlap concentration of PEG.


Neuroanatomical Correlates of Hypophonia in Subcortical Vascular Cognitive Impairment.
Early detection and intervention may alter the disease course of subcortical vascular cognitive impairment (SVCI). Patients with SVCI have white matter ischemia that disrupts connections between the cortex and subcortical gray matter and therefore manifest various symptoms such as motor disturbances and behavioral/cognitive dysfunction. Reduced vocal loudness, or hypophonia, is one of the common motor symptoms of SVCI, but few studies have systematically investigated it in this patient population. The main purpose of this investigation was to identify neural pathways underlying hypophonia in patients with SVCI. Eighty-eight patients with SVCI and 21 normal controls performed phonation tasks. Diffusion tensor imaging data from 73 patients were utilized to measure white matter changes associated with hypophonia. Correlational analyses between white matter fractional anisotropy values and the decibel level of the "sustained phonation" task identified the left midbrain cerebral peduncle (corticobulbar tract), external capsule, corona radiata/internal capsule, and bilateral frontal white matter as possible neural correlates for hypophonia. Our results support the notion that hypophonia in SVCI patients might be caused by the impairment of the pyramidal and extrapyramidal systems. This study provides a unique contribution towards understanding the neuropathology of hypophonic features in this population.


Psychosocial problems in cancer survivors.
Cancer is a disease with both physical and psychosocial sequelae. While much is being learned about the physical late effects of cancer and its treatment, less is known about its psychosocial morbidity. Research shows that cancer survivors typically function quite adequately in their daily lives but may experience distress related to their past illness. The cancer survivor's self-image is crucial to the way he or she reenters and adapts to family and social life, school, or work, and this reentry and adaptation in turn influences self-image. The physician plays as important a role in the survivor's psychosocial healing as he did in the patient's physical treatment.


A two-component signal transduction pathway regulates manganese homeostasis in Synechocystis 6803, a photosynthetic organism.
Elemental manganese is essential for the production of molecular oxygen by cyanobacteria, plants, and algae. In the cyanobacterium Synechocystis sp. PCC 6803, transcription of the mntCAB operon, encoding a high affinity Mn transporter, occurs under Mn starvation (nm Mn) conditions but not in Mn-sufficient (microm Mn) growth medium. Using a strain in which the promoter of this operon directs the transcription of the luxAB reporter genes, we determined that inactivation of the slr0640 gene, which encodes a histidine kinase sensor protein component of a two-component signal transduction system, resulted in constitutive high levels of lux luminescence. Systematic targeted inactivation mutagenesis also identified slr1837 as the gene encoding the corresponding response regulator protein. We have named these two genes manS (manganese-sensor) and manR (manganese-regulator), respectively. A polyhistidine-tagged form of the ManS protein was localized in the Synechocystis 6803 cell membrane. Directed replacement of the conserved catalytic His-205 residue of this protein by Leu abolished its activity, although the mutated protein was present in cyanobacterial membrane. This mutant also showed suboptimal rates of Mn uptake under either Mn-starved or Mn-sufficient growth condition. These data suggest that the ManS/ManR two-component system plays a central role in the homeostasis of manganese in Synechocystis 6803 cells.


Expression of alkaline phosphatase in murine B lymphocytes. Correlation with B cell differentiation into Ig secretion.
Alkaline phosphatases (ALPase) (orthophosphoric-monoester phosphohydrolase, EC 220.127.116.11) are implicated in many biologic phenomena including ossification and differentiation of human neutrophils and choriocarcinoma cells. Another trait, demonstrated by microinjection into Xenopus oocytes, is their ability to block the first mitotic division. Previous work in our laboratory has established that ALPase is also present on murine B lymphocytes activated by either polyclonal mitogens or Th cells. We have now characterized the ALPase present on murine B cells as belonging to the liver-bone-kidney isoenzyme and found it to be implicated in B cell differentiation into antibody secretion. Thus, B cell proliferative responses, elicited either by high concentrations of rabbit anti-IgM antibodies or by LPS in the presence of PMA, are characterized by the lack of both antibody secretion and expression of ALPase activity. In contrast, B cells stimulated to differentiate into Ig-secreting cells by B cell differentiation factors, nearly in the absence of a proliferative response, express high levels of ALPase activity, as did those that were LPS-stimulated. These data showing the association of the ALPase expression with the process of B cell differentiation into antibody-secreting cells are discussed in the context of the possible role that phosphorylation-dephosphorylation mechanism may play in controlling the growth/differentiation rate in the B cell lineage.


