Functional support and burden among out-of-home supporters of heart failure patients with and without depression.
Over 20% of patients with heart failure (HF) experience clinical depression, which is associated with higher rates of mortality, morbidity, and hospitalization. Support from family members or friends (whom we refer to as care partners [CPs]) can lower the risk of these outcomes. We examined whether HF patients with depression received assistance from CPs living outside of their homes. Further, we examined whether patient depression was associated with support-related strain among out-of-home CPs. We analyzed baseline survey data from 348 HF patients with reduced ejection fraction and their CPs. Patients with scores on the Center for Epidemiological Studies Depression Scale-10 (Kohout, Berkman, Evans, & Cornoni-Huntley, 1993) of ≥10 were classified as having clinically significant depressive symptoms (i.e., depression). Outcomes included CP-reported hr per week helping with health care and talking with patients via telephone and scores on the Modified Caregiver Strain Index. Negative binomial regression models examined differences in the amount of in-person and telephone support for patients with and without depression, controlling for patients' comorbidities, living alone, CP geographic distance, and CP emotional closeness to the patient. CPs provided more in-person support to HF patients with depression (M = 3.64 hr) compared with those without depression (M = 2.60 hr per week, incident rate ratio [IRR] = 1.40, p = .019). CPs provided more telephone support to patients with depression (M = 3.02 hr) compared with those without depression (M = 2.09 hr per week, IRR = 1.42, p < .001). Patient depression had no effect on caregiver burden (IRR = 1.00, p = .843). Patients with clinically significant depressive symptoms receive more in-person assistance and telephonic support from CPs. Despite that additional contact, caregiver burden was not greater among the supporters of depressed patients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Delayed immune mediated adverse effects to hyaluronic Acid fillers: report of five cases and review of the literature.
Hyaluronic acid (HA) fillers in cosmetic medicine have been considered relatively safe, though fillers used in European countries and throughout the world are not necessarily approved by the Food and Drug Administration. As their use continues to expand worldwide, physicians in a wide range of medical specialties are authorized to perform HA injections, including general medicine practitioners and even dentists. An increasing number of reports have appeared regarding side effects to these products. It is now known that reactions to Hyaluronic acid are related not only to technical faults of the injections, but also to immune responses, including delayed hypersensitivity and granulomatous reactions. Herein, we describe five cases treated by a variety of treatment modalities, all with delayed reactions to different brands of hyaluronic acid fillers. As there is currently no standardization of treatment options of adverse effects, these cases accentuate the debate regarding the approach to the individual patient and the possible need for pre-testing in patients with an atopic tendency.


Occurrence of long-chain fatty acids and glycolipids in the cell envelope fractions of baker's yeast.
1. The total yield of fatty acids from the whole envelopes was markedly higher than that obtained from the ordinary cell walls. In both samples the major fatty acids were C(16) and C(18) acids. 2. The whole envelopes contained C(18) acids and long-chain (C(19)-C(26)) fatty acids, in a higher proportion than did the ordinary cell walls. Fifteen fatty acids with more than 18 carbon atoms were identified, among which 2-hydroxy-C(26:0) and C(26:0) acids predominated. 3. A complex sphingolipid containing inositol, phosphorus and mannose was isolated from the whole cell envelopes. The main fatty acids of this lipid were 2-hydroxy-C(26:0) and C(26:0) acids. It was concluded that this sphingolipid is present both in the ordinary cell wall and in the plasma membrane of baker's yeast. 4. The neutral lipids amounted to over 50% and the glycerophosphatides to about 30% of the total fatty acid content of the whole envelope. The major fatty acids in these lipids were C(16:1), C(18:1) and C(16:0) acids. The proportion of fatty acids with more than 18 carbon atoms was lowest in the neutral lipids, whereas the neutral glycolipids contained the highest percentage of these fatty acids. Acidic glycolipids amounted to 14% of the total fatty acid content of the whole envelope. The presence of a cerebroside sulphate in this lipid fraction was demonstrated, whereas the high content of 2-hydroxy-C(26:0) acid found is caused by the complex inositol- and mannose-containing sphingolipid.


Reconstruction of 10 major mandibular defects using bioimplants containing BMP-7.
The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. A novel method of reconstruction was tested in this case series. Ten patients with major mandibular defects following resection of biopsy-proven ameloblastoma lesions or osteomyelitis of the mandibular body or ramus were included in this study. The resection defects were spanned with rigid reconstruction plates to hold the remaining mandibular segments in the correct position. The defects were filled with a bioimplant containing bone morphogenetic protein-7 (BMP-7) in a demineralized bone matrix (DBM) suspended in a reverse-phase medium to effect sustained BMP delivery. The postoperative course for all 10 patients was uneventful. Radiographic evidence of mandibular bone formation was found in all cases. At the end of 1 year, functional and esthetic reconstruction of the mandible was complete. Bioimplants containing BMP-7 in DBM suspended in a reverse phase medium were successful in restoring major mandibular defects in nonirradiated beds in this series of 10 patients.


Management of superior oblique palsy after surgery for true Brown's syndrome.
Thirty patients requiring surgery for true Brown's syndrome were examined postoperatively. Follow-up ranged from three months to 20 years. Eight-five percent of patients demonstrated some degree of superior oblique palsy, with 54% having a decompensated condition and 30% requiring a second surgical procedure. Patients with marked preoperative restriction appear to be at increased risk for developing a decompensated superior oblique palsy postoperatively. Solutions to this problem are suggested: 1) perform tenotomy at insertion and preserve the adjacent intermuscular septum so a less crippling effect is seen; 2) combine tenotomy with inferior oblique weakening initially in those patients with marked preoperative restriction.


Artificial selection for nonreproductive host killing in a native parasitoid on the invasive pest, Drosophila suzukii.
Establishment and spread of invasive species can be facilitated by lack of natural enemies in the invaded area. Host-range evolution of natural enemies augments their ability to reduce the impact of the invader and could enhance their value for biological control. We assessed the potential of the Drosophila parasitoid, Leptopilina heterotoma (Hymenoptera: Figitidae), to exploit the invasive pest Drosophila suzukii by focusing on three performance indices: (i) attack rate; (ii) host killing, consisting of killing rate and lethal attack rate (killing efficiency); and (iii) successful offspring development (reproductive success). We found significant intraspecific variation in attack rate and killing rate and lethal attack rate among seven European populations, but offspring generally failed to successfully develop from the D. suzukii host. We crossed these European lines to create a genetically variable source population and performed a half-sib analysis to quantify genetic variation. Using a Bayesian animal model, we found that attack rate and killing rate had a heritability of h 2 = 0.2 , lethal attack rate h 2 = 0.4 , and offspring development h 2 = 0 . We then artificially selected wasps with the highest killing rate of D. suzukii for seven generations to test whether host-killing could be improved. There was a small and inconsistent response to selection in the three selection lines. Realized heritability ( h r 2 ) after four generations of selection was 0.17 but near zero after seven generations of selection. The genetic response might have been masked by an increased D. suzukii fitness resulting from adaptation to laboratory conditions. Our study reveals that native, European, L. heterotoma can attack the invasive pest, D. suzukii and significantly reduce fly survival and that different steps of the parasitization process need to be considered in the evolution of host-range. It highlights how evolutionary principles can be applied to optimize performance of native species for biological control.


[Photoreceptor Transplantation into the Degenerative Retina].
Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models. This includes defining the necessary conditions, like the optimal ontogenetic stage of transplantable donor photoreceptors, cell-specific enrichment procedures and robust transplantation technologies. Moreover, first studies provided evidence for functional improvements by photoreceptor transplantation in mouse models of retinal dysfunction. Furthermore, advances in cell culture technology were made by introducing methods to generate photoreceptor-containing retinal organoids, derived from pluripotent stem cells, that provide theoretically unlimited sources for the production of photoreceptor transplants. Interestingly, the recently identified transfer of cytoplasmic material between donor and host photoreceptors might represent an additional treatment option for cell transplantation approaches. Within this review, we focus on the main developments within the photoreceptor transplantation field and discuss important achievements, challenges and hurdles to develop photoreceptor transplantation towards clinical applications.


On-line titrimetric monitoring of anaerobic-anoxic EBPR processes.
Denitrifying phosphorus accumulating organisms (DPAO) are able to remove nitrogen and phosphorus simultaneously. The use of DPAO in EBPR systems results in a substantial saving on aeration cost and a lower sludge production when compared to anaerobic-aerobic EBPR systems. This process is usually studied in sequencing batch reactors (SBR) and monitored with off-line measurements. However, off-line monitoring implies low frequency data sampling and delay between sampling and obtainment of the results. For this reason, an online measurement such as titrimetry is strongly recommended to improve the daily management of the lab-scale SBR. This paper shows different applications of titrimetric measurements for on-line monitoring of DPAO lab-scale SBR cycles. The results demonstrate that titrimetry is a suitable tool for detecting the end of phosphorus release and carbon substrate depletion point in the anaerobic phase. Moreover, this paper proposes the indirect measurement of nitrate/nitrite uptake rate with titrimetric measurements, which allows the on-line estimation of its concentration during the anoxic phase. Therefore, titrimetry is an on-line measurement with a high potential to implement new control strategies in DPAO lab-scale SBR systems.


