[Tonsillar and erythrocyte levels of superoxide dismutase in children with and without recurrent tonsillitis].
Oxidative stress secondary to infant tonsillar infection produces the expression of local and systemic antioxidants. Its determination seems to be useful as a marker of tonsillar suffering before tonsillectomy but is currently unknown. The aim of this study was to determine the evolution of this parameter in tonsillectomized children during a long-term follow-up. One hundred thirty-six children underwent tonsillectomy, 46 for tonsillar hypertrophy without infection and 90 for recurrent tonsillitis. Superoxide dismutase (SOD) concentrations were measured before tonsillectomy and at 6, 12, 24 and 36 months post-tonsillectomy. Infection provoked significantly higher SOD concentrations than tonsillar hypertrophy in tonsillar tissue (223.06 30.46 vs 156.39 54.05 U/l, p < 0.001) and in blood (1124.91 141.73 vs 1007.19 97.03 U/gr Hb, p < 0.001). There was a strong correlation between tonsillar and erythrocyte concentrations. During the 3-year follow-up, SOD concentrations in blood progressively decreased until stabilizing in all patients. Stabilization was reached at 6 months post-tonsillectomy in the group with tonsillar hypertrophy and at 2 years in the group with infection. Children with recurrent tonsillitis consistently showed higher SOD concentrations in blood throughout the follow-up. Oxidative damage in tonsillar tissue results from the incidence and severity of focal infections. Tonsillectomy reduces SOD levels but, as a consequence of oxidative stress, these do not return to normal.


Detection of apoptotic cells in intestines from horses with and without gastrointestinal tract disease.
To identify apoptosis in equine intestines and determine whether apoptosis is associated with gastrointestinal tract disease or a specific tissue layer of intestine. 38 horses that underwent surgery or were euthanatized for small or large intestine obstruction, strangulation, or distension and 9 control horses euthanatized for reasons other than gastrointestinal tract disease or systemic disease. Specimens were collected at surgery from intestine involved in the primary lesion and distant to the primary lesion site or at necropsy from several sites including the primary lesion site. Histologic tissue sections were stained with H&E, and apoptosis was detected by use of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. The number of apoptotic cells per hpf was counted in the mucosa, circular muscle, longitudinal muscle, and serosa. Apoptotic nuclei were seen in all layers of intestine. An increased number of apoptotic cells was found in the circular muscle of the intestine from horses with simple obstruction, compared with strangulating obstruction or healthy intestine. Intestine distant from a primary strangulating lesion had higher numbers of apoptotic cells than did intestine distant from a simple obstructive lesion or intestine taken at the site of a strangulating or simple obstructive lesion. Intestine from horses with obstructing or strangulating lesions in the small intestine and large colon had high numbers of apoptotic cells possibly because of ischemic cell injury and subsequent inflammation. Whether substantial apoptosis affects intestinal function is not yet known.


Emerging Pristine MOF-Based Heterostructured Nanoarchitectures: Advances in Structure Evolution, Controlled Synthesis, and Future Perspectives.
Metal-organic frameworks (MOFs) can be customized through modular assembly to achieve a wide range of potential applications, based on their desired functionality. However, most of the initially reported MOFs are limited to microporous systems and are not sufficiently stable, which restricts their popularization. Heterogeneity is introduced into a simple MOF framework to create MOF-based heterostructures with fascinating properties and interesting functions. Heterogeneity can be introduced into the MOFs via postsynthetic/ligand exchange. Although the ligand exchange has shown potential, it is difficult to precisely control the degree of exchange or position. Among the various synthesis strategies, hierarchical assembly is particularly attractive for constructing MOF-based heterostructures, as it can achieve precise regulation of MOF-based heterostructured nanostructures. The hierarchical assembly significantly expands the compositional diversity of MOF-based heterostructures, which has high elasticity for lattice matching during the epitaxial growth of MOFs. This review focuses on the synthetic evolution mechanism of hierarchical assemblies of MOF-based nanoarchitectures. Subsequently, the precise control of pore structure, pore size, and morphology of MOF-based nanoarchitectures by hierarchical assembly is emphasized. Finally, possible solutions to address the challenges associated with heterogeneous interfaces are presented, and potential opportunities for innovative applications are proposed.


Mechanisms mediating visual detection in static perimetry.
The usual stimuli in static perimetry are white-light luminance increments. However, the specific visual detection mechanisms involved in perimetry are unknown because all classes of neural mechanisms are sensitive to spectrally broadband stimuli. The objective of this study was to determine the relative sensitivities of nonopponent and opponent detecting mechanisms under standard perimetry test conditions. Using trained rhesus monkey subjects, the relative sensitivities of the vision mechanisms for the detection of perimetry test stimuli were determined through psychophysical measurements of spectral sensitivity at each of the test field locations of the C24-2 threshold program on the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA). The spectral sensitivity functions were analyzed by a three-channel model that incorporated independent short-wavelength-sensitive, nonopponent (luminance), and opponent (chromatic) spectral sensitivity mechanisms. The visual detection mechanisms for perimetry thresholds varied as a function of the size and wavelength of the test field. With the perimeter's standard stimulus (Goldmann Size III) and bowl illumination (31.5 asb), the presence of a short-wavelength-sensitive mechanism was clearly evident at all field locations, but its relative sensitivity systematically declined with eccentricity. Under these conditions, the sensitivities of the opponent and nonopponent mechanisms were approximately equal at most field locations. With a larger stimulus (Goldmann Size V), however, the contribution of the opponent spectral sensitivity mechanism was more apparent over most of the central field and the alterations of sensitivity with eccentricity were less pronounced. In contrast, a small test field (Goldmann Size II) appeared to bias detection toward nonopponent mechanisms. The results of these investigations indicate that detection thresholds during perimetry can be effectively biased toward different photopic, visual processing channels through the appropriate selection of size and wavelength of the test stimulus.


[Innovations and new techniques: tracheostomy cannulas].
In recent years, therapy by means of a tracheostomy has increased considerably due to the use of new trachea opening procedures and the development of the newest generation of tubes employed in tracheostomy. Percutaneous tracheostomy has become the preferred choice technique for patients in critical condition since it is a simple procedure, almost bloodless, and furthermore, this procedure can be carried out on a patient in a bed in a normal ward. The translaryngeal tracheostomy is one of the newest innovative techniques performed from inside the trachea; due to its complex nature, it is not commonly used yet although it promises to be an alternative procedure when confronting various counter-indications found in the percutaneous technique. In addition to the development of these techniques, substantial design modifications in the tubes used in tracheostomy have been produced; their objectives include improving a patient's comfortableness, reducing complications and easing a nurse's work.


[The Granada Diabetic Retinopathy Study. Direct screening of 8,244 patients. I].
To evaluate the results of regular screening for diabetic retinopathy in the geographic area assigned to the San Cecilio University Hospital of Granada. A multicenter prospective cohort study was carried out over a 2-year follow-up period. Retinal examinations were performed in 8244 diabetics in 14 health centres. 11,924 retinal examinations using an indirect ophthalmoscope, following pupil dilatation, were carried out. The classification of the lesions was as recommended by the simplified international scale of diabetic retinopathy and macular edema. The intervals between fundus examinations followed those recommended by the ETDRS. The crude prevalence of diabetes in the health area concerned was 2.77%. The average screening compliance of the program was 84.1%, and in only 0.3% of the patients was the fundus ophthalmoscopy ungradable. 91.3% of the known diabetic population attended for at least one fundus examination, with only 3.4% of the patients being referred for hospital treatment. The annual cost of the program was set at 53,173 Euros, with the average cost of each examination (6000 per year) being 8.87 Euros. The Diabetic Retinopathy Screening Program (through dilated pupils) carried out with indirect ophthalmoscopy is cost-effective. It provides coverage to the whole known diabetic population with a high level of compliance. The percentage of patients whose fundus can be considered ungradable is minimal.


Place, culture, and the social amplification of risk.
This article investigates the role of culture in the social production of risks and risk communication surrounding industrial development in a region located at a rural-urban interface. A case study examined a public consultation that was undertaken to inform local residents about an eco-industrial development proposal being planned near Edmonton, Alberta, Canada. The research employed the social amplification of risk framework (SARF) to examine the relationships among culture, place, and socially constructed risk. A total of 44 in-depth, semi-structured interviews were carried out with 33 landowners (farmers, acreage owners), public officials (municipal politicians, administrators), journalists, and industry representatives. Analysis revealed that risk communication occurred in relation to situated experiences of place that were based on conflicting cultural worldviews. The research shows that place is a useful component of the SARF, providing a spatial explanation for why some people amplify, and others attenuate, risks in locally contentious environmental debates.


