Regression of cetacean tattoo lesions concurrent with conversion of precipitin antibody against a poxvirus.
Tattoo lesions linked to the cetacean poxvirus of bottlenose dolphins regressed without treatment. Two types of regression were observed: (1) The tattoo lesions became raised and blanched, then disappeared along with sloughing skin. (2) When an incision was made through a tattoo lesion, the tattoo disappeared in a zone around the incision. Poxviruses removed from the raised, blanched skin lesions and from typical tattoo lesions were reacted with dolphin serums and examined by immunoelectron microscopy. Antibody was not detected against either of these poxvirus preparations when the dolphins had only typical tattoo lesions. However, after the raised, blanched lesions appeared, serums obtained during the acute or convalescent stages were positive for the poxvirus separated from the lesions. Regression of the typical tattoo lesions was concurrent with antibody conversion.


COVID-19 radiology CT personnel management.
A new coronavirus outbreak called COVID-19 started in December 2019. In Turkey, the first case was reported on 10 March 2020. In this article, information will be given about the patient and staff management and organization that we have implemented in the Radiology Department of our hospital during the COVID-19 pandemic. The rules we followed were: 1- Performing the examinations of COVID-19 patients and suspects with a CT device isolated from other patients; 2- Reducing the unnecessary workload in imaging modalities other than CT, emergency radiography, and emergency ultrasonography; 3- Directing and managing patients and their relatives in accordance with the mask and distancing rules; 4- Disinfecting the device with an appropriate disinfectant after each patient in order to prevent cross-contamination; 5- Protecting the entire technician team from infection by employing one week work, two weeks off shifts of fixed teams; 6- Ensuring adequate ventilation of the gantry room. Adhering to the above rules, no infection spread was reported from the Radiology department and especially the COVID-19 CT unit.


Diagnosis of patients with immediate hypersensitivity to beta-lactams using retest.
beta-Lactams are the drugs most frequently involved in hypersensitivity reactions mediated by immunoglobulin (Ig) E. To evaluate a population of patients with suspected B-lactam allergy using a validated algorithm that includes specific IgE antibodies, skin testing, and/or a drug provocation test. A total of 1032 patients with symptoms compatible with B-lactam allergy were evaluated by means of their clinical history, specific immunoglobulin (Ig) E antibody determinations (benzylpenicillin, ampicillin, and amoxicillin), and skin tests with major determinants (penicilloyl-polylysine) and minor determinants (minor determinant mixture) of benzylpenicillin, penicillin G, ampicillin, and amoxicillin-clavulanic acid. Patients whose skin test results were negative were challenged with amoxicillin-clavulanic acid. Only immediate hypersensitivity reactions were evaluated. All patients with negative study results and for whom a reaction occurred more than 1 year before were retested using the same protocol. A total of 170 patients (16.4%) were finally confirmed as having immediate allergic reactions to beta-lactams (62.3% by skin testing, 16.5% by specific IgE, and 21.2% by drug provocation test). The mean age of these patients was 43.3 years, and the drug most frequently involved in the reaction was amoxicillin (41.1%), followed by the combination amoxicillin-clavulanic acid (36.4%). In the remaining 22.5%, different beta-lactams were involved or the culprit drug was not known. Only mild reactions were observed after the drug provocation test. A retest was required in 23% of patients in order to confirm their hypersensitivity. These results indicate that a diagnostic protocol based on the combination of skin testing and in vitro determination of specific IgE antibodies plus, if required, drug provocation testing is an appropriate procedure for evaluating immediate hypersensitivity reactions to beta-lactams. Because the sensitivity of skin testing and in vitro IgE assays is not optimal and a considerable proportion of patients are tolerant, drug provocation tests are necessary to achieve the diagnosis or confirm tolerance. A large percentage of patients (23%) were diagnosed using retest.


Personality traits in children of parents with unipolar and bipolar mood disorders.
Using family study data, the following questions regarding the mechanisms of association between personality traits and mood disorders were addressed: 1) Is there an association between unipolar and bipolar mood disorders and personality traits in probands? 2) Are personality traits associated with depression in their 9 to 17 year-old children? 3) Is there an association between parental mood disorders and personality traits in offspring? 4) Are parental personality traits associated with the risk of depression in offspring? The study included 50 probands with bipolar and 37 with unipolar mood disorder, 34 healthy controls as well as 178 of their children between 9 and 17 years. Diagnoses were made according to a best-estimate procedure based on a semi-structured interview (DIGS), medical records and family history information. Personality traits were assessed using the Eysenck Personality Questionnaire in adults and the Eysenck Personality Questionnaire Junior in offspring. Personality traits, and in particular Neuroticism, were found to be associated with mood disorders in currently affected as well as remitted probands and offspring. However, there was no association between mood disorders in parents and personality traits in their children, and conversely, parental personality traits were not associated with the risk of depression in offspring. 1) Relatively small proportion of offspring who were still unaffected but likely to subsequently develop mood disorders; 2) cross-sectional design. The findings were best compatible with the complication or scar hypothesis, which assumes the occurrence of abnormal personality traits as a consequence of previous depressive episodes.


An investigation into pituitary gonadotrophic hormone synthesis, secretion, subunit gene expression and cell structure in normal and mutant male mice.
To investigate brain-pituitary-gonadal inter-relationships, we have compared the effects of mutations that perturb the hypothalamic-pituitary-gonadal axis in male mice. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, and gonadotroph structure and number were measured. Follicle-stimulating hormone (FSH)β knockout (FSHβKO), FSH receptor knockout (FSHRKO), luteinising hormone (LH) receptor knockout (LuRKO), hypogonadal (hpg), testicular feminised (tfm) and gonadectomised mice were compared with control wild-type mice or heterozygotes. Serum levels of LH were similar in FSHβKO, FSHRKO and heterozygote males despite decreased androgen production in KO males. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSHβ subunit gene in FSHβKO mice. However, there was a significant increase in expression of the common α and LHβ subunit genes in FSHRKO males. The morphology of FSHβKO and FSHRKO gonadotrophs was not significantly different from controls, except that the subpopulation of granules consisting of an electron-dense core and electron-lucent 'halo' was not observed in FSHβKO gonadotrophs and the granules were smaller in diameter. In the gonadotrophin-releasing hormone deficient hpg mouse, gonadotrophin mRNA and hormone levels were significantly lower compared to control mice and gonadotrophs were correspondingly smaller, with less abundant endoplasmic reticulum and reduced secretory granules. In LuRKO, tfm and gonadectomised mice, hyperstimulation of LHβ and FSHβ mRNA and serum protein concentrations was reflected by subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticulum and more secretory granules distributed adjacent to the plasma membrane. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH have been found between normal and mutant male mice. These changes are associated with changes in transcriptional activity of the gonadotrophin subunit genes and are reflected by changes in the cellular structure and secretory granule architecture within the gonadotroph cells.


