In vitro marginal microleakage: examination of measurements used in assessment.
Premolar teeth with Class II amalgam restorations placed after the application of cavity varnish (Group A), a light cured glass ionomer base (Group B) and 40 per cent polyacrylic acid as a pretreatment agent, followed by unset cermet cement (Group C) were examined for marginal leakage using dye penetration and image analysis. Including amongst the parameters examined were linear leakage length and leakage area, which were found to have no consistent correlation. Group A and C did not generally show significant differences in the parameters examined, whereas Group B exhibited significantly less linear leakage (P less than 0.001), and significantly less leakage area when the stained area was expressed as a percentage of available dentine (P less than 0.001). While allowing some linear leakage, it was found that the light cured glass ionomer base appeared to prevent the dye from entering the dentine. It is concluded that an assessment based solely on the leakage length is inadequate and that some measurement of penetration into dentine should be included in order to fully assess the microleakage potential of a material or technique.


Real-Time Radiofrequency Ablation Lesion Depth Estimation Using Multi-frequency Impedance With a Deep Neural Network and Tree-Based Ensembles.
Design and optimization of statistical models for use in methods for estimating radiofrequency ablation (RFA) lesion depths in soft real-time performance. Using tissue multi-frequency complex electrical impedance data collected from a low-cost embedded system, a deep neural network (NN) and tree-based ensembles (TEs) were trained for estimating the RFA lesion depth via regression. Addition of frequency sweep data, previous depth data, and previous RF power state data boosted accuracy of the statistical models. The root mean square errors were 2 mm for NN and 0.5 mm for TEs for previous statistical models and the root mean square errors were 0.4 mm for NN and 0.04 mm for TEs for the statistical models presented in this paper. Simulation ablation performance showed a mean difference against physical measurements of 0.5 ±0.2 mm for the NN-based depth estimation method and 0.7 ±0.4 mm for the TE-based depth estimation method. The results show that multi-frequency data significantly improves the depth estimation performance of the statistical models. The RFA lesion depth estimation methods presented in this work achieve millimeter-resolution accuracy with soft real-time performance on an ARMv7-based embedded system for potential translation to clinical RFA technologies.


Applications of the modified Cantwell-Ransley epispadias repair in the exstrophy-epispadias complex.
The Cantwell-Ransley technique is the most popular and widely used approach to epispadias repair. This is an evaluation and update of the long-term results of using the modified Cantwell-Ransley technique for epispadias repair. The modified Cantwell-Ransley epispadias repair technique was performed on 129 boys of which 97 had classic bladder exstrophy and 32 complete epispadias. For 106 boys this was primary urethral repair (82 with classic exstrophy, 24 with epispadias) and for the other 23 boys it was a repeat repair (15 with exstrophy, eight with epispadias). At a mean follow-up of 88 months, 120 had a penis that was inclined downward or horizontally while standing. In patients with exstrophy, fistulae were noted in 16% and 33% after primary and repeat urethral repair, respectively. In patients with epispadias, fistulae were noted in 13% and 25% after primary and secondary repair, respectively. In total, five boys with a fistula appearing in the immediate postoperative period following primary urethral repair demonstrated spontaneous healing by 3 months' follow-up. Urethral stricture requiring treatment developed in nine patients. Minor wound infection and skin separation occurred in nine with exstrophy and three with epispadias. Endoscopic examination or catheterization in 120 cases revealed an easily manipulated neourethra. Of 15 sexually active patients, all reported orgasms and ejaculation with a straight penis on erection, although one has complained that his penis is shorter since surgery. The modified Cantwell-Ransley technique for epispadias repair produces durable functional and cosmetic results, and fewer major complications than seen with other repairs. Fistulae occurring after primary urethral repair may close spontaneously, but all those occurring after repeat closure will require further surgery.


Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.
In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.


Risk factors for periprocedural complications in carotid artery stenting without filter protection: A serial diffusion-weighted MRI study.
In high-grade stenosis, carotid artery stenting (CAS) may be chosen as an alternative to carotid surgery. Ischemic periprocedural complications may be documented best with diffusion-weighted MRI (DWMRI). In this prospective study serial DW-MRI and color-coded duplex sonography (CCDS) were used to identify carotid stenosis, which is associated with an increased risk of ischemic events due to CAS. High resolution DW-MRI were performed in 74 out of 77 patients before and after CAS. All MRI scans were analyzed in a blinded manner. With CCDS each carotid stenosis was evaluated according to the grade, length, echo properties and plaque surface. In 42 out of 74 patients (56.8 %) a total of 188 new procedure- related DWI-lesions could be detected, while in 32 patients MRI-controls remained normal. Of the lesions 79.25 % had a size < 1 cm. In one major and two minor strokes due to CAS (total complication rate 3.9 %) corresponding territorial infarcts could be demonstrated. A highly significant correlation was found between the length of the stenosis and the incidence of new DWI-lesions (p = 0.0141). In contrast, neither the grade of ICA stenosis nor the sonographic plaque morphology or plaque surface correlated with the number of DWI-lesion in postinterventional scans. The length-and not the degree-of an ICA stenosis seems to be the most decisive sonographic factor for estimating the periprocedural risk of embolism. DWI-lesions are much more frequent than clinical complications and may represent an important surrogate marker for improving the techniques of carotid artery stenting, especially comparing the benefit of different mechanical protection devices.


Opportunities for maloccurrence in delivery of specialized care in the managed care environment.
Two patients lost eyes because of complications of retinal detachment in managed care situations. In both cases the eyes might have been saved had the patients been treated earlier by highly qualified subspecialists.


Characteristics and long-term survival of resected pancreatic cystic neoplasms in Finland. The first nationwide retrospective cohort analysis.
Pancreatic cystic neoplasms (PCN) are being found increasingly in imaging studies. Even though the characteristics of PCN lesions have been studied extensively in single and multicentre settings, nationwide data is lacking. The aim of this study was to determine the nationwide epidemiologic characteristics and long-term survival of all resected PCNs. For this retrospective cohort analysis, all PCNs operated on in Finland during the period 2000-2008 were identified. Data was collected from all patients: on demographics, comorbidities, symptoms, radiological findings, surgical procedures, complications, histopathological diagnoses and survival. Incomplete pathology reports and any uncertain diagnoses were re-assessed. Survival data was collected after a five-year follow-up period. The final database included 225 patients with operated PCN. After reviewing the incomplete pathology reports, in 44 cases the original diagnosis was changed, mostly from MCN to IPMN. The most common histopathological diagnoses were IPMN (94/225; 50/225 MD-IPMN, 30/225 MX-IPMN and 14/225 BD-IPMN), SCN (41/225) and MCN (40/225). Overall, 53/225 (23.6%) of the tumours were malignant. Malignancy was detected in MD-IPMN 29/50 (58%), MX-IPMN 10/30 (33.3%), MCN 12/40 (30%), BD-IPMN 2/14 (14.3%) patients. Median 5-year survival for all patients was 77%: 87% in patients without malignancy, 77% with HGD and 27% in patients with a malignant resected PCN. One fourth of the PCNs operated on nationwide were malignant, with a five-year survival of 27%, compared to overall survival of 87% in patients with non-malignant disease and 77% in those with HGD. Detecting - and operating on - a PCN before the malignant transfer remains a great challenge.


Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model.
There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be treated successfully by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ developing in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent the development of ONJ in a rat model. Thirty rats were randomly allocated to three groups (10 in each): (1) group I (controls): extraction, no drug treatment; (2) group II (non-coverage): extraction, dexamethasone plus alendronate; (3) group III (coverage): extraction, dexamethasone plus alendronate, plus coverage with a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.


Pinguecula with spheroidal degeneration: clinicopathologic correlation.
Clinicopathologic correlation of a pinguecula with spheroidal degeneration: a benign entity occasionally encountered in clinical practice.


The effect of alpha-fetoprotein on the growth of placental cells in vitro.
Cell cultures of early mouse placentae were studied in the presence of mouse amniotic fluid or isolated alpha-fetoprotein (AFP). Four cell types were observed: polygonal cells, giant cells, small round cells and fibroblasts. The number of polygonal cells increased in placental cultures in the presence of amniotic fluid or AFP, suggesting de novo formation and proliferation in vitro. These preparations were found to stimulate the DNA synthesis in polygonal cells, as demonstrated by 3H-thymidine labelling experiments. Polygonal cells also show a significant increase in 3H-leucine incorporation, indicating more active protein synthesis under the effect of amniotic fluid or AFP. These data suggest that AFP may be one of the fetal factors promoting trophoblastic differentiation.


An alkyl imidate labeling study of the organization of phospholipids and proteins in the lipid-containing bacteriophage PR4.
The structure of the lipid-containing bacteriophage PR4 was studied using two alkyl imidates, ethyl acetimidate (EAI), a reagent permeant to lipid bilayers and isethionyl acetimidate (IAI), which is impermeant to membranes. The virion is an icosahedral particle consisting of a protein coat surrounding a membrane of phospholipid and protein which in turn encloses the DNA genome. Upon exposure to the permeant reagent, EAI, 50% of the phosphatidylethanolamine (PE) molecules reacted rapidly (half-life less than 10 min). A similar fraction of the PE also reacted with IAI, the impermeant reagent. The remaining half of the PE molecules reacted slowly with EAI (half-life of 80 min) and failed to react with IAI. All of the phage proteins reacted with both EAI and IAI (except a DNA-associated protein which reacted only with EAI). These labeling results indicate that the phage membrane consists of a lipid bilayer and that at least a portion of each phage protein (except the DNA-associated protein) is exposed on the external face of the lipid bilayer. Several of the membrane proteins could be cross-linked either to the phage membrane PE after EAI treatment or to phage phosphatidylglycerol after periodate treatment. The major structural protein of the phage was readily cross-linked to PG but failed to cross-link to PE suggesting that the protein specifically interacts with PG.


