The interferon antiviral response: from viral invasion to evasion.
One of the initial responses of an organism to infection by pathogenic viruses is the synthesis of antiviral cytokines such as the type I interferons (interferon-alpha/beta), interleukins, and other proinflammatory cytokines and chemokines. Interferons provide a first line of defence against virus infections by generating an intracellular environment that restricts virus replication and signals the presence of a viral pathogen to the adaptive arm of the immune response. Interferons stimulate cells in the local environment to activate a network of interferon-stimulated genes, which encode proteins that have antiviral, antiproliferative and immunomodulatory activities. The present review focuses on recent reports that describe the activation of multiple signalling pathways following virus infection, new candidate genes that are implicated in the establishment of the antiviral state, and the strategies used by viruses and their specific viral products to antagonize and evade the host antiviral response.


Low bone density and low serum levels of soluble RANK ligand are associated with severe arterial calcification in patients with Takayasu arteritis.
Takayasu arteritis (TA) is a chronic inflammatory disorder affecting the aorta and its branches. Vascular calcification has been described in 29-54% of cases of TA, although its aetiology remains unknown. Recently the osteoprotegerin/RANKL/RANK system has emerged as an important contributing factor to atherogenesis and osteogenesis. Our aim is to investigate the association between vascular calcification, bone mineral density (BMD) and the osteoprotegerin/RANK/RANKL system in TA. Thirty pre-menopausal female TA patients and 30 age- and sex-matched controls were studied. BMD was measured by dual X-ray absorptiometry. Arterial calcification in TA patients was analysed by computed tomography in thoracic and abdominal sites. Serum levels of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) were quantified by enzyme-linked immunosorbent assay. Patients with severe arterial calcification showed lower BMD values than controls in lumbar spine (0.965 +/- 0.055 vs 1.126 +/- 0.153 g/cm2, P = 0.009) and total body (0.993 +/- 0.065 vs 1.085 +/- 0.082 g/cm2, P = 0.019). In contrast, TA patients without calcification presented BMD values similar to controls (P > 0.05). Interestingly, lower serum levels of sRANKL (1.89 +/- 2.35 vs 2.80 +/- 2.23 pg/ml, P = 0.031) and a longer disease duration (12.20 +/- 6.61 vs 3.56 +/- 5.33 yr, P = 0.004) were observed in TA patients with severe calcification compared with patients without calcification. Severe arterial calcification in TA is associated with low values of BMD and sRANKL, reinforcing the possible link between bone and vascular disease.


Results of Conserve Plus Hip Resurfacing: prospective clinical, radiographic and ion study.
We report the 3- to 5-year clinical, radiographic and serum ion level results of a prospective consecutive cohort of 42 hip resurfacing arthroplasties using the Conserve Plus implant in 39 male patients that were operated on by a single surgeon in a community hospital. Average age was 53 years (range 34-67) at surgery. There was one revision for a subcapital neck fracture. There were no surgery related complications. The survival of the implant was 95%. Clinical evaluation showed excellent results with a modified Charnley score of 17.6/18, Harris Hip Score of 96.2/100, WOMAC of 95.1/100, Oxford Score 15.3, and UCLA-Activity Score of 8/10. Radiographic analysis showed no implant at risk, no migration or signs of loosening, no neck narrowing and no osteolysis at final follow-up. Average cup inclination angle was 43.5° with 2 outliers (34° and 57°). Ion level study showed average cobalt in serum 1.04 µg/l (range 0-4) for the whole group, 0.7 µg/l (range 0-3) in patients with unilateral resurfacing and 2.0 µg/l (range 0-4) in patients with bilateral resurfacing. All patients had ion levels within the safe zone. This independent series of Conserve Plus HRA confirms good results at short- to mid-term with excellent wear characteristics. Results for avascular necrosis were equal to those for osteoarthritis.


The organization of carbohydrate in mouse synaptosomal plasma membrane.
Analysis of synaptosomal plasma membrane from mouse brain by SDS gel electrophoresis reveals a large number of glycoprotein and glycolipid species, as distinguished by periodic acid Schiff or by the distribution of in vivo incorporated 3H-fucose label. The topographical distribution of this carbohydrate in the plasma membrane was examined by labelling intact synaptosomes and isolated membrane with galactose oxidase (E.C. 126.96.36.199.)-3H-NaBH4. In both, gangliosides and a wide spectrum of glycoprotein species were labelled. Extraction of SPM with 0.05 N NaOH at 0 degrees C removed about two-thirds of the membrane's protein. Gel electrophoresis of the solubilized material revealed partial or complete extraction of a large number of polypeptide species; however, all of the glycoproteins, as well as the glycolipid, remained in the insoluble pellet. These results indicate a highly asymmetric arrangement of glycoproteins and glycolipids in SPM; most or all of these species reside on the external surface of the synaptosome, accessible to galactose oxidase. The glycoproteins appear to be more deeply-buried in the lipid bilayer than the other polypeptide species, as has been found in other systems.


Partial assembly of the yeast vacuolar H(+)-ATPase in mutants lacking one subunit of the enzyme.
Partial assembly of the peripheral and integral membrane sectors of the yeast vacuolar H(+)-ATPase has been detected in mutants lacking one subunit of the enzyme. Assembled complexes of the vacuolar H(+)-ATPase could be immunoprecipitated from biosynthetically labeled wild-type cells using monoclonal antibodies specific for the 69- and 60-kDa subunits of the enzyme, and assembled membrane (V0) sectors could be immunoprecipitated using a monoclonal antibody against the 100-kDa subunits. Parallel immunoprecipitations from mutant cells lacking one subunit of the vacuolar H(+)-ATPase revealed different degrees of assembly depending on the subunit that was missing. Partially assembled complexes of the peripheral subunits could also be detected in a soluble, cytoplasmic fraction from wild-type and mutant cells following glycerol gradient fractionation. The results indicate that the peripheral (V1) sector and integral membrane (V0) sectors of the yeast vacuolar H(+)-ATPase can assemble independently. The 69-, 60-, and 27-kDa subunits all appear to be necessary for any assembly of the V1 sector to occur, but these subunits and the 32-kDa subunit can assemble into a complex in the absence of the 42-kDa peripheral subunit. The implications of the results for the structure and assembly of the yeast vacuolar H(+)-ATPase are discussed.


Controlled trial of backrest elevation after coronary angiography.
Protocol at most centers requires keeping the head of the bed flat for at least 5.5 hours after coronary angiography. To determine the effect of head of bed elevation after diagnostic coronary angiography on patient comfort and on the incidence and timing of postprocedural complications. A convenience sample of 120 adult patients on the short-stay special procedures nursing unit of a university teaching hospital was used. Patients who had undergone elective diagnostic coronary angiography via the femoral artery were randomly assigned to a control or experimental group. The control group had the head of bed maintained at 15 degrees or less for 5.5 hours after the procedure. The experimental group had the head of bed gradually elevated from 15 degrees to 60 degrees over the 5.5 hours. Both groups dangled and ambulated after 5.5 hours. All other aspects of the procedure were identical. Outcome was measured by incidence and timing of dizziness, hypotension, bleeding, hematoma, and diminished foot pulses. Level of pain was assessed on a scale of 0 to 10. No statistically significant differences were noted between groups in the incidence of complications. The incidence of back pain at a level of more than 3 on a scale of 0 to 10 was less for the experimental group than for the control group. Elevation of the head of the bed after coronary angiography decreases discomfort with no increase in complications. Replication of this study is needed for verification.


Rapid group A streptococcal antigen detection kit: effect on antimicrobial therapy for acute pharyngitis.
Newly introduced rapid diagnostic tests for group A streptococcal pharyngitis should facilitate appropriate antimicrobial use in patients with group A streptococcal pharyngitis. Because of high rates of acute pharyngitis in Tuba City, AZ, at the Navajo Indian reservation, the use of rapid diagnostic test was prospectively evaluated. The sensitivity and specificity of the test was measured and changes in physician prescribing patterns attributable to use of the test were correlated. Of 320 patients with pharyngitis enrolled during the present 3-week study, 86 met the study's definition of a patient with streptococcal pharyngitis and 163 met the study's definition of a patient with nonstreptococcal pharyngitis. The rapid test was 62.8% sensitive and 96.9% specific in identifying patients from whom group A streptococci were isolated. Although treatment of patients with streptococcal pharyngitis at the time of the first visit increased from 36.5% in a retrospective sample to 72.5% during the study, treatment of patients in whom cultures were negative remained the same. Further analyses showed that physicians tended to treat patients with signs characteristic of streptococcal pharyngitis and, as the study progressed, to rely less on negative rapid test results as a reason to withhold antimicrobial agents. It was concluded that rapid tests with good specificity but limited sensitivity may improve treatment of patients with streptococcal pharyngitis by allowing earlier specific therapy. A more sensitive test with a higher negative predictive value would be necessary to prevent treatment of persons with nonstreptococcal pharyngitis.


System with temporal-spatial noise.
This paper investigates systems driven by temporal-spatial noise using two models, i.e., a spatially periodic model, and a model with infinite globally coupled oscillators. The study shows that, for the first model, the temporal-spatial noise has a stronger effect on the transport of particles than the usual additive and multiplicative noise; for the second model, the temporal-spatial noise can restrict the appearance of the symmetry-breaking nonequilibrium phase transition, in contrast with the case when the system is driven by the usual multiplicative noise.


