Continuous monitoring of the effect of pentagastrin on gastric emptying of solid food in man.
By continuous monitoring of a solid meal labelled with a radiopharmaceutical it has been possible to determine the effects of drugs on gastric emptying and motility during a single study. Predictably hyoscine delayed, and bethanechol increased, the rate of gastric emptying. Pentagastrin initially produced marked antral activity resulting in a physiological stricture and subsequent delay in the overall rate of gastric emptying. Fundal motility was unaffected though reflux from the antrum occurred.


Adaptive climatic molecular evolution in wild barley at the Isa defense locus.
Wild barley (Hordeum spontaneum) represents a significant genetic resource for crop improvement in barley (Hordeum vulgare) and for the study of the evolution and domestication of plant populations. The Isa gene from barley has a putative role in plant defense. This gene encodes a bifunctional alpha-amylase/subtilisin inhibitor that inhibits the bacterial serine protease subtilisin, fungal xylanase, and the plant's own alpha-amylase. The inhibition of plant alpha-amylases suggests this protein may also be important for grain quality from a human perspective. We identified 16 SNPs in the coding region of the Isa locus of 178 wild barley accessions from eight climatically divergent sites across Israel. The pattern of SNPs suggested a large number of recombination events within this gene, indicating that the low-outcrossing rate of wild barley is not a barrier to recombinant haplotypes becoming established in the population. Seven amino acid substitutions were present in the coding region. Genetic diversity for each population was calculated by using Nei's diversity index, and a Spearman rank correlation was carried out to test the association between gene diversity and 16 ecogeographical factors. Highly significant correlations were found between diversity at the Isa locus and key water variables, evaporation, rainfall, humidity, and latitude. The pattern of association suggests selective sweeps in the wetter climates, with resulting low diversity and weaker selection or diversifying selection in the dryer climates resulting in much higher diversity.


Swine models of cystic fibrosis reveal male reproductive tract phenotype at birth.
Nearly all male cystic fibrosis (CF) patients exhibit tissue abnormalities in the reproductive tract, a condition that renders them azoospermic and infertile. Two swine CF models have been reported recently that include respiratory and digestive manifestations that are comparable to human CF. The goal of this study was to determine the phenotypic changes that may be present in the vas deferens of these swine CF models. Tracts from CFTR(-/-) and CFTR(ΔF508/ΔF508) neonates revealed partial or total vas deferens and/or epididymis atresia at birth, while wild-type littermates were normal. Histopathological analysis revealed a range of tissue abnormalities and disruptions in tubular organization. Vas deferens epithelial cells were isolated and electrophysiological results support that CFTR(-/-) monolayers can exhibit Na(+) reabsorption but reveal no anion secretion following exposure to cAMP-generating compounds, suggesting that CFTR-dependent Cl(-) and/or HCO(3)(-) transport is completely impaired. SLC26A3 and SLC26A6 immunoreactivities were detected in all experimental groups, indicating that these two chloride-bicarbonate exchangers were present, but were either unable to function or their activity is electroneutral. In addition, no signs of increased mucus synthesis and/or secretion were present in the male excurrent ducts of these CF models. Results demonstrate a causal link between CFTR mutations and duct abnormalities that are manifested at birth.


Effect of hormones on growth and function of cultured canine tracheal epithelial cells.
Insulin (INS), endothelial cell growth supplement (ECGS), transferrin (TF), cholera toxin (CT), hydrocortisone (HC), triiodothyronine (T3), and epidermal growth factor (EGF) were systematically examined for their effects on proliferation, ion transport activity, and morphological differentiation of canine tracheal epithelial (CTE) cells in culture. INS, ECGS, TF, and CT increase proliferation of CTE cells cultured on plastic Petri dishes but exhibit no acute effect on the bioelectric activity of freshly excised CTE. CT increases amiloride-insensitive transepithelial ion transport across both freshly excised canine trachea and CTE cultures. EGF has no effect on proliferation of CTE cells on plastic but induces hyperplasia of CTE cells on collagen matrices. EGF does not alter basal transepithelial ion transport across cultures but increases cellular responsiveness to beta-adrenergic stimulation. HC and T3 have no effect on proliferation or transepithelial bioelectric properties of CTE cells but improve morphological differentiation yielding cultures of complex epithelia containing cuboidal ciliated and nonciliated cells. These results demonstrate that growth and function of cultured CTE cells are affected by specific growth factors.


A convenient renewable surface plasmon resonance chip for relative quantification of genetically modified soybean in food and feed.
The cultivation of genetically modified organisms (GMO) continues to expand worldwide. Still, many consumers express concerns about the use of GMO in food or feed, and many countries have legislated on labelling systems to indicate the presence of GMO in commercial products. To deal with the increased number of GMO events and to address related regulations, alternative detection methods for GMO inspection are required. In this work, a genosensor based on Surface Plasmon Resonance under continuous flow was developed for the detection and quantification of a genetically modified soybean (event GTS 40-3-2). In a single chip, the simultaneous detection of the event-specific and the taxon-specific samples were achieved, whose detection limits were 20 pM and 16 pM, respectively. The reproducibility was 1.4%, which supports the use of the chip as a reliable and cost-effective alternative to other DNA-based techniques. The results indicate that the proposed method is a versatile tool for GMO quantification in food and feed samples.


Interleukin-6 Disrupts Synaptic Plasticity and Impairs Tissue Damage Compensation in Multiple Sclerosis.
Background: Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). Objective: In the present study, we explored whether interleukin (IL)-6, a major proinflammatory cytokine involved in MS pathogenesis, alters synaptic plasticity and affects the ability to compensate for ongoing brain damage. Methods: The effect of IL-6 incubation on long-term potentiation (LTP) induction was explored in vitro, in mice hippocampal slices. We also explored the correlation between the cerebrospinal fluid (CSF) levels of this cytokine and the LTP-like effect induced by the paired associative stimulation (PAS) in a group of RR-MS patients. Finally, we examined the correlation between the CSF levels of IL-6 at the time of diagnosis and the prospective disease activity in a cohort of 150 RR-MS patients. Results:In vitro LTP induction was abolished by IL-6. Consistently, in patients with MS, a negative correlation emerged between IL-6 CSF concentrations and the effect of PAS. In MS patients, longer disease duration before diagnosis was associated with higher IL-6 CSF concentrations. In addition, elevated CSF levels of IL-6 were associated with greater clinical expression of new inflammatory brain lesions, unlike in patients with low or absent IL-6 concentrations, who had a better disease course. Conclusions: IL-6 interfering with synaptic plasticity mechanisms may impair the ability to compensate the clinical manifestation of new brain lesions in RR-MS patients.


Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism.
The relationship between glucokinase (GK) gene copy number and glucose homeostasis was studied in transgenic mice with additional copies of the entire GK gene locus (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, 22564-22569). The plasma glucose concentration was reduced by 25 +/- 3% and 37 +/- 4% in mice with one or two extra copies of the gene locus, respectively. The basis for the hypoglycemic phenotype was determined using metabolic tracer techniques in chronically cannulated, conscious mice with one extra GK gene copy. Under basal conditions (6-h fasted) transgenic mice had a lower blood glucose concentration (-12 +/- 1%) and a slightly higher glucose turnover rate (+8 +/- 3%), resulting in a significantly higher glucose clearance rate (+21 +/- 2%). Plasma insulin levels were not different, suggesting that increased glucose clearance was due to augmented hepatic, not islet, GK gene expression. Under hyperglycemic clamp conditions the transgenic mice had glucose turnover and clearance rates similar to the controls, but showed a lower plasma insulin response (-48 +/- 5%). Net hepatic glycogen synthesis was markedly elevated (+360%), whereas skeletal muscle glycogen synthesis was decreased (-40%). These results indicate that increased GK gene dosage leads to increased hepatic glucose metabolism and, consequently, a lower plasma glucose concentration. Increased insulin secretion was not observed, even though the transgene is expressed in islets, because hypoglycemia causes a down-regulation in islet GK content (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, in press).


[The malaria situation in the Syrian Arab Republic].
The problem of malaria in Syria is not large one, and because of good surveillance and management, malaria cases have decreased from 626 cases in 1995 to 68 cases in 1998, of which 14 cases were indigenous ones. Vivax malaria cases are registered in the country only.


Elastic contact conditions to optimize friction drive of surface acoustic wave motor.
The optimum pressing force, namely the preload, for a slider to obtain superior operation conditions in a surface acoustic wave motor have been examined. We used steel balls as sliders. The preload was controlled using a permanent magnet. The steel balls were 0.5, 1, and 2 mm diameter, with the differences in diameter making it possible to change contact conditions, such as the contact pressure, contact area, and deformation of the stator and the slider. The stator transducer was lithium niobate, 128 degrees rotated, y-cut x-propagation substrate. The driving frequency of the Rayleigh wave was about 10 MHz. Hence, the particle vibration amplitude at the surface is as small as 10 nm. For superior friction drive conditions, a high contact pressure was required. For example, in the case of the 1 mm diameter steel ball at the sinusoidal driving voltage of 180 V(peak), the slider speed was 43 cm/sec, the thrust output force was 1 mN, and the acceleration was 23 times as large as the gravitational acceleration at a contact pressure of 390 MPa. From the Hertz theory of contact stress, the contact area radius was only 3 microm. The estimation of the friction drive performance was carried out from the transient traveling distance of the slider in a 3 msec burst drive. As a result, the deformation of the stator and the slider by the preload should be half of the vibration amplitude. This condition was independent of the ball diameter and the vibration amplitude. The output thrust per square millimeter was 50 N, and the maximum speed was 0.7 m/sec. From these results, we conclude that it is possible for the surface acoustic wave motor to have a large output force, high speed, quick response, long traveling distance, and a thin micro linear actuator.


Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study.
Carotuximab (DE-122) is a novel endoglin antibody that exhibits potent anti-angiogenic activity. The aim of this study was to evaluate the safety and tolerability of a single intravitreal injection of four ascending doses of carotuximab in patients with persistent exudative age-related macular degeneration (AMD). In an open-label, dose-escalating, sequential cohort study, patients with persistent exudative AMD were assigned to an intravitreal injection of carotuximab 0.5 mg, 1.0 mg, 2.0 mg, or 4.0 mg (n = 3 per group). Safety and change in central subfield thickness (CST), as measured by spectral domain-optical coherence tomography, were assessed from baseline until day 90. Rescue therapy with an anti-vascular endothelial growth factor medication was allowed on days 8, 30, and 60. Seven patients (58%) experienced at least one adverse event (AE), including five patients (41.7%) who experienced one or more AEs in the study eye and two patients (16.7%) who experienced one or more non-ocular AEs. Posterior eye deposits were reported in one patient 2 days after receiving 1.0 mg, but they resolved spontaneously by day 43. A >50-µm reduction in CST on two consecutive visits was observed in four patients (33%), including one patient in each dose cohort. In this study, carotuximab was generally well tolerated, with no serious AEs reported, when administered as a single intravitreal injection to patients with persistent exudative AMD. Further characterization of the safety and efficacy of carotuximab will be needed to determine what role it may have in the treatment of exudative AMD.


The role of CD8(+) T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus.
Little is known about the role of CD8(+) T cells infiltrating the neural parenchyma during encephalitis induced by neurovirulent Sindbis virus (NSV). NSV preferentially infects neurons in the mouse brain and spinal cord; however, it is generally accepted that neurons can express few if any major histocompatibility complex (MHC) class I molecules. We evaluated the possible roles and interactions of CD8(+) T cells during NSV encephalitis and demonstrated that MHC class I antigen (H2K/D) was expressed on endothelial cells, inflammatory cells, and ependymal cells after intracerebral inoculation of NSV. No immunoreactivity was observed in neurons. On the other hand, in situ hybridization with probes for MHC class I heavy chain, beta2 microglobulin, and TAP1 and TAP2 mRNAs revealed increased expression in a majority of neurons, as well as in inflammatory cells, endothelial cells, and ependymal cells in the central nervous system of infected mice. NSV-infected neurons may fail to express MHC class I molecules due to a posttranscriptional block or may express only nonclassical MHC class I genes. To better understand the role CD8(+) T cells play during fatal encephalitis induced by NSV, mice lacking functional CD8(+) T cells were studied. The presence or absence of CD8 did not alter outcome, but absence of beta2 microglobulin improved survival. Interestingly, the intracellular levels of viral RNA decreased more rapidly in immunocompetent mice than in mice without functional CD8(+) T cells. These observations suggest that CD8(+) T cells may act indirectly, possibly via cytokines, to contribute to the clearance of viral RNA in neurons.


Sky-High Safety? A Qualitative Study of Physicians' Experiences of Patient Safety in Norwegian Helicopter Emergency Services.
Patients treated and transported by Helicopter Emergency Medical Services (HEMS) are prone to both flight and medical hazards, but incident reporting differs substantially between flight organizations and health care, and the extent of patient safety incidents is still unclear. A qualitative descriptive study based on in-depth interviews with 8 experienced Norwegian HEMS physicians from 4 different bases from February to July 2020 using inductive qualitative content analysis. The study objectives were to explore the physicians' experience with incident reporting and their perceived areas of risk in HEMS. The HEMS physicians stated that the limited number of formal incident reports was due to the "nature of the HEMS missions" and because reports were mainly relevant when deviating from procedures, which are sparse in HEMS. The physicians preferred informal rather than formal incident reporting systems and reporting to a colleague rather than a superior. The reasons were ease of use, better feedback, and less fear of consequences. Their perceived areas of risk were related to all the phases of a HEMS mission: the physician as the team leader, medication errors, the handover process, and the helicopter as a work platform. The sparse, informal, and fragmented incident reporting provides a poor overview of patient safety risks in HEMS. Focusing on organizational factors and system responsibility and research on environmental and contextual factors are needed to further improve patient safety in HEMS.


Classification and staging of melanoma.
Although a standardized and uniformly accepted cancer staging system is an essential and fundamental requirement to enable meaningful comparisons across patient populations, the sometimes capricious biologic behavior of melanoma makes developing such a staging system particularly difficult. Since the earliest well-documented attempts at classifying patients with cutaneous melanoma were described more than 50 years ago, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The current AJCC staging system is based on relatively well-established prognostic factors; however, several recent reports have identified additional prognostic factors not included in the current system, and other studies support the re-evaluation of some of the currently employed staging criteria. Some of the more controversial areas include the relevance of level of invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance of ulceration, the grouping of satellites with in-transit metastases, the inclusion of microsatellites and local recurrences as a separate staging criterion, the replacement of size of nodal mass with number of positive nodes, the importance of nodal metastases in more than one nodal basin, and the prognostic significance of distant metastases. Future modifications of the staging system are anticipated to better incorporate these observations. Stage-specific staging recommendations for the patient with melanoma provide the clinician with a framework to most efficiently assess extent of disease in an era of cost-conscious clinical practice. In the asymptomatic patient with primary melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of alkaline phosphatase and LDH levels; extensive radiologic evaluations are not indicated, because the rate of detection in this population is extremely low. Additional staging information should also be obtained by the technique of lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional disease (stage III, satellites, and local recurrence), a selective approach to imaging studies is warranted. For this patient population, we recommend complete blood count, liver function tests including alkaline phosphatase and LDH, a chest roentgenogram, and a CT scan of the abdomen. Although the yield of these tests, particularly CT of the abdomen, in detecting distant metastases in asymptomatic patients is low, they may identify false-positive abnormalities and provide an important baseline for future studies in this high-risk population. For patients with disease below the waist or in the head and neck region, we recommend CT of the pelvis and CT of the neck, respectively. Additional studies should be done only if clinically indicated. Finally, patients with known systemic disease (stage IV) should be more comprehensively evaluated, because the likelihood of detecting asymptomatic metastases is higher. Accordingly, in addition to the work-up outlined previously for stage III patients, we also perform a CT scan of the chest and MR imaging of the brain; other studies (e.g., bone scan, gastrointestinal series) are performed on the basis of symptoms.


Mechanical Control of Myotendinous Junction Formation and Tendon Differentiation during Development.
The development of the musculoskeletal system is a great model to study the interplay between chemical and mechanical inter-tissue signaling in cell adhesion, tissue morphogenesis and differentiation. In both vertebrates and invertebrates (e.g., Drosophila melanogaster) the formation of muscle-tendon interaction generates mechanical forces which are required for myotendinous junction maturation and tissue differentiation. In addition, these forces must be withstood by muscles and tendons in order to prevent detachment from each other, deformation or even losing their integrity. Extracellular matrix remodeling at the myotendinous junction is key to resist mechanical load generated by muscle contraction. Recent evidences in vertebrates indicate that mechanical forces generated during junction formation regulate chemical signaling leading to extracellular matrix remodeling, however, the mechanotransduction mechanisms associated to this response remains elusive. In addition to extracellular matrix remodeling, the ability of Drosophila tendon-cells to bear mechanical load depends on rearrangement of tendon cell cytoskeleton, thus studying the molecular mechanisms involved in this process is critical to understand the contribution of mechanical forces to the development of the musculoskeletal system. Here, we review recent findings regarding the role of chemical and mechanical signaling in myotendinous junction formation and tendon differentiation, and discuss molecular mechanisms of mechanotransduction that may allow tendon cells to withstand mechanical load during development of the musculoskeletal system.


The Social Physique Anxiety Scale: an example of the potential consequence of negatively worded items in factorial validity studies.
Social physique anxiety (SPA) based on Hart, Leary, and Rejeski's (1989) Social Physique Anxiety Scale (SPAS) was originally conceptualized to be a unidimensional construct. Empirical evidence on the factorial validity of the SPAS has been contradictory, yielding both one- and two-factor models. The two-factor model, which consists of separate factors associated with positively and negatively worded items, has stimulated an ongoing debate about the dimensionality and content of the SPAS. The present study employed confirmatory factor analysis (CFA) to examine whether the two-factor solution to the 12-item SPAS was substantively meaningful or a methodological artifact. Results of the CFAs, which were performed on responses from four different samples (Eklund, Kelley, and Wilson, 1997; Eklund, Mack, and Hart, 1996), supported the existence of a single substantive SPA factor underlying responses to the 12-item SPAS. There were, in addition, method effects associated with the negatively worded items that could be modeled to achieve good fit. Therefore, it was concluded that a single substantive factor and a non-substantive method effect primarily related to the negatively worded items best represented the 12-item SPAS.


Ultrasensitive time-resolved fluorescence method for alpha-fetoprotein.
We have examined the maximum sensitivity of a newly developed and optimized time-resolved fluorescence immunoassay system. The system, originally described elsewhere (Clin Biochem 1988:21:139-50), has undergone significant improvements in sensitivity through improvements of the labeled reagent used. We have chosen an alpha-fetoprotein (AFP) assay as a model and used monoclonal "capture" antibodies and monoclonal or polyclonal biotinylated antibodies in "sandwich-type" assay configurations. Streptavidin labeled with the europium chelator 4.7-bis(chlorosulfophenyl)-1,10-phenanthroline-2.9-dicarboxylic acid was used for detection. We can measure as few as 3 x 10(5) molecules of AFP with the optimized system. We have applied this assay to measure AFP in the serum of normal individuals after a 10-fold sample dilution. We conclude that this system is extremely sensitive and can be used in immunoassay or other applications where biotinylated reagents can be applied.