Automatic honesty forgoing reward acquisition and punishment avoidance: a functional MRI investigation.
Recent neuroimaging investigations into human honesty suggest that honest moral decisions in individuals who consistently behave honestly occur automatically, without the need for active self-control. However, it remains unclear whether this observation can be applied to two different types of honesty: honesty forgoing dishonest reward acquisition and honesty forgoing dishonest punishment avoidance. To address this issue, a functional MRI study, using an incentivized prediction task in which participants were confronted with real and repeated opportunities for dishonest gain leading to reward acquisition and punishment avoidance, was conducted. Behavioral data revealed that the frequency of dishonesty was equivalent between the opportunities for dishonest reward acquisition and for punishment avoidance. Reaction time data demonstrated that two types of honest decisions in the opportunity for dishonest reward acquisition and punishment avoidance required no additional cognitive control. Neuroimaging data revealed that honest decisions in the opportunity for dishonest reward acquisition and those for punishment avoidance required no additional control-related activity compared with a control condition in which no opportunity for dishonest behavior was given. These results suggest that honesty flows automatically, irrespective of the concomitant motivation for dishonesty leading to reward acquisition and punishment avoidance.


Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure.
1. Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved. 2. We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles. 3. Untreated MI rats had significant LV dilatation (10.6+/-0.4* vs 8.9+/(-0.3) mm, MI vs control), impaired systolic function (fractional shortening=11+/-2* vs 38+/-2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6+/(-0.5) mm) and systolic function (13+/(-2%). The propranolol treated animals had higher LV end-diastolic pressures (27+/-2* vs 20+/(-3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6+/(-0.3) vs 2.4+/(0.5 g mm(-2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6+/(-0.3 g mm(-2) or the duration of Ca transients during isoproterenol stimulation. 4. Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium.


Practicing preventive health: the underlying culture among low-income rural populations.
Health disparities on the basis of geographic location, social economic factors and education levels are well documented. However, even when health care services are available, there is no guarantee that all persons will take preventive health measures. Understanding the cultural beliefs, practices, and lifestyle choices that determine utilization of health services is an important factor in combating chronic diseases. The purpose of this study was to investigate personal, cultural, and external barriers that interfered with participating in a community-based preventive outreach program that included health screening for obesity, diabetes, heart diseases, and hypertension when cost and transportation factors were addressed. Six focus groups were conducted in a rural community of Louisiana. Focus groups were divided into 2 categories: participants and nonparticipants. Three focus groups were completed with Dubach Health Outreach Project (DUHOP) participants and 3 were completed with nonparticipants. The focus group interviews were moderated by a researcher experienced in focus group interviews; a graduate student assisted with recording and note-taking during the sessions. Four main themes associated with barriers to participation in preventive services emerged from the discussions: (1) time, (2) low priority, (3) fear of the unknown, and (4) lack of companionship or support. Health concerns, free services, enjoyment, and free food were identified as motivators for participation. The findings of this study indicated that the resulting synergy between low-income status and a lack of motivation regarding health care prevention created a complicated practice of health care procrastination, which resulted in unnecessary emergency care and disease progression. To change this practice to proactive disease prevention and self care, a concerted effort will need to be implemented by policy makers, funding agents, health care providers, and community leaders and members.


Aqueous two-phase systems strategies for the recovery and characterization of biological products from plants.
The increasing interest of the biopharmaceutical industry to exploit plants as economically viable production systems is demanding the development of new downstream strategies to maximize product recovery. Aqueous two-phase systems (ATPSs) are a primary recovery technique that has shown great potential for the efficient extraction and purification of biological compounds. The present paper gives an overview of the efficient use of ATPS-based strategies for the isolation and partial purification of bioparticles from plant origin. Selected examples highlight the main advantages of this technique, i.e. scaling-up feasibility, process integration capability and biocompatibility. An overview of the recent approach of coupling ATPSs with traditional techniques to increase bioseparation process performance is discussed. A novel approach to characterization protein from plants combining ATPSs and two-dimensional electrophoresis (2-DE) is introduced as a tool for process development. In the particular case of products from plant origin, early success has demonstrated the potential application of ATPS-based strategies to address the major disadvantages of the traditional recovery and purification techniques. This literature review discloses the relevant contribution of ATPSs to facilitate the establishment of bioprocesses in the growing field of high-value products from plants.


Cost savings using a stepped-care prescribing protocol for nonsteroidal anti-inflammatory drugs.
To lower nonsteroidal anti-inflammatory drug (NSAID) costs while maintaining quality patient care and clinician satisfaction. Before and after 21-month trial with one study site and two control sites and a questionnaire that was sent to 203 clinicians. Two military medical centers and two affiliated primary care clinics. All beneficiaries filling outpatient NSAID prescriptions. An NSAID prescribing protocol was implemented requiring a trial of either ibuprofen or indomethacin before new prescription of more expensive NSAIDs. One control center used an NSAID computer cost-prompt and the other had no intervention. The proportion of expensive NSAIDs prescribed at each institution and total NSAID costs adjusted for prescription volume. Clinician acceptance and patient impact were assessed by the questionnaire. Study site clinicians (n=158) reported very few protocol-related patient care problems. A minority (9%) of study site clinicians considered the protocol very bothersome, and only 2% felt it should be discontinued. Quarterly use of expensive NSAIDs at the study site fell from 34% to 21%, decreasing costs by 30% (P<.001). In contrast, the site with a computer cost-prompt had only a 5% decrease in NSAID costs, while costs at the site with no intervention increased 2%. For drugs with similar benefits and adverse effects, a "stepped formulary" approach requiring an initial trial of one of the less expensive agents can maintain physician prescribing choices and satisfaction while lowering costs.


The 2019 Philippine UHC Act, Pandemic Management and Implementation Implications in a Post-COVID-19 World: A Content Analysis.
The 2019 Philippine Universal Health Care Act (Republic Act 11223) was set for implementation in January 2020 when disruptions brought on by the pandemic occurred. Will the provisions of the new UHC Act for an improved health system enable agile responses to forthcoming shocks, such as this COVID-19 pandemic? A content analysis of the 2019 Philippine UHC Act can identify neglected and leverage areas for systems' improvement in a post-pandemic world. While content or document analysis is commonly undertaken as part of scoping or systematic reviews of a qualitative nature, quantitative analyses using a two-way mixed effects, consistency, multiple raters type of intraclass correlation coefficient (ICC) were applied to check for reliability and consistency of agreement among the study participants in the manual tagging of UHC components in the legislation. The intraclass correlation reflected the individuals' consistency of agreement with significant reliability (0.939, p < 0.001). The assessment highlighted a centralized approach to implementation, which can set aside the crucial collaborations and partnerships demonstrated and developed during the pandemic. The financing for local governments was strengthened with a new ruling that could alter UHC integration tendencies. A smarter allocation of tax-based financing sources, along with strengthened information and communications systems, can confront issues of trust and accountability, amidst the varying capacities of agents and systems.


Rescue of thymidine cytotoxicity in L1210 ascites by elevated endogenous levels of deoxycytidine.
Although the biochemical and cytokinetic effects of thymidine (TdR) have been extensively studied in vitro, other parameters may be encountered in vivo that could alter its therapeutic efficacy. L1210 cells in culture are sensitive to the growth inhibitory effects of TdR, while TdR infusions in mice bearing L1210 ascites fail to prolong survival. Our results demonstrate that the TdR levels achieved in the serum and ascites fluid during sc and iv infusions range between 10(-4) and 10(-3) M. These levels are sufficient to inhibit the growth of bone marrow and intestinal mucosa cells, as evidenced by 32P incorporation studies. However, these TdR levels fail to exhibit the growth of L1210 ascites, despite the fact that these cells are sensitive to similar concentrations in vitro. The absence of growth inhibition in the L1210 ascites is shown to be due to increased endogenous CdR levels (approximately 2 X 10(-5) M) in the ascites fluid. The concomitant serum CdR levels were at least ten times lower than those achieved in the ascites. This factor probably accounts for the differential effect of TdR on normal cells as compared in vivo with agents such as TdR or even antimetabolites, such as cytarabine, may be modulated by increased CdR levels in the local tumor milieu. These studies are relevant in that TdR is currently being used in a variety of clinical protocols using the nucleoside alone at high doses or in combination with methotrexate, 5-FU, or cytarabine.


A duodenal mucosal abnormality in the reduction of Fe(III) in patients with genetic haemochromatosis.
Previous in vitro studies have shown that the uptake of Fe(III) by freshly isolated duodenal mucosal biopsy specimens is increased in patients with genetic haemochromatosis. Moreover, in the mouse it has recently been found that reduction of Fe(III) to Fe(II) is a prerequisite for iron uptake by the proximal intestine. This study used the in vitro technique to investigate the rates of reduction and uptake of 59Fe(III) by duodenal mucosal biopsy specimens obtained at endoscopy from treated and untreated patients with genetic haemochromatosis. The rate of reduction of iron in the medium was proportional to the incubation time and was not caused by the release of reducing factors from the tissue fragments. Ferrozine, a specific Fe(II) chelator and ferricyanide, a non-permeable oxidising agent, inhibited uptake of 59Fe showing that reduction of Fe(III) precedes uptake. The rates (all values given as pmol/mg/min) of reduction (152 (49) v 92 (23)) and uptake (8.3 (4.0) v 3.6 (1.3), mean (SD)), were significantly increased in biopsy specimens from the untreated group (n = 6) compared with those from 10 control subjects (p < 0.04). Furthermore, the reduction and uptake rates were still increased in five patients in whom iron stores were normal after venesection treatment. These results show that there is a persistent abnormality in the reduction and uptake of iron by the intestine in genetic haemochromatosis.