[Use of amino acids in major burns].
The results of protein deficiency in major burn cases are examined. They include diminished organ resistance, deleyed wound haeling, proneness to infection, and increased sensitivity to liver-toxic substances, leading to the protracted course of the patient's conditions. Since his caloric intake also needs to be increased, the importance of protein replacement is apparent. A standardised 15-day treatment with daily administrations of 1000 cc of a 7.5% natural amino acid solution was experimented during the period following shock, to prevent loss of amino acids through the vessel walls, since permeability is high in this periodo. Marked improvement in blood proteins was noted, with normalisation in some instances. No chagens in blood chemistry attributable to the treatment were noted.


225Ac-PSMA-617 Radioligand Posttherapy Imaging in Metastatic Castrate-Resistant Prostate Cancer Patient Using 3 Photopeaks.
PSMA-based radioligand therapies have shown the beneficial effect in metastatic castrate-resistant prostate cancer (mCRPC) patients when they become refectory to the established treatments with associated potential toxicities and high mortality rate. Ac-PSMA therapy is known to be remarkably effective in substantially pretreated mCRPC patients. However, posttherapy imaging is usually not performed as alpha emitters are really difficult to image. We presents a patient of mCRPC treated with Ac-PSMA-617, and his posttherapy whole-body scans acquired by using 3 different photopeaks (78, 218, and 440 keV) fairly demonstrated the tracer's distribution and the efficacy of targeted alpha therapy.


Localization of Escherichia coli RNA polymerase-binding sites on bacteriophage S13 replicative form I DNA by protection of restriction enzyme cleavage sites.
Protection of restriction endonuclease cleavage sites by Escherichia coli RNA polymerase bound to the replicative form I of bacteriophage S13 DNA has been used to identify a number of regions of RNA polymerase binding. Digestion with HincII, AluI, HinfI, or HaeIII, under conditions optimized for "open" complex formation, revealed 12 regions of RNA polymerase binding. Based on differential salt sensitivities, five of the regions were classified as strong or tight binding sites. These were located before genes A (two sites), B, and D and at the 5' end of gene F. The seven regions which exhibited weaker binding were located at the 5' end of gene C (two sites), in the middle of gene D, just before and at the 3' end of gene F, at the 5' end of gene G, and in the middle of gene H. The sites before genes B and D coincide with sites previously identified as promoters in bacteriophage phi X174. One of the sites before gene A, that at nucleotides 5175-5211, represents a new putative promoter site in bacteriophage S13 and phi X174 located before the previously identified A gene promoter at nucleotides 10-45.


Knowledge and awareness of stroke in the United Arab Emirates: a cross-sectional study of the general population.
The study aimed to assess stroke knowledge among the general population in the United Arab Emirates (UAE) and determine the factors associated with stroke awareness among people. A cross-sectional study was conducted in the UAE between September and November 2021. The general population has self-administered an online bilingual survey (Arabic and English) distributed via social media platforms. The questionnaire covered general knowledge about stroke risk factors, consequences of stroke, and responding to somebody with acute stroke attack. A total of 545 surveys were completed, with more than half of the participants being female (58.5%), married (55.4%) and employed (59.4%). The majority were less than 50 years old (90.5%) and had a university degree (71.0%). Many of the participants (70.8%) had a good general knowledge of stroke; however, around 20% of the participants were able to recognize all symptoms and risk factors of stroke. The most common sources of stroke-related information were the internet/social media (53.6%). Females were better able to correctly identify at least one stroke symptom and outcome than males (p=0.008). University education has significantly affected participants' ability to identify early stroke symptoms (p=0.001) correctly. In addition, diabetic people were more likely to recognize at least one stroke outcome than non-diabetic people (p=0.039). The knowledge of stroke was good among highly educated people and females. However, the awareness of all stroke risk factors, symptoms, consequences and risk factors was inadequate among the general population of the UAE. Thus, there is still a gap between recognition of the relevant stroke and taking action among people.


Out-of-hospital cardiac arrest survivors sent for emergency angiography: a clinical score for predicting acute myocardial infarction.
Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Emergency coronary angiography and percutaneous coronary intervention might improve survival, especially when cardiac arrest is caused by acute myocardial infarction (AMI). However, identifying patients with AMI after OHCA remains challenging. The aim of this study was to determine the clinical and ECG criteria in OHCA that may help to identify better the patients with AMI. Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study. A total of 177 patients with complete datasets were included. Significant coronary artery disease was found in 71% of the patients, and 43% presented with AMI. The independent predictors of AMI were ST elevation in any lead including aVR (odds ratio (OR) 18.06; 95% confidence interval (CI) 6.6-49.38), chest pain before cardiac arrest (OR 4.05; 95% CI 1.55-10.54) and an initial shockable rhythm (OR 2.99; 95% CI 1.34-6.45). An additive score that included these three predictors yielded a sensitivity and a specificity for detecting AMI of 93% and 63%, respectively. These data suggest that fewer than half of patients with OHCA undergoing emergency coronary angiography present with AMI. The identification of OHCA patients with AMI might be improved by a simple score using post-resuscitation ECG and simple clinical criteria.


Cytidine 5'-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats.
Cytidine 5'-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury. Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function. The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P<0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume. In situ administration of 0.4 mL of 100 µmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury.


Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits.
Envenomation by haemotoxic enzymes remains a significant source of human morbidity and mortality worldwide, with administration of long-acting or multiple doses of antivenom first-line therapy. However, coagulopathy can still occur and recur. Of interest, it has been recently demonstrated that direct, isolated exposure of snake venom enzymes with fibrinogenolytic activity to carbon monoxide (CO) abrogates venom-mediated loss of coagulation in human plasma. These observations of CO inhibition of venom fibrinogenolytic activity were subsequently repeated in rabbit whole blood. This study sought to translate these findings in an in vivo rabbit model of envenomation with fibrinogenolytic Crotalus atrox venom. Sedated rabbits were intravenously administered C. atrox venom (400 μg/kg) pre-exposed to 0 or 1000 μM carbon monoxide-releasing molecule-2 (CORM-2) in vitro. Arterial whole-blood samples demonstrated that compared to pre-envenomation values, the CORM-2-naïve venom significantly prolonged the onset of coagulation, decreased the velocity of clot growth and decreased clot strength as determined by thromboelastography an hour after venom injection. In contrast, CORM-2 pre-exposure prevented or attenuated C. atrox venom effects on coagulation kinetics. Future studies to determine whether rabbits injected with such venom subcutaneously/intramuscularly can have consequent coagulopathy abrogated by injection of carbon monoxide-releasing molecules into the 'bite site' are justified.


Development of species identification in ducklings: XII. Ineffectiveness of auditory self-stimulation in wood ducklings (Aix sponsa).
A previous study revealed that wood ducklings vocalize copiously when in auditory isolation. However, such self-stimulation appeared to be ineffective in maintaining their preference for the characteristically descending frequency-modulated (FM) notes of the wood duck maternal call. Only isolated birds that had been exposed to a recording of descending sib calls showed the normal preference for descending maternal notes in a choice test with descending and ascending maternal calls. In this study, the actual vocalizations of stimulated and unstimulated wood ducklings were examined in order to explore the possibility that there is a difference in the kind and/or amount of auditory self-stimulation in the two groups (e.g., the stimulated birds might produce more descending calls). Although the stimulated birds produced more ascending notes than the unstimulated birds, no differences were found in the overall vocal behavior, vocal reactivity, or specific kinds of frequency modulation produced by the birds that preferred the descending maternal call and the other birds that responded in the choice test. The absence of a difference in vocal production between the birds that preferred the descending call and the other responding birds supports the previous conclusion that self-stimulation apparently plays no role in the development or maintenance of the species-typical perceptual preference for the descending FM notes of the wood duck maternal call.


Intraoperative Laser Speckle Contrast Imaging For Real-Time Visualization of Cerebral Blood Flow in Cerebrovascular Surgery: Results From Pre-Clinical Studies.
Cerebrovascular surgery can benefit from an intraoperative system that conducts continuous monitoring of cerebral blood flow (CBF). Such a system must be handy, non-invasive, and directly integrated into the surgical workflow. None of the currently available techniques, considered alone, meets all these criteria. Here, we introduce the SurgeON™ system: a newly developed non-invasive modular tool which transmits high-resolution Laser Speckle Contrast Imaging (LSCI) directly onto the eyepiece of the surgical microscope. In preclinical rodent and rabbit models, we show that this system enabled the detection of acute perfusion changes as well as the recording of temporal response patterns and degrees of flow changes in various microvascular settings, such as middle cerebral artery occlusion, femoral artery clipping, and complete or incomplete cortical vessel cautery. During these procedures, a real-time visualization of vasculature and CBF was available in high spatial resolution through the eyepiece as a direct overlay on the live morphological view of the surgical field. Upon comparison with indocyanine green angiography videoangiography (ICG-VA) imaging, also operable via SurgeON, we found that direct-LSCI can produce greater information than ICG-VA and that continuous display of data is advantageous for performing immediate LSCI-guided adjustments in real time.


Timecourse of object-related neural activity in the primate prefrontal cortex during a short-term memory task.
We studied the timecourse of neural activity in the primate (Macacca mulatta) prefrontal (PF) cortex during an object delayed-matching-to-sample (DMS) task. To assess the effects of experience on this timecourse, we conducted the task using both novel and highly familiar objects. In addition, noise patterns containing no task-relevant information were used as samples on some trials. Comparison of average PF ensemble activity relative to baseline activity generated by objects and noise patterns revealed three distinct activity periods. (i) Sample onset elicited a transient sensory visual response. In this sensory period, novel objects elicited stronger average ensemble activity than both familiar objects and noise patterns. (ii) An intermediate period of elevated activity followed, which began before sample offset, and continued well into the delay period. In the intermediate period, activity was elevated for noise patterns and novel objects, but near baseline for familiar objects. (iii) Finally, after average ensemble activity reached baseline activity at the end of the intermediate period, a reactivation period occurred late in the delay. Experience had little effect during reactivation, where activity was elevated for both novel and familiar objects compared to noise patterns. We show that the ensemble average resembles the activity timecourse of many single prefrontal neurons. These results suggest that PF delay activity does not merely maintain recent sensory input, but is subject to more complex experience-dependent dynamics. This has implications for how delay activity is generated and maintained.