Superselective microcoil embolization for the treatment of lower gastrointestinal hemorrhage.
To evaluate the safety and effectiveness of superselective microcoil embolization for the treatment of lower gastrointestinal (LGI) hemorrhage. A retrospective review of LGI superselective microcoil embolization data for a 10-year period was performed. During this period, twenty-two patients with evidence on angiography of LGI bleeding underwent superselective microcoil embolization. Hemorrhage was treated in the colon (n = 19) and jejunum (n = 3). Ivalon was used adjunctively in two patients and gelfoam was used as a secondary agent in two additional patients. Postembolization ischemia was evaluated objectively in 14 patients by colonoscopy (n = 10), surgical specimen (n = 3), and barium enema (n = 1). All patients were followed for clinical evidence of bowel ischemia. Four patients died before further follow-up could be performed. Additionally, 122 cases of LGI hemorrhage treated with superselective microcoil embolization were identified in a review of the literature. A meta-analysis was then performed, combining the data in this study and the data from the literature, to estimate the rate of major and minor ischemic complications on a total of 144 superselective microcoil embolizations. Immediate hemostasis was achieved in all 22 patients in this study. Complete clinical success was achieved in 86% of patients (19 of 22 patients). Rebleeding occurred in 14% of patients (3 of 22 patients) and each underwent colonoscopic intervention with success. Postembolization objective follow-up was performed in 64% of patients (14 of 22 patients). Ten patients underwent follow-up colonoscopy; one patient received a follow-up barium enema; and three patients underwent subsequent surgery. Colonic resection (one partial and one total) was performed in two patients. The partial colectomy was performed in a patient who had been diagnosed with colonic polyps and dysplasia. The total colectomy was performed on a patient with history of chronic LGI bleeding complicated by long-term anticoagulation therapy and a history of tubular adenoma resection. The third surgical patient (16 months old) underwent a follow-up exploratory laparotomy after embolization of a proximal jejunal branch of the superior mesenteric artery. None of the three patients who underwent surgery were found to have postembolic ischemic changes in the bowel specimen. Four patients in this study died, for reasons unrelated to hemorrhage or embolization, before further follow-up could be performed. The last four patients were followed clinically and experienced no symptoms of intestinal ischemia. A minor ischemic complication was reported in 4.5% of patients (1 of 22 patients), and there were no major ischemic complications (0%) in this series. A review of the data from 122 cases of LGI superselective microcoil embolization in the literature is also presented. Combined with the data in this study, the minor complication rate was 9% (13 of 144 patients), and the major complication rate was 0% (0 of 144 patients). Superselective microcoil embolization is a safe and effective treatment for LGI hemorrhage.


Classification of benzoyl peroxide as safe and effective and revision of labeling to drug facts format; topical acne drug products for over-the-counter human use; final rule.
We, the Food and Drug Administration (FDA), are issuing this final rule to include benzoyl peroxide as a generally recognized as safe and effective (GRASE) active ingredient in over-the-counter (OTC) topical acne drug products. In addition, this final rule includes new warnings and directions required for OTC acne drug products containing benzoyl peroxide. We are also revising labeling for OTC topical acne drug products containing resorcinol, resorcinol monoacetate, salicylic acid and/or sulfur to meet OTC drug labeling content and format requirements in a certain FDA regulation. This final rule is part of our ongoing review of OTC drug products and represents our conclusions on benzoyl peroxide in OTC acne drug products.


Rule-Based Cohort Definitions for Acute Respiratory Failure: Electronic Phenotyping Algorithm.
Acute respiratory failure is generally treated with invasive mechanical ventilation or noninvasive respiratory support strategies. The efficacies of the various strategies are not fully understood. There is a need for accurate therapy-based phenotyping for secondary analyses of electronic health record data to answer research questions regarding respiratory management and outcomes with each strategy. The objective of this study was to address knowledge gaps related to ventilation therapy strategies across diverse patient populations by developing an algorithm for accurate identification of patients with acute respiratory failure. To accomplish this objective, our goal was to develop rule-based computable phenotypes for patients with acute respiratory failure using remotely monitored intensive care unit (tele-ICU) data. This approach permits analyses by ventilation strategy across broad patient populations of interest with the ability to sub-phenotype as research questions require. Tele-ICU data from ≥200 hospitals were used to create a rule-based algorithm for phenotyping patients with acute respiratory failure, defined as an adult patient requiring invasive mechanical ventilation or a noninvasive strategy. The dataset spans a wide range of hospitals and ICU types across all US regions. Structured clinical data, including ventilation therapy start and stop times, medication records, and nurse and respiratory therapy charts, were used to define clinical phenotypes. All adult patients of any diagnoses with record of ventilation therapy were included. Patients were categorized by ventilation type, and analysis of event sequences using record timestamps defined each phenotype. Manual validation was performed on 5% of patients in each phenotype. We developed 7 phenotypes: (0) invasive mechanical ventilation, (1) noninvasive positive-pressure ventilation, (2) high-flow nasal insufflation, (3) noninvasive positive-pressure ventilation subsequently requiring intubation, (4) high-flow nasal insufflation subsequently requiring intubation, (5) invasive mechanical ventilation with extubation to noninvasive positive-pressure ventilation, and (6) invasive mechanical ventilation with extubation to high-flow nasal insufflation. A total of 27,734 patients met our phenotype criteria and were categorized into these ventilation subgroups. Manual validation of a random selection of 5% of records from each phenotype resulted in a total accuracy of 88% and a precision and recall of 0.8789 and 0.8785, respectively, across all phenotypes. Individual phenotype validation showed that the algorithm categorizes patients particularly well but has challenges with patients that require ≥2 management strategies. Our proposed computable phenotyping algorithm for patients with acute respiratory failure effectively identifies patients for therapy-focused research regardless of admission diagnosis or comorbidities and allows for management strategy comparisons across populations of interest.