An Unusual Etiology of Hypothyroidism and New-Onset Insulin-Dependent Diabetes: A Rare Side Effect of Nivolumab.
Nivolumab, a monoclonal antibody targeting programmed cell death 1 receptor, is prescribed for many advanced cancers like malignant melanoma, non-small cell lung cancer, renal cell cancer, etc. With the increase in the use of nivolumab like immunotherapy, the incidences of immune-related side effects are also on the rise. Immune-related endocrinopathies like hypothyroidism and new-onset type 2 diabetes mellitus associated with nivolumab use, although rare, are already documented in the literature. Here we present a case of hypothyroidism and new-onset type 2 diabetes mellitus in a renal cell cancer patient receiving nivolumab for the past six months. The patient was managed successfully with discontinuation of nivolumab, intravenous insulin, and thyroid hormone replacement therapy. These types of endocrinopathies can be fatal; hence, prompt diagnosis and management are required. Thus, not only physicians' awareness of such endocrinopathies among nivolumab-treated patients but also patients' awareness regarding warning signs and symptoms are essential.


EGb 761 inhibits Aβ1-42-induced neuroinflammatory response by suppressing P38 MAPK signaling pathway in BV-2 microglial cells.
Ginkgo biloba extract EGb 761 possesses a variety of biological effects and has been proved to be beneficial in Alzheimer's disease. This study aimed to explore the anti-inflammatory mechanisms of EGb 761 on the Aβ1-42-induced BV-2 microglial cells. We analyzed the production and gene expression of proinflammatory cytokines by enzyme-linked immunosorbent assay and qRT-PCR, examined phosphorylation of MAPKs by western blot and measured nuclear factor-κB nuclear translocation. Compared with Aβ1-42-treated group, EGb 761 inhibited release and gene expression of tumor necrosis factor-α and interleukin-1β, suppressed nuclear translocation of nuclear factor-κB and attenuated phosphorylation of p38 MAPK in a concentration-dependent manner, but not ERK and JNK. In summary, the results suggested that EGb 761 could attenuate Aβ1-42-induced neuroinflammatory response.


Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning.
Research has repeatedly suggested genetic and environmental factors in the etiology underlying female sexual dysfunction (FSD). Because sexual functioning is a highly variable trait, epigenetics could provide a promising approach to tackle the origins of FSD and consequently offer a step-change in our understanding of these problems. To identify differentially methylated CpG positions for sexual functioning in a sample of monozygotic twin pairs discordant for sexual functioning. The sample consisted of 33 trait-discordant monozygotic twin pairs (mean age = 54.1 years, SD = 9.05) from the Twins UK Registry. Phenotypic data on sexual desire, arousal, lubrication, orgasm, satisfaction, and pain were collected using the Female Sexual Function Index-Lifelong (FSFI-LL). The Illumina Infinium HumanMethylation 450 DNA BeadChip was used for epigenome-wide analyses of DNA methylation in whole-blood samples. Comparison of DNA methylation patterns associated with the FSFI-LL total score and its six subdomains. Two differentially methylated CpG positions (cg09580409 and cg14734994) reaching experiment-wide statistical significance were found for overall sexual functioning, mapping to MGC45800 and the threonine synthase-like 2 gene (THNSL2), respectively. Furthermore, potential biologically relevant candidates for sexual desire (CUB and zona pellucida-like domains 1, CUZD1) and satisfaction (solute carrier family 6 member 19, SLC6A19) were identified. THNSL2 and SLC6A19, which have been linked to weight and adiposity, might represent novel candidates for sexual problems in women. This is the first study to investigate epigenetic mechanisms underlying FSD. The study used a relative small sample of monozygotic female twins. The cutoff to determine discordance in sexual problems was chosen based on a 10% FSFI score difference. Therefore, the results have to be interpreted with caution and need replication in larger clinical samples. Understanding how genes and environment interact to influence our sexuality might inform clinical practice and lead to new treatments for women experiencing FSD. Burri A, Leupin M, Spector T, Marinova Z. Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning. J Sex Med 2017;14:1357-1364.


Signatures of new d-wave vortex physics in overdoped Tl2Ba2CuO(6+x) revealed by TF-µ(+)SR.
The spontaneous expulsion of applied magnetic field, the Meissner effect, is a defining feature of superconductors; in Type-II superconductors above the lower critical field, this screening takes the form of a lattice of magnetic flux vortices. Using implanted spin-1/2 positive muons, one can measure the vortex lattice field distribution through the spin precession and deduce key parameters of the superconducting ground state, and thereby fundamental properties of the superconducting pairing. Muon spin rotation/relaxation (µSR) experiments have indeed revealed much interesting physics in the underdoped cuprates, where superconductivity is closely related to, or coexistent with, disordered or fluctuating magnetic and charge excitations. Such complications should be absent in overdoped cuprates, which are believed to exhibit conventional Fermi liquid behaviour. These first transverse field (TF)-µ(+)SR experiments on heavily-overdoped single crystals reveal a superfluid density exhibiting a clear inflection point near 0.5Tc, with a striking doping-independent scaling. This reflects hitherto unrecognized physics intrinsic to d-wave vortices, evidently generic to the cuprates, and may offer fundamentally new insights into their still-mysterious superconductivity.


Harnessing aptamers for electrochemical detection of endotoxin.
Lipopolysaccharide (LPS), also known as endotoxin, triggers a fatal septic shock; therefore, fast and accurate detection of LPS from a complex milieu is of primary importance. Several LPS affinity binders have been reported so far but few of them have proved their efficacy in developing electrochemical sensors capable of selectively detecting LPS from crude biological liquors. In this study, we identified 10 different single-stranded DNA aptamers showing specific affinity to LPS with dissociation constants (K(d)) in the nanomolar range using a NECEEM-based non-SELEX method. Based on the sequence and secondary structure analysis of the LPS binding aptamers, an aptamer exhibiting the highest affinity to LPS (i.e., B2) was selected to construct an impedance biosensor on a gold surface. The developed electrochemical aptasensor showed excellent sensitivity and specificity in the linear detection range from 0.01 to 1 ng/mL of LPS with significantly reduced detection time compared with the traditional Limulus amoebocyte lysate (LAL) assay.


The ventromedial hypothalamic nucleus is not essential for the prefeeding corticosterone peak in rats under restricted daily feeding.
The role of the ventromedial hypothalamic nucleus (VMH) in the generation of the prefeeding corticosterone peak was examined in rats under restricted daily feeding, under which daily meal supply was restricted to a fixed time in the early light period. Rats were lesioned in the VMH bilaterally and subjected to restricted daily feeding during two different post-operative phases and with two different durations of food presentation. A restricted feeding with free access to meal for 4 hr was imposed on the VMH-lesioned rats from 2 to 4 weeks after the lesion, when the daily food intake increased significantly (dynamic phase). The restricted feeding induced the prefeeding hormone peak in sham operated rats, but failed to develop it in the VMH-lesioned rats. On the other hand, the hormone peak appeared in the VMH-lesioned rats subjected to the feeding schedule from 8 to 10 weeks after the lesion, when the daily food intake was not different from the control (static phase). Moreover, the VMH-lesioned rats showed the hormone peak even in the dynamic phase when the access to meal was shortened to 1 hr. These results indicate that the VMH is not essential for the generation of the prefeeding corticosterone peak under restricted daily feeding, and suggest that a special metabolic state observed during the dynamic phase of VMH lesion prevents the development of the feeding-associated oscillation or its expression upon plasma corticosterone level.


Integrating biomechanics with stakeholder perspectives to inform safety in grassroots dirt track racing.
Grassroots dirt track racing is a foundational part of motorsports with a high risk of severe injury. This study aimed to gather perspectives and experiences of motorsports drivers surrounding safety and head acceleration events experienced during grassroots dirt track racing to inform strategies to improve driver safety. Thirteen drivers (n=9 who primarily race on dirt tracks; n=4 who primarily race on pavement tracks) with prior dirt track racing experience participated in separate, group-specific focus groups and/or one-on-one interviews where video, simulations of head motion, and head acceleration data were shared. Peak kinematics of laps and crash contact scenarios were recorded, and head perturbations (i.e., deviations in head motion relative to its moving-average trajectory) were quantified for each lap and presented through guided discussion. Responses were summarized using Rapid Assessment Process. Audio recordings and field notes were collected from focus groups and interviews and analyzed across 25 domains. Drivers described dirt track racing as short, fast bursts of racing. Benefits of dirt track racing for driver development were described, including learning car control. Drivers acknowledged risks of racing and expressed confidence in safety equipment but identified areas for improvement. Drivers observed lateral bouncing of the head in video and simulations but recognized that such motions were not noticed while racing. Track conditions and track type were identified as factors influencing head perturbations. Mean PLA (5.5 g) and PRV (3.07 rad/s) of perturbations experienced during racing laps and perturbation frequencies of 5 and 7 perturbations per second were reported. Generally, drivers accurately estimated the head acceleration magnitudes but were surprised by the frequency and maximum magnitude of perturbations. Maximum perturbation magnitudes (26.8 g and 19.0 rad/s) were attributed to hitting a "rut" in the dirt. Drivers described sudden stops, vertical loads due to landing from a large height, and impacts to the vehicle frame as crash events they physically feel the most. Summary statistics for crashes (medians = 7.30 g, 6.94 rad/s) were reported. Typical impact magnitudes measured in other sports (e.g., football) were provided for context. Upon reviewing the biomechanics, drivers were surprised that crash accelerations were relatively low compared to other contact/collision sports. Pavement drivers noted limited safety features in dirt track racing compared to pavement, including rigidity of vehicle frames, seat structure, seatbelt integration, and lack of oversight from sanctioning bodies. Most drivers felt seat inserts and head and neck restraints are important for injury prevention; however, usage of seat inserts and preferred head and neck restraint system differed among drivers. Drivers described their perspectives and experiences related to safety and identified strategies to improve safety in grassroots dirt track racing. Drivers expressed support for future safety research.