Regional variation of the alphabeta T cell repertoire in the colon of healthy individuals and patients with Crohn's disease.
Clonally expanded T cells might be involved in the pathogenesis of Crohn's disease (CD). To test the impact of CD on the regional distribution of expanded T cells, this study analyzed the T cell receptor beta (TCRB) repertoire within colonic biopsy specimens from 12 CD patients and 6 noninflammatory controls by TCR spectratyping. Migration characteristics of dominant CDR3 bands from different sites of the normal mucosa suggested focal, segmental, or ubiquitous spreading of individual expanded clones. Similar patterns were observed when inflamed and noninflamed areas of the colon of CD patients were compared, suggesting that regional expansion of T cells was more closely related to anatomic proximity than to local inflammatory activity. CDR3-sequence analysis of TCRBV12+ T cells, which were selectively expanded in the inflamed colon of 3 CD patients, failed to reveal a public CDR3 motif. Our data indicate the existence of distinct patterns of regional T cell expansions in the normal gut mucosa, which are not significantly disrupted by chronic intestinal inflammation. This does not exclude a pathogenic role of expanded T cells in CD through more subtle changes, but emphasizes the need to distinguish them from a discontinuous distribution of clonally expanded T cells in normal colon.


High-κ Lanthanum Zirconium Oxide Thin Film Dielectrics from Aqueous Solution Precursors.
Metal oxide thin films are critical components in modern electronic applications. In particular, high-κ dielectrics are of interest for reducing power consumption in metal-insulator-semiconductor (MIS) field-effect transistors. Although thin-film materials are typically produced via vacuum-based methods, solution deposition offers a scalable and cost-efficient alternative. We report an all-inorganic aqueous solution route to amorphous lanthanum zirconium oxide (La2Zr2O7, LZO) dielectric thin films. LZO films were spin-cast from aqueous solutions of metal nitrates and annealed at temperatures between 300 and 600 °C to produce dense, defect-free, and smooth films with subnanometer roughness. Dielectric constants of 12.2-16.4 and loss tangents <0.6% were obtained for MIS devices utilizing LZO as the dielectric layer (1 kHz). Leakage currents <10-7 A cm-2 at 4 MV cm-1 were measured for samples annealed at 600 °C. The excellent surface morphology, high dielectric constants, and low leakage current densities makes these LZO dielectrics promising candidates for thin-film transistor devices.


Neurosarcoidosis which manifested as acute hydrocephalus: diagnosis and treatment.
Neurosarcoidosis is generally expressed by various symptoms; it is exceptionally revealed by hydrocephalus. We report a 27-year-old African man hospitalized with acute neurological deterioration due to hydrocephalus. The treatment consisted of ventriculostomy and corticosteroid therapy; however a permanent shunt was not required. After six months of follow-up, the patient had fully recovered. Clinical presentation, neuroimaging findings and treatment modalities are discussed.


Patient Admission and Mechanical Ventilator Allocation Decision-Making Processes by Frontline Medical Professionals in a Japanese ICU During the COVID-19 Pandemic: A Qualitative Study.
During the COVID-19 pandemic, the need to triage COVID-19 patients in ICUs emerged globally. Triage guidelines were established in many countries; however, the actual triage decision-making processes and decisions themselves made by frontline medical providers may not have exactly reflected those guidelines. Despite the need to understand decisions and processes in practice regarding patient ICU admission and mechanical ventilator usage to identify areas of improvement for medical care provision, such research is limited. This qualitative study was conducted to identify the decision-making processes regarding COVID-19 patient ICU admissions and mechanical ventilator allocation by frontline medical providers and issues associated with those processes in an ICU during the COVID-19 pandemic. Semi-structured, in-depth interviews were conducted with ICU physicians and nurses working at an urban tertiary referral hospital in Japan between February and April 2022. Patient characteristics that influenced triage decisions made by physicians and the interaction between physicians, nurses, and senior management staff upon making such decisions are discussed in this article. An implicated issue was the lack of legal support for Japanese physicians to practice withdrawal of life-sustaining treatments even during emergencies. Another issue was the impact of non-clinical forces-likely specific to health emergencies-on physicians' decisions regarding mechanical ventilator allocation, where such forces imposed a significant mental burden on the medical providers. We consider public policy and legal implications for future pandemics.


[Management of patients with intermittent claudication].
Management of patients with intermittent claudication must be first the treatment of the atherosclerosis process: cessation of smoking, antiplatelet therapy, betablockers, angiotensin-converting-enzyme inhibitor and cholesterol lowering in order to have a LDL cholesterol < 1 g/L. Treatment of intermittent claudication depends of the arterial lesions. If an endovascular procedure is feasible and safe, iliac stenosis or short iliac occlusion, it permits a spectacular improvement. Most often only medical treatment with physical training is advisable. Surgical revascularisation is rarely justified in patients with intermittent claudication.


Relationship of arterial compliance to baroreflex function in hypertensive patients.
The objectives of this study were to determine whether carotid arterial compliance is reduced in patients with hypertension and to assess whether reduced arterial compliance is related to abnormal arterial baroreflex function. Accordingly, concurrent measurements of carotid arterial diameter (via computerized high resolution B-mode ultrasonography) and blood pressure were made to determine carotid arterial compliance in 23 normotensive and 16 age-matched hypertensive patients. In addition, arterial baroreflex function was assessed in 12 of the normal subjects and nine of the hypertensive patients by measuring the infusions of nitroprusside and phenylephrine. Compared with the normotensive subjects, the patients with hypertension had reduced compliance (5.9 +/- 0.7 vs. 16.6 +/- 1.8 10(-7) m2/kPa, mean +/- SE, P < 0.001). The baroreflex slope relating the change in R-R interval to the change in systolic blood pressure during the drug infusions was less in the hypertensive than normotensive subjects (12.3 +/- 2 vs. 18.9 +/- 2 ms/mmHg, P < 0.05). Consequently, when both normotensive and hypertensive subjects were considered, there was a significant correlation between the baroreflex slope and compliance (r = 0.53, P < 0.05). However, there was no correlation between the baroreflex slope and compliance within either the normotensive group (r = 0.04, P = NS) or the hypertensive group (r = 0.43, P = NS) when analyzed separately. There was a significant correlation between age and compliance (r = -0.48, P < 0.01) but not between age and baroreflex function.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and efficacy of Ofatumumab in chronic lymphocytic leukemia: a systematic review and meta-analysis.
Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia (CLL) but no studies have yet reported a pooled estimate of the treatment effect. We performed a meta-analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL. Relevant publications from PubMed, Web of Science, Embase, and ClinicalTrials.gov were searched. The primary efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. The pooled efficacy analysis showed that there were no significant difference in PFS [hazard ratios (HR) = 0.88, 95% confidence interval (CI) = 0.47-1.63, p = 0.677, I2 = 94.9%] and OS (HR = 0.97, 95% CI = 0.70-1.36, p = 0.878, I2 = 58.7%) between Ofatumumab-based therapy and non-Ofatumumab therapy. The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy. Moreover, infections, and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies. Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments (including Ofatumumab alone, Ofatumumab plus chemotherapy) for CLL compared with observation or chemotherapy-based regimen groups. Ofatumumab had no statistically significant improvement on the OS of patients with CLL. The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections.


The NEAT Equating Via Chaining Random Forests in the Context of Small Sample Sizes: A Machine-Learning Method.
The part of responses that is absent in the nonequivalent groups with anchor test (NEAT) design can be managed to a planned missing scenario. In the context of small sample sizes, we present a machine learning (ML)-based imputation technique called chaining random forests (CRF) to perform equating tasks within the NEAT design. Specifically, seven CRF-based imputation equating methods are proposed based on different data augmentation methods. The equating performance of the proposed methods is examined through a simulation study. Five factors are considered: (a) test length (20, 30, 40, 50), (b) sample size per test form (50 versus 100), (c) ratio of common/anchor items (0.2 versus 0.3), and (d) equivalent versus nonequivalent groups taking the two forms (no mean difference versus a mean difference of 0.5), and (e) three different types of anchors (random, easy, and hard), resulting in 96 conditions. In addition, five traditional equating methods, (1) Tucker method; (2) Levine observed score method; (3) equipercentile equating method; (4) circle-arc method; and (5) concurrent calibration based on Rasch model, were also considered, plus seven CRF-based imputation equating methods for a total of 12 methods in this study. The findings suggest that benefiting from the advantages of ML techniques, CRF-based methods that incorporate the equating result of the Tucker method, such as IMP_total_Tucker, IMP_pair_Tucker, and IMP_Tucker_cirlce methods, can yield more robust and trustable estimates for the "missingness" in an equating task and therefore result in more accurate equated scores than other counterparts in short-length tests with small samples.


