The frequency of molecular detection of virulence genes encoding cytolysin A, high-pathogenicity island and cytolethal distending toxin of Escherichia coli in cases of sudden infant death syndrome does not differ from that in other infant deaths and healthy infants.
Consistent pathological findings in sudden infant death syndrome (SIDS) are seen which display similarities to the pathogenesis of toxaemic shock and/or sepsis. A key candidate infectious agent that is possibly involved is Escherichia coli, given its universal early colonization of the intestinal tract of infants and an increased frequency of toxigenic and mouse-lethal isolates from SIDS compared with comparison infants. An explanation for these findings has yet to be identified. Using PCR, we screened E. coli isolates from 145 SIDS and 101 dead control and healthy infants for three new candidate pathogenicity-related genes: clyA (cytolysin A), irp2 [high-pathogenicity island (HPI)-specific gene] and cdt (cytolethal distending toxin). The results failed to show a positive correlation with SIDS, instead proving that clyA and irp2 genes were common to the infant intestinal E. coli. Interestingly we observed a high rate of carriage of these two potentially pathogenic genes in E. coli from healthy infants in the absence of diarrhoeal disease, and we report that in a number of cases, the detection of HPI-specific genes was predictable by serotype. Despite the lack of associations defined so far, there remains the likelihood that genetic determinants influence the interactions between E. coli and the host, so these factors may be part of the multi-factorial aspect of SIDS.


[Central hemodynamics in conditions of combined intravenous anesthesia using propofol and ketamine in pediatric ophthalmology].
A total of 152 patients aged 4-14 years at risk of ASA I or II were examined. Planned operations were carried out: correction of myopia, strabismus, and eyelid ptosis. The patients were divided into 4 groups: 1) 54 patients operated on under combined anesthesia (propofol infusion and ketamine bolus), 2) 60 children operated on under combined anesthesia by ketamine and propofol infusions, 3) 24 patients operated on under ketamine + seduxene infusion narcosis, and 4) 34 children in whom ketamine and seduxen were injected in boluses. All operations were carried out under conditions of spontaneous respiration. Central hemodynamic parameters were studied by tetrapolar chest rheography with NCCOM3-R7 device (BIOMED). Methods of combined anesthesia with diprivan (propofol) are indicated for children subjected to ophthalmological surgery as methods with the minimum effects on the hemodynamics and ensuring adequate anesthesiological protection as regards the clinical and hemodynamic status.


Diagnostic and therapeutic issues for patients with advanced non‑small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (review).
The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.


Comparative Analysis of Manual Dexterity of Dental Students at Ajman University following One Academic Year of Preclinical Training Sessions: A Longitudinal Cohort Study.
Dental students must complete two stages of training, namely, preclinical training on phantom head models and clinical training on actual patients to acquire the practical skills required by their Bachelor of Dental Surgery program.Our objectives are to evaluate the level of improvement of the manual skills obtained by third-year dental students after one full academic year of preclinical training courses using dexterity tests under direct and indirect vision and to compare the improvement among male and female dental students under the same conditions. A total of 72 preclinical students participated in our cohort trial, each of whom was assigned a random identification number that was only known to the researchers. After the beginning of the academic year, the experiment was performed under identical conditions for both the O'Connor Tweezer Dexterity Test and the Purdue Pegboard Test. The examinations were conducted at two distinct times: T0 before phantom laboratory training (the beginning of preclinical sessions) and T1 after phantom laboratory training (9 months after T0). Signed-rank test of Wilcoxon over two separate periods (T0 and T1), comparisons were made between the direct and indirect visual dexterity test scores. In addition, the Mann-Whitney U test was used to compare results across gender. The statistical significance (p-value) was set at below 0.05 with a confidence level of 95%. A statistically significant difference was detected between the T0 and T1 assessments on the Purdue Pegboard Test and the O'Connor Tweezer Dexterity Test for all selected dentistry students in both direct and indirect conditions (p < 0.001). Further investigation in other dental departments or schools, particularly those with different entry standards, is required prior to making a definitive conclusion about the use of these dexterity assessments as predictors of prospective dental students' performance.


TGF-β, EMT, and resistance to anti-cancer treatment.
Transforming growth factor-β (TGF-β) signaling regulates cell-specific programs involved in embryonic development, wound-healing, and immune homeostasis. Yet, during tumor progression, these TGF-β-mediated programs are altered, leading to epithelial cell plasticity and a reprogramming of epithelial cells into mesenchymal lineages through epithelial-to-mesenchymal transition (EMT), a critical developmental program in morphogenesis and organogenesis. These changes, in turn, lead to enhanced carcinoma cell invasion, metastasis, immune cell differentiation, immune evasion, and chemotherapy resistance. Here, we discuss EMT as one of the critical programs associated with carcinoma cell plasticity and the influence exerted by TGF-β on carcinoma status and function. We further explore the composition of carcinoma and other cell populations within the tumor microenvironment, and consider the relevant outcomes related to the programs associated with cancer treatment resistance.


Level of sustained glycemic control and associated factors among patients with diabetes mellitus in Ethiopia: a hospital-based cross-sectional study.
The level of sustained glycemic control in patients with diabetes mellitus (DM) is a major determinant of the occurrence of both acute and chronic complications. However, information about the level of glycemic control among patients in the follow-up care at the University of Gondar Referral Hospital is scanty. The study assessed the degree of glycemic control and associated factors among diabetic patients in the study area. A hospital-based cross-sectional study was conducted at the University of Gondar Referral Hospital. All diabetic patients aged ≥18 years who visited the Diabetes Clinic in January and February 2013 for follow-up medical evaluation and medication participated in the study. Patients with glycosylated hemoglobin test (HbA1c) of ≥7% were classified as having a poor level of glycemic control. Propensity score was used to estimate the treatment effect. Multivariable logistic regression analysis was applied to determine the associated factors. Two hundred and fifty three (64.7%) of the 391 diabetic patients included in the study had a poor level of glycemic control, as evidenced by HbA1c ≥7%. Poor glycemic control was much higher among Type 1 patients (82.9%) compared with Type 2 patients (57.5%). Being on insulin treatment (AOR =2.51; 95% CI =1.25, 5.04) and reporting poor medication adherence (AOR =3.19; 95% CI =1.76, 5.80) were found to be associated with poor glycemic control among Type 2 DM patients. High waist circumference was inversely associated with a poor level of glycemic control in Type 1 DM patients (AOR =0.05; 95% CI =0.01, 0.85). The proportion of diabetic patients with a poor level of glycemic control is high. We recommend a comprehensive intervention to improve the overall treatment adherence with special attention to DM patients receiving insulin.


Thrombolysis Versus Nonthrombolyzed in Patients With Mild Strokes and Large Vessel Occlusions: Results of a Multicenter Stroke Registration.
The safety and efficacy of intravenous thrombolysis (IVT) in acute ischemic stroke patients with large vessel occlusions and mild neurological deficits are controversial. Data of stroke patients presenting with mild initial stroke, which was defined as the National Institutes of Health Stroke Scale score (NIHSS) ≤5 and large vessel occlusion, were extracted from a large provincewide stroke registry. A total of 619 IVT and 2170 non-IVT patients were identified in this study. IVT patients had higher rates of favorable functional outcome Modified Rankin Scale(mRS) ≤1 (74.6% vs. 70.6%; P=0.047), lower mRS scores (1 vs. 1, P=0.001), and higher NIHSS score decreased (1 vs. 0, P<0.001) at discharge compared with the non-IVT patients. The rates were similar in symptomatic intracranial hemorrhage (2.1% vs. 2.0%, P=0.853), severe systemic bleeding (0.8% vs. 0.6%, P=0.474), and mortality at discharge (0.2% vs. 0.2%, P=0.906) between the 2 groups. A multiple Logistic regression model found that age above 80 years [adjusted OR (aOR) 2.056 (95% CI, 1.125 to 3.756)], history of stroke [aOR 1.577 (95% CI, 1.303 to 1.910)], hyperlipidemia [aOR 2.156 (95% CI, 1.059 to 4.388)], high admission NIHSS score [aOR 1.564 (95% CI, 1.473 to 1.611)], and non-IVT [aOR 1.667 (95% CI, 1.337 to 2.077)] were independent risk factors for mRS >1. IVT administration is safe and effective in eligible acute ischemic stroke patients. Age above 80 years, with a history of stroke and hyperlipidemia, high admission NIHSS score, and non-IVT were independent risk factors for mRS >1 at discharge in these patients.


Mortality after acute myocardial infarction is lower in metropolitan regions than in non-metropolitan regions.
To compare in-hospital mortality for acute myocardial infarction (AMI) between metropolitan and non-metropolitan hospitals after adjustment for patients' severity; to examine the role of the use of effective cardiac medications in the possible mortality difference between these types of hospital. Retrospective cohort study. 47 acute public hospitals in metropolitan and non-metropolitan areas of New South Wales, Australia, taking part in the Acute Cardiac Care Project based on medical record review. 1665 patients with principal discharge diagnosis of AMI from February to June 1996. There was no difference in crude mortality rate (assessed as seven day mortality) between metropolitan and non-metropolitan hospitals (11.0% compared with 10.7% respectively, p=0.893). After adjustment for severity in a logistic regression model, the odds of death in non-metropolitan hospitals was significantly higher than in metropolitan hospitals (odds ratio = 1. 90; 95% CI 1.21, 3.23). The addition of the use of effective cardiac medications to the model resulted in the difference between hospital type becoming non-significant (odds ratio=1.09; 95% CI 0.57, 2.07). In-hospital mortality in non-metropolitan hospitals was higher than that in metropolitan hospitals, after adjustment for patients' severity. This might partly be explained by the difference in use of effective cardiac medications between hospital type.