Functionality and stability of heparin immobilized onto poly(dimethylsiloxane).
Poly(dimethylsiloxane) (PDMS) has become an attractive material when working in the field of microfluidics, mainly because of the rapid prototyping process it involves. The increased surface volume ratio in microchannels makes the interaction between sample and material surface highly important, evident when handling complex biological samples such as plasma or blood. This study demonstrates a new grade of non-covalent heparin surface that adds efficient anticoagulant property to the PDMS material. The surface modification is a simple and fast one-step process performed at neutral pH, optimal when working with closed microsystems. The heparin formed a uniform and functional coating on hydrophobic PDMS with comparatively high level of antithrombin-binding capacity. In addition, long-term studies revealed that the immobilized heparin was more or less stable in the microchannels over a time of three weeks. Recalcified plasma in contact with native PDMS showed complete coagulation after 1h, while no fibrin formation was detected in plasma incubated on heparin-coated PDMS within the same time. In conclusion, we see the heparin coating developed and evaluated in this study as a tool that greatly facilitates the use of PDMS in microfluidics dealing with plasma or blood samples.


Binocular beats: psychophysical studies of binocular interaction in normal and stereoblind humans.
We describe a psychophysical method for assessing binocular integration using dichoptically-presented uniform fields. By temporally modulating uniform field luminances at different frequencies between the eyes, a rhythmic beat is produced--a visual percept characterized by undulations in luminance at a frequency equal to the arithmetic difference between the two monocular stimulus frequencies. Using a signal detection paradigm, we studied the beat as a function of modulation depth in normal and binocularly deficient subjects. Normal subjects easily detected the beat, even at low modulation depths, while stereoblind subjects (with stereoacuity worse than 2000 sec arc) failed to detect beats at any modulation depth or with any combination of stimulus frequencies tested. The beat provides evidence for the confluence of monocular signals into binocular integrating mechanisms. Our results therefore suggest that the status of functioning binocular mechanisms is related to the detectability of the beat. This uniform-field stimulus does not require accurate accommodation, fixation, vergence or high spatial resolution, thus making this technique particularly attractive for the study of binocular interaction in developing infants and in binocularly deficient adults.


Short-term effects of air pollution on pulse pressure among nonsmoking adults.
Previous studies on the effects of acute air pollution have focused primarily on blood pressure (BP). Our study enrolled 9238 nonsmoking adults over 30 years of age from 6 townships in Taiwan: 1 seaport, 1 urban, 1 industrial, and 3 rural. Using generalized additive models, we evaluated the associations between brachial BP and short-term exposure to 5 air pollutants: particulate matter with diameter <10 μm (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), carbon monoxide (CO), and ozone (O(3)). After adjusting for individual and meteorologic factors, the systolic BP was decreased by all 5 pollutants, whereas the diastolic BP was increased by SO(2), NO(2), and O(3). The pulse pressure was consistently decreased by all 5 pollutants, with changes of -1.5 (95% confidence interval = -2.0 to -1.1), -0.6 (-0.9 to -0.4), -2.4 (-3.0 to -1.8), -1.2 (-1.6 to -0.9), and -1.4 (-1.8 to -0.9) mm Hg for interquartile range increases in 3-day lagged PM(10), SO(2), NO(2), carbon monoxide, and O(3), respectively. PM(10) exposure was more strongly associated with reduction of pulse pressure among men, persons >60 years of age, those with hypertension, and those living in the industrial township. Short-term exposure to air pollution reduces pulse pressure. PM(10) in industrial emissions may contribute to pulse pressure changes. Age, sex, and hypertensive status may modify the effects of PM(10) on pulse pressure.


Traditional medicine for the treatment of common cold in Korean adults: A nationwide population-based study.
Traditional medicines (TMs) have been used to treat common cold in Asia, but no studies have been conducted to examine the trend of use for several years. The objective of this study was to analyze the prescription patterns of TMs for common cold using national claims data accrued over 7 years in Korea. This will contribute to the scientific evidence enhancing the understanding of TM use for the treatment of common cold. This study analyzed national claims data from the Health Insurance Review and Assessment Service database. We extracted data for diagnosis of common cold (Korean Standard Classification of Diseases: J00, Acute nasopharyngitis) and prescriptions of TMs for adults who visited all types of oriental medical institutions during 2010-2016. We estimated the prescription patterns of TMs by sex, age group, and year. We extracted 3,014,428 prescriptions. The total number of prescriptions increased by 125.1% in 2016 compared to that in 2010. For all ages and periods, the number of prescriptions in women was higher than that in men. The age range with the most prescriptions was 70-79 years. The seven most prescribed TMs for common cold were Socheongnyongtang, Samso-eum, Yeongyopaedoksan, Insampaedoksan, Gumigohwaltang, Galgeuntang, and Hyeonggae-yeongyotang. This was the first study to analyze the prescription patterns of TMs for common cold using National Health Insurance data in Korea. This study provides scientific evidences on the disease burden and the utilization pattern of TMs for common cold to support decision making on initiatives such as allocation and management of health resources.


Performance evaluation of a novel two-stage biodegradation technique through management of toxic lignocellulosic terrestrial weeds.
The present study investigates the biodegradation of two potentially toxic terrestrial weeds Parthenium hysterophorus and Lantana camara, implementing a novel two-stage biodegradation technique; Rotary drum composting followed by vermicomposting (RV). The RV approach was refined for a 7-day thermophilic degradation in an in-vessel rotary drum composter, followed by a 20-day mesophilic degradation utilizing Eisenia fetida and Eudrilus eugeniae vermi-monocultures. However, rotary drum composting (RDC) was performed for both the weeds (for 27 days), facilitating only initial thermophilic degradation to compare the efficacy of the RV technique. Lignocelluloses analysis revealed that cellulose degradation doubled during RV technique, indicating efficient biodegradation in reactors administered with E. fetida vermiculture compared to RDC (19.60 to 42.80% and 26.80 to 66.50% in P. hysterophorus and L. camara feedstocks). Further, these results also correlated with the X-Ray diffractograms of all trials showing the degradation of crystalline cellulose at 2θ: 20-50° for RV. Moreover, to ensure product safety, the analyzed total heavy metals content also unveiled the advantage of RV over RDC as validated by the accumulation of higher concentrations of zinc (45% and 33% in P. hysterophorus and L. camara feedstocks) and lead (55% and 45% in P. hysterophorus and L. camara feedstocks) in reactors with E. fetida. The material's seed germination index increased to 80% in the final product of all trials in the RV technique, indicating the diminishing of the phytotoxic nature. Subsequently, pot studies also indicated that the RV technique was coherent in managing noxious weeds.


Muscle cell migrations of C. elegans are mediated by the alpha-integrin INA-1, Eph receptor VAB-1, and a novel peptidase homologue MNP-1.
Cell migration is a fundamental process occurring during embryonic development and tissue morphogenesis. In the nematode Caenorhabditis elegans, morphogenesis of the body-wall musculature involves short-range migrations of 81 embryonic muscle cells from the lateral surface of the embryo towards the dorsal and ventral midlines. This study shows that mutations in ina-1 (alpha-integrin), as well as vab-1 (Eph receptor), and vab-2 (ephrin), display defects in embryonic muscle cell migration. Furthermore, an RNAi-based enhancer screen in an ina-1 weak loss-of-function background identified mnp-1 (matrix non-peptidase homologue-1) as a previously uncharacterized gene required for promoting proper migration of the embryonic muscle cells. mnp-1 encodes a membrane associated metalloproteinase homologue that is predicted to be catalytically inactive. Our data suggest that MNP-1 is expressed in migrating muscle cells and localizes to the plasma membrane with the non-peptidase domain exposed to the extra-cellular environment. Double-mutant analysis between mnp-1(RNAi), ina-1, and vab-1 mutations; as well as tissue specific rescue experiments; indicated that each of these gene products function predominantly independent of each other and from different cell types to affect muscle cell migration. Together these results suggest complex interactions between the adjacent epidermal, neuronal, and muscle cells are required to promote proper muscle cell migration during embryogenesis.


Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1/2 signaling pathways.
Cardiomyocytes apoptosis is an important contributor to myocardial dysfunction and heart failure. Adiponectin has cardioprotective effects, potential mechanisms behind it are not clear in cardiomyocytes. The purpose of the study was to investigate whether adiponectin can block palmitate-induced apoptosis and the underlying biochemical mechanism in H9c2 cells. H9c2 cells were treated with palmitate presence or absence of 2.5 μg/mL globular adiponectin. The effect on the cell viability of H9c2 cells was evaluated using MTT assay, and cell apoptosis was determined by Hoechst 33342 staining. Protein expression was measured using the western blot method. Our results showed that the palmitate treatment induced apoptosis in H9c2 cells, which was associated with increasing the level of cleaved caspase-3 and cleaved PARP. Meanwhile, palmitate-induced apoptosis increased the protein level of p-ERK1/2, and decreased the protein level of p-Akt significantly. However, levels of both of these proteins were restored to the normal when pretreated with adiponectin, and followed with the decrease of cleaved caspase-3 and cleaved PARP. In line with these results, the protective effect of adiponectin can be blocked by PI3K/Akt inhibitor LY294002, and palmitate-induced apoptosis can be attenuated by ERK1/2 inhibitor U0126. Taken together, the present study demonstrated that adiponectin protects H9c2 cells from palmitate-induced apoptosis via PI3K/Akt and ERK1/2 signaling pathways. Our results reveal a link between adiponectin and cardiomyocytes apoptosis, suggesting that adioponectin may be a promising therapeutic for the treatment of lipotoxicity cardiomyopathy.