[Molecular biology of familial cases of human melanoma].
Skin melanoma is an etiologically heterogeneous disease, the development of which is related to a complex interaction of environmental factors and individual genetic characteristics. This article provides current molecular-genetic aspects of familial cases of melanoma and polymorphism of genes directly related to the risk of developing this hereditary disease. The studies of hereditary cancer cases add our knowledge of mechanisms oncotransformation, genetic changes in signaling pathways, which are responsible for invasiveness, metastasis and drug resistance of melanoma cells of the skin.


Effect of sterol side chain on ion channel formation by amphotericin B in lipid bilayers.
Amphotericin B (AmB) is one of the most efficient antimycotic drugs used in clinical practice. AmB interacts with membrane sterols increasing permeability of fungal membranes; however, it is still unclear how AmB selectively recognizes the fungal sterol, ergosterol (Erg), over other sterols in cell membranes. In this study, we investigated the effect of an Erg side chain on AmB activity by testing a series of Erg analogues that shared the same alicyclic structure as Erg but varied in the side chain structure by using the K(+) influx assay. The results clearly showed that the sterol side chain is essential for AmB selectivity toward Erg and for the activity of AmB-sterol ion channels. In agreement with our previous findings showing the direct interaction between the drug and Erg, these data suggested that AmB directly recognizes the sterol side chain structure, consequently promoting the formation of ion channels by AmB. Furthermore, the C24 methyl group and Δ22 double bond in the side chain of Erg are equally important for the interaction with AmB. Conformational analysis revealed that the C24 methyl group contributes to the interaction by increasing the van der Waals (VDW) contact area of the side chain, while the Δ22 double bond restricts the side chain conformation to maximize the VDW contact with the rigid AmB aglycone. This study provides direct experimental evidence of the mechanism of AmB selectivity toward fungal Erg.


Colony immunoblot assay of botulinal toxin.
Botulinal neurotoxin in and around colonies of Clostridium botulinum types A, B, and E and of toxigenic Clostridium butyricum was detected by an enzyme-linked immunoassay procedure whereby the toxin was transferred from the agar medium to a nitrocellulose support and the immobilized toxin was probed with type-specific antibodies. The method identified the toxin types of the colonies grown from a mixed inoculum of C. botulinum serotypes. The specificity of the antitoxins for type A and B toxins was improved by adsorption of the antitoxins with the antigens of heterologous type cultures.


Biocrusts protect the Great Wall of China from erosion.
The Great Wall of China, one of the most emblematic and historical structures built by humankind throughout all of history, is suffering from rain and wind erosion and is largely colonized by biocrusts. However, how biocrusts influence the conservation and longevity of this structure is virtually unknown. Here, we conducted an extensive biocrust survey across the Great Wall and found that biocrusts cover 67% of the studied sections. Biocrusts enhance the mechanical stability and reduce the erodibility of the Great Wall. Compared with bare rammed earth, the biocrust-covered sections exhibited reduced porosity, water-holding capacity, erodibility, and salinity by 2 to 48%, while increasing compressive strength, penetration resistance, shear strength, and aggregate stability by 37 to 321%. We further found that the protective function of biocrusts mainly depended on biocrust features, climatic conditions, and structure types. Our work highlights the fundamental importance of biocrusts as a nature-based intervention to the conservation of the Great Wall, protecting this monumental heritage from erosion.


Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients.
During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.


Complementary and alternative medicine use among women with breast cancer: a systematic review.
Patients with breast cancer use complementary and alternative medicine (CAM) despite the fact that no studies have shown altered disease progression attributable to CAM use. The purpose of this systematic review is to summarize research as it relates to CAM use among women with breast cancer. Among the many findings of the review, biologically based practices were noted as the types of CAM most used by women with breast cancer, followed by mind-body medicine, whole medical systems, and energy medicine. Sources of information about CAM use for women with breast cancer vary widely, including family, friends, mass media, healthcare providers, CAM providers, and self-help groups. Sociodemographic factors that appear to be related to CAM use were younger age, higher education, higher income, married status, involvement in a support group, and health insurance. The reasons for CAM use reported by women with breast cancer were to help healing, to promote emotional health, and to cure cancer. Oncology nurses should learn more about CAM use among women with breast cancer. Open communication about CAM use helps ensure that safe and holistic care is provided. Additional research in this particular area is needed.


Macrophage-melanoma cell heterokaryons. IV. Unmasking the macrophage-specific membrane receptor.
Mouse peritoneal macrophages possess a specific plasma membrane receptor for antibody-coated particles. Sheep red cells coated with rabbit 7S antibody attach readily to the macrophage surface and are subsequently interiorized. The fusion of macrophage with nonphagocytic mouse melanoma cells produces heterokaryons in which the macrophage receptor is drastically altered. The receptor is present shortly after fusion and heterokaryons are actively phagocytic. The ability to bind and ingest red cells is, however, progressively lost over the next 12-24 hr and does not reappear thereafter. Exposure of heterokaryons to trypsin (1-100 microg/ml for 30 min at 37 degrees C) results in the reappearance of initial receptor activity and the unmasking of the surface receptor. This property is again lost upon subsequent cultivation. The masking process takes place when cells are cultivated in the absence of IgG so that the adsorption of antibody from the medium is not responsible for this phenomenon. Inhibition of heterokaryon protein synthesis preserves phagocytic activity in a reversible fashion and prevents the masking of macrophage receptors. Inhibition of melanoma RNA synthesis before fusion is also able to block subsequent masking, but is ineffective if delayed until after fusion. Ultraviolet irradiation of the melanoma cell before fusion prevents subsequent masking, whereas similar treatment of the macrophage has no effect. Cells differ markedly in their ability to mask the macrophage phagocytic receptor after fusion. Ehrlich ascites tumor cells mask the receptor rapidly, primary chick fibroblasts minimally, and embryonic chick erythrocytes not at all.


Psychosocial support interventions for improved adherence and retention in ART care for young people living with HIV (10-24 years): a scoping review.
Mental health disorders such as high levels of anxiety, isolation, depression and suicide ideation reported among young people living with HIV (10-24 years;YPLHIV) contribute significantly to poor medication adherence and retention in care. While there is evidence supporting the role of psychosocial support interventions in promoting adherence and retention in antiretroviral treatment (ART) among adults living with HIV, there is little evidence on the role of psychosocial support on medication adherence among YPLHIV. This scoping review was designed to identify and classify the types and effects of psychosocial support interventions designed to improve adherence and retention in ART among YPLHIV globally. We searched six electronic databases (i.e., Scopus, Pubmed and EBSCOHost (Academic Search Premier, CINAHL, Psycarticles and Medline). Six relevant articles published between 2011 and 2019 met our inclusion criteria. We extracted information relevant to the nature and outcomes of the reported interventions using thematic content analysis informed by the Population, Intervention, comparison, outcome, and time (PICOT) framework. Four distinctive treatment modalities that focused on improving ART adherence and retention in care were identified: individual counselling, support groups, family-centered services, and treatment supporters. There is a dearth of psychosocial support interventions to improve adherence and retention in ART amongst adolescents and young adults living with HIV. Future research and programming should seek to address psychosocial support interventions or approaches specifically designed to address the needs of YPLHIV. PROSPERO: Registration CRD42018105057 .


Evolutionary analysis of the Chikungunya virus epidemic in Mexico reveals intra-host mutational hotspots in the E1 protein.
The epidemic potential of Chikungunya virus (CHIKV) was recently made evident by its introduction and rapid expansion in the Caribbean and the Americas. We sought to gain a detailed understanding of the dynamics of the epidemic in Mexico, the country with the highest number of confirmed CHIKV cases in the Americas, and to characterise viral evolution at the population and intra-host level. Analysis of the spatiotemporal distribution of 2,739 diagnosed cases in Mexico from December 2014 to December 2015 showed a rapid nationwide expansion of the epidemic with focalisation in the South West of the country. We sequenced the envelope glycoprotein 1 gene (E1) from 25 patients using the Illumina MiSeq platform and report synonymous and non-synonymous consensus mutations. Bayesian phylogenetic analysis using 249 Asian lineage E1 sequences gave updated estimates of nucleotide substitution rates for E1 and time to most recent common ancestor of major lineages. The analysis indicates phylogenetically-related emergent Latin American clusters in South Western Mexico, Nicaragua and Honduras and transmission of American strains in the Pacific islands. Detailed analysis showed that intra-host changes in E1 mainly occurred in two variable regions (E1:189-220 and E1:349-358) in domains II and III, respectively, in residues involved in inter and intra-envelope spike interactions. At the population level, this study sheds light on the introduction and evolutionary dynamics of CHIKV in the Americas. At the intra-host level, this study identifies mutational hotspots of the E1 protein with implications for understanding the relationship between the CHIKV quasispecies, viral fitness and pathogenesis.


Purification and some properties of a novel L-2,4-diaminobutyric acid decarboxylase from Vibrio alginolyticus.
Previous investigations have shown that members of the genus Vibrio possess a novel enzyme activity decarboxylating L-2,4-diaminobutyric acid (DABA) to 1,3-diaminopropane (DAP). In this paper we describe the purification, by about 3600-fold, of the enzyme from V. alginolyticus. The purified enzyme was apparently homogeneous, and had a specific activity of 4200 nmol DAP min-1 (mg protein)-1. The enzyme protein has an Mr of 450,000 +/- 20,000 and is apparently comprised of four identical subunits (Mr 109,000 +/- 1,000). Neither 2,3-diaminopropionic acid, ornithine, lysine nor arginine served as substrates. Some properties of the enzyme were determined. Cultivation of this bacterium in the presence of added DABA brought about increased production of norspermidine (NSPD), characteristically present in this species as well as DAP, suggesting that the enzyme may be functionally implicated in the formation of DAP, a biosynthetic precursor of NSPD.


