Flow Cytometric Immunophenotyping Is Sensitive for the Early Diagnosis of De Novo Aggressive Natural Killer Cell Leukemia (ANKL): A Multicenter Retrospective Analysis.
Aggressive natural killer cell leukemia (ANKL) is a fatal hematological neoplasm characterized by a fulminating clinical course and extremely high mortality. Current diagnosis of this disease is not effective during the early stages and it is easily misdiagnosed as other NK cell disorders. We retrospectively analyzed the clinical characteristics and flow cytometric immunophenotype of 47 patients with ANKL. Patients with extranodal NK/T cell lymphoma, nasal type (ENKTL) and chronic lymphoproliferative disorder of NK cell (CLPD-NK), who were diagnosed during the same time period were used for comparisons. Abnormal NK cells in ANKL were found to have a distinctiveCD56bright/CD16dim immunophenotype and markedly increased Ki-67 expression, whereas CD57 negativity and reduced expression of killer immunoglobulin-like receptor (KIR), CD161, CD7, CD8 and perforin were exhibited compared with other NK cell proliferative disorders (p<0.05). The positive rates of flow cytometry detection (97.4%) was higher than those of cytomorphological (89.5%), immunohistochemical (90%), cytogenetic (56.5%) and F-18 fluorodeoxyglucose positron emission tomography/computer tomography (18-FDG-PET/CT) examinations (50%) (p<0.05). ANKL is a highly aggressive leukemia with high mortality. Flow cytometry detection is sensitive for the early and differential diagnosis of ANKL with high specificity.


Germ-line gene therapy and the medical imperative.
Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has a prima facie moral obligation to do so.


Short-term exposure to ambient air pollution and individual emergency department visits for COVID-19: a case-crossover study in Canada.
Ambient air pollution is thought to contribute to increased risk of COVID-19, but the evidence is controversial. To evaluate the associations between short-term variations in outdoor concentrations of ambient air pollution and COVID-19 emergency department (ED) visits. We conducted a case-crossover study of 78 255 COVID-19 ED visits in Alberta and Ontario, Canada between 1 March 2020 and 31 March 2021. Daily air pollution data (ie, fine particulate matter with diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone were assigned to individual case of COVID-19 in 10 km × 10 km grid resolution. Conditional logistic regression was used to estimate associations between air pollution and ED visits for COVID-19. Cumulative ambient exposure over 0-3 days to PM2.5 (OR 1.010; 95% CI 1.004 to 1.015, per 6.2 µg/m3) and NO2 (OR 1.021; 95% CI 1.015 to 1.028, per 7.7 ppb) concentrations were associated with ED visits for COVID-19. We found that the association between PM2.5 and COVID-19 ED visits was stronger among those hospitalised following an ED visit, as a measure of disease severity, (OR 1.023; 95% CI 1.015 to 1.031) compared with those not hospitalised (OR 0.992; 95% CI 0.980 to 1.004) (p value for effect modification=0.04). We found associations between short-term exposure to ambient air pollutants and COVID-19 ED visits. Exposure to air pollution may also lead to more severe COVID-19 disease.


Pathogenicity of Blastocystis hominis, a clinical reevaluation.
Blastocystis (B.) hominis was considered to be a member of normal intestinal flora in the past, but in recent years it has been accepted as a very controversial pathogenic protozoan. In this study, 52 individuals whose stool examination revealed B. hominis were evaluated for clinical symptoms. Metronidazole was administered for 2 weeks to the patients infected with B. hominis. After 2 weeks of treatment they were called for a follow-up stool examination. No other bacteriological and parasitological agents were found during stool examination of these patients. The frequency rate of intestinal symptoms was 88.4% in the B. hominis cases. Abdominal pain was the most frequent symptom (76.9%). Diarrhea and distention followed at a rate of 50.0% and 32.6%. Intestinal symptoms may be seen frequently together with the presence of B. hominis and this protozoan may be regarded as an intestinal pathogen, especially when other agents are eliminated.


[Living the mother-child-family triad in the Kangaroo Method].
This study focuses on the experience of families in the Kangaroo Mother Method (KM) and aims to understand the functioning of the family dynamics and to apprehend the family transformations as a result of their experience in the method. The study used Symbolic Interactionism as a theoretical and Grounded Theory as a methodological reference framework. Data revealed the following phenomena: having an unexpected evolution and outcome of pregnancy, which is a phase in which the parents go through a pregnancy and suffer due to its premature interruption; coping with the prematurity of the child, in which the parents get into the world of prematurity and face the need to act for the child's survival; and living with the decision and the experience together with the child, which reveals the possibility of staying in hospital in the KM or not. These phenomena led to the central category: weighing the risks and benefits between staying with the child in the kangaroo method or with the family.


Quantitative and Qualitative Changes in Diet Associated with the Consumption of Ultra-Processed Foods: A Survey on a Representative Sample of Manufacturing Workers in Brazil.
The increasing intake of ultra-processed (UP) foods is causing changes in the profile of food and nutrient consumption, negatively influencing consumer behavior. The present study aimed to evaluate the influence of UP foods on the diet of Brazilian adults, verifying the association between its increasing contribution to total energy and trends in the consumption of other NOVA groups, food subgroups, energy consumption, and macro- and micronutrients. We conducted an observational, cross-sectional study of a probability sample of 921 manufacturing workers in the state of Rio Grande do Norte, Brazil, from a combined stratified and two-stage survey. Trends in consumption across quintiles of UP food contribution to the total energy intake were tested with linear regression. The results showed that higher UP food consumption is associated with a higher intake of energy, carbohydrates and total-, mono- and polyunsaturated fats, saturated fats and trans fats, and the micronutrients calcium, iron and thiamine; and higher consumption of ready-to-eat foods, accompanied by lower consumption of foods that require preparation, such as beans, tubers and roots, vegetables and fruits, which may represent a risk for the development of non-transmissible chronic diseases in this population.


Pavement Disease Detection through Improved YOLOv5s Neural Network.
An improved Ghost-YOLOv5s detection algorithm is proposed in this paper to solve the problems of high computational load and undesirable recognition rate in the traditional detection methods of pavement diseases. Ghost modules and C3Ghost are introduced into the YOLOv5s network to reduce the FLOPs (floating-point operations) in the feature channel fusion process. Mosaic data augmentation is also added to improve the feature expression performance. A public road disease dataset is reconstructed to verify the performance of the proposed method. The proposed model is trained and deployed to NVIDIA Jetson Nano for the experiment, and the results show that the average accuracy of the proposed model reaches 88.17%, increased by 4.01%, and the model FPS (frames per second) reaches 12.51, increased by 184% compared with the existing YOLOv5s. Case studies show that the proposed method satisfies the practical application requirements of pavement disease detection.


Association of plasminogen activator inhibitor-type 1 (-675 4G/5G) polymorphism with pre-eclampsia: systematic review.
Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia and related conditions. The PAI-1 (-675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative genetic risk factor for pre-eclampsia. The aim of this study was identify, appraise and synthesise the available evidence for the association of the PAI-1 (-675 4G/5G) polymorphism with pre-eclampsia. Systematic review and random effects meta-analysis of genetic association studies. We found 12 eligible genetic association studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls participated. The studies were generally small (median number of cases 102, range 24 to 403) and underpowered to detect plausible association sizes. Meta-analysis of all of the studies detected statistically significant gene-disease associations in the recessive [pooled odds ratio 1.28 (95% confidence interval 1.09, 1.50); population attributable risk 7.7%] and dominant [pooled odds ratio 1.21 (95% confidence interval 1.01, 1.44); population attributable risk 13.7%] models. We did not find evidence of statistical heterogeneity, funnel plot asymmetry or small study bias. These data suggest that the fibrinolytic pathway regulated by the PAI-1 gene may contribute to the pathogenesis of pre-eclampsia and related conditions. This association, if confirmed in larger genetic association studies, may inform research efforts to develop novel interventions or help to prioritise therapeutic targets that merit evaluation in randomised clinical trials.


The Empirical Relationship between Mining Industry Development and Environmental Pollution in China.
This study uses a vector autoregression (VAR) model to analyze changes in pollutants among different mining industries and related policy in China from 2001 to 2014. The results show that: (1) because the pertinence of standards for mining waste water and waste gas emissions are not strong and because the maximum permissible discharge pollutant concentrations in these standards are too high, ammonia nitrogen and industrial sulfur dioxide discharges increased in most mining industries; (2) chemical oxygen demand was taken as an indicator of sewage treatment in environmental protection plans; hence, the chemical oxygen demand discharge decreased in all mining industries; (3) tax reduction policies, which are only implemented in coal mining and washing and extraction of petroleum and natural gas, decreased the industrial solid waste discharge in these two mining industries.


When cognitive control harms rather than helps: individuals with high working memory capacity are less efficient at infrequent contraction of attentional breadth.
Different attentional breadths facilitate performance on different types of perceptual tasks. For instance, a narrow attentional breadth improves spatial resolution; whereas a broad attentional breath enhances face perception. This means that to optimise attention for the dynamic demands of real-world vision, it is necessary to efficiently resize attentional breadth. Previous research has shown that individuals differ considerably in how efficiently they can resize their attentional breadth. Since working memory capacity can be conceptualised as the ability to effectively regulate one's attentional resources, the present study examined whether individual differences in attentional resizing efficiency were related to working memory capacity. Tasks that gauge the efficiency of attentional contraction (resizing from broad to narrow focus) and attentional expansion (resizing from narrow to broad) were used, in addition to standard working memory measures. It was found that individuals high in working memory capacity experienced a greater cost in attentional contraction, that is, they were less efficient in resizing from a broad to a narrow attentional focus. This is likely because the attentional resizing tasks encourage the setting of a particular attentional breadth for the majority of trials in a block, and then gauge efficiency in changing from this breadth on the minority of trials. This means that high-capacity individuals may have more readily adopted the dominant attentional breadth, particularly in the majority-global condition, thereby incurring a greater cost on the infrequent trials requiring resizing to the local level. This shows that at least in some circumstances, greater cognitive control can be a relative disadvantage.