Astroglial cells as neuroendocrine targets in forebrain development: Implications for sex differences in psychiatric disease.
Astroglial cells are the most abundant cell type in the mammalian brain. They are implicated in almost every aspect of brain physiology, including maintaining homeostasis, building and maintaining the blood brain barrier, and the development and maturation of neuronal networks. Critically, astroglia also express receptors for gonadal sex hormones, respond rapidly to gonadal hormones, and are able to synthesize hormones. Thus, they are positioned to guide and mediate sexual differentiation of the brain, particularly neuronal networks in typical and pathological conditions. In this review, we describe astroglial involvement in the organization and development of the brain, and consider known sex differences in astroglial responses to understand how astroglial cell-mediated organization may play a role in forebrain sexual dimorphisms in human populations. Finally, we consider how sexually dimorphic astroglial responses and functions in development may lead to sex differences in vulnerability for neuropsychiatric disorders.


Estimation of effective dose of propofol mono-sedation for successful insertion of upper gastrointestinal endoscope in healthy, non-obese Chinese adults.
Propofol is effective in sedation for upper gastrointestinal (UGI) endoscopy. However, the optimum dose is ill-defined. This study aimed to estimate the effective dose of propofol mono-sedation for successful endoscope insertion in healthy, non-obese Chinese adults undergoing single UGI endoscopy. Twenty-six adult patients undergoing elective single UGI endoscopy were enrolled in this study. A modified Dixon's up-and-down method was utilized to assess the effective dose of propofol for successful endoscope insertion. The initial dose of propofol administered, 1.6 mg/kg, was adjusted with 0.1 mg/kg as a step size. The patient's responses to endoscope insertion were classified as either 'movement' or 'no movement'. When patient's responses were changed from 'movement' to 'no movement' or from 'no movement' to 'movement', a crossover was defined. After eight crossovers had been obtained, patient recruitment was stopped. The mean of midpoints of all crossovers obtained by the modified Dixon's up-and-down method in all 26 patients was defined as calculated median effective dose (ED50 ) of propofol for successful endoscope insertion. Furthermore, probit regression analysis was used to determine the dose of propofol where 50% (ED50 ) and 95% (ED95 ) of endoscope insertion attempts were successful. The calculated ED50 of propofol for successful endoscope insertion was 1.89 ± 0.12 mg/kg. The probit regression analysis showed that ED50 and ED95 of propofol for successful endoscope insertion were 1.90 mg/kg (95% CI, 1.78-2.10 mg/kg) and 2.15 mg/kg (95% CI, 2.01-3.56 mg/kg), respectively. No any patient had hypoxaemia and gag reflex during the UGI endoscopy with propofol mono-sedation. In healthy, non-obese Chinese adults, propofol mono-sedation can provide excellent conditions of UGI endoscopy and the estimated ED50 of propofol for successful endoscope insertion is 1.89 ± 0.12 mg/kg.


Parvalbumin and calretinin in the avian thymus.
The avian thymic hormone, known to support the maturation of T-lymphocytes, is biochemically similar to parvalbumin. However, its exact cellular distribution in the thymus is unknown. We have therefore studied the occurrence of parvalbumin and other related calcium-binding proteins in this organ by immunohistochemistry during development and after hatching. Parvalbumin immunoreactivity appears in the epithelial cells on embryonic day 9, and is expressed in the cortical reticular cells in the adult. Calretinin is found in the clusters of medullary epithelial cells from embryonic day 11, whereas calbindin D-28k is absent from this organ. Thus, calcium binding-proteins are excellent markers for different compartments of the avian thymus in embryonic life and after hatching, and their expression seems to coincide with their functional maturation.


Adenosine uptake site heterogeneity in the mammalian CNS? Uptake inhibitors as probes and potential neuropharmaceuticals.
Inhibitors of adenosine uptake or transport have been used clinically for some time in certain cardiovascular diseases. More recently, some of them have also been investigated for possible clinical use in combination with antimetabolites based on the observed heterogeneity of nucleoside transport in mammalian tumor cells. Such a heterogeneity of adenosine uptake and uptake sites has now also been suggested in the mammalian CNS. The aim of this article is, therefore, to review the present status of our knowledge of adenosine uptake in the mammalian CNS, compare it with our far more advanced knowledge of nucleoside transport in other mammalian cells and suggest direction of future research. The possible implications for the development of adenosine uptake inhibitors as adenosinergic neuropharmaceuticals will be discussed based on our knowledge of the physiological function of adenosine in the CNS.


Dairy intake in relation to metabolic health status in overweight and obese adolescents.
There was a lack of evidence on the association between dairy intake and metabolic health status in overweight/obese adolescents. This study evaluated the association between dairy intake and metabolic health status in overweight/obese Iranian adolescents. Overweight/obese adolescents (n = 203; 101 boys and 102 girls) selected by a multistage cluster random sampling method have participated in this cross-sectional study. Dietary intake was assessed using a validated 147-item food frequency questionnaire. Anthropometric indices, blood pressure, fasting glucose, insulin, and lipid profile were measured. Participants were categorized to metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) according to International Diabetes Federation (IDF) criteria and a combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR) criteria. The frequency of MUO based on IDF, and IDF/HOMA-IR definitions was 38.9% and 33.0%, respectively. In fully-adjusted model, participants in the highest tertile of dairy intake had 61% lower odds of MUO based on IDF criteria (OR = 0.39, 95% CI 0.15-0.99). Higher dairy intake was associated with a non-significant lower risk of MUO according to IDF/HOMA-IR definition in the maximally-adjusted model (OR = 0.44, 95% CI 0.17-1.16). Stratifies analysis by sex and body mass index revealed that the association was stronger in girls and overweight subjects. Furthermore, higher intake of low-fat dairy was related to a reduced likelihood of MUO, while higher intake of high-fat dairy was related to increased odds of MUO. This community-based cross-sectional study revealed that higher intake of dairy was associated with a significant lower odd of MUO among Iranian adolescents, especially in girls and overweight subjects.


Beliefs about Obedience Levels in Studies Conducted within the Milgram Paradigm: Better than Average Effect and Comparisons of Typical Behaviors by Residents of Various Nations.
The article presents studies examining whether the better than average (BTA) effect appears in opinions regarding obedience of individuals participating in an experiment conducted in the Milgram paradigm. Participants are presented with a detailed description of the experiment, asked to declare at what moment an average participant would cease their participation in the study, and then asked to declare at what moment they themselves would quit the experiment. It turned out that the participants demonstrated a strong BTA effect. This effect also concerned those who had known the results of the Milgram experiment prior to the study. Interestingly, those individuals-in contrast to naive participants-judged that the average person would remain obedient for longer, but at the same time prior familiarity with the Milgram experiment did not impact convictions as to own obedience. By the same token, the BTA effect size was larger among those who had previously heard of the Milgram experiment than those who had not. Additionally, study participants were asked to estimate the behavior of the average resident of their country (Poland), as well as of average residents of several other European countries. It turned out that in participants' judgment the average Pole would withdraw from the experiment quicker than the average Russian and average German, but later than average residents of France and England.


Development and characterization of polymorphic microsatellite markers in Cyclobalanopsis glauca (Fagaceae).
We isolated and characterized polymorphic microsatellite loci in Cyclobalanopsis glauca (Fagaceae), an evergreen broadleaved monoecious tree, to provide tools for analyzing parentage and mating system. Thirteen polymorphic microsatellite markers were developed and tested in three C. glauca populations. The number of alleles per locus varied from two to 22. The observed and expected heterozygosities within populations were 0.000-0.967 and 0.033-0.949, respectively. These polymorphic primers showed high levels of polymorphism within tested populations, and can be used in parentage analysis and mating system estimation of C. glauca.


Factors associated with diphtheria vaccination completion among children under five years old in Peru 2010-2019: A cross-sectional population-based study.
The World Health Organization (WHO) recommends a minimum of 90% coverage of diphtheria three-dose complete vaccination scheme (DPT) as part of routine immunization programs in children. However, diphtheria coverage in Peru has not reached the minimum recommended during the last decades. Our study aimed to determine the complete three-dose DPT coverage and factors associated with compliance towards complete vaccination in Peru between 2010-2019. We conducted a secondary cross-sectional study using the "Encuesta Demográfica y de Salud Familiar (ENDES)"- Demographic and Family Health Survey, which is a survey that targets mothers between 15 and 49 years of age. DPT vaccination coverage was 72.4% and several factors were associated with the DPT scheme completion. Women in the age groups 18 to 24 (ORa = 2.31, 95%CI: 2.11-2.52), 25 to 34 (ORa = 3.37, 95% CI: 3.08-3.69), and 35 to 49 (ORa = 4.74, 95% CI: 4.29-5.22) were more likely to complete their children's DPT vaccination scheme compared to those between 15 to 17 years of age. Both Spanish (ORa = 1.39, 95% CI: 1.31-1.48) and Quechua (ORa = 1.34, 95% CI: 1.25-1.43) as first spoken language were associated with DPT completion compared to native language speaking mothers. Women who worked (ORa = 1.72, 95% CI: 1.57-1.88), studied (ORa = 1.47, 95% CI: 1.33-1.62), or were housewives (ORa = 1.41, 95% CI: 1.29-1.54) during the previous week were more likely to complete their children's DPT scheme compared to participants that did not work during the previous week. Women with the financial capability to access health care were less likely to complete the DPT scheme (ORa = 0.95, 95% CI: 0.92-0.97). Considering the accessibility to health care centers, women who knew the nearest location (ORa = 1.07, 95% CI: 1.03-1.11), had geographic accessibility (ORa = 1.09, 95% CI: 1.06-1.13) or a current transport (ORa = 1.06, 95% CI: 1.02-1.09) were more likely to complete their children 's DPT scheme. Our results highlight low diphtheria vaccine coverage levels in Peru, with values lower than what is recommended by the WHO. Results may serve as a baseline for future studies to improve vaccination programs, reduce barriers and increase DPT coverage in Peru.