The molecular mechanisms and environmental effects of modified clay control algal blooms in aquacultural water.
Modified clay (MC) technology is an effective method for controlling harmful algal blooms (HABs). Based on field experience, a bloom does not continue after treatment with MC, even though the residual HAB biomass accounts for 20-30% of the initial biomass. Laboratory studies using unialgal cultures have found that MC could inhibit the growth of the residual algal cells to prevent HABs. Nevertheless, the phytoplankton in field waters is diverse. Therefore, unclassified complex mechanisms may exist. To illustrate the molecular mechanisms through which MC controls HABs in the field and verify the previous laboratory findings, a series of experiments and bioinformatics analyses were conducted using bloom waters from aquacultural ponds. The results showed that a 72.29% removal efficiency of algal biomass could effectively control blooms. The metatranscriptomic results revealed that the number of downregulated genes (131,546) was greater than that of upregulated genes (24,318) at 3 h after MC addition. Among these genes, several genes related to DNA replication were downregulated; however, genes involved in DNA repair were upregulated. Metabolism-related pathways were the most significantly upregulated (q < 0.05), including photosynthesis and oxidative phosphorylation. The results also showed that MC reduced most of the biomass of the dominant phytoplankton species, likely by removing apical dominance, which increased the diversity and stability of the phytoplankton community. In addition to reducing the pathogenic bacterial density, MC reduced the concentrations of PO43- (96.22%) and SiO32- (66.77%), thus improving the aquaculture water quality, altering the phytoplankton community structure (the proportion of Diatomea decreased, and that of Chlorophyta increased), and inhibiting phytoplankton growth. These effects hindered the rapid development of large phytoplankton biomasses and allowed the community structure to remain stable, reducing HAB threats. This study illustrates the molecular mechanisms through which MC controls HABs in the field and provides a scientific method for removing HABs in aquacultural waters.


The Evolution of Microstructure and Magnetic Properties of the Bismuth Layer Compounds with Cobalt Ions Substitution.
One of the core issues for the A/B site doping in the bismuth layer magnetoelectric materials is to find out the evolution of the magnetic structure, crystal structure and elemental distribution, and the coupling effects between spin and lattice with the increase of ion substitution. Here, we have conducted systematic structural and physical property studies on the series samples of Bi5Ti3Fe1-xCoxO15. This work presents that Bi5Ti3Fe1-xCoxO15 forms a single four layer perovskite-like structure for 0 ≤ x < 0.67, while a three layer perovskite-like structure block begins to arise for x ≥ 0.67. With different cobalt content, the sample demonstrates antiferromagnetism, spin state determined magnetism, or magnetic anisotropy determined magnetism. The weak ferromagnetism is considered to be induced by the larger displacement of Co3+ ions from the center of octahedra and the change of the spin state of Co3+ ions. It is also observed that Fe and Co elements are homogeneously substituted in the three layer structure block, accompanied by the rotation (and/or distortion) of BO6 octahedra.


Flexible Strain-Sensitive Sensors Assembled from Mussel-inspired Hydrogel with Tunable Mechanical Properties and Wide Temperature Tolerance in Multiple Application Scenarios.
Conductive hydrogels, exhibiting wide applications in electronic skins and soft wearable sensors, often require maturely regulating of the hydrogel mechanical properties to meet specific demands and work for a long-term or under extreme environment. However, in situ regulation of the mechanical properties of hydrogels is still a challenge, and regular conductive hydrogels will inevitably freeze at subzero temperature and easily dehydrate, which leads to a short service life. Herein, a novel adhesive hydrogel (PAA-Dopa-Zr4+) capable of strain sensing is proposed with antifreezing, nondrying, strong surface adhesion, and tunable mechanical properties. 3,4-Dihydroxyphenyl-l-alanine (l-Dopa)-grafted poly(acrylic acid) (PAA) and Zr4+ ion are introduced into the hydrogel, which broadly alters the mechanical properties via tuning the in situ aggregation state of polymer chains by ions based on the complexation effect. The catechol groups of l-Dopa and viscous glucose endow the hydrogel with high adhesiveness for skin and device interface (including humid and dry environments) and exhibit an outstanding temperature tolerance under extreme wide temperature spectrum (-35 to 65 °C) or long-lasting moisture retention (60 days). Furthermore, this PAA-Dopa-Zr4+ can be assembled as a flexible strain-sensitive sensor to detect human motions based on specific mechanical properties requirements. This work, enabling superior adhesive and temperature tolerance performance and broad mechanical tenability, presents a new paradigm for numerous applications to wearable sensing and personalized healthcare monitoring.


Apparent destruction of bovine blood group determinants by chymotrypsin.
Although chymotrypsin treatment eliminated the reactivity of many antigenic determinants on the bovine red cell, haemolytic inhibition tests, double diffusion in agar tests, and immunizations provided no conclusive evidence of any of the affected determinants in the soluble digest. Chymotryptic digestion unmasked an apparent cryptantigen, rendering Q-positive cells reactive with a previously Q-negative anti-serum.


Carbon sandwich preparation preserves quality of two-dimensional crystals for cryo-electron microscopy.
Electron crystallography is an important method for determining the structure of membrane proteins. In this paper, we show the impact of a carbon sandwich preparation on the preservation of crystalline sample quality, using characteristic examples of two-dimensional (2D) crystals from gastric H(+),K(+)-ATPase and their analyzed images. Compared with the ordinary single carbon support film preparation, the carbon sandwich preparation dramatically enhanced the resolution of images from flat sheet 2D crystals. As water evaporation is restricted in the carbon-sandwiched specimen, the improvement could be due to the strong protective effect of the retained water against drastic changes in the environment surrounding the specimen, such as dehydration and increased salt concentrations. This protective effect by the carbon sandwich technique helped to maintain the inherent and therefore best crystal conditions for analysis. Together with its strong compensation effect for the image shift due to beam-induced specimen charging, the carbon sandwich technique is a powerful method for preserving crystals of membrane proteins with larger hydrophilic regions, such as H(+),K(+)-ATPase, and thus constitutes an efficient and high-quality method for collecting data for the structural analysis of these types of membrane proteins by electron crystallography.


Effect on the diffraction efficiency from the surface absorption of echelle grating in Littrow mounting.
[Opt. Express31, 26156202310.1364/OE.495525] shows an anomalous absorption of the echelle grating in TM polarization light near the pseudo-Brewster angle. On top of that, more generally, we relate the absorptions of echelle grating to the Al materials with an absorption spectral band. The blaze diffraction efficiencies (DEs), absorption strengths and electric field distributions, and the energy of non-blaze diffraction orders of the echelle are analyzed in detail. The computing reveals that the interaction between the incident light for TM polarization and the echelle structure leads to amplifying the absorption strength of Al materials with an absorption spectral band from visible to near IR. The deepening groove depth not only suppresses the absorption strength of the Al-echelle grating under TM polarization closer to the absorption spectra of Al materials but improves the light-collecting ability (LCA) at both polarizations. Therefore, the DE differences of different blaze wavelengths for the wideband blaze are explained. The Ag materials echelle with lower absorption is to further validate the results. From the point of view of the effects of absorption and LCA, the novel echelles with high DE can be designed and fabricated.


[Antiarrhythmic drugs in chronic ventricular extrasystole (author's transl)].
Several class I antiarrhythmic drugs were used in an intraindividual comparative study in 15 patients with chronic stable ventricular extrasystole of various origins. In a randomised sequence lidocaine, ajmalin and, in a cross-over double blind study with placebo, the new antiarrhythmic Org 6001 were tested. Propafenon was given as a final preparation. Each substance was administered parentally in therapeutic doses. A significant placebo effect could be excluded, baseline control values before administration of individual substances correlated well. Comparing mean values obtained over one hour before and after administration of the substance it was shown that the effectiveness of drugs decreased as follows: ajmalin, propafenon, lidocaine, Org 6001. Whereas suppression of extrasystole was most marked after ajmalin, propafenon showed the longest period of activity. After Org 6001 divergent activity of arrhythmia could be observed; in some patients good antiarrhythmic effects could be demonstrated. For evaluation of effectiveness and validity of new antiarrhythmic substances intraindividual comparison with placebo and well established standard antiarrhythmic drugs is advisable.


Adenoid cystic carcinoma of larynx.
This case report presents the clinical picture, diagnostic methodology, and surgical treatment of a 30 years old female patient, who presented with hoarseness of voice and difficulty in breathing. Direct laryngoscopy showed mass in right side of subglottic region, and biopsy-proven adenoid cystic carcinoma. Total laryngectomy was performed and patient was discharged three weeks postoperatively and doing well.


Functional restoration of acoustic units and adult-generated neurons after hypothalamic lesion.
The hypothalamus of the adult ring dove contains acoustic units that respond to species-specific coo vocalization. Loss of nest coo leads to unsuccessful breeding. However, the recovery of nest coo in some doves suggests that these units are capable of self-renewal. We have previously shown that lesioning the hypothalamus generates the addition of new neurons at the lesioned area. In this study, we sought to determine whether lesion-induced new neurons are involved in the recovery of coo-responsive units. We systematically recorded electrical activity in the ventromedial nucleus (VMN) of the hypothalamus, before and after lesion, for varying periods up to 3 months. Recordings were made when the birds were at rest (spontaneous discharge) and when the birds were exposed to acoustic stimulations (evoked discharge). Concurrently, the lesioned area was monitored for changes in cell types by using bromodeoxyuridine (BrdU) to label newly divided cells and NeuN to identify mature neurons. For 1 month after lesion, there was no sign of electrical activity, and only BrdU-labeled cells were present. When the first electrical activity occurred, it displayed abnormal spontaneous bursting patterns. The mature discharge patterns (both spontaneous and evoked) occurred after detection of BrdU+/NeuN+ double-labeled cells 2-3 months postlesion and were similar to those found in intact and sham-lesioned birds. Double-labeled cells bore morphologic characteristics of a neuron and were confirmed with z-stack analysis using confocal laser scanning microscopy. Moreover, double-labeled cells were not stained for glial fibrillary acidic protein (GFAP), suggesting that they were neurons. The number of coo-responsive units was significantly correlated with that of BrdU+/NeuN+ cells. Furthermore, the marker for recording sites revealed that coo-responsive units were colocalized with BrdU+/NeuN+ cells. Taken together, the evidence strongly suggests that lesion-induced addition of new neurons promotes the functional recovery of the adult hypothalamus.