Respiration-averaged CT versus standard CT attenuation map for correction of 18F-sodium fluoride uptake in coronary atherosclerotic lesions on hybrid PET/CT.
To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of 18F-sodium fluoride (18F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). This study comprised 23 patients who underwent 18F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBRMAX) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBRMAX (median [Interquartile range]): CTAC = 1.65 [1.23 to 2.38], RACTAC = 1.63 [1.23 to 2.33], p = 0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC = 0.10 [0 to 1.0], RACTAC = 0.15 [0 to 1.03], p = 0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary 18F-NaF uptake on PET/CT.


Postdates induction with an unfavorable cervix and risk of cesarean.
Objective: To determine the risk of cesarean delivery associated with postdates induction (≥41 weeks) compared to term induction (37-40w6d) among women with an unfavorable cervix, and to examine the risk factors associated with cesarean among women undergoing postdates induction. Methods: A planned secondary analysis of a large prospective cohort study on induction (n = 854) was performed. Women with a singleton gestation, intact membranes, and an unfavorable cervix (Bishop score of ≤6 and dilation ≤2 cm) who were undergoing a term (≥37 weeks) induction for any indication were included. Women with a prior cesarean were excluded. The primary outcome was cesarean delivery. Relative risk of cesarean was estimated using a modified Poisson's regression model. Results: There was a significantly increased risk of cesarean for women undergoing postdates induction (n = 154) compared to women 37-40w6d (n = 700), (46.8 versus 26.0%, p < .001). This increased risk of cesarean remained after adjustment for race, parity, and pregnancy-related hypertension (aRR 1.70 [1.39-2.09], p < .001). Risk factors independently associated with cesarean among women ≥41 weeks included nulliparity (aRR 3.38 95%CI (2.42-4.74)), BMI ≥30 (aRR 1.72 95%CI (1.34-2.21)), and starting cervical dilation <1 cm (aRR 1.37 95%CI (1.11-1.70)). Conclusions: Women ≥41 weeks undergoing an induction with an unfavorable cervix are at a significantly increased risk of cesarean compared to women 37-40w6d, with nulliparity, obesity, and cervical dilation <1 cm being independent risk factors. These data can be used to augment patient counseling and support the ongoing discussion regarding the risk of post dates induction.


Pediatric spinal tumors.
We present an overview of the clinical outcome and surgical treatment of 34 pediatric spinal tumors, carried out in our center from 1981 to 1999. Follow-ups were available for 25.5 months on average. Clinical history, signs, surgical approach, outcome and radiological reports were obtained by review of the patients' charts. These pediatric tumors formed a very heterogeneous group, with a predominance of neurinomas and neurofibromas in older children and neuroblastomas or primitive neuroectodermal tumors in younger ones. Ependymomas and astrocytomas were the most frequent intramedullary tumors. Extradural tumors included tumors such as aneurysmal bone cysts, Ewing's sarcoma, histiocytomas, chordomas and an angiofibroma. Following decompression of the spinal cord, the neurological status improved with good functional recovery in 23 children and had deteriorated at follow-up in 5 children. Relapse occurred in 12 cases, including histiocytomas, chordomas, medulloblastoma and tumors associated with genetic disorders. Eighteen children underwent a combined treatment with chemotherapy and/or radiotherapy. The spectrum of pathology is wide and requires multidisciplinary treatment.


Risk assessment of dietary supplements.
Risk assessment of dietary supplements shares many of the requirements of that for other chemicals, although there are some important differences. Amongst these is the essential nature of some nutrients so that it may be necessary to balance the need to minimize toxicological risk with the need to avoid deficiency. There may also be limitations on experimental design, in that high doses may not be achievable for nutritional reasons and available human data on toxicological hazard is likely to be very limited. Prior to embarking on a risk assessment the problem needs to be formulated. This involves risk assessors, risk managers and relevant stakeholders. A key decision is whether a risk assessment is necessary and, if so, what is required of the assessment. This will shape the nature and output of the assessment. Risk assessment itself is a scientific process comprising four steps, hazard identification, hazard characterization, exposure assessment and risk characterization. Hazard identification involves determining the range of toxicological effects that might be caused by the substance, whilst hazard characterization establishes dose-response relationships, toxicological and species relevance of the findings and establishes health based guidance values. Exposure assessment involves predicting or measuring the level, pattern and duration of intake of the substance by exposed individuals. This may require dietary consumption data. Finally, risk characterization is the process whereby all of the prior information is integrated to reach conclusions in a form appropriate to the question posed. The nature of the output can take several different forms, and may be qualitative or quantitative. There are some cross-cutting issues in risk assessment, primarily on uncertainty and variability. The sources of uncertainty at each step of the risk assessment should be clearly identified and quantified to the extent possible. Variability requires that the risk assessment should take into account all relevant subpopulations and groups, where there might be differences on the basis of intake or sensitivity. This would very often include different life stages, but may also include gender, ethnic or genetic differences. The report of the risk assessment should be systematic and transparent, identifying all key assumptions and defaults used.


Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of acinetobacter ventilator-associated pneumonia.
Acinetobacter organisms, which are a common cause of ventilator-associated pneumonia (VAP) in some health care centers, are becoming more resistant to such first-line agents as imipenem-cilastatin (Imi-Cil). Sulbactam has good in vitro activity against Acinetobacter organisms; thus, ampicillin-sulbactam (Amp-Sulb) may be a viable treatment alternative. The outcomes for critically ill trauma patients with Acinetobacter VAP treated with either Amp-Sulb or Imi-Cil were compared retrospectively. A total of 77 episodes in 75 patients were studied. Fourteen patients were treated with Amp-Sulb, and 63 patients were treated with Imi-Cil. Treatment efficacy was similar in the Amp-Sulb and Imi-Cil groups (93% vs. 83%, respectively; P>.05). No statistically significant differences between groups were noted with regard to associated mortality, duration of mechanical ventilation, or length of stay in the intensive care unit or hospital. However, adjunctive aminoglycoside therapy was used more often in the Amp-Sulb group. Patients generally received Amp-Sulb because of imipenem resistance. Amp-Sulb was effective in treating a small number of patients with Acinetobacter VAP; however, more data are needed.


[Cytoflavin efficacy in the treatment of disseminated encephalomyelitis in children].
To evaluate the efficacy of cytoflavin in the complex therapy of disseminated encephalomyelitis in children. A blind, placebo - controlled, randomized study was carried out. Thirty-two patients, aged form 1 to 17 years, received cytoflavin from the first day after admission in intravenous drips in 5% glucose solution during 10 days. The control group consisted of 30 children who received a standard infusion therapy. Clinical and laboratory evaluation was carried out on the 11th and 30th days, MRT was performed before hospitalization and on the 30th day. Cytoflavin had a positive effect on the rate of recovery of the majority of neurological symptoms. The average EDSS score decreased by 1.5 times to the 30th day compared with the control group. The complete regression of clinical symptoms and focal changes on MRI on the 30th day was observed in 25% of children of the main group and in 3.3% in the control group (р=0.001). The drug exerted the endothelium protective and antioxidant effects, improved blood rheology and restored the content of circulating endothelial cells, the level of D-dimer and indicators of free radical oxidation to the 30th day of treatment.


Long-term thalamic stimulation in Parkinson's disease: postmortem anatomoclinical study.
Parkinsonian tremor may be suppressed by thalamic stimulation. For an equivalent clinical efficacy, its obvious advantage over micro-thalamotomy is its reversibility. This patient experienced postural tremor at the age of 44 years and akineto-rigid syndrome 8 years later. At the age of 60 years, intrathalamic stimulation was applied over a long-term period of 43 months until death and was efficient on tremor with low stimulation. This case is the first with anatomic verification. The extent of the lesion provoked by the electrode is very small. The location of the stimulation site was in the medio-inferior part of the intermedius complex at the entrance of cerebello-thalamic fibers. The stimulation of the cerebellar afferent axons could be the cause of the clinical effect. The stimulation site corresponds to the thalamic source of the precentral and accessory motor cortex, which correlates with changes observed in our PET study showing a regional cerebral blood flow decrease in cerebellar nuclei and also in precentral and accessory motor cortex. The places and mechanisms of the effects of stimulations and lesions could be different.


Behavioral change communications on malaria prevention in Ghana.
The purpose of this study is to assess the various communications strategies designed to promote insecticide-treated nets (ITN) use among pregnant women and children. This study is an exploratory study into the communications activities by institutions involved in malaria prevention in Ghana. In-depth interviews were conducted and the data were analyzed. We found that most of the interventions are aimed at encouraging the target markets to acquire ITNs, although most messages on malaria prevention are not integrated. Several challenges were noted, including financial constraints, lack of human resources, cultural barriers, negative publicity, and negative perceptions on malaria.