Nano-elemental selenium particle developed via supramolecular self-assembly of chondroitin sulfate A and Na2SeO3 to repair cartilage lesions.
Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate A‑selenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na2SeO3 and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of l-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, -2, -3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na2SeO3, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.


Histamine and peptic ulcer disease: histamine methyltransferase activity in gastric mucosa of control subjects and duodenal ulcer patients before and after surgical treatment.
Histamine methyltransferase (HMT) activity was determined by a modified isotope assay in biopsy specimens from gastric mucosa of control subjects, duodenal ulcer patients and after various gastric operations. Enzymic activity of male control subjects who were 'healthy' with respect to their upper gastrointestinal tract was 70.4 +/- 12.8 pmol/(min x mg protein). In male duodenal ulcer patients HMT-activity was significantly lowered by 15%; following selective vagotomy with pyloroplasty a significant increase of 14% was observed as compared to controls. The difference between values before (59.9 +/- 13.3) and after (80.4 +/- 11.7) this operation was highly significant (p less than 0.001). Experiments in a small number of patients showed that after other modifications of vagotomy elevated HMT-activities were also found, whereas after resection procedures such changes of enzymic activity did not occur. According to these results the low gastric HMT-activity of duodenal ulcer patients could play a role in the pathogenesis of a chronic peptic ulcer by being responsible for reduced histamine inactivation and - as a consequence - enhanced acid secretion. Furthermore, vagotomy seemed to influence acid secretion in human subjects not only by direct effects on the parietal cells, but also by an activation of histamine catabolism. One patient, who despite complete vagotomy showed both no reduction in acid secretion and a low gastric HMT-activity, may be the representative of a new population of peptic ulcer patients.


Novel phthalide derivatives identified from Ligusticum chuanxiong (Chuanxiong).
Ligusticum chuanxiong Hort. (Chuanxiong) is a well-known Chinese medicine, and studies on its chemical constituents are important for explaining its mechanism of action and quality control. This study aims to investigate the chemical constituents of the dried rhizome of. L. chuanxiong. The dried rhizome of L. chuanxiong was extracted with 60 % ethanol, and the concentrated extract was isolated by silica gel, octadecyl silane, and Sephadex LH-20 columns, followed by preparative/semipreparative high-performance liquid chromatography (HPLC) to obtain the pure chemical constituents. The structures of the constituents were elucidated by HR-ESI-MS, UV, IR, 1D NMR, and 2D NMR methods. Enantiomeric separation was achieved by a chiral HPLC method. The absolute configuration was determined by the modified Mosher's method. Six novel phthalide derivatives, (+)/(-)-chuanxiongins A-F (1-6), together with four known phthalides (7-10) were isolated from Chuanxiong. All of the new compounds (1-6) were present as pairs of enantiomers. Enantiomeric separation of 1 was successfully achieved by HPLC on a chiral column. The absolute configuration of (-)-1 was determined by a modified Mosher's method. The six novel phthalide derivatives (1-6) isolated from Chuanxiong were phthalide fatty acid esters that were structurally analogous and characterized by fatty acid acylation at 6-OH or 7-OH.


Expert opinion and controversies in musculoskeletal and sports medicine: femoroacetabular impingement.
Femoroacetabular impingement (FAI) has been proposed as a distinct clinical entity that may be a potentially significant cause of hip osteoarthritis (OA). There is a growing body of literature on this condition, including descriptions of biomechanic mechanisms of impingement, anatomic and radiographic findings, and surgical interventions. Although a connection between anatomic abnormalities of the hip and the development of OA has been recognized for some time, there are limited data on the natural history of FAI and no long-term studies on the effect of surgical treatment. Thus, the diagnosis engenders a degree of controversy in multiple regards, including the diagnostic criteria and the role of operative intervention.


[Monoclonal gammopathy of uncertain significance].
Monoclonal gammopathy of uncertain significance is a premalignant plasma cell neoplasm with a high prevalence in the population over 50 years of age and an annual risk of progression of 1%. Multiple recent studies have led to advances in understanding both the pathogenesis of these disorders and their risk of progression to other diseases. Patients require lifelong follow-up, and a multidisciplinary and risk-adapted approach is essential. In recent years, an increasing number of entities associated with a paraprotein, known as clinically significant monoclonal gammopathies, have been recognized.


An in-house centrifugation and membrane filtration technique for identifying microorganisms from positive blood culture bottles with high identification rates using matrix-assisted laser desorption ionization-Time-of-flight mass spectrometry: A preliminary report.
Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is one of the most promising technologies for the identification of microbial pathogens directly from positive blood culture bottles. As blood culture bottle medium contains various nonbacterial proteins, including those derived from blood cells, pretreatment to effectively remove host cells is key for successful proteome-based identification of microorganisms. Although the Sepsityper® kit is the most widely used pretreatment protocol, its performance is not satisfactory, particularly for gram-positive isolates. We developed a new in-house protocol, the centrifugation and membrane filtration technique (CMFT), in which vacuum-filtration is coupled with differential centrifugation. We prospectively evaluated the performance of this novel method compared with that of the Sepsityper®. For gram-negative bacterial isolates, the species-level identification rates obtained with the CMFT and the Sepsityper® were comparable (98.8% vs 92.9%). By contrast, for gram-positive isolates, the performance of the CMFT was significantly better than that of the Sepsityper® (P < 0.05). Using our new protocol, 81 (95.3%) isolates were identified with a score >2.0, and 85 (100%) isolates were identified with a score >1.7, versus 46 (54.1%) and 69 (81.2%), respectively, for the Sepsityper®. These results are preliminary, but considering that this novel protocol provides notably high species-level identification rates for gram-positive isolates, it deserves assessment in a larger-scale study with a variety of platforms for MS-based identification of microorganisms.


Cryopreservation of the rabbit cornea: freezing with dimethyl sulphoxide in air or in medium.
There have been considerable difficulties in developing a satisfactory method for the cryopreservation of corneas. In this paper we describe the effect of two variables that appear to influence the effectiveness of preservation, the concentration of cryoprotectant and the medium that surrounds the cornea during freezing. Rabbit corneas were exposed to the cryoprotectant dimethyl sulphoxide (Me2SO) in concentrations of 1 or 2 mol/l in a high-potassium well-buffered solution, and then cooled to -196 degrees C either in air or surrounded by 5 ml of the Me2SO solution. After storage at -196 degrees C, thawing and removal of the Me2SO, survival was assessed by electron microscopy and measurement of stromal thickness during perfusion on the specular microscope. The least degree of damage was observed when corneas were equilibrated with 1M Me2SO and frozen in air. The evidence suggests that 2M may be an excessive concentration of Me2SO in this system and that damage to the stroma may be reduced by freezing the cornea in air rather than surrounded by the Me2SO solution.


Indirect fluorescent antibody test for the detection of antibodies to Echinococcus granulosus in experimentally infected pups.
Adult parasites of Echinococcus granulosus of buffalo origin were used as antigen in the indirect fluorescent antibody test (IFA) for detection of antibodies to E. granulosus in experimentally infected pups. The technique permitted detection of antibodies on Day 5 post-infection (p.i.) and up to Day 80 p.i. in infected animals. The antigen-antibody reaction was characterized by the appearance of a specific brilliant greenish yellow fluorescence on the embryophore of mature eggs present within and outside the gravid segment of the cestode. A maximum antibody titre of 1:320 at Day 50 p.i. was observed in the infected pups, coinciding with maturation of adult worms in the intestine of the host.


Face masks: a COVID-19 protector or environmental contaminant?
Face masks, a prime component of personal protective equipment (PPE) items, have become an integral part of human beings to survive under the ongoing COVID-19 pandemic situation. The global population requires an estimated 130 billion face masks and 64 billion gloves/month, while the COVID-19 pandemic has led to the daily disposal of approximately 3.5 billion single-use face masks, resulting in a staggering 14,245,230.63 kg of face mask waste. The improper disposal of face mask wastes followed by its mismanagement is a challenge to the scientists as the wastes create pollution leading to environmental degradation, especially plastic pollution (macro/meso/micro/nano). Each year, an estimated 0.15-0.39 million tons of COVID-19 face mask waste, along with 173,000 microfibers released daily from discarded surgical masks, could enter the marine environment, while used masks have a significantly higher microplastic release capacity (1246.62 ± 403.50 particles/piece) compared to new masks (183.00 ± 78.42 particles/piece). Surgical face masks emit around 59 g CO2-eq greenhouse gas emissions per single use, cloth face masks emit approximately 60 g CO2-eq/single mask, and inhaling or ingesting microplastics (MPs) caused adverse health problems including chronic inflammation, granulomas or fibrosis, DNA damage, cellular damage, oxidative stress, and cytokine secretion. The present review critically addresses the role of face masks in reducing COVID-19 infections, their distribution pattern in diverse environments, the volume of waste produced, degradation in the natural environment, and adverse impacts on different environmental segments, and proposes sustainable remediation options to tackle environmental challenges posed by disposable COVID-19 face masks.


Excitation functions of the Zn(p,xn)Ga reactions.
The excitation functions for 64,66,67,68,70Zn(p,n)64,66,67,68,70Ga and 64,66,67,68,70Zn(p,2n)63,65,66,67,69Ga have been calculated for incident proton energies from threshold values to 30 MeV using the statistical model code TALYS-1.6. The (p,n) and (p,2n) cross sections have been calculated using both phenomenological Koning and Delaroche (KD) and semimicroscopic Jeukenne-Lejeune-Mahaux-Bruyeres (JLMB) optical model potentials. The phenomenological back-shifted Fermi gas model (BFM) and microscopic Hartree-Fock (HF) approaches for calculation of level densities have been compared in the present work. The pre-equilibrium process has been treated using exciton model. The sensitivity of cross section data to different models of optical model potential and level density have been investigated. It is found that the (p,n) and (p,2n) cross section calculations with semimicroscopic JLMB optical model potential and microscopic HF level density show agreement with the data. The (p,n) and (p,2n) cross section calculations have been compared with corresponding cross sections from nuclear data library, TENDL-2019. The (p,xn) cross sections obtained will be useful in several applications, particularly, for optimization of production routes for Ga isotopes.