Glutamic acid decarboxylase 65 and islet cell antigen 512/IA-2 autoantibodies in relation to human leukocyte antigen class II DR and DQ alleles and haplotypes in type 1 diabetes mellitus.
The frequencies of autoantibodies against glutamic acid decarboxylase 65 (GAD65) and islet cell antigen (ICA) 512/IA-2 (512/IA-2) are functions of the specific human leukocyte antigen (HLA) in type 1 diabetes mellitus (T1D). We investigated the association of HLA class II (DR and DQ) alleles and haplotypes with the presence of GAD and IA-2 autoantibodies in T1D. Autoantibodies were tested in 88 Tunisian T1D patients and 112 age- and gender-matched normoglycemic control subjects by enzyme immunoassay. Among T1D patients, mean anti-GAD antibody titers were higher in the DRB1*030101 allele (P < 0.001), together with the DRB1*030101/DQB1*0201 (P < 0.001) and DRB1*040101/DQB1*0302 (P = 0.002) haplotypes, while lower anti-GAD titers were associated with the DRB1*070101 (P = 0.001) and DRB1*110101 (P < 0.001) alleles and DRB1*070101/DQB1*0201 (P = 0.001) and DRB1*110101/DQB1*030101 (P = 0.001) haplotypes. Mean anti-IA-2 antibody titers were higher in the DRB1*040101 allele (P = 0.007) and DRB1*040101/DQB1*0302 (P = 0.001) haplotypes but were lower in the DRB1*110101 allele (P = 0.010) and the DRB1*110101 (P < 0.001) and DRB1*110101/DQB1*030101 (P = 0.025) haplotypes. Multinomial regression analysis confirmed the positive association of DRB1*030101 and the negative association of DRB1*110101 and DQB1*030101, along with the DRB1*070101/DQB1*0201 and DRB1*110101/DQB1*030101 haplotypes, with anti-GAD levels. In contrast, only the DRB1*040101/DQB1*0302 haplotype was positively associated with altered anti-IA-2 titers. Increased GAD65 and IA-2 antibody positivity is differentially associated with select HLA class II alleles and haplotypes, confirming the heterogeneous nature of T1D.


Chemico-genetic identification of drebrin as a regulator of calcium responses.
Store-operated calcium channels are plasma membrane Ca(2+) channels that are activated by depletion of intracellular Ca(2+) stores, resulting in an increase in intracellular Ca(2+) concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca(2+) concentration serve as signals that activate a number of cellular processes, however, little is known about the regulation of these channels. We have characterized the immuno-suppressant compound BTP, which blocks store-operated channel mediated calcium influx into cells. Using an affinity purification scheme to identify potential targets of BTP, we identified the actin reorganizing protein, drebrin, and demonstrated that loss of drebrin protein expression prevents store-operated channel mediated Ca(2+) entry, similar to BTP treatment. BTP also blocks actin rearrangements induced by drebrin. While actin cytoskeletal reorganization has been implicated in store-operated calcium channel regulation, little is known about actin-binding proteins that are involved in this process, or how actin regulates channel function. The identification of drebrin as a mediator of this process should provide new insight into the interaction between actin rearrangement and store-operated channel mediated calcium influx.


Genetic analysis of intraoral KIT-positive gastrointestinal stromal tumor (GIST).
Gastrointestinal stromal tumors (GISTs), mesenchymal neoplasms originating from the cells of Cajal, usually appear in the gastrointestinal tract and abdomen. They often mimic other lesions, including smooth muscle cell tumors and neurogenic tumors. This study presents a case in which a GIST appeared over a 2-month period and was treated by excision and curettage, with no sign of recurrence during the next 42 months. The study also aims to characterize the GIST. Histopathologic analysis and KIT gene amplification and sequencing were performed. On mutation analysis of the GIST material, the novel 69338Tdel mutation was found in exon 11, and the diagnosis of intraoral stromal tumor was made. GISTs in the intraoral region display pathologic properties similar to others developed throughout the gastrointestinal system. Diagnosis is the first step of treatment for a patient. The discovery of oncogenic KIT mutations in GISTs has led to the development of targeted molecular therapy using tyrosine kinase inhibitors. This study investigates the histopathologic and molecular diagnostics of GISTs, and, to the authors' knowledge, it represents the first genetic study of a GIST developing in the intraoral region.


The relation of novel cardiovascular risk parameters in patients with familial Mediterranean fever.
In this study, we aimed at correlating the thickness of epicardial adipose tissue and levels of Vitamin D with cardiac risk in patients with familial Mediterranean fever. Sixty-five patients with familial Mediterranean fever and 38 healthy controls with matching age and sex were included in the study. The patients with a history of familial Mediterranean fever attacks within the previous two weeks or with any history of inflammatory or cardiovascular disease were excluded. Data regarding age, gender, weight, height, waist circumference, body mass index (calculated as weight/height2), pulse wave velocity, serum Vitamin D levels from fasting blood samples, and Homeostatic Model Assessment for insulin resistance were obtained for the patients and controls. The epicardial adipose tissue was visualized as an echo-free space between the outer surface of myocardium and visceral pericardium using two-dimensional echocardiography, and the thickness of epicardial adipose tissue was measured in parasternal long-axis view at the end of diastole. The patients with familial Mediterranean fever had significantly higher levels of C-reactive protein, epicardial adipose tissue, and pulse wave velocity (p < 0.001, <0.05, <0.005, respectively) as compared with the control group. However, the serum Vitamin D levels in the two groups were observed to be similar (p = 0.486). Weak but significant positive correlations were observed between epicardial adipose tissue thickness and C-reactive protein (r = 0.302, p < 0.005), epicardial adipose tissue thickness and pulse wave velocity (r = 0.263, p < 0.01), and C-reactive protein and pulse wave velocity (r = 0.235, p < 0.05). Thickness of epicardial adipose tissue and pulse wave velocity were observed to increase in patients with familial Mediterranean fever.