Computed protonation properties: unique capabilities for protein functional site prediction.
Prediction of protein functional sites from 3D structure is an important problem, particularly as structural genomics projects produce hundreds of structures of unknown function, including novel folds and the structures of orphan sequences. The present paper shows how computed protonation properties provide unique and powerful capabilities for the prediction of catalytic sites from the 3D structure alone. These protonation properties of the ionizable residues in a protein may be computed from the 3D structure using the calculated electrical potential function. In particular, the shapes of the theoretical microscopic titration curves (THEMATICS) enable selection of the residues involved in catalysis or small molecule recognition with good sensitivity and precision. Results are shown for 169 annotated enzymes in the Catalytic Site Atlas (CSA). Performance, as measured by residue recall and precision, is clearly better than that of other 3D-structure-based methods. When compared with methods based on sequence alignments and structural comparisons, THEMATICS performance is competitive for well-characterized enzymes. However THEMATICS performance does not degrade in the absence of similarity, as do the alignment-based methods, even if there are few or no sequence homologues or few or no proteins of similar structure. It is further shown that the protonation properties perform well on open, unbound structures, even if there is substantial conformational change upon ligand binding.


FLASH radiotherapy sparing effect on the circulating lymphocytes in pencil beam scanning proton therapy: impact of hypofractionation and dose rate.
The sparing effect of ultra-high dose rate (FLASH) radiotherapy has been reported, but its potential to mitigate depletion of circulating blood and lymphocytes (CL) hasn't been investigated in pencil-beam scanning-based (PBS) proton therapy, which could potentially reduce the risk of radiation-induced lymphopenia.
Material and methods: A time-dependent framework was used to score the dose to the CL during the course of radiotherapy. For brain patients, cerebral vasculatures were semi-automatic segmented from 3T MR-angiography data. A dynamic beam delivery system was developed capable of simulating spatially varying instantaneous dose rates of PBS treatment plans, and which is based on realistic beam delivery parameters that are available clinically. We simulated single and different hypofractionated PBS intensity modulated proton therapy (IMPT) FLASH schemes using 600 nA beam current along with conventionally fractionated IMPT treatment plan at 2 nA beam current. The dosimetric impact of treatment schemes on CL was quantified, and we also evaluated the depletion in subsets of CL based on their radiosensitivity.
Results: The proton FLASH sparing effect on CL was observed. In single-fraction PBS FLASH, just 1.5% of peripheral blood was irradiated, whereas hypofractionated FLASH irradiated 7.3% of peripheral blood. In contrast, conventional fractionated IMPT exposed 42.4% of peripheral blood to radiation. PBS FLASH reduced the depletion rate of CL by 69.2% when compared to conventional fractionated IMPT.
Conclusion: Our dosimetric blood flow model provides quantitative measures of the PBS FLASH sparing effect on the CL in radiotherapy for brain cancer. FLASH Single treatment fraction offers superior CL sparing when compared to hypofractionated FLASH and conventional IMPT, supporting assumptions about reducing risks of lymphopenia compared to proton therapy at conventional dose rates. The results also indicate that faster conformal FLASH delivery, such as passive patient-specific energy modulation, may further enhance the sparing of the immune system.&#xD.


Optical Biosensors for Label-Free Detection of Small Molecules.
Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations associated with the analysis of biologically, pharmacologically, or environmentally relevant compounds of low molecular weight, recent advances in the field have improved the detection of these analytes using outstanding methodology, instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small molecule detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.


A two-state Raman coupler for coherent atom optics.
We present results on a Raman laser-system that resonantly drives a closed two-photon transition between two levels in different hyperfine ground states of (87)Rb. The coupler is based on a novel optical design for producing two phase-coherent optical beams to drive a Raman transition. Operated as an outcoupler, it produces an atom laser in a single internal atomic state, with the lower divergence and increased brightness typical of a Raman outcoupler. Due to the optical nature of the outcoupling, the two-state outcoupler is an ideal candidate for transferring photon correlations onto atom-laser beams. As our laser system couples just two hyperfine ground states, it has also been used as an internal state beamsplitter, taking the next major step towards free space Ramsey interferometry with an atom laser.


[Ecologically-dependent vitamin-minerals insufficiency in the sportsmen's organism].
The authors revealed the reduction of saturation of iron, copper, zinc, E and B2 vitamins in sportsmen's organism under high physical exercise. The negative effect was associated with the duration of training - competition cycles. The reduced vitamin-mineral saturation of the organism was associated with the low ferritin level and an imbalance in the hormonal regulation of erythropoiesis. The state of erythropoiesis can be a criterion performance of athletes, whereas a degree of saturation of the body with minerals and vitamins can be the criterion for prenosological diagnosis of their health and professional relevance.


Endometrial echotexture variables in postpartum cows with subclinical endometritis.
The aim of this study was to evaluate endometrial echotexture changes on ultrasonographic digital images during subclinical endometritis using a computer-assisted image analysis program. Endometrial samples were collected from 140 Brown Swiss cows (days in milk = 35 ± 3) using a cytobrush method and classified as having a non-inflamed uterus (n = 66) and uterus with acute (n = 42), subacute (n = 21), and chronic (n = 11) inflammations. The mean cellular infiltration density was 0%, 31 ± 5%, 37 ± 6%, and 16 ± 8% for cows with non-inflamed uterus and cows with acute, subacute, and chronic uterine inflammations (P < 0.0001). As the cell infiltration density increased, both cervical diameter and mean gray level did not change. There were a liner decrease in homogeneity and a linear increase in contrast in response to increased cellular infiltration density. The sensitivity and specificity were 79.73% and 46.97% for the homogeneity value and 59.46% and 69.70% for the contrast value, respectively. In conclusion, monitoring endometrial echotexture alterations, especially homogeneity and contrast, changed depending on the cellular density and inflammation status and may be potential diagnostic markers for subclinical endometritis in cows.


Imaging of nitric oxide in a living vertebrate using a diamino-fluorescein probe.
Numerous approaches have been described to identify nitric oxide (NO), a free radical involved in various physiological and pathophysiological processes. One of these approaches is based on the use of chemical probes whose transformation by NO generates highly fluorescent derivatives, permitting detection of NO down to nanomolar concentrations. Here, we show that the cell-permeant diamino-fluorophore 4-amino-5-methylamino-2'-7'-difluoro-fluorescein diacetate (DAF-FM-DA) can be used to detect NO production sites in a living vertebrate, the zebrafish Danio rerio. The staining pattern obtained in larvae includes the bulbus arteriosus, forming bones, the notochord, and the caudal fin. The specificity of the signal was confirmed by its decrease in animals exposed to a NO scavenger or a NO synthase inhibitor and its increase in the presence of a NO donor. Using this method, NO production was observed to change along development in the notochord and the caudal fin whereas it remained stable in the bulbus arteriosus. Local changes in NO production in response to stressful conditions were also detected by this method. Altogether, labeling with DAF-FM DA is an efficient method to monitor changes in NO production in live zebrafish under physiological as well as pathophysiological conditions, suggesting applications to drug screening and molecular pharmacology.


A meta-analysis of COVID-19 vaccine attitudes and demographic characteristics in the United States.
Despite the potential for COVID-19 vaccination to prevent severe disease and death, vaccine hesitancy is common in the United States, with more than a quarter of eligible Americans yet to receive the first dose. We draw on existing published studies on COVID-19 vaccine attitudes to estimate the overall prevalence of vaccine hesitancy and assess how it varies across demographic groups. A systematic literature search was conducted to identify and meta-analyze relevant studies, which examined vaccine acceptance and hesitancy in the context of the COVID-19 vaccine. We meta-analyzed the prevalence rate of vaccine acceptance across all participants as well as for specific demographic subgroups. To assess time effects, we coded each study for the month during which data were collected and subjected the meta-analytic data to a regression analysis. To assess the magnitude of differences between demographic subgroups, we conducted a separate meta-analysis of odds ratios. Across the 46 samples, an average of 61% of participants indicated they were willing to receive the COVID-19 vaccine. The biggest demographic differences were found for race and political affiliation, with Black respondents and Republicans reporting significantly higher vaccine hesitancy than White respondents and Democrats. These results inform current vaccination efforts by identifying the groups that are least likely to get vaccinated and supporting the need for tailored vaccine strategies to alleviate the concerns specific to those populations. Comparing intentions to vaccinate with actual vaccination rates, vaccine hesitancy appears to have declined considerably among women and Black Americans.