Effect of acid adaptation on the environmental stress tolerance of three strains of Vibrio parahaemolyticus.
Three strains of Vibrio parahaemolyticus (690, BCRC 13023, and BCRC 13025), involved in foodborne outbreaks in Taiwan, were subjected to acid adaptation at pH 5.5 for 90 min. The effects of acid adaptation on the tolerance of V. parahaemolyticus to various environmental stresses, including heat (47°C), cold (4°C and -20°C), ethanol (8%), high salt (20% NaCl), and hydrogen peroxide (20 ppm) were examined. Results showed that acid adaptation increased the thermal tolerance of the three test strains of V. parahaemolyticus, while it did not affect their cold tolerance. Acid adaptation also increased the ethanol tolerance in V. parahaemolyticus 690 and BCRC 13025, but not in BCRC 13023. Differences in the tolerance to high salts were noted among the three strains after prior acid adaptation. However, these acid-adapted V. parahaemolyticus strains were more susceptible to hydrogen peroxide than their nonadapted controls. These findings demonstrated that acid adaption responses of V. parahaemolyticus varied among strains and types of stress challenge.


Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events.
The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process. A systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types. A total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4-6.6%) of ETFO, 28.6% (26.6-30.6%) of ESD, and 0.53% (0.2-1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1-1.3%), 11% (9.2-13.0%), and 3.2% (2.5-3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed. Considering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications.


Ecological convergence of secondary phytochemicals along elevational gradients.
Biologists still strive to identify the ecological and evolutionary drivers of phytochemical variation that mediate biotic interactions. We hypothesized that plant species growing at sites characterized by high herbivore pressure would converge to produce highly toxic blends of secondary metabolites, independent of phylogenetic constraints. To address the role of shared evolutionary history and ecological niches in driving variation in plant phytochemistry, we combined targeted metabolomics with insect herbivore bioassays and with a set of growth-related traits of several Cardamine species growing along the entire elevational gradient of the Alps. We observed that Cardamine phytochemical profiles grouped according to previously established growth form categorizations within specific abiotic conditions, independently of phylogenetic relationship. We also showed that novel indices summarizing functional phytochemical diversity better explain plant resistance against chewing and sap-feeding herbivores than classic diversity indices. We conclude that multiple functional axes of phytochemical diversity should be integrated with the functional axis of plant growth forms to study phenotypic convergence along large-scale ecological gradients.


Precise assignment of the light-strand promoter of mouse mitochondrial DNA: a functional promoter consists of multiple upstream domains.
Using deletion mutagenesis we localized the promoter for the light strand of mouse mitochondrial DNA to a 97-base-pair region, from -88 to +9 nucleotides of the transcriptional initiation site. Within this region the light-strand promoter could be dissected into at least three different functional domains. The specificity region, a maximum of 19 base pairs between -10 and +9 of the transcriptional initiation site, was essential and sufficient for accurate transcriptional initiation. A second region, extending to -29 nucleotides from the initiation site, facilitated the formation of a preinitiation complex between the template DNA and factor(s) present in the mitochondrial RNA polymerase fraction and was required for efficient transcription. A third, ill-defined upstream region, which extended up to -88 nucleotides from the initiation site, appeared to influence template transcriptional efficiencies in competition assays. Without the specificity domain, the upstream regions were incapable of supporting any transcription. The presence of multiple upstream domains was confirmed by disrupting nucleotide sequences in the upstream region by using linker insertion and linker replacement techniques.


Neurotrophic factors in the treatment of peripheral neuropathy.
Peripheral neuropathies are common and frequently debilitating disorders which may include various subpopulations of motor, sensory or autonomic neurons depending on the underlying aetiology. They are likely to be the first group of neurological disorders to be successfully treated with growth factors since peripheral nerves are accessible to proteins given systemically. Preclinical and ongoing clinical trials of nerve growth factor (NGF) suggest that it will be useful for the treatment of diabetic, toxic and compressive sensory neuropathies. At appropriate doses NGF has no significant side effects in humans. Since NGF administration to mature animals stimulates synthesis of brain-derived neurotrophic factor and perhaps other neurotrophins in peripheral nerves, the spectrum of neuropathies treatable with NGF is wider than might be predicted. Preclinical studies suggest that insulin-like growth factor 1 (IGF-1) will be useful for the treatment of mixed motor and sensory neuropathies. For example, IGF-1 treatment can prevent the experimental motor and sensory neuropathies caused by the antitumour drugs, vincristine and cisplatin. Other neurotrophic factors have also shown promise in preclinical trials. The successful use of growth factors in the treatment of peripheral neuropathies may provide the first true therapy for this previously untreatable and devastating group of neurological disorders.


[Isolation and characterization of wild Sporothrix schenkii strains and investigation of sporototrichin reactors].
We conducted a study in the southern mountains of the Mexican State of Oaxaca that consisted of isolation of wild Sporothrix schenckii strains obtained from soil samples and investigation of positive reactors to skin test reaction with sprotrichin antigen. The study was conducted by means of recollection of soil samples and processing of these with dilution methods and fungal isolation in ordinary culture media Sabouraud simple Agar with and without antibiotics (SS, SA). Suspected strains underwent dimorphism, melanin formation, and virulence confirmation tests. Investigation of positive reactors to sporotrichin Y (yeast) was also conducted. Three supposed strains were identified due to their reproductive characteristics, melanin production, and virulence. In the community, 144 individuals were studied, of whom 6.25% were positive to sporotichin. Isolation of virulent strains of Sporothrix schenkii from nature (soil) and primoinfection of a percentage of the studied population were confirmed.


Sleep disordered breathing may not be an independent risk factor for diabetes, but diabetes may contribute to the occurrence of periodic breathing in sleep.
(a) To determine if self-reported diabetes mellitus is independently associated with sleep-disordered breathing (SDB); (b) to determine if diabetes mellitus is specifically associated with central sleep apnea including periodic breathing (Cheyne-Stokes breathing pattern) during sleep. The study population reflected participants in the on-going Sleep Heart Health Study (SHHS). Analyses were conducted utilizing data obtained from 4872 SHHS participants without prevalent cardiovascular disease (CVD) and 1002 participants with self-reported CVD, defined as hospitalization for non-fatal coronary heart disease, congestive heart failure, myocardial infarction, coronary artery bypass graft, and stroke. SHHS methodologies have been previously reported and include performance of overnight, in-home polysomnography (PSG), which recorded variables reflecting sleep architecture and breathing, permitting identification of obstructive and central apneas, hypopneas, periodic breathing and oxyhemoglobin saturation (SpO(2)). Anthropomorphic metrics as well as systemic blood pressure measurements were obtained at the time of PSG. Other health data were available from questionnaires and the data sets of the parent cohorts from whom SHHS participants were recruited. The investigators assessed and compared breathing parameters, sleep architecture and CVD variables in diabetic and non-diabetic participants. The relationships between diabetes and the various study parameters, independent of potential confounders, were examined by multivariable modeling. Linear regression modeling was employed to examine the relationship between continuously distributed variables such as respiratory disturbance index log (RDI). The relationships between diabetes and dichotomous outcome variables such as central apnea index (CAI), obstructive apnea index (OAI), periodic breathing and the percentage of time spent at various levels below SpO(2) 90% were examined by the logistic regression model. Age, gender, race, BMI and neck circumference were forced into all multivariable analyses since these factors are associated with both diabetes mellitus and SDB. The investigators reported that the prevalence of CVD risk factors including increased BMI, waist circumference, neck circumference, triglycerides, reduced HDL cholesterol and hypertension was greater in diabetic than non-diabetic participants. Native Americans represented a disproportionately high percentage of the diabetic population. Unadjusted data obtained from participants without prevalent CVD indicated that the mean RDI was higher in the diabetic participants. Moreover, there was a greater percentage of diabetic participants in the higher RDI categories (e.g. 23.8% of the 470 diabetics and 15.6% of the 4402 non-diabetics had RDI>15, P<0.001). Similarly, the unadjusted data indicated that a significantly greater proportion of the diabetic participants spent >5% and >10% of sleep time below SpO(2) 90%, compared with the non-diabetic participants. The unadjusted data from participants without prevalent CVD indicated that the diabetic and non-diabetic participants did not differ with regard to distribution by category of OAI severity (e.g. > or =2 events/h, > or =3 events/h, or > or =4 events/h). On the other hand, although the prevalence of central apneas was low, a significantly greater proportion of diabetic participants were in the CAI categories (> or =2 events/h and > or =3 events/h) than non-diabetic subjects. There was no difference between diabetic and non-diabetic individuals with regard to CAI prevalence in the > or =4 events/h category. Of note, a greater percentage of diabetic patients exhibited periodic breathing (3.8% vs. 1.8%, diabetic and non-diabetic participants, respectively, P=0.002). Repeating the above analyses with inclusion of the participants with prevalent CVD did not change these relationships, and in fact, the differences between diabetic and non-diabetic participants with respect to central events and periodic breathing became more evident (the data forre evident (the data for this were not provided in the paper). Linear regression analyses demonstrated that BMI, age and male gender were independently related to increased RDI among participants without prevalent CVD. Furthermore, after adjusting for age, gender, race, BMI and neck circumference, there was no difference in geometric mean RDI between the diabetic and non-diabetic participants. The adjusted odds of having RDI> or =15 and the adjusted odds for spending> or =5% or > or =10% of sleep time with SpO(2) <90% did not differ between the diabetic and non-diabetic individuals. The investigators also examined sleep architecture in the study cohort. There were no differences between the diabetic and non-diabetic groups with regard to the adjusted proportion of time spent in non-REM sleep stages, although the mean percent time spent in REM sleep was 1.1% less in the diabetic individuals. The findings were the same with or without inclusion of participants with known CVD. Even after adjustment for potential confounders, in a sample without or with prevalent CVD, diabetic participants had increased adjusted odds for periodic breathing odds ratio (1.8, 95% confidence interval (CI) with a range of 1.02--3.15 in diabetic participants without prevalent CVD vs. 1.74, 95% CI with a range of 1.16--2.62 in diabetic participants with prevalent CVD). There was a suggestion of increased odds for CAI in diabetic subjects when analyzing populations with and without prevalent CVD. The authors concluded that diabetes mellitus is associated with sleep apnea but that this association is largely explained by risk factors in common for both disorders, most notably obesity. After adjusting for confounding factors there was no difference between diabetic and non-diabetic participants with regard to obstructive events. However, even after adjusting for potential confounders, there was a greater prevalence of periodic breathing in diabetic subjects. Although not reaching statistical significance, there was a suggestion of an increased prevalence of central events in the diabetic population, particularly when the sample included participants with known CVD. The investigators believed it unlikely that the findings were attributable to underlying congestive heart failure in as much as the diabetic subjects without prevalent CVD exhibited increased prevalence of periodic breathing and possibly increased central events. The authors proposed that diabetes mellitus might be a cause of SDB, mediated through autonomic neuropathy that may alter ventilatory control mechanisms. In this context, the authors commented that autonomic neuropathy may cause perturbations in ventilatory control by altering chemoreceptor gain or altering cardiovascular function (although the authors discounted underlying congestive heart failure as an explanation for the higher prevalence of periodic breathing in diabetic participants). To reinforce their conclusions, the authors cited the literature indicating increased prevalence of sleep apnea in diabetic patients with autonomic dysfunction, as well as the association between Shy--Drager syndrome, in which autonomic insufficiency is a constitutive element, and central sleep apnea.


Mitochondrial mayhem: the mitochondrion as a modulator of iron metabolism and its role in disease.
The mitochondrion plays vital roles in various aspects of cellular metabolism, ranging from energy transduction and apoptosis to the synthesis of important molecules such as heme. Mitochondria are also centrally involved in iron metabolism, as exemplified by disruptions in mitochondrial proteins that lead to perturbations in whole-cell iron processing. Recent investigations have identified a host of mitochondrial proteins (e.g., mitochondrial ferritin; mitoferrins 1 and 2; ABCBs 6, 7, and 10; and frataxin) that may play roles in the homeostasis of mitochondrial iron. These mitochondrial proteins appear to participate in one or more processes of iron storage, iron uptake, and heme and iron-sulfur cluster synthesis. In this review, we present and critically discuss the evidence suggesting that the mitochondrion may contribute to the regulation of whole-cell iron metabolism. Further, human diseases that arise from a dysregulation of these mitochondrial molecules reveal the ability of the mitochondrion to communicate with cytosolic iron metabolism to coordinate whole-cell iron processing and to fulfill the high demands of this organelle for iron. This review highlights new advances in understanding iron metabolism in terms of novel molecular players and diseases associated with its dysregulation.


Selective purging by human interleukin-2 activated lymphocytes of bone marrows contaminated with a lymphoma line or autologous leukaemic cells.
The ability of recombinant interleukin 2 (rIL2) activated lymphocytes (LAK) to purge BM samples contaminated by tumour cells was evaluated. Human BM mononuclear cells were contaminated with 10% of the lymphoma line CA46 and then cultured in liquid medium containing 1000 U/ml of rIL2 and/or LAK autologous to the used BM. At the end of coculture the growth of residual tumour cells and of CFU-GM were evaluated by clonogenic assay. No tumour cell growth was observed in 5/5 independent experiments after 18 h of coculture with LAK. No significant inhibition of CFU-GM growth was also noted. Subsequently, the effect of LAK on BM obtained from four leukaemic patients and contaminated with 20-50% of their own AML and ALL cells was studied using MAb as a tool for identifying leukaemic cells. LAK eliminated 24-78% of contaminating cryopreserved uncultured autologous leukaemic cells. In five cases the BM was contaminated by a low (2%) amount of ALL cells. In these patients the monoclonal heavy chain rearrangement typical of ALL was no longer visible after coculture with LAK. Evidence for selective tumour cytotoxicity by LAK was confirmed by using autologous BM cells as hot and cold targets in a 51Cr release assay. Finally, successful haematologic reconstitution of lethally irradiated BALB/c mice was obtained using syngeneic BM cocultured with LAK. These results support the investigational use of rIL2 and LAK in the treatment of human leukaemia.


Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.
The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.


Pilus backbone protein PitB of Streptococcus pneumoniae contains stabilizing intramolecular isopeptide bonds.
Streptococcus pneumoniae type 2 pili are recently identified fimbrial structures extending from the bacterial surface and formed by polymers of the structural protein PitB. Intramolecular isopeptide bonds are a characteristic of the related pilus backbone protein Spy0128 of group A streptococci. Based on the identification of conserved residues in PitB, we predicted two intramolecular isopeptide bonds in PitB. Using a combination of tandem mass spectrometry and Edman sequencing, we show that these bonds were formed between Lys(63)-Asn(214) and Lys(243)-Asn(372) in PitB. Mutant proteins lacking the intramolecular isopeptide bonds retained the proteolytic stability observed with the wild type protein. However, absence of these bonds substantially decreased the melting temperature of the PitB-derivatives, indicating a stabilizing function of these bonds in PitB of the pneumococcal type 2 pilus.


The improvement on the skin surface by a new type of dermocosmetic loaded plant extract: A split face skin topographic study.
Various extrinsic and intrinsic origins slant skins and pledge evident vicissitudes of the skin surface. We explored the effects of dermocosmetic loaded medical Cannabis seed extract and evaluate the improvement on the skin surface in Asian and male volunteers in a split face topographic study. Dermocosmetic and base (without extract) fabricated were directed to apply by volunteers (Asian male) on their right and left cheek, respectively, in the split face skin topographic study up to three months. Efficacy of dermocosmetic versus base was assessed by non- invasive diagnostic technique focusing on skin texture parameters (energy, contrast and variance) and surface evaluation of the living skin (SELS), SEr (skin roughness), SEsc (skin scaliness), SEsm (skin smoothness), SEw (skin wrinkles). Unlike base, dermocosmetic showed significant effects on skin texture parameters (energy, variance and contrast) and SELS (SEr, SEsc, SEsm and SEw) parameters in Asian male volunteers when ANOVA applied. The level of significance was 5%. Dermocosmetic ultimately improved on skin surface and advocacies for anti-aging effects on skin appearance.


Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice.
MMPs are implicated in LV remodeling after acute myocardial infarction (MI). To analyze the role of MMP-2, we generated MI by ligating the left coronary artery of MMP-2-KO and WT mice, the latter of which were administered orally an MMP-2-selective inhibitor or vehicle (TISAM). The survival rate was significantly higher in MMP-2-KO and TISAM-treated mice than in control WT mice. The main cause of mortality in control WT mice was cardiac rupture, which was not observed in MMP-2-KO or TISAM-treated mice. Control WT mice, but not MMP-2-KO or TISAM-treated mice, showed activation of the zymogen of MMP-2, strong gelatinolytic activity, and degradation of ECM components, including laminin and fibronectin, in the infarcted myocardium. Although infarcted cardiomyocytes in control WT mice were rapidly removed by macrophages, the removal was suppressed in MMP-2-KO and TISAM-treated mice. Macrophage migration was induced by the infarcted myocardial tissue from control WT mice and was inhibited by treatment of macrophages with laminin or fibronectin peptides prior to migration assay. These data suggest that inhibition of MMP-2 activity improves the survival rate after acute MI by preventing cardiac rupture and delays post-MI remodeling through a reduction in macrophage infiltration.


Cardiac Tissue Engineering as Use Case to Connect Biomedical Research Laboratories to an Emerging Global Data Infrastructure.
Methods for cardiac tissue engineering and application in experiments are core technologies developed at the Institute of Pharmacology and Toxicology in Göttingen. As is the case in many academic research laboratories data capture and documentation may be improved to latest methods of digital research. A comprehensive information system infrastructure is the foundation of further advances toward automation of lab processes. A data management system concept is proposed and prototypically deployed that enables traceability of assets within the lab and reproducibility of published assays and results. The prototype integrates existing electronic lab notebook, experiment result database, and a newly introduced research data management system by means of a custom developed portal and integration component. The architecture concept and developed integration tools explore connection of routine experimental work in a biomedical research lab to a universal infrastructure of data.


Comparing the Accuracy of Digital Subtraction Angiography, CT Angiographyand MR Angiography at Estimating the Volume of Cerebral Aneurysms.
While there are many studies that compare imaging modalities in the detection of cerebralaneurysms there are no existing studies that compare two dimensional digital subtraction angiography (DSA), CT angiography (CTA) and MR angiography (MRA) in calculating the volume of cerebral aneurysms. This study will compare these imaging modalities on seven in vitro models of known volume. Seven silicone models of cerebral aneurysms were chosen representing slight variations in geometric shape and size. The volume of each model was measured by weighing the amount of water required to fill the aneurysm to the parentartery. Contrast enhanced images of the modelswere taken with DSA, CTA and MRA. The images were interpreted by four independent readers and the volumes were calculated. The measured volumes from the water weight analysis were compared to the volumes calculated from the interpreter's measurements. The accuracy of DSA, CTA and MRA were compared using the percent of absolute and true variance from the measured volume. The average percent absolute variance for DSA was 14.3%, CTA was 16.8% and MRA was 18.6%. While these differences were minimal, comparing the percent of true variance demonstrated an average variance of -1.9% for DSA, 16.1% for CTA and -15.9% for MRA. Calculating the volume of cerebral aneurysms, while increasingly important, is difficult and error prone. It is important to understand the limitations and inherent errors before relyingon calculated volumes in clinical decision making. Regardless of imaging modality, one should consider error rates of 14-19% for calculatingvolume while keeping in mind the tendencyfor CTA to overestimate volume, MRA to underestimate volume and DSA to both under and overestimate equally.


[Prognostication of the performance possibility for laparoscopic exploration of common biliary duct in an acute calculous cholecystitis].
The results of miniinvasive treatment of 319 patients, suffering complicated acute calculous cholecystitis, using laparoscopic technologies, were analyzed in retrospective investigation. The risk factors for unfaithful conduction of laparoscopic intervention on biliary ducts were determined. The chances for possibility of laparoscopic choledocholithoextraction performance on biliary ducts were established, using binary regressive analysis. Reduction of rate of unfaithful laparoscopic interventions, made on common biliary duct, from 18.6 to 5.9% was promoted by application of mathematically elaborated criteria in accordance to the prospective investigation data.


[Pituitary gonadotropic function in uterine trophoblastic tumor].
A simultaneous determination of 3 gonadotropic hormones of the hypophysis (follitropin, lutronin and prolactin) using a radioimmunoassay in 33 patients with trophoblastic uterine tumors and 22 women on the 1st-8th day after normal delivery, has shown that there are not only significant differences in the nature of the secretion of hypophyseal gonadotropic hormones in pathology as compared to the normal postnatal period but also differences in different forms of trophoblastic tumors. These differences were characterized by a progressive, according to the severity of disease, independence between trophoblastic tissue function and gonadotropic function of the hypophysis. A marked suppression of follicle-stimulating function of the hypophysis after normal delivery decreased hydatidiform mole and trophoblastic tumors and was not observed in patients with chorioepithelioma of the uterus.


High prevalence of erythromycin-resistant, clindamycin/miocamycin-susceptible (M phenotype) Streptococcus pyogenes: results of a Spanish multicentre study in 1998. Spanish Group for the Study of Infection in the Primary Health Care Setting.
Using the standard agar dilution method we studied the prevalence of susceptibility to 14-, 15- and 16-membered ring macrolides and clindamycin in Streptococcus pyogenes isolated in 1998 from 21 laboratories in Spain. The number of strains admitted to the study was proportional to the numbers of inhabitants in each geographical area. We also determined the susceptibility phenotypes and the genetic basis for the antibiotic resistance. A total of 486 unduplicated isolates of S. pyogenes were used. Throat swab samples provided 359 (73.9%) isolates, and the remaining 127 isolates were from other sources. One hundred and fourteen (23.5%) isolates were resistant to erythromycin, a 14-membered ring macrolide, and azithromycin, a 15-membered macrolide, whereas only 1% of isolates were resistant to miocamycin, a 16-membered macrolide and 0.8% were resistant to clindamycin. Of the 114 erythromycin-resistant strains, 109 (95.6%) were susceptible to clindamycin and miocamycin. Since induction with erythromycin did not modify susceptibility to the latter antibiotics, these 109 strains were considered to have the M phenotype. Twenty strains with the M phenotype, one per laboratory, were assayed by PCR and showed the presence of the mef gene, which is responsible for antibiotic resistance by an efflux system. Among comparable studies covering entire countries, ours demonstrates one of the highest rates of S. pyogenes erythromycin resistance and clindamycin and miocamycin susceptibility in the world. Strains with the M phenotype account for the great majority of these isolates.


Prostatic Artery Embolization: Technical Pearls.
Benign prostatic hyperplasia (BPH) is a condition that primarily affects men between the fourth and seventh decades of life, occurring due to enlargement of the prostate which subsequently causes compression of the prostatic urethra causing chronic obstruction of the urinary outflow tract. BPH can cause significant quality-of-life issues such as urinary hesitancy, intermittency, decreased urinary stream, a sensation of incomplete emptying, dysuria, urinary retention, hematuria, and nocturia. Several medical and surgical treatment modalities are available for the treatment of lower urinary tract symptoms and other BPH-related sequela; however, increasingly prostate artery embolization is being utilized in this patient population. Technical demands for this procedure in this population can be significant. This article describes the optimal techniques, tricks, and advanced imaging techniques that can be used to achieve desired technical outcomes.


[The Swiss gatekeeper system--a model for improving capacity development and economic effectiveness].
The German as well as the Swiss health care system are facing similar problems. However, in Switzerland different gatekeeper systems to improve the capacity and economic efficiency were successfully tried and tested. The main structures of gatekeeping are the HMO health centres and different GP systems. Central to this idea is the primary care physician functioning as a gatekeeper. He has to control the demands of medical services according to the patient's needs to fulfil integral, comprehensive and economic criteria. Although data processing has not yet been completed yet, first results show clear advantages of the gatekeeper system in respect of the costs and quality of health care compared with the customary Swiss health insurance. Although in Switzerland there are still relatively few persons insured according to the gatekeeper system, it is expected that particularly the family physician systems will expand considerably in the future. Reorganisation and rearrangements of the medical care providers are likely.


[ADHD should be given more attention--early interventions prevents unnecessary suffering].
ADHD is a common neurodevelopmental/neuropsychiatric disorder affecting about 5 percent of children. About 2-3 percent meet diagnostic criteria in adulthood as well. The core symptoms include inattention with or without hyperactivity/restlessness and impulsivity. The main cognitive deficit involves executive functions, probably related to a weak reward system. Symptoms will affect daily functioning at home, among friends and at school/work. In girls and women particularly, a correct diagnosis of ADHD is often late, or is not at all appropriately considered. Co-existing disorders are common; dyslexia, developmental coordination disorder, emotional lability, conduct disorder, autistic symptoms, obsessive compulsive disorder, depression, bipolar disorder, Tourette syndrome, eating disorder, sleeping disorder, and substance abuse. Extensive research in ADHD has increased knowledge in genetics, neurobiology, neuropsychology, intervention, and treatment. Despite this, many individuals with ADHD are not offered a correct assessment, and accordingly, not given appropriate support and treatment.


Determination of 3',4',5',5,7-pentamethoxyflavone in the plasma and intestinal mucosa of mice by HPLC with UV detection.
In a preliminary experiment 3',4',5',5,7-pentamethoxyflavone (PMF) inhibited adenoma development in Apc(Min) mice, a model of the human heritable condition familial adenomatous polyposis. An HPLC method for tricin was modified and validated to permit measurement of PMF in mouse plasma and intestinal mucosa. HPLC analysis was carried out on a Hypersil-BDS C(18) column with detection at 324 nm and tricin as internal standard. The assay was linear in the range of 100-2000 ng/mL plasma and 1.0-40 microg/mL mucosa. PMF in plasma was efficiently extracted using solid-phase columns. In the case of mucosa organic solvent protein precipitation displayed satisfactory accuracy and precision. The assay recovery at low, medium and high concentrations was between 85 and 103% for both biomatrices, with a relative standard deviation of <15%. The lower limits of quantitation for plasma and mucosa were 100 ng/mL and 1.0 microg/mL, respectively. This method allowed measurement of PMF steady-state median concentrations in plasma (1.08 nmol/mL, n = 11; 10th and 90th percentiles: 0.633 and 2.385 nmol/mL) and mucosa (108.5 nmol/g, n = 9; 10th and 90th percentiles: 38.9 and 164.4 nmol/g) in mice which had received PMF (0.2%, w/w) with their diet.


[Infantile myasthenia gravis: report of a case diagnosed clinically].
A rare case of infantile myasthenia gravis (congenital type) is reported. The child was 16 months old at the time of the diagnosis, although she presented signs suggestive of the disease since two months earlier. The diagnosis was based solely upon clinical criteria, including immediate response to a therapeutic test with Neostigmine, followed by excellent response to treatment with Mestinon. A review of the different types of myasthenia gravis in infancy is made, with emphasis on the clinical criteria for differential diagnosis of these cases.


Dual action of isoflurane on the gamma-aminobutyric acid (GABA)-mediated currents through recombinant alpha(1)beta(2)gamma(2L)-GABA(A)-receptor channels.
Isoflurane (ISO) increased the agonist-induced chloride flux through the gamma-aminobutyric acid A receptor (GABA(A)R). This may reflect an anesthetic-induced increase in the apparent agonist affinity. A dual effect of anesthetics was postulated for both the nicotinic acetylcholine receptor (nAChR) and the GABA(A)R. We tested the hypothesis that, in addition to a blocking effect, ISO increases gamma-aminobutyric acid (GABA)-gated currents through recombinant GABA(A)R channels. HEK293 cells were transfected with rat cDNA for alpha(1),beta(2),gamma(2L) subunits. Currents elicited by 1 mM or 0. 01 mM GABA, respectively, alone, or with increasing concentrations of ISO, were recorded by using standard patch clamp techniques. ISO reduced the peak current elicited by 1 mM GABA. Currents induced by 0.01 mM GABA were potentiated by small ISO (twofold at 0.5 mM ISO) and inhibited by larger concentrations. Withdrawal of ISO and GABA induced rebound currents, suggesting an open-channel block by ISO. These currents increased with increasing concentrations of ISO. At large concentrations of ISO, the inhibitory effect predominated and was caused by, at least partly, an open-channel block. At small concentrations of ISO, potentiation of the GABA-gated currents was more prominent. This dual action of ISO indicates different binding sites at the GABA(A)R. The balance between potentiation and block depends on the concentrations of both ISO and GABA.


Intravenous isosorbide dinitrate in patients with refractory pump failure and acute myocardial infarction.
We studied the hemodynamic effects of isosorbide dinitrate administered by continuous i.v. infusion to 22 patients with chronic refractory pump failure and 18 with pump failure due to acute myocardial infarction. In patients with severe pump failure, i.v. ISDN markedly decreased pulmonary capillary wedge pressure (p less than 0.001), moderately increased cardiac output (p less than 0.01), and decreased systemic vascular resistance (SVR) (p less than 0.001). There were no deleterious effects on arterial pressure and heart rate. The effects obtained in acute and chronic left ventricular failure were similar. Patients with initial SVR levels lower than 1500 dyn-sec-cm-5 did not significantly increase their cardiac output (p less than 0.005). Cardiac output increased more than 25% only in patients with initial high SVR levels (greater than 2000 dyn-sec-cm(-)5). Positive correlations were found between high SVR and elevated plasma catecholamines (r = 0.53, p less than 0.05) and between the initial SVR and initial heart rate (r = 0.70, p less than 0.01). The i.v. administration of isosorbide dinitrate appears to be an efficient therapy, particularly in selected patients with ischemic pump failure.


Expression of tachykinin3 and related reproductive markers in the brain of the African cichlid fish Astatotilapia burtoni.
Neurokinin B, encoded by the tachykinin3 gene, plays a crucial role in regulating reproduction in mammals via KNDy neurons and interaction with GnRH. Previous work in teleost fishes has focused on hypothalamic tac3 expression for its role in reproduction, but detailed studies on extra-hypothalamic tac3 expression are limited. Here, we identified two tac3 genes in the social African cichlid fish Astatotilapia burtoni, only one of which produces a functional protein containing the signature tachykinin motif. In situ hybridization for tac3a mRNA identified cell populations throughout the brain. Numerous tac3a cells lie in several thalamic and hypothalamic nuclei, including periventricular nucleus of posterior tuberculum, lateral tuberal nucleus (NLT), and nucleus of the lateral recess (NRL). Scattered tac3-expressing cells are also present in telencephalic parts, such as ventral (Vv) and supracomissural (Vs) part of ventral telencephalon. In contrast to other teleosts, tac3 expression was absent from the pituitary. Using double-fluorescent staining, we localized tac3a-expressing cells in relation to GnRH and kisspeptin cells. Although no GnRH-tac3a colabeled cells were observed, dense GnRH fibers surround and potentially synapse with tac3a cells in the preoptic area. Only minimal (<5%) colabeling of tac3a was observed in kiss2 cells. Despite tac3a expression in many nodes of the mesolimbic reward system, it was absent from tyrosine hydroxylase (TH)-expressing cells, but tac3a cells were located in areas with dense TH fibers. The presence of tac3a-expressing cells throughout the brain, including in socially relevant brain regions, suggest more diverse functions beyond regulation of reproductive physiology that may be conserved across vertebrates.


Sex-biased effects on hippocampal circuit development by perinatal SERT expression in CA3 pyramidal neurons.
Neurodevelopmental disorders ranging from autism to intellectual disability display sex-biased prevalence and phenotypical presentations. Despite increasing knowledge about temporospatial cortical map development and genetic variants linked to neurodevelopmental disorders, when and how sex-biased neural circuit derailment may arise in diseased brain remain unknown. Here, we identify in mice that serotonin uptake transporter (SERT) in non-serotonergic neurons - hippocampal and prefrontal pyramidal neurons - confers sex-biased effects specifically during neural circuit development. A set of gradient-patterned CA3 pyramidal neurons transiently express SERT to clear extracellular serotonin, coinciding with hippocampal synaptic circuit establishment. Ablating pyramidal neuron SERT (SERTPyramidΔ) alters dendritic spine developmental trajectory in the hippocampus, and precipitates sex-biased impairments in long-term activity-dependent hippocampal synaptic plasticity and cognitive behaviors. Transcriptomic analyses identify sex-biased alterations in gene sets associated with autism, dendritic spine structure, synaptic function and male-specific enrichment of dysregulated genes in glial cells in early postnatal SERTPyramidΔ hippocampus. Our data suggest that SERT function in these pyramidal neurons underscores a temporal- and brain region-specific regulation of normal sex-dimorphic circuit development and a source for sex-biased vulnerability to cognitive and behavioral impairments. This article has an associated 'The people behind the papers' interview.


The brain-specific gene 1B236 is expressed postnatally in the developing rat brain.
The rat brain-specific polypeptide 1B236 was previously characterized by molecular cloning and nucleotide sequence determination of its mRNA. It has been shown to exist in rat brain in discrete neuronal circuits, primarily as a 100,000 Da glycoprotein. We now have determined the time course of expression of 1B236 mRNA and protein in rat brain during fetal and postnatal development, detecting 1B236 mRNA by RNA blotting and assaying 1B236 protein by electroblotting and radioimmunoassay with antibodies against synthetic peptides. By both indices, expression of the 1B236 gene products is found to be a relatively late event in neuronal development. 1B236 mRNA is first detectable in extracts of whole rat brain at Postnatal Day 5 (PD 5) and increases to a maximum concentration at PD 25. In extracts of dissected brain regions, 1B236 mRNA is first detectable at PD 5 in hindbrain and cerebellum, at PD 9 in midbrain/diencephalon, but not until PD 13 in telencephalon. The appearance of 1B236 protein follows a very similar time course to that of its mRNA in both whole brain and dissected brain regions, suggesting that the expression of the protein during development is regulated largely by transcription of its mRNA. The pattern of 1B236 expression was confirmed by immunocytochemical localization of 1B236 protein: Immunoreactive material can be detected first in spinal cord at PD 3-PD 5 and then appears in progressively more rostral brain regions in increasingly older animals. Several brain regions, however, that do not contain 1B236 immunoreactivity in the adult, such as optic nerve and somatic efferent cranial nerve nuclei, show transient expression of 1B236 during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)


N-acetyl-B-D-glucosaminidase and inflammatory response after cardiopulmonary bypass.
To determine the changes in activity of plasma N-acetyl-beta-D-glucosaminidase, a marker for inflammation as well as renal, pulmonary and cardiac damage and proinflammatory cytokines in patients undergoing coronary artery bypass grafting and find out the relationship between their plasma levels with clinical outcome of patients. Cross-sectional study. The Aga Khan University, Karachi, from January to June 2003. N-acetyl-beta-D-glucosaminidase (NAG) activity and concentrations of tumor necrosis factor-alpha of (TNFalpha), interleukin 6 (IL-6), interleukin 8 (IL8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were monitored in plasma samples of 12 angina patients undergoing coronary artery bypass grafting (CABG), before, immediately after and 5 days post-surgical procedure. Serum glucose concentrations were also monitored in those patients. Patient's clinical condition was monitored during this time period. No significant increase was observed in plasma NAG activity (a marker of inflammation) or in plasma levels of TNFalpha, IL-6, IL-8 and GM-CSF immediately after surgery, indicating that cardiopulmonary bypass itself does not produce any significant amount of inflammation immediately after CABG. However, 5 days post surgery, there was a significant increase in plasma NAG activity (p=0.001), TNFalpha (p=0.047) and GM-CSF (p=0.045). There was no relationship between plasma NAG activity and clinical outcome because various parameters of renal, cardiac and pulmonary functions, though slightly affected, remained within the normal limits. Increased levels of NAG and TNFalpha did not affect clinical outcome. However, data suggest that NAG can be a potential marker for inflammation and end organ damage following CABG. An increase in GM-CSF on day 5 following CABG indicates enhanced body's defense mechanism against infection.


Sexual Abuse of Children With Disabilities: Key Lessons and Future Directions Based on a Scoping Review.
In recent years there has been a growing public and professional interest in situations of risk, abuse, and exploitation of children with disabilities (CWDs). Despite the increasing awareness of CWDs experiencing child sexual abuse (CSA) at high rates, research in this area is still in its infancy. The current study seeks to identify, map, and thoroughly analyze the existing knowledge to better inform future research, policy, and practice. A scoping review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying 35 articles addressing CSA among CWDs based on self-report surveys, official report data, and qualitative interviews. The findings addressed the phenomenon's epidemiology, disclosure, identification patterns, and consequences. Studies showed that CWDs experience CSA two to four times more often than children without disabilities and that they suffer longer and harsher abuse due to factors that complicate the identification of CSA of CWDs. This review highlights the diverse methodologies, producing a high variance in phenomenon rates, as well as unique methodological strategies for addressing challenges in CSA and disability research. Future research should focus on qualitative-retrospective studies of the perceptions of survivors and significant others in their lives (e.g., parents). Moreover, an intersectionality paradigm must be adopted in future studies to address the diverse contexts that construct the phenomenon (including sociocultural contexts). There is also a need to develop integrative interventions to allow higher accessibility of services, adaptive identification mechanisms, and more effective collaboration between professionals and CWDs.


Cost of treatment of childhood-onset systemic lupus erythematosus.
To determine the direct cost of care of children with childhood-onset systemic lupus erythematosus (cSLE), and to determine the direct cost per quality-adjusted life year (QALY) with cSLE. Administrative databases from 2 large tertiary pediatric rheumatology centers in the United States were reviewed for all patients with cSLE (n = 119) diagnosed and regularly treated in these centers between January 2001 and April 2004. Health-related quality of life estimates for patients with cSLE (n = 297) reported in the literature were used to calculate QALYs based on global health ratings of the Child Health Questionnaire (range 0-100). Information on 3,184 patient-months of followup was included in the analysis. During a mean +/- SD followup of 27 +/- 11.8 months, the direct cost of care for the cohort amounted to $3,965,048, excluding outpatient medications. Irrespective of patient sex, the mean +/- SD cost of cSLE per month was $1,245 +/- $2,352, or approximately $14,944 per year. Inpatient and day hospital care accounted for 28% of the cost, laboratory testing accounted for 21%, inpatient/day-patient medication costs accounted for 13%, and dialysis accounted for 11%. Visits to the rheumatology clinic only contributed 9% to the direct cost of care. When including an estimated outpatient medication cost of $1,190, the direct cost of cSLE per QALY was $30,908. Children diagnosed with cSLE were found to have a considerable direct cost of care. The treatment of cSLE appears to be far more costly than that of adult SLE and juvenile idiopathic arthritis reported in the literature.


Wearables for running gait analysis: A study protocol.
Quantitative running gait analysis is an important tool that provides beneficial outcomes to injury risk/recovery or performance assessment. Wearable devices have allowed running gait to be evaluated in any environment (i.e., laboratory or real-world settings), yet there are a plethora of different grades of devices (i.e., research-grade, commercial, or novel multi-modal) available with little information to make informed decisions on selection. This paper outlines a protocol that will examine different grades of wearables for running gait analysis in healthy individuals. Specifically, this pilot study will: 1) examine analytical validity and reliability of wearables (research-grade, commercial, high-end multimodal) within a controlled laboratory setting; 2) examine analytical validation of different grades of wearables in a real-world setting, and 3) explore clinical validation and usability of wearables for running gait analysis (e.g., injury history (previously injured, never injured), performance level (novice, elite) and relationship to meaningful outcomes). The different grades of wearable include: (1) A research-grade device, the Ax6 consists of a configurable tri-axial accelerometer and tri-axial gyroscope with variable sampling capabilities; (2) attainable (low-grade) commercial with proprietary software, the DorsaVi ViMove2 consisting of two, non-configurable IMUs modules, with a fixed sampling rate and (3) novel multimodal high-end system, the DANU Sports System that is a pair of textile socks, that contain silicone based capacitive pressure sensors, and configurable IMU modules with variable sampling rates. Clinical trial registration: Trial registration: NCT05277181.


[Gastric mucus glycoproteins: structure, functions and pathology (author's transl)].
O-glycosylated glycoproteins are the main constituents of gastric mucus. They are responsible for its viscosity and for its gel-forming properties. Recent advances accomplished over the last years on its physical and chemical characterization are briefly reviewed. Many issues remain still unsettled concerning the modification of its structure and composition in diseases as well as details of its biosynthesis and its pharmacology.


Efficacy and Adherence Rates of a Novel Community-Informed Virtual World-Based Cardiac Rehabilitation Program: Protocol for the Destination Cardiac Rehab Randomized Controlled Trial.
Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology-based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center-based CR. This study aims to evaluate efficacy and adherence of the virtual world-based CR program compared with center-based CR within a community-informed, implementation science framework. Using a noninferiority, hybrid type 1 effectiveness-implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12-week Destination Cardiac Rehab or the center-based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board-approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05897710.


A brief-review of the risk factors for covid-19 severity.
The World Health Organization has emphasized that one of the most important questions to address regarding the covid-19 pandemic is to understand risk factors for disease severity. We conducted a brief review that synthesizes the available evidence and provides a judgment on the consistency of the association between risk factors and a composite end-point of severe-fatal covid-19. Additionally, we also conducted a comparability analysis of risk factors across 17 studies. We found evidence supporting a total of 60 predictors for disease severity, of which seven were deemed of high consistency, 40 of medium and 13 of low. Among the factors with high consistency of association, we found age, C-reactive protein, D-dimer, albumin, body temperature, SOFA score and diabetes. The results suggest that diabetes might be the most consistent comorbidity predicting disease severity and that future research should carefully consider the comparability of reporting cases, factors, and outcomes along the different stages of the natural history of covid-19.


Skin characteristics by laser generated surface waves.
This paper discusses a study into the suitability of using laser generated surface acoustic waves for the characterisation of skin properties without causing any damage to the skin thermally or by mechanical disruption. Using commercial Finite Element Code ANSYS, the effects of laser wavelength, laser beam radius and laser rise time on generation of laser generated ultrasonic waves in a 3-layered elastic isotropic model of human skin were studied. The FE model is an example of a sequential coupled field analysis where the thermal and mechanical analyses are treated separately. The heating of the skin model due to the short laser pulse is simulated by a dynamic thermal analysis with the laser pulse modeled as volumetric heat generation and the results from this analysis subsequently applied as a load in the mechanical analysis where the out-of-plane displacement histories are analyzed. The technique described in this paper also involves measuring the propagation velocity of SAWs, which are directly related to the material properties, and thickness of layers, this is done over a wide frequency range in order to obtain maximum information regarding the material under test.


Ventilatory compensation for inspiratory resistive loads during anaesthesia with halothane or isoflurane.
We have analysed the ventilatory response to sustained inspiratory resistive loads in 14 patients, while awake and during halothane (n = 7) or isoflurane (n = 7) anaesthesia. Patients breathed halothane or isoflurane in oxygen at 1.2 minimum alveolar concentration (MAC). Inspiratory resistances of 0, 12 and 37 cm H2O litre-1 s were applied. Tidal volume (VT) was maintained with the greater loads. At the greatest resistance, a significant reduction in minute ventilation occurred in both awake (-18.9%) and anaesthetized states, with both halothane (-10.4%) and isoflurane (-14.5%). Ventilatory frequency decreased significantly from mean 14.6 (SD 4.7) to 12.5 (4.3) bpm in the awake state and during anaesthesia, with increasing inspiratory resistance (29.5 (3.6) to 23.7 (7.2) bpm and 25.8 (3.3) to 23.4 (4.0) bpm, respectively, for halothane and isoflurane) because inspiratory time (TI) was significantly longer (P < 0.01). End-tidal PCO2 increased by 0.3 kPa, on average, from baseline to the highest level of resistance (P < 0.01). Inspiratory occlusion pressure at 100 ms increased significantly with increased loading in all situations (P < 0.001). We found a similar pattern of ventilatory adaptation to sustained inspiratory flow resistive loads both in awake and anaesthetized states. VT was maintained at increased loads because of an increase in inspiratory neuromuscular output and inspiratory duration.


Reduced hepatic sterol carrier protein-2 expression in the streptozotocin treated diabetic rat.
While a strong relationship between the hypercholesterolemia of diabetes and premature atherosclerosis is established, the etiology for the elevation in serum cholesterol in this disease is unknown. To determine whether diabetic hypercholesterolemia may be related to alterations in hepatic cholesterol transport capacity, sterol carrier protein-2 (SCP2) expression was examined in rats treated with streptozotocin (SZT). Furthermore, this study examined whether 17β-estradiol and insulin confer a protective effect on liver cholesterol homeostasis by maintaining hepatic SCP2 levels. SCP2 protein and mRNA expression were examined 13 days following SZT-induced diabetes onset and in diabetic rats treated with estradiol (1 cm silastic implant) or insulin (12 units/day). Data indicate that SCP2 protein levels were significantly reduced in the diabetic animals and that SCP2 protein expression in the liver was inversely related to the level of serum cholesterol in the diabetic animals. In contrast, SCP2 mRNA levels examined by slot blot, ribonuclease protection assay, and Northern blot analysis were significantly elevated. Both insulin and estradiol were able to enhance the expression of SCP2 protein in the liver following SZT treatment. The results of this investigation clearly indicate that hepatic SCP2 protein levels are significantly altered in the diabetic state suggesting that cholesterol transport capacity is reduced in the SZT-treated diabetic rat. The inverse relationship between serum cholesterol and hepatic SCP2 protein content suggests that the reduction in this protein may be a contributing factor in diabetic hypercholesterolemia.


Intrathyroideal papillary thyroid carcinoma presenting with a solitary brain metastasis.
Papillary thyroid carcinoma (PTC) is the most common type of well-differentiated thyroid carcinoma and typically has an excellent prognosis. The incidence of distant metastasis from PTC is low. However, once metastasis has developed in a distant site, prognosis is markedly diminished. Brain metastases from PTC are extremely rare. No consensus regarding management has yet been reached. We report on the case of a patient who presented with signs of intracranial hypertension. Cranial magnetic resonance imaging (MRI) identified a lesion of the right temporofrontoparietal lobe. The patient underwent a craniotomy with a total removal of the tumor. Histologic examination of the lesion showed a metastasis of papillary adenocarcinoma. We observed a cold nodule in the right lobe of the thyroid on physical examination and imaging techniques (e.g., CT and scintigraphy). Fine-needle-aspiration cytology of the nodule was reported as PTC. A total thyroidectomy was performed and histopathological examination showed intrathyroidal variant of PTC. Postoperatively adjuvant whole brain radiation therapy with 44 Gy to multiple brain metastases of PTC was applied. One month later, the patient then underwent 131I radioiodine therapy with 150 mCi of 131I given orally. In conclusion, the present case underwent an aggressive multimodal approach to therapy. This report indicates that the early detection and control of brain metastases may contribute to a better quality of life for patients affected by brain metastases.