Effects of a Rhodiola rosea extract on mental resource allocation and attention: An event-related potential dual task study.
Rhodiola rosea extract is widely used to alleviate stress and improve cognition and mental resources. A total of 50 adult participants were treated with 2 × 200 mg R. rosea extract (Rosalin®, WS® 1,375) for 12 weeks and were subjected to a neuropsychological test battery as well as an event-related brain potential measurement in a dual task paradigm prior to administration, after 6 weeks and after 12 weeks. The study followed a single-arm open-label design. Reaction times improved for the attention network task (ANT), the Go/Nogo task, and the divided attention task. Moreover, the orienting effect and the executive effect in the ANT showed an improvement. The P3 component in a dual task paradigm was increased in amplitude. The results of this pilot study show an improvement of mental speed and moreover, suggest improved mental resources. As the current study is single-armed these findings need to be replicated in a double-blind placebo controlled study.


PBL curriculum improves medical students' participation in small-group tutorials.
Group learning is the core of problem-based learning (PBL) but has not been extensively studied, especially in Asian students. This study compared students of PBL and non-PBL curricula in students' talking time and participation in small-group tutorials in a medical school in Asia. The proportions of student talking of 46 tutorials in three teaching rotations of the PBL curriculum and those of 43 corresponding tutorials in the non-PBL curriculum were counted. Twelve videotapes of tutorials (six from each curriculum), stratified for tutor, case scenario and students' learning stage, were randomly selected and transcribed. They were rated with the group-interaction (5 items) and active-participation (four items) tutorial assessment scales developed by Valle et al. These outcomes were compared between the students of PBL and non-PBL curricula. Students from the PBL curriculum talked significantly more. In only two (4.7%) of 43 tutorials in the non-PBL curriculum did the students talk more than the tutors; but students talked more than the tutors in 17 (37.0%) of 46 tutorials in the PBL curriculum. PBL students scored significantly higher than non-PBL students in all items except one item (respect to peers) of the tutorial assessment scales, and in the mean scores of both the group interaction scale (items 1-5) and the active participation scale (items 6-9). The results suggested that PBL starting from the early years of a medical curriculum was associated with more active student participation, interaction and collaboration in small-group tutorials.


Estimation of the mean from sums with unknown numbers of summands.
Using dye intensity measurements at synaptic terminals to examine neurotransmitter release leads to the problem of estimating an expectation when, instead of observing independent random variables with the same expectation, one observes, with error, independent random sums of independent variables with the same expectation--but with the number of summands in the random sums unobserved. Here, a relatively convenient nonparametric approach to estimation is presented. Data from an experiment in which cationic styrylpyridinium dye FM4-64 was used in cultured mouse hippocampal neurons are used to illustrate the approach.


Removal of pharmaceuticals, perfluoroalkyl substances and other micropollutants from wastewater using lignite, Xylit, sand, granular activated carbon (GAC) and GAC+Polonite® in column tests - Role of physicochemical properties.
This study evaluated the performance of five different sorbents (granular activated carbon (GAC), GAC + Polonite® (GAC + P), Xylit, lignite and sand) for a set of 83 micropollutants (MPs) (pharmaceuticals, perfluoroalkyl substances (PFASs), personal care products, artificial sweeteners, parabens, pesticide, stimulants), together representing a wide range of physicochemical properties. Treatment with GAC and GAC + P provided the highest removal efficiencies, with average values above 97%. Removal rates were generally lower for Xylit (on average 74%) and lignite (on average 68%), although they proved to be highly efficient for a few individual MPs. The average removal efficiency for sand was only 47%. It was observed that the MPs behaved differently depending on their physicochemical properties. The physicochemical properties of PFASs (i.e. molecular weight, topological molecular surface area, log octanol water partition coefficient (Kow) and distribution coefficient between octanol and water (log D)) were positively correlated to observed removal efficiency for the sorbents Xylit, lignite and sand (p < 0.05), indicating a strong influence of perfluorocarbon chain length and associated hydrophobic characteristics. In contrast, for the other MPs the ratio between apolar and polar surface area (SA/SP) was positively correlated with the removal efficiency, indicating that hydrophobic adsorption may be a key feature of their sorption mechanisms. GAC showed to be the most promising filter medium to improve the removal of MPs in on-site sewage treatment facilities. However, more studies are needed to evaluate the removal of MPs in field trials.