Properties, performance and associated hazards of state-of-the-art durable water repellent (DWR) chemistry for textile finishing.
Following the phase-out of long-chain per- and polyfluoroalkyl substances (PFASs), the textile industry had to find alternatives for side-chain fluorinated polymer based durable water repellent (DWR) chemistries that incorporated long perfluoroalkyl side chains. This phase-out and subsequent substitution with alternatives has resulted in a market where both fluorinated and non-fluorinated DWRs are available. These DWR alternatives can be divided into four broad groups that reflect their basic chemistry: side-chain fluorinated polymers, silicones, hydrocarbons and other chemistries (includes dendrimer and inorganic nanoparticle chemistries). In this critical review, the alternative DWRs are assessed with regards to their structural properties and connected performance, loss and degradation processes resulting in diffuse environmental emissions, and hazard profiles for selected emitted substances. Our review shows that there are large differences in performance between the alternative DWRs, most importantly the lack of oil repellence of non-fluorinated alternatives. It also shows that for all alternatives, impurities and/or degradation products of the DWR chemistries are diffusively emitted to the environment. Our hazard ranking suggests that hydrocarbon based DWR is the most environmentally benign, followed by silicone and side-chain fluorinated polymer-based DWR chemistries. Industrial commitments to reduce the levels of impurities in silicone based and side-chain fluorinated polymer based DWR formulations will lower the actual risks. There is a lack of information on the hazards associated with DWRs, in particular for the dendrimer and inorganic nanoparticle chemistries, and these data gaps must be filled. Until environmentally safe alternatives, which provide the required performance, are available our recommendation is to choose DWR chemistry on a case-by-case basis, always weighing the benefits connected to increased performance against the risks to the environment and human health.


Feeling depleted and powerless: the construal-level mechanism.
Individuals exercise self-control daily to achieve desired goals; at the same time, people engage in social interaction daily and influence (feel powerful) or are influenced (feel powerless) by others. Does controlling the self have an unforeseen consequence for people's perception of their capacity to control others? Five studies-one correlational and four experimental-demonstrate that ego depletion from prior self-control determines one's personal sense of power; low-level, concrete mental construals account for this relationship. Our results showed that people with higher trait self-control reported a greater sense of power (Study 1). People who had depleted their self-control-related regulatory resources (vs. those who had not) experienced a lower sense of power (Study 2). The relationship between ego depletion and low sense of power was mediated by construal level (Study 3) and observed only when low-level, concrete construals were present, but not under high-level, abstract construals (Studies 4 and 5).


Antioxidant Properties of Ferulic Acid and Its Possible Application.
Ferulic acid has low toxicity and possesses many physiological functions (anti-inflammatory, antioxidant, antimicrobial activity, anticancer, and antidiabetic effect). It has been widely used in the pharmaceutical, food, and cosmetics industry. Ferulic acid is a free radical scavenger, but also an inhibitor of enzymes that catalyze free radical generation and an enhancer of scavenger enzyme activity. Ferulic acid has a protective role for the main skin structures: keratinocytes, fibroblasts, collagen, elastin. It inhibits melanogenesis, enhances angiogenesis, and accelerates wound healing. It is widely applied in skin care formulations as a photoprotective agent, delayer of skin photoaging processes, and brightening component. Nonetheless, its use is limited by its tendency to be rapidly oxidized.


Phylogeny of the class Actinobacteria revisited in the light of complete genomes. The orders 'Frankiales' and Micrococcales should be split into coherent entities: proposal of Frankiales ord. nov., Geodermatophilales ord. nov., Acidothermales ord. nov. and Nakamurellales ord. nov.
The phylogeny of the class Actinobacteria remains controversial, essentially because it is very sensitive to the choice of dataset and phylogenetic methods. We used a test proposed recently, based on complete genome data, which chooses among candidate species phylogenies based on the number of lateral gene transfers (LGT) needed to explain the diversity of histories among gene trees for a set of genomes. We used 100 completely sequenced genomes representing 35 families and 17 orders of the class Actinobacteria and evaluated eight different hypotheses for their phylogeny, including one based on a concatenate of 54 conserved proteins present in single copy in all these genomes, trees based on 16S and 23S rRNA gene sequences or their concatenation, and a tree based on the concatenation of MLSA genes (encoding AtpI, GyrA, FtsZ, SecA and DnaK). We used Prunier to infer the number of LGT in 579 proteins (different from those used to build the concatenated tree) present in at least 70 species, using the different hypothetical species trees as references. The best tree, with the lowest number of lateral transfers, was the one based on the concatenation of 54 proteins. In that tree, the orders Bifidobacteriales, Coriobacteriales, 'Corynebacteriales', 'Micromonosporales', 'Propionibacteriales', 'Pseudonocardiales', Streptomycetales and 'Streptosporangiales' were recovered while the orders 'Frankiales' and Micrococcales were not. It is thus proposed that the order 'Frankiales', which has an effectively but not validly published name, be split into Frankiales ord. nov. (type family Frankiaceae), Geodermatophilales ord. nov. (Geodermatophilaceae), Acidothermales ord. nov. (Acidothermaceae) and Nakamurellales ord. nov. (Nakamurellaceae). The order Micrococcales should also be split into Micrococcales (genera Kocuria, Rothia, Micrococcus, Arthrobacter, Tropheryma, Microbacterium, Leifsonia and Clavibacter), Cellulomonales (Beutenbergia, Cellulomonas, Xylanimonas, Jonesia and Sanguibacter) and Brachybacteriales (Brachybacterium) but the formal proposal for this will have to wait until more genomes become available for a significant proportion of strains in this order.


A cross-sectional analysis of factors associated with the intention to engage in tobacco treatment among inpatients in a state psychiatric hospital.
WHAT IS KNOWN ON THE SUBJECT?: People admitted to psychiatric facilities have high rates of tobacco use and hospitalizations present an opportunity for patients to have conversations about tobacco use treatment. Clinicians may believe that people with mental illnesses are not interested in quitting or that they do not understand the importance of treatment. Positive attitudes towards tobacco treatment, viewing that participating in treatment is normal care, and feeling that one is quite able to participate in such treatment predicts intentions to participate in treatment, which, in turn, predicts actual participation. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: Psychiatric patients who use tobacco use report poor prior involvement with tobacco treatment. Positive attitudes towards, encouraging opinions of other people about, and having a sense of control over taking part in tobacco treatment increases plans to engage in treatment. Having a sense of control in taking part in tobacco treatment is strongly associated with prior experiences with evidence-based treatment. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Because psychiatric hospitalizations are an opportunity for addressing tobacco use and treatment, clinicians should be prepared to support willing patients, especially those with prior substance use histories. Support should include providing them with information regarding tobacco treatment options during their hospital stay and ways that they can continue to receive care after discharge. Clinicians should be promoters of pro-tobacco treatment attitudes and supporting patients' sense of control over participating in treatment during hospitalization. Introduction Hospitalized tobacco users with mental illnesses (MI) may face several barriers to stopping smoking. However, motivational factors that affect the intention to engage in tobacco treatment have been shown to predict actual engagement. Aim To use the Theory of Planned Behavior to assess intentions to and prior experiences of engaging in evidence-based tobacco treatment among hospitalized individuals with MI. Method A cross-sectional survey was conducted among 115 patients in a state psychiatric hospital. Multivariate analyses were used to examine associations with the intentions and prior experiences of engaging in tobacco treatment. Results After controlling for demographic and smoking history, attitudes, subjective norms and perceived behavioural control towards engaging in tobacco treatment were significantly associated with intentions towards treatment engagement. Only higher scores on perceived behavioural control and lower education levels were associated with reported prior experiences of tobacco treatment. Discussion The low prior treatment engagement scores, but relatively higher intention to engage scores among participants suggests the need for deliberate support for evidence-based tobacco treatment during psychiatric hospitalizations. Implications for practice Clinician training in tobacco treatment can promote self-efficacy to engage patients while supporting patients' control so that tobacco treatment is an expected component of psychiatric care.


Pain palliation in patients with bone metastases using magnetic resonance-guided focused ultrasound with conformal bone system: a preliminary report.
We evaluated the safety and effectiveness of the Magnetic Resonance-guided Focused Ultrasound (MRgFUS) with the ExAblate Conformal Bone System for the palliation of painful bone metastases. Our Institutional Review Board approved this study, and all patients gave informed consent prior to enrollment. A total of six painful metastatic bone lesions in five patients were treated using MRgFUS with the ExAblate Conformal Bone System for pain palliation. The follow-up sessions were at 3 days, 2 weeks, 1, 2, and 3 months, and 1 year after treatment. Efficacy was evaluated by the changes in visual analog scale (VAS) scores. At 3-months and 1-year follow-ups, unenhanced computed tomography and contrast-enhanced MR imaging examinations were performed. All adverse events were assessed to evaluate treatment safety. All patients showed significant pain relief within 2 weeks. Two patients experienced complete pain reduction that lasted for 1 year. Two other patients showed pain relief measured as VAS scores of 2 and 4 on their last follow-up. Although the remaining patient had experienced significant pain relief in two lesions, the VAS score re-increased on his last follow-up. The size of the enhancing soft tissue mass in metastatic lesions decreased, and new bone formation was seen on follow-up images. Although adverse events were not serious, non-specific leg pain and second degree skin burn were noted. MRgFUS was demonstrated to be effective palliative treatment within 2 weeks in selected patients with painful bone metastases.