Quantitative characterization of pore structure of several biochars with 3D imaging.
Pore space characteristics of biochars may vary depending on the used raw material and processing technology. Pore structure has significant effects on the water retention properties of biochar amended soils. In this work, several biochars were characterized with three-dimensional imaging and image analysis. X-ray computed microtomography was used to image biochars at resolution of 1.14 μm and the obtained images were analysed for porosity, pore size distribution, specific surface area and structural anisotropy. In addition, random walk simulations were used to relate structural anisotropy to diffusive transport. Image analysis showed that considerable part of the biochar volume consist of pores in size range relevant to hydrological processes and storage of plant available water. Porosity and pore size distribution were found to depend on the biochar type and the structural anisotopy analysis showed that used raw material considerably affects the pore characteristics at micrometre scale. Therefore, attention should be paid to raw material selection and quality in applications requiring optimized pore structure.


Exposure of Students to Emotional and Physical Violence in the School Environment.
While peer abuse or physical violence in school is emphasized more, the physical and emotional violence caused by school staff has been emphasized less. The purpose of this study was to investigate the variables related to emotional and physical violence that students are exposed to in the school environment. This cross-sectional and descriptive study was conducted by applying a questionnaire to 434 fifth-grade students receiving education in the primary schools in Konak district of Izmir province. Being prepared by the researchers of this study, the questionnaire consisted of questions about the socio-demographic features of the child and the family, the place where the child has been raised, family income, average grade, and the emotional and physical violence of teachers, parents, and peers s/he has been exposed to within the last year. The Chi-square test, Mann-Whitney U test, and logistic regression analysis were used for statistical analyses. The study group consisted of 214 (49.3%) female and 220 (50.7%) male students. Students reported that they were exposed to at least one type of emotional violence from 59.4% of teachers, 52.8% of parents, and 61.8% of children at school; they were exposed to at least one type of physical violence from 42.9% of teachers, 33.6% of parents, and 24.9% of children at school. While the rate of encountering with the beating of another child was 53%, the rate of watching this in television/cinema was 52.8%. Regarding exposure to at least one type of violence, males were found to be significantly more exposed to emotional and physical violence from male teachers, female teachers, and fathers and physical violence from children at school. The factors regarding the exposure to emotional and physical violence by teachers were evaluated using logistic regression analysis, and it was determined that the physical violence from teachers, emotional violence from children in school, and emotional violence from parents could predict the emotional violence from teachers. For males, physical violence from children in school and emotional violence from teachers could predict the physical violence from teachers. In this study, the determination of the tendency of togetherness of different types of violence applied to students from different people groups like teachers, parents, and children in school makes us think about the possibility of common risk factors in terms of violence exposure. The risk factors determined in this study may guide us in planning protective interventions aimed at violence.


A spatial haplotype copying model with applications to genotype imputation.
Ever since its introduction, the haplotype copy model has proven to be one of the most successful approaches for modeling genetic variation in human populations, with applications ranging from ancestry inference to genotype phasing and imputation. Motivated by coalescent theory, this approach assumes that any chromosome (haplotype) can be modeled as a mosaic of segments copied from a set of chromosomes sampled from the same population. At the core of the model is the assumption that any chromosome from the sample is equally likely to contribute a priori to the copying process. Motivated by recent works that model genetic variation in a geographic continuum, we propose a new spatial-aware haplotype copy model that jointly models geography and the haplotype copying process. We extend hidden Markov models of haplotype diversity such that at any given location, haplotypes that are closest in the genetic-geographic continuum map are a priori more likely to contribute to the copying process than distant ones. Through simulations starting from the 1000 Genomes data, we show that our model achieves superior accuracy in genotype imputation over the standard spatial-unaware haplotype copy model. In addition, we show the utility of our model in selecting a small personalized reference panel for imputation that leads to both improved accuracy as well as to a lower computational runtime than the standard approach. Finally, we show our proposed model can be used to localize individuals on the genetic-geographical map on the basis of their genotype data.


The patient perspective: utilizing focus groups to inform care coordination for high-risk medicaid populations.
Care coordination programs for high-risk, high-cost patients are a critical component of population health management. These programs aim to improve outcomes and reduce costs and have proliferated over the last decade. Some programs, originally designed for Medicare patients, are now transitioning to also serve Medicaid populations. However, there are still gaps in the understanding of what barriers to care Medicaid patients experience, and what supports will be most effective for providing them care coordination. We conducted two focus groups (n = 13) and thematic analyses to assess the outcomes drivers and programmatic preferences of Medicaid patients enrolled in a high-risk care coordination program at a major academic medical center in Boston, MA. Two focus groups identified areas where care coordination efforts were having a positive impact, as well as areas of unmet needs among the Medicaid population. Six themes emerged from the focus groups that clustered in three groupings: In the first group (1) enrollment in an existing medical care coordination programs, and (2) provider communication largely presented as positive accounts of assistance, and good relationships with providers, though participants also pointed to areas where these efforts fell short. In the second group (3) trauma histories, (4) mental health challenges, and (5) executive function difficulties all presented challenges faced by high-risk Medicaid patients that would likely require redress through additional programmatic supports. Finally, in the third group, (6) peer-to-peer support tendencies among patients suggested an untapped resource for care coordination programs. Programs aimed at high-risk Medicaid patients will want to consider programmatic adjustments to attend to patient needs in five areas: (1) provider connection/care coordination, (2) trauma, (3) mental health, (4) executive function/paperwork and coaching support, and (5) peer-to-peer support.


Coordinating ecological risk assessment with natural resource damage assessment: A panel discussion.
Contaminated sites in the United States undergo remediation and restoration through regulatory programs that lead the 2 processes through independent but often parallel pathways with different objectives. The objective of remediation is to reduce risk to human health and the environment, whereas that of restoration is to restore injured resources and compensate the public for lost use of the services that natural resources provide. More complex sites, such as those associated with large river systems and urban waterways, have resulted in increasingly larger-scale ecological risk assessments (ERAs) and natural resource damage assessments (NRDAs) that take many years and involve diverse practitioners including scientists, economists, and engineers. Substantial levels of effort are now frequently required, creating a need for more efficient and cost-effective approaches to data collection, analyses, and assessments. Because there are commonalities in the data needs between ERAs and NRDAs, coordination of the design and implementation of site-specific studies that meet the needs of both programs could result in increased efficiency and lower costs. The Association for Environmental Health and Sciences Foundation convened a panel of environmental practitioners from industry, consulting, and regulatory bodies to examine the benefits and challenges associated with coordinating ERA and NRDA activities in the context of a broad range of regulatory programs. This brief communication presents the opinions and conclusions of the panelists on these issues and reports 2 case studies for which coordinated ERA and NRDA activities produced a positive outcome. Integr Environ Assess Manag 2016;12:616-621. © 2015 SETAC.


Comparative properties of the Charcot-Leyden crystal protein and the major basic protein from human eosinophils.
Guinea pig eosinophil granules contain a protein, the major basic protein (MBP), which accounts for more than half of the total granule protein, has a high content of arginine, and displays a remarkable tendency to form disulfide-linked aggregates. In this study we have purified a similar protein from human eosinophil granules and have compared the human MBP to the protein comprising the Charcot-Leyden crystal (CLC). Eosinophils from patients with various diseases were purified and disrupted, and the granule fraction was obtained. Examination of the granule fraction by transmission electron microscopy showed numerous typical eosinophil granules. Analyses of granule lysates by gel filtration and by polyacrylamide gel electrophoresis revealed the presence of peroxidase and MBP with properties similar to that previously found in guinea pig eosinophil granules. The human MBP had a molecular weight of 9,200, contained less than 1% carbohydrate, was rich in arginine, and readily formed disulfide-bonded aggregates. CLC were prepared from eosinophil-rich cell suspensions by homogenization in hypotonic saline. The supernates following centrifugation of cell debris spontaneously formed CLC. Analysis of CLC revealed the presence of a protein with a molecular weight of 13,000 containing 1.2% carbohydrate. The protein displayed a remarkable tendency to aggregate even in the presence of 0.2 M acetic acid. Human MBP and CLC protein differed in their molecular weights, carbohydrate compositions, and amino acid analyses. Mixtures of the MBP and the CLC protein yielded two bands in polyacrylamide gel electrophoresis. Neither eosinophil protein increased vascular permeability in the guinea pig skin or contracted the guinea pig ileum. The results indicate that the human MBP and the CLC are distinct substances with properties such that one cannot be derived from the other.


Closing the loop of patient care--a clinical trial of a computerized discharge medication program.
A frustrating time for hospitalized patients and their primary care providers is after discharge from the hospital, because of changes in patients' medications. We developed a computer program to improve the discharge process, by providing guidance to the physician writing the prescriptions, offering educational material to the patients, and providing electronic notification of medication changes to the primary care providers. During a one-year clinical evaluation of this system, in which use of the program was voluntary, 1000 patients were discharged through the program. House officers tended to use the program more often for patients who were older and in the hospital longer. Both house officers and primary care physicians found the program extremely useful, and the process took no longer than the manual method of creating discharge medication lists. Patients who were discharged using this program may have had better adherence to medication regimens. We conclude that computer-assisted compilation of a discharge medication list is a useful method for improving the discharge process.