Generation and characterization of fully human monoclonal antibodies against human Orai1 for autoimmune disease.
Calcium entry into T cells following antigen stimulation is crucial for nuclear factor of activated T cells (NFAT)-mediated T cell activation. The movement of calcium is mediated by calcium release-activated calcium (CRAC) channels. There are two key components of this channel: Orai1 is the pore-forming subunit located in the plasma membrane, and stromal interaction molecule 1 (STIM1) functions as a Ca(2+) sensor in the endoplasmic reticulum. A subset of human patients carry mutations in either STIM1 or Orai1 that affect protein function or expression, resulting in defective store-operated Ca(2+) influx and CRAC channel function, and impaired T cell activation. These patients suffer from a hereditary form of severe combined immune deficiency syndrome, highlighting the importance of the CRAC channel for T lymphocyte function in humans. Since autoreactive T cells play an important role in the development of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and organ transplantation, Orai1 becomes an attractive therapeutic target for ameliorating autoimmune disease. We developed a novel approach to inhibiting CRAC function by generating high-affinity fully human monoclonal antibodies to human Orai1. These antibodies inhibited ICRAC current, store-operated Ca(2+) influx, NFAT transcription, and cytokine release. These fully human antibodies to human Orai1 may represent a novel therapeutic approach for the treatment of autoimmunity.


Aminomethylphosphonic acid accumulation in plant species treated with glyphosate.
Aminomethylphosphonic acid (AMPA) is the most frequently detected metabolite of glyphosate in plants. The objective of this study was to determine if there is any correlation of metabolism of glyphosate to AMPA in different plant species and their natural level of resistance to glyphosate. Greenhouse studies were conducted to determine the glyphosate I 50 values (rate required to cause a 50% reduction in plant growth) and to quantify AMPA and shikimate concentrations in selected leguminous and nonleguminous species treated with glyphosate at respective I 50 rates. Coffee senna [ Cassia occidentalis (L.) Link] was the most sensitive ( I 50 = 75 g/ha) and hemp sesbania [ Sesbania herbacea (P.Mill.) McVaugh] was the most resistant ( I 50 = 456 g/ha) to glyphosate. Hemp sesbania was 6-fold and Illinois bundleflower [ Desmanthus illinoensis (Michx.) MacM. ex B.L.Robins. & Fern.] was 4-fold more resistant to glyphosate than coffee senna. Glyphosate was present in all plant species, and its concentration ranged from 0.308 to 38.7 microg/g of tissue. AMPA was present in all leguminous species studied except hemp sesbania. AMPA concentration ranged from 0.119 to 4.77 microg/g of tissue. Shikimate was present in all plant species treated with glyphosate, and levels ranged from 0.053 to 16.5 mg/g of tissue. Non-glyphosate-resistant (non-GR) soybean accumulated much higher shikimate than glyphosate-resistant (GR) soybean. Although some leguminous species were found to be more resistant to glyphosate than others, and there was considerable variation between species in the glyphosate to AMPA levels found, metabolism of glyphosate to AMPA did not appear to be a common factor in explaining natural resistance levels.


Investigation of an outbreak of Aleutian disease on a commercial mink ranch.
To determine the modes of transmission of Aleutian mink disease in a natural outbreak. 5,580 black and 9,087 brown mink from a ranch with an outbreak of Aleutian mink disease. Each mink had serum tested by counter-electrophoresis for Aleutian disease antibody. If a mink was seropositive for Aleutian disease virus by counter-electrophoresis, it was considered to be infected. Correlation of prevalence of the disease in kits and parents was determined. Spatial arrangement of infected and un-infected mink also was studied. Infected black dams were more likely to produce infected kits than were uninfected dams. In contrast, infected black sires were less likely to produce infected kits than were uninfected sires. In brown mink, in which prevalence of Aleutian disease was lower, transmission from infected dams and sires to kits was apparent. Infected black mink appeared to be more efficient in transmitting the disease horizontally than were infected brown mink. Although the spatial arrangement of infected mink indicated that mechanical transmission of the disease may be the most efficient mode of horizontal transmission, airborne transmission also occurred. Infected sires with nonprogressive Aleutian disease may confer protection to their kits in the face of a severe outbreak. Brown mink may be less able to transmit the virus horizontally than are black mink. Airborne transmission is substantial, but may not be as efficient as mechanical transmission.


Cep97 Is Required for Centriole Structural Integrity and Cilia Formation in Drosophila.
Centrioles are highly elaborate microtubule-based structures responsible for the formation of centrosomes and cilia. Despite considerable variation across species and tissues within any given tissue, their size is essentially constant [1, 2]. While the diameter of the centriole cylinder is set by the dimensions of the inner scaffolding structure of the cartwheel [3], how centriole length is set so precisely and stably maintained over many cell divisions is not well understood. Cep97 and CP110 are conserved proteins that localize to the distal end of centrioles and have been reported to limit centriole elongation in vertebrates [4, 5]. Here, we examine Cep97 function in Drosophila melanogaster. We show that Cep97 is essential for formation of full-length centrioles in multiple tissues of the fly. We further identify the microtubule deacetylase Sirt2 as a Cep97 interactor. Deletion of Sirt2 likewise affects centriole size. Interestingly, so does deletion of the acetylase Atat1, indicating that loss of stabilizing acetyl marks impairs centriole integrity. Cep97 and CP110 were originally identified as inhibitors of cilia formation in vertebrate cultured cells [6], and loss of CP110 is a widely used marker of basal body maturation. In contrast, in Drosophila, Cep97 appears to be only transiently removed from basal bodies and loss of Cep97 strongly impairs ciliogenesis. Collectively, our results support a model whereby Cep97 functions as part of a protective cap that acts together with the microtubule acetylation machinery to maintain centriole stability, essential for proper function in cilium biogenesis.


Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands.
The molecular mechanisms underlying the ability of muscarinic agonists to enhance the metabolism of inositol phospholipids were studied using rat parotid gland slices prelabelled with tracer quantities of [3H]inositol and then washed with 10 mM unlabelled inositol. Carbachol treatment caused rapid and marked increases in the levels of radioactive inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate and an accumulation of label in the free inositol pool. There were much less marked changes in the levels of [3H]phosphatidylinositol, [3H]phosphatidylinositol 4-phosphate and [3H]phosphatidylinositol 4,5-bisphosphate. At 5 s after stimulation with carbachol there were large increases in [3H]inositol 1,4-bisphosphate and [3H]inositol 1,4,5-trisphosphate, but not in [3H]inositol 1-phosphate. After stimulation with carbachol for 10 min the levels of radioactive inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate greatly exceeded the starting level of radioactivity in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively. When carbachol treatment was followed by addition of sufficient atropine to block all the muscarinic receptors the radioactive inositol phosphates rapidly returned towards control levels. The carbachol-evoked changes in radioactive inositol phosphate and phospholipid levels were blocked in the presence of 2,4-dinitrophenol (an uncoupler of oxidative phosphorylation). The results suggest that muscarinic agonists stimulate a polyphosphoinositide-specific phospholipase C and that these lipids are continuously replenished from the labelled phosphatidylinositol pool. [3H]Inositol 1-phosphate in the stimulated glands probably arises via hydrolysis of inositol 1,4-bisphosphate and not directly from phosphatidylinositol.


Resource Type and Availability Regulate Fungal Communities Along Arable Soil Profiles.
Soil fungi play an essential role in the decomposition of plant-derived organic material entering soils. The quality and quantity of organic compounds vary seasonally as well as with soil depth. To elucidate how these resources affect fungal communities in an arable soil, a field experiment was set up with two plant species, maize and wheat. Resource availability was experimentally manipulated by maize litter input on one half of these maize and wheat plots after harvest in autumn. Fungal biomass was determined by ergosterol quantification, and community structure was investigated by fungal automated ribosomal intergenic spacer analysis (F-ARISA). An annual cycle was assessed across a depth gradient, distinguishing three soil habitats: the plough layer, rooted soil below the plough layer, and deeper root-free soil. Fungal communities appeared highly dynamic and varied according to soil depth and plant resources. In the plough layer, the availability of litter played a dominant role in shaping fungal communities, whereas in the rooted layer below, community structure and biomass mainly differed between plant species. This plant effect was also extended into the root-free soil at a depth of 70 cm. In winter, the availability of litter also affected fungal communities in deeper soil layers, suggesting vertical transport processes under fallow conditions. These distinct resource effects indicate diverse ecological niches along the soil profile, comprising specific fungal metacommunities. The recorded responses to both living plants and litter point to a central role of fungi in connecting primary production and decomposition within the plant-soil system.


Khat chewing and mental distress: a community based study, in jimma city, southwestern ethiopia.
Khat (Catha edulis) contains a psychoactive substance, cathinone, which produces central nervous system stimulation analogous to amphetamine. It is believed that khat chewing has a negative impact on the physical and mental health of individuals as well as the socioeconomic condition of the family and the society at large. There is lack of community based studies regarding the link between khat use and poor mental health. The objective of this study was to evaluate the association between khat use and mental distress and to determine the prevalence of mental distress and khat use in Jimma City. A cross-sectional community-based study was conducted in Jimma City from October 15 to November 15, 2009. The study used a structured questionnaire and Self Reporting Questionnaire-20 designed by WHO and which has been translated into Amharic and validated in Ethiopia. By multi stage sampling, 1200 individuals were included in the study. Data analysis was done using SPSS for window version 13. The Khat use prevalence was found to be 37.8% during the study period. Majority of the khat users were males (73.5%), age group 18-24 (41.1%), Muslims (46.6%), Oromo Ethnic group (47.2%), single (51.4%), high school students (46.8%) and employed (80%). Using cut-off point 7 out of 20 on the Self Reporting Questionnaire-20, 25.8% of the study population was found to have mental distress. Males (26.6%), persons older than 55 years (36.4%), Orthodox Christians (28.4%), Kefficho Ethnic groups (36.4%), widowed (44.8%), illiterates (43.8%) and farmers (40.0%) had higher rates of mental distress. We found that mental distress and khat use have significant association (34.7% Vs 20.5%, P<0.001). There was also significant association between mental distress and frequency of khat use (41% Vs 31.1%, P<0.001) The high rate of khat use among the young persons calls for public intervention to prevent more serious forms of substance use disorders. Our findings suggest that persons who use khat suffer from higher rates of mental distress. However, causal association could not be established due to cross-sectional study design.