Chronic iron deficiency as an emerging risk factor for osteoporosis: a hypothesis.
Iron is essential in oxygen transport and participates in many enzymatic systems in the body, with important roles in collagen synthesis and vitamin D metabolism. The relationship between iron and bone health comes from clinical observations in iron overload patients who suffered bone loss. The opposite scenario--whether iron deficiency, with or without anemia, affects bone metabolism--has not been fully addressed. This is of great interest, as this nutrient deficiency is a worldwide public health problem and at the same time osteoporosis and bone alterations are highly prevalent. This review presents current knowledge on nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron status and bone formation and resorption, and the link between iron and bone metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone resorption and risk of osteoporosis, thus complete recovery from anemia and its prevention should be promoted in order to improve quality of life including bone health. Several mechanisms are suggested; hence, further investigation on the possible impact of chronic iron deficiency on the development of osteoporosis is needed.


Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.
The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.


Differences in intracellular location of pp60src in rat and chicken cells transformed by Rous sarcoma virus.
We have investigated the intracellular location of pp60src in Rous sarcoma virus-transformed rat cells (RR1022) by indirect immunofluorescence microscopy and cell fractionation. Immunofluorescence data suggest that pp60src is predominantly associated with the nuclear envelope and the juxtanuclear reticular membrane structures. The bulk of pp60src and of the associated phosphotransferase activity fractionated with nuclei and not with plasma membranes in disrupted cells. This localization contrasts strikingly with the association of pp60src with the plasma membrane of Rous sarcoma virus-transformed chicken fibroblasts. We propose that pp60src is a membrane protein that associates with cellular membranes through hydrophobic regions and that this membrane association is a general feature of the interaction of pp60src with avian and mammalian cells. Although there are major differences in the intracellular localizations of pp60src, it may interact with cellular membranes through one or more NH2-terminal hydrophobic regions.


A study of alpha-helix hydration in polypeptides, proteins, and viruses using vibrational raman optical activity.
A vibrational Raman optical activity (ROA) study, supplemented by protein X-ray crystal structure data, of alpha-helices in polypeptides, proteins, and viruses has suggested that ROA bands in the extended amide III spectral region may be used to distinguish between two types of right-handed alpha-helix. One type, associated with a positive ROA band at approximately 1300 cm(-1), dominates in hydrophobic environments and appears to be unhydrated; the other, associated with a positive ROA band at approximately 1340 cm(-1), dominates in hydrophilic environments and appears to be hydrated. Evidence is presented to support the hypothesis that unhydrated alpha-helix corresponds to the canonical conformation alpha(c) and hydrated alpha-helix to a more open conformation alpha(o) stabilized by hydrogen bonding of a water molecule or a hydrophilic side chain to the peptide carbonyl. Alpha-helical poly(L-lysine) and poly(L-ornithine) in aqueous solution and poly(L-alanine) in dichloracetic acid display both bands, but alpha-helical poly(l-glutamic acid) in aqueous solution and poly(gamma-benzyl L-glutamate) in CHCl(3) display only the approximately 1340 cm(-1) band and so may exist purely as alpha(o) due to enhanced stabilization of this conformation by particular side chain characteristics. The ROA spectrum of poly(beta-benzyl L-aspartate) in CHCl(3) reveals that it exists in a single left-handed alpha-helical state more analogous to alpha(o) than to alpha(c).


Suppression of STAT5A and STAT5B chronic myeloid leukemia cells via siRNA and antisense-oligonucleotide applications with the induction of apoptosis.
Signal transducers and activators of transcription (STAT) proteins function in the JAK/STAT signaling pathway and are activated by phosphorylation. As a result of this signaling event, they affect many cellular processes including cell growth, proliferation, differentiation, and survival. Increases in the expressions of STAT5A and STAT5B play a remarkable role in the development of leukemia in which leukemic cells gain uncontrolled proliferation and angiogenesis ability. At the same time, these cells acquire ability to escape from apoptosis and host immune system. In this study, we aimed to suppress STAT-5A and -5B genes in K562 CML cells by siRNA transfection and antisense oligonucleotides (ODN) targeting and then to evaluate apoptosis rate. Finally, we compared the transfection efficiencies of these approaches. Quantitative RT-PCR and Western blot results indicated that STAT expressions were downregulated at both mRNA and protein levels following siRNA transfection. However, electroporation mediated ODN transfection could only provide limited suppression rates at mRNA and protein levels. Moreover, it was displayed that apoptosis were significantly induced in siRNA treated leukemic cells as compared to ODN treated cells. As a conclusion, siRNA applications were found to be more effective in terms of gene silencing when compared to ODN treatment based on the higher apoptosis and mRNA suppression rates. siRNA application could be a new and alternative curative method as a supporting therapy in CML patients.


Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity.
Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Abeta42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Abeta42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Abeta and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism.


Role of deferred stenting in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention: A systematic review and meta-analysis.
We conducted a meta-analysis of studies comparing deferred stenting strategy versus the conventional approach with immediate stenting in patients with ST elevation myocardial infarction. Deferring stent after mechanical flow restoration has been proposed as a strategy to reduce the risk of "no reflow" in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). Conflicting evidence is available currently, especially after the recent publication of three randomized clinical trials. Searches in electronic databases were performed. Comparisons between the two strategies were performed for both hard clinical endpoints (all cause-mortality, cardiovascular mortality, unplanned revascularization, myocardial infarction and readmission for heart failure) and surrogate angiographic endpoints (TIMI flow < 3 and myocardial blush grade (MBG) < 2). Eight studies (three randomized and five non-randomized) were deemed eligible, accounting for a total of 2101 patients. No difference in terms of hard clinical endpoints was observed between deferred and immediate stenting (OR [95% CI]: 0.79 [0.54-1.15], for all-cause mortality; odds ratio (OR) [95% CI]: 0.79 [0.47-1.31] for cardiovascular mortality; OR [95% CI]: 0.95 [0.64-1.41] for myocardial infarction; OR [95% CI]: 1.37 [0.87-2.16], for unplanned revascularization and OR [95% CI]: 0.50 [0.21-1.17] for readmission for heart failure). Notably, the deferred stenting approach was associated with improved outcome of the surrogate angiographic endpoints (OR [95% CI]: 0.43 [0.18-0.99] of TIMI flow < 3 and OR [95% CI]: 0.25 [0.11-0.57] for MBG < 2. A deferred stenting strategy could be a feasible alternative to the conventional approach with immediate stenting in "selected" STEMI patients undergoing pPCI.