Intestinal Lipodystrophy, Serum Cholesterol Levels and Inositol Deficiency in Gerbils.
High fat diets containing saturated fats produce hypercholesterolemia in male gerbils. In female gerbils, this effect is offset by the development of a severe intestinal lipodystrophy, which can be prevented by feeding inositol. Inositol biosynthesis in the testis protects the male from the intestinal syndrome. The chain length of the fatty acid modifies the lipid accumulation in the gut.


Molecular characterization of immunoglobulin variable regions from murine monoclonal antibodies specific for simian virus 40 large tumour antigen.
In this report we compare the immunoglobulin variable (IgV) region function and structure relationships of murine monoclonal antibodies that recognize simian virus 40 (SV40) large tumour antigen (T ag). Comparison of monoclonal antibody V region function is based on SV40 T ag epitope recognition and idiotype (Id) expression. Structural comparisons are based on V region gene sequence determination. The data presented herein, suggests that a high degree of homology within both the V kappa and VH regions, along with minor differences within V kappa complementarity determining regions (CDR) may result in the detection of similar SV40 T ag epitopes by the monoclonal anti-SV40 T ag preparations. The expression of a cross-reactive Id also appears to be based on the high degree of homology within both V kappa and VH regions and depends on conformational interactions imparted by both regions.


The bilateral reach-to-grasp movement of Parkinson's disease subjects.
The performance of simultaneous movements is said to be disrupted in Parkinson's disease, yet there are some indications that this dysfunction is less evident for bilateral inter-limb actions, as opposed to unilateral simultaneous actions. Focussing specifically upon natural actions, this study uses a three-dimensional kinematics system (ELITE) to assess the movement kinematics of a bilateral non-homologous reach-to-grasp action. The target device consisted of a large cylinder (diameter 8 cm) to which a handle (diameter 0.8 cm) was attached. The task was to reach and grasp the cylinder with one hand (gross grasp) while reaching to grasp the handle with the contralateral hand (precision grasp). Overall the results indicated that Parkinson's disease subjects, like controls, showed independent and appropriate kinematic parameterization of each limb. For example, and as a reflection of task precision requirements, the time taken to decelerate upon the item to be grasped was longer for the limb grasping the handle than for the limb grasping the cylinder. Subtle indications of compensatory mechanisms, in response to left upper limb inadequacies of Parkinson's disease subjects, were suggested by findings of an earlier timing of maximum hand grip aperture for the left than for the right hand, and adjustments to the final transport phase of the left arm under bilateral conditions. It is proposed that left-right hand differences are more evident with basal ganglia dysfunction, but that these differences are compensated for by CNS mechanisms so that natural non-homologous reach-to-grasp actions are performed in a functional, coordinated and appropriate manner.


What do I do now?: clinical decision making by new graduates.
Newly graduated nurses (NGNs) are thrust into roles that some purport they are inadequately prepared to handle. This study investigated the experience of NGNs as they made clinical judgments in the critical care setting. Three themes emerged: developing confidence in practice, seeking assistance, and decision making. Nursing professional development educators can use the results to coordinate an education plan that extends beyond formal orientation and provides support for NGNs throughout the first year of practice.


Profiled bar transmission gratings: soft-x-ray calibration of new Kirchoff solutions.
A new analytical model, derived rigorously from scalar diffraction theory, accurately fits soft-x-ray measurements of symmetrical profile gold transmission gratings in all diffracted orders. The calibration system selects numerous photon energies by use of a high-resolution grazing-incidence monochromator and a dc e-beam source. Fine-period free-standing gratings exhibit limited performance and require such testing to determine parameters of and select acceptable gratings for use in time-resolved (0.25 ns) spectrographs of known radiometric response. Unfolded spectra yield a Z-pinch plasma peak kT approximately 250 eV, total radiated energy approximately 900 kJ, and a pinch-driven gold-wall hohlraum Planckian kT approximately 86 eV.


Niche-specific macrophage loss promotes skin capillary aging.
All mammalian organs depend upon resident macrophage populations to coordinate repair processes and facilitate tissue-specific functions1-3. Recent work has established that functionally distinct macrophage populations reside in discrete tissue niches and are replenished through some combination of local proliferation and monocyte recruitment4,5. Moreover, decline in macrophage abundance and function in tissues has been shown to contribute to many age-associated pathologies, such as atherosclerosis, cancer, and neurodegeneration6-8. Despite these advances, the cellular mechanisms that coordinate macrophage organization and replenishment within an aging tissue niche remain largely unknown. Here we show that capillary-associated macrophages (CAMs) are selectively lost over time, which contributes to impaired vascular repair and tissue perfusion in older mice. To investigate resident macrophage behavior in vivo, we have employed intravital two-photon microscopy to non-invasively image in live mice the skin capillary plexus, a spatially well-defined model of niche aging that undergoes rarefication and functional decline with age. We find that CAMs are lost with age at a rate that outpaces that of capillary loss, leading to the progressive accumulation of capillary niches without an associated macrophage in both mice and humans. Phagocytic activity of CAMs was locally required to repair obstructed capillary blood flow, leaving macrophage-less niches selectively vulnerable to both homeostatic and injury-induced loss in blood flow. Our work demonstrates that homeostatic renewal of resident macrophages is not as finely tuned as has been previously suggested9-11. Specifically, we found that neighboring macrophages do not proliferate or reorganize sufficiently to maintain an optimal population across the skin capillary niche in the absence of additional cues from acute tissue damage or increased abundance of growth factors, such as colony stimulating factor 1 (CSF1). Such limitations in homeostatic renewal and organization of various niche-resident cell types are potentially early contributors to tissue aging, which may provide novel opportunities for future therapeutic interventions.


Separation and characterization of mares' milk alpha(s1)-, beta-, kappa-caseins, gamma-casein-like, and proteose peptone component 5-like peptides.
The equine alpha(s1)- and beta-caseins (CN) were purified by chromatography on DEAE-cellulose and by reversed-phase HPLC. The alpha(s1)-, beta-, and kappa-CN were characterized either by monodimensional urea-PAGE or sodium dodecylsulfate (SDS)-PAGE or by bidimensional electrophoresis. Kappa-casein was characterized after electrophoresis by glycoprotein-specific staining. To identify alpha(s1)-CN without ambiguity, internal sequences were determined after trypsin or chymosin digestion of purified alpha(s1)-CN. These sequences, that could be estimated to correspond to 62% of the full protein, presented strong identities with regions of alpha(s1)-CN primary structures of other species. In particular, 51, 48, 43, and 40% identities were obtained with corresponding regions of sow, dromedary, cow, and human alpha(s1)-CN, respectively. On the other hand, trace amounts of equine gamma-CN-like and proteose peptone component 5-like peptides were found in the whole CN. They were identified by microsequencing and corresponded to beta-CN peptides generated by plasmin action on the whole CN. The equine alpha(s1), beta-, and kappa-CN were separated by bidimensional electrophoresis in numerous isoelectric variants with apparent isoelectric points distributed between pH 4.4 to 6.3, 4.4 to 5.9, and 3.5 to 5.5, respectively. The beta- and kappa-CN displayed a more acidic character in the mare than in the cow.


Severe systemic inflammatory response syndrome immediately after spinal surgery in a patient with axial gout.
We report a 55-year-old man with gouty arthritis who developed a 3-month history of low back pain, gradual lower extremities weakness and urinary incontinence. Lumbar MRI showed an exophytic lesion at L3-L4. Immediately after spinal decompression surgery, he developed fever, disorientation, polyarthritis, acute kidney injury and leucocytosis. He was treated with multiple antimicrobial agents for presumed spinal abscess but did not improve. Multiple body site cultures were negative. Aspiration of the sacroiliac joint revealed the presence of monosodium uric acid crystals. A diagnosis of acute gout was done, and he was treated with high-dose intravenous methylprednisolone and colchicine. Within 48 hours, he had a remarkable clinical improvement. At discharge, neurological and laboratory abnormalities had resolved. Awareness of risk factors for axial gout and a high degree of suspicion are important to establish a prompt diagnosis and treatment to prevent severe complications as seen in this case.


Successful repair of ectopia cordis using alloplastic materials.
Ectopia cordis is a very rare congenital anomaly associated with a high mortality rate. A successful repair of ectopia cordis with complete absence of sternum was achieved in a two-stage procedure. Initial management consisted of coverage of skin over the malpositioned heart using bilateral pectoral skin flaps. A second more definitive repair was undertaken at age 14 months. Four methyl methacrylate struts were used to reconstruct the anterior chest wall and were then covered with bilateral pectoralis major muscle flaps. At the 2.5-year follow-up there is no evidence of cardiopulmonary compromise and the development of the thorax appears normal. We advise that use of alloplastic materials is a valid option in managing this difficult congenital anomaly.


Adaptive Neuro-Fuzzy Inference System Applied QSAR with Quantum Chemical Descriptors for Predicting Radical Scavenging Activities of Carotenoids.
One of the physiological characteristics of carotenoids is their radical scavenging activity. In this study, the relationship between radical scavenging activities and quantum chemical descriptors of carotenoids was determined. Adaptive neuro-fuzzy inference system (ANFIS) applied quantitative structure-activity relationship models (QSAR) were also developed for predicting and comparing radical scavenging activities of carotenoids. Semi-empirical PM6 and PM7 quantum chemical calculations were done by MOPAC. Ionisation energies of neutral and monovalent cationic carotenoids and the product of chemical potentials of neutral and monovalent cationic carotenoids were significantly correlated with the radical scavenging activities, and consequently these descriptors were used as independent variables for the QSAR study. The ANFIS applied QSAR models were developed with two triangular-shaped input membership functions made for each of the independent variables and optimised by a backpropagation method. High prediction efficiencies were achieved by the ANFIS applied QSAR. The R-square values of the developed QSAR models with the variables calculated by PM6 and PM7 methods were 0.921 and 0.902, respectively. The results of this study demonstrated reliabilities of the selected quantum chemical descriptors and the significance of QSAR models.