[Stage Ⅳ Breast Cancer with Difficulty in Initiating Chemotherapy-A Case Report].
We report a case of breast cancer(T4b[skin], N1, M1[lung], ER-, PR-, HER2 3+)in a 63-year-old woman with liver dysfunction of unknown cause(T-Bil 3.6mg/dL, ALP 3,483 U/L, AST 214 U/L, ALT 320 U/L, g / -GTP 1,943 U/L). Further- more, serum CA19-9(4,670 U/mL)and HbA1c(8.8%)levels were both elevated. First, she underwent chemotherapy with trastuzumab and capecitabine. Subsequently, liver dysfunction relieved gradually. CA19-9 and HbA1c levels were also decreased, but the tumor size was NC. Subsequently, trastuzumab, pertuzumab, and docetaxel were administered, as liver function became normal. The tumor shrank significantly after this treatment. Finally, she underwent mastectomy. Five years after the first visit, she has continued chemotherapy, with lung metastases almost scarred(CR).


[Functional transswitching of dominant motivation in the systems organization of behavioral acts].
In experiments on rabbits, instrumental and complex conditioned alimentary behaviour was studied at various ways of raising alimentary motivation to extreme levels. Animals behaviour in these conditions could acquire an outwardly non-motivated (in relation to alimentary need) character. It is suggested that these phenomena are based on the transformation of the dominant motivation and not on the mechanism of "shifted" activity. In experiments on rats, a long "pseudoreinforcement" of extremely enhanced motivation of thirst by ethanol led to profound changes of physiological and neurochemical properties of the primary drinking motivation centres of the hypothalamus. It is suggested that such changes underlie the realization of plasticity properties of the dominant motivation.


Feasibility of Machine Learning and Logistic Regression Algorithms to Predict Outcome in Orthopaedic Trauma Surgery.
Statistical models using machine learning (ML) have the potential for more accurate estimates of the probability of binary events than logistic regression. The present study used existing data sets from large musculoskeletal trauma trials to address the following study questions: (1) Do ML models produce better probability estimates than logistic regression models? (2) Are ML models influenced by different variables than logistic regression models? We created ML and logistic regression models that estimated the probability of a specific fracture (posterior malleolar involvement in distal spiral tibial shaft and ankle fractures, scaphoid fracture, and distal radial fracture) or adverse event (subsequent surgery [after distal biceps repair or tibial shaft fracture], surgical site infection, and postoperative delirium) using 9 data sets from published musculoskeletal trauma studies. Each data set was split into training (80%) and test (20%) subsets. Fivefold cross-validation of the training set was used to develop the ML models. The best-performing model was then assessed in the independent testing data. Performance was assessed by (1) discrimination (c-statistic), (2) calibration (slope and intercept), and (3) overall performance (Brier score). The mean c-statistic was 0.01 higher for the logistic regression models compared with the best ML models for each data set (range, -0.01 to 0.06). There were fewer variables strongly associated with variation in the ML models, and many were dissimilar from those in the logistic regression models. The observation that ML models produce probability estimates comparable with logistic regression models for binary events in musculoskeletal trauma suggests that their benefit may be limited in this context.


[Comparison of the thrombogenic properties of vascular wall after exposure to different lasers].
Quantitative thrombogenic assessment of the inner arterial surface after laser exposure was made in 33 experiments with peripheral arterial strips of dogs. In one experiment, vascular strips with native, mechanically de-endotheliazed or laser-damaged surface were consecutively placed in a platelet-enriched plasma recirculation system, after which platelet adhesion was estimated on vascular surface of the three types, using a scanning electron microscope, and the relative thrombogenic index was calculated. The laser models used included: 1) the AIG-neodymium model, 1.06 micron; 2) the argon model with visible (488 and 514 nm) and ultraviolet (350 nm) spectra; 3) the XeCl excimer type, 308 nm, as well as a preheated metal rod, imitating a ceramic or metal tip of the light guide outlet. The thrombogenic index was 83 +/- 7; 72 +/- 8; 57 +/- 9; 63 +/- 7 and 82 +/- 9%, respectively, for the above types of exposure, the differences being virtually insignificant. It is suggested that, irrespective of the type of laser employed, laser angioplasty should at least be accompanied with intensive anticoagulant therapy.


Characterization of a gene cluster and its putative promoter region for violacein biosynthesis in Pseudoalteromonas sp. 520P1.
Violacein, a purple pigment produced by some Gram-negative bacteria, has various physiological properties, such as antitrypanosomal and antitumoral activities. A gene cluster that encodes five enzymes, VioA-VioE, is responsible for synthesizing violacein. The expression of these enzymes is known to be regulated by a quorum sensing mechanism in Chromobacterium violaceum and Pseudoalteromonas sp. 520P1. To clarify the molecular mechanism of regulation of violacein synthesis, we cloned and characterized the gene cluster from Pseudoalteromonas sp. 520P1. A fosmid library of strain 520P1 was constructed and clones containing the gene cluster were isolated. The gene cluster was 7383 bp in length and encoded five enzyme genes, vioA-vioE. A putative promoter sequence was predicted in the upstream region of the cluster. In the promoter region, two contiguous palindromic sequences, a possible quorum sensing regulatory site, were found. However, the isolated Escherichia coli clones harboring the gene cluster and its upstream region were unable to produce violacein probably due to the lack of quorum sensing machinery for expression. To further examine the ability of vioA-vioE genes to synthesize violacein in vivo, the upstream promoter region was removed from the cluster and heterologous expression of the treated cluster was performed in E. coli using a recombinant pET vector with T7 promoter. Purple pigment was expressed, and the pigment was identified to be violacein using ultraviolet and visible light and HPLC analysis. These results will contribute to further studies regarding violacein biosynthesis and its mass production.


SCOPA-sleep and PDSS: two scales for assessment of sleep disorder in Parkinson's disease.
This study evaluated the comparative validity and usefulness of the Parkinson's Disease Sleep Scale (PDSS) and the Scales for Outcomes in PD-Sleep Scale (SCOPA-S), two disease-specific rating scales for assessing sleep disorders in Parkinson's disease (PD). Hoehn and Yahr staging (HY), SCOPA-Motor, Mini-Mental State Examination, Clinical Impression of Severity Index for PD, Hospital Anxiety and Depression Scale, EuroQoL, and SCOPA-Psychosocial, in addition to PDSS and SCOPA-S (night-time sleep (NS) and daytime sleepiness (DS) subscales), were applied to 187 consecutive PD patients. PDSS and SCOPA-S proved similar in acceptability, scaling assumptions, precision, and internal consistency (Cronbach's alpha = 0.82-0.84). Factor analysis revealed five separate factors for PDSS (67% of the variance) and one factor for each SCOPA-S subscale (60% of the variance for NS and 57% for DS). Correlation coefficient between PDSS and SCOPA-S NS was -0.60. Sleep scales correlated moderately with mood, low-to-moderate with HRQoL, and low with the rest of measures. PDSS and SCOPA-S DS discriminated between patients grouped by HY severity levels and disease duration. Cutoff points of 82/83 for PDSS and 6/7 for SCOPA-S NS were drawn to identify PD patients with sleep problems. Depression/anxiety scores explained 26% for PDSS and 22% for SCOPA-S NS scores. Both scales provide valid, reliable, and useful means to evaluate sleep disorders in PD. PDSS may be used to obtain a profile about potential causes of "bad sleep," but is barely useful to assess DS, whereas SCOPA-S assesses nocturnal sleep disorders and daytime somnolence at a similar extent, without exploring the potential causes.


Perfluorooctanoic acid (PFOA) removal by flotation with cationic surfactants.
Perfluorooctanoic acid (PFOA) was separated and recovered using a foam flotation process aided by cationic surfactants. The PFOA removal efficiency was in the following decreasing order: OTAB (C8TAB) > DTAB (C10TAB) > CTAB (C16TAB) > TBAB, which indicates that cationic surfactants with an alkyl chain that had a similar length to that of PFOA had higher affinities to PFOA. PFOA removal slightly decreased with increasing ionic strength of the surfactant but did not change with the pH. PFOA could be completely removed in 20 min with 1.25 mM of OTAB in actual wastewater. The energy yield value of foam flotation with a cationic surfactant was much higher than those of other methods, which means that using foam flotation with a cationic surfactant as the collector is a simple, fast, and energy-efficient method to separate and recover PFOA from dilute water solutions.