Nanotechnologies in Pancreatic Cancer Therapy.
Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. These chemotherapies are not effective often because patients are diagnosed at late stages and tumour metastasis has occurred. Nanotechnology can be used in order to formulate potent anticancer agents to improve their physicochemical properties such as poor aqueous solubility or prolong circulation times after administration resulting in improved efficacy. Studies have reported the use of nanotechnologies to improve the efficacy of gemcitabine (the current first line treatment) as well as investigating the potential of using other drug molecules which have previously shown promise but were unable to be utilised due to the inability to administer through appropriate routes-often related to solubility. Of the nanotechnologies reported, many can offer site specific targeting to the site of action as well as a plethora of other multifunctional properties such as image guidance and controlled release. This review focuses on the use of the major nanotechnologies both under pre-clinical development and those which have recently been approved for use in pancreatic cancer therapy.


Isolation of Bluetongue virus from canine abortions.
Three aborted canine fetuses were submitted to the Animal Health Diagnostic Center at Cornell University in November 2011 and September 2012 for diagnostic workups to determine the causes of the reproductive difficulties. Histological assessments of the sampled tissues were inconclusive due to the autolysis. Tests to detect bacterial causes of the abortions were also negative. Virus isolation testing on pooled tissues from the fetuses identified a cytopathogenic agent in cell cultures. Fluorescent antibody tests on the infected cells gave a positive reaction for Bluetongue virus, and subsequent serotype specific reverse transcription polymerase chain reaction assays identified the isolates as Bluetongue virus serotype 11. The current report describes the isolation of Bluetongue virus from dogs unrelated to contaminated vaccines and in the absence of a raw meat diet.


Analysis of polyphenols using capillary zone electrophoresis and HPLC: detection of soy, lupin, and pea protein in meat products.
The analysis of polyphenols, which are characteristic of certain legumes, enables a rapid and sensitive detection of legume proteins in meat products. Separation of specific isoflavones can be achieved by capillary zone electrophoresis (CZE) or high-performance liquid chromatography (HPLC), both coupled with a photodiode array detector (DAD). The use of CZE in the identification process is an appropriate means of rapid screening; the HPLC is less dependent on matrix effects and clearly more sensitive. Additives of soy protein isolates up to 0.1% could be detected in meat products, even in sausages heated to a high temperature or with hydrolyzed soy proteins. A solid-phase extraction procedure with polyamide cartridges has been developed to concentrate polyphenols. A similar detection of lupin protein is possible in principle. In the case of pea protein, a reliable detection was not possible depending on the coincidental appearance of polyphenols as indicating substances.


Proteomic profiling of 13 paired ductal infiltrating breast carcinomas and non-tumoral adjacent counterparts.
According to recent statistics, breast cancer remains one of the leading causes of death among women in Western countries. Breast cancer is a complex and heterogeneous disease, presently classified into several subtypes according to their cellular origin. Among breast cancer histotypes, infiltrating ductal carcinoma represents the most common and potentially aggressive form. Despite the current progress achieved in early cancer detection and treatment, including the new generation of molecular therapies, there is still need for identification of multiparametric biomarkers capable of discriminating between cancer subtypes and predicting cancer progression for personalized therapies. One established step in this direction is the proteomic strategy, expected to provide enough information on breast cancer profiling. To this aim, in the present study we analyzed 13 breast cancer tissues and their matched non-tumoral tissues by 2-DE. Collectively, we identified 51 protein spots, corresponding to 34 differentially expressed proteins, which may represent promising candidate biomarkers for molecular-based diagnosis of breast cancer and for pattern discovery. The relevance of these proteins as factors contributing to breast carcinogenesis is discussed.


Characterization of muscarinic receptors in human lens cells by pharmacologic and molecular techniques.
Activation of muscarinic receptors has been implicated in an increased risk of cataract after anticholinesterase treatment for glaucoma. The purpose of the present study was to determine the acetylcholine muscarinic receptor subtype(s) present in native human lens epithelial cells (NHLECs) and a human lens cell line, HLE-B3, and to compare the distribution in other ocular cells. Human lens cells were perfused with artificial aqueous humor (35 degrees C) after fura-2 incorporation, and calcium levels were measured using a fluorometric single-cell digital imaging system. Acetylcholine was the primary muscarinic agonist, and the receptor subtypes were elucidated by determining the relative effectiveness of pirenzepine and AF-DX 384 in blocking the agonist-induced response. The levels of expression of mRNA for the receptor subtypes M1 through M5 were determined by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) using a sequence detection system (ABI Prism 7700; Perkin-Elmer, Foster City, CA). This was performed using total RNA extracted from native lens, retina, iris, and sclera and also cultured lens cells. Acetylcholine induced a similar concentration-dependent increase in peak-amplitude cytosolic calcium in the range 100 nM to 100 microM in both native and HLE-B3 cells. However, the kinetics of the response waveforms to 30-second pulses of acetylcholine were different in the two cell types. At higher concentrations (> 1 microM), a second phase appeared in the HLE-B3 cells that was absent in the NHLEC response. The 50% inhibitory concentration (IC50) values for blockade of a 1 microM acetylcholine response by pirenzepine and AF-DX 384 were 30 nM and 230 nM, respectively, for NHLECs, and 300 nM and 92 nM, respectively, for HLE-B3 cells. The QRT-PCR data showed that more than 90% of the total muscarinic receptor mRNA from NHLEC was of M1 origin. In the HLE-B3 cells, however, more than 95% of the mRNA was of M3 origin. mRNA for M3 was also in greatest abundance in other eye tissues, although there was a significant contribution from M1 in iris and sclera. Both NHLECs and HLE-B3 cells express muscarinic receptors that produce significant changes in cytosolic calcium in response to acetylcholine. Both pharmacologic and QRT-PCR evidence shows that whereas the M1 subtype predominates in NHLECs, M3 is the major contributor in HLE-B3 cells. In all other eye tissues, M3 appears to be the major contributor. These data should be taken into account when choosing particular models to investigate cataract mechanisms and also when designing muscarinic agonists to treat glaucoma.


[Alcoholic liver cirrhosis, portal hypertension, and behavior of different lymphocyte populations].
There is no clear explanation for the known fact that peripheral levels of T lymphocytes are decreased in alcoholic hepatic cirrhosis. Cellular immune deficiency in cirrhosis has been attributed to this phenomenon. In order to confirm this observation and clarify its cause, the different lymphocyte populations of the peripheral blood of 52 patients with alcoholic hepatic cirrhosis and of 30 control subjects were studied. Absolute lymphocyte counts were decreased in cirrhotic patients (p less than 0.05) due to a marked reduction of T lymphocytes (p less than 0.001). Furthermore, T lymphocytes and, to a lesser degree, B lymphocytes, but not the remaining lymphocyte populations (referred to as "other lymphocytes" in this study), were decreased in relation to the existence of portal hypertension. Thus, a significant reduction of T and B lymphocytes (p less than 0.001) exists in cirrhotics with portal hypertension with respect to those without portal hypertension. The sequestering action of the hypertrophic spleen in patients with portal hypertension could be responsible for this phenomenon.


Cancer Incidence and Mortality in the Elderly: Profile of the Italian Problem.
In Italy, 28% of all deaths are due to cancer. Of the 15% of the population that is 65 years or older, 65% of cancer deaths occur in men and 69.5% in women. The proportional mortality and incidence of cancer in Italy varies with increasing age. All patients over 65 years are found to be at increased risk for intestinal cancers. In older men, the proportion of lung and urinary tract cancers decreases, while prostate, intestinal and gastric cancers increases. Prostate cancer predominates in men over 85 years and intestinal and gastric cancers are relatively more common than lung cancer. In women over age 74, intestinal cancer is most common. Breast, genital and lung cancers decrease rapidly with age, while stomach, liver, gallbladder and pancreatic cancers increase with age. The ratio of incidence to mortality for all cancers studied is shown to equalize with increased age, the probable result of lower hospitalization rates and less adequate cancer therapy for the elderly.


Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. The 3 PPAR isoforms (alpha, delta/beta and gamma) are known to control many physiological functions including glucose absorption, lipid balance, and cell growth and differentiation. Of interest, PPAR-gamma activation was recently shown to mitigate the inflammation associated with chronic and acute neurological insults. Particular attention was paid to test the therapeutic potential of PPAR agonists in acute conditions like stroke, spinal cord injury (SCI) and traumatic brain injury (TBI), in which massive inflammation plays a detrimental role. While 15d-prostaglandin J2 (15d PGJ2) is the natural ligand of PPAR-gamma, the thiazolidinediones (TZDs) are potent exogenous agonists. Due to their insulin-sensitizing properties, 2 TZDs rosiglitazone and pioglitazone are currently FDA-approved for type-2 diabetes treatment. Recent studies from our laboratory and other groups have shown that TZDs induce significant neuroprotection in animal models of focal ischemia and SCI by multiple mechanisms. The beneficial actions of TZDs were observed to be both PPAR-gamma-dependent as well as -independent. The major mechanism of TZD-induced neuroprotection seems to be prevention of microglial activation and inflammatory cytokine and chemokine expression. TZDs were also shown to prevent the activation of pro-inflammatory transcription factors at the same time promoting the anti-oxidant mechanisms in the injured CNS. This review article discusses the multiple mechanisms of TZD-induced neuroprotection in various animal models of CNS injury with an emphasis on stroke.


Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells.
BACKGROUND Alzheimer disease (AD) is a significant health issue for the elderly, and there are at present no clinically effective anti-AD agents. Prevention of Aß-induced neurotoxicity is proposed as a possible modality for treatment of AD. miR-33 has been proven to promote Aß secretion and impair Aß clearance in neural cells. The present study assessed whether miR-33 is involved in AD pathology. MATERIAL AND METHODS miR-33 level was detected by qRT-PCR. The Akt/mTOR pathway was analyzed by Western blot analysis. Neuron inflammation and oxidative stress were measured using commercial detection kits. Flow cytometry and Western blot assay were conducted to assess cell apoptosis, and Western blot assay was used to assess synaptic protein levels. RESULTS miR-33 expression level was markedly upregulated in SH-SY5Y cells treated with Aß₂₅₋₃₅. miR-33 knockdown suppressed inflammation, oxidative stress, and cell apoptosis. In addition, miR-33 knockdown improved synaptic plasticity, and the protective effect of miR-33 knockdown was discovered through suppressing activation of the Akt/mTOR signaling pathway. CONCLUSIONS Taken together, these findings suggest that miR-33 knockdown protects against Aß₂₅₋₃₅-induced inflammation, oxidative stress, apoptosis, and synaptic damage by suppressing activation of the Akt/mTOR pathway.


Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.
CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.


[Evaluation of a strategy adopted to expand adherence to breast cancer screening in Brazilian Northeast].
To evaluate the actions of the "Um Beijo Pela Vida" Program developed in a Brazilian Northeast city to increase adherence to breast cancer screening by women registered by the Brazilian Family Health Strategy for breast cancer screening. A quantitative approach was used to evaluate the coverage of screening actions for aged 40 years-old or more. Community workers from the nine Family Health Teams of the town carried out an active search. The percentage of eligible women who were screened for breast cancer by clinical breast examination or mammography, mammogram classification according to BI-RADS®, women screened who were referred for further testing and treatment, and the number of breast cancers detected were collected by means of a structured questionnaire, analyzed with the EPI-INFO TM software and compared to previously defined patterns. 3,608 women were included, corresponding to 68.4% of the target population registered in the Brazilian Family Health Strategy. Coverage rates of clinical breast examination for women aged 40 to 49 years-old and of mammograms for women aged 50 to 69 years-old were 58.9 and 56.7%, respectively. All women with highly suspicious mammographic lesions were submitted to fine needle aspiration or core biopsy (100%). Six new cases of cancer were detected and 80% of the standards established for this evaluation were carried out. The evaluation of the actions of the Program suggests its adequacy considering the degree of fulfillment of the previously defined requirements.


Functional expression of an ajmaline pathway-specific esterase from Rauvolfia in a novel plant-virus expression system.
Acetylajmalan esterase (AAE) plays an essential role in the late stage of ajmaline biosynthesis. Based on the partial peptide sequences of AAE isolated and purified from Rauvolfia cell suspensions, a full-length AAE cDNA clone was isolated. The amino acid sequence of AAE has the highest level of identity of 40% to putative lipases known from the Arabidopsis thaliana genome project. Based on the primary structure AAE is a new member of the GDSL lipase superfamily. The expression in Escherichia coli failed although a wide range of conditions were tested. With a novel virus-based plant expression system, it was possible to express AAE functionally in leaves of Nicotiana benthamiana Domin. An extraordinarily high enzyme activity was detected in the Nicotiana tissue, which exceeded that in Rauvolfia serpentina (L.) Benth. ex Kurz cell suspension cultures about 20-fold. This expression allowed molecular analysis of AAE for the first time and increased the number of functionally expressed alkaloid genes from Rauvolfia now to eight, and the number of ajmaline pathway-specific cDNAs to a total of six.


Fetal Right Ventricular Prominence: Associated Postnatal Abnormalities and Coarctation Clinical Prediction Tool.
Fetal right ventricular (RV) prominence is a known indicator of possible left-sided structural heart disease with a low positive predictive value for aortic coarctation. There is a paucity of data on identifying which fetuses with RV prominence will have postnatal arch obstruction. Our study objectives were to create a clinical prediction tool for coarctation and to describe the diagnostic outcomes of our cohort with fetal RV prominence. We performed a retrospective review of patients referred with fetal RV prominence from January 2009 to October 2015. Recorded fetal echocardiographic variables included gestational age, semilunar and atrioventricular valve dimensions, left and right ventricular mid-cavitary dimensions, foramen ovale and aortic arch flow direction, and isthmal diameter. Postnatal cardiac and non-cardiac diagnoses were documented. We performed descriptive analysis for postnatal outcomes and classification tree analysis to create a clinical prediction tool. Eighty-eight patients were reviewed; 58 (66%) had abnormal postnatal echocardiograms, 45 (51%) had left-sided lesions, including 26 (30%) with coarctation, and 6 (7%) had pulmonary hypertension. Our clinical prediction tool employs gestational age, RV mid-cavitary dimension z-score, and isthmal diameter z-score to predict coarctation with 85% accuracy, 95% confidence interval [75.3, 92.4%]. Our model correctly classified 45/54 non-coarctation and 19/21 coarctation cases, with 90% sensitivity and 83% specificity. Developing an accurate prediction tool for coarctation in cases of fetal RV prominence is an important first step in improving our management of these challenging cases.


Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.
Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with hepatorenal syndrome were treated with a combination of ornipressin, a potent vasoconstrictor agent, and plasma volume expansion with albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with ornipressin and albumin was associated with a normalization of the overactivity of renin-angiotensin and sympathetic nervous systems, a marked increase in atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when ornipressin and albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of vasoconstrictor systems. However, 3 of 8 patients on 15-day therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of vasoconstrictor systems play a crucial role in the pathogenesis of hepatorenal syndrome. Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.


Use of Serogroup B Meningococcal Vaccines in Persons Aged ≥10 Years at Increased Risk for Serogroup B Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices, 2015.
In October 2014, the Food and Drug Administration (FDA) licensed the first serogroup B meningococcal (MenB) vaccine (MenB-FHbp [Trumenba, Wyeth Pharmaceuticals, Inc.]) as a 3-dose series. In January 2015, FDA licensed a second MenB vaccine (MenB-4C [Bexsero, Novartis Vaccines]) as a 2-dose series. Both vaccines were approved for use in persons aged 10-25 years. Following outbreaks of serogroup B meningococcal disease on two college campuses in 2013, both MenB vaccines were granted Breakthrough Therapy designations, which expedites drug development and review by FDA, and were licensed based on accelerated approval regulations. On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended use of MenB vaccines among certain groups of persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease. This report summarizes information on MenB administration and provides recommendations and guidance for use of these vaccines among persons aged ≥10 years in certain groups who are at increased risk for serogroup B meningococcal disease, and reviews the evidence considered by ACIP to make these recommendations. Recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by ACIP.


Coronavirus infection in a litter of pups.
An outbreak of a coronavirus infection in a litter of 10-week-old poodle pups from a commercial kennel is described. Coronavirus-like particles were demonstrated by electron microscopy in the intestinal contents and in the colonic mucosa. Treponemas and campylobacters were excreted in great numbers in the faeces. The gastrointestinal disturbances were complicated by hepatic and renal degeneration and severe bronchopneumonia.


Cyclosporine drug monitoring with C0 and C2 concentrations in children with stable renal allograft function.
Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring of blood concentration. We aimed to evaluate trough (C0) and second hour (C2) level after ingestion of drug monitoring in renal allograft recipients. In this retrospective study, 12 children eight boys and four girls; mean age at transplantation 14.6 +/- 3.7 yr (ranges: 7.0-19.0), mean age post-transplant 17.8 +/- 4.9 yr (ranges: 9.0-24.0) who were transplanted >6 months were enrolled in this evaluation. Ten were recipients of a living related donor and two deceased donor grafts. While six children were receiving CsA, steroids and azathioprine, the other six received CsA, steroids and mycophenolate mofetil. Clinical course, blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were 96.2 +/- 59.5 and 504 +/- 305.4 ng/mL respectively. Mean serum creatinine level was 1.2 +/- 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 +/- 36.8 mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl and C2 levels. However, no correlation was found between C0 levels and any of the above parameters. In conclusion, our data suggest that C2 levels are correlated better with dose and serum creatinine level.


Protocol for the RELATE trial: a feasibility and pilot randomised controlled trial of a low-intensity group intervention for young people in care with elevated posttraumatic stress symptoms.
Young people in out-of-home care have often experienced trauma, such as direct maltreatment or witnessing violence. There is good evidence that rates of mental health difficulties are high in this group, including posttraumatic stress disorder (PTSD), a trauma-specific mental health outcome. There remains less evidence to guide how to effectively address elevated PTSD symptoms (PTSS) in these young people, particularly in ways that are feasible and scalable for stretched social-care and mental health services. This protocol describes a feasibility study comprising a pilot two-arm randomised controlled trial (RCT). Participants (N = 50) will be randomised to either (a) a group-based trauma-focused programme (Teaching Recovery Techniques), delivered by mental health practitioners both online and in-person, or (b) care-as-usual. Primarily, the trial aims to explore the key feasibility and protocol acceptability questions, including rates of recruitment and retention, as well as the acceptability of the intervention (particularly the online delivery format) to participants and services. In addition, outcomes including PTSS (primary clinical outcome), depression and functioning will be assessed at baseline (pre-randomisation), post-intervention and at a 3-month follow-up. Ethical approval has been received from the Health Research Authority (Wales REC1 Ref 20/WA/0100) and University, with further approval from the host trust and social care site. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries. ClinicalTrials.gov, NCT04467320 . Registered on 13 July 2020.