[Development of growth medium from meat processing waste products and assessment of its properties].
New growth medium based on inedible substrate - meat processing waste products of slaughterhouses - was developed. New medium was characterized by physical, chemical, and biological properties using exacting and non-exacting microorganisms, as well as by periodical cultivation of Corynebacterium diphtheriae strain and obtaining the preparation of its antigens. The experimental medium provided the growth of chosen test-strains with typical properties. From biomass obtained during the periodic cultivation of model toxigenic strain of C. diphtheriae on liquid experimental growth medium, preparation with antigenic properties was extracted. It has been shown that biologic characteristics of experimental growth medium did not differ from those of meat-peptone medium that allows to use it for cultivation of bacteria from various taxonomic groups.


Enhancement Effects of Co Doping on Interfacial Properties of Sn Electrode-Collector: A First-Principles Study.
The Co doping effects on the interfacial strength of Sn electrode-collector interface for lithium-ion batteries are investigated by using first-principles calculations. The results demonstrate that by forming strong chemical bonds with interfacial Sn, Li, and Cu atoms, Co doping in the interface region can enhance interfacial strengths and stabilities during lithiation. With doping, the highest strengths of Sn/Cu (1.74 J m-2) and LiSn/Cu (1.73 J m-2) interfaces are 9.4 and 17.7% higher than those of the corresponding interface systems before doping. Besides, Co doping can reduce interface charge accumulation and offset the decreasing interfacial strength during lithiation. Furthermore, the interfacial strength and electronic stability increase with rising Co content, whereas the increasing formation heat may result in thermodynamic instability. On the basis of the change of formation heat with Co content, an optimal Co doping content has been provided.


Graphite oxide-intercalated anionic clay and its decomposition to graphene-inorganic material nanocomposites.
A graphite oxide-intercalated anionic clay (nickel zinc hydroxysalt) has been prepared using the aqueous colloidal dispersions of negatively charged graphite oxide sheets and aminobenzoate-intercalated anionic clay layers as precursors. When the two colloidal dispersions are reacted, the interlayer aminobenzoate ions are displaced from the anionic clay and the negatively charged graphite oxide sheets are intercalated between the positively charged layers of the anionic clay. The thermal decomposition of the intercalated solid at different temperatures yields graphene-metal oxide/metal nanocomposites. Electron microscopic analysis of the composites indicates that the nanoparticles are intercalated between the layers of graphite in many regions of these solids although the graphite layers are largely exfoliated and not stacked well together.


Tumor response and patient outcome after preoperative radiotherapy in locally advanced non-inflammatory breast cancer patients.
The purpose of this analysis was to assess the tumor response and long-term outcome in patients treated with preoperative radiotherapy (PRT) without systemic therapy. Between 1997 and 2000, 134 patients with non-inflammatory locally advanced breast cancer (LABC) were treated with PRT. The tumor dose was 45 Gy in 15 fractions to the breast and to regional lymph nodes over 6 weeks. Radical mastectomy was performed 6 weeks after PRT to all patients and adjuvant systemic therapy was administered as per protocol. The measures of disease outcome were overall survival (OS) and disease-free survival (DFS) which estimated using the Kaplan-Meier method. Median follow-up was 74 months (range 4-216). Objective clinical tumor response after PRT was observed in 77.6% of the patients. Clinical complete tumor response (cCR) was achieved in 21.6% of the patients. Pathological CR in the breast was achieved in 15% of the patients. The 5- and 10-year OS were 55.1 and 37.8%, respectively. The 5- and 10-year DFS were 39.2 and 27%, respectively. Patients who achieved cCR had significantly longer OS in comparison with patients achieving clinical partial response (cPR) and clinical stable disease (cSD). Similarly, DFS of patients in the cCR group was longer compared with patients with cPR and cSD, yet without statistical significance. Our results showed that local control in LABC patients achieved by primary PRT, followed by radical mastectomy was comparable with the results reported in the literature. Complete pathologic response to PRT identified a subgroup of patients with a trend toward better DFS and OS.