Exploring guideline adaptation strategy for Turkey: Is "ADAPTE" feasible or does it need adaptation as well?
Clinical Practice Guidelines are mostly developed by 3 methods; namely, de novo, adoption, and adaptation. Nonpublished studies and authors experience shows that most guidelines in Turkey are either by adoption or by adaptation. There is no available local tool for adaptation, so the process is not standardized and most of the time not explicitly defined. The objective of this study is to search for international guideline adaptation tools and test their feasibility in Turkish context, to serve a final goal of developing a unique local strategic tool for guideline adaptation. The methodological design of this study includes selection of an international tool for Clinical Practice Guideline adaptation, piloting this tool with selected Turkish guidelines, identifying the feasibility of this tool and exploring the needs for adaptation of the tool, drawing recommendations for adaptation of the strategies, and validation of the process by local experts. The study from planning phase to finalizing the guidance, including pilot studies and panel but excluding translation of ADAPTE, lasted 18 months. Nine researchers were involved in the adaptation process and 15 more experts were involved in the validation panel. Following the suggestions of the research team on modifications and validation through the expert panel; 2 steps of the ADAPTE toolkit were rejected, 2 steps were accepted by modification, 7 steps were accepted by additional recommendations. In addition, 2 tools were suggested to be added to the toolkit. This is the first study on adaptation of guidelines in Turkey. Pilot adaptation of 2 guidelines with ADAPTE revealed that ADAPTE is a useful and feasible tool in Turkish setting, but might require certain changes in recommendations and revision of tools.


Management of hemangioma of the liver: surgical therapy or observation?
Elective surgery for liver hemangioma is controversial. We reviewed long-term outcomes following elective hepatectomy or observation only for symptomatic and asymptomatic liver hemangioma. All patients (n = 307) with liver hemangioma referred to our hospital for surgical evaluation from January 1988 to December 2009 were identified, and imaging results, tumor characteristics, surgical indication, surgical mode, outcome of observation, clinical and/or postoperative outcome, and adverse events were retrospectively evaluated. Complete median follow-up for 246 patients was 124 months. Elective surgery was performed in 103 patients (symptomatic [n = 62] and asymptomatic [n = 41]). Postoperative morbidity occurred in 17 % of the patients and was significantly lower in asymptomatic patients (p = 0.002). No perioperative mortality was registered. Surgery relieved complaints in most (88 %) patients. In the observation group (n = 143), 56 % of patients had persistent or new onset of hemangioma-associated symptoms. Major hemangioma-related complications occurred in 12 patients (9 %) during the follow-up period, and 2 patients died after traumatic hemangioma rupture. Overall the rate of adverse events was by trend lower in the surgical group than in the observation group (35 versus 57 %; p = 0.08). The majority of patients with liver hemangioma can be safely managed by clinical observation. In a subset of patients, especially those with giant hemangioma and/or occurrence of symptoms, surgical treatment could be considered and is justified in high-volume centers.


Hypertrophic cardiomyopathy: a review.
Hypertrophic cardiomyopathy (HCM) is a relatively common disorder that anesthesiologists encounter among patients in the perioperative period. Fifty years ago, HCM was thought to be an obscure disease. Today, however, our understanding and ability to diagnose patients with HCM have improved dramatically. Patients with HCM have genotypic and phenotypic variability. Indeed, a subgroup of these patients exhibits the HCM genotype but not the phenotype (left ventricular hypertrophy). There are a number of treatment modalities for these patients, including pharmacotherapy to control symptoms, implantable cardiac defibrillators to manage malignant arrhythmias, and surgical myectomy and septal ablation to decrease the left ventricular outflow obstruction. Accurate diagnosis is vital for the perioperative management of these patients. Diagnosis is most often made using echocardiographic assessment of left ventricular hypertrophy, left ventricular outflow tract gradients, systolic and diastolic function, and mitral valve anatomy and function. Cardiac magnetic resonance imaging also has a diagnostic role by determining the extent and location of left ventricular hypertrophy and the anatomic abnormalities of the mitral valve and papillary muscles. In this review on hypertrophic cardiomyopathy for the noncardiac anesthesiologist, we discuss the clinical presentation and genetic mutations associated with HCM, the critical role of echocardiography in the diagnosis and the assessment of surgical interventions, and the perioperative management of patients with HCM undergoing noncardiac surgery and management of the parturient with HCM.


Current perspectives on reperfusion therapy for acute ST-segment elevation myocardial infarction: integrating pharmacologic and mechanical reperfusion strategies.
The therapeutic approach to patients with acute ST-segment elevation myocardial infarction (STEMI) has advanced rapidly over the past decade. Intravenous fibrinolytic therapy remains the most common form of reperfusion therapy worldwide, since fibrinolytics are associated with a dramatic reduction in mortality rates. However, primary percutaneous coronary intervention (PCI) is associated with improved outcomes and less bleeding complications compared with fibrinolytic therapy, but it is not widely available. Adjunctive therapies with intracoronary stents, glycoprotein (GP) IIb/IIIa inhibitors, and more potent antithrombin agents have shown great promise for the initial treatment of STEMI and have stimulated further investigation of combined pharmacological/mechanical reperfusion strategies that may be synergistic. Although the optimal combination of fibrinolytics, antiplatelet agents, antithrombins, and mechanical reperfusion at hospitals with and without primary PCI facilities remains elusive, results from recent studies suggest that such a combined approach may facilitate transfer of patients with STEMI from a referral hospital to an invasive hospital for definitive primary PCI after administration of a potent pharmacologic regimen designed to enhance early infarct-related artery reperfusion. Thus, as the reperfusion era continues to evolve, the ideal treatment strategy for patients with STEMI is being redefined to integrate pharmacologic and mechanical approaches to reperfusion.


[Computerized monitoring of patients in the intensive care and resuscitation unit].
Monitoring-computed systems were used during the therapeutic-diagnostic process at the resuscitation department of the All-Union Surgery Research Center in more than 1,000 patients who underwent operations on the heart, coronary arteries, bronchi, trachea, and esophagus. The main importance is attached to examination of the cardiorespiratory system. More than 90 derived parameters characterizing intracardiac hemodynamics, ventricular contractility, and oxygen transport are calculated according to special programs. For evaluation of the function of the lungs in an automated regimen, 32 parameters characterizing lung ventilation, gas exchange in the lungs, mechanism of respiration, and metabolism are calculated. Monitoring-computed care makes it possible to appraise the patient's condition in a given situation, the transient nature of changes in the physiological systems of the organism under the effect of therapy, and helps in choice of the optimal regimens of artificial lung ventilation and the methods of treatment. Computed appraisal of hemodynamics by means of the algorithm of the nearest point was found to be correct in 93% of cases. Storage of the results in the computer memory ensures an operative approach to information on any of the patients.


Investigation of protein refolding using a fractional factorial screen: a study of reagent effects and interactions.
A recurring obstacle for structural genomics is the expression of insoluble, aggregated proteins. In these cases, the use of alternative salvage strategies, like in vitro refolding, is hindered by the lack of a universal refolding method. To overcome this obstacle, fractional factorial screens have been introduced as a systematic and rapid method to identify refolding conditions. However, methodical analyses of the effectiveness of refolding reagents on large sets of proteins remain limited. In this study, we address this void by designing a fractional factorial screen to rapidly explore the effect of 14 different reagents on the refolding of 33 structurally and functionally diverse proteins. The refolding data was analyzed using statistical methods to determine the effect of each refolding additive. The screen has been miniaturized for automation resulting in reduced protein requirements and increased throughput. Our results show that the choice of pH and reducing agent had the largest impact on protein refolding. Bis-mercaptoacetamide cyclohexane (BMC) and tris (2-carboxyethylphosphine) (TCEP) were superior reductants when compared to others in the screen. BMC was particularly effective in refolding disulfide-containing proteins, while TCEP was better for nondisulfide-containing proteins. From the screen, we successfully identified a positive synergistic interaction between nondetergent sulfobetaine 201 (NDSB 201) and BMC on Cdc25A refolding. The soluble protein resulting from this interaction crystallized and yielded a 2.2 Angstroms structure. Our method, which combines a fractional factorial screen with statistical analysis of the data, provides a powerful approach for the identification of optimal refolding reagents in a general refolding screen.


[Primary immunodeficiency in adults: common variable immunodeficiency--clinical manifestations, immunological and genetic defects, treatment].
The most prevalent form of primary immunodeficiency with a total defect of antibody production in adults is common variable immunodeficiency (CVID). Compared to other forms of primary immunodeficiency, CVID is characterized by later onset of clinical manifestations represented by infectious, autoimmune and malignant diseases. To avoid development of complications and patient incapacitation, it is necessary to make an early diagnosis and initiate regular replacement therapy with intravenous immunoglobulins.


Effects of allergic inflammation of the nasal mucosa on the severity of rhinovirus 16 cold.
Despite the strong association of asthma exacerbations with rhinovirus (RV) infection, inoculation of asthmatic subjects with RV only causes small changes in lower airway function, suggesting that RV infection is not itself sufficient to provoke asthma exacerbations. Our purpose was to test whether allergic inflammation increases the airway response to RV infection. We compared the severity of RV type 16-induced colds in 2 groups of 10 subjects with allergic rhinitis. One group received 3 nasal challenges with allergen and the other received challenges with placebo over the week before nasal inoculation with RV type 16 (4000 tissue culture infective dose 50% per subject). Subjects kept symptom diaries and were assessed with spirometry, methacholine challenge, nasal lavage, and sputum induction on days 2, 4, 7, 10, 15, and 30 after inoculation. The 2 groups developed equal rates of infection (90%), similar cold symptoms (Jackson score median [interquartile range], 11 [6-33] vs 20.5 [6-42] for allergen and placebo groups respectively, P =.54), and similar changes in cellular profile and in IL-6 and IL-8 concentrations in nasal lavage fluid and induced sputum after RV inoculation. The incubation period was significantly longer in the allergen group (2.5 [1-5.5] vs 1 [1-1] day, P =.03) and the duration of cold symptoms was shorter (5 [4-7] vs 8.5 [6-10] days, P =.008). We also found an inverse correlation between the percent of eosinophils in nasal lavage fluid before inoculation and the severity of cold symptoms (r = -0.58, P =. 008). In subjects with allergic rhinitis, augmented nasal allergic inflammation before inoculation with RV type 16 does not worsen the severity of cold symptoms but delays their onset and shortens their duration.