Spectropotentiometric analysis of metal binding to structural zinc-binding sites: accounting quantitatively for pH and metal ion buffering effects.
Studies of the metal-binding affinity of protein sites are ubiquitous in bioinorganic chemistry and are valuable for the information that they can provide about metal speciation and exchange in biological systems. The potential for error in these studies is high, however, since many competing equilibria are present in solution and must be taken into consideration. Here, we report a new spectropotentiometric titration apparatus that allows pH and UV-vis absorption to be monitored simultaneously on small samples under inert atmosphere. In addition, we explain how data obtained from the complex equilibria can be combined with tabulated information about the protonation and metal-binding constants for common buffers to provide detailed, quantitative information about metal-protein interactions. Application of this approach to the investigation of metal binding to structural zinc-binding domains and common pitfalls encountered when performing these experiments are also discussed. We have used this approach to reevaluate the metal-binding constants of the N-terminal zinc-binding peptide from the HIV-1 nucleocapsid protein (10(-8)M</=K(d)(Co)</=10(-7)M; 10(-11)M</=K(d)(Zn)</=10(-10)M).


Identification of astrocyte- and oligodendrocyte-like cells of goldfish optic nerves in culture.
Fish glial cells were obtained from cultivated segments of the optic nerve and raised in vitro. Two types of cells were identified as astrocyte- and oligodendrocyte-like glia by the monoclonal antibody Mab O1 (specific for oligodendrocytes) and the rabbit serum anti-goldfish glial fibrillary acidic protein (anti-G-GFAP). Cells of compact morphology were rare, and anti-G-GFAP positive and O1 negative. Multipolar cells in 5-day-old cultures were anti-G-GFAP but rarely O1 positive. In 5-week-old cultures, however, roughly 75% of the multipolar cells were double-labeled with both anti-G-GFAP and O1; 10% were single labeled with Mab O1 and 15% with anti-G-GFAP, respectively.


Network effects of glutamate on neuronal activity in the medial septum/diagonal band complex in vitro.
Inter-neuronal interactions within the medial septum/diagonal band complex (MSDB) are of great interest as this region is believed to be the hippocampal theta rhythm pacemaker. However, the role of glutamatergic system in functioning of the septal cells is yet unclear. Here, we demonstrate for the first time the effects of glutamate in physiological concentration (1 microM) on the MSDB neuronal spontaneous and evoked activities in vitro. These effects (activation of 70% and inhibition of 30% of responsive neurons) differed in pacemaker and non-pacemaker cells. Pacemaker cells were always activated under glutamate, whereas non-pacemaker neurons could be either activated or inhibited. Indeed, in the burst pacemakers, glutamate increased the frequency of rhythmic activity. In a total MSDB neuron population, in 30% of neurons glutamate applications modified responses to the electrical stimulation by unifying the temporal parameters of neuron responses. Along with the increase in the theta-burst frequency, this indicates that the glutamatergic system is involved in the process ofintraseptal synchronization. Obtained data shed light on the role ofglutamatergic system in septal neuron interactions and broaden our understanding of theta oscillation mechanisms in the septo-hippocampal system.


Impact of lambda-cyhalothrin on a macroinvertebrate assemblage in outdoor experimental channels: implications for ecosystem functioning.
In this study, the impact of a single pulse of the pyrethroid lambda-cyhalothrin was tested on a macroinvertebrate assemblage consisting of Gammarus pulex, Leuctra nigra, Heptagenia sulphurea and Ancylus fluviatilis in outdoor experimental stream channels. Channels (4m long, 0.1m wide) were groundwater fed and had natural substratum. Macroinvertebrates were exposed to 10.65 or 106.5 ng L(-1) lambda cyhalothrin for 90 min in the laboratory and after 24h introduced to the experimental stream channels with four replicates of each treatment and controls. Drift samples were taken with 24-h interval for 10 days and behaviour of drifted macroinvertebrates was assessed. Microalgae biomass was measured on days 1, 5, 8 and 10 along with leaf litter decomposition using leaf packs of beech (Fagus sylvatica). Numbers of drifting G. pulex and L. nigra with reduced mobility increased significantly with concentration of lambda-cyhalothrin. Increase of algal biomass was significantly greater in stream channels with macroinvertebrates exposed to 106.5 ng L(-1) compared to controls and 10.65 ng L(-1) treatments. Accrual of microalgal biomass was significantly higher in the high concentration treatment and decomposition of leaf litter was significantly greater in control channels compared to channels with exposed macroinvertebrates. This study may apply valuable knowledge to the understanding and assessment of how pyrethroids impact ecosystem functioning in streams.


Mechanisms and therapeutic implications of cellular senescence in osteoarthritis.
The development of osteoarthritis (OA) correlates with a rise in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) has been implicated in cartilage degradation and OA. Age-related mitochondrial dysfunction and associated oxidative stress might induce senescence in joint tissue cells. However, senescence is not the only driver of OA, and the mechanisms by which senescent cells contribute to disease progression are not fully understood. Furthermore, it remains uncertain which joint cells and SASP-factors contribute to the OA phenotype. Research in the field has looked at developing therapeutics (namely senolytics and senomorphics) that eliminate or alter senescent cells to stop disease progression and pathogenesis. A better understanding of how senescence contributes to joint dysfunction may enhance the effectiveness of these approaches and provide relief for patients with OA.


Effect of Ajwa date pits powder (Phoenix dactylifera L.) on body composition, lipid profile and blood pressure in patients with hyperlipidemia: A randomized clinical trial.
To evaluate the effect of Ajwa dates pit powder (ADP) on lipid profile, body composition and blood pressure in patients with hyperlipidemia. This randomized controlled clinical study was carried out on 40 patients with total cholesterol >200 mg/dl, triglycerides >150 mg/dl and BMI >25, of either sex, aged 30-50 years, who were recruited through written consent. The patients were divided into two groups (n=20 each): the ADP and the control group (CG). All patients received the doctor's prescribed class A statin (Rosuvastatin/ Atorvastatin) 10 mg/day, while 2.7 g ADP was given on daily basis before breakfast with lukewarm water for 40 days and the control group received the same amount of wheat flour. Body composition, blood pressure and lipid profile were determined at baseline, and after 20 and 40 days. Data were analyzed by using SPSS and GraphPad Prism. ADP significantly reduced body weight (p<0.001), BMI (p<0.001), fat mass, body fat percentage, visceral fat area and waist circumference compared to the control group. Similarly, ADP significantly (p=0.000) decreased the serum level of total cholesterol and low-density lipoprotein. ADP may have the potential to improve dyslipidemia and obesity.


Fibroblast-epithelial metabolic coupling in laryngeal cancer.
To explore the Fibroblast-epithelial metabolic coupling among laryngeal cancers and its prognostic roles METHODS: We reviewed the clinical information of patients with laryngeal cancer in our department. Paraffin-embedded tissues from included patients were immune-stained with antibodies towards MCT4 and TOMM20 and evaluated for stromal and epithelial expression. Survival analysis and Cox regression analysis were applied to investigate the prognostic factor of laryngeal squamous cell carcinoma. TCGA database was used to validate our result. Stromal MCT4 and TOMM20 were both significantly associated with each other among laryngeal cancer tissues. High expression of both Stromal MCT4 and TOMM20 is related to poor prognosis in laryngeal cancer. Stromal MCT4 expression was an independent prognostic indicator for laryngeal cancer. Furthermore, cancer cell MCT4 expression has no relationship with the clinical characteristics of laryngeal cancer. Our results support that the phenomenon of metabolic symbiosis was exist in the laryngeal cancer tissue. In addition, TOMM20 and stromal MCT4 could be used as new therapeutic targets for laryngeal cancer.


Prolactin-secreting pituitary microadenoma: detection and evaluation.
Eleven women with secondary amenorrhea associated with hyperprolactinemia were studied. Base line evaluations, visual field determinations, and routine sella turcica x-rays were normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were carried out. These studies included polytomography of the sella turcica; dynamic pituitary testing of growth hormone reserve, adrenocorticotropic hormone reserve, and gonadotropin reserve; and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are utilized. The most sensitive diagnostic indices available are (1) polytomography, (2) the magnitude of the plasma prolactin elevation, and (3) the failure to suppress prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.


Purulent meningitis and secondary epilepsy caused by Mycobacterium iranicum infection: A case report.
Mycobacterium iranicum is characterized by rapid growth and orange-pigmented scotochromogenic colonies. However, it is uncommon for M. iranicum to invade the central nervous system. A man nearly 60 years old was referred to our hospital because of a seizure and unconsciousness. After admission, the patient had fever and dizziness without obvious abnormalities in the cerebrospinal fluid, except for an increase in neutrophils. Metagenomic next-generation sequencing and DNA testing were positive for M. iranicum. The patient was treated with imipenem, minocycline, moxifloxacin, and linezolid, and he gradually recovered during follow-up.


[Primary Salmonella vascular graft infection and conservative treatment].
The authors report an unusual case of prosthetic vascular graft infection due to Salmonellatyphimurium. The initial treatment combined antibiotherapy and surgical replacement of the arteriovenous graft. The infection relapsed within 6 weeks and was successfully treated with antibiotics only. Five cases of vascular graft infection due to Salmonella have been reported so far, but only one occurred in a previously healthy man and was not related to local infection, but to bacteremic seeding. Specific features of vascular graft infection and importance of prevention are discussed.