Fracture resistance of overtly flaring root canals filled with resin-based obturation material.
Reinforcement of root canals obturated with Resilon was reported by several investigators, but no studies reported the reinforcement of overtly flared root canals obturated with Resilon material. The aim of this study was to investigate the fracture resistance of overtly flared root canals filled with Resilon as compared to similar root canals filled with gutta-percha (GP). Sixty single-rooted premolars were divided randomly into six groups. Group 1 served as control group. The control group was sub-divided into two groups, a negative group and a positive group. The negative group consisted of root canals that were only cleaned from residual pulpal tissues, however, the positive group had prepared and overtly flared root canals without obturation. Groups 2 and 4 were shaped using 0.04 taper rotary files, while groups 3 and 5 were shaped using 0.06 taper rotary files. Before obturation, the last four groups were further flared coronally with a reverse cone diamond bur. Groups 2 and 3 were obturated with GP and a resin-based sealer, while groups 4 and 5 were obturated with Resilon and Epiphany self-etching primer and Epiphany sealer. Roots were then fixed into a universal testing machine and vertically loaded until fracture. SPSS software (Release 9.0 for Windows, SPSS, Chicago, USA) was used to perform the statistical analysis. Fracture resistance measurements showed that there were differences in resistance to fracture among the experimental groups (ANOVA, P < 0.0001). Mean values of the loading force applied to the negative control group were the highest at 1.81 KN, whereas the mean values for the Resilon groups (Groups 4 and 5) at 1.13 KN and 1.54 KN were found to be higher than the GP groups (Groups 2 and 3) at 0.45 KN and 0.88 KN, respectively. Tukey's post hoc test showed that there was no statistical difference between the mean values of the negative control group and Group 5 (P = 0.69). Obturation of overtly flared roots with Resilon material increased the resistance of these teeth to vertical root fracture.


Intrinsic spin fluctuations reveal the dynamical response function of holes coupled to nuclear spin baths in (In,Ga)As quantum dots.
The problem of how single central spins interact with a nuclear spin bath is essential for understanding decoherence and relaxation in many quantum systems, yet is highly nontrivial owing to the many-body couplings involved. Different models yield widely varying time scales and dynamical responses (exponential, power-law, gaussian, etc.). Here we detect the small random fluctuations of central spins in thermal equilibrium [holes in singly charged (In,Ga)As quantum dots] to reveal the time scales and functional form of bath-induced spin relaxation. This spin noise indicates long (400 ns) spin correlation times at a zero magnetic field that increase to ∼5 μs as dominant hole-nuclear relaxation channels are suppressed with small (100 G) applied fields. Concomitantly, the noise line shape evolves from Lorentzian to power law, indicating a crossover from exponential to slow [∼1/log(t)] dynamics.


[Introduction to myocardial doppler imaging].
Introduced in 1989, the myocardial doppler tissue imaging has now many clinical applications. Doppler tissue imaging explores the proper systolic and diastolic regional function of myocardial fibers. We can measure myocardial velocities by recording signals of low velocitiy and high magnitude, the strain and the strain rate are then derived from velocities. Specific software is therefore necessary. There are many ways of recording and representing myocardial doppler tissue parameters. Diagnostic and prognostic value of myocardial doppler tissue imaging is now proved and this method has many applications in ischemic cardiopathy and in cardiomyopathies. The development of powerful software is promising for the applications of the strain in the future.


Detection of multiple human papillomavirus types in condylomata acuminata from immunosuppressed patients.
Using the hybrid capture method, condylomata acuminata from healthy patients (controls) and patients with altered cell-mediated immunity were analyzed for multiple human papillomavirus (HPV) DNA: 82.9% and 38.0% of lesions from 41 controls and 21 patients, respectively, were HPV DNA-positive only with probes for low-risk HPV types (P = .00035). Using probes for both low- and high-risk HPV types, 16.3% and 52.3% of lesions from 43 controls and 21 patients, respectively, were positive for both probes (P = .0038). Evidence of multiple HPV types was also found by Southern blot and in situ hybridization studies. The mean HPV copy number detected by either probe did not differ significantly among patient groups. Using sensitive techniques, such as hybrid capture, multiple HPV types, including those associated with genital malignancy, can be detected in condylomata acuminata. Serial biopsies demonstrate the dynamic nature of genital HPV infection and that changes in the predominant HPV types may be reflected in tissue pathology.


In vitro generation of antigen-specific hemolytic plaque-forming cells from human peripheral blood mononuclear cells.
We have described a culture and assay system for the sensitization of human peripheral blood mononuclear cells with a T cell-dependent antigen, sheep erythrocytes, in the absence of nonspecific stimulatory agents and with the subsequent generation of macroscopic hemolytic plaques. We have shown that the antibody produced by the plaque-forming cells generated in this culture system is specific for the sensitizing antigen, and that the plaques created are not false plaques because their formation is inhibited by cycloheximide. The success of this system can be attributed to several critical factors including large numbers of peripheral blood mononuclear cells (5 x 10(6) culture), a prolonged period of incubation (10-11 d), continuous rocking during the entire period of incubation, culturing in large (35-mm) flat-bottomed culture dishes in the presence of human plasma, and the appropriate antigen concentration (5 x 10(6) sheep erythrocytes/culture). Furthermore, the generation of macroscopic hemolytic plaques requires plaquing sensitized peripheral blood mononuclear cells in target cell monolayers fixed in an agarose matrix with an incubation period of 2-3 h. We have further shown that the antigen-specific response measured by this system is dependent on adherent cells and T lymphocytes. At least one population of the helper T cells is sensitive to 2,000 rad irradiation. This system is simple, sensitive, and should serve as an effective tool for the analysis of cellular interactions involved in the generation of human antigen-specific plaque-forming cells, the genetic control the human immune response, and the pathophysiology of altered immunoregulation in disease.


Determinants of incomplete childhood immunization among children aged 12-23 months in Dabat district, Northwest Ethiopia: Unmatched case- control study.
Despite the effort to increase access to routine immunization, majority of children in low-resource countries including Ethiopia are still either unvaccinated or under-vaccinated. In Ethiopia for the past four decades, the completion rate of routine childhood immunization remains low particularly in a rural area. In this study setting, evidence regarding the socio-economic, maternal continuum care, and caregiver characteristics effect on child immunization is limited. Hence, this study aimed to identify the determinants of incomplete vaccination among children aged 12-23 months in Dabat district, Northwest Ethiopia. A community-based unmatched case-control study design was employed among 132 cases and 262 controls. Multi-stage sampling method was used to recruit eligible study participants. Logistic regression analysis was used to identify the determinants to children's incomplete vaccination. Caregivers' attitude towards vaccine (AOR: 6.1, 95% CI 3.4 to 11.1), knowledge on the schedule of vaccination (AOR: 4, 95% CI 2.2 to 7.1), Place of delivery (AOR: 2.7, 95% CI 1.3 to 5.5), and marital status (AOR: 2.36, 95% CI 1.22 to 4.56) were statistically significant association with incomplete childhood vaccination. Home delivery, caregivers' poor knowledge on the schedule of vaccination, caregivers' negative perception towards vaccine and unmarried marital status were predictors to incomplete vaccination. Therefore, to enhance full vaccination coverage, immunization health education program needs to address vaccine related safety enquiries in a meaningful method to caregivers, in order to improve the perception of caregivers towards vaccine. Moreover, improving maternal continuum care coverage is crucial.


A genetic framework for grain size and shape variation in wheat.
Grain morphology in wheat (Triticum aestivum) has been selected and manipulated even in very early agrarian societies and remains a major breeding target. We undertook a large-scale quantitative analysis to determine the genetic basis of the phenotypic diversity in wheat grain morphology. A high-throughput method was used to capture grain size and shape variation in multiple mapping populations, elite varieties, and a broad collection of ancestral wheat species. This analysis reveals that grain size and shape are largely independent traits in both primitive wheat and in modern varieties. This phenotypic structure was retained across the mapping populations studied, suggesting that these traits are under the control of a limited number of discrete genetic components. We identified the underlying genes as quantitative trait loci that are distinct for grain size and shape and are largely shared between the different mapping populations. Moreover, our results show a significant reduction of phenotypic variation in grain shape in the modern germplasm pool compared with the ancestral wheat species, probably as a result of a relatively recent bottleneck. Therefore, this study provides the genetic underpinnings of an emerging phenotypic model where wheat domestication has transformed a long thin primitive grain to a wider and shorter modern grain.