Extrahepatic biliary atresia versus neonatal hepatitis. Review of 137 prospectively investigated infants.
In a prospective regional survey of neonatal hepatitis syndrome 32 infants had extrahepatic biliary atresia (EHBA) and 103 had hepatitis. No cause for the lesion was found in infants with extrahepatic biliary atresia, but in 32 with hepatitis a specific cause was identified, 24 having genetic deficiency of the serum protein alpha1-antitrypsin. No differences were observed in parental age, mother's health in pregnancy, month of birth, birth order, or sex of the infants. Familial idiopathic hepatitis occurred in 3 of 67 sibs of patients with idiopathic hepatitis, but the 33 sibs of EHBA patients had no liver disease. Of the infants with hepatitis, 36 were of low birthweight, less than 2.5 kg, and 23 were born prematurely. Infants with biliary atresia were all of normal birthweight and only one was born prematurely. Consideration of clinical and biochemical abnormalities in the first 2 months of life showed no differences between the two groups except that infants with EHBA were more commonly jaundiced from birth (80%) and had more frequently acholic stools (83%). The frequency of these features in patients with hepatitis being 68% and 52%. Standard tests of liver function were not discriminatory. Percutaneous liver biopsies were diagnostic in 75% of those with EHBA and in 92% of those with hepatitis. The I131 Rose Bengal faecal excretion was less than 10% in 26 of 28 infants with EHBA and in only 5 of 18 with hepatitis. These latter two investigations together allowed a correct preoperativer diagnosis of EHBA in all instances. Bile drainage was achieved surgically in only 3 cases. A major reason for these poor results may have been the late referral of cases for diagnosis and laparotomy, which should be performed as soon as the diagnosis is suspected and always by 70 days of age.


Effects of acute dilutional hyponatremia on acid-base changes and electrolyte concentrations in rats with bilateral renal pedicle ligation.
To describe the effects of increasing the extracellular fluid (ECF) volume by approximately 20% on acid-base changes and electrolyte concentrations in anesthetized rats. 18 adult male Sprague-Dawley rats. Rats were assigned to a control group (n = 6 rats) and a treatment group (12). All rats were anesthetized, and instrumentation and bilateral renal pedicle ligation were performed. The treatment group was infused IV with sterile water throughout a 30-minute period. Acid-base variables and concentrations of electrolytes, lactate, albumin, phosphorus, and hemoglobin were measured before (baseline) and 30 and 60 minutes after onset of infusion. Anion gap, strong ion difference, strong ion gap, and contributions of sodium, chloride, albumin, phosphorus, and lactate concentrations to base excess were calculated at each time point. Infusion of sterile water led to an increase in ECF volume of approximately 18%. This had no effect on acid-base balance, compared with that in control rats. Infusion of sterile water caused a significant decrease in sodium, chloride, ionized calcium, lactate, and albumin concentrations, compared with concentrations in the control group. Anion gap and calculated effects of sodium, chloride, albumin, and lactate concentrations on base excess at 60 minutes differed significantly between infused and control rats. Infusion of sterile water did not cause clinically relevant dilutional acidosis. The acidotic impact of water administration was offset by generation of new bicarbonate via carbonic acid equilibration and intracellular buffering in combination with the alkalotic effects of decreases in albumin, phosphorus, and lactate concentrations.


[Thoracoamniotic shunts and thoracocentesis in fetal therapy].
The not heart thoracic anomalies are caused by different abnormalities in the embryonic period with similar physiopathologic mechanisms. The prenatal treatment by means of decompression can improve substantially the clinical results in these patients. To evaluate, in a qualitative way, the effect of the thoracoamniotic shunts and thoracocentesis in the perinatal outcome in fetuses with not heart thoracic anomalies. Twenty-two articles were revised describing 308 cases of fetuses with congenital cystic adenomatoid malformation (CCAM), 25 cases of hydrothorax and 55 cases of broncopulmonary sequestration (BPS). We analyzed the adverse prognostic factors that indicated the treatment election in uterus as well as complications and perinatal outcome. Of the 388 cases of not heart thoracic anomalies, 250 fetuses were managed conservatively, and in 102 fetuses handling in uterus was started. Hydrops was identified as the worst prognostic factor to these fetuses, with a survival rate of 55.7%. The global survival was of 56.5% (155 cases) in the fetuses with CCAM, 98.1% (52 cases) in the fetuses with BPS and of 80% (20 cases) in the fetuses with hydrothorax. When having a fetus with some of these pathologies, it should be evaluated in an individual and integral way; according to the gestational age when diagnosed, as well as the type of lesion and the presence or absence of fetal dropsy to decide between fetal therapy or expectant handling.


Dilated gut conditions: diagnosis and management.
Dilatation of the gut occurs in response to either mechanical obstruction or aperistalsis. The hallmark features are symptoms of bowel obstruction with vomiting, constipation, abdominal pain and distension. This review will primarily deal with the non-mechanical causes of gut dilatation, both intestinal and colonic, and differentiate between acute and chronic presentations.


The state and significant drivers of health systems efficiency in Africa: A systematic review and meta-analysis.
Low-and-middle-income countries, especially in Africa, lack the capacity to adequately invest in health systems to attain universal health coverage (UHC). As such, countries must improve efficiency and provide more services within the available resources. This systematic review synthesised evidence on the efficiency of health systems in the African region and its drivers. We conducted a systematic literature review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Related studies were grouped and meta-analysed, while others were descriptively analysed. We employed a qualitative content synthesis for synthesising the drivers of efficiency. Overall, 39 studies met a predetermined inclusion criterion and were included from a possible 4 609 records retrieved through a rigorous search and selection process. Using a random effects restricted maximum likelihood method, the pooled efficiency score for the Africa region was estimated to be 0.77, implying that on the flip side, health system inefficiency across countries in the African region was approximately 23%. Across 22 studies that used data envelopment analysis to examine efficiency at the level of health facilities and sub-national entities, the efficiency level was 0.67. Facility-level studies tended to estimate low levels of efficiency compared to health system-level studies. Across the 39 studies, 21 significant drivers of inefficiency were reported, including population density of the catchment area, governance, health facility ownership, health facility staff density, national economic status, type of health facility, education index, hospital size and bed occupancy rate. With approximately 23% of the inefficiency of health systems in Africa, improving efficiency alone will yield an average of 34% improvement in resource availability, assuming all countries are performing similarly to the frontier countries. However, with the low level of health expenditure per capita in Africa, the efficiency gains alone will be insufficient to meet the minimum funding requirement for UHC. PROSPERO: CRD42022318122.


Microplastic ingestion decreases energy reserves in marine worms.
The indiscriminate disposal of plastic to the environment is of concern. Microscopic plastic litter (<5 mm diameter; 'microplastic') is increasing in abundance in the marine environment, originating from the fragmentation of plastic items and from industry and personal-care products [1]. On highly impacted beaches, microplastic concentrations (<1mm) can reach 3% by weight, presenting a global conservation issue [2]. Microplastics are a novel substrate for the adherence of hydrophobic contaminants [1], deposition of eggs [3], and colonization by unique bacterial assemblages [4]. Ingestion by indiscriminate deposit-feeders has been reported, yet physical impacts remain understudied [1]. Here, we show that deposit-feeding marine worms maintained in sediments spiked with microscopic unplasticised polyvinylchloride (UPVC) at concentrations overlapping those in the environment had significantly depleted energy reserves by up to 50% (Figure 1). Our results suggest that depleted energy reserves arise from a combination of reduced feeding activity, longer gut residence times of ingested material and inflammation.


SQUAMOUS CELL CARCINOMA IN TWO SNOW LEOPARDS (UNCIA UNCIA) WITH UNUSUAL AURICULAR PRESENTATION.
Squamous cell carcinoma (SCC) is well documented in snow leopards ( Uncia uncia ) and most common locations are oral, facial, or pedal. These two cases illustrate an unusual auricular presentation, which is more often reported in white domestic cats. The animals were aged and presented clinical signs of otitis such as head shaking and ear scratching. Clinical examinations showed auricular canal masses with chronic purulent otitis. In both cases, clinical deterioration led to euthanasia and histology of the ear canal was consistent with SCC and showed numerous vascular emboli. These cases illustrate an unreported aggressive localization for SCC in snow leopards, which should be included in the differential diagnosis of otitis in this species. Auricular SCC may be underdiagnosed as the ear canal is infrequently sampled for histopathology. This auricular localization should be considered when metastases are found upon necropsy without internal primary tumor.


A probabilistic framework for region-specific remodeling of dendrites in three-dimensional neuronal reconstructions.
Dendritic arborization is an important determinant of single-neuron function as well as the circuitry among neurons. Dendritic trees undergo remodeling during development, aging, and many pathological conditions, with many of the morphological changes being confined to certain regions of the dendritic tree. In order to analyze the functional consequences of such region-specific dendritic remodeling, it is essential to develop techniques that can systematically manipulate three-dimensional reconstructions of neurons. Hence, in this study, we develop an algorithm that uses statistics from precise morphometric analyses to systematically remodel neuronal reconstructions. We use the distribution function of the ratio of two normal distributed random variables to specify the probabilities of remodeling along various regions of the dendritic arborization. We then use these probabilities to drive an iterative algorithm for manipulating the dendritic tree in a region-specific manner. As a test, we apply this framework to a well-characterized example of dendritic remodeling: stress-induced dendritic atrophy in hippocampal CA3 pyramidal cells. We show that our pruning algorithm is capable of eliciting atrophy that matches biological data from rodent models of chronic stress.