The origin of the exceptionally low activation energy of oxygen vacancy in tantalum pentoxide based resistive memory.
It is well known that collective migrations of oxygen vacancies in oxide is the key principle of resistance change in oxide-based resistive memory (OxRAM). The practical usefulness of OxRAM mainly arises from the fact that these oxygen vacancy migrations take place at relatively low operating voltages. The activation energy of oxygen vacancy migration, which can be inferred from the operational voltage of an OxRAM, is much smaller compared to the experimentally measured activation energy of oxygen, and the underlying mechanism of the discrepancy has not been highlighted yet. We ask this fundamental question in this paper for tantalum oxide which is one of the most commonly employed oxides in OxRAMs and try the theoretical answer based on the first-principles calculations. From the results, it is proven that the exceptionally large mobility of oxygen vacancy expected by the switching model can be well explained by the exceptionally low activation barrier of positively charged oxygen vacancy within the two-dimensional substructure.


Little genetic structure in a Bornean endemic small mammal across a steep ecological gradient.
Janzen's influential "mountain passes are higher in the tropics" hypothesis predicts restricted gene flow and genetic isolation among populations spanning elevational gradients in the tropics. Few studies have tested this prediction, and studies that focus on population genetic structure in Southeast Asia are particularly underrepresented in the literature. Here, we test the hypothesis that mountain treeshrews (Tupaia montana) exhibit limited dispersal across their broad elevational range which spans ~2,300 m on two peaks in Kinabalu National Park (KNP) in Borneo: Mt Tambuyukon (MT) and Mt Kinabalu (MK). We sampled 83 individuals across elevations on both peaks and performed population genomics analyses on mitogenomes and single nucleotide polymorphisms from 4,106 ultraconserved element loci. We detected weak genetic structure and infer gene flow both across elevations and between peaks. We found higher genetic differentiation on MT than MK despite its lower elevation and associated environmental variation. This implies that, contrary to our hypothesis, genetic structure in this system is not primarily shaped by elevation. We propose that this pattern may instead be the result of historical processes and limited upslope gene flow on MT. Importantly, our results serve as a foundational estimate of genetic diversity and population structure from which to track potential future effects of climate change on mountain treeshrews in KNP, an important conservation stronghold for the mountain treeshrew and other montane species.


Pharmacokinetics of phenobarbital in childhood.
In 14 neonates 1-4 weeks old, 30 babies aged 1-12 months, and 7 infants of 1-5 years of age, the serum levels of phenobarbital were determined by a gas chromatographic micro-method after intravenous injection of phenobarbital 5-10 mg per kg body weight. It was possible to calculate the pharmacokinetic parameters using a two compartment open model. The distribution volumes within the individual age groups and the rate constants k12 and k21 showed no significant differences, but the elimination half-life was significantly longer in neonates (118.6+/-16.1h) than in babies (62.9+/-5.2h) or infants (68.5+/-3.2h).


Sympathetic innervation of the cornea from the superior cervical ganglion. An HRP study in the cat.
Horseradish peroxidase (HRP) was applied to the cornea in cats using a variety of methods. Small numbers of labeled neurons were observed in the superior cervical ganglion (SCG), the majority were located in the rostral half. This confirms previous histofluorescence data which indicated the SCG was the likely source of adrenergic fibers to the cornea.


Prevention of thrombophlebitis in spinal injury patients.
This paper deals with the prevention of thrombophlebitis by means of massage and elastic stocking compression. In a group of 26 patients no evidence of thrombophlebitis or pulmonary embolism was observed.


Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.
Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016.


Impact of Prolonged Operative Duration on Postoperative Symptomatic Venous Thromboembolic Events After Thoracolumbar Spine Surgery.
To determine the effect of operative duration on the rate of postoperative symptomatic venous thromboembolic (VTE) events in patients undergoing thoracolumbar spine fusion. We identified all thoracolumbar spine fusion patients between 2012 and 2021. Operative duration was defined as time from skin incision to skin closure. A 1:1 propensity match was conducted incorporating patient and surgical characteristics. Logistic regression was performed to assess predictors of postoperative symptomatic VTE events. A receiver operating characteristic curve was created to determine a cutoff time for increased likelihood of VTE. We identified 101 patients with VTE and 1108 patients without VTE. Seventy-five patients with VTE were matched to 75 patients without VTE. Operative duration (339 vs. 262 minutes, P = 0.010) and length of stay (5.00 vs. 3.54 days, P = 0.008) were significantly longer in patients with a VTE event. Operative duration was an independent predictor of VTE on multivariate regression (odds ratio: 1.003, 95% confidence interval: 1.001-1.01, P = 0.021). For each additional hour of operative duration, the risk of VTE increased by 18%. A cutoff time of 218 minutes was identified (area under the curve [95% confidence interval] = 0.622 [0.533-0.712]) as an optimal predictor of increased risk for a VTE event. Operative duration significantly predicted symptomatic VTE, especially after surgical time cutoff of 218 minutes. Each additional hour of operative duration was found to increase VTE risk by 18%. We also identify the impact of VTE on 90-day readmission rates, suggesting significantly higher costs and opportunity for hospital acquired conditions, in line with prior literature.


Tumour angiogenesis.
A variety of different factors has been implicated in inducing angiogenesis. Their identity and precise mechanisms of action remain elusive. The present treatise summarises the state of our knowledge not only in relation to tumour-induced capillary growth but also for non-neoplastic situations and mechanisms.


Strain variation in the frequency of Abelson murine leukemia virus-transformed fetal liver pre-B cells bearing complete immunoglobulin heavy chain rearrangements.
Fetal liver Abelson pre-B cell lines obtained from CBA/Tufts.xid and (CBA/Tufts.xid x CBA/Tufts)F1 mice have complete VDJH rearrangements on at least one allele. Such high frequencies of VDJH rearrangements have previously been observed in adult derived but not fetal liver derived Abelson pre-B cell lines. Genetic analyses suggest that CBA/Tufts.xid carries an autosomal dominant gene(s) that determines the predominance of VDJH rearrangements among transformants. This autosomal gene(s) might affect the intrinsic development of the early B cell lineage in the fetus or the fetal microenvironment, expanding pre-B cells of the "more mature" VDJH phenotype.


Serial evaluation of atrial tachyarrhythmia burden and frequency after implantation of a dual-chamber cardioverter-defibrillator.
Serial evaluation of AT burden and frequency after implantation of D-ICD. We sought to characterize atrial tachyarrhythmia (AT) burden and frequency after implantation of a dual-chamber implantable cardioverter-defibrillator (D-ICD). A total of 149 subjects underwent implantation of a D-ICD (Jewel AF model 7250, Medtronic, Inc.) for the primary indication of drug-resistant AT, and were followed for at least 12 months during which device programming was constant. The device employed atrial overdrive pacing as well as shocks to terminate episodes of AT. Arrhythmia burden and frequency were evaluated during the 0- to 6-month follow-up and and 6- to 12-month follow-up intervals. A majority of subjects (62%) received a type I/III antiarrhythmic drug during follow-up. The median arrhythmia burden decreased from 8.2 hours/month during 0-6 months to 3.3 hours/month during 6-12 months (P=0.004); this result was driven primarily by the subgroup with persistent AT prior to device implantation. There was no significant change in the median AT frequency (2.2 vs 1.0 episodes/month). There was a significant decrease in the median shock frequency (0.32 vs 0.00 shocks/month, P=0.003) and an increase in shock efficacy (85.5% vs 94.9%, P=0.01). Device-based treatment of AT, in association with antiarrhythmic drugs, yields a significant time-dependent decrease in AT burden but not frequency.


Masson trichrome stain helps differentiate myofibroma from smooth muscle lesions in the head and neck region.
Myofibromas are well described in the head and neck region, but differentiating them from smooth muscle lesions is still difficult using smooth muscle immunohistochemical stains. This study evaluated the usefulness of the Masson trichrome stain in differentiating myofibromas from smooth muscle lesions in the head and neck region. Samples of 11 oral myofibromas, two leiomyomas, one angioleiomyoma, and one smooth muscle hamartoma were retrieved from our archives. Immunohistochemistry and Masson trichrome stains were performed on tissue sections of these lesions. All 11 oral myofibromas, seven from male patients and four from female patients, were solitary myofibromas. The patients' mean age at diagnosis was 32.8 years. Oral myofibromas occurred most commonly on the gingiva (four cases) and in the mandible (three cases). With the Masson trichrome stain, the smooth muscle cell cytoplasm was stained red, while the collagenous fibrous tissue was stained blue. Myofibromas and smooth muscle lesions demonstrated different characteristic patterns with the Masson trichrome stain. Myofibromas were composed of a much more collagenous stroma intermixed with the spindle cells. Thick fibrous bundles with random, irregularly intersecting angles were prominent in myofibromas. Smooth muscle lesions showed only minimal delicate fibrous tissue surrounding the smooth muscle cells and in the septa between the smooth muscle masses. On low-power view, red masses of smooth muscle tumor surrounded by blue fibrous tissue were observed. The Masson trichrome stain can be a useful tool to differentiate myofibromas from smooth muscle lesions, but immunohistochemical methods to rule out other spindle cell lesions are still needed.


Ocular pathology in shaken baby syndrome and other forms of infantile non-accidental head injury.
Retinal and optic nerve sheath hemorrhages are an essential part of the various forms of inflicted neurotrauma in infants, especially in its most common variant, the shaken baby syndrome (SBS). Clinically, ophthalmologists play an important part for the diagnosis and further management of patients with SBS. For the forensic pathologist, a thorough understanding of the basic principles behind the morphological phenomena commonly encountered in the orbita is required. This review summarizes the present knowledge of ocular pathology in inflicted infantile neurotrauma, focusing strongly on SBS. Furthermore, a review of the most recent literature on the subject is given.