Public and biobank participant attitudes toward genetic research participation and data sharing.
Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public's needs.


Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension.
Factors contributing to the development of a fibrotic vascular scar and pulmonary vascular remodeling leading to chronic thromboembolic pulmonary hypertension (CTEPH) are still unknown. This study investigates the potential contribution of multipotent progenitor cells and myofibroblasts to the development and progression of CTEPH. Histological examination of endarterectomized tissues from patients with CTEPH identified significant neointimal formation. Morphological heterogeneity was observed in cells isolated from these tissues, including a network-like growth pattern and the formation of colony-forming unit-fibroblast-like colonies (CFU-F). Cells typically coexpressed intermediate filaments vimentin and smooth muscle alpha-actin. Cells were characterized by immunofluorescence and quantitated by fluorescent-activated cell sorting (FACS) for the presence of cell surface markers typical of mesenchymal progenitor cells; cells were >99% CD44(+) CD73(+), CD90(+), CD166(+); >80% CD29(+); 45-99% CD105(+); CD34(-) and CD45(-). Cells were capable of adipogenic and osteogenic differentiation, determined by Oil Red O and Alizarin Red staining, respectively. Additionally, a population of Stro-1(+) cells, a marker of bone marrow-derived stromal cells (4.2%), was sorted by FACS and also capable of adipogenic and osteogenic differentiation. In conclusion, this study is the first to identify a myofibroblast cell phenotype to be predominant within endarterectomized tissues, contributing extensively to the vascular lesion/clot. This cell may arise from transdifferentiation of adventitial fibroblasts or differentiation of mesenchymal progenitor cells. The unique microenvironment created by the stabilized clot is likely a factor in stimulating such cellular changes. These findings will be critical in establishing future studies in the development of novel and much needed therapeutic approaches for pulmonary hypertension.


Recovering genetic regulatory networks from chromatin immunoprecipitation and steady-state microarray data.
Recent advances in high-throughput DNA microarrays and chromatin immunoprecipitation (ChIP) assays have enabled the learning of the structure and functionality of genetic regulatory networks. In light of these heterogeneous data sets, this paper proposes a novel approach for reconstruction of genetic regulatory networks based on the posterior probabilities of gene regulations. Built within the framework of Bayesian statistics and computational Monte Carlo techniques, the proposed approach prevents the dichotomy of classifying gene interactions as either being connected or disconnected, thereby it reduces significantly the inference errors. Simulation results corroborate the superior performance of the proposed approach relative to the existing state-of-the-art algorithms. A genetic regulatory network for Saccharomyces cerevisiae is inferred based on the published real data sets, and biological meaningful results are discussed.


The investigation and comparison of the underlying needs of common disruptive behaviours in patients with Alzheimer's disease.
Management of the disruptive behaviours is one of the most challenging aspects of caring for patients with Alzheimer's dementia (PwAD). The underlying needs of disruptive behaviours in PwAD had rarely been studied, especially the comparison of the underlying needs of disruptive behaviours in PwAD have never been mentioned. The purpose of this study was to investigate and compare the underlying needs of five common disruptive behaviours including hoarding, aggressive behaviour, repetitive behaviour, altered eating behaviour and delusion in PwAD, as perceived by family caregivers, and to relate these needs from the perspective of Maslow's hierarchy. An exploratory research design with qualitative data collection techniques was employed. Informed consent was obtained from each participant prior to the data collection. A total of 65 pairs of caregiver-patient with Alzheimer's disease participated in the study. A semi-structured interview guide was used during the interview, and the directed content analysis method was conducted to analyse data. Four themes related to the underlying needs of the five selected disruptive behaviours emerged from the data, and these included a desire for comfort (physical and psychological), a desire for security (psychological and economic), a need for a sense of belonging (including a need to connect with the outside world and a need for attention) and a need for self-control. These behaviour features were found closely related to Maslow's hierarchy model of human needs. Although the data were gathered from the caregivers, and the views of the patients were thus not included in the analysis, the findings provide information for health providers that can enable them to better understand the underlying needs of common disruptive behaviours in patients with Alzheimer's disease and thus help develop better patient-centred care plans.


Effect of clomiphene citrate on in vitro ovulated ova.
The effect of clomiphene citrate (CC) on developmental capacity of ovulated ova was studied with isolated in vitro perfused rabbit ovaries. Fifty-two ovulated ova were recovered from ovaries perfused with human chorionic gonadotropin (hCG) in a medium containing CC and 45 ova from ovaries perfused with hCG in a CC-free medium. Ova were cultured and inseminated with capacitated sperm and observed serially for evidence of fertilization and stage of development. CC did not affect the fertilization of ovulated ova. However, the percentage of ova which had reached the morula stage by 60 hours was significantly reduced in the CC-treated (15.4%) group, compared with the control group of ovaries (48.9%). A significant percentage of inseminated ova from CC-treated ovaries (65.4%) showed evidence of degeneration, as compared with control ovaries (37.8%). Thus, a partial loss of developmental capacity may explain the discrepancy observed between the rate of successful ovulation induction and the establishment of pregnancy associated with CC administration in humans.