Intraocular pressure measurements with Goldmann applanation tonometry and dynamic contour tonometry in eyes after IntraLASIK or LASEK.
Myopic photorefractive surgery induces a reduction in central corneal thickness, which may lead to underestimation of intraocular pressure. This retrospective clinical study compared intraocular pressure measurements obtained by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT-Pascal) in eyes undergoing myopic intralaser-assisted in situ keratomileusis (IntraLASIK) or laser-assisted subepithelial keratomileusis (LASEK). Of a total of 51 eyes, 21 underwent LASEK and 30 underwent IntraLASIK. By GAT, mean preoperative intraocular pressure was 16.2 ± 1.99 mmHg and postoperatively was 10.84 ± 1.45 mmHg. By DCT, mean preoperative intraocular pressure was 15.9 ± 2.08 mmHg and postoperatively was 16.1 ± 2.3 mmHg. Both preoperative and postoperative differences between measurements made by GAT and DCT were found to be statistically significant (P < 0.04 and P < 0.01, respectively). GAT and DCT readings were unaffected by type of surgery (P = 0.74 and P = 0.46, respectively). Postoperative GAT measurements were lower than those obtained by DCT. The difference between preoperative and postoperative DCT measurements was minimal, so DCT may be preferable for the measurement of intraocular pressure in eyes undergoing myopic IntraLASIK or LASEK.


Redox-dependent internalization of the purinergic P2Y6 receptor limits colitis progression.
After ligand stimulation, many G protein–coupled receptors (GPCRs) undergo β-arrestin–dependent desensitization, during which they are internalized and either degraded or recycled to the plasma membrane. Some GPCRs are not subject to this type of desensitization because they lack the residues required to interact with β-arrestins. We identified a mechanism of redox-dependent alternative internalization (REDAI) that promotes the internalization and degradation of the purinergic P2Y6 receptor (P2Y6R). Synthetic and natural compounds containing electrophilic isothiocyanate groups covalently modified P2Y6R at Cys220, which promoted the ubiquitylation of Lys137 and receptor internalization and degradation in various mouse and human cultured cell lines. Endogenous electrophiles also promoted ligand-dependent P2Y6R internalization and degradation. P2Y6R is highly abundant in inflammatory cells and promotes the pathogenesis of colitis. Deficiency in P2Y6R protected mice against experimentally induced colitis, and mice expressing a form of P2Y6R in which Cys220 was mutated to nonmodifiable serine were more sensitive to the induction of colitis. Several other GPCRs, including A2BAR, contain cysteine and lysine residues at the appropriate positions to mediate REDAI, and isothiocyanate stimulated the internalization of A2BAR and of a form of P2Y2R with insertions of the appropriate residues. Thus, endogenous and exogenous electrophiles may limit colitis progression through cysteine modification of P2Y6R and may also mediate internalization of other GPCRs.


Altered iron metabolism in lymphocytes from subjects with restless legs syndrome.
Studies using cerebrospinal fluid, magnetic resonance imaging, and autopsy tissue have implicated a primary role for brain iron insufficiency in restless legs syndrome (RLS). If the abnormalities of brain iron regulation reflect a basic disturbance of iron metabolism, then this might be expressed at least partially in some peripheral systems. Thus the study aim was to determine whether patients with RLS and control subjects show differences in lymphocyte iron regulator proteins. Fasting morning blood samples were used to obtain common serum measures of iron status and to determine lymphocyte iron management proteins. Twenty-four women with early-onset RLS and 25 control women without RLS symptoms were studied. RLS and control subjects were matched for age, hemoglobin, and serum iron profile. However, transferrin receptor (TfR) and DMT1 (divalent metal transporter 1 protein) levels in lymphocytes were significantly higher for RLS patients than for controls. No significant differences in ferritin subtypes or transferrin levels were found. No significant correlations were found between lymphocyte and serum indices of iron status. RLS lymphocytes showed an increase in ferroportin, implying increased cellular iron excretion, in the face of increased iron need (increased TfR and DMT1). In the absence of changes in H-ferritin, the findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover. The lack of any significant correlation between serum and lymphocyte iron indices indicates that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.


Cripto forms a complex with activin and type II activin receptors and can block activin signaling.
Activin, nodal, Vg1, and growth and differentiation factor 1 are members of the transforming growth factor beta superfamily and signal via the activin type II (ActRII/IIB) and type I (ALK4) serine/threonine kinase receptors. Unlike activins, however, signaling by nodal, Vg1, and growth and differentiation factor 1 requires a coreceptor from the epidermal growth factor-Cripto-FRL1-Cryptic protein family such as Cripto. Cripto has important roles during development and oncogenesis and binds nodal or related ligands and ALK4 to facilitate assembly of type I and type II receptor signaling complexes. Because Cripto mediates signaling via activin receptors and binds directly to ALK4, we tested whether transfection with Cripto would affect the ability of activin to signal and/or interact with its receptors. Here we show that Cripto can form a complex with activin and ActRII/IIB. We were unable to detect activin binding to Cripto in the absence of ActRII/IIB, indicating that unlike nodal, activin requires type II receptors to bind Cripto. If cotransfected with ActRII/IIB and ALK4, Cripto inhibited crosslinking of activin to ALK4 and the association of ALK4 with ActRII/IIB. In addition, Cripto blocked activin signaling when transfected into either HepG2 cells or 293T cells. We have also shown that under conditions in which Cripto facilitates nodal signaling, it antagonizes activin. Inhibition of activin signaling provides an additional example of a Cripto effect on the regulation of signaling by transforming growth factor-beta superfamily members. Because activin is a potent inhibitor of cell growth in multiple cell types, these results provide a mechanism that may partially explain the oncogenic action of Cripto.


The impact of light intensity on shade-induced leaf senescence.
Plants often have to cope with altered light conditions, which in leaves induce various physiological responses ranging from photosynthetic acclimation to leaf senescence. However, our knowledge of the regulatory pathways by which shade and darkness induce leaf senescence remains incomplete. To determine to what extent reduced light intensities regulate the induction of leaf senescence, we performed a functional comparison between Arabidopsis leaves subjected to a range of shading treatments. Individually covered leaves, which remained attached to the plant, were compared with respect to chlorophyll, protein, histology, expression of senescence-associated genes, capacity for photosynthesis and respiration, and light compensation point (LCP). Mild shading induced photosynthetic acclimation and resource partitioning, which, together with a decreased respiration, lowered the LCP. Leaf senescence was induced only under strong shade, coinciding with a negative carbon balance and independent of the red/far-red ratio. Interestingly, while senescence was significantly delayed at very low light compared with darkness, phytochrome A mutant plants showed enhanced chlorophyll degradation under all shading treatments except complete darkness. Taken together, our results suggest that the induction of leaf senescence during shading depends on the efficiency of carbon fixation, which in turn appears to be modulated via light receptors such as phytochrome A.


Discriminating Between Legitimate and Predatory Open Access Journals: Report from the International Federation for Emergency Medicine Research Committee.
Open access (OA) medical publishing is growing rapidly. While subscription-based publishing does not charge the author, OA does. This opens the door for "predatory" publishers who take authors' money but provide no substantial peer review or indexing to truly disseminate research findings. Discriminating between predatory and legitimate OA publishers is difficult. We searched a number of library indexing databases that were available to us through the University of California, Irvine Libraries for journals in the field of emergency medicine (EM). Using criteria from Jeffrey Beall, University of Colorado librarian and an expert on predatory publishing, and the Research Committee of the International Federation for EM, we categorized EM journals as legitimate or likely predatory. We identified 150 journal titles related to EM from all sources, 55 of which met our criteria for OA (37%, the rest subscription based). Of these 55, 25 (45%) were likely to be predatory. We present lists of clearly legitimate OA journals, and, conversely, likely predatory ones. We present criteria a researcher can use to discriminate between the two. We present the indexing profiles of legitimate EM OA journals, to inform the researcher about degree of dissemination of research findings by journal. OA journals are proliferating rapidly. About half in EM are legitimate. The rest take substantial money from unsuspecting, usually junior, researchers and provide no value for true dissemination of findings. Researchers should be educated and aware of scam journals.


Treatment of borderline personality disorder with risperidone.
Of the various Axis II disorders, borderline personality disorder (BPD) is among the more critical to treat. There are at present few results in terms of clinical outcome with the psychotropic agents available. Possible targets for pharmacotherapy are affective symptoms, cognitive disturbances, and impulsive, self-injurious behaviors. In previous studies, atypical antipsychotics at low-to-moderate doses provided symptom reduction with good tolerability. Our purpose was to assess the efficacy of risperidone in BPD, focusing on its effects on impulsive-aggressive behavior. Fifteen BPD outpatients (DSM-IV diagnosis) with prominent histories of aggressive behavior were included in an 8-week open-label study with risperidone at low-to-moderate doses. Axis II codiagnoses included antisocial personality disorder (N = 4). Exclusion criteria included current Axis I diagnosis or any major medical or neurologic illness. Efficacy measures were the 21-item Hamilton Rating Scale for Depression, the Brief Psychiatric Rating Scale, the DSM-IV Global Assessment of Functioning, and the self-rated Aggression Questionnaire. Evaluations were carried out at baseline and at the end of the treatment. Thirteen patients completed the trial; 2 patients dropped out because of lack of compliance. Final mean dose of risperidone was 3.27 mg/day. There was a significant (p = .0057) reduction in aggression based on Aggression Questionnaire scores. This amelioration was coupled with an overall improvement, including a reduction in depressive symptoms and an increase in energy and global functioning. Risperidone at low-to-moderate doses can improve BPD symptomatology. Further studies are needed to explore the efficacy of risperidone versus placebo as well as in comparison to other potential treatments for BPD.