Structural determinants of hydration, mechanics and fluid flow in freeze-dried collagen scaffolds.
Freeze-dried scaffolds provide regeneration templates for a wide range of tissues, due to their flexibility in physical and biological properties. Control of structure is crucial for tuning such properties, and therefore scaffold functionality. However, the common approach of modeling these scaffolds as open-cell foams does not fully account for their structural complexity. Here, the validity of the open-cell model is examined across a range of physical characteristics, rigorously linking morphology to hydration and mechanical properties. Collagen scaffolds with systematic changes in relative density were characterized using Scanning Electron Microscopy, X-ray Micro-Computed Tomography and spherical indentation analyzed in a time-dependent poroelastic framework. Morphologically, all scaffolds were mid-way between the open- and closed-cell models, approaching the closed-cell model as relative density increased. Although pore size remained constant, transport pathway diameter decreased. Larger collagen fractions also produced greater volume swelling on hydration, although the change in pore diameter was constant, and relatively small at ∼6%. Mechanically, the dry and hydrated scaffold moduli varied quadratically with relative density, as expected of open-cell materials. However, the increasing pore wall closure was found to determine the time-dependent nature of the hydrated scaffold response, with a decrease in permeability producing increasingly elastic rather than viscoelastic behavior. These results demonstrate that characterizing the deviation from the open-cell model is vital to gain a full understanding of scaffold biophysical properties, and provide a template for structural studies of other freeze-dried biomaterials. Freeze-dried collagen sponges are three-dimensional microporous scaffolds that have been used for a number of exploratory tissue engineering applications. The characterization of the structure-properties relationships of these scaffolds is necessary to understand their biophysical behavior in vivo. In this work, the relationship between morphology and physical properties in the dry and hydrated states was investigated across a range of solid concentrations in the scaffolds. The quantitative results provided can aid the design of scaffolds with a target trade-off between mechanical properties and structural features important for their biological activity.


Adrenomedullin Promotes the Proliferation and Inhibits Apoptosis of Dental Pulp Stem Cells Involved in Divergence Pathways.
Adrenomedullin (ADM) is highly expressed in dental tissues at the critical developmental time points during tooth development. However, its role in pulp repair and pulp injury is still unknown. The study aimed to investigate the mechanisms by which ADM affects the proliferation and apoptosis of human dental pulp stem cells (DPSCs). Fifty-four freshly extracted wisdom teeth were obtained from 27 patients with caries and 27 without. Enzyme-linked immunosorbent assay and immunohistochemistry were used to examine the expression levels of ADM in caries and normal pulp tissues. Human primary DPSCs from the third passage were incubated with ADM (10(-8) mol/L) for 24 hours; the cell cycle and apoptosis were investigated by flow cytomery, and protein expression was investigated using Western blot analysis. The levels of ADM in caries pulp tissues were significantly higher than those in normal pulp tissues. Incubation with ADM enhanced the percentage of G2/S/M phase DPSCs (P < .01) by the addition of a JNK/c-Jun inhibitor. Incubation with ADM reduced DPSC apoptosis by the addition of the Src/glycogen synthase kinase-3 inhibitor. ADM also ameliorated CoCl2-induced apoptosis and caspase-3 expression. ADM enhances the proliferation of DPSCs through activation of the JNK/c-Jun signaling pathway and inhibits apoptosis of DPSCs through activation of the Src/glycogen synthase kinase-3 signaling pathway.


Breast cancer in Western Australia in 1989. V: Outcome at 5 years after diagnosis.
A follow-up study was undertaken of all Western Australian women who had a new diagnosis of breast cancer during 1989. The aims were to determine survival, frequency of recurrence and quality of life (QoL) of Western Australian women 5 years after a diagnosis of breast cancer; to determine reasons for choice or rejection of reconstructive surgery in those women treated by mastectomy, and to determine if the choice of lumpectomy or mastectomy affects subsequent QoL. The vital status as at 1st June 1994 of all 692 women who had a new diagnosis of breast cancer in 1989 was ascertained by electronic linkage to official mortality registrations. A subsample of 215 survivors who had originally been treated by the nine surgeons who had managed 20 or more cases each was sent a reply-paid postal questionnaire asking about follow-up treatment since diagnosis, recurrence of disease, current QoL and attitudes to, and use of, reconstructive surgery. The overall survival rate at 5 years was 80.8% (85.9% and 78.8% for Stage I and II, respectively). Cumulative mortality was 35% lower among the third of patients treated by the nine most active surgeons (14% vs 22%, P < 0.02), but this may be subject to referral bias. The subsample was representative of all surviving cases except for being an average of 2.7 years younger at diagnosis (mean ages 55.2 and 57.9 years). The response rate of the subsample to the postal questionnaire was 78%. Of women who had had a mastectomy, 40% had considered having a reconstruction, but only nine (11%) had undergone this operation. Median QoL on the Rosser scale (maximum = 1.0) was 0.9. QoL was worse for the 23% of patients with a recurrence of breast cancer. Patients treated by breast-conserving surgery showed a trend toward a better QoL compared with those treated by mastectomy. At 5 years after the diagnosis of breast cancer, one in five women had died and an estimated one in four of the survivors had recurrent disease. Quality of life in the remaining patients, half of whom had undergone adjuvant treatment, was very good. These are important baseline data against which to judge the impact of mammographic screening.