[Efficacy of combined use of glycosaminoglycan peptide complex for intramuscular administration and oral diacerein in osteoarthritis: evaluation according to an observational multicenter clinical trial].
The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA). Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice. A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.411.8 and 61.911.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.11.8/6.01.6 and 4.92.1/5.11.8 (according to the numerical rating scale 010). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment. In the majority of patients with OA both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction 50% was 54.3 and 62.8% (p0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension in 6.3 and 4.6%, allergic reactions in 0.3 and 0.5% of patients (not significant). The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.


[Female physicians and pregnancy. Does the working climate discourage starting a family?]
Female physicians, especially those in surgical subspecialties, have an increased risk on subfertility and pregnancy complications, amongst preterm birth, compared to the general population. Long hours and unpredictable work weeks in a working climate that seems to discourage to start a family are contributing to these increased risks. Many physicians were unaware of the negative impact of delayed family planning and often regretted their decision to postpone pregnancy. Although differences between countries exist, also in the Netherlands, despite paid pregnancy and maternity leave, we also may not create the right working climate and truthful pregnancy-protective circumstances for female doctors to be able to work as safely as possible on something that could conceivably be viewed upon as their most important life's work. This American study with provocative title makes worrisome generic matters visible to us as profession, but also to employers in a labor market predominantly staffed by women.


Influences on older women's adherence to a low-fat diet in the Women's Health Initiative.
Most studies of dietary change during aging have focused on maintaining adequate intake by impaired elderly, and little is known about factors affecting dietary change for preventive purposes in older individuals. The purpose of this exploratory study was to determine the major behavioral influences on older women's adherence to a dietary fat reduction intervention. A diverse sample of 92 women aged 55 to 80 was recruited from two East Coast sites of the Women's Health Initiative. All the women were participating in the dietary modification arm of WHI, had received the same dietary instruction, and were in the maintenance phase of the intervention. The women were classified by nutritionists as adherent or nonadherent to a diet limiting fat intake to <20% of total calories. Focus groups and telephone interviews were conducted, and textual data were coded and sorted using content analysis techniques within the four categories of the Stimuli-Organismic Factors-Response Repertoire-Consequences (SORC) behavioral model. Frequencies of responses within categories were tabulated and compared qualitatively. Adherent women were more likely to report assertiveness, a lifelong commitment to reduced dietary fat, satisfaction with their lifestyle changes, and having applicable knowledge and skills. Nonadherent women reported more difficulty resisting negative emotions and prior food preferences and habits; they were also more concerned about negative responses from others. Enhancing adherence of older women to a dietary fat reduction program will require shifting priorities away from conforming to social pressure and using high-fat foods for personal satisfaction and moving toward enhancing motivation and commitment to long-term health.


ISSOP position statement on migrant child health.
Greater numbers of children are on the move than ever before. In 2015, the number of forcibly displaced people across the globe reached 65.3 million. Of the more than 1 million migrants, asylum seekers, and refugees who arrived in Europe in 2015, nearly one third were children, and 90,000 of these children were unaccompanied. Child migrants are among the most vulnerable, even after arriving at their destination. The health of migrant children is related to their health status before their journey, the conditions during their journey and at their destination, and the physical and mental health of their caregivers. These children may have experienced numerous forms of trauma including war, violence, separation from family, and exploitation. They may suffer from malnutrition and communicable diseases including vaccine-preventable diseases. Pregnant women, newborns, and unaccompanied minors are particularly vulnerable groups. Social isolation is a major risk factor for all migrant children that compound other health risks even after settlement in their new home. Lack of health information, language, and cultural differences serve as major barriers to adequate, timely, and appropriate healthcare. In spite the challenges they face, migrant children demonstrate remarkable resilience that can be nurtured to promote good mental and physical health. Migrant children, irrespective of their legal status, are entitled to healthcare of the same standard provided to children in the resident population, as stated in the UN Convention on the Rights of the Child. It is imperative that the health sector includes informed health workers who are able to identify the health risks and needs of these children and provide culturally competent care. In order to achieve this and promote the rights of migrant children to optimal health and well-being, ISSOP recommends that Programmes and activities designed to promote and protect migrant child health and well-being must be designed in collaboration with all sectors involved, including the education and social sectors, and should always include the voices of migrant children and their families. Health services should be readily available and easily accessible for preventive, maintenance, and curative care regardless of the child's legal status. Care should be of the same standard as care provided to the local population. Health information should be provided that is culturally sensitive and readily available in a language that migrant children and families can understand. Medical interpreters and cultural mediators should be available during healthcare encounters, and personnel working with migrants should receive training in cultural competence. Health professionals should not participate in age determination until methods with acceptable scientific and ethical standards have been developed. Professionals working with migrant children and families should have access to emotional support services. Evidence-based best practices in the care of migrant children should be identified and made widely available to health workers. An observatory should be established to study the factors leading to poor psychosocial and mental health in migrant children and youth. Paediatricians and paediatric societies should work to improve the sensitivity of their respective populations towards migrants, asylum seekers, and refugees.


[A preliminary study on the effect of prepubertal exposure of male rats to diethylstilbestrol on the apoptosis of spermatogenic cells after sexual maturation and its mechanism].
To preliminarily study the effect of prepubertal exposure of male SD (Sprague-Dawley) rats to diethylstilbestrol (DES) on the apoptosis of spermatogenic cells after sexual maturation and its mechanism. Thirty 21-day-old male SD rats were randomly divided into 4 experimental groups, DES 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) and 1 control group. The experimental groups were injected (s.c.) with different doses of DES (dissolved in corn oil) during prepuberty [from postnatal day (PND) 22 to PND 35] and the control group with medium only. The apoptosis and related proteins Bcl-2 and Bax expressions of testicular spermatogenic cells were studied with TUNEL and immunohistochemistry after the rats sexual maturation (at PND 64). Compared with the control group, the apoptosis of testicular spermatogenic cells in the DES 0.01 microg/kg group had no difference, but significantly increased in the DES 0.1, 1.0 and 10.0 microg/kg groups and the apoptosis increased with the increase of DES dose. In the control and DES 0.01 microg/kg groups, Bax protein expressed weakly but Bcl-2 protein strongly in spermatogenic cells. With the increase of DES exposure, Bax protein expression in spermatogenic cells increased but Bcl-2 protein expression decreased. Prepubertal exposure of SD rats to inappropriate dose of DES can make the apoptosis of spermatogenic cells increase after sexual maturation. Bax and Bcl-2 proteins participate in the apoptotic course caused by prepubertal DES exposure.


[Full-dose combinations of antihypertensive drugs: what has changed in experts' guidelines?].
The 2013 European Society of Hypertension guidelines, including treatment policy changes presupposing that one two-component combination of antihypertensive agents may be substituted for another and their full-dose combinations may be prescribed if monotherapy is ineffective, are discussed. A rationale is provided for the most effective two-component full-dose combinations of antihypertensive drugs.


Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells.
Glutathione (GSH) is one of the most important physiological antioxidants involved in detoxification of hydrogen peroxide and lipid hydroperoxide. Previous studies have shown that cells can maintain and even increase cellular GSH content in response to sublethal oxidative stress. We hypothesized that gamma-glutamylcysteine synthetase (gamma GCS), the rate-limiting enzyme in de novo GSH synthesis, could be induced by oxidative stress. Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling. Exposure of confluent L2 cells with sublethal doses of DMNQ caused sustained elevation of cellular GSH levels over a 24-h period (to 2.5-fold with 10 microM). DMNQ caused increases in gamma GCS activity (70% at 24 h with 10 microM), the gamma GCS catalytic heavy subunit (gamma GCS-HS) protein level, and gamma GCS-HS mRNA content (approximately 4-fold after 6 h with 10 microM). The elevation of gamma GCS-HS mRNA by DMNQ was eliminated by co-incubation with actinomycin D. Nuclear run-on experiments demonstrated that the transcriptional rate of the gamma GCS-HS gene was increased by 3- or 6-h exposure to 10 microM DMNQ. Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity. Unlike simpler quinones, DMNQ cannot form a GSH conjugate. Thus, the induction of gamma GCS-HS gene transcription does not require formation of an electrophile-glutathione conjugate.


Parent Participation in Pediatric Intensive Care Unit Rounds via Telemedicine: Feasibility and Impact.
To evaluate feasibility and impact of telemedicine for remote parent participation in pediatric intensive care unit (PICU) rounds when parents are unable to be present at their child's bedside. Parents of patients admitted to a 14-bed PICU were approached, and those unable to attend rounds were eligible subjects. Nurse and physician caregivers were also surveyed. Parents received an iPad (Apple Inc, Cupertino, California) with an application enabling audio-video connectivity with the care team. At a predetermined time for bedside rounds with the PICU team, parents entered a virtual meeting room to participate. Following each telemedicine encounter, participants (parent, physician, nurse) completed a brief survey rating satisfaction (0?=?not satisfied, 10?=?completely satisfied) and disruption (0?=?no disruption at all, 10?=?very disruptive). A total of 153 surveys were completed following 51 telemedicine encounters involving 13 patients. Parents of enrolled patients cited work demands (62%), care for other dependents (46%), and transportation difficulties (31%) as reasons for study participation. The median levels of satisfaction and disruption were 10 (range 5-10) and 0 (range 0-5), respectively. All parents reported that telemedicine encounters had a positive effect on their level of reassurance regarding their child's care and improved communication with the care team. This proof-of-concept study indicates that remote parent participation in PICU rounds is feasible, enhances parent-provider communication, and offers parents reassurance. Providers reported a high level of satisfaction with minimal disruption. Technological advancements to streamline teleconferencing workflow are needed to ensure program sustainability.