Surgical anatomy of the perineal muscles and their role in perineal disorders.
The anterior perineum contains the perineal body and muscles. It is the site of functional and pathological disorders, many of which have not yet been related to a precise cause. In the present study, we investigated the anatomy of the perineal muscles with the aim of elucidating their function in light of their anatomic structure. Knowledge of their functional-structural relationship is deemed necessary for the understanding of the disorders that affect this part of the perineum. The perineal muscles of 28 cadaveric specimens were studied by direct dissection, as well as histologically. Fifteen male and 13 female specimens were collected from 18 adult (mean (+/- SD) age 31.6 +/- 9.8 years) and 10 neonate cadavers. Histological sections were stained with hematoxylin and eosin and Masson's trichrome stain. The fibers of the superficial transverse perineal muscle proceeded medially to decussate in a criss-cross pattern with the muscle fibers of the contralateral muscle; a few muscle fibers passed directly without decussation. Similarly, the fibers of the deep transverse perineal muscle decussated with their fellows on the opposite side. The two decussation raphes constituted the main bulk of the perineal body. A 'digastric' pattern could be identified for each of the superficial transverse perineal muscle and deep transverse perineal muscle. This pattern allows simultaneous contraction of the muscles on both sides as a single unit. The perineal muscles, forming the floor of the anterior perineum, are apparently subjected to variations in intra-abdominal pressure, which, if exceeding normal physiological limits, may lead to weakening, subluxation and sagging of the perineal muscles and, eventually, to perineocele. Further studies to investigate the role of the perineal muscles in the functional disorders of the perineum are needed.


Three new ascomycetes from freshwater in China.
Three new freshwater ascomycetes, Diaporthe aquatica sp. nov. (Diaporthaceae), Ophioceras aquaticus sp. nov. (Magnaporthaceae) and Togninia aquatica sp. nov. (Togniniaceae), are described and illustrated based on morphological and molecular data (ITS, 18S, 28S rDNA sequences). Diaporthe aquatica is characterized by globose to subglobose, black ascomata with long necks, broadly cylindrical to obclavate asci, and small, ellipsoidal to fusiform, one-septate, hyaline ascospores; it is unusual among Diaporthe species in the fact that it lacks a stroma and has freshwater habitat. Ophioceras aquaticus is characterized by globose ascomata with a long beak, cylindrical, eight-spored asci with J- subapical rings and 3-5-septate filiform ascospores with slightly acute ends. Togninia aquatica is characterized by globose ascomata with long necks, clavate and truncate asci clustered on distinct ascogenous hyphae, and small, reniform, hyaline ascospores. Differences among the new taxa and similar species are discussed.


MKP-3 suppresses LPS-induced inflammatory responses in HUVECs via inhibition of p38 MAPK/NF-κB pathway.
Endothelial cell dysfunction and inflammatory responses play critical roles in the development of atherosclerosis. Recent data on the processes underlying atherogenesis indicate the substantial role of endotoxins (lipopolysaccharides; LPS) of the intestinal microflora in the initiation and progression of atherosclerosis. Mitogen-activated protein (MAP) kinase phosphatase-3 (MKP-3) is a cytoplasmic dual-specificity protein phosphatase that specifically binds to and inactivates MAP kinases in mammalian cells, but its biological function in endothelial cell dysfunction and inflammatory responses remains largely unknown. The aim of the present study was to investigate the role of MKP-3 in endotoxin-induced endothelial inflammation by western blotting, quantitative polymerase chain reaction, and immunofluorescence. The results of our study demonstrated that MKP-3 overexpression markedly inhibited the adhesion of human monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) by downregulating the expression of vascular cell adhesion protein 1 (VCAM-1) and pro-inflammatory cytokines. In contrast, MKP-3-encoding gene knockdown by small interfering RNA (siRNA) exacerbated LPS-induced endothelial dysfunction. Additionally, we found that MKP-3 overexpression inhibited LPS-induced p38 MAPK phosphorylation and decreased the nuclear translocation of nuclear factor kappa B (NF-κB) after LPS treatment, suggesting its implication in the LPS/Toll-like receptor 4 (TLR4)/p38/NF-κB pathway. Overall, these observations suggest that MKP-3 plays a protective role in endothelial dysfunction and may be a therapeutic target.


Evaluation and prognostic value of Cv-aCO2/Da-vO2 in patients with septic shock receiving fluid resuscitation Cv-aCO2/Ca-vO2.
The present study aimed to evaluate the prognostic value of venous-arterial CO2 to arterial-venous O2 (Cv-aCO2/Da-vO2) for patients with septic shock treated by fluid resuscitation. A total of 108 cases who received fluid resuscitation for septic shock at the Intensive Care Unit were retrospectively screened according to the 2012 surviving sepsis campaign guidelines. Patients were divided into 2 groups according to the Cv-aCO2/Da-vO2 ratio at 6 h after fluid resuscitation: Group A, Cv-aCO2/Da-vO2 >1; group B, Cv-aCO2/Da-vO2 ≤1. The resuscitation target rate and transfused resuscitation volume at 6 h exhibited no significant difference between the 2 groups. The cardiac output at 6 and 24 h, as well as the ratio of patients who reached the target of resuscitation within 24 h, the 24-h lactic acid clearance rate and the number of cases with central venous oxygen saturation >70% were significantly decreased in group A compared with those in group B (all P<0.05). The Sequential Organ Failure Assessment score at day 3 in group A was higher compared with that in group B (7.94±1.6 vs. 6.82±1.9; P=0.0013). The mortality rate at day 7 and 35 was higher in group A compared with that in group B (29/52 vs. 6/56, P<0.001; 48/52 vs. 36/56; P<0.001). In conclusion, the Cv-aCO2/Da-vO2 was able to effectively evaluate the success rate of resuscitation and, regarding prognosis, it was able to identify patients at high risk of adverse outcomes.


Obesity Paradox in the Course of Cerebrovascular Diseases.
Obesity remains an important risk factor of cardiovascular and cerebrovascular diseases. However, it has been observed that increased body fat and body mass index predicted longer survival after the occurrence of a cardiovascular event. This observation has been named the obesity paradox. Initially, the term obesity paradox referred to the observation of the better outcome of cardiovascular diseases, such as heart failure and coronary heart disease, in obese patients as compared to underweight and normal-weight patients. Recently, similar, although fewer, observations confirm the occurrence of the obesity paradox in patients with acute cerebrovascular diseases. The underlying reasons for the protective effects of excessive body fat tissue against the consequences of acute cardiovascular and cerebrovascular diseases are poorly understood. The effect of preconditioning may be associated with the obesity paradox. The issue of the correlation between obesity and better survival of patients with cardiovascular and cerebrovascular diseases still remains largely unexplored. Debates for and against the obesity paradox continue.


Enhanced ultrafast optical nonlinearity of porous anodized aluminum oxide nanostructures.
Enhanced ultrafast optical nonlinearities of porous anodized aluminum oxide (AAO) nanostructures, well-known templates for quantum dots fabrication, have been investigated using the differential optical Kerr gate technique at 800 nm. The optical nonlinearity is strongly influenced by the pore number density, the pore size and the shape. Large values of the third-order nonlinear optical susceptibility (chi((3))) of the order of 10(-10)esu are measured. The nonlinear response time is faster than or comparable to the laser pulse width (90 fs) used. The origin and variation of such remarkable optical nonlinearities has been discussed by considering the nanoporous AAO as an effective medium and utilizing the extended Maxwell Garnet theory, and by considering the additional influence from pore diameter, pore shape and surface states.


ISO 11137, requirements for radiation sterilisation: current revisions.
The major changes that are expected in a revised standard on radiation sterilisation are discussed. Manufacturers should anticipate some challenges in meeting the proposed requirements.


Silk Fibroin Films for Corneal Endothelial Regeneration: Transplant in a Rabbit Descemet Membrane Endothelial Keratoplasty.
Develop a silk fibroin (SF)-based artificial endothelial graft for its use in a rabbit Descemet membrane endothelial keratoplasty (DMEK). Human and rabbit artificial corneal endothelial grafts were developed through the culture of human and rabbit corneal endothelial cells (CECs) on SF films. Rabbit artificial SF endothelial grafts were transplanted in a DMEK surgery into a rabbit in vivo model. SF artificial endothelial grafts showed the characteristic endothelial markers: zonula occludens (ZO-1) and Na+/K+ ATPase. In a rabbit model of DMEK surgery, SF artificial endothelial graft restored the corneal transparency and thickness at 6 week of follow-up. Anterior segment optical coherence tomography revealed the SF graft as a fully integrated component in the corneal tissue, displaying a similar corneal thickness and endothelial cell count when compared with its healthy contralateral cornea. Histologic analysis showed that the SF artificial endothelial graft was attached and integrated on the surface of the corneal stroma without a significant inflammatory reaction, and rabbit CECs consisted in a monolayer that showed their characteristic markers ZO-1 and Na+/K+ ATPase, suggesting proper intercellular junctions and cellular pump function. We have developed SF films with biological properties that supported the growth of rabbit and human CECs, which showed normal morphology and characteristic markers; and with mechanical properties that allowed its use in a DMEK surgery, proving its in vivo functionality in a rabbit model of endothelial dysfunction.


Methods of nursing certification in North America-A scoping review.
Definitions of nursing certification are lacking in the research literature and research on certification in nursing is remarkably limited. A six-stage scoping review framework was used to identify the nature, extent, and range of certification within the nursing literature. Thirty-six articles were included in this scoping review. Most originated in the United States (89%), were classified as research articles (56%), and used a quantitative approach (90%). The majority focused on initial certification (50%), and written examination was the most prevalent approach to certification (39%). Missing and incomplete data were prevalent. The overall lack of nursing certification origin, focus, methodological rigor, and clear certification mastery criteria have hindered meaningful study of the relationship between nursing certification and patient outcomes. Common data elements, reporting standards, and observational studies linking common data elements and patient outcomes could guide future research and improve the transparency of certification processes and reporting.