Predictors and Outcomes of Pediatric Firearm Injuries Treated in the Emergency Department: Differences by Mechanism of Intent.
Firearm injuries among children are a major clinical and public health concern and one of the leading causes of pediatric fatalities. Our objective was to investigate differences in predictors and clinical outcomes between self-inflicted, violent, and unintentional pediatric firearm injuries for patients who present to pediatric emergency departments (EDs). We conducted a retrospective study of patients 0 to 21 years old treated in 37 pediatric academic EDs from 2004 to 2014. Patients were classified into the injury intent categories of self-inflicted, violent, and unintentional firearm injury using the International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) diagnoses and external causes of injury codes. Multivariable multinomial regression models compared groups. We identified 9,628 firearm injuries from 2004 to 2014: 109 (1%) self-inflicted, 2,394 (25%) violent, and 7,125 (74%) unintentional. Male sex, increasing age, nonwhite race, public insurance, residing in an urban zip code, and lower zip code-level median household income were all independently associated with violent firearm injuries, relative to self-inflicted and unintentional injuries. Self-inflicted injuries were at the highest risk for hospital admission, death, intensive care unit services, surgical services, and increased length of stay, followed by violent injuries with intermediate risk and unintentional injuries at the lowest risk Self-inflicted, violent, and unintentional firearm injuries in children had distinct demographic risk factors and clinical and utilization outcomes. Targeted prevention and intervention efforts should be developed to reduce the incidence and severity of these injuries.


Structure of polyglycerol oleic acid ester nonionic surfactant reverse micelles in decane: growth control by headgroup size.
The structure of polyglycerol oleic acid ester nonionic surfactant micelles in n-decane has been investigated at room temperature by small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and densiometry techniques. The scattering data were evaluated by indirect Fourier transformation (IFT) or generalized indirect Fourier transformation (GIFT) methods depending on the volume fractions of the surfactants and also by model fit. A simple route to the growth control of reverse micelles by headgroup size of the surfactant was investigated. Additionally, the dependence of reverse micellar structure (shape and size) on temperature, composition, and added water was also investigated. The indirect Fourier transformation gives the real space pair-distance distribution function, p(r): a facile way for the quantitative estimation of structure parameters of the aggregates. It was found that the size of the reverse micelles increases with increasing the headgroup size of the surfactant. Globular type of micelles with maximum diameter ca. 6 nm observed in the monoglycerol oleic acid ester/decane system at 25 degrees C transferred into elongated prolate type micelles with maximum diameter ca. 19.5 nm in the hexaglycerol oleic acid ester/decane system. In a particular surfactant and oil system, increasing temperature decreased the micellar size. The size of the micelle was decreased by approximately 25% upon increasing temperature from 25 to 75 degrees C in the 5 wt % diglycerol oleic acid ester/decane system. Concentration could not modulate the structure of micelles despite a wide variation in the surfactant concentration (5-25 wt %). Nevertheless, increasing surfactant concentration reduces the intermicellar distance, and a strong repulsive interaction peak was observed in the scattering curves at higher surfactant concentrations. Besides, the results obtained from the dynamic light scattering have shown the signature of diffusion hindrance relative to hard sphere with the surfactant concentration. Interestingly, the reverse micelles of the 10 wt % diglycerol oleic acid ester/decane system could incorporate approximately 1.2% water in the micellar core and cause a dramatic growth to the micelles size. The size of the water swollen micelles was approximately 40% bigger than the empty micelle.


Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.
Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.


Comparison of distortion-product otoacoustic emission growth rates and slopes of forward-masked psychometric functions.
Slopes of forward-masked psychometric functions (FM PFs) were compared with distortion-product otoacoustic emission (DPOAE) input/output (I/O) parameters at 1 and 6 kHz to test the hypothesis that these measures provide similar estimates of cochlear compression. Implicit in this hypothesis is the assumption that both DPOAE I/O and FM PF slopes are functionally related to basilar-membrane (BM) response growth. FM PF-slope decreased with signal level, but this effect was reduced or reversed with increasing hearing loss; there was a trend of decreasing psychometric function (PF) slope with increasing frequency, consistent with greater compression at higher frequencies. DPOAE I/O functions at 6 kHz exhibited an increase in the breakpoint of a two-segment slope as a function of hearing loss with a concomitant decrease in the level of the distortion product (L(d)). Results of the comparison between FM PF and DPOAE I/O parameters revealed only a weak correlation, suggesting that one or both of these measures may provide unreliable information about BM compression.


Three-dimensional printing in cardiology: Current applications and future challenges.
Three-dimensional (3D) printing has attracted a huge interest in recent years. Broadly speaking, it refers to the technology which converts a predesigned virtual model to a touchable object. In clinical medicine, it usually converts a series of two-dimensional medical images acquired through computed tomography, magnetic resonance imaging or 3D echocardiography into a physical model. Medical 3D printing consists of three main steps: image acquisition, virtual reconstruction and 3D manufacturing. It is a promising tool for preoperative evaluation, medical device design, hemodynamic simulation and medical education, it is also likely to reduce operative risk and increase operative success. However, the most relevant studies are case reports or series which are underpowered in testing its actual effect on patient outcomes. The decision of making a 3D cardiac model may seem arbitrary since it is mostly based on a cardiologist's perceived difficulty in performing an interventional procedure. A uniform consensus is urgently necessary to standardize the key steps of 3D printing from imaging acquisition to final production. In the future, more clinical trials of rigorous design are possible to further validate the effect of 3D printing on the treatment of cardiovascular diseases. (Cardiol J 2017; 24, 4: 436-444).


Magnetoconductance, Quantum Hall Effect, and Coulomb Blockade in Topological Insulator Nanocones.
Magnetotransport through cylindrical topological insulator (TI) nanowires is governed by the interplay between quantum confinement and geometric (Aharonov-Bohm and Berry) phases. Here, we argue that the much broader class of TI nanowires with varying radius-for which a homogeneous coaxial magnetic field induces a varying Aharonov-Bohm flux that gives rise to a nontrivial masslike potential along the wire-is accessible by studying its simplest member, a TI nanocone. Such nanocones allow us to observe intriguing mesoscopic transport phenomena: While the conductance in a perpendicular magnetic field is quantized due to higher-order topological hinge states, it shows resonant transmission through Dirac Landau levels in a coaxial magnetic field. Furthermore, it may act as a quantum magnetic bottle, confining surface Dirac electrons and leading to a largely interaction-dominated regime of Coulomb blockade type. We show numerically that the above-mentioned effects occur for experimentally accessible values of system size and magnetic field, suggesting that TI nanocone junctions may serve as building blocks for Dirac electron optics setups.


Immunologic and hematopoietic alterations by 2,450-MHz electromagnetic radiation.
A biphasic modulation of responsiveness of spleen lymphocytes to mitogens was observed in mice exposed to 2,450-MHz radiation at power densities of 5-15 mW/cm2 over various periods ranging between one and 17 days. This modulated phenomenon may be explained on the basis of 1) suppression of lymphocyte response to microwave-activated macrophages which persists throughout the entire course of radiation, and 2) concurrent progressive direct stimulation of lymphocytes which culminates around day 9 of exposure. Tumor cytotoxicity of killer lymphocytes from mice exposed to five or nine days of radiation did not appear different from sham controls. The highly proliferative hematopoietic marrow cells were sensitive to microwave radiation. Nine days of exposure to radiation (15 mW/cm2) reduced the colony-forming units of myeloid and erythroid series by 50%. This observation may offer a new and more sensitive assay for studying biological effects of electromagnetic radiation.


Percutaneous Retrieval of IVC Filters With Struts Penetrating the Vertebral Body.
Inferior vena cava (IVC) filter penetration of the caval wall is a well-documented complication. Less frequently, the struts of an IVC filter can penetrate a vertebral body that can lead to symptoms of abdominal pain. Vertebral penetration poses a management challenge, and characteristics for successful endovascular retrieval of such filters has not been reported. We present 2 cases of IVC filters with vertebral body penetration that were successfully retrieved through an endovascular approach. On preprocedure computed tomography, both patients had a small zone of osteolysis surrounding the penetrated struts into the vertebral body. The procedures were done via right internal jugular access using an Ensnare device. In one of the cases, the hangman technique was used to release the filter apex from the vessel wall. Both filters were able to be retrieved without using excessive force, follow-up venacavograms showed no sign of extravasation, and no postprocedure complications developed. Preprocedure CT imaging is essential prior to IVC filter removal if vertebral penetration is suspected. The zone of osteolysis seen around the struts in both cases are likely the result of constant cardiorespiratory motion of the filter. Based on the fact that in both cases the filter legs were able to be disengaged from the vertebral body without the use of excessive force, we hypothesize that if a zone of osteolysis surrounding the struts can be confirmed on preprocedural CT, the filter removal can be safely attempted by the standard percutaneous endovascular approach.


Role of Primary Care in Suicide Prevention During the COVID-19 Pandemic.
Primary care providers have an important role in suicide prevention, knowing that among people who die by suicide, 83% have visited a primary care provider in the prior year, and 50% have visited that provider within 30 days of their death, rather than a psychiatrist. The psychosocial impact of the coronavirus disease 2019 pandemic poses increased risk for suicide and other mental health disorders for months and years ahead. This article focuses on screening tools, identification of the potentially suicidal patient in the primary care setting, and a specific focus on suicide prevention during widespread, devastating events, such as a pandemic.


Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: results from the phase 3 CORAL study.
Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized 1:1 to once-daily, blinded zuranolone+ADT or placebo+ADT for 14 days, then continued open-label SOC ADT for 28 more days. The primary endpoint was change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 3. Among 425 patients in the full analysis set, CFB in HAMD-17 total score at Day 3 was significantly improved with zuranolone+ADT vs placebo+ADT (least squares mean [standard error], -8.9 [0.39] vs -7.0 [0.38]; p = 0.0004). The majority of patients receiving zuranolone+ADT that experienced treatment-emergent adverse events (TEAEs) reported mild or moderate events. The most common TEAEs present in ≥10% of patients in either zuranolone+ADT or placebo+ADT groups were somnolence, dizziness, headache, and nausea. These results demonstrate that zuranolone+ADT provided more rapid improvement in depressive symptoms compared with placebo+ADT in patients with MDD, with a safety profile consistent with previous studies. Clinical trial registration: ClinicalTrials.gov identifier: NCT04476030.