Fate of benzotriazole and 5-methylbenzotriazole in recycled water recharged into an anaerobic aquifer: column studies.
The fate of benzotriazole (BTri) and 5-methylbenzotriazole (5-MeBT) was investigated under anaerobic conditions at nano gram per litre concentrations in large-scale laboratory columns to mimic a managed aquifer recharge replenishment strategy in Western Australia. Investigations of BTri and 5-MeBT sorption behaviour demonstrated mobility of the compounds with retardation coefficients of 2.0 and 2.2, respectively. Degradation processes over a period of 220 days indicated first order biodegradation of the BTri and 5-MeBT under anaerobic aquifer conditions after a biological lag-time of approximately 30-60 days. Biodegradation half-lives of 29 ± 2 and 26 ± 1 days for BTri and 5-MeBT were respectively observed, with no threshold effect to biodegradation observed at the 200 ng L(-1). The detection of degradation products provided further evidence of BTri and 5-MeBT biodegradation. These results suggested that if BTri and 5-MeBT were present in recycled water recharged to the Leederville aquifer, biodegradation during aquifer passage is likely given sufficient aquifer residence times or travel distances between recycled water injection and groundwater extraction.


Signals in vestibular nucleus mediating vertical eye movements in the monkey.
The action potentials of single neurons were recorded extracellularly throughout the rostral vestibular nuclei and subadjacent reticular formation in three alert, juvenile, rhesus monkeys. Neuronal responses were tested during a) sinusoidal pitch oscillations in darkness, b) cancellation of the vestibuloocular reflex (VOR) during similar oscillations by fixation of a target moving with the head, c) sinusoidal vertical smooth pursuit, d) vertical saccades, and e) fixation with the head stationary. Eye movements were measured using the magnetic field-search coil technique. Of the 527 neurons isolated, 318 responded to pitch oscillation and/or vertical eye movements. The latter cells could be classified into six categories. Of this group, 273 cells were recorded from for sufficient time to allow them to be fully tested and form the basis of this report. Cells were classified as follows: pure-vestibular cells with firing rates modulated only by head velocity (15%), vestibular-pause cells that were similar to the pure-vestibular cells but paused for saccades in all directions (10%), gaze-velocity cells that modulated their rates in proportion to vertical eye velocity in space (7%), position cells with rates modulated by changes in eye position in the head but that did not burst or pause during saccades (33%), position-burst cells that also carried an eye-position signal but did burst during saccades in one direction and paused in the opposite direction (15%), and position-vestibular-pause cells that carried signals proportional to eye position in the head and head velocity and paused during all saccades (20%). Most cells that carried an eye-position signal also carried an eye-velocity signal during pursuit. Position and position-burst cells could be divided into two subcategories. Position cells that also reported head velocity represented 20% of the total sample, while those without head-velocity signals made up the remaining 13%. Position-burst cells were divided into two subcategories based on their behavior during pitch oscillation in darkness. Both carried eye-velocity signals during pursuit, but only one type (8% of the total sample) also carried an eye-velocity signal during vestibular eye movements in the dark, while the other (7%) did not. Some cells in all six categories except the pure-vestibular cells responded antidromically to stimulation of the medial longitudinal fasciculus (MLF). Only the position-vestibular-pause, position-burst, and gaze-velocity cells, however, were judged to be commonly antidromically activated, suggesting that these three cell types are the major contributors to the MLF from the rostral vestibular nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)


Role of circulating granulocytes in sheep lung injury produced by phorbol myristate acetate.
Phorbol myristate acetate (PMA) and endotoxin cause pulmonary granulocyte sequestration and alteration in lung fluid and solute exchange in awake sheep that are felt to be analogous to the adult respiratory distress syndrome in humans. The basic hypothesis that PMA causes lung injury by activating circulating granulocytes has never been tested. The effects of infused PMA on lung mechanics and the cellular constituents of lung lymph have also not been reported. We therefore characterized the effects of intravenous PMA, 5 micrograms/kg, on lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, blood and lymph leukocyte counts, and plasma and lymph cyclooxygenase products of arachidonate metabolism in 10 awake sheep with normal granulocyte counts and after granulocyte depletion with hydroxyurea. PMA significantly altered lung mechanics from base line in both nongranulocyte depleted and granulocyte-depleted sheep. Dynamic compliance decreased by over 50% and resistance to airflow across the lungs increased over threefold acutely following PMA infusion in both sets of experiments. Changes in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, and plasma and lymph arachidonate metabolites were not significantly affected by greater than 99% depletion of circulating granulocytes. We conclude that the lung injury caused by PMA in chronically instrumented awake sheep probably is not a result of activation of circulating granulocytes.


Breast-feeding habits among Jewish and Arab mothers in Hadera County, Israel.
A survey of breast-feeding habits of Jewish and Arab mothers was carried out in Hadera county in Israel. Jewish mothers breast-fed their babies approximately 3 months, while Arab mothers did so for 5 months. The rate of breast-feeding among Jewish and Arab mothers was 84% and 94.4%, respectively. The results indicated that education, previous experience, enjoyment, husband's encouragement, previous information about the importance of breast-feeding, belief that breast-feeding strengthens the mother-child relationship, and the convenience of breast- over bottle-feeding were all factors that had an impact on breast-feeding habits among Jewish but not Arab mothers. Breast-feeding as a means of birth control, religion, and impairment of the breast's shape were factors that had no effect on either Arab or Jewish mothers. Complications during pregnancy and cesarean delivery decrease the probability of breast-feeding in Arab and Jewish mothers. Jewish mothers stopped breast-feeding because of insufficient milk, fatigue, work obligations, and physician's recommendation. Among Arab mothers the main reasons were insufficient milk, physician's recommendation, baby's refusal, and nipple problems. Jewish mothers who decided not to breast-feed stated that the reasons were previous experience with insufficient milk, nipple problems, and unpleasant feelings. The few Arab mothers who did not breast-feed cited medical or nipple problems.


Anterior Segment Optical Coherence Tomography of Tear Film and Cornea in Systemic Lupus Erythematosus Patients.
To study tear film and corneal thickness measurements in systemic lupus erythematosus (SLE) patients compared to age-matched controls using anterior segment optical coherence tomography (AS-OCT). This was a cross-sectional study. Study participants were divided into 3 groups: Group A: SLE patients with clinical dry eye, Group B: SLE patients without clinical dry eye and Group C: healthy controls. The lower tear meniscus parameters measured using AS-OCT were tear meniscus height (TMH), tear meniscus depth (TMD) and tear meniscus area (TMA). The central corneal and corneal epithelial thickness were automatically calculated. The study included 40 eyes in Group A, 60 in Group B, and 100 in Group C. Mean age was 26.9±6.6 years for Group A, 27.6±7.3 years for Group B and 35.7±9.2 years for Group C (p= 0.06). All subjects were females except for 1 male patient in Group A. Mean TMH, TMA and TMD in Group C were 487.7±185.6 µm, 0.068±0.040 mm2, and 341.2±99.1 µm, respectively, which was significantly higher compared to Group A (225.5±27.9 µm, 0.018±0.004 mm2 and 171.9±26.0 µm, respectively, all p < 0.001) and Group B (395.4±118.8 µm, p < 0.001; 0.05±0.04 mm2, p=0.016 and 280.6±93.4 µm, p < 0.001, respectively). Group B eyes also had significantly higher parameters compared to Group A (all p < 0.001). Mean corneal and epithelial thickness in Group C were 501.6±37.5 µm and 53.3±4.5 µm, respectively, which was significantly higher compared to Group A (496.1±24.1 µm, p=0.044 and 49.5±3.5 µm, p < 0.001, respectively) and Group B (504.2±22.03 µm, p=0.046 and 47.5±5.6 µm, p < 0.001, respectively). Group B eyes also had a significantly higher corneal thickness (p=0.031) and epithelial thickness (p=0.011) compared to Group A. We demonstrated significant reduction of tear meniscus dimensions, central corneal thickness and epithelial thickness in SLE patients compared to age-matched controls using AS-OCT.


[Novel therapeutics strategies in benign hypertrophy of prostate management].
The benign hypertrophy of prostate (BPH) is a progressive disease which can assign all the men to various degrees, involving an unquestionable repercussion on the quality of life. The two types of drugs commonly used for the treatment of the symptomatic BPH are the inhibitors of 5-alpha-reductase and the alpha-blockers. They last one relatively long action, making it possible to prevent occurred of complications like the acute urinary retention or the prostatic recourse to the surgery. A risk of progression and development of urinary complications can require an association of these two therapeutic agents in order to obtain a faster and durable improvement of symptomatology. The results of various studies are reported which highlight the interest of this therapeutic combination and underline the contribution of an inhibitor of 5-alpha-reductase among patients presenting a significant prostatic volume and a high PSA. Taking into account the risk of bad compliance and side effects with the long course, after a treatment combined for six months by tamsulosine and dutasteride, the stop of the alpha-blocker allows a maintenance of the situation obtained. Lastly, several clinical studies made it possible to draw the attention to the potentially preventive action of the inhibitors of 5-alpha-reductase in the development of the prostate cancer by its action to the DHT. These observational studies left the place to the PCPT study which made it possible to confirm a reduction in the prevalence of the cancer of prostate in a group of patients treated by finasteride compared with a placebo group. Currently, the preventive potential role of the dutasteride is also the subject of a study (REDUCE). These results are necessary in order to better define the interest and the role of the inhibition of 5-alpha-reductase in a strategic attitude of prostate cancer prevention.