Eating disorder treatment among women forty and older: increases in prevalence over time and comparisons to young adult patients.
There is limited information on the prevalence of middle-aged women seeking specialized treatment for an eating disorder and whether middle-aged patients are significantly different from young-adult patients. This two-part study sought to identify changes in the past two decades in the prevalence of middle-aged (MA; 40+ years) and young-adult (YA; 18-39 years) women seeking treatment for an eating disorder (ED) and to identify differences and similarities between both groups. For study 1, all unique female inpatient admissions from 1989 to 2006 were reviewed (n=1,040). For study 2, women admitted to any treatment level from January-May 2007 were compared, based on age at intake admission, on psychological questionnaires and factors relevant to an eating disorder. In study 1, the overall percent of MA women who presented for inpatient ED treatment increased significantly from an average of 4.7% (1989-2001) to an average of 11.6% (2002-2006). In study 2, at intake, MA women were more likely than YA to be married, be older at ED onset and report a longer duration of illness. Self-esteem, depression, anxiety, ED psychopathology, and BMI were not significantly different between groups. Findings indicate an increase in the prevalence of inpatient admissions among middle-aged women, but few differences between middle-aged and younger-aged women at treatment admission. However, the longer duration of illness among MA warrants in-depth investigation of factors related to resistance to seeking treatment and to existing treatments failing patients, and consideration of tailoring treatment to course of illness.


Ectopic intratracheal thyroid.
Ectopic intratracheal thyroid (EITT) is a rare abnormality, with few cases reported in the literature. We describe a case of a 36-year-old woman with dyspnea due to EITT. We also discuss the epidemiology, etiologies, presentation, diagnosis, and management of EITT. Because EITT is a rare cause of airway obstruction, we hope to remind the clinician of it by presenting this case.


Health benefits of weight reduction in postmenopausal women: a systematic review.
The objective of this systematic review was to determine the effect on long-term health outcomes of lifestyle interventions designed to produce weight loss in postmenopausal women. A systematic search of the MEDLINE, EMBASE, PsychINFO and CINAHL databases retrieved four randomized controlled trials (RCTs) and one controlled clinical trial (CCT) of at least 24 weeks' duration as well as one systematic review. The majority of the studies recruited from the community, had samples with similar baseline characteristics and assessed completers only. Drop-out rates varied from 2.5% to 16%. All active-treatment arms demonstrated significant improvements in weight and body composition from baseline. Significant effects between treatment groups were shown only in intervention versus control studies. Significant weight loss was not accompanied by beneficial changes in cardiovascular risk factors in the majority of studies. None of the studies of weight loss reported disease outcomes. Weight loss in active-treatment arms varied from 1.5 kg to 9 kg over 6-12 months. The study that produced the greatest weight loss demonstrated improvements in risk factors and it may be that only this one study produced sufficient weight loss to do so. Many of the studies were probably underpowered and too short in duration to detect change in risk factors. Lifestyle interventions do produce weight loss in overweight postmenopausal women and have the potential to improve disease outcomes associated with overweight.


Mammary tumor formation and metastasis evoked by a HER2 splice variant.
The HER2 gene is amplified and overexpressed in approximately 20% of invasive breast cancers where it is associated with metastasis and poor prognosis. Here, we describe a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells that evokes aggressive breast cancer phenotypes. Delta-HER2 overexpression in mammary epithelial cells was sufficient to reduce apoptosis, increase proliferation, and induce expression of mesenchymal markers, features that were associated with greater invasive potential in three-dimensional cultures in vitro and more aggressive tumorigenicity and metastasis in vivo. In contrast, overexpression of wild-type HER2 was insufficient at evoking such effects. Unbiased protein-tyrosine phosphorylation profiling in Delta-HER2-expressing cells revealed increased phosphorylation of several signaling proteins not previously known to be controlled by the HER2 pathway. Furthermore, microarray expression analysis revealed activation of genes known to be highly expressed in ER-negative, high-grade, and metastatic primary breast tumors. Together, our results provide mechanistic insights into the activity of a highly pathogenic splice variant of HER2.