Exped 2010--the challenges of an expedition doctor.
'Exped 2010', a climbing and trekking expedition to the Everest region of Nepal, marked the 150th anniversary of the Army Cadet Force, during October 2010. A team of 20 cadets aged 14-18 years together with a combination of adults, mountain leaders and the expedition doctor, completed the trek to Everest Base Camp with a small number summiting Island Peak. The junior team, consisting of younger members aged 14-16 years, were limited to sleeping at a maximum altitude of 4240m but nevertheless, achieved a trekking altitude of 5000m. Over the three week period, there were a number of challenges for the expedition doctor--integrating into the team, finding time to rest and acclimatise along with the others whilst dealing with over 35 consultations, numerous cases of traveller's diarrhoea, several helicopter evacuations and also managing cases of altitude illness both within the group and for several foreign trekkers along the way.


Spinach (Spinacia oleracea) chloroplast sedoheptulose-1,7-bisphosphatase. Activation and deactivation, and immunological relationship to fructose-1,6-bisphosphatase.
In this paper we study activation by dithiothreitol and reduced thioredoxins and deactivation by oxidized thioredoxins f of sedoheptulose-1,7-bisphosphatase. The behaviour of the enzyme when chromatographed on a thioredoxin-Sepharose column is also described. The enzyme is autoxidizable upon removal of reducing agents, and is activated when reduced by any of the thioredoxins. This mechanism may allow the regulation of the Calvin cycle upon light-dark and dark-light transitions. The formation of a stable complex between enzyme and thioredoxin could explain the inhibitory effect of high thioredoxin concentrations. The use of immunological techniques shows that sedoheptulose-1,7-bisphosphatase and fructose-1,6-bisphosphatase are poorly related immunologically.


Bullous systemic lupus erythematosus with lupus nephritis: a rare case of a subepidermal bullous disorder in a child.
Bullous systemic lupus erythematosus (BSLE) is a rare subset of systemic lupus erythematosus (SLE) with bullous lesions in a case fulfilling the American Rheumatism Association (Atlanta) criteria, histologically characterized by a neutrophil-predominant infiltrate in the upper dermis with immunoglobulin (IgG, IgA, IgM) and C3 deposition at the basement membrane zone (BMZ). It often is associated with autoimmunity to type VII collagen (NC1 [noncollagenous domain 1] domain), although occasionally other antigens such as laminin 5, laminin 6, and BP230 (bullous pemphigoid antigen) have been described. Bullous systemic lupus erythematosus is extremely rare in children. We report here a case of a 9-year-old girl with BSLE as an initial presentation with lupus nephritis class III, a rare occurrence at such a young age. Despite the rarity, we suggest that BSLE should be considered in the differential diagnosis of subepidermal bullous diseases in children in view of associated potentially serious systemic manifestations.


Late presentation of triceps rupture. A case report and review of the literature.
Rupture of the triceps tendon is a rare injury. The treatment protocol for acute injuries is well described and predictably successful. However, if the diagnosis is missed, the surgeon is presented with a more difficult management problem. We report the case of a 19-year-old woman who presented 8 months following a triceps tendon rupture. The diagnosis and technique for repair and postoperative rehabilitation are described. A review of the literature is also presented. Although our patient regained excellent motion and function, we feel the injury is best managed by avoiding misdiagnosis via a high index of suspicion and a careful examination at the time of injury.


Analysis of group ICA-based connectivity measures from fMRI: application to Alzheimer's disease.
Functional magnetic resonance imaging (fMRI) is a powerful tool for the in vivo study of the pathophysiology of brain disorders and disease. In this manuscript, we propose an analysis stream for fMRI functional connectivity data and apply it to a novel study of Alzheimer's disease. In the first stage, spatial independent component analysis is applied to group fMRI data to obtain common brain networks (spatial maps) and subject-specific mixing matrices (time courses). In the second stage, functional principal component analysis is utilized to decompose the mixing matrices into population-level eigenvectors and subject-specific loadings. Inference is performed using permutation-based exact logistic regression for matched pairs data. The method is applied to a novel fMRI study of Alzheimer's disease risk under a verbal paired associates task. We found empirical evidence of alternative ICA-based metrics of connectivity when comparing subjects evidencing mild cognitive impairment relative to carefully matched controls.


Enhancement of health research capacity in Nigeria through north-south and in-country partnerships.
Research productivity in Sub-Saharan Africa has the potential to affect teaching, student quality, faculty career development, and translational country-relevant research as it has in developed countries. Nigeria is the most populous country in Africa, with an academic infrastructure that includes 129 universities and 45 medical schools; however, despite the size, the country has unacceptably poor health status indicators. To further develop the research infrastructure in Nigeria, faculty and research career development topics were identified within the six Nigerian universities of the nine institutions of the Medical Education Partnership Initiative in Nigeria (MEPIN) consortium. The consortium identified a training model that incorporated multi-institutional "train-the-trainers" programs at the University of Ibadan, followed by replication at the other MEPIN universities. More than 140 in-country trainers subsequently presented nine courses to more than 1,600 faculty, graduate students, and resident doctors throughout the consortium during the program's first three years (2011-2013). This model has fostered a new era of collaboration among the major Nigerian research universities, which now have increased capacity for collaborative research initiatives and improved research output. These changes, in turn, have the potential to improve the nation's health outcomes.


Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.
Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.


Effects of hypoxia, pH, and growth stage on cell killing in Chinese hamster V79 cells in vitro by activated cyclophosphamide.
Several factors which influence the sensitivity of Chinese hamster V79 cells to cyclophosphamide (CY) have been studied in vitro in both suspension and monolayer cultures. Activated CY was obtained from the blood of mice 15 to 30 min after i.p. injection of CY (400 mg/kg). At pH 7.4, hypoxia rendered the cells more sensitive to activated CY. At lower values of pH (6.6 and 7.0), there was no difference between the sensitivities of oxic and hypoxic cells, although cells in both conditions were more sensitive to CY than at pH 7.4. Drug sensitivity was markedly affected by the stage of cell growth. Monolayer cultures were most sensitive to CY within a few hours of plating. Cultures then rapidly became less sensitive, with maximum resistance occurring between 24 and 48 h after plating, while the cells were still exhibiting rapid exponential growth. This development of resistance parallelled the formation of small colonies (2 to 4 cells), implying that intercellular contact may confer resistance to killing by activated CY.