The injured lung: clinical issues and experimental models.
Exposure of military and civilian populations to inhaled toxic chemicals can take place as a result of deliberate release (warfare, terrorism) or following accidental releases from industrial concerns or transported chemicals. Exposure to inhaled toxic chemicals can result in an acute lung injury, and in severe cases acute respiratory distress syndrome, for which there is currently no specific medical therapy, treatment remaining largely supportive. This treatment often requires intensive care facilities that may become overwhelmed in mass casualty events and may be of limited benefit in severe cases. There remains, therefore, a need for evidence-based treatment to inform both military and civilian medical response teams on the most appropriate treatment for chemically induced lung injury. This article reviews data used to derive potential clinical management strategies for chemically induced lung injury.


Oxidative Stress: A Putative Link Between Lower Urinary Tract Symptoms and Aging and Major Chronic Diseases.
Aging and major chronic diseases are risk factors for lower urinary tract symptoms (LUTS). On the other hand, oxidative stress (OS) is one of the fundamental mechanisms of aging and the development of chronic diseases. Therefore, OS might be a candidate mechanism linking these two clinical entities. This article aims to summarize the studies on the prevalence of LUTS, the role of OS in aging and chronic diseases, and the potential mechanisms supporting the putative link. A comprehensive literature search was performed to identify recent reports investigating LUTS and OS in major chronic diseases. In addition, studies on the impact of OS on the lower urinary tract, including bladder, urethra, and prostate, were collected and summarized. Many studies showed LUTS are prevalent in aging and major chronic diseases, including obesity, metabolic syndrome, diabetes, cardiovascular disease, hypertension, obstructive sleep apnea, autoimmune diseases, Alzheimer's disease, and Parkinson's disease. At the same time, OS is a key component in the pathogenesis of those chronic diseases and conditions. Recent studies also provided evidence that exacerbated OS can cause functional and/or structural changes in the bladder, urethra, and prostate, leading to LUTS. The reviewed data support the concept that OS is involved in multiple risk factors-associated LUTS, although further studies are needed to confirm the causative relationship. The specific ROS/RNS and corresponding reactions/pathways involved in chronic diseases and associated LUTS should be identified in the future and could serve as therapeutic targets.


Enzymatic hydrolysis of lignocellulosic materials: II. Experimental investigations of theoretical hydrolysis--process models for an increased enzyme recovery.
Stream pretreatment of wheat straw solubilized most of the xylan present. Xylose and other sugars were recovered by washing the substrate with water but only a minor part (34%) was monomeric. Treatment of this solutions with celulases and hemicellulases improved the yield of monomeric sugars to 69%, the main product being xylose. Some xylose was also obtained during enzymatic hydrolysis of the solid substrate although the pretreatment step contributed 64% (mean value) of total xylose formed. A reference model, No. 1, and two other models, Nos. 2 and 4, described in the first part of this article series (this issue) have been studied experimentally and results confirm the theoretical conclusions. An uninterrupted hydrolysis over a given time period leads to a lower degree of saccharification than when hydrolysate is withdrawn several times. Saccharification is also favored if the residue is removed at a late stage, i.e., at the end of the 24 h hydrolysis cycle. Extended recirculation of the enzymes during a 4 x 24-h experimental period gave the following average yields of saccharification on a 24-h basis: 65% (Reference), 73% (Model 2), and 79% (Model 4). It is concluded that enzyme recovery with model 4 is 70% or more, while the Reference and Model 2 attain a lower level of recovery. The design of an improved hydrolysis model is also discussed.


Prediction of oesophageal varices in patients with primary biliary cirrhosis by non-invasive markers.
Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured. Performance of non-invasive markers for OV was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). Oesophageal varices were found in 54 (50.9%) and large OV in 28 of the 106 patients. Variables found to differ significantly between patients with any grade or large and without OV included increased spleen length, increased portal vein diameter, low platelet count, and low levels of albumin or low γ-glutamyltranspeptidase (γ-GTP) values. Area under the receiver operating characteristic curve showed that spleen length (cutoff = 156.0) had AUC 0.753 (95% CI: 0.657-0.849), and high NPV (82.1%) to exclude any grade OV. Large OV could be excluded with NPV 70.6% by spleen length. Predictive risk factors that use readily available laboratory results and ultrasound scan results may reliably identify esophageal varices in patients with PBC.


One-point feedback control method for phenytoin dosage adjustment.
Routine clinical pharmacokinetic data collected from patients receiving phenytoin have been analysed to propose a new and simple equation to aid the dosage adjustment of this drug. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The rate equation for the elimination of phenytoin can be written as Do = kCssn, which fits the steady-state serum concentration (Css) and daily dose data (Do). The parameter n is the kinetic order and the parameter k is an arbitrary rate constant. From the above equation, D2 = D1C1 -nC2n can be derived, which forms the basis of predicting the dosage, D2, to obtain a desired Css, C2, using one initial Css, C1, obtained with an initial dose, D1, and using a population value of n. The value of n for phenytoin was estimated to be 0.312 in this study. The predictive performance of this equation was compared with the Richens and Dunlop nomogram and Bayesian feedback method using two or more steady-state concentration/dose pairs from each of 78 outpatients. This equation allowed the prediction of a dose needed to produce a desired steady-state concentration with errors comparable with the Bayesian feedback method for therapeutic drug monitoring.


Technical complications of implant-supported fixed partial dentures in partially edentulous cases after an average observation period of 5 years.
The purpose of this prospective long-term study was to evaluate the incidence of the most common technical problems, namely screw loosening, screw fracture, fracturing of veneering porcelain and framework fracture in implant-supported fixed partial dentures (FPDs), and assess the survival and success rate (event-free survival) after 5 years of function. In 76 partially edentulous patients, a total of 205 3i-implants (machined surface) were placed and restored with 112 implant-supported FPDs (46 single crowns, 81 splinted crowns, seven FPD bridges and 23 FPDs with cantilevers). The survival rate of FPDs supported by implants was 94.5% (CI-95: 90.1-98.8) after an average observation period of 5 years. The success rate (event-free survival) of the FPDs was 80% (CI-95: 87.3-72.7). After an observation period of 5 years the cumulative incidence of screw loosening was 6.7% (CI-95: 1.8-11.5), the cumulative incidence for screw fracture was 3.9% (CI-95: 0.1-7.7). Fracture of the veneering porcelain occurred in 5.7% (CI-95: 1.2-10.2) of all FPDs. Fracturing of the suprastructure framework was rare (1%; CI-95: 0-2.9). The overall complication incidence after 5 years was highest in the group of FPDs with cantilever, which showed the lowest success rate 68.6% (CI-95: 50-87.3), followed by single crowns (77.6%; CI-95: 53.3-100) and splinted crowns (86.1%; CI-95: 59.5-100). No complication occurred in FPD bridges. Fixed partial dentures supported by 3i-implants showed low technical complications rates, the most common being loosening of the abutment screw. Managing these complications can cause extra amount of chair-side time and patient dissatisfaction.


Prenatal ultrasound characterization of the suprarenal mass: distinction between neuroblastoma and subdiaphragmatic extralobar pulmonary sequestration.
With the increased routine use of prenatal ultrasonography, subdiaphragmatic masses in the fetus are identified more frequently. Suprarenal masses often are presumed to be neuroblastoma and are removed surgically postnatally. We sought to better understand the natural history of subdiaphragmatic extralobar pulmonary sequestration, and to determine if subdiaphragmatic extralobar pulmonary sequestration can be distinguished preoperatively from neuroblastoma. The literature was reviewed for cases of prenatally diagnosed suprarenal masses that proved ultimately to be either subdiaphragmatic extralobar pulmonary sequestration or neuroblastoma. The distinguishing features of the two lesions were identified and an algorithm was created on the basis of these distinctions. Prenatally diagnosed subdiaphragmatic extralobar pulmonary sequestration is no longer rare, with one case being reported for every 2.5 cases of neuroblastoma. On prenatal ultrasonography subdiaphragmatic extralobar pulmonary sequestration usually is echogenic, is left-sided, and can be identified in the second trimester. Neuroblastoma is most often cystic, right-sided, and identified in the third trimester. In summary, subdiaphragmatic extralobar pulmonary sequestration must be considered in the differential diagnosis of the suprarenal mass identified on prenatal ultrasonography. Using the algorithm which we propose, the correct diagnosis can be determined prenatally in 95% of patients.


Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study.
Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88-1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78-1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort (p = 0.0089). Fever within 24 h (p = 0.0092) and early skin and soft tissue infections (p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients.


PSA Response to Lenalidomide Therapy in a Pre-Treated Patient with Metastatic Prostate Cancer Refractory to Hormones and Chemotherapy: A Case Report.
Hormone-resistant prostate cancer (HRPC) occurs when prostate cancer is no longer responsive to hormone therapy. Treatment options are limited, and there is a clear necessity for therapies that improve outcome. Preclinical and clinical evidence supports the role of the immunomodulatory agent lenalidomide in HRPC. In this paper, we report that lenalidomide showed antitumoral activity in a patient with HRPC and bone metastases pre-treated with chemotherapy, decreased the PSA level and improved the patient's health status for the first 5 months. It is important to emphasize that it was not associated with hematologic toxicity.


[The Chance fracture and its variants].
Five cases of Chance fracture are reported, representing 0.6% of the spinal fractures treated at the Orthopedic Clinic of the University of Athens during the last 10 years. This fracture is frequently not recognized and diagnosis is delayed because of this fact. The mechanism and the clinical and radiological signs are discussed. A classification is proposed that contains four varieties of this lesion. The Chance fracture is discussed with regard to stability, as surgical stabilization is reserved for unstable fractures (types B, C, D).


Toward commercial applications of LED and laser-induced fluorescence techniques for food identity, quality, and safety monitoring: A review.
The assessment of food safety and quality is a matter of paramount importance, especially considering the challenges posed by climate change. Convenient, eco-friendly, and non-destructive techniques have attracted extensive attention in the food industry because they can retain food safety and quality. Fluorescence radiation, the process by which fluorophore emits light upon the absorption of ultraviolet or visible light, offers the advantages of high sensitivity and selectivity. The use of excitation-emission matrix (EEM) has been extensively explored in the food industry, but on-site detection of EEMs remain a challenge. To address this limitation, laser-induced fluorescence (LIF) and light emitting diode-induced fluorescence (LED-IF) have been implemented in many cases to facilitate the transition of fluorescence measurements from the laboratory to commercial applications. This review provides an overview of the application of commercially available LIF/LED-IF devices for non-destructive food measurement and recent studies that focus on the development of LIF/LED-IF devices for commercial applications. These studies were categorized into two stages: the preliminary exploration stage, which emphasizes the selection of an appropriate excitation wavelength based on the combination of EEM and chemometrics, and the pre-application stage, where experiments were conducted on scouting with specific excitation wavelength. Although commercially available devices have emerged in many research fields, only a limited number have been reported for use in the food industry. Future studies should focus on enhancing the diversity of test samples and parameters that can be measured by a single device, exploring the application of LIF techniques for detecting low-concentration substances in food, investigating more quantitative approaches, and developing embedded computing devices.


Molecular Dynamics Study of the Electric Double Layer and Nonlinear Spectroscopy at the Amorphous Silica-Water Interface.
The electrical double layer (EDL) at the amorphous silica-aqueous electrolyte interface is of long-standing scientific interest and current technological relevance. Using extensive molecular dynamics simulations, we have studied this EDL as a function of salt concentration for a silica surface charge density of -0.82e/nm2 (e = electron charge). The simulation results can be captured with a simple model by breaking the double-layer region into three zones: an inner region in which the Na+ counterion population is independent of [NaCl] and there are no Cl- co-ions, an intermediate region which hosts a population of nonexchangeable Na+ plus another group of Na+ and Cl- ions whose population is described by a Langmuir adsorption model, and an outer region where the ion distribution is well-described using the Poisson-Boltzmann theory. When the asymptotic [NaCl] >0.17 M, the adsorption of Na+ in the intermediate zone leads to an overcompensation of the negatively charged silica surface. Nonlinear spectroscopic experiments on the water-amorphous silica interface have been interpreted by others using the Gouy-Chapman model at low salt concentration and the constant capacitance model at high salt concentration. We discuss the applicability of these and other models and the implications for interpretation of the results of second harmonic and sum frequency generation experiments.


A case of nonseminomatous testicular tumor with liver metastases, treated by intrahepatic arterial cisplatinum-diaminedichloride infusion.
We report a case of nonseminomatous testicular tumor with lymph node involvement and multiple lung and liver metastases. The patient was considered to have a poor prognosis. He received systemic chemotherapy and cytoreductive surgery. Postoperatively a residual metastatic tumor in the liver was treated by intrahepatic arterial cisplatinum-diaminedichloride infusion. Follow-up observation has revealed no evidence of recurrence for 30 months since the last treatment.


Evaluation of Psychopathologies and Health-Related Quality of Life in Patients With Macular Amyloidosis.
Macular amyloidosis (MA) is a skin condition with predominance in young women. We aimed to evaluate quality of life (QoL) and psychopathologies in these patients. In this cross-sectional study, patients with MA referring to the Imam Reza Hospital, Mashhad during 2018-2020, and their matched controls were included. Participants completed the 36-item short form survey (SF-36), the revised symptom checklist-90 (SCL-90-R), and the dermatology life quality index (DLQI). Overall, 40 women with a mean age of 36.80±10.19 years were studied. In the MA group, the SF-36 score was lower (P<0.001), and the SCL-90-R score was higher (P<0.001). The DLQI score was correlated with age (r=0.447; P=0.048) and pruritus severity (r=0.776; P<0.001), and was lower in patients with uncovered lesions (P=0.005). MA was associated with impaired QoL, which was determined by pruritus severity and lesion location; these patients can benefit from psychiatric interventions in this regard.


Obstetrical nurses' attitude toward fetal monitoring.
A 24-item tool, using a Likert attitudinal scale, was developed to measure labor and delivery nurses' attitudes toward fetal monitoring and was administered to 124 nurses. For each of the 24 attitude statements, cumulative responses were over 50% positive at least. Fifty-two percent of the nurses felt that routine continuous monitoring of all labor patients would be ideal, and 88% felt that the fetal surveillance achieved by monitoring cannot be matched by intermittent auscultation.


Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model.
Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia. Liver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining. Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001). FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.


A Trainee-Led Quality Improvement Project Using Change Management Theory to Improve Bedside Rounding.
The coronavirus disease 2019 pandemic disrupted the practice of family-centered rounds. After the height of the pandemic, a trainee-led team identified a low percentage of bedside rounds on general pediatrics resident teams and combined a quality improvement framework and change management theory to increase bedside rounds. Initial efforts focused on a single general pediatrics team with the aim to increase bedside rounds from 18% to 50% within 6 months and sustain improvement for 12 months. A second aim was to increase bedside rounds from 7% to 50% for all general pediatrics resident teams within 6 months of spread. The Model for Improvement informed the identification of 3 primary drivers of bedside rounds: knowledge, culture, and logistics. Twelve plan-do-study-act (PDSA) cycles were implemented. Measures included the percentage of bedside rounds (primary outcome), caregiver attendance (secondary outcome), and nurse attendance and rounding time (balancing measures). For the initial team, 13 522 patient days were analyzed for the primary outcome with the average percentage of weekly bedside rounds increasing from 18% to 89% with 12 months of sustained improvement. The spread of the intervention to all teams revealed an increase in bedside rounding from 7% to 54%. The most significant improvements occurred after PDSA cycle 2, a communication bundle, and PDSA cycle 5, when the project was spread to all teams. This trainee-led initiative reveals the strength of the incorporation of change management theory within a quality improvement framework, resulting in rapid and sustainable increase in bedside rounds.


A holistic approach to development of diets for Ballan wrasse (Labrus berggylta) - a new species in aquaculture.
Wild wrasses are used for delousing of farmed salmon but increasing demands have prompted the salmon industry to develop cultures of Ballan wrasse. One of the bottlenecks has been nutrition and feed intake in the juvenile phase, while broodstock nutrition is considered critical for production of viable offspring. The present study was aimed at developing functioning ongrowing and broodstock diets for Ballan wrasse. In juveniles the best lengthwise growth was identified at 65% dietary protein, 12% lipid and 16% carbohydrate. To investigate if the requirements for the other nutrients were covered by the diets developed for the species, the nutrient composition in juveniles (whole body) and broodstock (female gonad) were analyzed and compared to the composition in wild fish. We found that the levels of the lipid soluble Vitamins A, K and D were lower in cultured than in wild fish, however, the requirements for these nutrients in Ballan wrasse are not known. Other candidate nutrients for more in-depth investigation are the bone minerals, zinc, taurine and fatty acids.


Follicular hybrid cyst on the cheek: a combination of infundibular, isthmic, and pilomatrical differentiation.
A hybrid cyst is a rare condition which includes any type of cyst arising from the various parts of the pilosebaceous unit. We report a case of hybrid cyst with infundibular, isthmic, and pilomatrical differentiation. A 12-year-old boy presented with a mass on the right cheek. The physical examination revealed an oval-shaped, dark-gray protruding mass with dimensions of 0.9 cm×0.6 cm that was non-tender to palpation. The mass was totally excised. The diagnosis of a hybrid cyst was confirmed by histological evaluation. It was a well-encapsulated mass and showed combined histologic features of infundibular, isthmus, and pilomatrical differentiation. The hybrid cyst is a follicular cyst that includes two or more components of a cystic lesion arising from the pilosebaceous unit. Occasionally, there have been reports of hybrid cysts consisting of two components in differentiation, but those showing more than two components of differentiation have been extremely rare. The pathogenesis of this unusual disease is not yet known.


Losing all sense: a case of meningeal carcinomatosis.
Meningeal carcinomatosis (MC) is diffuse infiltration of the meninges by metastatic carcinoma. Though a known complication of solid tumours, it is rarely seen as a presenting feature of such cancers. Here, the authors describe the case of a 64-year-old lady who presented with rapid-onset hearing loss and progressive visual loss, among other cranial nerve palsies. A primary non-small cell lung cancer was later identified by CT, but the diagnosis of MC was only confirmed after cytological analysis of a repeat lumbar puncture. Immunophenotyping of cells from the lung biopsy correlated with cells obtained from cerebrospinal fluid. In view of her rapid clinical deterioration, chemotherapy was not pursued, and the patient was transferred to a hospice 3 weeks after admission.