Biomechanics or necromechanics? Or how to interpret biomechanical studies.
The field of biomechanics is inextricably linked with orthopaedic surgery: loads and load distribution play a major role in the problems we treat and in the success and failure of many of our treatments. Nonetheless, despite powerful investigational tools, I would argue biomechanics has made a relatively minor impact in clinical practice primarily because most studies fail to account for the major distinction between living and non-living systems: adaptability. While any study requires a clear question or hypothesis or goal, without accounting for adaptability and tissue tolerance, these studies might well be termed "necromechanical." These studies will always have limited clinical relevance unless they contain several key features: 1.) A choice of a mechanical parameter which is arguably a surrogate for relevant biological behavior; 2.) A set of loading regimens which arguably represent the entire range of loadings experienced in vivo; 3.) An explicit discussion of tissue tolerance to the mechanical perturbations of the study; 4.) When appropriate (i.e., the question relates to longer-term effects), an explicit exploration of tissue adaptation over time. Without meeting these requirements, any biomechanical study is suspect and requires interpretation with great caution. When meeting these requirements, biomechanics can provide powerful tools to explain the function of the body and to predict the success or failure of treatments prior to using them on patients.


Impact of nursing interventions on discharge disposition in patients with postoperative delirium.
To identify patient characteristics and perioperative factors associated with non-home patient discharges and the impact of current delirium nursing interventions on discharge disposition, especially non-home dispositions. A retrospective pilot chart review was conducted using electronic health records from five networked hospitals in the Mountain West region of the US. The sample comprised 75 randomly selected patients aged 65 or older who screened positive for delirium during hospitalization. Relationships between patient characteristics, nursing interventions, and discharge dispositions were analyzed using chi-square tests and logistic regression. Most participants (69.3%) were discharged to non-home facilities. Delayed urinary catheter removal was a significant nursing intervention factor. Patients with delayed urinary catheter removal were at increased risk of being discharged to a non-home setting compared with those with early urinary catheter removal (aOR: 14.11, P = .010). Preoperative hypoalbuminemia and surgery durations exceeding 60 minutes were associated with non-home dispositions. Delayed urinary catheter removal, surgery duration greater than 1 hour, and preoperative hypoalbuminemia increased the likelihood of non-home discharge placement for older adults who experience postoperative delirium.


Thoracic duct cyst of posterior mediastinum: a "challenging" differential diagnosis.
Thoracic duct cysts of the mediastinum are extremely rare entities and their pathogenesis still remains unknown. Imaging methods are not specific and show a cystic mass, however the real nature of the lesion is confirmed only with the help of histopathological examination after surgical excision. Here, we present a case of thoracic cyst in a 28-year-old female, lining in posterior lower mediastinum. The cyst was removed by video-assisted thoracic surgery (VATS) and the histopathological findings were that of thoracic duct cyst. Through this case, we propose an ideal surgical approach and diagnostic procedure.


Interventions targeted at reducing diagnostic error: systematic review.
Incorrect, delayed and missed diagnoses can contribute to significant adverse health outcomes. Intervention options have proliferated in recent years necessitating an update to McDonald et al's 2013 systematic review of interventions to reduce diagnostic error. (1) To describe the types of published interventions for reducing diagnostic error that have been evaluated in terms of an objective patient outcome; (2) to assess the risk of bias in the included interventions and perform a sensitivity analysis of the findings; and (3) to determine the effectiveness of included interventions with respect to their intervention type. MEDLINE, CINAHL and the Cochrane Database of Systematic Reviews were searched from 1 January 2012 to 31 December 2019. Publications were included if they delivered patient-related outcomes relating to diagnostic accuracy, management outcomes and/or morbidity and mortality. The interventions in each included study were categorised and analysed using the six intervention types described by McDonald et al (technique, technology-based system interventions, educational interventions, personnel changes, structured process changes and additional review methods). Twenty studies met the inclusion criteria. Eighteen of the 20 included studies (including three randomised controlled trials (RCTs)) demonstrated improvements in objective patient outcomes following the intervention. These three RCTs individually evaluated a technique-based intervention, a technology-based system intervention and a structured process change. The inclusion or exclusion of two higher risk of bias studies did not affect the results. Technique-based interventions, technology-based system interventions and structured process changes have been the most studied interventions over the time period of this review and hence are seen to be effective in reducing diagnostic error. However, more high-quality RCTs are required, particularly evaluating educational interventions and personnel changes, to demonstrate the value of these interventions in diverse settings.


Application of Deep Learning Algorithm to Monitor Upper Extremity Task Practice.
Upper extremity hemiplegia is a serious problem affecting the lives of many people post-stroke. Motor recovery requires high repetitions and quality of task-specific practice. Sufficient practice cannot be completed during therapy sessions, requiring patients to perform additional task practices at home on their own. Adherence to and quality of these home task practices are often limited, which is likely a factor reducing rehabilitation effectiveness post-stroke. However, home adherence is typically measured by self-reports that are known to be inconsistent with objective measurement. The objective of this study was to develop algorithms to enable the objective identification of task type and quality. Twenty neurotypical participants wore an IMU sensor on the wrist and performed four representative tasks in prescribed fashions that mimicked correct, compensatory, and incomplete movement qualities typically seen in stroke survivors. LSTM classifiers were trained to identify the task being performed and its movement quality. Our models achieved an accuracy of 90.8% for task identification and 84.9%, 81.1%, 58.4%, and 73.2% for movement quality classification for the four tasks for unseen participants. The results warrant further investigation to determine the classification performance for stroke survivors and if quantity and quality feedback from objective monitoring facilitates effective task practice at home, thereby improving motor recovery.