Gender Variations in In-Hospital Mortality in Patients Hospitalized With Dizziness: A Retrospective Study.
Women with cardiac diseases generally have a higher mortality than men. Suggested reasons include delay in reporting to hospital, less aggressive management, and higher cardiovascular risk profiles in women. We assessed gender differences in patients hospitalized with dizziness. We retrospectively reviewed the database of patients hospitalized with acute cardiac disease in Qatar from 1991 to the end of 2010. Patients hospitalized with dizziness were analyzed; 1611 (3.8%; 95% confidence interval [CI]: 3.6%-4%) of the total N = 42 144 patients were hospitalized with dizziness during the 20 years: 410 (25.5%) females and 1201 (74.5%) males. Mean age (female 55 [16] and male 53 [16] years) was comparable ( P = .06). Women had more hypertension, diabetes mellitus, palpitation, and arrhythmia compared with men. In-hospital mortality was 3.8% (women 5.6% vs men 3.2%, P = .03). After adjusting for potential confounders, female gender remained an independent factor for increased in-hospital mortality (adjusted odds ratio: 2.2, 95% CI: 1.21-4, P = .01). In this 20-year data set from a Middle Eastern country, female gender was an independent factor associated with increased in-hospital mortality in patients hospitalized with dizziness after adjusting for confounders. Further research is warranted to confirm this novel gender difference.


Approaches for the inhibition and elimination of microbial biofilms using macromolecular agents.
Biofilms are complex three-dimensional structures formed at interfaces by the vast majority of bacteria and fungi. These robust communities have an important detrimental impact on a wide range of industries and other facets of our daily lives, yet their removal is challenging owing to the high tolerance of biofilms towards conventional antimicrobial agents. This key issue has driven an urgent search for new innovative antibiofilm materials. Amongst these emerging approaches are highly promising materials that employ aqueous-soluble macromolecules, including peptides, proteins, synthetic polymers, and nanomaterials thereof, which exhibit a range of functionalities that can inhibit biofilm formation or detach and destroy organisms residing within established biofilms. In this Review, we outline the progress made in inhibiting and removing biofilms using macromolecular approaches, including a spotlight on cutting-edge materials that respond to environmental stimuli for "on-demand" antibiofilm activity, as well as synergistic multi-action antibiofilm materials. We also highlight materials that imitate and harness naturally derived species to achieve new and improved biomimetic and biohybrid antibiofilm materials. Finally, we share some speculative insights into possible future directions for this exciting and highly significant field of research.


Bacterial, archaeal and micro-eukaryotic communities characterize a disease-suppressive or conducive soil and a cultivar resistant or susceptible to common scab.
Control of common scab disease can be reached by resistant cultivars or suppressive soils. Both mechanisms are likely to translate into particular potato microbiome profiles, but the relative importance of each is not known. Here, microbiomes of bulk and tuberosphere soil and of potato periderm were studied in one resistant and one susceptible cultivar grown in a conducive and a suppressive field. Disease severity was suppressed similarly by both means yet, the copy numbers of txtB gene (coding for a pathogenicity determinant) were similar in both soils but higher in periderms of the susceptible cultivar from conducive soil. Illumina sequencing of 16S rRNA genes for bacteria (completed by 16S rRNA microarray approach) and archaea, and of 18S rRNA genes for micro-eukarytes showed that in bacteria, the more important was the effect of cultivar and diversity decreased from resistant cultivar to bulk soil to susceptible cultivar. The major changes occurred in proportions of Actinobacteria, Chloroflexi, and Proteobacteria. In archaea and micro-eukaryotes, differences were primarily due to the suppressive and conducive soil. The effect of soil suppressiveness × cultivar resistance depended on the microbial community considered, but differed also with respect to soil and plant nutrient contents particularly in N, S and Fe.


Rhabdomyosarcoma: a rare laryngeal neoplastic entity.
A case of pleomorphic rhabdomyosarcoma of the larynx is presented, which is extremely rare in a laryngeal site. The symptomatology and macroscopic aspect of the neoplasm can simulate the presence of other neoplastic variants of the larynx, and, for this reason, histological examination must be associated with immunohistochemistry for correct diagnosis and treatment.


[Giant cell tumor of the lumbar vertebra].
A rare observation of the lumbar vertebra giant-cell tumour with growth into the surrounding soft tissue in a girl of 12, is described. It is pointed out that only radical surgical intervention is required for the treatment of giant-cell tumours, with subsequent replacement of the bone defect with an auto- or allotransplant. The authors state that one cannot judge the malignant course of the tumour basing on the histological picture only. Therefore the subdividing giant-cell tumours into "benign" and "malignant" is largely formal.


Cognitive-constructivist Approach in Medical Settings: The Use of Personal Meaning Questionnaire for Neurological Patients' Personality Investigation.
Objective: The cognitive-constructivist psychotherapy approach considers the self as a continuous regulation process between present and past experience, in which attributions of meaning is characterized by the use of internal rules. In this conception, everyone would be driven by a specific inner coherence called Personal Meaning Organization (PMO). Such approach has never been applied to neurological patients by means of ad hoc developed tools. We performed an explorative study aimed to characterize personality styles in different neurological conditions within the theoretical framework of cognitive-constructivist model. Materials and Methods: Three groups of neurological patients (Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Primary Headache) and a sample of healthy participants, each composed by 15 participants, for a total of 60 participants, were recruited. The Personal Meaning Questionnaire (PMQ), an Italian questionnaire assessing PMOs construct, and other clinical tools for psychological and quality of life assessment were administered to all subjects. Results: The main finding concerned the detection, across all clinical conditions, of a higher prevalence of phobic personality style, with Amyotrophic Lateral Sclerosis showing a relevant prevalence of such PMO with respect to all other neurological conditions and controls. However, with respect to controls, in all clinical conditions, PMQ highlighted a tendency, even if not statistically significant, to codify experience by means of specific cognitive and emotional patterns. Conclusion: Our findings represent the first contribution towards understanding the personality profiles of patients affected by neurological conditions according to cognitive-constructivist theory.


Drug delivery of oral anti-cancer fluoropyrimidine agents.
Sixty years since its introduction, 5-FU still forms the core of chemotherapy regimens for many types of malignancies. 5-FU is a time-dependent drug but is rapidly degraded in plasma by dihydropyrimidine dehydrogenase (DPD). Although originally developed in an intravenous form, 5-FU oral prodrugs were developed with the goal of improving efficacy and minimizing toxicity as well as to capitalize on the advantages of oral drug administration. The inactive 5-FU prodrug is gradually converted into the active form in the systemic circulation. UFT, S-1, and capecitabine are oral 5-FU prodrugs currently in clinical use. However, the efficacy of 5-FU can be further improved by its combination with DPD inhibitors and biochemical modulators, such as uracil and leucovorin, in addition to modifying administration schedules. Areas covered: We focused on the drug delivery of oral 5-FU prodrugs, their pharmacokinetics, and the development of DPD inhibitors. Since oral 5-FU prodrugs have been formulated into combination drugs, we also discussed the regulatory approval of combination drugs. Expert opinion: Many regimens that include intravenously administered 5-FU can be replaced by oral 5-FU prodrugs. Patients would benefit from development of combination 5-FU oral prodrug formulations and its associated path through the combination drug regulatory approval process.


[The German early lexical development inventory ELAN in parent's opinion].
The ELAN is a valid and reliable German questionnaire scale (parent report measure) which aims to assess the size of expressive vocabulary of children aged 16 to 26 months. It is used as a screening tool to detect late talkers. The ELAN also meets the quality criteria usefulness, economy and standardization. The purpose of the present study was to investigate the acceptance of the ELAN by a specially designed standardized evaluation questionnaire consisting of 17 items with a closed response-set and 2 items focusing on suggestions for improvement (open response-set). ELAN and evaluation questionnaire were filled out by 123 primary care givers for monolingual German children growing up in Heidelberg and Stuttgart and their surrounding areas (68 boys, 55 girls; mean age: 21.8; SD 3.3 months). The number of missing answers was low, on average 5.9 %. About half of the participants (n = 61) needed 15 minutes or less to fill out the ELAN. The majority felt the ELAN was well-structured (96 %) and neither too long nor too short. 98 % found the wording easily understandable. 87% of the participants enjoyed filling it out. 76 % believed that the ELAN recorded the lexical abilities of a child correctly. 22 % became uncertain whether their child's verbal development is age-adequate. The ELAN helped 37% to better assess the verbal abilities of their child. 58% got an idea of the words which young children are able to use. 67% rated the diagnostic utility of the ELAN for early detection of retarded language development as "very good" or "good" and only 3% as "bad" 67% preferred to apply the ELAN at the German pediatric screening U7, but would not like to fill it out in the waiting room (77%), but at home (69%) to reduce stress experience. It can be concluded that the ELAN was accepted by its respondents.