Increase of forage dryness induces differentiated anatomical response in the sheep rumen compartments.
The aim of this study was to investigate how the Surface Enlargement Factor (SEF) and the epithelial keratinization degree of sheep rumen change in response to phytomass production, and to forage fiber and water content during the pasture vegetative cycle. The study used eighteen sheep nourished with dry hay and cereals during the winter season and with fresh hay during the pasture vegetative cycle. We collected samples from rumen indicative regions for two consecutive years characterized by different rainfall and pasture productivity values. We evaluated the densities (D) of rumen papillae to estimate the rumen SEF, and the keratinization percentage of the epithelial lining; these parameters showed differentiated modifications in the four ruminal analyzed compartments in response to pasture seasonal conditions. In addition, we performed Canonical Redundancy Analysis (RDA) on the "keratinization and SEF" matrix constrained by phytomass, water, and crude fiber contents of pasture at different time in the two considered years to highlight how rumen features answer to pasture conditions. Atrium (A) and ventral sac (VS) keratinization showed a strict positive correlation to crude fiber, while SEF of VS was positively related to phytomass and forage water content. The degree of keratinization of the rumen VS epithelium proved to be a useful parameter for evaluating anatomical variations in the short term period related to pasture features; in addition, its monitoring could be carried out through biopsy, thus avoiding the killing of animals. The study also leads to the application of the 3Rs (Replacement; Reduction; and Refinement). Microsc. Res. Tech. 79:738-743, 2016. © 2016 Wiley Periodicals, Inc.


Location-Scale Matching for Approximate Quasi-Order Sampling.
Quasi-orders are reflexive and transitive binary relations and have many applications. Examples are the dependencies of mastery among the problems of a psychological test, or methods such as item tree or Boolean analysis that mine for quasi-orders in empirical data. Data mining techniques are typically tested based on simulation studies with unbiased samples of randomly generated quasi-orders. In this paper, we develop techniques for the approximately representative sampling of quasi-orders. Polynomial regression curves are fitted for the mean and standard deviation of quasi-order size as a function of item number. The resulting regression graphs are seen to be quadratic and linear functions, respectively. The extrapolated values for the mean and standard deviation are used to propose two quasi-order sampling techniques. The discrete method matches these location and scale measures with a transformed discrete distribution directly obtained from the sample. The continuous method uses the normal density function with matched expectation and variance. The quasi-orders are constructed according to the biased randomized doubly inductive construction, however they are resampled to become approximately representative following the matched discrete and continuous distributions. In simulations, we investigate the usefulness of these methods. The location-scale matching approach can cope with very large item sets. Close to representative samples of random quasi-orders are constructed for item numbers up to n = 400.


Simplified wave function models in thermochemical protocols based on bond separation reactions.
The ATOMIC protocol is a quantum-chemical thermochemistry protocol designed to obtain accurate atomization energies and derived heats of formation. It reduces errors of computationally tractable composite schemes through the use of bond separation reactions, which are implemented in a consistent ab initio framework. The present work explores possible simplification of previously introduced ATOMIC models. While coupled cluster calculations with singles and doubles excitations and perturbational treatments of connected triples excitations [CCSD(T)] are still required for high accuracy, basis-set truncations are possible in the CCSD-MP2 and CCSD(T)-CCSD components. The resulting models B4, B5, and B6 show root-mean-square (RMS) errors of only 0.21 to 0.46 kcal/mol for the AE set, which is a benchmark comprising complete-basis-set CCSD(T)(full) atomization energies of 73 neutral, closed-shell molecules composed of H, C, N, O, and F atoms. The evaluation of connected triples excitations can be avoided at medium levels of accuracy if the complete-basis-set MP2 energy is augmented with an empirically calibrated fraction of the difference between MP3 (or CCSD) and MP2 energies, calculated with small basis sets. The corresponding EMP3 and ECCSD models show RMS errors of 1.01 and 0.70 kcal/mol, respectively. Spin-component scaling is an option to rely entirely on the MP2 level of theory and still cut the RMS error of 4.38 kcal/mol by roughly a factor of 2 and achieve an accuracy comparable to accurate density functionals, such as M05-2X. The proposed new models are additionally tested with the HOF benchmark, a subset of G3/99 heats of formation that includes only neutral closed-shell molecules composed of H, C, N, O, and F atoms. The assessment shows that a number of experimental reference values are in error and should be replaced with more recent data. Results obtained with the new models are compared to original HOF (G3/99) reference data, to updated reference data, and to accurate ATOMIC/A theoretical data.


The Onset of IgG4-related Retroperitoneal Fibrosis under Administration of a TNF Inhibitor in a Rheumatoid Arthritis Patient.
An 80-year-old woman with rheumatoid arthritis during treatment with etanercept, a tumor necrosis factor (TNF) inhibitor, showed swelling of the salivary glands and retroperitoneal fibrosis, which was diagnosed as IgG4-related disease. Although some reports have shown the efficacy of TNF inhibitors for IgG4-related disease or retroperitoneal fibrosis, TNF inhibitors sometimes cause paradoxical reactions like psoriasis, and the mechanisms are considered to involve the upregulation of plasmacytoid dendritic cells and IFN-α, which is also common in patients with IgG4-related disease. This is a case report of IgG4-related retroperitoneal fibrosis with the possibility of a rare paradoxical reaction by a TNF inhibitor.


Effect of vitamin E supplementation on the regular treatment of seasonal allergic rhinitis.
Vitamin E supplementation is widely used in clinical practice for the prevention and treatment of different medical conditions. Evidence from basic science studies suggests that vitamin E may reduce immune allergic responses. However, only a few clinical studies of the effect of vitamin E on allergic conditions have been performed in patients with atopic dermatitis and asthma, and none have been performed in patients with allergic rhinitis. To determine the effect of high-dose vitamin E supplementation in combination with the usual ("real-life") treatment on the symptoms of seasonal allergic rhinitis during the pollen season. In a double-blind, placebo-controlled, randomized study, 112 patients with documented hay fever received either vitamin E (800 mg/d) or placebo in addition to their regular antiallergic treatment during the pollen season. Patients recorded their daily nasal and eye symptoms and their daily need for other medications to control allergic symptoms. Although no effect was observed on ocular symptoms, nasal symptom scores were lower in patients who received vitamin E supplementation during the hay fever season. However, there was no reduction in the percentage of days with serious symptoms or in the percentage of days that medications were used to control allergic symptoms during the pollen season. Vitamin E supplementation may be a valuable addition to the treatment of patients with seasonal allergic rhinitis. However, further clinical and basic science studies are needed to determine its real value.


Accuracy of Routine Endoscopy Diagnosing Colonic Ischaemia After Abdominal Aortic Aneurysm Repair: A Meta-analysis.
Colonic ischaemia (CI) is a devastating complication after abdominal aortic aneurysm (AAA) surgery. The aim of this review was to evaluate the diagnostic test accuracy of routine endoscopy in diagnosing CI after treatment for elective and acute AAA. The Pubmed and Embase database searches resulted in 1188 articles. Prospective studies describing routine post-operative colonoscopy or sigmoidoscopy after elective or emergency AAA repair were included. The study quality was assessed with the QUADAS-2 tool. Sensitivity and specificity forest plots were drawn. Diagnostic odds ratios were calculated by a random effect model. Twelve articles were included consisting of 718 AAA patients of whom 44% were treated electively, 56% ruptured and, 6% by endovascular repair. Of all patients, 20.8% were identified with CI (all grades), and 6.5% of patients had Grade 3 CI. The pooled diagnostic odds ratio for all grades of CI on endoscopy was 26.60 (95% CI 8.86-79.88). The sensitivity and specificity of endoscopy for detection of Grade 3 CI after AAA repair was 0.52 (95% CI, 0.31-0.73) and 0.97 (95% CI 0.95-0.99) respectively. The positive post-test probability is up to 60% in all kinds of AAA patients and 68% in ruptured AAA patients. Routine endoscopy is highly accurate for ruling out CI after AAA repair. Clinicians should be aware that endoscopy is less accurate in diagnosing the presence of the clinically relevant transmural CI. Endoscopy is a safe diagnostic test to use routinely as none of the studies reported adverse events.


Acute-on-chronic liver failure.
Acute-on-chronic liver failure combines an acute deterioration in liver function in an individual with pre-existing chronic liver disease and hepatic and extrahepatic organ failures, and is associated with substantial short-term mortality. Common precipitants include bacterial and viral infections, alcoholic hepatitis, and surgery, but in more than 40% of patients, no precipitating event is identified. Systemic inflammation and susceptibility to infection are characteristic pathophysiological features. A new diagnostic score, the Chronic Liver Failure Consortium (CLIF-C) organ failure score, has been developed for classification and prognostic assessment of patients with acute-on-chronic liver failure. Disease can be reversed in many patients, and thus clinical management focuses upon the identification and treatment of the precipitant while providing multiorgan-supportive care that addresses the complex pattern of physiological disturbance in critically ill patients with liver disease. Liver transplantation is a highly effective intervention in some specific cases, but recipient identification, organ availability, timing of transplantation, and high resource use are barriers to more widespread application. Recognition of acute-on-chronic liver failure as a clinically and pathophysiologically distinct syndrome with defined diagnostic and prognostic criteria will help to encourage the development of new management pathways and interventions to address the unacceptably high mortality.