Amylosucrase, a glucan-synthesizing enzyme from the alpha-amylase family.
Amylosucrase (E.C. 126.96.36.199) is a member of Family 13 of the glycoside hydrolases (the alpha-amylases), although its biological function is the synthesis of amylose-like polymers from sucrose. The structure of amylosucrase from Neisseria polysaccharea is divided into five domains: an all helical N-terminal domain that is not similar to any known fold, a (beta/alpha)(8)-barrel A-domain, B- and B'-domains displaying alpha/beta-structure, and a C-terminal eight-stranded beta-sheet domain. In contrast to other Family 13 hydrolases that have the active site in the bottom of a large cleft, the active site of amylosucrase is at the bottom of a pocket at the molecular surface. A substrate binding site resembling the amylase 2 subsite is not found in amylosucrase. The site is blocked by a salt bridge between residues in the second and eight loops of the (beta/alpha)(8)-barrel. The result is an exo-acting enzyme. Loop 7 in the amylosucrase barrel is prolonged compared with the loop structure found in other hydrolases, and this insertion (forming domain B') is suggested to be important for the polymer synthase activity of the enzyme. The topology of the B'-domain creates an active site entrance with several ravines in the molecular surface that could be used specifically by the substrates/products (sucrose, glucan polymer, and fructose) that have to get in and out of the active site pocket.


Apoptosis in the muscular arteries from young spontaneously hypertensive rats.
The purpose of this study was to test the hypothesis that a different incidence of apoptosis occurs in the mesenteric arteries of the spontaneously hypertensive rat (SHR) compared with its normotensive control the Wistar-Kyoto rat (WKY) at 1-2 weeks of age. We examined the incidence of apoptotic cells in the blood vessel wall of muscular arteries from the SHR and WKY at 1-2 weeks of age using two techniques of apoptosis measurement DNA laddering and 3'-OH end labelling. We also measured the volume of the blood vessel wall components and lumen sizes with the confocal microscope to determine whether a differential incidence of apoptosis occurred between the two rat strains. We used phenol/chloroform extraction to isolate genomic DNA and assess DNA fragmentation, with gel electrophoresis to determine DNA laddering, and 3'-OH end labelling, where the enzyme terminal deoxynucleotidyl transferase catalyses the addition of fluorescein-conjugated nucleotides to the cut ends of DNA, to detect in situ DNA fragmentation. The volume per unit length of the blood vessel structural components was measured by optical sectioning with the confocal microscope. We found that the SHR had a significantly decreased incidence of cellular apoptosis over WKY. This was true for both the electrophoretic method where SHR had significantly less fragmented DNA (molecular size < 600 bp) than WKY (P= 0.01), and for the microscopic method where SHR had fewer labelled cells in both the adventitia (P= 0.01) and the media (P= 0.0001) layers of large mesenteric arteries. The volumes of the adventitia, media and lumen in the large mesenteric arteries were similar between the two strains at this age. These findings suggest that a differential incidence of cellular apoptosis at the age of 1 -2 weeks may be responsible for the larger media volume found in older SHR and thus contributes to the development of hypertension in these animals.


Ultrafast x-ray Thomson scattering of shock-compressed matter.
Spectrally resolved scattering of ultrafast K-alpha x-rays has provided experimental validation of the modeling of the compression and heating of shocked matter. The elastic scattering component has characterized the evolution and coalescence of two shocks launched by a nanosecond laser pulse into lithium hydride with an unprecedented temporal resolution of 10 picoseconds. At shock coalescence, we observed rapid heating to temperatures of 25,000 kelvin when the scattering spectra show the collective plasmon oscillations that indicate the transition to the dense metallic plasma state. The plasmon frequency determines the material compression, which is found to be a factor of 3, thereby reaching conditions in the laboratory relevant for studying the physics of planetary formation.


The first international meeting of the Research Initiative on Traditional Antimalarial Methods (RITAM).
The first international meeting of the Research Initiative on Traditional Antimalarial Methods (RITAM) was held at the Regional Dermatology Training Centre (RDTC) of the Tumaini University of Health Sciences, Moshi, Tanzania, on December 8-11, 1999. This Inaugural Meeting of RITAM, jointly hosted by the Global Initiative for Traditional Systems of Health (GIFTS) at Oxford University and the World Health Organization (WHO), was designed to develop a strategy for more effective, evidence-based use of traditional medicines that can also inform malaria-control policy decisions. RITAM was established during 1999 as a network of researchers and other people who are active or interested in the study and use of traditional, plant-based antimalarials. RITAM is a partnership between GIFTS of Health, University of Oxford and the Tropical Disease Research (TDR) Programme of WHO. Malaria is one of the key health issues affecting developing countries, particularly in sub-Saharan Africa and Asia. With increasing drug resistance and the high cost of pharmaceutical drugs, the use of herbal antimalarials is popular. The conference was attended by biologic and social scientists, clinicians, traditional healers, and policy makers from Africa, Asia, Europe, and the Americas. The meeting was funded by the Rockefeller Foundation, the Nuffield Foundation's Commonwealth Programme, WHO's TDR Programme, and direct support to delegates was provided by other funders. The meeting addressed the need for research and policy on the prophylactic and therapeutic effects of medicinal plants as well as on vector control and repellence. There were five main outputs from the meeting: (1) targets for making a significant contribution to the control of malaria through the use of traditional antimalarial methods; (2) methods for achieving these targets, including ethical guidelines; (3) an implementation strategy for moving this field ahead quickly and soundly and for putting research findings into practice; (4) linkages established between researchers working on traditional antimalarial methods, based on agreed research priorities and designed to avoid unnecessary replication; and (5) strengthening the RITAM database of current knowledge on traditional herbal antimalarial methods. Four specialist groups were established to develop the above: (1) policy, advocacy, and funding; (2) preclinical studies; (3) clinical development; and (4) repellance and vector control. These will be coordinated by an executive committee managed by GIFTS. Two meetings are planned in 2000: a natural-products chemistry meeting at WHO in Geneva, Switzerland, in June; and a symposium at the World Congress on Tropical Medicine in Cartagena, Colombia, in August.