Assessment in the context of uncertainty using the script concordance test: more meaning for scores.
The Script Concordance Test (SCT) uses authentic, ill-defined clinical cases to compare medical learners' judgment skills with those of experienced physicians. SCT scores are meant to measure the degree of concordance between the performance of examinees and that of the reference panel. Raw test scores have meaning only if statistics (mean and standard deviation) describing the panel's performance are concurrently provided. The purpose of this study is to suggest a method for reporting scores that standardizes panel mean and standard deviation, allowing examinees to immediately gauge their performance relative to panel members. Based on a statistical method of standardization, a new method for computing SCT scores is described. According to this method, test raw scores are converted into a scale in which the panel mean is set as the value of reference, and the standard deviation of the panel serves as a yardstick by which examinee performance is measured. The effect of this transformation on four data sets obtained from SCTs in radio-oncology, surgery, neurology, and nursing is discussed. This transformation method proposes a common metric basis for reporting SCT scores and provides examinees with clear, interpretable insights into their performance relative to that of physicians of the field. We recommend reporting SCT scores with the mean and standard deviation of panel scores set at standard scores of 80 and 5, respectively. Beyond SCT, our transformation method may be generalizable to the scoring of other test formats in which the performance of examinees and those of a panel of reference undertaking the same cognitive tasks are compared.


Markers of airway inflammation in preschool wheezers.
Airways inflammation markers may help in predicting prognosis, in diagnosis and in monitoring respiratory diseases. Inflammation markers specific for certain cells may indicate the nature of the inflammatory processes, whilst others indicate stage and intensity. Intercellular adhesion molecule 1 (ICAM-1) helps to establish contact between the antigen-presenting cell and T-lymphocytes. Soluble serum ICAM-1 is increased in developing chronic lung disease of the newborn and atopic bronchial asthma. ICAM-1 is also the major human rhinovirus receptor. Interleukin 4 and interferon-gamma regulate the immunoglobulin E response, are difficult to measure in serum, and most groups employ stimulated cell cultures. These early inflammation markers may have predictive value. The leukotrienes are released from mast cells and eosinophils. Leukotriene (LT) B4 may be analysed in serum, whereas the cysteinyl leukotrienes, LTC4, LTD4, LTE4, may be assessed in urine. Serum LTB4 and urinary LTE4 have been found to be elevated during acute wheezy exacerbations. Tryptase is released from mast cells and is elevated in serum during acute anaphylaxis. However, tryptase has not been found to be related to inflammatory activity under other conditions. Myeloperoxidase is released from neutrophils, and serum levels are elevated in asthma, respiratory infections and other chronic lung diseases. The eosinophil markers eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflect eosinophil activation. ECP in serum and EPX in urine are elevated in asthma, atopic eczema and other conditions with eosinophil activation. They are related to symptom activity in asthma and atopic eczema and are influenced by anti-inflammatory therapy. In early wheezing, serum ECP may have predictive value. Serum ECP is dependent upon sampling procedures. Nitrogen oxide in exhaled air reflects inflammatory activity in asthma, and is influenced by anti-inflammatory therapy. However, in young children there are sampling difficulties.


CD8 T cells utilize TRAIL to control influenza virus infection.
Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8(+) T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8(+) T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8(+) T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8(+) T cell cytotoxicity in TRAIL(-/-) mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8(+) T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8(+) T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL(+/+) but not TRAIL(-/-) CD8(+) effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8(+) T cell-mediated cytotoxicity, leading to more severe influenza infections.


Clinical impact of human parainfluenza virus infections before and during the COVID-19 pandemic in Southern China.
Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Non-pharmaceutical interventions (NPIs) were widely administered to combat the pandemic of the coronavirus disease 2019 (COVID-19). Respiratory specimens were obtained from 10,454 hospitalized children with ARTIs to detect HPIV. We investigated differences in epidemiological and clinical characteristics of HPIV infections before (2017-2019) and during the COVID-19 pandemic (2020-2022). HPIVs were detected in 392 (3.75%, 392/10,454) patients, of whom 70 (17.86%), 48 (12.24%), and 274 (69.90%) were positive for HPIV1, HPIV2, and HPIV3, respectively. Detection rates of HPIV3 were higher in 2020-2022 than in 2017-2019 (3.38% vs. 2.24%). The seasonal distribution of HPIV1 showed no difference, but HPIV3 peaked between September and December during the COVID-19 pandemic, which differed from previous epidemiological patterns. Compared to the period before the COVID-19 pandemic, there has been a noticeable decrease in the incidence of asthma, moist rales, and emesis in patients infected with HPIV1 and in asthma, expectoration, and severe pneumonia in patients infected with HPIV3 during 2020-2022. The detection rates of HPIV increased in Southern China during the COVID-19 outbreak, which underlines the importance of continuous surveillance of HPIV in the next epidemic season.


Idiopathic pulmonary fibrosis in a Christmas Island nuclear test veteran.
We describe the case of a 71-year-old man with idiopathic pulmonary fibrosis (usual interstitial pneumonia (UIP) pattern) diagnosed on clinical, radiological and lung function criteria, in accordance with the American Thoracic Society/European Respiratory Society consensus criteria (2000), who had been in close proximity to three atmospheric nuclear bomb blasts during military service in 1957. He does not have clubbing and clinically and radiologically his lung disease is stable. He also has bladder carcinoma and carotid arteriosclerosis, both recognised consequences of radiation injury. This is the first reported case of UIP in a nuclear test veteran. Awareness of this potential association is important given the current attempts of the British Nuclear Test Veterans Association to gain compensation for claimed injuries.


Early-return-to-work in the context of an intensification of working life and changing employment relationships.
Many Western welfare states have introduced early-return-to-work policies, in which getting sick-listed people back to work before they have fully recovered is presented as a rather unproblematic approach. This reflects a belief in the ability of employers and the labour market to solve sickness absence. Against this background, the aim of this study was to analyse return-to-work practice in local workplace contexts, in relation to Swedish early-return-to-work policy. Semi-structured interviews were conducted with 18 matched pairs of workers and managers. The material, comprising a total of 36 interviews, was analysed using qualitative content analysis. Three main themes were identified: (1) intensive workplaces and work conditions (2) employer support-a function of worker value and (3) work attachment and resistance to job transition. The results reflected the intensity of modern working life, which challenged return-to-work processes. Managers had different approaches to workers' return-to-work, depending on how they valued the worker. While managers used the discourse of 'new opportunities' and 'healthy change' to describe the transition process (e.g. relocation, unemployment and retirement), workers regularly experienced transitions as difficult and unjust. In the context of early-return-to-work policy and the intensity of modern working life, a great deal of responsibility was placed on workers to be adaptable to workplace demands in order to be able to return and stay at work. Overall, this study illustrates an emerging social climate where sick-listed workers are positioned as active agents who must take responsibility for sick leave and return-to-work process.


Towards an Understanding of Molecule Capture by the Antennae of Male Beetles Belonging to the Genus Rhipicera (Coleoptera, Rhipiceridae).
Working on the hypothesis that an important function of the lamellate antennae of adult male beetles belonging to the genus Rhipicera is to detect scent associated with female conspecifics, and using field observations, anatomical models derived from X-ray microcomputed tomography, and scanning electron microscopy, we have investigated the behavioral, morphological, and morphometric factors that may influence molecule capture by these antennae. We found that male beetles fly upwind in a zigzag manner, or face upwind when perching, behavior consistent with an animal that is tracking scent. Furthermore, the ultrastructure of the male and female antennae, like their gross morphology, is sexually dimorphic, with male antennae possessing many more of a particular type of receptor-the sensillum placodeum-than their female counterparts (approximately 30,000 vs. 100 per antenna, respectively). Based on this disparity, we assume that the sensilla placodea on the male antennae are responsible for detecting scent associated with female Rhipicera beetles. Molecule capture by male antennae in their alert, fanned states is likely to be favoured by: (a) male beetles adopting prominent, upright positions on high points when searching for scent; (b) the partitioning of antennae into many small segments; (c) antennal morphometry (height, width, outline area, total surface area, leakiness, and narrow channels); (d) the location of the sensilla placodea where they are most likely to encounter odorant molecules; and (e) well dispersed sensilla placodea. The molecule-capturing ability of male Rhipicera antennae may be similar to that of the pectinate antennae of certain male moths.


Human dermal fibroblasts do not exhibit directional migration on collagen I in direct-current electric fields of physiological strength.
Endogenous electric fields are generated lateral to skin wounds, with the cathodal pole of the field residing in the center of the wound. These fields are thought to be an important mechanism in guiding the migration of keratinocytes and other cells into wounds to effect healing. In this work, human dermal fibroblasts were exposed to direct current electric fields of physiological strength, and their migrational behavior was quantitated. Only random migration of human dermal fibroblasts was observed in direct-current electric fields under conditions that support the directional migration of human epidermal keratinocytes. Additionally, neither the presence of serum nor serum plus additional Mg++ in the experimental medium supported directional migration. Migratory rates of fibroblasts varied depending on the experimental medium used: in serum-containing medium the average velocity was as low as 0.23 micro m/min, while in serum-free keratinocyte medium the average velocity was as high as 0.36 micro m/min. These studies suggest that dermal fibroblasts do not respond to the endogenous electric field of a wound, and use other migratory cues to direct their movement into the wound bed.