Suspected Accidental Infiltration of Rocuronium During General Anesthesia Induction: A Case Report.
There are few reports on rocuronium infiltration under general anesthesia. We report a case of suspected accidental rocuronium infiltration during anesthesia induction. A 25-year-old woman with autism spectrum disorder, intellectual disability, and epilepsy was scheduled for the extraction of 4 impacted third molars under general anesthesia. After induction with sevoflurane, an intravenous (IV) line was established in the left cephalic vein. Rocuronium was administered; however, subcutaneous swelling at the IV site was observed immediately. Spontaneous ventilations were maintained until additional rocuronium was administered via a new IV line. After heat pack application, the swelling disappeared 60 minutes after infiltration, and no tissue damage was observed. A strategy was developed to continue neuromuscular monitoring until recovery occurred. Acceleromyography was used, and the train-of-4 ratios at 99, 130, and 140 minutes after infiltration were 0.79, 0.91, and 1.0, respectively. Sugammadex was administered to prevent neuromuscular blockade recurrence. The patient was extubated once adequate return of muscle function and consciousness were observed. No neuromuscular block prolongation or recurrence were observed postoperatively. When rocuronium infiltration is suspected, it is important to eliminate swelling at the infiltration site and determine a management strategy based on neuromuscular monitoring.


The Use of Eye-Movement Desensitization Reprocessing (EMDR) Therapy in Treating Post-traumatic Stress Disorder-A Systematic Narrative Review.
Aim: There is an extensive body of research examining the efficacy of Eye-Movement Desensitization Reprocessing (EMDR) therapy in treatment of Post-traumatic Stress Disorder (PTSD). This systematic narrative review aimed to systematically, and narratively, review robust evidence from Randomized-Controlled Trials examining the efficacy of EMDR therapy. Method: Eight databases were searched to identify studies relevant to the study aim. Two separate systematic searches of published, peer-reviewed evidence were carried out, considering relevant studies published prior to April 2017. After exclusion of all irrelevant, or non-robust, studies, a total of two meta-analyses and four Randomized-Controlled Trials were included for review. Results: Data from meta-analyses and Randomized-Controlled Trials included in this review evidence the efficacy of EMDR therapy as a treatment for PTSD. Specifically, EMDR therapy improved PTSD diagnosis, reduced PTSD symptoms, and reduced other trauma-related symptoms. EMDR therapy was evidenced as being more effective than other trauma treatments, and was shown to be an effective therapy when delivered with different cultures. However, limitations to the current evidence exist, and much current evidence relies on small sample sizes and provides limited follow-up data. Conclusions: This systematic narrative review contributes to the current evidence base, and provides recommendations for practice and future research. This review highlights the need for additional research to further examine the use of EMDR therapy for PTSD in a range of clinical populations and cultural contexts.


Interaction between prenatal risk and infant parasympathetic and sympathetic stress reactivity predicts early aggression.
Nonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is known about the PNS and SNS in interaction with early adversity during infancy. Yet this is when the physiological systems involved in emotion regulation are emerging and presumably most responsive to environmental influences. We examined whether parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) response and recovery at six months, moderate the association between cumulative prenatal risk and physical aggression at 20 months (N=113). Prenatal risk predicted physical aggression, but only in infants exhibiting coactivation of PNS and SNS (i.e., increase in RSA and decrease in PEP) in response to stress. These findings indicate that coactivation of the PNS and SNS in combination with prenatal risk is a biological marker for the development of aggression.


Structural motifs in the RNA encoded by the early nodulation gene enod40 of soybean.
The plant gene enod40 is highly conserved among legumes and also present in various non-legume species. It is presumed to play a central regulatory role in the Rhizobium-legume interaction, being expressed well before the initiation of cortical cell divisions resulting in nodule formation. Two small peptides encoded by enod40 mRNA as well as its secondary structure have been shown to be key elements in the signalling processes underlying nodule organogenesis. Here results concerning the secondary structure of mRNA of enod40 in soybean are presented. This study combined a theoretical approach, involving structure prediction and comparison, as well as structure probing. Our study indicates five conserved domains in enod40 mRNA among numerous leguminous species. Structure comparison suggests that some domains are also conserved in non-leguminous species and that an additional domain exists that was found only in leguminous species developing indeterminate nodules. Enzymatic and chemical probing data support the structure for three of the domains, and partially for the remaining two. The rest of the molecule appears to be less structured. Some of the domains include motifs, such as U-containing internal loops and bulges, which seem to be conserved. Therefore, they might be involved in the regulatory role of enod40 RNA.


Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study.
This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.


Pain as a metaphor for illness. Part II: Family caregivers' management of pain.
Changes in the healthcare system have made the patient's home the primary site of cancer care. Family members, already burdened with the psychological impact of having a loved one with cancer, take on caregiving roles to meet the multiple and complex needs of the patient. Part I of this two-part article focused on family caregivers' descriptions of the patients' pain and the impact of this pain on caregivers. A model of the Caregiver Experience of Pain is provided along with implications for future inquiry and clinical practice. Themes identified in caregiver roles in medication administration included deciding what to give, deciding when to give, night duty, reminding/encouraging, keeping records, fear of addiction, and doing everything. Caregiver roles in nondrug interventions included positioning/mobility, massage, use of ointments/lotions, cold, heat, being there through touch, avoiding touch, and talk and other distractions. Caregiver perceptions of what doctors or nurses could do better included themes of being there, explain, be honest/listen, addiction concern, and giving medication. Caregiver questions included areas of future, understanding why, death, concern about medications, and fear about what to do at home. The study results offer important suggestions for oncology nurses in supporting family caregivers in the management of the patient in pain.


High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?
Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the β-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR34/L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.


Radioimmunotherapy for indolent B-cell non-Hodgkin lymphoma in relapsed, refractory and transformed disease.
Radioimmunotherapy (RIT) is a new treatment modality that combines the benefits of radiotherapy and immunotherapy. In RIT, a radionuclide is coupled to a monoclonal antibody, directed against an antigen expressed on tumor cells. Recently, RIT has been introduced targeting the CD20 surface antigen, which is expressed on nearly all B-cell non-Hodgkin lymphomas (NHL). Clinical experience with RIT in the treatment of patients with indolent NHL is increasing. To date, two commercially available agents are used: yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab. In general, there is no organ-specific non-hematologic toxicity when a standard dose of RIT is used. Bone marrow suppression is the dose-limiting RIT toxicity; therefore, bone marrow infiltration by NHL should be investigated before treatment. Treatment-related myelodysplastic syndromes and acute myeloid leukemia after RIT are being investigated but long-term data are needed for final evaluation. Results are quite encouraging with respect to complete remission and overall response, even in pretreated patients with unconjugated monoclonal antibodies. RIT induces high response rates and a significant subgroup of patients has achieved long-term durable responses. RIT is feasible in heavily pretreated patients and does not compromise future treatments in the event of progressive disease. Randomized phase III studies are in progress to evaluate the timing of RIT in the overall management of indolent NHLInvestigations of new emerging therapeutic strategies for patients with indolent NHL are underway, with research into the feasibility of RIT as first-line therapy and in advanced disease, RIT dose escalation and combined modality approaches with autologous stem cell transplantation. The encouraging results of RIT in indolent NHL have initiated studies focusing on its benefit for patients with aggressive NHL.


Could a brief assessment of negative emotions and self-esteem identify adolescents at current and future risk of self-harm in the community? A prospective cohort analysis.
Self-harm is common in adolescents, but it is often unreported and undetected. Available screening tools typically ask directly about self-harm and suicidal ideation. Although in an ideal world, direct enquiry and open discussion around self-harm would be advocated, non-psychiatric professionals in community settings are often reluctant to ask about this directly and disclosure can be met with feeling of intense anxiety. Training non-specialist staff to directly ask about self-harm has limited effects suggesting that alternative approaches are required. This study investigated whether a targeted analysis of negative emotions and self-esteem could identify young adolescents at risk of self-harm in community settings. Data were collected as part of a clinical trial from young people in school years 8-11 (aged 12-16) at eight UK secondary schools (N = 4503 at baseline, N = 3263 in prospective analysis). The Short Mood and Feelings Questionnaire, Revised Child Anxiety and Depression Scale, Rosenberg Self-Esteem Scale, personal failure (Children's Automatic Thoughts Scale), and two items on self-harm were completed at baseline, 6 and 12 months. Following a process of Principal Components Analysis, item reduction, and logistic regression analysis, three internally reliable factors were identified from the original measures that were independently associated with current and future self-harm; personal failure (3 items), physical symptoms of depression/anxiety (6 items), positive self-esteem (5 items). The summed score of these 14 items had good accuracy in identifying current self-harm (AUC 0.87 girls, 0.81 boys) and at six months for girls (0.81), and fair accuracy at six months for boys (AUC 0.74) and 12 months for girls (AUC 0.77). A brief and targeted assessment of negative emotions and self-esteem, focusing on factors that are strongly associated with current and future self-harm, could potentially be used to help identify adolescents who are at risk in community settings. Further research should assess the psychometric properties of the items identified and test this approach in more diverse community contexts.