Vasodilator action of calcium antagonists in coronary arteries in vitro.
Calcium antagonists have routinely been assumed to inhibit the contractions of arterial smooth muscle through block of membrane channels. The effects of nifedipine and diltiazem on contractions were examined in in vitro preparations of cattle coronary artery, one of the key therapeutic targets of calcium antagonists, to determine if alternate mechanisms of action are involved. Contractions elicited in calcium-free Krebs, in the presence of U 46619, to potassium channel inhibitors (4-aminopyridine and tetraethylammonium) and to a Na(+)-K(+)-ATPase inhibitor (ouabain), were antagonized by low concentrations of nifedipine (3 x 10(-9)-3 x 10(-8) M) and by diltiazem (3 x 10(-8) and 1 x 10(-7) M). Contractions produced in calcium-free Krebs to KCl (50 mM) were antagonized similarly by calcium antagonists. Contractions to depolarizing agents in calcium-free Krebs were antagonized at lower concentrations of nifedipine than comparably elicited responses in Krebs containing 2.3 mM calcium. In addition, higher concentrations of nifedipine were required to antagonize contractions to extracellular calcium, produced in preparations maintained in calcium-free Krebs in the presence of KCl (50 mM), than were needed to block contractions to KCl or to potassium channel inhibitors elicited in calcium-free Krebs. Pretreatment of preparations in calcium-free Krebs with ryanodine (30 microM) did not reduce the nifedipine-sensitive contractions elicited in calcium-free Krebs. It is concluded that at least some of the therapeutic effects of calcium antagonists on arterial tone may be the consequence of antagonism at vascular smooth muscle cell site(s) at which calcium is released or interacts, rather than of block of calcium entry through membrane L channels.


Inhibition of plasmodium falciparum triose-phosphate isomerase by chemical modification of an interface cysteine. Electrospray ionization mass spectrometric analysis of differential cysteine reactivities.
Plasmodium falciparum triose-phosphate isomerase, a homodimeric enzyme, contains four cysteine residues at positions 13, 126, 196, and 217 per subunit. Among these, Cys-13 is present at the dimer interface and is replaced by methionine in the corresponding human enzyme. We have investigated the effect of sulfhydryl labeling on the parasite enzyme, with a view toward developing selective covalent inhibitors by targeting the interface cysteine residue. Differential labeling of the cysteine residues by iodoacetic acid and iodoacetamide has been followed by electrospray ionization mass spectrometry and positions of the labels determined by analysis of tryptic fragments. The rates of labeling follows the order Cys-196 > Cys-13 Cys-217/Cys-126, which correlates well with surface accessibility calculations based on the enzyme crystal structure. Iodoacetic acid labeling leads to a soluble, largely inactive enzyme, whereas IAM labeling leads to precipitation. Carboxyl methylation of Cys-13 results in formation of monomeric species detectable by gel filtration. Studies with an engineered C13D mutant permitted elucidation of the effects of introducing a negative charge at the interface. The C13D mutant exhibits a reduced stability to denaturants and 7-fold reduction in the enzymatic activity even under the concentrations in which dimeric species are observed.


Functional Connectivity Differences in the Insular Sub-regions in Migraine without Aura: A Resting-State Functional Magnetic Resonance Imaging Study.
Objective: The objective of this study was to investigate resting-state functional connectivity (FC) differences in insular sub-regions during the interictal phase in patients with migraine without aura (MWoA). Methods: Forty-nine MWoA patients (MWoA group) and 48 healthy individuals (healthy control group) were recruited for this study. All of the subjects underwent neurological examination and magnetic resonance imaging (MRI). The MRI data were processed using Brat 1.0 software to obtain a whole-brain FC diagram and using Rest 1.8 software to obtain the FC z-score of the sub-regions of both insulas (six sub-regions on each side). Therefore, there were a total of 12 regions of interest (ROIs) that were used as seed points for the statistical analysis. Results: There was abnormal FC between the insular sub-regions and multiple brain regions in the MWoA patients compared with the healthy control group, and a clear laterality was also observed. In addition, the FC z-score of certain sub-regions was negatively correlated with the disease duration. Conclusion: Different insular sub-regions are functionally associated with different regions of the brain and therefore have different functions. In MWoA, the FC between the insular sub-regions and other brain regions was mostly reduced, while a small amount was increased; additionally, the FC may be ipsilateral with a right-side advantage. Variations in the FC of insular sub-regions can be observed as an important indicator of MWoA.


Abdominal pain in pregnancy.
Abdominal pain in pregnancy is most commonly caused by complications of the pregnancy, e.g., abortion, ectopic pregnancy and abruptio placentae. A careful history and methodical physical examination and, if necessary, simple ultrasonographic investigations will reveal the cause in most of these conditions. In a few cases of abdominal pain in pregnancy a gynaecological condition, such as torsion of an ovarian cyst, or a nongynaecological (medical or surgical) one is the cause. Some of these conditions are serious, e.g., acute appendicitis, and unless the correct diagnosis is made and the appropriate management promptly instituted both the mother and her baby may suffer tragic consequences. Moreover, these conditions are more likely to be misdiagnosed during pregnancy. This is because the anatomical and physiological changes which occur in pregnancy tend to change and obtund the expected clinical features and laboratory data which are used to diagnose these conditions. Their early diagnosis therefore requires a high index of suspicion together with awareness of the ways in which they may present in pregnancy.


Anaerobes in cystic fibrosis patients' airways.
Anaerobes are known to constitute an important part of the airway microbiota in both healthy subjects and cystic fibrosis (CF) patients. Studies on the potential role of anaerobic bacteria in CF and thus their involvement in CF pathophysiology have reported contradictory results, and the question is still not elucidated. The aim of this study was to summarize anaerobe diversity in the airway microbiota and its potential role in CF, to provide an overview of the state of knowledge on anaerobe antibiotic resistances (resistome), and to investigate the detectable metabolites produced by anaerobes in CF airways (metabolome). This review emphasizes key metabolites produced by strict anaerobic bacteria (sphingolipids, fermentation-induced metabolites and metabolites involved in quorum-sensing), which may be essential for the better understanding of lung disease pathophysiology in CF.


Genome-wide analyses of retrogenes derived from the human box H/ACA snoRNAs.
The family of box H/ACA snoRNA is an abundant class of non-protein-coding RNAs, which play important roles in the post-transcriptional modification of rRNAs and snRNAs. Here we report the characterization in the human genome of 202 sequences derived from box H/ACA snoRNAs. Most of them were retrogenes formed using the L1 integration machinery. About 96% of the box H/ACA RNA-related sequences are found in corresponding locations on the chimpanzee and human chromosomes, while the mouse shares approximately 50% of these human sequences, suggesting that some of the H/ACA RNA-related sequences in primate occurred after the rodent/primate divergence. Of the H/ACA RNA-related sequences, 49% are found in intronic regions of protein-coding genes and 64 H/ACA-related sequences can be folded to the typical secondary structure of the box H/ACA snoRNA family, while 30 of them were recognized as functional homologs of their corresponding box H/ACA snoRNAs previously reported. Of the 64 sequences with the typical secondary structure of the box H/ACA RNA family, 11 were found in EST databases and 5 among which were shown to be expressed in more than one human tissue. Notably, U107f is nested in an intron of a protein gene coding for nudix-type motif 13, but expressed from the opposite strand, and the searching of EST databases revealed it can be expressed in liver and spleen, even in melanotic melanoma.


Reaction Rate Acceleration of Cooperative Catalytic Systems: Metal Nanoparticles and Lewis Acids in Arene Hydrogenation.
Employing two distinct catalysts in one reaction medium synergistically is a powerful strategy for activating less reactive substrates. Although the approach has been well-developed in homogeneous conditions, it remains challenging and rare in heterogeneous catalysis, especially under gas-liquid-solid multiphase reaction conditions. Here, we describe the development of cooperative and synergistic catalyst systems of heterogeneous Rh-Pt bimetallic nanoparticle catalysts, Rh-Pt/DMPSi-Al2 O3 , and Sc(OTf)3 in the liquid phase for the hydrogenation of arenes under very mild conditions. Dramatic rate acceleration was achieved with cooperative activation. Remarkably, more challenging substrates that contained strong electron-donating groups and sterically hindered substituents were smoothly hydrogenated. Mechanistic insights into the cooperative activation of an aromatic substrate by heterogeneous metal nanoparticles and a soluble Lewis acid was obtained by kinetic studies and by direct observation of 1 H and 45 Sc NMR spectra.