Rapid G0/1 transition and cell cycle progression in CD8+ T cells compared to CD4+ T cells following in vitro stimulation.
T-cell population consists of two major subsets, CD4+ T cells and CD8+ T cells, which can be distinguished by the expression of CD4 or CD8 molecules, respectively. Although they play quite different roles in the immune system, many of their basic cellular processes such as proliferation following stimulation are presumably common. In this study, we have carefully analyzed time-course of G0/1 transition as well as cell cycle progression in the two subsets of quiescent T-cell population following in vitro growth stimulation. We found that CD8+ T cells promote G0/1 transition more rapidly and drive their cell cycle progression faster compared to CD4+ T cells. In addition, expression of CD25 and effects of its blockade revealed that IL-2 is implicated in the rapid progression, but not the earlier G0/1 transition, of CD8+ T cells.


Characteristics of the ribonucleoprotein of influenza virus A.
Ribonucleoproteins (RNP) of influenza viruses A/Singapore/1/57, A/Victoria/35/72 and those isolated in the course of passaging in persistent infection systems (influenza virus--diploid human lung cells) were subjected to desimentation analysis. In viruses of different antigenic structure the 3 RNP fragments had the same sedimentation coefficients (63, 53, and 42 S, respectively). The ratios of RNP fragment concentrations had an individual character and were in relation with the antigenic differences between the strains studied.


Revealing Nucleic Acid Mutations Using Förster Resonance Energy Transfer-Based Probes.
Nucleic acid mutations are of tremendous importance in modern clinical work, biotechnology and in fundamental studies of nucleic acids. Therefore, rapid, cost-effective and reliable detection of mutations is an object of extensive research. Today, Förster resonance energy transfer (FRET) probes are among the most often used tools for the detection of nucleic acids and in particular, for the detection of mutations. However, multiple parameters must be taken into account in order to create efficient FRET probes that are sensitive to nucleic acid mutations. In this review; we focus on the design principles for such probes and available computational methods that allow for their rational design. Applications of advanced, rationally designed FRET probes range from new insights into cellular heterogeneity to gaining new knowledge of nucleic acid structures directly in living cells.


[Construction and identification of rpoS gene inserted and fused in frame with the promoterless lacZ in Pseudomonas sp. M18].
With hybridization in situ and Southern blots, an Eco RI- Xho I DNA fragment of 3.1 kb in length containing an rpoS gene and its flanking sequence was first cloned into pBluescript SK to generate pBLS by screening the genomic DNA library of Pseudomonas sp. M18. In order to identify the potential factors involved in rpoS gene expression and the regulatory mechanism of RpoS in strain M18, the rpoS gene was inserted and fused in frame with a promoterless and truncated lacZ gene, and a mutant named as M18SZ was then constructed through homologous recombination. Growth curves in KMB medium indicated that loss of RpoS made the mutant strain M18SZ more sensitive to alteration of some environmental factors. With detection and comparison of beta-galactosidase activities from both the wild type strain M18 and its derivative M18SZ cultivated in KMB medium respectively, it was found that the expression level of beta-galactosidase activities in the mutant M18SZ was high and could come to 480U. Expression of beta-galactosidase activities of the wild type strain M18 in KMB medium was not almost detected during its whole growth phase. With these results, it was confirmed that the rpoS gene did be fused in frame with the truncated lacZ gene in chromosome of the mutant M18SZ. Meanwhile, it is suggested that construction of a mutation, which is made with fusion in frame with the truncated lacZ gene, may be verified by detecting its beta-galactosidase activity, not using Southern blot or PCR.


Multifocal electroretinography in patients with exudative amd and intravitreal treatment with pegaptanib sodium.
To objectively investigate central retinal function in patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) before and after treatment with pegaptanib sodium (PS). Patients with CNV due to exudative AMD received intravitreal injections of 0.3 mg PS every sixth week if angiographic activity was evident. Longitudinal observation included recordings with multifocal electroretinography (mfERG) before the first treatment and before each injection at follow-up intervals. During the observation period of 30.5 +/- 8 weeks (mean +/- SD) a mean number of 5.3 +/- 1.3 injections were applied. Final mean log(MAR) visual acuity decreased, statistically nonsignificant, from 0.67 +/- 0.3 at baseline to 0.74 +/- 0.16. mfERG recordings in 12 patients after 25 +/- 9 weeks evinced a decrease in response density which was statistically significant in the central 5 degrees . Mean P1-amplitudes of ring 1, 2, and 3 were reduced by 66%, 39% and 30%, respectively. During follow-up, implicit times of the P1 components remained stable within 4% of baseline. In three of four patients with vision loss of 2 lines or more, P1-response amplitudes decreased substantially at least 6 weeks prior vision loss. Treatment with PS resulted in a decrease of central retinal function more obvious in mfERG than in VA longitudinal testing. Good correlations were seen between changes in mean vision and changes in mfERG response density components. As a decline in P1-response amplitudes anteceded vision loss in this study, our results indicate a possible role of mfERG to predict vision loss during intravitreal pharmacotherapy.


Determination of the electronic transport in type separated carbon nanotubes thin films doped with gold nanocrystals.
We report a systematic theoretical and experimental investigation on the electronic transport evolution in metallic and semiconducting carbon nanotubes thin films enriched by gold nanocrystals. We used an ultra-clean production method of both types of single-walled carbon nanotube thin films with/without gold nanocrystals, which were uniformly dispersed in the whole volume of the thin films, causing a modification of the doping level of the films (verified by Raman spectroscopy). We propose a modification of the electronic transport model with the additional high-temperature features that allow us to interpret the transport within a broader temperature range and that are related to the conductivity type of carbon nanotubes. Moreover, we demonstrate, that the proposed model is also working for thin films with the addition of gold nanocrystals, and only a change of the conductivity level of our samples is observed caused by modification of potential barriers between carbon nanotubes. We also find unusual behavior of doped metallic carbon nanotube thin film, which lowers its conductivity due to doping.


[Plea for the terminal anastomosis of aortic prostheses. Theoretical and practical impact].
End-to-end anastomosis of an aortic prosthesis was used during reconstructive surgery in 100 patients. The advantages of this method are analyzed and compared with those of end-to-side implantation, the former procedure providing improved hemodynamic and long-term results: absence of anastomotic dilatation, regularity of aortic blood flow distribution, lack of competitive or superfluous flow, a guaranteed pelvic circulation and simplicity of later repeat surgery following thrombosis. Tactical indications for this method of anastomosis are defined and depend mainly upon the type of lesions at the iliac bifurcation. The greater complexity of this method would appear to be acceptable in view of the possible improved long-term permeability when compared with the conventional procedure.


Hydroxytyrosol: Health Benefits and Use as Functional Ingredient in Meat.
Hydroxytyrosol (HXT) is a phenolic compound drawn from the olive tree and its leaves as a by-product obtained from the manufacturing of olive oil. It is considered the most powerful antioxidant compound after gallic acid and one of the most powerful antioxidant compounds between phenolic compounds from olive tree followed by oleuropein, caffeic and tyrosol. Due to its molecular structure, its regular consumption has several beneficial effects such as antioxidant, anti-inflammatory, anticancer, and as a protector of skin and eyes, etc. For these reasons, the use of HXT extract is a good strategy for use in meat products to replace synthetics additives. However, this extract has a strong odour and flavour, so it is necessary to previously treat this compound in order to not alter the organoleptic quality of the meat product when is added as ingredient. The present review exposes the health benefits provided by HXT consumption and the latest research about its use on meat. In addition, new trends about the application of HXT in the list of ingredients of healthier meat products will be discussed.


Anxiety and Risk of Vascular Dementia in an Elderly Community Sample: The Role of Sex.
Background: To assess the association between anxiety and risk of vascular dementia (VaD), as well as potential sex differences, in a community-based cohort. Methods: A random sample of 4057 dementia-free community participants aged 55 or older, from the longitudinal, community-based Zaragoza Dementia and Depression Project (ZARADEMP) study were followed for 4.5 years. Geriatric Mental State B (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) was used for the assessment and diagnosis of anxiety, and a panel of research psychiatrists diagnosed the incident cases of VaD according to DSM-IV (Diagnostic and Statistical Manual of mental disordes). Multivariate survival analysis with competing risk regression model was performed. Results: In men, the incidence rate of VaD was significantly higher among anxiety subjects compared with non-anxiety subjects (incidence rate ratio (IRR) (95% confidence interval (CI)): 3.24 (1.13-9.35); p = 0.029), and no difference was observed in women (IRR (95%CI): 0.68 (0.19-2.23); p = 0.168). In the multivariate model, for men, cases of anxiety had 2.6-fold higher risk of VaD (subdistribution hazard ratio (SHR): 2.61; 95%CI: 0.88-7.74) when all potential confounding factors were controlled, with no statistical significance (p = 0.084), but a clinically relevant effect (Cohen's d: 0.74). No association was found in women. Conclusions: In men, but not in women, risk of VaD was higher among individuals with anxiety, with a clinically relevant effect. Potential anxiety-related preventive interventions for VaD might be tailored to men and women separately.


Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes.
To investigate the effect of buserelin on gonadal structure and function in adult male rats. Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.


[Behavioral pharmacological and electroencephalographic effects of the 5-HT1A partial agonist ipsapirone].
The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.


Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake.
Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D1-like receptor antagonist SCH 23390 (1 mg kg bwt-1 day-1, sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression (P < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in MD (P < 0.001 vs. NS) and cortical nitrates+nitrites (NOx) production (NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein-1, P < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion (P < 0.001 vs. HS) while NOS I expression, NADPH-d activity and NOx production increased (P < 0.05 vs. HS for NOS I and P < 0.001 vs. HS for NADPH-d and NOx). SCH 23390 increased RPF and GFR in HS rats (P < 0.01 HS+SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D1R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron.