Parents' intention to vaccinate their child for COVID-19: A mixed-methods study (CoVAccS-wave 3).
To investigate UK parents' vaccination intention at a time when COVID-19 vaccination was available to some children. Data reported are from the second wave of a prospective cohort study. We conducted a mixed-methods study using an online survey of 270 UK parents (conducted 4-15 October 2021). At this time, vaccination was available to 16- and 17-year-olds and had become available to 12- to 15-year-olds two weeks prior. We asked participants whose child had not yet been vaccinated how likely they were to vaccinate their child for COVID-19. Linear regression analyses were used to investigate factors associated with intention (quantitative component). Parents were also asked for their main reasons behind vaccination intention. Open-ended responses were analysed using content analysis (qualitative component). Parental vaccination intention was mixed (likely: 39.3%, 95% CI 32.8%, 45.7%; uncertain: 33.9%, 95% CI 27.7%, 40.2%; unlikely: 26.8%, 95% CI 20.9%, 32.6%). Intention was associated with: parental COVID-19 vaccination status; greater perceived necessity and social norms regarding COVID-19 vaccination; greater COVID-19 threat appraisal; and lower vaccine safety and novelty concerns. In those who intended to vaccinate their child, the main reasons for doing so were to protect the child and others. In those who did not intend to vaccinate their child, the main reason was safety concerns. Parent COVID-19 vaccination status and psychological factors explained a large percentage of the variance in vaccination intention for one's child. Further study is needed to see whether parents' intention to vaccinate their child is affected by fluctuating infection rates, more children being vaccinated, and the UK's reliance on vaccination as a strategy to live with COVID-19.


[Cardiotropic properties of lithium oxybutyrate in an experiment and in the clinic].
Lithium oxybutyrate was shown to exert pronounced coronarolytic effects, to increase volume velocity of the coronary blood flow, to improve blood supply to ischemic myocardial areas thereby providing oxygen reserve. Lithium oxybutyrate improves the functional state of the ischemic focus, limits zone of experimental myocardial necroses, exerts an antifibrillatory action, increases pain sensitivity threshold. A high efficacy of the drug was established during clinical study in patients with cardiac rhythm disorders.


Transdermal lovastatin enhances fracture repair in rats.
Statins have been shown to stimulate BMP2 transcription and bone formation. This raises the possibility that they could be useful for enhancing rates of fracture repair. Observational studies in patients treated with oral statins for lipid-lowering have been controversial. The likely reason for their inconsistent effects is that the statin concentration reaching the periphery was too low after oral administration to produce a reproducible biologic effect. Thus, we examined the effects of lovastatin (LV) given transdermally in a well-described preclinical model of fracture repair. Effects on the healing fracture callus were assessed by biomechanical strength, radiographs, and quantitative morphology. LV was administered transdermally (TD) for 5 days after fracture in several doses (0.1-5 mg/kg/d) and compared with vehicle-treated control rats and rats treated with LV by oral gavage (PO) at 5-25 mg/kg/d for 5 days from the day of fracture. Radiological evaluation of bones treated with TD LV showed enhanced fracture repair at 2 and 6 wk. BMD in the callus area at 6 wk was also increased in the TD group compared with vehicle-treated controls (p < 0.05). The force required to break TD-treated bones (0.1 mg/kg/d for 5 days) was 42% greater than vehicle-treated controls (p < 0.02), and there was a 90% increase in stiffness (p < 0.01). PO LV at much higher doses (10 and 25 mg/kg/d) showed increased stiffness but no change in other biomechanical properties. By histological examination, a significant increase was also observed in the size of the callus, surrounding proliferating cell nuclear antigen-positive cells, and osteoblast and osteoclast number in TD-treated rats compared with controls at day 8 after fracture (n = 6). In summary, we found that TD LV in low doses accelerates fracture healing, whereas 10-fold the lipid-lowering dose was required to produce any effect when it was administered orally. These studies provide valuable information on the potential of statins and TD delivery as a new and effective therapeutic modality in fracture repair.


Differential effects of cytokines on proliferative response of human CD4+ T lymphocyte subsets stimulated via T cell receptor-CD3 complex.
We report that the subsets of CD4+ T cells characterized by differential expression of CD45RA (2H4) Ag showed significant differences in proliferative response to immobilized anti-CD3 antibody (Ab) and cytokines: IL-1, IL-2, IL-4, and IL-6. Most strikingly, CD4+/45RA+ but not CD4+/45RA- T cells responded to anti-CD3 Ab and IL-4. Similar difference in response to IL-4 occurred when the subsets were stimulated by two "alternative" T cell activation pathways via CD2 and GD3 Ag. The response of CD4+/45RA+ cells to anti-CD3 Ab and IL-4 was enhanced by the two monokines: IL-1 and IL-6. Further differences between the subsets included the preferential response of the CD4+/45RA+ cells to enhancing effect of IL-6 on proliferation mediated by the anti-CD3 Ab and IL-2. In contrast to IL-6, IL-1 was unable to increase this proliferation significantly. In turn, the CD4+/45RA- cells responded preferentially to a weak stimulation mediated by anti-CD3 Ab either alone, or together with IL-1 and IL-6. Existence of these significant differences in the response of CD4+ T cell subsets costimulatory effects of the cytokines, suggests that the in vivo events resulting in an accumulation of the cytokines in particular combinations may lead to selective activation of one of the CD4+ T cell subsets during the immune response.


Effects of an immersion disinfection regime on rigid impression materials.
This laboratory study investigated the dimensional stability and surface detail reproduction of rigid impression materials after a 20-minute immersion in 2% ID 210 solution. The chemical disinfectant and regime of use appear to be compatible with the impression materials tested. The dyed disinfectant not only penetrated into impression plaster but also diffused into stone casts poured against such impressions.


The superior colliculus of the ferret: cortical afferents and efferent connections to dorsal thalamus.
By injecting both biotinylated and fluorescent dextran amines into the superior colliculus of the ferret we traced its afferent connections from the cerebral cortex and its projections to nuclei of the dorsal thalamus. All visual and auditory cortical areas had retrogradely labelled layer 5 pyramidal neurons projecting to the superior colliculus, with the highest density in areas 18 and 21. Secondary somatosensory and motor cortical regions also projected to the superior colliculus. No retrograde labelling was observed in primary somatosensory, primary motor or prefrontal cortex. All visual dorsal thalamic nuclei received connections from the superior colliculus. Within the LGN, lamina C and the medial interlaminar nucleus (MIN) received dense afferents terminating with large labelled boutons. Within the lateral posterior nucleus (LP) a distinct band of moderately dense small, labelled boutons was observed, and within the pulvinar a broader and less dense region of small bouton labelling was observed. For the most part these connections are similar to those seen in the cat and other mammals, however, specific comparisons appear to delineate potential evolutionary trends related to complexity of the visual system.


Purification and characterization of a DNA polymerase beta from Drosophila*.
A DNA polymerase with properties similar to mammalian polymerase beta has been isolated to near homogeneity from embryos of Drosophila melanogaster. A combination of exclusion chromatography and sodium dodecyl sulfate-gel electrophoresis indicates that this enzyme is composed of a single polypeptide of molecular weight-110,000. Optimum activity on a nicked template occurs at pH 8.4 in the presence of 15 mM MgCl2 and 250 mM NaCl. Enzyme activity is strongly inhibited by dideoxythymidine triphosphate but is relatively insensitive to aphidicolin and N-ethylmalemide. These properties clearly distinguish this enzyme from polymerase alpha, which has previously been characterized from this tissue. This report represents the first extensive purification of a beta-like polymerase from the Protostomic branch of the animal phylogenetic tree. It furthermore generates the potential for a genetic analysis of the function of polymerase beta in DNA recombination, repair, and synthesis.


Tranexamic acid (class I drug) reduced and capped gold nanoparticles as a potential hemostatic agent with enhanced performance.
External hemostatic agents play a crucial role in stabilizing an impaired process during pathological conditions. The idea is to stabilize thein vivosystem as soon as possible. This study uses a class I hemostatic drug tranexamic acid as a reducing and capping agent for synthesizing the gold nanoparticles (Tr-AuNPs). Being the synthetic analogue of lysine and a biologically inspired alkylamine molecule, the chemistry can be fine-tuned for stable material that can simultaneously target the intrinsic and extrinsic hemostatic pathway, making it promising for hemostatic applications. The Tr-AuNPs of hydrodynamic diameter ∼46 nm were synthesized and evaluated physio-chemically using various analytical techniques wherein they showed hemocompatibility and increased thrombus weight compared to the native drug. The decrease in prothrombin time (PT) and international normalized ratio supported by the dynamic thromboelastography (TEG) study indicates the prepared nano-conjugate's potential in reducing time for attaining hemostasis as compared to the native tranexamic acid drug. At a 9μg ml-1concentration, Tr-AuNPs had a procoagulant effect, shown by decreased reaction time (R) and coagulation time (K) with improvedαangle and MA. There was a significant increase in the rate of coagulationin vivoby Tr-AuNPs, i.e. (52 s) compared to the native tranexamic acid (360 s). Radiolabelling studies ascertained thein vivobiocompatibility (non-invasive distribution, residence, clearance, and stability) of the Tr-AuNPs. The short-term toxicity studies were conducted to establish a proof of concept for the biomedical application of the material. The results highlighted the use of biologically alkyl amine molecules as capping and reducing agents for the synthesis of nanoparticles, which have shown a synergistic effect on the coagulation cascade while holding the potential for also acting as potential theranostic agents.


[Renal syndrome in amebic lesions of the liver].
The author observed 315 patients with the amebic liver abscess. Of them in 134 (42.5%), the renal syndrome was diagnosed. The kidney damage had the course of the secondary pyelonephritis type, or in the form of a toxic kidney. On the basis of clinico-laboratory analysis, the author distinguishes the mild, moderate and severe degrees of kidney damage, recommends an adequate transfusion-infusion, antibacterial and specific therapy.


[The decrease of risk of occupational diseases among rail road workers: future strategies].
Diagnosis, registration and prophylaxis of occupational diseases among railway workers remain unsatisfactory so far. Thus, creation of the Railway Register of Occupational Diseases is essential. The Register includes several blocks related to each other and covering enterprises, medical and social institutions. Given relatively low primary occupational morbidity in railway transport, the Register's software considers incidence of occupational diseases in Russian Federation among analogous occupations, matched in working environment classes, length of service and occupational hazard. The authors obtained the matched incidences of occupational diseases, and can extrapolate the relationships revealed to railway workers, forecast high risk of occupational diseases among these workers.


Tetragonality induced superconductivity in anti-ThCr2Si2-type RE2O2Bi (RE = rare earth) with Bi square nets.
We report a series of layered superconductors, anti-ThCr2Si2-type RE2O2Bi (RE = rare earth), composed of electrically conductive Bi square nets and magnetic insulating RE2O2 layers. Superconductivity was induced by separating the Bi square nets as a result of excess oxygen incorporation, irrespective of the presence of magnetic ordering in RE2O2 layers. Intriguingly, the transition temperature of all RE2O2Bi including nonmagnetic Y2O2Bi was approximately scaled by unit cell tetragonality (c/a), implying a key role in the relative separation of the Bi square nets to induce superconductivity.


Lavandula angustifolia Effects on Rat Models of Alzheimer's Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics.
Alzheimer's Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aβ-induced rat Alzheimer's models was investigated through nuclear magnetic resonance spectrometry. For the establishment of rat Alzheimer's models, 10 μg of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 MHz 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment. Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism. As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed.


Interrater Reliability of Dynamic Muscle Testing After Breast Cancer Surgery in Women at High Risk of Lymphedema: To Improve Quality in Clinical Practice.
Background: The purpose of this study is to determine the interrater reliability of dynamic muscle tests in the early rehabilitation phase in women after breast cancer surgery with axillary lymph node dissection (ALND) based on the "preventive intervention against lymphedema after breast cancer" (LYCA) randomised controlled trial. Methods: Fifteen women treated with breast cancer surgery including ALND were recruited from participants in the LYCA trial. In this interrater reliability study, women were tested in 4 dynamic muscle tests by 2 physiotherapists at a Capital Hospital in Denmark. Intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs) was used to assess the relative reliability between raters. A Bland-Altman plot and limits of agreement were calculated to describe the absolute reliability. Results: All 6 subtests displayed high interrater reliability. ICC values were: leg press 0.96 (95% CI = 0.87-0.99), elbow flexion (contralateral) 0.94 (0.83-0.98), elbow flexion (affected arm) 0.93 (0.80-0.98), elbow extension 0.80 (0.41-0.93), shoulder abduction (contralateral) 0.89 (0.68-0.96), and shoulder abduction (affected arm) 0.91 (0.74-0.97). Cumulated interrater reliability for the test battery was very high (ICC = 0.99, 95% CI = 0.990-1.0). The absolute reliability of this study was considered high, and the absence of large shifts between mean and the line of 0 difference suggest no systematic bias that could influence clinical interpretation. Conclusions: The dynamic muscle tests evaluated in this study had high interrater reliability and can be used reliably in women in the postoperative phase after breast cancer surgery with ALND.


Gastrointestinal parasites of birds in zoological gardens in south-west Nigeria.
Infections with gastrointestinal parasites are a major health issue in captive birds. However, prevalence data of gastrointestinal parasites of birds in zoological gardens in Nigeria are scarce. This study was carried out to establish the gastrointestinal parasite profile of birds kept in zoological gardens in the University of Ibadan, Obafemi Awolowo University, University of Ilorin, University of Lagos and Federal University of Agriculture Abeokuta, all in south-west Nigeria. A total of 178 fecal samples from 83 birds (14 species in eight orders) were examined using three techniques; Feacal sedimentation using ethyl acetate, McMaster Egg Counting Technique and Petri Dish-Filter Paper Slant culture technique (modified Harada-Mori Technique). A total of 39(21.9%) of the 178 samples were infected. The highest prevalence (100%) of infection was recorded in Unilag zoo and a total of five species of parasites including two protozoans (coccidian and Balantidium spp.); and three nematodes Capillaria spp., Ascaris spp. and Strongyloides spp.) were recorded with Capillaria spp. (14.1%) as the most prevalent gastrointestinal parasite. Mixed infections were found in 18(10.1%) samples. Strongyloides larvae were observed in 6(3.4%) samples. All Anseriformes were infected but the Struthioniformes had the highest infection rate. The geometric mean intensity of eggs ranged from 101.98 ± 10.36 to 63.00 ± 16.67 epg and oocyst counts ranged from 332.47 ± 16.67 to 297.89 ± 20.41 opg. Balantidium cyst count was 324.04 ± 25.00. Count of oocyst of coccidian species was significantly higher in all the zoos. The feacal culture yielded Strongyloides species. Regular deworming and hygienic measures are necessary to prevent gastrointestinal infections in captive birds. So also, improved funding and management are necessary to ensure sustainability of Nigerian zoological gardens.


Eukaryotic translation initiation factor 5A small interference RNA-liposome complexes reduce inflammation and increase survival in murine models of severe sepsis and acute lung injury.
Many novel therapeutics have failed to reduce all-cause mortality associated with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of apoptosis as well as inflammatory cell activation, making it a potential target for sepsis therapy. In a murine model of severe sepsis, mice were intraperitoneally challenged with lipopolysaccharide (LPS). Mice were treated both before and after LPS challenge with liposome complexes containing either an eIF5A-specific or control small interference RNA (siRNA), and both survival and serum concentrations of inflammatory cytokines were monitored. The ability of eIF5A siRNA to reduce inflammatory cytokines was also tested in a model of acute lung injury established by intranasal administration of LPS to mice. There was a statistically significant increase in the rate of survival for mice intraperitoneally challenged with LPS that received eIF5A siRNA, compared with that noted for mice that received control siRNA (71% vs. 5%; P< .001), as well as a reduction in cytokine expression in serum. Concentrations of proinflammatory cytokines were also reduced in the lung homogenates and serum of mice that were intranasally challenged with LPS and received eIF5A siRNA (P< or = .05). eIF5A siRNA-liposome complexes reduced inflammation and contributed to increased survival in a model of severe sepsis, decreased inflammation in a model of acute lung injury, and should be considered for clinical use.


Organization of NMDA receptors at extrasynaptic locations.
NMDA receptors are found in neurons both at synapses and in extrasynaptic locations. Extrasynaptic locations are poorly characterized. Here we used preembedding immunoperoxidase and postembedding immunogold electron microscopy and fluorescence light microscopy to characterize extrasynaptic NMDA receptor locations in dissociated hippocampal neurons in vitro and in the adult and postnatal hippocampus in vivo. We found that extrasynaptic NMDA receptors on neurons in vivo and in vitro were usually concentrated at points of contact with adjacent processes, which were mainly axons, axon terminals, or glia. Many of these contacts were shown to contain adhesion factors such as cadherin and catenin. We also found associations of extrasynaptic NMDA receptors with the membrane associated guanylate kinase (MAGUKs), postsynaptic density (PSD)-95 and SAP102. Developmental differences were also observed. At postnatal day 2 in vivo, extrasynaptic NMDA receptors could often be found at sites with distinct densities whereas dense material was seen only rarely at sites of extrasynaptic NMDA receptors in the adult hippocampus in vivo. This difference probably indicates that many sites of extrasynaptic NMDA receptors in early postnatal ages represent synapse formation or possibly sites for synapse elimination. At all ages, as suggested in both in vivo and in vitro studies, extrasynaptic NMDA receptors on dendrites or the sides of spines may form complexes with other proteins, in many cases, at stable associations with adjacent cell processes. These associations may facilitate unique functions for extrasynaptic NMDA receptors.


Neuropeptides as mediators of the early-life impact on the brain; implications for alcohol use disorders.
The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behavior. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD). In clinical research the studies of mechanisms, mediators, and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data and multivariate data analysis with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids, and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.


Transition from paediatric care to adult care for patients with mucopolysaccharidosis.
Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.


The swinging doors of perception: stereomotion without binocular matching.
Until recently, it was considered necessary for features in the two eyes to be matched before the evaluation of differences in their locations (binocular disparities) could reveal depth information. Motion in depth can also be perceived binocularly from related changes in the locations of matched binocular features. However, unmatched features can arise when a binocular object occludes more distant features in one eye but not the other. The presence and extent of such features can provide quantitative depth information, although perceived depth relative to geometrical predictions may vary from one such arrangement to another. The ability of humans to perceive motion in depth from unmatched stimuli has not previously been explored. Here, we use B. Gillam, S. Blackburn, and K. Nakayama's (1999) "monocular gap" stimuli to investigate perception of motion in depth simulated by a change in the extent of a monocularly occluded feature in a binocular display. Settings of a motion in depth probe revealed that the magnitude of perceived motion in depth is generally as large as that for a stimulus containing matchable binocular features. We show that our stimuli provide disambiguating information not present in similar static stimuli. We conclude that in the computation of motion in depth, a binocular match is not required. A new cue-dynamic half-occlusion-can be used to reach an accurate percept.


On learning context-free and context-sensitive languages.
The long short-term memory (LSTM) is not the only neural network which learns a context sensitive language. Second-order sequential cascaded networks (SCNs) are able to induce means from a finite fragment of a context-sensitive language for processing strings outside the training set. The dynamical behavior of the SCN is qualitatively distinct from that observed in LSTM networks. Differences in performance and dynamics are discussed.


Key Parameters for the Use of AbobotulinumtoxinA in Aesthetics: Onset and Duration.
Time to onset of response and duration of response are key measures of botulinum toxin efficacy that have a considerable influence on patient satisfaction with aesthetic treatment. However, there is no overall accepted definition of efficacy for aesthetic uses of botulinumtoxinA (BoNT-A). Mechanical methods of assessment do not lend themselves to clinical practice and clinicians rely instead on assessment scales such as the Frontalis Activity Measurement Standard, Frontalis Rating Scale, Wrinkle Severity Scale, and Subject Global Assessment Scale, but not all of these have been fully validated. Onset of activity is typically seen within 5 days of injection, but has also been recorded within 12 hours with abobotulinumtoxinA. Duration of effect is more variable, and is influenced by parameters such as muscle mass (including the effects of age and sex) and type of product used. Even when larger muscles are treated with higher doses of BoNT-A, the duration of effect is still shorter than that for smaller muscles. Muscle injection technique, including dilution of the toxin, the volume of solution injected, and the positioning of the injections, can also have an important influence on onset and duration of activity. Comparison of the efficacy of different forms of BoNT-A must be made with the full understanding that the dosing units are not equivalent. Range of equivalence studies for abobotulinumtoxinA (Azzalure; Ipsen Limited, Slough UK/Galderma, Lausanne CH/Dysport, Ipsen Biopharm Limited, Wrexham UK/Galderma LP, Fort Worth, TX) and onabotulinumtoxinA (Botox; Allergan, Parsippany, NJ) have been conducted, and results indicate that the number of units of abobotulinumtoxinA needs to be approximately twice as high as that of onabotulinumtoxinA to achieve the same effect. An appreciation of the potential influence of all of the parameters that influence onset and duration of activity of BoNT-A, along with a thorough understanding of the anatomy of the face and potency of doses, are essential to tailoring treatment to individual patient needs and expectations.


Progress in the treatment of blunt thoracic aortic injury: 12-year single-institution experience.
Recent advancements in the diagnosis and management of blunt thoracic aortic injury have improved outcomes after operative repair. With consideration of these advancements, we analyzed our level 1 trauma experience with blunt traumatic aortic injury. Between January 1997 and March 2009, 255 patients with blunt traumatic aortic injury were entered into the Utah Trauma Registry-Trauma Center Registry. Of these, 145 (58%) patients underwent thoracic aortic repair, with 12 (5%) undergoing aortic exploration without repair. Median age was 32 years (range, 13 to 87), with 43 (30%) women. Repair approach included open repair without adjunct (clamp), open with distal aortic perfusion, open with cardiopulmonary bypass, and thoracic endovascular aortic repair. The affect of management modifications, which included use of distal aortic perfusion (1999), delayed repair (2002), and use of thoracic endovascular aortic repair (2005) was analyzed. We used multiple logistic regression to evaluate the changes in morbidity (paraplegia and stroke) and mortality attributable to changes in surgical practice, adjusted for calendar time and injury severity score. Mortality from operative aortic intervention for blunt thoracic aortic injury (BTAI) was 17% (24 of 145). Delayed repair, used in 41% (59 of 145) of repairs, was associated with only 1 death (2%), which was significantly lower than immediate repair 28% (23 of 86) mortality (p < 0.002). Mean injury severity score was 39 +/- 11. Adjusted for injury severity score and calendar time, delayed repair resulted in a greater than tenfold reduction in mortality compared with immediate open intervention (odds ratio 0.07, p < 0.02). Use of thoracic endovascular aortic repair was associated with zero mortality (p < 0.03 versus other treatments). Mortality with open repair with and without distal aortic perfusion was 14% and 31%, respectively, p < 0.02. Paraplegia occurred in 10% with open repair without distal aortic perfusion, and in no cases in open with distal aortic perfusion and thoracic endovascular aortic repair. Although thoracic aortic injury still accounts for significant mortality during blunt trauma, patients reaching specialized trauma centers can achieve good results with thoracic aortic repair. Improved early outcomes have been observed with delayed selective management and thoracic endovascular repair. Long-term results of thoracic endovascular aortic repair, however, need further study.


Improved Survival With Favorable Neurological Outcome in Elderly Individuals With Out-of-Hospital Cardiac Arrest in Japan - A Nationwide Observational Cohort Study.
There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital cardiac arrest (OHCA). OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend <0.001). In particular, outcomes of OHCA patients aged 75 to 84 years and those aged 85 to 94 years significantly improved (0.98% to 1.28%, P for trend=0.01; 0.46% to 0.70%, P for trend <0.001, respectively). However, in OHCA patients aged ≥95 years, the outcomes did not improve. Multivariate logistic regression analysis indicated that younger age, shockable first documented rhythm, witnessed arrest, earlier emergency medical service (EMS) response time, and cardiac etiology were significantly associated with the 1-month CPC 1-2. Under these conditions, elderly OHCA patients who had cardiac etiology, shockable rhythm and had a witnessed arrest had acceptable 1-month CPC1-2 rate; 7.98% in cases where OHCA was witnessed by family, 15.2% by non-family, and 25.6% by EMS. The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile. (Circ J 2016; 80: 1153-1162).


Wastewater treatment using a novel bioreactor with submerged packing bed of polyethylene tape.
The performance of a novel aerobic bioreactor with a specially designed submerged packing bed of high specific surface area density, made of polyethylene tape, was studied for the treatment of domestic wastewater. The reactor has a volume of 0.71 m(3) and the specific area of the packing bed was 1,098 m(2)/m(3). The operation was performed with and without effluent recycling, applying different organic loads in the range of 4.0-17.6 g COD m(-2) d(-1). No back-washings were carried out. Overall BOD(5) removals of 90-95% were obtained with organic loads of 4.0-17.6 g COD m(-2) d(-1) and HRT of 0.2-1.1 h. Overall TN removal of 69-72% was obtained at loads of 0.8-4.6 g TN m(-2) d(-1) when effluent recycling was used. The reactor allowed obtaining high quality water for urban reuse and demonstrated an effective process performance and resistance to load variations. The developed biofilm was completely penetrated by the organic matter, ammonia and oxygen, providing high removal rates. Large biomass quantities, up to 13 g dry VS/m(2), were reached in the reactor and the determined sludge yield coefficient was relatively low, of 0.25 g VSS/g COD. These results allow obtaining compact treatment systems with low sludge production and make the technology a suitable option for small wastewater treatment plants.


Differences in presentation, treatment, and outcomes among minority head and neck cancer patient groups in Los Angeles County.
While minorities represent around 20 % of all HNC patients, these demographics are largely understudied. Furthermore, trends in national studies may not always be fully replicated in locoregional populations, indicating a need for more nuanced study. To better understand our patient population, we sought to understand differences in presentation, management, and outcome between Caucasians and minority groups with HNC. Retrospective cohort analysis of the Los Angeles County Surveillance Epidemiology and End Results (SEER) database. Los Angeles County. All patients in Los Angeles County diagnosed with cancer of the head and neck from January 1, 1988 to December 31, 2018. The primary outcome in our study was significant differences between racial and ethnic groups in age of diagnosis, sex, socioeconomic quintile, insurance status, stage at diagnosis, treatment modality, time to first treatment, and cancer-specific cause of death. Our 18,510-patient cohort was largely male (64.35 %), white (69.57 %), and were on average 62.84 years old (SD = 20.07). When stratifying patients by race and ethnicity, significant differences were found in average age at diagnosis, sex, socioeconomic quintile, insurance status, and stage at diagnosis, treatment modalities utilized, and time to first treatment (all p < 0.001). Relative to all other head and neck patients, minority groups were significantly younger, had lower proportions of male patients, were less likely to pursue surgery, were more likely to pursue chemotherapy or radiation, and endorsed longer time to first treatment (all p < 0.001). The distribution of socioeconomic quintile (all p < 0.001), insurance status (all p < 0.001), and stage at diagnosis (all p < 0.05) also significantly varied between minority and reference groups. Only African Americans exhibited significantly higher rates of cancer-specific cause of death relative to non-African Americans (p < 0.001). Pervasive socioeconomic disparities between Caucasian HNC patients and those of other minority racial and ethnic groups in Los Angeles County that likely and significantly impact the diagnosis and management of HNC and its resultant outcomes. We encourage others to similarly examine their local populations to tailor the quality of care provided to patients.


Anaesthesia for day case surgery: a survey of adult clinical practice in the UK.
In October 2000, we conducted a national postal survey of consultant day case anaesthetists in the UK to explore the range and variation in the practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). The survey was carried out as part of a larger study that comprised a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). We report the findings of this national survey of adult urology and orthopaedic day case anaesthetic practice in the UK. The survey used a structured postal questionnaire and collected data on the duration of the surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flows used for anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. The overall response rate for the survey was 74% (63% for urology, 67% for orthopaedics). The survey indicated the following practice in adult urology and adult orthopaedic day case surgery: 6 and 12% used premedication; propofol was the preferred induction agent (96 and 97%) and isoflurane the preferred maintenance agent (56 and 58%); 32 and 41% used prophylactic antiemetics; 86 and 93% used a laryngeal mask. This survey identifies the variation in current clinical practice in adult day surgery anaesthesia in the UK and discusses this variation in the context of current published evidence.


Experimental evidence for exciton scaling effects in self-assembled molecular wires.
Resonant Rayleigh scattering from self-assembled one-dimensional molecular J-aggregate wires reveals a distinct dependence of the exciton energy on the width of lateral extension. For the J aggregates used in this study, strong in-line dipole coupling leads to a delocalization of the exciton wave function over several molecular units. Polarization dependent measurements of resonantly scattered light from the wires show that the exciton dipole moment is oriented perpendicular to the long axis. The experimental observations can be described by applying a quantization condition to the center of mass motion of the J-band exciton in the wires.


Cadmium, lead and their mixtures with copper: Paracentrotus lividus embryotoxicity assessment, prediction, and offspring quality evaluation.
The aim of this research was to assess the combined effects of three heavy metals (copper, lead, cadmium) on the fertilization and offspring quality of the sea urchin Paracentrotus lividus at EC50, NOEL, and EC1 concentrations. The observed data were compared with the predictions derived from approaches of Concentration Addition (CA) and Independent Action (IA) in order to evaluate the proper prediction of the observed mixture toxic effect. The P. lividus embryotoxicity of trace metals decreases as follows: Cu > Pb > Cd at all toxicity concentration tested. EC50 mixture revealed less toxic only than Cu; EC50 was 0.80 (± 0.07) mg/l, the offspring malformations were mainly P1 type (skeletal alterations) up to 20% mixture concentration, and P2 type from 70% concentration. The NOEL and EC1 mixtures evidenced that all compounds contribute to the overall toxicity, even if present at low concentrations: the former EC50 was 0.532 (± 0.058) mg/l and the latter was 1.081 (± 0.240) mg/l. The developmental defects observed were mainly P1 type in both mixtures. Both CA and IA models did not accurately predict mixture toxicity for EC50 and NOEL mixtures. Instead, EC1 mixture effects seemed well represented by the IA model. The protective action of the CA model, although quite accurate when applied to simple biological systems like algae and bacteria, but failed to represent the worst-case in this study with more complex organisms. It would be useful to introduce in the models one or more factors that take into account the complexity of these biological systems.


Abscisic acid-mediated developmental flexibility of stigmatic papillae in response to ambient humidity in Arabidopsis thaliana.
Stigmatic papillae develop at the apex of the gynoecium and play an important role as a site of pollination. The papillae in Brassicaceae are of the dry and unicellular type, and more than 15,000 genes are expressed in the papillae; however, the molecular and physiological mechanisms of their development remain unknown. We found that the papillae in Arabidopsis thaliana change their length in response to altered ambient humidity: papillae of flowers incubated under high humidity elongated more than those under normal humidity conditions. Genetic analysis and transcriptome data suggest that an abscisic acid-mediated abiotic stress response mechanism regulates papilla length. Our data suggest a flexible regulation of papilla elongation at the post-anthesis stage, in response to abiotic stress, as an adaptation to environmental conditions.


Expanded roles of pyruvate-sensing PdhR in transcription regulation of the Escherichia coli K-12 genome: fatty acid catabolism and cell motility.
The transcription factor PdhR has been recognized as the master regulator of the pyruvate catabolism pathway in Escherichia coli, including both NAD-linked oxidative decarboxylation of pyruvate to acetyl-CoA by PDHc (pyruvate dehydrogenase complex) and respiratory electron transport of NADH to oxygen by Ndh-CyoABCD enzymes. To identify the whole set of regulatory targets under the control of pyruvate-sensing PdhR, we performed genomic SELEX (gSELEX) screening in vitro. A total of 35 PdhR-binding sites were identified along the E. coli K-12 genome, including previously identified targets. Possible involvement of PdhR in regulation of the newly identified target genes was analysed in detail by gel shift assay, RT-qPCR and Northern blot analysis. The results indicated the participation of PdhR in positive regulation of fatty acid degradation genes and negative regulation of cell mobility genes. In fact, GC analysis indicated an increase in free fatty acids in the mutant lacking PdhR. We propose that PdhR is a bifunctional global regulator for control of a total of 16-23 targets, including not only the genes involved in central carbon metabolism but also some genes for the surrounding pyruvate-sensing cellular pathways such as fatty acid degradation and flagella formation. The activity of PdhR is controlled by pyruvate, the key node between a wide variety of metabolic pathways, including generation of metabolic energy and cell building blocks.


Birth weight and body composition in 6-to-8 years old Maya children.
To test the hypothesis that fetal growth, indexed by birth weight (BW), induce metabolic adjustments in the fetus that will be reflected in differences in body composition in a sample of 6-to 8-years old urban Maya children from Yucatan, Mexico. We measured height (cm), weight (kg) and triceps skinfold (mm) in 260 children (boys: 132, girls: 128), and height (cm) and weight (kg) in their mothers. Body composition was estimated in children through bioelectrical impedance analysis. Outcome variables were fat free-mass index (FFMI = fat-free mass [kg]/height [m]2 ) and fat mass index (FMI = fat mass [kg]/height [m]2 ). The main independent variable was BW z-scores. Multiple linear regression models were used to analyze the association between BW z-scores and outcome variables measured during childhood. Separate analyses were done for boys and girls. Complementary models were run using outcomes as z-scores. Models were adjusted for location, children's and mothers' age, mother's body mass index and household overcrowding index. BW in boys was positively associated with FFMI and FMI. FFMI increase 0.34 kg/m2 per 1-SD increase in BW and FMI increase 0.40 kg/m2 per 1-SD increase in BW. When outcomes were used as z-scores, FFMI increase 0.24 SD and FMI increase 0.18 SD per 1-SD increase in BW, respectively. Our results are in contrast with previous findings that birth weight is more consistently associated with subsequent lean mass than with fat mass. Associations, detected only in boys, may be explained by sex differences in sensitivity to early life environments.


Power Analysis and Sample Size Determination in Metabolic Phenotyping.
Estimation of statistical power and sample size is a key aspect of experimental design. However, in metabolic phenotyping, there is currently no accepted approach for these tasks, in large part due to the unknown nature of the expected effect. In such hypothesis free science, neither the number or class of important analytes nor the effect size are known a priori. We introduce a new approach, based on multivariate simulation, which deals effectively with the highly correlated structure and high-dimensionality of metabolic phenotyping data. First, a large data set is simulated based on the characteristics of a pilot study investigating a given biomedical issue. An effect of a given size, corresponding either to a discrete (classification) or continuous (regression) outcome is then added. Different sample sizes are modeled by randomly selecting data sets of various sizes from the simulated data. We investigate different methods for effect detection, including univariate and multivariate techniques. Our framework allows us to investigate the complex relationship between sample size, power, and effect size for real multivariate data sets. For instance, we demonstrate for an example pilot data set that certain features achieve a power of 0.8 for a sample size of 20 samples or that a cross-validated predictivity QY(2) of 0.8 is reached with an effect size of 0.2 and 200 samples. We exemplify the approach for both nuclear magnetic resonance and liquid chromatography-mass spectrometry data from humans and the model organism C. elegans.


Description of Mogibacterium pumilum gen. nov., sp. nov. and Mogibacterium vescum gen. nov., sp. nov., and reclassification of Eubacterium timidum (Holdeman et al. 1980) as Mogibacterium timidum gen. nov., comb. nov.
A new genus, Mogibacterium, is proposed for anaerobic, non-spore-forming, Gram-positive, rod-shaped bacteria which have been isolated from the periodontal pockets of adult human patients with periodontal disease and infected root canals. The novel isolates, strains D2-18T, BA11a-f and D5-2T, were inert in most of the conventional biochemical tests and phenotypically resemble asaccharolytic Eubacterium species. The protein profiles of whole cells on SDS-PAGE gels and Western immunoblotting reaction analysis distinguished these organisms from type strains belonging to the previously described Eubacterium species. The G + C content of the DNA is 45-46 mol% for Mogibacterium pumilum and 46 mol% for Mogibacterium vescum. The levels of DNA-DNA relatedness of these new species to other Eubacterium species, including Eubacterium limosum, Eubacterium brachy, Eubacterium lentum, Eubacterium nodatum, Eubacterium saphenum, and the more recently proposed Eubacterium minutum and Eubacterium exiguum (reclassified as Slackia exigua), are less than 2%. The DNA-DNA hybridization value between M. pumilum and M. vescum was 30%. Eubacterium timidum exhibited DNA homologies with Mogibacterium species which were low (17 and 18%) but clearly higher than with all the other Eubacterium species. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the closest phylogenetic neighbour of Mogibacterium species was E. timidum, and that these three species represent a novel lineage distinct from the previously described genera of Gram-positive, rod-shaped bacteria. On the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons, it is also proposed that E. timidum is transferred to the genus Mogibacterium gen. nov. as Mogibacterium timidum gen. nov., comb. nov. (type strain ATCC 33093T).


Systematic spatial bias in DNA microarray hybridization is caused by probe spot position-dependent variability in lateral diffusion.
The hybridization of nucleic acid targets with surface-immobilized probes is a widely used assay for the parallel detection of multiple targets in medical and biological research. Despite its widespread application, DNA microarray technology still suffers from several biases and lack of reproducibility, stemming in part from an incomplete understanding of the processes governing surface hybridization. In particular, non-random spatial variations within individual microarray hybridizations are often observed, but the mechanisms underpinning this positional bias remain incompletely explained. This study identifies and rationalizes a systematic spatial bias in the intensity of surface hybridization, characterized by markedly increased signal intensity of spots located at the boundaries of the spotted areas of the microarray slide. Combining observations from a simplified single-probe block array format with predictions from a mathematical model, the mechanism responsible for this bias is found to be a position-dependent variation in lateral diffusion of target molecules. Numerical simulations reveal a strong influence of microarray well geometry on the spatial bias. Reciprocal adjustment of the size of the microarray hybridization chamber to the area of surface-bound probes is a simple and effective measure to minimize or eliminate the diffusion-based bias, resulting in increased uniformity and accuracy of quantitative DNA microarray hybridization.


Clinical utility of residual latency in ulnar neuropathy at elbow: Is there any correlation?
Residual latency is the time difference between measured and predicted distal conduction time. We investigated ulnar nerve residual latency in patients with ulnar neuropathy at elbow for the possibility of its clinical utility. In a cross-sectional study and based on the inclusion and exclusion criteria, ulnar nerve residual latency was calculated by using standard settings in 63 hands of patients who had signs and symptoms suggesting ulnar neuropathy at elbow and 94 healthy hands as the control group. Mean ulnar nerve residual latency for case and control groups were 1.82 ± 0.45 and 1.59 ± 0.54 ms, respectively, which showed a statistically significant difference (P = 0.01). There was no significant difference in mean ulnar nerve residual latency between males and females and also between right and left hands (P > 0.05). By considering different cut-off points, the sensitivity and specificity of a residual latency of 2.86 ms were 70% and 56%, respectively. Ulnar nerve residual latency may reflect the effects of an axonal injury at elbow on distal ulnar motor fibers. So, its measurement may help in the diagnosis of ulnar neuropathy at elbow.


Homologous recombination in the tandem calmodulin genes of Trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification.
Homologous recombination between a calmodulin-neomycin-resistance fusion gene and the Trypanosoma brucei chromosome takes place not only in the large 5'- and 3'-flanking segments of the calmodulin locus but also in any of the four tandem genomic calmodulin genes. This results in a recombined locus consisting of the chimeric neor gene and four, three, two, one, or zero functional calmodulin genes. Cells bearing this latter event have half of their normal number of intact calmodulin genes and an accompanying phenotype of slow growth. Over months of propagation, these lines acquire additional calmodulin genes, frequently by amplifying a calmodulin gene at the untargeted locus, and concomitantly revert to normal growth rate. This response could be related to the property of the trypanosome of maintaining most housekeeping genes in tandem chromosomal arrays. Recombination appears to be initiated by a crossover event between the linearized end of the transfecting plasmid and a homologous region in the host genome; the second crossover generally occurs internally and in that region requires no more than 87 bp of homology.


[Spectral EEG characteristics in students with different anxiety profile during tests].
EEG spectral power was calculated in 39 students at the age of 19-21 years in two experimental conditions: during the common educational process and immediately before an examination (stress condition). During the education process, in subjects with high anxiety (tested by Spielberger) the relative spectral power of the delta activity was higher than in the other group in the occipital, parietal, central, and right frontal brain areas, whereas the power of the EEG alpha in these areas was lower. Before examination tests, in subjects with high activity the delta power bilaterally increased in the temporal areas, whereas in subjects with low anxiety there was a decrease in the alpha rhythm power, especially in the right frontal area. In stress condition, the relative power of the delta activity in both occipital and temporal, right parietal and central areas was higher in subjects with low anxiety, whereas their alpha power was lower in both frontal and in occipital, parietal, and temporal areas of the left hemisphere.


The spatial attention network interacts with limbic and monoaminergic systems to modulate motivation-induced attention shifts.
How does the human brain integrate information from multiple domains to guide spatial attention according to motivational needs? To address this question, we measured hemodynamic responses to central cues predicting locations of peripheral attentional targets (food or tool images) in a novel covert spatial attention paradigm. The motivational relevance of food-related attentional targets was experimentally manipulated via hunger and satiety. Amygdala, posterior cingulate, locus coeruleus, and substantia nigra showed selective sensitivity to food-related cues when hungry but not when satiated, an effect that did not generalize to tools. Posterior parietal cortex (PPC), including intraparietal sulcus, posterior cingulate, and the orbitofrontal cortex displayed correlations with the speed of attentional shifts that were sensitive not just to motivational state but also to the motivational value of the target. Stronger functional coupling between PPC and posterior cingulate occurred during attentional biasing toward motivationally relevant food targets. These results reveal conjoint limbic and monoaminergic encoding of motivational salience in spatial attention. They emphasize the interactive role of posterior parietal and cingulate cortices in integrating motivational information with spatial attention, a process that is critical for selective allocation of attentional resources in an environment where target position and relevance can change rapidly.


Acute type A aortic dissection surgery in retrosternal gastric tube reconstruction patient.
Retrosternal gastric tube reconstruction is a common surgical technique for managing esophageal cancer, but it complicates acute type A aortic dissection repair and raises concerns about gastric tube damage. A 73-year-old female, who underwent esophagectomy with retrosternal gastric tube reconstruction 6 months ago for esophageal cancer, presented with severe chest pain. Acute type A aortic dissection was confirmed by contrast-enhanced computed tomography, and emergency hemiarch replacement through a median sternotomy was performed, preserving the gastric tube without injury. The patient recovered well and was discharged after 3 weeks, showing no gastrointestinal symptoms or signs of mediastinitis.


Article I: Prevention and education regarding rabies in human beings. National Working Group on Rabies Prevention and Control.
Substantial changes in the epizootic characteristics of rabies have transpired in the United States during the past 50 years. Traditional veterinary practices and public health recommendations have effectively controlled rabies in dogs and prevented associated human fatalities; however, they have been unable to adequately address the problem of rabies in wildlife. Attributable in part to a renewed focus on emerging infectious diseases, a conference was held at the Centers for Disease Control and Prevention in 1993 to begin discussion focused on the reemergence of rabies and to formulate new suggestions for prevention and control of rabies in the United States. Three major working groups were formed from a national committee of professionals representing a broad array of biomedical disciplines. These groups concentrated on prevention of rabies in human beings, education, laboratory diagnosis of rabies, and rabies control in animals. The groups described the perceived minimum requirements to promote prevention and control of rabies in the United States into the next century. The following article describes the needs and recommendations identified by the prevention and education working group. Two other articles, scheduled for the Nov 15 and Dec 1, 1999 issues of JAVMA, will relay the needs and recommendations of the working groups on laboratory diagnosis of rabies and rabies in wildlife.


Restraint stress promotes nonalcoholic steatohepatitis by regulating the farnesoid X receptor/NLRP3 signaling pathway.
Psychological stress promotes nonalcoholic steatohepatitis (NASH) development. However, the pathogenesis of psychological stress-induced NASH remains unclear. This study aims to explore the underlying mechanism of restraint stress-induced NASH, which mimics psychological stress, and to discover potential NASH candidates. Methionine choline deficient diet- and high fat diet-induced hepatosteatotic mice are subjected to restraint stress to induce NASH. The mice are administrated with Xiaoyaosan granules, NOD-like receptor family pyrin domain containing 3 (NLRP3) inhibitors, farnesoid X receptor (FXR) agonists, or macrophage scavengers. Pathological changes and NLRP3 signaling in the liver are determined. These results demonstrate that restraint stress promotes hepatic inflammation and fibrosis in hepatosteatotic mice. Restraint stress increases the expressions of NLRP3, Caspase-1, Gasdermin D, interleukin-1β, cholesterol 7α-hydroxylase, and sterol 12α-hydroxylase and decreases the expression of FXR in NASH mice. Xiaoyaosan granules reverse hepatic inflammation and fibrosis and target FXR and NLRP3 signals. In addition, inhibition of NLRP3 reduces the NLRP3 inflammasome and liver damage in mice with restraint stress-induced NASH. Elimination of macrophages and activation of FXR also attenuate inflammation and fibrosis by inhibiting NLRP3 signaling. However, NLRP3 inhibitors or macrophage scavengers fail to affect the expression of FXR. In conclusion, restraint stress promotes NASH-related inflammation and fibrosis by regulating the FXR/NLRP3 signaling pathway. Xiaoyaosan granules, NLRP3 inhibitors, FXR agonists, and macrophage scavengers are potential candidates for the treatment of psychological stress-related NASH.


Purification, molecular cloning and ethylene-inducible expression of a soluble-type epoxide hydrolase from soybean (Glycine max [L.] Merr.).
A soybean protein was purified from mature dry seeds. Amino-acid sequencing of the nine internal peptides derived from this N-terminally blocked protein showed that it has a significant similarity to the soluble epoxide hydrolases known to date. A degenerate series of 23-mer oligonucleotides with sequences corresponding to an internal region of eight amino-acid residues was synthesized as a probe mixture for detection of a putative epoxide hydrolase cDNA in a developing cotyledon cDNA library. The 1332-bp cDNA obtained was found to have an open-reading frame encoding the seed epoxide hydrolase-like precursor consisting of 341 amino-acid residues, suggesting that 25 amino-acid residues upstream from the second methionine correspond to a transit peptide. Employing an Escherichia coli expression system, the putative mature epoxide hydrolase-like protein was overexpressed and purified to homogeneity. This recombinant protein was confirmed to exhibit its epoxide-diol converting activity using styrene oxide as substrate. The Vmax and Km values for styrene oxide are 1.36 micromol x min-1 x mg-1 and 1500 microM, respectively. Sedimentation equilibrium experiments showed that the active form of this epoxide hydrolase is monomeric in solution. Using the above cDNA as a probe, a 12-kb genomic clone was selected and the sequence of a 1933-bp fragment from this clone was found to cover the entire coding region together with 5'- and 3'-flanking regions of the soybean epoxide hydrolase gene. The coding region of the gene, interrupted by two short introns, was identical to the corresponding regions of the cDNA. Northern blot analyses showed that this epoxide hydrolase gene was expressed strongly at a very early stage (13 days after flowering) and then the level of expression gradually decreased and almost ceased at a very late stage (58 days after flowering) of seed development, whereas its expression was markedly up-regulated by ethylene treatment. In stems (hypocotyl portion), the epoxide hydrolase transcript was detected at significant levels and was also up-regulated in response to ethylene. On the other hand, it is hardly expressed in leaves, even though they were treated with the phytohormone. Overall, the results obtained may indicate that soluble-type epoxide hydrolase mRNA is expressed at the maximum level in an early stage of seed development. Later, oil bodies are formed and subsequently epoxy fatty acids, naturally occurring metabolites, accumulate within those bodies. The temporal induction of this epoxide hydrolase transcript in some tissues in response to ethylene also indicates that this epoxide hydrolase may play a crucial role in self-defense systems of plant.


Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in humans.
Our aim was to determine whether sympathetic withdrawal alone can account for the profound forearm vasodilation that occurs during syncope in humans. We also determined whether either vasodilating beta 2-adrenergic receptor or nitric oxide (NO) contributes to this dilation. Forearm blood flow was measured bilaterally in healthy volunteers (n = 10) by using plethysmography during two bouts of graded lower body negative pressure (LBNP) to syncope. In one forearm, drugs were infused via a brachial artery catheter while the other forearm served as a control. In the control arm, forearm vascular resistance (FVR) increased from 77 +/- 7 units at baseline to 191 +/- 36 units with -40 mmHg of LBNP (P < 0.05). Mean arterial pressure fell from 94 +/- 2 to 47 +/- 4 mmHg just before syncope, and all subjects demonstrated sudden bradycardia at the time of syncope. At the onset of syncope, there was sudden vasodilation and FVR fell to 26 +/- 6 units (P < 0.05 vs. baseline). When the experimental forearm was treated with bretylium, phentolamine, and propranolol, baseline FVR fell to 26 +/- 2 units, the vasoconstriction during LBNP was absent, and FVR fell further to 16 +/- 1 units at syncope (P < 0.05 vs. baseline). During the second trial of LBNP, mean arterial pressure again fell to 47 +/- 4 mmHg and bradycardia was again observed. Treatment of the experimental forearm with the NO synthase inhibitor NG-monomethyl-L-arginine in addition to bretylium, phentolamine, and propranolol significantly increased baseline FVR to 65 +/- 5 units but did not prevent the marked forearm vasodilation during syncope (FVR = 24 +/- 4 vs. 29 +/- 8 units in the control forearm). These data suggest that the profound vasodilation observed in the human forearm during syncope is not mediated solely by sympathetic withdrawal and also suggest that neither beta 2-adrenergic-receptor-mediated vasodilation nor NO is essential to observe this response.


Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound.
The present study was performed to examine pressure transduction to the thoracic cavity during topical negative pressure (TNP) therapy of a sternotomy wound. Seven pigs underwent median sternotomy. Pressure transduction catheters were placed on the anterior surface of the heart (under the foam), in the pericardium (under the heart), in the left pleura and in the oesophagus at the level of the heart. The wound was sealed as for TNP therapy. The vacuum source was set to deliver negative pressures between -50 and -200 mmHg. The pressure on the anterior surface of the heart changed in a linear relationship with the applied negative pressure and was slightly lower than the applied negative pressure (-102 +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the pericardium (under the heart), in the left pleura and in the oesophagus, the wound pressure was only slightly affected by TNP therapy. In conclusion during TNP therapy, negative pressure is effectively transmitted to anterior portions of the heart. This may explain our recent findings that TNP increases microvascular blood flow in the myocardium. The pressure difference between the anterior and the posterior portions of the heart causes the right ventricle to be sucked up towards the posterior parts of the sternum, where it might be exposed to the sharp edges of the sternal bone, which may result in heart injury.


Süleymaniye Külliyesi: a historically important medical, scientific, and cultural center.
SCIENCE HAS MANY Western and Eastern historical roots. All of these contributed to the body of academic literature. One of the most important aspects of scientific progress is educational institutions, including hospitals, schools, and libraries. Some of these institutions may offer an identity for a city, as well as contribute to its development. Süleymaniye Külliyesi is one such institution. Süleymaniye Külliyesi, established in the 16th century, contains many centers, including a mosque, surrounded by a hospital, school of medicine, central pharmacy, and library. It once served both the Ottoman Empire and the Turkish Republic. The school of medicine of this complex was the first school of medicine in the Ottoman period that functioned in coordination with the hospital and central pharmacy. The library contains many rare books and manuscripts. Currently, it is one of the richest centers in the field of oriental studies. We conclude that Süleymaniye Külliyesi, with its health-related elements and library, contributed to the development and progress of science and deserves to be cited in the literature of the Western world.


The impact of being homeless on the unsuccessful outcome of treatment of pulmonary TB in São Paulo State, Brazil.
Tuberculosis (TB) is a major public health problem requiring complex treatment, the success of which depends on biological, social, and institutional factors. São Paulo State (SPS), in Brazil, has a high TB burden. Because of high socioeconomic heterogeneity and chaotic urbanisation, homelessness might play an important role in the TB burden in SPS. Our aim was to determine the association between homelessness and outcome of treatment of pulmonary TB (PTB) in SPS. A historical cohort from the routine SPS TB database for 2009-2013 was analysed. The study population was newly diagnosed adult patients with PTB. Homelessness was ascertained at notification or when treatment started. Our outcome was unsuccessful outcome of treatment. We used logistic regression to adjust for potential confounders and multiple imputation for missing data. We analysed 61,817 patients; 1726 (2.8 %, 95%CI 2.7-2.9 %) were homeless. Homeless patients were concentrated in bigger cities, were more frequently middle-aged males, had black/brown skin colour, and had received less education (P < 0.001, for all). Alcohol and drug use was three times more frequent in homeless patients (43.2 % vs 14.4 %, 30.2 % vs. 9.4 %, P < 0.001, respectively). HIV testing was less common among the homeless, of whom 17.3 % were HIV positive compared with 8.5 % among the not homeless population (P < 0.001). Microbiologic confirmation was more frequent among the homeless (91.6 % vs. 84.8 %, P < 0.001). Unsuccessful outcome of treatment was 57.3 % among the homeless and 17.5 % among the not homeless (OR = 6.32, 95%CI 5.73-6.97, P < 0.001), mainly due to loss to follow-up (39 %) and death (10.5 %). After full-adjustment for potential confounders, homelessness remained strongly associated with lower treatment success (aOR = 4.96, 95 % CI 4.27-5.76, P < 0.001). HIV status interacted with homelessness: among HIV-infected patients, the aOR was 2.45 (95%CI 1.90-3.16, Pinteraction < 0.001). The population attributable fraction for the joint effect of homelessness, alcohol and drug use was almost 20 %. Confirming our hypothesis, homelessness led to a marked reduction in the successful treatment of newly diagnosed pulmonary tuberculosis. Homelessness and associated conditions were important contributors to lack of treatment success in pulmonary tuberculosis in São Paulo. A multifaceted intervention must be implemented to target this vulnerable population.


Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers.
PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism and humoral hypercalcemia of malignancy (HHM), respectively. These syndromes are similar in several important ways, but differ in several characteristic, yet unexplained, ways. Two of the unresolved questions in HHM and hyperparathyroidism involve renal physiology. 1) Why does renal proximal tubular production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] differ between the two syndromes? 2) Do distal tubular calcium responses to PTH and PTHrP differ in the two syndromes? To address these questions, we compared the two peptides, human PTH-(1-34) and PTHrP-(1-36), in a direct, head to head study using a continuous, steady state infusion of each peptide at the same dose in normal human volunteers for 46 h. We had previously described such methods as applied to PTHrP, but a direct multiday comparison of PTHrP to PTH has not previously been reported. In two groups (seven subjects each) of healthy young (25- to 35-yr-old) normal volunteers, PTH and PTHrP infused at 8 pmol/kg.h displayed similar calcemic effects, although PTH was slightly more potent in this regard. Both peptides also displayed similar phosphaturic effects. In addition, both peptides had similar effects on renal tubular calcium handling, yielding fractional calcium excretion values of approximately 3.5%, some 50% below the values (6.5%) observed in subjects rendered similarly hypercalcemic by the infusion of calcium. In contrast to these several quantitatively similar effects of PTH and PTHrP, PTH tended to be selectively more effective than PTHrP in stimulating renal production of 1,25-(OH)(2)D. These studies indicate that renal tubular calcium reabsorption is likely to contribute to hypercalcemia in patients with HHM. In addition, PTH may be selectively more effective than PTHrP in stimulating 1,25-(OH)(2)D production, in contrast to its phosphaturic, calcemic effects and its effects to stimulate nephrogenous cAMP excretion and renal tubular calcium reabsorption.


Toxaphene insecticide: a complex biodegradable mixture.
Adsorption and gas-liquid chromatography separate toxaphene into at least 175 polychlorinated 10-carbon compounds including Cl(6), Cl(7), Cl(8), Cl(9), and Cl(10) derivatives. One toxic component is 2,2,5-endo,6-exo,8,9,10-heptachlorobornane. Rats metabolically dechlorinate toxaphene, removing about half of the chlorine from the technical insecticide and from each of seven subfractions of varying composition and toxicity.


Recapitulation of the cellular xeroderma pigmentosum-variant phenotypes using short interfering RNA for DNA polymerase H.
The lesion-specific DNA polymerase POLH gene is mutated in xeroderma pigmentosum variant (XP-V) patients who exhibit an increased skin cancer incidence from UV exposure. Normal cells in which POLH expression was reduced using short interfering RNAs (siRNAs) were compared with the XP-V cellular phenotype that results from naturally occurring inactivating mutations. Stable clones expressing siRNA had partially reduced POLH protein levels, and intermediate levels of UV sensitivity and S phase checkpoint activation, but similar levels of Mre11 foci as in XP-V cells. Therefore, suppression of POLH expression levels by siRNA recapitulates most of the phenotypes seen in cells from XP-V patients with inactivating mutations in POLH.


The Effects of the MORE Wisdom Resources on Spousal Caregivers' Life Satisfaction: An Application of the Resilience Model.
Models of resilience suggest that psychosocial resources and their interactions facilitate resilience while experiencing life challenges of caregiving. The MORE wisdom resources (sense of Mastery, Openness to experience, Reflective attitude, and Emotion regulation) have been suggested as possible personal resources of resilience that predict positive health outcomes of caregivers. Applying a model of resilience, this study examined the direct and indirect effects of the three of the MORE wisdom resources (sense of Mastery, Openness to experience, and Emotion regulation) on caregiving spouses' life satisfaction and perceived physical health. Using data from the survey of Midlife in the United States, caregiving spouses (n = 114) and matched non-caregivers (n = 114) were included. We compared the direct and indirect effects of the wisdom resources on life satisfaction and physical health between the two groups. The simple mediation model proposed in 2008 by Preacher and Hayes revealed that openness to experience was directly associated with better life satisfaction among caregiving spouses. Sense of mastery and emotion regulation had indirect effects on life satisfaction through spousal support. The effects the wisdom resources on caregiving spouses' perceived physical health were not found. This study demonstrated that the three of the MORE wisdom resources are possible personal resilience factors influencing life satisfaction among caregiving spouses. Moreover, the study showed how spousal support mediates the relationship between the wisdom resources and life satisfaction. Interventions aiming to increase life satisfaction among caregiving spouses should focus on increasing both personal and environmental resources and strengthening the relationship of the caregiver and care recipient.


[Effect of amphotericin B on the diuretic action of diacarb and various indicators of water-salt metabolism in healthy and tumor-bearing animals].
The experiments with albino rats, Wistar rats and SHK mice showed that the combined use of amphotericin B and diacarb markedly potentiated the effect of the latter: the amount of the urine excreted within 6 h and the renal excretion of sodium ions increased 1.8 and 1.5 times, respectively. Analogous trends were observed in the experiments with stabilization of the animal water balance by 2 per cent water loading. The studies on rats with Pliss lymphosarcoma showed that the diuresis level in the tumor-bearing animals was 3 times lower than that in healthy rats. The treatment with 5-fluorouracil lowered this index more significantly. With the use of amphotericin B, diacarb and their combination the urination level came to normal. The cyclophosphamide therapy of mice with sarcoma 180 was accompanied by accumulation of water in the tumor tissue. The combined use of the cytostatic with the polyenic antibiotic and diuretic resulted in a significant lowering of this index. In rats with Walker-256 carcinosarcoma, the treatment with the above three drugs lowered the sodium ion concentration and increased the calcium ion concentration in the tumor tissue. At the same time the electrolyte level in some organs not affected with malignant tumor (spleen, thymus, liver and adrenal glands) returned to normal.


Progress in Sol-Gel Technology for the Coatings of Fabrics.
The commercial availability of inorganic/organic precursors for sol-gel formulations is very high and increases day by day. In textile applications, the precursor-synthesized sol-gels along with functional chemicals can be deposited onto textile fabrics in one step by rolling, padding, dip-coating, spraying or spin coating. By using this technology, it is possible to provide fabrics with functional/multi-functional characteristics including flame retardant, anti-mosquito, water- repellent, oil-repellent, anti-bacterial, anti-wrinkle, ultraviolet (UV) protection and self-cleaning properties. These surface properties are discussed, describing the history, basic chemistry, factors affecting the sol-gel synthesis, progress in sol-gel technology along with various parameters controlling sol-gel technology. Additionally, this review deals with the recent progress of sol-gel technology in textiles in addressing fabric finishing, water repellent textiles, oil/water separation, flame retardant, UV protection and self-cleaning, self-sterilizing, wrinkle resistance, heat storage, photochromic and thermochromic color changes and the improvement of the durability and wear resistance properties.


Wavelet transform domain filters: a spatially selective noise filtration technique.
Wavelet transforms are multiresolution decompositions that can be used to analyze signals and images. They describe a signal by the power at each scale and position. Edges can be located very effectively in the wavelet transform domain. A spatially selective noise filtration technique based on the direct spatial correlation of the wavelet transform at several adjacent scales is introduced. A high correlation is used to infer that there is a significant feature at the position that should be passed through the filter. The authors have tested the technique on simulated signals, phantom images, and real MR images. It is found that the technique can reduce noise contents in signals and images by more than 80% while maintaining at least 80% of the value of the gradient at most edges. The authors did not observe any Gibbs' ringing or significant resolution loss on the filtered images. Artifacts that arose from the filtration are very small and local. The noise filtration technique is quite robust. There are many possible extensions of the technique. The authors see its applications in spatially dependent noise filtration, edge detection and enhancement, image restoration, and motion artifact removal. They have compared the performance of the technique to that of the Weiner filter and found it to be superior.


Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.
The Msh2-Msh3 mismatch repair (MMR) complex in Saccharomyces cerevisiae recognizes and directs repair of insertion/deletion loops (IDLs) up to ∼17 nucleotides. Msh2-Msh3 also recognizes and binds distinct looped and branched DNA structures with varying affinities, thereby contributing to genome stability outside post-replicative MMR through homologous recombination, double-strand break repair (DSBR) and the DNA damage response. In contrast, Msh2-Msh3 promotes genome instability through trinucleotide repeat (TNR) expansions, presumably by binding structures that form from single-stranded (ss) TNR sequences. We previously demonstrated that Msh2-Msh3 binding to 5' ssDNA flap structures interfered with Rad27 (Fen1 in humans)-mediated Okazaki fragment maturation (OFM) in vitro. Here we demonstrate that elevated Msh2-Msh3 levels interfere with DNA replication and base excision repair in vivo. Elevated Msh2-Msh3 also induced a cell cycle arrest that was dependent on RAD9 and ELG1 and led to PCNA modification. These phenotypes also required Msh2-Msh3 ATPase activity and downstream MMR proteins, indicating an active mechanism that is not simply a result of Msh2-Msh3 DNA-binding activity. This study provides new mechanistic details regarding how excess Msh2-Msh3 can disrupt DNA replication and repair and highlights the role of Msh2-Msh3 protein abundance in Msh2-Msh3-mediated genomic instability.


Organic law regulating euthanasia: knowledge and involvement of doctors in Spain one year after its implementation.
The Organic Law Regulating Euthanasia (LORE, for its initials in Spanish) came into force in June 2021. This study aims to examine knowledge of the LORE among physicians licensed in Spain as well as their involvement with and the impact of the law. This work is a descriptive, cross-sectional study conducted by means of a survey. Information was gathered through a self-administered questionnaire. The survey was answered by 1446 physicians licensed in Spain. The samples' demographic characteristics were as follows: 54.7% were women, the mean age was 52 ± 14 years, and 66.0% worked in a hospital. Catalonia was the autonomous community with the most participants (44.6%). Regarding specialties, anesthesiology and resuscitation had the highest number of participants (21.9%), followed by family and community medicine (18.5%). The LORE was known in detail by 24.3% of physicians, 58.0% had a positive opinion of it, and 31.1% had direct experience with the euthanasia procedure. Practitioners working in the hospital setting perceived the law more favorably compared to those in the primary care setting (62.3% vs. 47.3%, p < 0.01). Most doctors did not have in-depth knowledge of the LORE, although a majority supported its existence, particularly those in hospital medicine. Most physicians who viewed the LORE negatively were male, older, and worked in primary care. A minority of physicians considered registering as conscientious objectors.


Longitudinal Photogrammetric Analysis of the Columellar-Labial Angle following Primary Repair of Bilateral Cleft Lip and Nasal Deformity.
The changing nasolabial dimensions after repair of bilateral cleft lip and nasal deformity can be documented by anthropometry; however, the columellar-labial angle is rarely measured. This is a study of white patients who had synchronous repair of bilateral cleft lip performed by one surgeon (J.B.M.). The columellar-labial angle was measured on lateral photographs with the subject in neutral head position. Average values for columellar-labial angle at two or more time points were analyzed with a general estimating equation and cubic modeling. Values for complete and incomplete bilateral cleft lips were compared to each other and to Farkas' norms. Direct anthropometric measurements of intraoperative columellar length were compared to the postoperative columellar-labial angle using Pearson correlation analysis. Eighty-five patients were studied (64 complete and 21 incomplete clefts). The average photographic follow-up interval was 10 years (range, 1.8 to 19.5 years). The columellar-labial angle in bilateral complete clefts was significantly greater than in incomplete forms (p = 0.002). Although the angles decreased with time, they remained significantly greater than Farkas' normative values in both cleft groups (all p < 0.05). There was no correlation between the magnitude of columellar lengthening achieved during primary nasal correction and the postoperative columellar-labial angle. An obtuse columellar-labial angle can occur following synchronous nasolabial repair of a bilateral cleft lip, particularly in patients with a complete deformity. Although the angle narrows in time, it remains 1 to 2 SD greater than normal values. Secondary nasal correction may be needed if there is excessive tip rotation after completion of growth and orthognathic surgery. Therapeutic, IV.


Left ventricular diastolic suction with zero left atrial pressure in open-chest dogs.
We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.


Mechanism of fibrin(ogen) forced unfolding.
Fibrinogen, upon enzymatic conversion to monomeric fibrin, provides the building blocks for fibrin polymer, the scaffold of blood clots and thrombi. Little has been known about the force-induced unfolding of fibrin(ogen), even though it is the foundation for the mechanical and rheological properties of fibrin, which are essential for hemostasis. We determined mechanisms and mapped the free energy landscape of the elongation of fibrin(ogen) monomers and oligomers through combined experimental and theoretical studies of the nanomechanical properties of fibrin(ogen), using atomic force microscopy-based single-molecule unfolding and simulations in the experimentally relevant timescale. We have found that mechanical unraveling of fibrin(ogen) is determined by the combined molecular transitions that couple stepwise unfolding of the γ chain nodules and reversible extension-contraction of the α-helical coiled-coil connectors. These findings provide important characteristics of the fibrin(ogen) nanomechanics necessary to understand the molecular origins of fibrin viscoelasticity at the fiber and whole clot levels.


Weighted Gate Layer Autoencoders.
A single dataset could hide a significant number of relationships among its feature set. Learning these relationships simultaneously avoids the time complexity associated with running the learning algorithm for every possible relationship, and affords the learner with an ability to recover missing data and substitute erroneous ones by using available data. In our previous research, we introduced the gate-layer autoencoders (GLAEs), which offer an architecture that enables a single model to approximate multiple relationships simultaneously. GLAE controls what an autoencoder learns in a time series by switching on and off certain input gates, thus, allowing and disallowing the data to flow through the network to increase network's robustness. However, GLAE is limited to binary gates. In this article, we generalize the architecture to weighted gate layer autoencoders (WGLAE) through the addition of a weight layer to update the error according to which variables are more critical and to encourage the network to learn these variables. This new weight layer can also be used as an output gate and uses additional control parameters to afford the network with abilities to represent different models that can learn through gating the inputs. We compare the architecture against similar architectures in the literature and demonstrate that the proposed architecture produces more robust autoencoders with the ability to reconstruct both incomplete synthetic and real data with high accuracy.


Heat Death Associations with the built environment, social vulnerability and their interactions with rising temperature.
In an extreme heat event, people can go to air-conditioned public facilities if residential air-conditioning is not available. Residences that heat slowly may also mitigate health effects, particularly in neighborhoods with social vulnerability. We explored the contributions of social vulnerability and these infrastructures to heat mortality in Maricopa County and whether these relationships are sensitive to temperature. Using Poisson regression modeling with heat-related mortality as the outcome, we assessed the interaction of increasing temperature with social vulnerability, access to publicly available air conditioned space, home air conditioning and the thermal properties of residences. As temperatures increase, mortality from heat-related illness increases less in census tracts with more publicly accessible cooled spaces. Mortality from all internal causes of death did not have this association. Building thermal protection was not associated with mortality. Social vulnerability was still associated with mortality after adjusting for the infrastructure variables. To reduce heat-related mortality, the use of public cooled spaces might be expanded to target the most vulnerable.


Effects of ventriculoarterial coupling changes on renal function, echocardiographic indices and energy efficiency in patients with acute decompensated systolic heart failure under furosemide and dopamine treatment: a comparison of three therapeutic protocols.
Ventriculoarterial coupling (VAC) status relates to tissue perfusion and its optimization may improve organ function and energy efficiency (EE) of the cardiovascular system. The effects of non-invasively calculated VAC improvement on echocardiographic parameters, renal function indices and EE improvement in patients with acute decompensated systolic heart failure were studied. Furthermore, effects of different treatment modalities on VAC, renal function and echocardiographic parameters were compared. Systolic heart failure patients with ejection fraction <50% were studied, who, at the treating physician's discretion, received 8-hour infusions of: high dose furosemide (20mg/h), low dose furosemide (5mg/h) or dopamine (5μg/kg/min) combined with furosemide (5mg/h). Echocardiographic assessments were performed at 0 and 24h. Renal function was evaluated using serum creatinine and creatinine clearance. VAC and EE were assessed noninvasively, by echocardiography. Significant correlations were noted between VAC improvement and improvements in EE and serum creatinine (rho=0.96, p<0.001, rho=0.32, p=0.04 respectively). Dopamine-furosemide combination had a borderline effect on creatinine (p=0.08) and led to significant improvements in e', E/e' ratio (p=0.015 and p=0.009 respectively) and VAC (value closer to 1). VAC improvement correlated with EE and creatinine improvement, regardless of treatment, supporting a potential role for VAC status assessment and improvement in acute decompensated systolic heart failure. Dopamine and furosemide combination seemed to improve VAC and diastolic function but only had a borderline effect on renal function.


Sex Hormone-Binding Globulins and Testosterone Levels as a Risk Marker for Type 2 Diabetes Mellitus among Postmenopausal Women.
Endogenous sex hormones and sex hormone-binding globulins (SHBG) determine the risk of occurrence of Type 2 diabetes mellitus (T2DM) in postmenopausal (PM) women. To investigate the association between sex hormones (estradiol and testosterone) and SHBG with plasma glucose, fasting insulin levels, HbA1c, and homeostasis model assessment insulin resistance (HOMA-IR) and also to investigate independent role of sex hormones in the occurrence of T2DM among PM. Cross-sectional case-control study. The present study was conducted in Endocrinology department Guwahati, Medical College, Assam, India. The participants included cases - PM women with T2DM (n = 100) and controls - Healthy PM women (n = 86). The medical history, clinical examination, and investigations including total testosterone, serum estradiol, SHBG, free testosterone index, high sensitivity C-reactive protein (hs-CRP), lipid profile, fasting insulin, fasting plasma glucose (FPG), and postprandial plasma glucose (PPPG) were done and analyzed. HOMA-IR was calculated. Pearson correlation between sex hormone level and SHBG with plasma glucose, HbA1c, fasting insulin, hs-CRP, and HOMA-IR was seen. Multivariance logistic analysis was done to find the independent association between sex hormones/SHBG and the occurrence of T2 DM. P < 0.05 was considered statistically significant. Among the cases, a significant positive correlation was found between total testosterone/free testosterone index with waist circumference, FPG PPPG, HbA1c, fasting insulin, and HOMA-IR, and a significant negative correlation was found between SHBG and FPG, PPPG, HbA1c, fasting insulin, and HOMA-IR (P < 0.01). The logistic analysis showed total testosterone levels and SHBG are independently associated with the occurrence of T2 DM among PM (P < 0.01). SHBG and testosterone levels in PM can be a risk marker for the development of T2DM.


Identification of chemical structure and free radical scavenging activity of diphlorethohydroxycarmalol isolated from a brown alga, Ishige okamurae.
To obtain a natural antioxidant from a marine biomass, this study investigated the antioxidative activity of methanolic extracts from the marine brown alga, Ishige okamurae collected off Jeju Island. A potent free radical scavenging activity was detected in the ethyl acetate fraction containing polyphenolic compounds, and the potent antioxidant elucidated as a kind of phlorotannin, diphlorethohydroxycarmalol, by NMR and mass spectroscopic data. The free radical scavenging activities of the diphlorethohydroxycarmalol were investigated in relation to 1,1-diphenyl-2-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals using an electron spin resonance (ESR) system. The diphlorethohydroxycarmalol was found to scavenge DPPH (IC50=3.41 microM) and alkyl (IC50=4.92 microM) radicals more effectively than the commercial antioxidant, ascorbic acid. Therefore, these results present diphlorethohydroxycarmalol as a new phlorotannin with a potent antioxidative activity that could be useful in cosmetics, foods, and pharmaceuticals.


Short- and long-periods of neonatal maternal separation differentially affect anxiety and feeding in adult rats: gender-dependent effects.
Environmental manipulations during early development can induce permanent alterations in hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stressors. However, little is known about the impact of early life experiences on appetitive responses. The present investigation assessed the effects of brief handling/separation or protracted separation from the dams, on feeding and anxiety responses during development. During the first 3 weeks post-partum, Sprague-Dawley rat pups were exposed daily to either brief (15 min) handling/isolation (H), a more protracted (3 h) period of maternal separation (MS), or were not handled (NH). When tested on the elevated plus-maze (at 5-6 weeks) H groups displayed less anxiety than NH gender-matched controls. Surprisingly, so did the MS females. At weaning (Day 22), the MS rats weighed significantly less than both the H and NH animals; the difference between the H and MS was more robust and persisted throughout the experiment (D 62). The H animals of both genders, and the females of the MS group, consumed more of the palatable 'snack' than their NH counterparts. The feeding suppressant response to the various satiety peptides (bombesin, cholecystokinin, and amylin) was not affected by the early life experience, with exception of cholecystokinin (CCK) effects, which were more pronounced in H and MS males. These results suggest that early life events may contribute to anxiety and/or ingestive disorders such as anorexia nervosa, bulimia and obesity.


Dosimetry in the therapy of metastatic differentiated thyroid cancer administering high 131I activity: the experience of Busto Arsizio Hospital (Italy).
The purpose of the present work was to evaluate the impact of 131I high activity therapy treatments of metastatic differentiated thyroid cancer (MDTC) in terms of feasibility, tolerance, efficacy, and the impact of dosimetry in order to optimize the process. Seventeen MDTC patients underwent 27 treatments with 131I, with activity ranging from 6.2 GBq to 24.1 GBq. Red marrow (RM) peritherapy dosimetry was based on the Standard Operating Procedure of European Association of Nuclear Medicine (EANM SOP), while metastases dosimetry on the guidelines of Italian Association of Physicists in Medicine and Italian Association of Nuclear Medicine. In 12 cases prospective dosimetry was performed too, with the purpose of evaluating the possibility of maximizing the therapeutic activity, complying the 2 Gy red marrow (RM) dose constraint. The absorbed dose to 45 lesions was evaluated. The severity of myelotoxic effects was monitored during the follow-up. Treatments were generally well tolerated, also at the highest RM absorbed doses. RM absorbed doses ranged from 0.49 to 6.67 Gy, lesion doses from 1.1 Gy to 778 Gy. In case of repeated treatments on the same site, in 13 cases on a total of 15, an absorbed dose reduction was observed. RM prospective and peritherapeutic dosimetry differed somewhat: absorbed doses measured during therapy ranged from -7% to +40% with respect to provisional absorbed doses. In our experience high activity treatments were well-tolerated. Prospective dosimetry needs further investigation to become sufficiently reliable in order to comply the 2 Gy constraint. Lesions became progressively less iodine-avid in case of repeated treatments, so the "first big-shoot" treatment with the highest safe activity seems to be desirable to obtain the maximum efficacy.