Correlates of inadequate sleep health among primary school children.
The aim of the present study was to explore potential factors of inadequate sleep health (i.e. sleep duration, quality, and timing) of school-aged children. Data were collected among 382 primary school children (aged 4-13 years) and their parents. Personal characteristics (i.e. age, sex), individual lifestyle behaviours (i.e. screen use, sleep hygiene behaviour), social and community factors (i.e. parental sleep-related practices, parental barriers, perceived ethnicity), and living conditions (i.e. parental educational level, sleep environment) were assessed with a parental questionnaire. Sleep duration, quality, and timing were assessed with a sleep diary. Associations were analysed using linear mixed models and logistic regression analyses. In total, 332 children, with a mean (range) age of 7.5 (4-13) years, were included in the analyses. The mean sleep duration was 632 min/night, the mean sleep quality score was 40, on a scale from 10 to 50, and 25% had a bedtime that varied >40 min between weekdays. Factors negatively associated with children's sleep health included older age, perceived non-Dutch cultural background, lower parental pre-sleep emotional support, the parental barrier to get their child to bed on time when siblings have a later bedtime, high parental educational level, sleeping in a darkened bedroom, and being brought to bed after falling asleep. On average, children in the present study had adequate sleep health. The factors found to be associated with children's sleep health are useful for future healthy sleep research and intervention development.


Association between the upper instrumented vertebra screw angles and proximal junctional complications in patients with de novo degenerative lumbar scoliosis.
The aim of this study was to investigate the impact of upper instrumented vertebra (UIV) screw angles on proximal junctional complications in patients with de novo degenerative lumbar scoliosis (DNDLS). A total of 120 patients with DNDLS who underwent posterior long-segment instrumentation and fusion were included. Patients were divided into a proximal junctional kyphosis/failure (PJK/PJF) group and a non-PJK/PJF group. Radiographic parameters were measured, including UIV screw angle, UIV slope, UIV screw slope, fixed segmental angle (FSA), and spinopelvic parameters. Clinical and radiographic data were compared between the two groups. Multivariate logistic regression was used to analyze the independent risk factors of PJK/PJF. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value to predict PJK/PJF. Thirty-six patients (30.0%) developed PJK or PJF during follow-up. Patients in the PJK/PJF group had a larger postoperative UIV screw angle, a larger postoperative UIV screw slope, and a larger postoperative PJA. A significant increase was observed in UIV screw angle from immediately postoperative assessment to the final follow-up in two groups (p < 0.001). Multivariate logistic analysis indicated that a larger positive postoperative UIV screw angle was an independent risk factor for PJK/PJF (OR 1.546, 95% CI 1.274-1.877). ROC curve analysis indicated that a UIV screw angle ≥ 1° is more likely to develop PJK/PJF. Compared with group A patients (UIV screw angle < 1°), group B patients (UIV screw angle ≥ 1°) had a higher incidence of PJK, PJF, UIV screw loosening, and worse functional scores at the final follow-up. Avoiding insertion of cranially directed UIV pedicle screws may help prevent the development of PJK and PJF in patients with DNDLS.


Two O-methyltransferases involved in the biosynthesis of methoxypyrazines: grape-derived aroma compounds important to wine flavour.
Methoxypyrazines (MPs) are volatile, grape-derived aroma compounds that contribute to the distinct herbaceous characters of some wines. Although the full pathway leading to MP production has not been elucidated, there is strong evidence that the final step involves the methylation of non-volatile hydroxypyrazine (HP) precursors. Two cDNA encoding O-methyltransferases (OMTs) that have homology to an enzyme previously purified and shown to catalyse the methylation of HPs were isolated from Cabernet Sauvignon. Recombinant protein from the cDNAs (VvOMT1 and VvOMT2) was produced in E. coli and activity assays demonstrated that both encode OMTs able to methylate HPs to produce MPs, however both showed greatest activity against the flavonol quercetin. VvOMT1 has higher catalytic activity against isobutyl hydroxypyrazine compared to isopropyl hydroxypyrazine, whereas the converse is true for VvOMT2. The timing of the expression of VvOMT1 in the skin and the flesh of developing Cabernet Sauvignon grape berries was associated with the period of MP accumulation in these tissues, while VvOMT2 expression was greatest in roots, which were found to contain high levels of MPs. The MP composition of these tissues also reflects the relative levels of expression of these genes and their substrate preference. The identification of genes responsible for MP production in grapevine will help in understanding the effect of different viticultural and environmental factors on MP accumulation.


[Efficacy on perennial allergic rhinitis treated with acupuncture at three nasal poinits and the acupoints selected by syndrome differentiation].
To compare the difference in the clinical efficacy on perennial allergic rhinitis between three nasal points acupuncture therapy and the oral administration of loratadine so as to provide the better acupuncture program in clinical treatment. Sixty cases were randomized into an acupuncture group (30 cases) and a medication group (30 cases). In the acupuncture group, acupuncture was applied to three nasal points [Yingxiang (LI 20), Yintang (EX-HN 3), Bitong (Extra)] and acupoints selected by syndrome differentiation. Acupuncture was given once every two days, three times a week, for 4 weeks totally. In the medication group, loratadine was prescribed for oral administration, 10 mg every day, for 4 weeks. The symptom and physical sign scores before and after treatment, as well the short-term and long-term efficacy were compared between the two groups. The total effective rate was 96.7% (29/30) in the acupuncture group and was 93.3% (28/30) in the medication group after treatment. The efficacy was similar between the two groups (P>0.05). In follow-up, the total effective rate was 86.7% (26/30) in the acupuncture group, which was better than 56.7% (17/30, P<0.05) in the medication group. The scores of symptoms and physical signs after treatment and in follow-up were all reduced apparently as compared with those before treatment in the patients of the two groups (all P<0.05). The scores of symptoms and physical signs were reduced more apparently in the acupuncture group as compared with those in the medication group in follow-up (all P<0.05). The acupuncture at three nasal points and the acupoints selected by syndrome differentiation achieves the similar short-term efficacy on perennial allergic rhinitis as compared with the oral administration of loratadine. The acupuncture therapy presents the obvious advantages on long-term efficacy.


Advanced-Glycation Endproducts: How cross-linking properties affect the collagen fibril behavior.
Advanced-Glycation-Endproducts (AGEs) are known to be a major cause of impaired tissue material properties. In collagen fibrils, which constitute a major building component of human tissue, these AGEs appear as fibrillar cross-links. It has been shown that when AGEs accumulate in collagen fibrils, a process often caused by diabetes and aging, the mechanical properties of the collagen fibril are altered. However, current knowledge about the mechanical properties of different types of AGEs, and their quantity in collagen fibrils is limited owing to the scarcity of available experimental data. Consequently, the precise relationship between the nano-scale cross-link properties, which differ from type to type, their density in collagen fibrils, and the mechanical properties of the collagen fibrils at larger scales remains poorly understood. In our study, we use coarse-grained molecular dynamics simulations and perform destructive tensile tests on collagen fibrils to evaluate the effect of different cross-link densities and their mechanical properties on collagen fibril deformation and fracture behavior. We observe that the collagen fibril stiffens at high strain levels when either the AGEs density or the loading energy capacity of AGEs are increased. Based on our results, we demonstrate that this stiffening is caused by a mechanism that favors energy absorption via stretching rather than inter-molecular sliding. Hence, in these cross-linked collagen fibrils, the absorbed energy is stored rather than dissipated through friction, resulting in brittle fracture upon fibrillar failure. Further, by varying multiple AGEs nano-scale parameters, we show that the AGEs loading energy capacity is, aside from their density in the fibril, the unique factor determining the effect of different types of AGEs on the mechanical behavior of collagen fibrils. Our results show that knowing AGEs properties is crucial for a better understanding of the nano-scale origin of impaired tissue behavior. We further suggest that future experimental investigations should focus on the quantification of the loading energy capacity of AGEs as a key property for their influence on collagen fibrils.


Airway management and perioperative concerns in acromegaly patients undergoing endoscopic transsphenoidal surgery for pituitary tumors.
Patients with acromegaly present unique challenges to cranial base surgery and anesthesia teams in the perioperative period, especially with regard to airway management. Abnormal airway anatomy may result from soft tissue hypertrophy and bony alterations. Additional perioperative challenges relate to the management of medical comorbidities. We aim to review perioperative airway concerns in acromegalic patients for the skull base surgeon in order to reduce preventable perioperative complications. Case series with chart review. Tertiary care academic institution. Thirty-two acromegaly patients undergoing endoscopic transsphenoidal pituitary surgery. Videoscopic direct laryngoscopy intubation was required in 7 of 32 patients (21.9%) and fiberoptic intubation in 4 of 32 patients (12.5%). Overall failure rate for first intubation technique used was 12.5% (4/32). Cardiovascular comorbidities (hypertension and conduction abnormalities predominated) were present in 16 of 32 patients (50%), and obstructive sleep apnea, or other respiratory conditions, existed in 12 of 32 patients (37.5%). Acromegaly patients present a particular challenge to the endoscopic skull base surgeon. Despite preoperative anesthesia and otolaryngology evaluation, many of these patients will experience an unanticipated airway challenge during intubation. Preoperative preparation and perioperative awareness of anatomic and physiologic abnormalities of acromegalic patients is essential for successful endoscopic surgery in this unique population.


Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging.
In women, the risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that menopausal type, natural versus surgical, or the age at natural menopause has on CVD needs further investigation. To this end, we assessed the association between menopausal type and timing and the 10-year office-based Framingham Risk Score (FRS) in women from the Canadian Longitudinal Study on Aging. We included women aged 45 to 85 years from the Canadian Longitudinal Study on Aging Comprehensive cohort of seven Canadian provinces who were menopausal at the time of recruitment and had no prior CVD. Poisson regressions were used to evaluate the association between menopausal characteristics and the FRS. Natural menopause was defined as the cessation of menstrual periods for at least 1 year in women with no history of hysterectomy. Surgical menopause was defined as hysterectomy with or without oophorectomy prior to natural menopause. As main covariates, we examined age, education, province of residency, and hormone therapy. A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. In the multivariable model, surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, P < 0.001). Compared with women with age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, P < 0.001). Our study supports an association between menopausal type and timing on CVD risk prediction and highlights the need to be judicious about surgical menopause. Preventative interventions for CVD should be considered in surgical menopausal women and women with an age at natural menopause less than 45 years.


Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study.
In a recent study, we showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double-blind double-dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective. Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.


Opportunities and challenges in developing a whole-of-government national food and nutrition policy: lessons from Australia's National Food Plan.
The present article tracks the development of the Australian National Food Plan as a 'whole of government' food policy that aimed to integrate elements of nutrition and sustainability alongside economic objectives. The article uses policy analysis to explore the processes of consultation and stakeholder involvement in the development of the National Food Plan, focusing on actors from the sectors of industry, civil society and government. Existing documentation and submissions to the Plan were used as data sources. Models of health policy analysis and policy streams were employed to analyse policy development processes. Australia. Australian food policy stakeholders. The development of the Plan was influenced by powerful industry groups and stakeholder engagement by the lead ministry favoured the involvement of actors representing the food and agriculture industries. Public health nutrition and civil society relied on traditional methods of policy influence, and the public health nutrition movement failed to develop a unified cross-sector alliance, while the private sector engaged in different ways and presented a united front. The National Food Plan failed to deliver an integrated food policy for Australia. Nutrition and sustainability were effectively sidelined due to the focus on global food production and positioning Australia as a food 'superpower' that could take advantage of the anticipated 'dining boom' as incomes rose in the Asia-Pacific region. New forms of industry influence are emerging in the food policy arena and public health nutrition will need to adopt new approaches to influencing public policy.


A single electroporation delivery of a DNA vaccine containing the hemagglutinin gene of Asian H5N1 avian influenza virus generated a protective antibody response in chickens against a North American virus strain.
Protection against the avian influenza (AI) H5N1 virus is suspected to be mainly conferred by the presence of antibodies directed against the hemagglutinin (HA) protein of the virus. A single electroporation delivery of 100 or 250 μg of a DNA vaccine construct, pCAG-HA, carrying the HA gene of strain A/Hanoi/30408/2005 (H5N1), in chickens led to the development of anti-HA antibody response in 16 of 17 immunized birds, as measured by a hemagglutination inhibition (HI) test, competitive enzyme-linked immunosorbent assay (cELISA), and an indirect ELISA. Birds vaccinated by electroporation (n = 11) were protected from experimental AI challenge with strain A/chicken/Pennsylvania/1370/1/1983 (H5N2) as judged by low viral load, absence of clinical symptoms, and absence of mortality (n = 11). In contrast, only two out of 10 birds vaccinated with the same vaccine dose (100 or 250 μg) but without electroporation developed antibodies. These birds showed high viral loads and significant morbidity and mortality after the challenge. Seroconversion was reduced in birds electroporated with a low vaccine dose (10 μg), but the antibody-positive birds were protected against virus challenge. Nonelectroporation delivery of a low-dose vaccine did not result in seroconversion, and the birds were as susceptible as those in the control groups that received the control pCAG vector. Electroporation delivery of the DNA vaccine led to enhanced antibody responses and to protection against the AI virus challenge. The HI test, cELISA, or indirect ELISA for anti-H5 antibodies might serve as a good predictor of the potency and efficacy of a DNA immunization strategy against AI in chickens.


Recent advances toward understanding the role of transplanted stem cells in tissue-engineered regeneration of musculoskeletal tissues.
Stem cell-based tissue engineering is poised to revolutionize the treatment of musculoskeletal injuries. However, in order to overcome scientific, practical, and regulatory obstacles and optimize therapeutic strategies, it is essential to better understand the mechanisms underlying the pro-regenerative effects of stem cells. There has been an attempted paradigm shift within the last decade to think of transplanted stem cells as "medicinal" therapies that orchestrate healing on the basis of their secretome and immunomodulatory profiles rather than acting as bona fide stem cells that proliferate, differentiate, and directly produce matrix to form de novo tissues. Yet the majority of current bone and skeletal muscle tissue engineering strategies are still premised on a direct contribution of stem cells as building blocks to tissue regeneration. Our review of the recent literature finds that researchers continue to focus on the quantification of de novo bone/skeletal muscle tissue following treatment and few studies aim to address this mechanistic conundrum directly. The dichotomy of thought is reflected in the diversity of new advances ranging from in situ three-dimensional bioprinting to a focus on exosomes and extracellular vesicles. However, recent findings elucidating the role of the immune system in tissue regeneration combined with novel imaging platform technologies will have a profound impact on our future understanding of how stem cells promote healing following biomaterial-mediated delivery to defect sites.


The study of aquatic macrophytes in Neotropics: a scientometrical view of the main trends and gaps.
Aquatic macrophytes comprises a diverse group of organisms including angiosperms, ferns, mosses, liverworts and some macroalgae that occur in seasonally or permanently wet environments. Among other implications, aquatic macrophytes are highly productive and with an important structuring role on aquatic environments. Ecological studies involving aquatic plants substantially increased in the last years. However, a precise view of researches devoted to aquatic macrophytes in Neotropics is necessary to reach a reliable evaluation of the scientific production. In the current study, we performed a scientometrics analysis of the scientific production devoted to Neotropical macrophytes in an attempt to find the main trends and gaps of researches concerning this group. The publication devoted to macrophytes in Neotropics increased conspicuously in the last two decades. Brazil, Argentina, Mexico and Chile were the most productive among Neotropical countries. Our analyses showed that the studies dealt mostly with the influences of aquatic macrophytes on organisms and abiotic features. Studies with a predictive approach or aiming to test ecological hypothesis are scarce. In addition, researches aiming to describe unknown species are still necessary. This is essential to support conservation efforts and to subsidize further investigations testing ecological hypotheses.


Unbiased interrogation of functional lysine residues in human proteome.
CRISPR screens have empowered the high-throughput dissection of gene functions; however, more explicit genetic elements, such as codons of amino acids, require thorough interrogation. Here, we establish a CRISPR strategy for unbiasedly probing functional amino acid residues at the genome scale. By coupling adenine base editors and barcoded sgRNAs, we target 215,689 out of 611,267 (35%) lysine codons, involving 85% of the total protein-coding genes. We identify 1,572 lysine codons whose mutations perturb human cell fitness, with many of them implicated in cancer. These codons are then mirrored to gene knockout screen data to provide functional insights into the role of lysine residues in cellular fitness. Mining these data, we uncover a CUL3-centric regulatory network in which lysine residues of CUL3 CRL complex proteins control cell fitness by specifying protein-protein interactions. Our study offers a general strategy for interrogating genetic elements and provides functional insights into the human proteome.


ED Patients with Prolonged Complaints and Repeat ED Visits Have an Increased Risk of Depression.
The objective of this study was to explore associations between presenting chief complaints of prolonged symptomatology, patient usage of the emergency department (ED), and underlying depression so that emergency physicians may better target patients for depression screening. A convenience sample of ED patients were administered the Beck Depression Inventory-II (BDI-II) to assess for depression. We correlated completed BDI-II surveys to patient information including demographics, pertinent history of present illness information, and past medical history. Out of 425 participants screened, we identified complaints of two weeks or longer in 92 patients (22%). Of these patients, mild to severe depression was recognized in over half of the population (47), yet only nine patients reported a prior depression diagnosis. These 92 patients also visited the ED three times as frequently as those patients with more acute complaints (p<0.001). Finally, our study showed that patients with mild to severe depression had three times as many ED visits compared to patients with minimal or no depression (p<0.001). Patients with complaints of symptomatology two weeks or longer are more likely to have underlying depression when presenting to the ED. Patients with three or more ED visits within the past year also have a greater incidence of underlying depression. We found a strong correlation between complaints with symptomatology of two weeks or longer and multiple ED visits, in which underlying depression may have contributed to these patients' ED visits.


Retrospective Analysis of Drug Prescription Statistics in a Tertiary Care Center in India: Recommendations for Promoting Prudent Utilization of Drugs.
Drug utilization studies provide information regarding the drug usage pattern in hospital settings, which can be used to promote cost-efficient uses of drugs. The present observational retrospective study was conducted to evaluate the drug utilization pattern in a tertiary care center in India and create a baseline consumption data for the drugs, simultaneously identifying targets for improving drug prescribing pattern. The current retrospective cross-sectional study was conducted at All India Institute of Medical Sciences Raipur, wherein the 217 medical records of different departments for August 2019 were chosen randomly (using systematic random sampling) for evaluation. The information was extracted from medical records regarding the basic demographic details, drug strength, route, and total amount, and eventually, the World Health Organization (WHO) core indicators were estimated. Drug utilization data were assessed using the WHO Anatomical Therapeutic Chemical/Defined Daily Dose (ATC-DDD) methodology. Potential drug-drug interactions were also analyzed. Most of the records analyzed were of male patients (56.2%). Drugs prescribed by their generic name were 50%. Prescriptions containing injection and antimicrobials were 68.1% and 83.6%, respectively. 49.3% of the patients had received a fixed-dose combination, and 60.9% of drugs belonged to the National List of Essential Medicines 2015. A total of 15 potential drug interactions were found. Calculated prescribed daily dose of most of the antimicrobials and other groups of drugs was close to the WHO-DDD. Trade name prescription and polypharmacy were very common. Antibiotics accounted for the majority of drug costs.


Neither B cell nor T cell - The unique group of innate lymphoid cells.
This special issue contains four review articles that analyze the development and biology of innate lymphoid cells (ILCs), which are the most recently-discovered group of innate immune cells. This unique group of lymphoid cells lacks the RAG gene and consequently does not express B cell nor T cell antigen-specific receptors. They are abundant at mucosal surfaces, where they play a role in immunity and homeostasis. The ILCs are the focus of intensive research efforts to understand their development and function.


Somewhere I belong: phylogeny and morphological evolution in a species-rich lineage of ectoparasitic flatworms infecting cichlid fishes.
A substantial portion of biodiversity has evolved through adaptive radiation. However, the effects of explosive speciation on species interactions remain poorly understood. Metazoan parasites infecting radiating host lineages could improve our knowledge because of their intimate host relationships. Yet limited molecular, phenotypic and ecological data discourage multivariate analyses of evolutionary patterns and encourage the use of discrete characters. Here, we assemble new molecular, morphological and host range data widely inferred from a species-rich lineage of parasites (Cichlidogyrus, Platyhelminthes: Monogenea) infecting cichlid fishes to address data scarcity. We infer a multimarker (28S/18S rDNA, ITS1, COI mtDNA) phylogeny of 58 of 137 species and characterize major lineages through synapomorphies inferred from mapping morphological characters. We predict the phylogenetic position of species without DNA data through shared character states, a morphological phylogenetic analysis, and a classification analysis with support vector machines. Based on these predictions and a cluster analysis, we assess the systematic informativeness of continuous characters, search for continuous equivalents for discrete characters, and suggest new characters for morphological traits not analysed to date. We also model the attachment/reproductive organ and host range evolution using the data for 136 of 137 described species and multivariate phylogenetic comparative methods (PCMs). We show that discrete characters not only can mask phylogenetic signals, but also are key for characterizing species groups. Regarding the attachment organ morphology, a divergent evolutionary regime for at least one lineage was detected and a limited morphological variation indicates host and environmental parameters affecting its evolution. However, moderate success in predicting phylogenetic positions, and a low systematic informativeness and high multicollinearity of morphological characters call for a revaluation of characters included in species characterizations.


Artificial Intelligence and Acute Stroke Imaging.
Artificial intelligence technology is a rapidly expanding field with many applications in acute stroke imaging, including ischemic and hemorrhage subtypes. Early identification of acute stroke is critical for initiating prompt intervention to reduce morbidity and mortality. Artificial intelligence can help with various aspects of the stroke treatment paradigm, including infarct or hemorrhage detection, segmentation, classification, large vessel occlusion detection, Alberta Stroke Program Early CT Score grading, and prognostication. In particular, emerging artificial intelligence techniques such as convolutional neural networks show promise in performing these imaging-based tasks efficiently and accurately. The purpose of this review is twofold: first, to describe AI methods and available public and commercial platforms in stroke imaging, and second, to summarize the literature of current artificial intelligence-driven applications for acute stroke triage, surveillance, and prediction.


Insulin stimulation of hepatic triacylglycerol secretion in the insulin-replete state: implications for the etiology of peripheral insulin resistance.
Observations on humans, on rats in vivo, and on isolated perfused rat livers indicate that insulin stimulates hepatic very-low-density lipoprotein (VLDL)-TAG secretion when the liver is chronically exposed to the hormone. They suggest that frequent stimulation of insulin secretion throughout the diurnal cycle may result in a chronic stimulation of VLDL secretion and increased delivery of acyl moieties to the periphery, particularly to muscle, the most important site of insulin-sensitive glucose disposal. If acyl groups are provided in excess of the oxidative needs of the tissue, this may lead to induction of insulin resistance, irrespective of whether obesity is established concomitantly. Dietary factors that stimulate hepatic VLDL secretion may have the same effect and contribute to the induction of a vicious spiral leading to the development of the full-blown Metabolic Syndrome and its pathological consequences, including type-2 diabetes, stroke, and cardiovascular disease.


Co-Processed Excipients for Dispersible Tablets-Part 2: Patient Acceptability.
Palatability and patient acceptability are critical attributes of dispersible tablet formulation. Co-processed excipients could provide improved organoleptic profile due to rational choice of excipients and manufacturing techniques. The aim of this study was to identify the most suitable co-processed excipient to use within directly compressible dispersible tablet formulations. Nine excipients, selected based on successful manufacturability, were investigated in a randomised, preference and acceptability testing in 24 healthy adult volunteers. Excipients were classified in order of preference as follows (from most preferred): SmartEx QD100 > F-Melt Type C > F-Melt Type M > MicroceLac > Ludiflash > CombiLac > Pharmaburst 500 > Avicel HFE-102 > Avicel PH-102. Broad differences were identified in terms of acceptability, with SmartEx QD100 being 'very acceptable', F-Melt Type C, F-Melt Type M and MicroceLac being 'acceptable', Ludiflash, CombiLac and Pharmaburst 500 being 'neutral' and Avicel products being 'very unacceptable' based on ratings using five-point hedonic scales. Organoleptic differences were ascribed to different composition and physical properties of excipients, resulting in dissimilar taste and mouth-feel. Excipients with particle size in water larger than 200-250 μm were considered poorly acceptable, which supports the use of this value as a threshold for maximum particle size of dispersible formulation. The most promising co-processed excipients for directly compressible dispersible tablets were successfully identified.


[The prognosis of the development of recurrent bronchitis based on immunogenetic indices].
It is worthy to carry out the prognosis of recurrent bronchitis development on the basis of immunogenetic markers. It was shown that HLA-A10 and B13 antigens occurred in Dnepropetrovsk Province significantly more often and HLA-A19, B12, B15, and B21 antigens more rare than in European population. It has been demonstrated that HLA-B35, HLA-B38 and HLA-B-blanks are found with significantly higher frequency in patients with recurrent bronchitis and it has been associated with low immune indices. HLA-B40 and Cw2 antigens were found as protective against development of recurrent bronchitis.


Langerhans Cell Hyperplasia Mimicking Langerhans Cell Histiocytosis: A Rare Complication of COVID-19 Vaccination.
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the abnormal proliferation of Langerhans cells, a type of immune cell that is normally present in the skin and various other tissues. LCH can affect people of any age but is most commonly diagnosed in children. We report a case of a patient with LCH who developed ipsilateral axillary lymphadenopathology post-COVID-19 vaccination. Lymph node biopsy showed diffuse Langerhans cell hyperplasia which mimicked LCH. Clinically and radiologically, it looked to be a reactive lymph node. The patient was kept on follow up only and after 1 year of follow up the size of lymph nodes regressed confirming to be reactive in nature rather than neoplastic. To the best of our knowledge, this is the second case of Langerhans cell hyperplasia post-COVID-19 vaccination being reported in the literature.


[Comparison of ultrasound-controlled fine needle and coarse needle puncture of defined lesions in the abdomen].
Within a 2-year period 677 diagnostic fine needle (DFP) and coarse needle punctures (DGP) were performed in 536 patients. In 34 patients (14 women; 20 men; 54 +/- 17.6 years) the abdominal tumour mass was punctured with the fine needle (22 g) as well as with the coarse (18 g) needle. Sensitivity of DGP accounted for 72%, sensitivity of DFP was 82.6%. Specificity was 100%, respectively. Complications could not be observed, neither with the coarse needle nor with the fine needle. Due to the high sensitivity of DFP this method should be employed first in the diagnostic work up of abdominal tumours.


Language Usage and Second Language Morphosyntax: Effects of Availability, Reliability, and Formulaicity.
A large body of psycholinguistic research demonstrates that both language processing and language acquisition are sensitive to the distributions of linguistic constructions in usage. Here we investigate how statistical distributions at different linguistic levels - morphological and lexical (Experiments 1 and 2), and phrasal (Experiment 2) - contribute to the ease with which morphosyntax is processed and produced by second language learners. We analyze Chinese ESL learners' knowledge of four English inflectional morphemes: -ed, -ing, and third-person -s on verbs, and plural -s on nouns. In Elicited Imitation Tasks, participants listened to length- and difficulty-matched sentences each containing one target morpheme and typed the whole sentence as accurately as they could after a short delay. Experiment 1 investigated lexical and morphemic levels, testing the hypotheses that a morpheme is expected to be more easily processed when it is (1) highly available (i.e., occurring in frequent word-forms), and (2) highly reliable (i.e., occurring in lemma words that are consistently conjugated in the form containing this morpheme). Thirty sentences were made for each morpheme, divided into three Availability-Reliability Distribution (ARD) groups on the basis of corpus analysis in the Corpus of Contemporary American English (COCA; Davies, 2008-): 10 target words high in availability, 10 high in reliability, and 10 low in both reliability and availability. Responses were scored on whether the target morpheme was accurately reproduced given the provision of the correct lemma. A generalized linear mixed-effects logit model (GLMM) revealed fixed effects of morpheme type, availability, and reliability on the accuracy of morpheme provision. There were no effects of lemma frequency. Experiment 2 successfully replicated these results and extended the investigation to explore phrasal formulaicity by manipulating the frequency of the four-word strings in which the morpheme was embedded. GLMMs replicated the effects of word-form availability and reliability and additionally revealed independent phrase-superiority effects where morphemes were better reproduced in contexts of higher string-frequency. Taken together, these findings demonstrate that morpheme acquisition reflects the distributional properties of learners' experience and the mappings therein between lexis, morphology, phraseology, and semantics. These conclusions support an emergentist view of the statistical symbolic learning of morphology where language acquisition involves the satisfaction of competing constraints across multiple grain-sizes of units.


Intraventricular hemorrhage in preterm infants: coagulation perspectives.
It has long been considered that a severe coagulation deficiency in premature newborns could be a major contributing factor in the occurrence of intraventricular hemorrhage (IVH). High-grade IVH has also been shown to coincide with severe derangement of coagulation in extremely low birth weight infants. This review focuses on the relevance of the physiologically developing immature hemostatic system to IVH, and the potential benefit of agents affecting hemostasis for IVH therapy or prevention in preterm infants. The findings of small, open-label interventional studies on the effect of ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII, and prothrombin complex concentrate on the premature coagulation system will be reviewed.


American Society of Anesthesiologists Score is Not Predictive of Complication Incidence After Minimally Invasive Posterior Lumbar Spine Procedures.
Complications occurring after spinal procedures are associated with recurrent symptomatology, new-onset symptomatology, and increased health care costs. The American Society of Anesthesiologists (ASA) score is a commonly cited risk factor for complication incidence. Few investigations have been performed analyzing the relationship between ASA score and complication rate following spinal minimally invasive surgery (MIS) decompressions or fusions. Therefore, the purpose of this study is to determine whether an association exists between preoperative ASA score and the incidence of postoperative complications among patients undergoing MIS posterior lumbar decompression or fusion. A surgical registry of patients undergoing single-level MIS posterior lumbar decompressions or fusions between 2007 and 2016 was retrospectively reviewed. Patients were stratified by preoperative ASA score (≤2, >2). The ASA score was tested for an association with preoperative demographic, comorbidity, and perioperative characteristics using the Student t test or χ2 analysis. Multivariate Poisson regression with robust error variance was used to test for an association between ASA score and the incidence of complications up to 6 months postoperatively. A total of 772 patients were analyzed. Of those, 86.7% had an ASA score ≤2, whereas 13.3% had an ASA score >2. An ASA score >2 was associated with older age (P < .001), higher comorbidity burden (P < .001), and higher rates of obesity (P < .001). An ASA score >2 was also associated with significantly longer operative time (P = .001) and longer length of hospital stay (P < .001). Upon multivariate analysis, ASA score category was not associated with the incidence of any complication (P = .248), medical complications (P = .227), or surgical complications (P = .816). The ASA score was not a predictive factor for complication incidence up to 6 months postoperatively. Thus, a higher ASA score should not preclude patients from being surgical candidates for MIS posterior lumbar decompressions or fusions. Further investigation is required to identify other predictive factors for complication incidence after minimally invasive spine surgery. 3.


Central and peripheral anti-hyperalgesic effects of diosmin in a neuropathic pain model in rats.
Flavonoids are natural compounds showing anti-hyperalgesic activity in models of pain. Diosmin is a compound poorly studied in the treatment of neuropathic pain. This study evaluates the anti-hyperalgesic actions of diosmin and possible mechanisms of action involved by using a neuropathic pain model in rats. Experimental neuropathic pain was induced by chronic constriction injury (CCI) in male Wistar rats, then aesthesiometric index and plantar tests were assessed to evaluate mechanical and thermal hyperalgesia, respectively, in order to explore the analgesic effects of acute and sub-chronic treatment with diosmin. The GABAA, 5-HT1A, D2-like and opioid receptors participation, as well as levels of TNF-α, IL-1β and IL-6, were evaluated in the spinal cord and sciatic nerve tissues after acute and subchronic diosmin administration. In addition, the presence of diosmin on cerebral samples was determined by UHPLC-MS analysis. Acute and sub-chronic treatment with diosmin significantly diminished the mechanical and thermal hyperalgesia induced by CCI in rats. This anti-hyperalgesic effects of diosmin were modified in the presence of naloxone (1mg/kg, i.p.) and haloperidol (0.1mg/kg, i.p.), but not by GABAA and 5-HT1A receptor antagonists. The anti-hyperalgesic effects of diosmin were also linked with reduced levels of TNF-α, IL-1β and IL-6. The presence of diosmin in the cerebral samples was confirmed by chromatographic analysis. In conclusion, our results provide evidence that diosmin produces significant anti-hyperalgesic effects acting at central level by an opioid and D2 dopaminergic receptors participation, and at peripheral level by reducing proinflammatory cytokines.


Do tinted spectacle lens wearers have a different personality?
The wearing of tinted spectacle lenses is considered by some health care workers to be a marker of psychopathology or a hypochondriacal personality type. The purpose of this study was to determine whether there is a relationship between the wearing of tinted spectacle lenses and personality type in physically healthy subjects. The Sixteen Personality Factor Questionnaire 5th Edition, a multidimensional standardized self-report inventory, was used to determine the personality type of 98 participants. Twenty currently wore tinted spectacle lenses for reasons other than ocular disease, sun protection, outdoor or indoor glare reduction, pattern sensitive epilepsy, migraines, reading difficulties or fashion. The remainder did not wear tinted spectacle lenses for any purpose other than sun protection. Tinted lens wear and no tinted lens wear groups were age and gender matched. There was no statistically significant difference in five global personality factors between the no-tint and tint groups: extraversion (p = 0.31), anxiety (p = 0.75), tough-mindedness (p = 0.96), independence (p = 0.63), and self-control (p = 0.87). This suggests that the use of tinted lenses by physically healthy people is unlikely to be an indicator of personality type.


Postoperative adjuvant transarterial chemoembolization for multinodular hepatocellular carcinoma within the Barcelona Clinic Liver Cancer early stage and microvascular invasion.
The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) remained controversial. We aimed to investigate the prognosis effect of PA-TACE on the Barcelona Clinic Liver Cancer (BCLC) early stage multinodular hepatocellular carcinoma (MHCC) patients with/without microvascular invasion (MVI). Two hundred and seventy-one patients from January 2010 to December 2014 undergoing curative hepatectomy were included in this study. Disease-free survival (DFS) rates and overall survival (OS) rates as well as prognostic factors were analyzed by the Kaplan-Meier method, the log-rank test and the Cox proportional hazard model. Thirty-four point four percent (44/128) MVI positive and 55.2% (79/143) MVI negative patients underwent PA-TACE. Multivariate analysis revealed that HBV DNA load >103 copy/mL, >three tumors, MVI, and without PA-TACE were independent risk factors for poor DFS. Higher alkaline phosphatase (ALP), three tumors, MVI, and without PA-TACE were independent risk factors for poor OS. Both DFS and OS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent hepatic resection alone (5-year DFS, 26.3% vs. 20.7%, P=0.038; 5-year OS, 73.6% vs. 47.7%, P=0.005). No differences were noted in DFS and OS among MVI negative patients with or without PA-TACE (5-year DFS, 33.7% vs. 33.0%, P=0.471; 5-year OS, 84.1% vs. 80.3%, P=0.523). Early recurrence was more likely to occur in patients without PA-TACE (P=0.001). PA-TACE was a safe intervention and could effectively prevent tumor recurrence and improve the survival of the BCLC early stage MHCC patients with MVI.


Marked intraocular pressure rise following Nd:YAG laser capsulotomy.
A Nd:YAG laser was used to perform a posterior capsulotomy on a patient one and a half years after phacoemulsification. Within 24 hours the intraocular pressure had increased to 67 mm Hg despite pre-treatment with timolol and acetazolamide. Intraocular pressure eventually returned to pre-capsulotomy levels after several days. A mechanism is postulated for the particularly high pressures encountered in this case.


Differential regulation of human RecQ family helicases in cell transformation and cell cycle.
Three human RecQ DNA helicases, WRN, BLM and RTS, are involved in the genetic disorders associated with genomic instability and a high incidence of cancer. RecQL1 and RecQL5 also belong to the human RecQ helicase family, but their correlation with genetic disorders, if any, is unknown. We report here that in human B cells transformed by Epstein-Barr virus (EBV), human fibroblasts and umbilical endothelial cells transformed by simian virus 40, the expression of WRN, BLM, RTS and RecQL1 was sharply up-regulated. In B cells this expression was stimulated within 5-40 h by the tumor promoting agent phorbol myristic acetate (PMA). Interestingly, RecQL5beta, an alternative splicing product of RecQL5 with a nuclear localization signal, is expressed in resting B cells without significant modulation of its synthesis by EBV or PMA, suggesting it has a role in resting cells. We also roughly determined the number of copies per cell for the five RecQ helicase in B cells. In addition, levels of the different RecQ helicases are modulated in different ways during the cell cycle of actively proliferating fibroblasts and umbilical endothelial cells. Our results support the view that the levels of WRN, BLM, RTS and RecQL1 are differentially up-regulated to guarantee genomic stability in cells that are transformed or actively proliferating.


Loss of the Phenolic Hydroxyl Group and Aromaticity from the Side Chain of Anti-Proliferative 10-Methyl-aplog-1, a Simplified Analog of Aplysiatoxin, Enhances Its Tumor-Promoting and Proinflammatory Activities.
Aplysiatoxin (ATX) is a protein kinase C (PKC) activator with potent tumor-promoting activity. In contrast, 10-methyl-aplog-1 (1), a simplified analog of ATX, was anti-proliferative towards several cancer cell lines without significant tumor-promoting and proinflammatory activities. To determine the effects of the phenolic group on the biological activities of 1, we synthesized new derivatives (2, 3) that lack the phenolic hydroxyl group and/or the aromatic ring. Compound 2, like 1, showed potent anti-proliferative activity against several cancer cell lines, but little with respect to tumor-promoting and proinflammatory activities. In contrast, 3 exhibited weaker growth inhibitory activity, and promoted inflammation and tumorigenesis. The binding affinity of 3 for PKCδ, which is involved in growth inhibition and apoptosis, was several times lower than those of 1 and 2, possibly due to the absence of the hydrogen bond and CH/π interaction between its side chain and either Met-239 or Pro-241 in the PKCδ-C1B domain. These results suggest that both the aromatic ring and phenolic hydroxyl group can suppress the proinflammatory and tumor-promoting activities of 1 and, therefore, at least the aromatic ring in the side chain of 1 is indispensable for developing anti-cancer leads with potent anti-proliferative activity and limited side effects. In accordance with the binding affinity, the concentration of 3 necessary to induce PKCδ-GFP translocation to the plasma membrane and perinuclear regions in HEK293 cells was higher than that of 1 and 2. However, the translocation profiles for PKCδ-GFP due to induction by 1-3 were similar.


Herpes zoster ophthalmicus in patients with human immunodeficiency virus infection.
To investigate the ocular complications of herpes zoster ophthalmicus in patients with human immunodeficiency virus (HIV) infection. This was a retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San Francisco General Hospital for herpes zoster ophthalmicus from December 1985 through March 1994. All patients were initially treated with either intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was 48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild, and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four study patients (50%) had iritis, but only three (6%) had elevations in intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two others (4%) had zoster-associated central nervous system disease. Only two patients (4%) developed necrotizing retinitis, both in the form of the progressive outer retinal necrosis syndrome. Excluding the patients with retinitis and central nervous system disease, the rate of sight-threatening complications in our series was lower than expected. Almost one third of study patients had no ocular complications or only mild surface epithelial disease. Although the relatively low incidence of sight-threatening disease in our study population may have been a consequence of aggressive management with acyclovir, chronic infectious pseudodendritic keratitis, retinitis, and central nervous system disease, complications of ophthalmic zoster whose pathogenesis is largely a consequence of active viral replication, were particularly devastating and difficult to manage.


Validation and reliability of a disease-specific quality-of-life measure in patients with cutaneous lupus erythematosus.
Cutaneous lupus erythematosus (CLE) is a potentially disfiguring, chronic autoimmune disease with variable skin manifestations, negatively affecting patients' quality of life (QoL). Patient-reported outcome (PRO) measures assessing QoL in patients with CLE have been generic or developed without input from patients. To demonstrate the reliability and validity of a disease-specific QoL measure for CLE - the cutaneous lupus erythematosus quality of life (CLEQoL). One hundred and one patients with CLE were recruited, and each patient was asked to complete the CLEQoL. Internal consistency was used as a measure of reliability. Validity was measured in two ways - structural validity via exploratory factor analysis and convergent validity via Spearman correlations between CLEQoL and the Short Form 36 (SF-36), visual analogue scales and clinical variables. Patient demographic and disease characteristics were collected. The mean ± SD age of patients with CLE was 48 ± 13 years, with discoid lupus (n = 72; 71.3%) being the most predominant CLE subtype. Patients were mostly female (n = 88; 87·1%) and African American/Black (n = 59; 58·4%). Internal consistency ranged from 0·67 to 0·97. Five domains (functioning, emotions, symptoms, body image/cosmetic effects and photosensitivity) were extracted with a total explained variance of 71·1%. CLEQoL-related domains correlated with SF-36 domains (r range -0·39 to -0·65). The CLEQoL was found to be a valid and reliable PRO measure for assessing QoL in patients with CLE. Demonstrating that the CLEQoL has strong psychometric properties is an important step towards the development of a disease-specific PRO measure that future clinical trials can use.


Solubilization of single-walled carbon nanotubes by using polycyclic aromatic ammonium amphiphiles in water--strategy for the design of high-performance solubilizers.
We describe the design of polycyclic aromatic compounds with high performance that dissolve single-walled carbon nanotubes (SWNTs). Synthetic amphiphiles trimethyl-(2-oxo-2-phenylethyl)-ammonium bromide (1) and trimethyl-(2-naphthalen-2-yl-2-oxo-ethyl)-ammonium bromide (2) carrying a phenyl or a naphtyl moiety were not able to dissolve/disperse SWNTs in water. By contrast, trimethyl-(2-oxo-2-phenanthren-9-yl-ethyl)-ammonium bromide (3) solubilized SWNTs, although the solubilization ability was lower than that of trimethyl-(2-oxo-2-pyrene-1-yl-ethyl)-ammonium bromide (4) (solubilization behavior observed by using 4 was described briefly in reference 4a). Transmission electron microscopy (TEM), as well as visible/near-IR, fluorescence, and near-IR photoluminescence spectroscopies were employed to reveal the solubilization properties of 4 in water, and to compare these results with those obtained by using sodium dodecyl sulfate (SDS) and hexadecyltrimethylammonium bromide (HTAB) as solubilizers. Compound 4 solubilized both the as-produced SWNTs (raw-SWNTs) and purified SWNTs under mild experimental conditions, and the solubilization ability was better than that of SDS and HTAB. Near-IR photoluminescence measurements revealed that the chiral indices of the SWNTs dissolved in an aqueous solution of 4 were quite different from those obtained by using micelles of SDS and HTAB; for a SWNTs/4 solution, the intensity of the (7,6), (9,5), and (12,1) indices were strong and the chirality distribution was narrower than those of the micellar solutions. This indicates that the aqueous solution of 4 has a tendency to dissolve semiconducting SWNTs with diameters in the range of 0.89-1.0 nm, which are larger than those SWNTs (0.76-0.97 nm) dissolved in the aqueous micelles of SDS and HTAB.


Neutralization by metal ions of the toxicity of sodium selenide.
Inert metal-selenide colloids are found in animals. They are believed to afford cross-protection against the toxicities of both metals and selenocompounds. Here, the toxicities of metal salt and sodium selenide mixtures were systematically studied using the death rate of Saccharomyces cerevisiae cells as an indicator. In parallel, the abilities of these mixtures to produce colloids were assessed. Studied metal cations could be classified in three groups: (i) metal ions that protect cells against selenium toxicity and form insoluble colloids with selenide (Ag⁺, Cd²⁺, Cu²⁺, Hg²⁺, Pb²⁺ and Zn²⁺), (ii) metal ions which protect cells by producing insoluble metal-selenide complexes and by catalyzing hydrogen selenide oxidation in the presence of dioxygen (Co²⁺ and Ni²⁺) and, finally, (iii) metal ions which do not afford protection and do not interact (Ca²⁺, Mg²⁺, Mn²⁺) or weakly interact (Fe²⁺) with selenide under the assayed conditions. When occurring, the insoluble complexes formed from divalent metal ions and selenide contained equimolar amounts of metal and selenium atoms. With the monovalent silver ion, the complex contained two silver atoms per selenium atom. Next, because selenides are compounds prone to oxidation, the stabilities of the above colloids were evaluated under oxidizing conditions. 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), the reduction of which can be optically followed, was used to promote selenide oxidation. Complexes with cadmium, copper, lead, mercury or silver resisted dissolution by DTNB treatment over several hours. With nickel and cobalt, partial oxidation by DTNB occurred. On the other hand, when starting from ZnSe or FeSe complexes, full decompositions were obtained within a few tens of minutes. The above properties possibly explain why ZnSe and FeSe nanoparticles were not detected in animals exposed to selenocompounds.


Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.
To document the clinical, laboratory, and epidemiologic characteristics of pediatric patients with murine typhus. Pediatric patients were diagnosed using serologic testing, and clinical, laboratory, and epidemiologic data were retrospectively reviewed. Of 97 patients, 77 (79%) were identified and treated as inpatients and 20 (21%) were treated as outpatients; most resided in south Texas. Between 1979 and 1996, medical records and patient-physician interviews were available for 97 patients aged 16 years and younger with murine typhus. The frequency of clinical symptoms and signs, abnormal laboratory findings, epidemiologic findings, and measures of disease severity were determined. The clinical triad of fever, headache, and rash occurred in only 43 (49%) of 87 pediatric patients throughout the illness. Musculoskeletal symptoms were experienced by 43% of patients, whereas gastrointestinal tract symptoms (nausea, vomiting, anorexia, and diarrhea) occurred in 77%. Systemic involvement was evident by the frequent occurrence of abnormal laboratory findings referable to multiple organ systems, including the liver, kidney, blood, and central nervous system. Pediatric infection by Rickettsia typhi usually causes mild to moderate systemic illness. In children, the median duration of illness was 12 days (range, 5-29 days), but severe complications were rare. Length of illness was significantly related to the initial diagnosis, whereas the interval to defervescence was related to therapy with a tetracycline or chloramphenicol. Early recognition and treatment is important to prevent prolonged morbidity.


Characterisation of the QM gene of Trypanosoma brucei.
The QM protein has been reported to have roles in both tumour suppression and transcription factor regulation in vertebrate cells, and in ribosome stability in both yeast and mammals. The present study isolated the QM gene of Trypanosoma brucei and determined its sequence. Alignment with QM sequences from Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster and Homo sapiens revealed greater than 60% identity. Southern blot analysis revealed multiple copies of QM within the trypanosome genome. An epitope tag was inserted into the C-terminus of the T. brucei QM and the protein expressed under inducible control in procyclic form trypanosomes. Immune fluorescence microscopy revealed co-localisation with the GPI:protein transamidase component, GPI8, a distribution indicative of ribosome association with the rough endoplasmic reticulum.


The involvement of hydrogen peroxide in the differentiation of secondary walls in cotton fibers
H2O2 is a widespread molecule in many biological systems. It is created enzymatically in living cells during various oxidation reactions and by leakage of electrons from the electron transport chains. Depending on the concentration H2O2 can induce cell protective responses, programmed cell death, or necrosis. Here we provide evidence that H2O2 may function as a developmental signal in the differentiation of secondary walls in cotton (Gossypium hirsutum) fibers. Three lines of evidence support this conclusion: (a) the period of H2O2 generation coincided with the onset of secondary wall deposition, (b) inhibition of H2O2 production or scavenging the available H2O2 from the system prevented the wall differentiation process, and (c) exogenous addition of H2O2 prematurely promoted secondary wall formation in young fibers. Furthermore, we provide support for the concept that H2O2 generation could be mediated by the expression of the small GTPase Rac, the accumulation of which was shown previously to be strongly induced during the onset of secondary wall differentiation. In support of Rac's role in the activation of NADPH oxidase and the generation of reactive oxygen species, we transformed soybean (Glycine max) and Arabidopsis cells with mutated Rac genes. Transformation with a dominantly activated cotton Rac13 gene resulted in constitutively higher levels of H2O2, whereas transformation with the antisense and especially with dominant-negative Rac constructs decreased the levels of H2O2.


Alveolar capillary dysplasia.
Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, fatal developmental lung disorder of neonates and infants. This review aims to address recent findings in the etiology and genetics of ACD/MPV and to raise awareness of this poorly known disease, which may also present as milder, unclassified forms. Successively discussed are what is known about the epidemiology, pathogenesis, pathophysiology, diagnostic indicators and approaches, genetic testing, treatment, and cases of delayed onset. The review concludes with suggestions for future directions to answer the many unknowns about this disorder.


Formation of compound I by the reaction of catalase with peroxoacetic acid.
1. The formation of Compound I by the reactions of bacterial and ox liver catalases with peroxoacetic acid was examined. In both cases the process occurs almost entirely by reaction of catalase with un-ionized peroxoacetic acid molecules. The result suggests an important role for the bound peroxidic proton in the enzyme-substrate interaction. 2. The peroxidatic properties of the Compounds I formed when peroxoacetic acid was used were examined by studying the oxidations of ethanol and formate; the results closely resemble those previously reported when H(2)O(2) and alkyl hydroperoxides were used. 3. Compound I formed with bacterial catalase and peroxoacetic acid is remarkably stable in the absence of added donor and the preparation has considerable potential for detailed studies of the nature of this intermediate.


Target size of the adenosine Ri receptor.
The adenosine receptor of rat cerebral-cortical membranes was examined by radiation inactivation. In control membranes the receptor is distributed between high- and low-affinity states, that can be preferentially expressed by Mg2+ ions and guanine nucleotides respectively. Upon exposure to increasing doses of radiation, the high-affinity receptor decayed linearly as a function of radiation dose. This decay rate corresponded to a target size of 63,000 Da, when compared with the decay of the muscarinic cholinergic receptor that was also measured in these membranes.


Fungal Biomineralization of Manganese as a Novel Source of Electrochemical Materials.
Electrical energy storage systems such as rechargeable lithium-ion batteries (LiBs) and supercapacitors have shown great promise as sustainable energy storage systems [1-4]. However, LiBs have high specific energy density (energy stored per unit mass) and act as slow, steady suppliers for large energy demands. In contrast, supercapacitors possess high specific power (energy transferred per unit mass per unit time) and can charge and discharge quickly for low energy demands. In LiBs, graphite is the most common anode material, although high electrolyte sensitivity and low charge capacity can limit performance. Efforts have been made to improve LiB or supercapacitor performance using alternative electrode materials such as carbon nanotubes and manganese oxides (MnxOy) [3, 5-14]. Microorganisms play significant roles in metal and mineral biotransformations [15-22]. Fungi possess various biomineralization properties, as well as a filamentous mycelium, which may provide mechanical support for mineral deposition. Although some research has been carried out on the application of biological materials as carbon precursors [8, 9, 23], biomineralizing fungal systems have not been investigated. In this research, novel electrochemical materials have been synthesized using a fungal Mn biomineralization process based on urease-mediated Mn carbonate bioprecipitation [24]. The carbonized fungal biomass-mineral composite (MycMnOx/C) showed a high specific capacitance (>350 F g(-1)) in a supercapacitor and excellent cycling stability (>90% capacity was retained after 200 cycles) in LiBs. This is the first demonstration of the synthesis of electrode materials using a fungal biomineralization process, thus providing a novel strategy for the preparation of sustainable electrochemical materials.


Determinants of microvascular damage recovery after acute myocardial infarction: results from the acute myocardial infarction contrast imaging (AMICI) multi-centre study.
Microvascular damage (MD) occurring soon after primary percutaneous coronary intervention (PPCI) may reverse or remain sustained within the first week after ST-elevation myocardial infarction (STEMI). We investigated the incidence, determinants, and long-term clinical relevance of MD reversal after PPCI. Serial two-dimensional echocardiograms (2DE) and a myocardial contrast study were obtained within 24 h of PPCI (T1) and at pre-discharge (T2) in 110 successfully re-perfused STEMI patients. Six months 2DE and 2-year clinical follow-up were obtained. After PPCI myocardial re-perfusion was normal at T1 only in 40 patients (36%, 'normal reflow'), recovered at T2 in 33 (30%, 'reversible MD'), and remained abnormal in 37 (34%, 'sustained MD'). At follow-up, normal reflow and reversible MD were coupled with a significant reduction in the infarct area, decrease in cardiac volumes, and a slight non-significant improvement in systolic function. Conversely, in the sustained MD group, the infarct area did not change and cardiac volumes significantly increased with a parallel worsening in systolic function. By multivariate analysis, independent predictors of reversible MD were: absence of family history of coronary artery disease (CAD), younger age, shorter time to re-perfusion, and absence of diabetes. The 2-year combined events rate was significantly lower in reversible MD (log-rank test P= 0.03) compared with sustained MD patients. In STEMI patients treated according to the current guidelines, MD frequently occurs soon after re-perfusion but it is reversible in ~50% of cases and it is associated with a favourable functional and clinical outcome. Family history of CAD, aging, time to re-perfusion, and diabetes are independent predictors of MD reversibility.


Translating endoplasmic reticulum biology into the clinic: a role for ER-targeted natural products?
ER stress has been identified as a hallmark, and sometimes trigger, of several pathologies, notably cancer, inflammation and neurodegenerative diseases like Alzheimer's and Parkinson's. Among the molecules described in literature known to affect ER function, the majority are natural products, suggesting that natural molecules may constitute a significant arsenal of chemical entities for modulating this cellular target. In this review, we will start by presenting the current knowledge of ER biology and the hallmarks of ER stress, thus paving the way for presenting the natural products that have been described as being ER modulators, either stress inducers or ER protectors. The chemistry, distribution and mechanism of action of these compounds will be presented and discussed.


Was access to health care easy for immigrants in Spain? The perspectives of health personnel in Catalonia and Andalusia.
Until April 2012, all Spanish citizens were entitled to health care and policies had been developed at national and regional level to remove potential barriers of access, however, evidence suggested problems of access for immigrants. In order to identify factors affecting immigrants' access to health care, we conducted a qualitative study based on individual interviews with healthcare managers (n=27) and professionals (n=65) in Catalonia and Andalusia, before the policy change that restricted access for some groups. A thematic analysis was carried out. Health professionals considered access to health care "easy" for immigrants and similar to access for autochthons in both regions. Clear barriers were identified to enter the health system (in obtaining the health card) and in using services, indicating a mismatch between the characteristics of services and those of immigrants. Results did not differ among regions, except for in Catalonia, where access to care was considered harder for users without a health card, due to the fees charged, and in general, because of the distance to primary health care in rural areas. In conclusion, despite the universal coverage granted by the Spanish healthcare system and developed health policies, a number of barriers in access emerged that would require implementing the existing policies. However, the measures taken in the context of the economic crisis are pointing in the opposite direction, towards maintaining or increasing barriers.


[Access to information about how to prevent oral problems among school children in the public school network].
The scope of this study is to identify the prevalence of access to information about how to prevent oral problems among schoolchildren in the public school network, as well as the factors associated with such access. This is a cross-sectional and analytical study conducted among 12-year-old schoolchildren in a Brazilian municipality with a large population. The examinations were performed by 24 trained dentists and calibrated with the aid of 24 recorders. Data collection occurred in 36 public schools selected from the 89 public schools of the city. Descriptive, univariate and multiple analyses were conducted. Of the 2510 schoolchildren included in the study, 2211 reported having received information about how to prevent oral problems. Access to such information was greater among those who used private dental services; and lower among those who used the service for treatment, who evaluated the service as regular or bad/awful. The latter use toothbrush only or toothbrush and tongue scrubbing as a means of oral hygiene and who reported not being satisfied with the appearance of their teeth. The conclusion drawn is that the majority of schoolchildren had access to information about how to prevent oral problems, though access was associated with the characteristics of health services, health behavior and outcomes.