Diaphragm pacing. Evaluation of current waveforms for effective ventilation.
To evaluate the effectiveness of the configuration of the stimulating waveform on diaphragm pacing, we evaluated several different current forms: UDC-bipolar, UDC-monopolar cathodal, UDC-monopolar anodal, and ABDC. During stimulation with a pulse interval of 37 msec., a decrease in tidal volume was observed during the initial 30 hours with UDC-bipolar and UDC-monopolar anodal waveforms. Both UDC-monopolar cathodal and ABDC stimulation maintained the initial effectiveness for 6 hours. The decrease in tidal volume of UDC-monopolar anodal closely paralleled that of UDC-bipolar stimulation. Decreasing the pulse interval to 20 msec. caused a decrease in tidal volume with both UDC-monopolar cathodal and ABDC waveforms. Arterial oxygen tension (PaO2) in these experiments decreased to about 60 mm. Hg soon after the onset of unilateral diaphragm pacing. The concomitant decrease in tidal volume seen with UDC-bipolar stimulation could be avoided through the administration of oxygen to keep the animal's PaO2 about 100 mm. Hg. The amplitude of the evoked diaphragmatic action potentials decreased significantly under hypoxemia and returned to normal with hyperoxygenation. From these short-term experiments, our findings indicate that waveform configuration does influence the time of onset of diaphragm fatigue due to either an neuromuscular junction. Further, hypoxemia accelerates the occurrence of fatigue.


[Biochemical parameters of blood plasma of the harp seal Pagophilus groenlandicus Erxleben, 1777 (Pinnipedia, Procidae) of various ages].
Results of study of several blood biochemical parameters of the harp seal Pagophilus groenlandicus Erxleben, 1777, from birth to the adult state are presented. The following age groups of the animals have been studied--newborns, 1.5-2 months, 1 year, 2 years, 3 years, and adults (older than 6 months). The content of total protein and its fractions, free amine nitrogen, urea, creatinine, glucose, total lipids, total calcium, and inorganic phosphorus was determined in the seal blood plasma. Differences of the degree of expression of levels of all studied parameters in the course of early postnatal ontogenesis of the animals have been established. The most significant metabolic changes in the harp seals were revealed at the period of end of weaning and transition to independent ingestion and then after the first year of life.


Emergence and prevention of resistance against small molecule inhibitors.
Small molecule inhibitors target specific metabolic pathways in tumor cells and are a promising class of drugs for the treatment of cancers. The best known example is the treatment of chronic myeloid leukemia (CML) with Gleevec. This is a small molecule inhibitor of the Bcr-Abl kinase which has been shown to drive the initiation and progression of CML. While treatment of early stage CML with Gleevec has been quite successful, later stages of the disease (blast crisis) are not successfully treated due to the emergence of drug resistant cells. It is therefore important to understand the principles according to which drug resistant cells evolve, so that we can design treatment strategies which aim to prevent the rise of resistant cells. Such evolutionary dynamics can be studied with mathematical models, and this article reviews such an approach. We address three specific questions: (i) Do resistant cells emerge before or after the start of therapy? (ii) How does the turnover rate of cancer cells influence the evolution of drug resistant cells? (iii) Can combination therapy be used to prevent drug resistance? We apply our model to the treatment of CML with Gleevec, in order to demonstrate how this mathematical framework can be applied to the treatment of a specific cancer with small molecule inhibitors.


Automated analysis of hydroxyproline with elimination of non-specific reacting substances.
A modified urinary hydroxyproline method is presented which utilizes an automated technique, Technicon instrumentation and Ehrlich's reagent. Acid hydrolysates are neutralized automatically. Non-specific reacting substances are determined simultaneously with each sample and subtracted as a blank. This method has been found to be superior to the use of charcoal-resin as an absorbent. After blank correction, the mean hydroxyproline excretion of normal and osteoporotic patients are similar. In all groups studied, including Paget's disease, the blanks reresent a significant fraction of total reacting substances and show wide variation between samples. Multiple samples from patients over a two year period show little variation in hydroxyproline excretion when corrected for non-specific reacting substances.


Procedural (in)justice in children: Children choose procedures that favor their ingroup.
Research has shown that both ingroup bias and concern for procedural justice emerge early in development; however, these concerns can conflict. We investigated whether 6- to 8-year-old children are more influenced by procedural justice versus ingroup favoritism in a resource allocation task. In our first study, children played a novel spinner game in which they chose among fair, ingroup favoring, and outgroup favoring procedures to decide whether a resource would go to an unfamiliar ingroup or outgroup recipient. We found that 6- to 8-year-olds overall chose ingroup favoring procedures. However, this tendency decreased with age; whereas younger children were more likely to select procedures that were advantageous to their ingroup, older children (7- and 8-year-olds) mostly chose fair procedures. Our second study investigated the motivations underpinning children's choices by testing whether children's fair procedure choices were in part driven by a desire to appear fair. Here we varied whether children made procedure choices in public, allowing them to manage their reputation, versus in private, where reputational concerns should not guide their choices. We found that from 6 to 8 years of age children chose ingroup favoring procedures and that this tendency was slightly stronger when choosing in private. Taken together, our research suggests that ingroup favoritism often trumps procedural justice in resource allocation tasks, especially for younger children and especially when reputation is not in play.


Best practices guide statewide QI project.
Improvement was seen in activities of daily living, pain, and depression management. Multidiscipline team was employed to identify best practices. Participating nursing homes received technical assistance.


Some (Fish Might) Like It Hot: Habitat Quality and Fish Growth from Past to Future Climates.
Current expectation is that projected climate change may have adverse effects on fish habitats and survival. The analysis leading to these concerns is typically done at large scale with limited possibility to quantify the local biological response and compare with previous conditions. Our research investigated the effects of recorded climate conditions on Chinook salmon (Oncorhynchus tshawytscha) spawning and rearing habitats and growth responses to the local climate and compared those conditions to predicted responses to a climate change. The study site was a 7 km long reach of Bear Valley Creek, an important spawning stream for this US Endangered Species Act listed species, in the Pacific Northwest of United States. We used 2D numerical modeling supported by accurate, high-resolution survey data to calculate flow hydraulics at various discharges from base to bankfull flows. For past and future conditions, computed flow hydraulics were combined with habitat suitability indices (SI) to compute spawning and rearing habitat suitability. Information on habitat suitability along with fish density and stream water temperature informed a growth model to quantify the potential fish size, an index of survival rates and fitness. Our results indicate that yearly-averaged rearing habitat quality remains similar to historic, but the timing of high- and low-quality habitat periods shift within the calendar year. Future spawning habitat quality may be significantly reduced during the seasonal period to which Chinook have currently adapted their spawning behavior. The growth model indicates an increase in anticipated size of Chinook salmon for predicted future climate conditions due to water temperature increase. Consequently, future climate conditions may have a substantial negative impact on spawning and limited impact on rearing conditions due to flow reduction and thus quality and extent of available habitat. However, the expected warmer stream water temperatures may benefit rearing, because of increased fish size in these high elevation streams.


Neurotransmitters increase cyclic nucleotides in postganglionic neurons: immunocytochemical demonstration.
Dopamine increases adenosine 3',5'-monophosphate (cyclic AMP) but not guanosine 3',5'-monophosphate (cyclic GMP) in slices of bovine sympathetic ganglion; this increase is localized to the postganglionic neurons. Conversely, acetylcholine increases cyclic GMP but not cycle AMP in the ganglion; this increase also occurs within postganglionic neurons. Thus, different neurotransmitters can selectively alter cyclic nucleotide levels within the same neuronal population.


Severe adalimumab-induced thrombocytopenia in a patient with Crohn's disease.
Crohn's disease is a chronic transmural inflammatory disorder characterized by inflammation of the intestine. Anti-TNF-α drugs are used for induction and maintenance of remission in patients with this condition. Thrombocytopenia is an uncommon side effect of treatment with anti-TNF-α drugs. We report the case of a 71-year-old woman diagnosed with Crohn's disease who developed severe adalimumab-induced thrombocytopenia and who did not respond to standard therapy for thrombocytopenia.


Vaccinia virus K1L protein mediates host-range function in RK-13 cells via ankyrin repeat and may interact with a cellular GTPase-activating protein.
The K1L protein of vaccinia virus is required for its growth in certain cell lines (RK-13 and human). The cowpox host-range protein CP77 has been shown to complement K1L function in RK-13 cells, despite a lack of homology between the two proteins except for ankyrin repeats. We investigated the role of ankyrin repeats of K1L protein in RK-13 cells. The growth of a recombinant vaccinia virus, with K1L gene mutated in the most conserved ankyrin repeat, was severely impaired. Infection with the mutant virus caused shutdown of cellular and viral protein synthesis early in infection. We also investigated the interaction of K1L protein with cellular proteins and found that K1L interacts with the rabbit homologue of human ACAP2, a GTPase-activating protein with ankyrin repeats. Our result suggests the importance of ankyrin repeat for host-range function of K1L in RK-13 cells and identifies ACAP2 as a cellular protein, which may be interacting with K1L.


Observations about utilitarian coherence in the avian compass.
It is hypothesised that the avian compass relies on spin dynamics in a recombining radical pair. Quantum coherence has been suggested as a resource to this process that nature may utilise to achieve increased compass sensitivity. To date, the true functional role of coherence in these natural systems has remained speculative, lacking insights from sufficiently complex models. Here, we investigate realistically large radical pair models with up to 21 nuclear spins, inspired by the putative magnetosensory protein cryptochrome. By varying relative radical orientations, we reveal correlations of several coherence measures with compass fidelity. Whilst electronic coherence is found to be an ineffective predictor of compass sensitivity, a robust correlation of compass sensitivity and a global coherence measure is established. The results demonstrate the importance of realistic models, and appropriate choice of coherence measure, in elucidating the quantum nature of the avian compass.