The role of individual cysteine residues in the structure and function of the v-sis gene product.
The v-sis oncogene encodes a platelet-derived growth factor (PDGF)-related product whose transforming activity is mediated by its functional interaction with the PDGF receptor. PDGF, as well as processed forms of the v-sis gene product, is a disulfide-linked dimer with eight conserved cysteine residues in the minimum region necessary for biologic activity. Site-directed mutagenesis of the v-sis gene revealed that each conserved cysteine residue was required directly or indirectly for disulfide-linked dimer formation. However, substitution of serine for cysteine codons at any of four positions had no detrimental effect on transforming activity of the encoded v-sis protein. These results establish that interchain disulfide bonds are not essential in order for this protein to act as a functional ligand for the PDGF receptor. The remaining four substitutions of serine for cysteine each inactivated transforming function of the molecule. In each case this was associated with loss of a conformation shown to involve intramolecular disulfide bonds. These studies provide insight into the role of individual cysteine residues in determining the structure of the sis/PDGF molecule critical for biological activity.


Parental assessment of adolescent quality of life: can it replace self-assessment?
(a) To compare the agreement between adolescent assessments of their quality of life (QoL) and that of their mothers; (b) to explore how the comparison is influenced by the method of analysis. Forty-nine adolescents aged 12-18 years who received liver transplants, and their mothers completed the Child Health Questionnaire self (CF87) and parent (PF50) report. There was wide variation in agreement between adolescent and parent responses depending on the method of analysis used. Analysis with t test showed no differences in physical function (t = 1.42, P = 0.16), role/social-physical (t = 0.07, P = 0.94), mental health (t = 0.55, P = 0.59) and family activities (t = -0.40, P = 0.69). Using Pearson correlation coefficients, there were significant correlations in every domain; however, there were no intraclass correlation or concordance correlation coefficients ≥0.80 suggesting less than strong agreement. Finally, the Bland-Altman comparison indicated wide variation in the 95% limits of agreement ranging from -46 to 58.5. There was considerable inconsistency in agreement according to the methods of analysis. The wide variation in scores between adolescent and parent assessment of QoL suggests self rather than proxy report should be used as the primary outcome where possible.


Iodine intake as a possible cause of discontinuous decline in sperm counts: a re-evaluation of historical and geographic variation in semen quality.
In order to examine whether iodine supplements may have caused a global decline in sperm concentrations during the past several decades, the synchronicity of the decline in mean sperm counts and the introduction of iodine supplements was analyzed statistically. A positive correlation between the incidence of thyroid disease and sperm counts has been detected in Europe. In addition, it has been shown that sperm counts began falling around 1965 in the United States, 40 years after iodine supplements were introduced. Mean sperm counts before and after 1965 were 111 x 10(6)/ml and 70 x 10(6)/ml, respectively, in calculations weighted by the number of subjects included in each individual publication. The timing of the declines coincided with the introduction of iodine supplements in the United States, France, and the United Kingdom. The implications are that the global decline in sperm concentrations may be caused by iodine intake. Geographical variation in the types of sperm count decline also appears to be present.


Species ecological similarity modulates the importance of colonization history for adaptive radiation.
Adaptive radiation is an important evolutionary process, through which a single ancestral lineage rapidly gives rise to multiple newly formed lineages that specialize in different niches. In the first-arrival hypothesis, David Lack emphasized the importance of species colonization history for adaptive radiation, suggesting that the earlier arrival of a diversifying species would allow it to radiate to a greater extent. Here, we report on the first rigorous experimental test of this hypothesis, using the rapidly evolving bacterium Pseudomonas fluorescens SBW25 and six different bacterial competitors. We show that the earlier arrival of P. fluorescens facilitated its diversification. Nevertheless, significant effects of colonization history, which led to alternative diversification trajectories, were observed only when the competitors shared similar niche and competitive fitness with P. fluorescens. These results highlight the important role of species colonization history, modified by their ecological differences, for adaptive radiation.


Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.
Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl) phthalate (DEHP) in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity. DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP), were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables. The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity. It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.


DATA RESOURCES AND ANALYSES FAIR Header Reference genome: A TRUSTworthy standard.
The lack of interoperable data standards among reference genome data-sharing platforms inhibits cross-platform analysis while increasing the risk of data provenance loss. Here, we describe the FAIR-bioHeaders Reference genome (FHR), a metadata standard guided by the principles of Findability, Accessibility, Interoperability, and Reuse (FAIR) in addition to the principles of Transparency, Responsibility, User focus, Sustainability, and Technology (TRUST). The objective of FHR is to provide an extensive set of data serialisation methods and minimum data field requirements while still maintaining extensibility, flexibility, and expressivity in an increasingly decentralised genomic data ecosystem. The effort needed to implement FHR is low; FHR's design philosophy ensures easy implementation while retaining the benefits gained from recording both machine and human-readable provenance.


Self-assessment in schizophrenia: Accuracy of evaluation of cognition and everyday functioning.
Self-assessment deficits, often referred to as impaired insight or unawareness of illness, are well established in people with schizophrenia. There are multiple levels of awareness, including awareness of symptoms, functional deficits, cognitive impairments, and the ability to monitor cognitive and functional performance in an ongoing manner. The present study aimed to evaluate the comparative predictive value of each aspect of awareness on the levels of everyday functioning in people with schizophrenia. We examined multiple aspects of self-assessment of functioning in 214 people with schizophrenia. We also collected information on everyday functioning rated by high contact clinicians and examined the importance of self-assessment for the prediction of real-world functional outcomes. The relative impact of performance-based measures of cognition, functional capacity, and metacognitive performance on everyday functioning was also examined. Misestimation of ability emerged as the strongest predictor of real-world functioning and exceeded the influences of cognitive performance, functional capacity performance, and performance-based assessment of metacognitive monitoring. The relative contribution of the factors other than self-assessment varied according to which domain of everyday functioning was being examined, but, in all cases, accounted for less predictive variance. These results underscore the functional impact of misestimating one's current functioning and relative level of ability. These findings are consistent with the use of insight-focused treatments and compensatory strategies designed to increase self-awareness in multiple functional domains.


1-Aminoindan-1,5-dicarboxylic acid and (S)-(+)-2-(3'-carboxybicyclo[1.1.1] pentyl)-glycine, two mGlu1 receptor-preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia.
Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently-characterized and relatively selective mGlu1 receptor antagonists 1-aminoindan-1,5-dicarboxylic acid (AIDA) and (S)-(+)-2-(3'-carboxybicyclo[1.1.1]pentyl)-glycine (CBPG) could reduce neuronal death in vitro, following oxygen-glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine [(+)MCPG] and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (-)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid [(1S,3R)-ACPD] and the group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (3,5-DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i. c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection.


Factor Structure of the Spiritual Well-Being Scale: Cross-Cultural Comparisons Between Jordanian Arab and Malaysian Muslim University Students in Jordan.
This study reported the differences in factor structure of the Spiritual Well-Being Scale (SWBS) among Jordanian Arab and Malaysian Muslim participants and further examined its validity and reliability. A convenience sample of 553 Jordanian Arab and 183 Malaysian Malay Muslim university students was recruited from governmental universities in northern Jordan. The findings of this study revealed that this scale consists of two factors for the Jordanian Arab group, representing the "Religious Well-Being" and the "Existential Well-Being" subscales, and consists of three factors for the Malaysian group, representing the "Affiliation/Meaning and Purpose," "Positive Existential Well-Being/God Caring and Love," and "Alienation/Despair" subscales. In conclusion, the factor structure of the SWBS for both groups in this study was psychometrically sound with evidence of acceptable to good validity and reliability. Furthermore, this study supported the multidimensional nature of the SWBS and the earlier notion that ethnicity shapes responses to this scale.


From loss to loneliness: The relationship between bereavement and depressive symptoms.
Spousal bereavement can cause a rise in depressive symptoms. This study empirically evaluates 2 competing explanations concerning how this causal effect is brought about: (a) a traditional latent variable explanation, in which loss triggers depression which then leads to symptoms; and (b) a novel network explanation, in which bereavement directly affects particular depression symptoms which then activate other symptoms. We used data from the Changing Lives of Older Couples (CLOC) study and compared depressive symptomatology, assessed via the 11-item Center for Epidemiologic Studies Depression Scale (CES-D), among those who lost their partner (N = 241) with a still-married control group (N = 274). We modeled the effect of partner loss on depressive symptoms either as an indirect effect through a latent variable, or as a direct effect in a network constructed through a causal search algorithm. Compared to the control group, widow(er)s' scores were significantly higher for symptoms of loneliness, sadness, depressed mood, and appetite loss, and significantly lower for happiness and enjoyed life. The effect of partner loss on these symptoms was not mediated by a latent variable. The network model indicated that bereavement mainly affected loneliness, which in turn activated other depressive symptoms. The direct effects of spousal loss on particular symptoms are inconsistent with the predictions of latent variable models, but can be explained from a network perspective. The findings support a growing body of literature showing that specific adverse life events differentially affect depressive symptomatology, and suggest that future studies should examine interventions that directly target such symptoms.


[Fructosamine, a new marker of blood glucose control in the diabetic].
Serum fructosamine assay is a new, simple and fast method used to evaluate serum glycosylprotein concentrations. We performed this assay in 96 healthy controls, 95 patients with diabetes (insulin-dependent in 71, non insulin-dependent in 24) and 23 non diabetic pregnant women. Serum fructosamine concentrations were increased and correlated with percents of glycosyl haemoglobin in all diabetics, irrespective of the type of diabetes. However, the low correlation coefficient and the fact that some individual values plotted were distant from the regression slope suggested that fructosamine does not have the same biological significance as glycosyl haemoglobin: the formation and degradation kinetics of these two substances are known to be very different. Fructosamine values were tightly close together in controls and in pregnant women, the latter showing lower values.