Pharmacokinetics of cefprozil in infants and children.
Twenty pediatric patients (ages, between 8 months and 8 years) received a single oral dose of cefprozil at levels of 15 and 30 mg/kg of body weight. Cefprozil consists of cis (BMY-28100) and trans (BMY-28167) isomers in an approximately 90:10 ratio. Six plasma samples were collected from each pediatric patient and assayed for drug concentrations. As measured by a microbiological assay, peak concentrations of 11.16 and 15.93 micrograms of cefprozil per ml occurred at 1 h for patients who received the 15- and 30-mg/kg doses, respectively. The respective mean half-lives of cefprozil were 1.77 and 2.14 h, and the respective mean areas under the curve were 28.05 and 45.28 micrograms.h/ml for patients who received the 15- and 30-mg/kg doses. When measured by a high-pressure liquid chromatography method, peak concentrations of 12.09 and 18.04 micrograms of the cis isomer per ml were obtained at 1 h, with mean half-lives of 1.63 and 2.06 h and mean areas under the curve of 30.48 and 49.34 micrograms.h/ml in patients who received the 15- and 30-mg/kg doses, respectively. For the trans isomer, peak concentrations of 1.16 and 1.63 micrograms/ml occurred at 1 h, respectively, with mean half-lives of 1.61 and 1.65 h and mean areas under the curve of 2.89 and 4.34 micrograms.h/ml in patients who received the 15- and 30-mg/kg doses, respectively.


Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing.
Craniofacial defects often result in aesthetic and functional deficits, which affect the patient's psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template's size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment.


Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B.
The primary aim of this study is to determine whether treatment with lamivudine improved pre-liver transplantation (pre-LT) and LT-free survival of patients awaiting LT for hepatitis B virus (HBV)-related cirrhosis. Data from 162 lamivudine-treated and 147 untreated transplant candidates managed at 20 North American transplant centers between 1996 and 1998 were collected and compared. Lamivudine-treated patients were more likely to be men, hepatitis B e antigen positive, HBV DNA positive, and have lower serum albumin levels at listing (P <.05). Actuarial pre-LT and LT-free survival were similar in lamivudine-treated and untreated patients. Using Cox regression analysis, the only significant predictor of pre-LT patient survival was the modified Child-Turcotte-Pugh (mCTP) score, whereas significant predictors of LT-free survival included ethnic background, lamivudine treatment, indication for LT, baseline serum alanine aminotransferase level, and baseline mCTP score. Lamivudine had no apparent effect on liver disease severity in patients undergoing LT, but appeared to improve disease severity in patients still awaiting LT. Breakthrough infection was noted in 11% of lamivudine-treated patients. We conclude that lamivudine therapy is not associated with improved pre-LT or LT-free survival in LT candidates with chronic hepatitis B. However, a subset of patients with less advanced liver failure may derive clinical benefit from lamivudine therapy, thus delaying the need for LT. In the absence of prospective, randomized, controlled trials of lamivudine in patients with decompensated cirrhosis, careful selection of patients and optimal timing of treatment are needed to balance the risk versus benefit of lamivudine therapy in LT candidates.


[Comparative clinical appraisal of the effectiveness and tolerability of paclitaxel-LANCE and taxol in combination chemotherapy for recurrences and platinum-refractory ovarian carcinoma].
A clinical appraisal of efficacy and tolerability of taxol (T) and a generic drug--paclitaxel--LANCE (P)--was carried out in two groups of patients with recurrences (9) or platinum-refractory ovarian carcinoma (17). In group I, patients aged 19-71 (mean age--47 yrs) had received 6-7 courses, while, in group II, patients aged 44-72 (mean age--52 yrs) who suffered tumor progression--15.0 courses of various chemotherapeutic regimens. Following standard premedication, T and P were injected 135 mg/sq., intravenously, dropwise, during 3 hrs, as a rule, either concurrently with platinum drugs or with hemzar. In the final analysis, there was no clinically significant difference in overall response--44-30% and 44-48%, respectively, nor any significant difference in side-effect incidence was reported.


The predictive significance of fluctuations in early maternal sensitivity for secure base script knowledge and relationship effectiveness in adulthood.
Attachment theory suggests that both the quality and consistency of early sensitive care should shape an individual's attachment working models and relationship outcomes across the lifespan. To date, most research has focused on the quality of early sensitive caregiving, finding that receiving higher quality care predicts more secure working models and better long-term relationship outcomes than receiving lower quality care. However, it remains unclear whether or how the consistency of early sensitive care impacts attachment working models and adult relationship functioning. In this research, we utilized data from the Minnesota Longitudinal Study of Risk and Adaptation to examine to what extent the quality (i.e., mean levels) and consistency (i.e., within-person fluctuations) in behaviorally coded maternal sensitive care assessed 7 times from 3 months to 13 years prospectively predicts secure base script knowledge and relationship effectiveness (i.e., interpersonal competence in close relationships) in adulthood. We found that larger fluctuations and lower mean levels of early maternal sensitivity jointly predict lower relationship effectiveness in adulthood via lower secure base script knowledge. These findings reveal that nonlinear models of early caregiving experiences more completely account for relationship outcomes across the lifespan, beyond what traditional linear models have documented. Implications for attachment theory and longitudinal methods are discussed.


Serotypic classification of hantaviruses by indirect immunofluorescent antibody and plaque reduction neutralization tests.
Antisera prepared against 16 strains of hantaviruses isolated from patients with hemorrhagic fever with renal syndrome (HFRS) or from rodents captured in HFRS-endemic and nonendemic regions were titrated against Hantaan virus strain 76-118, Puumala virus strain Sotkamo, and Prospect Hill virus strain Prospect Hill-I by using the indirect immunofluorescent antibody and plaque reduction neutralization tests. Isolates fell into one of four distinct groups or serotypes. Serotype 1 included Apodemus-derived strains, serotype 2 included Rattus-derived strains, serotype 3 included Clethrionomys-derived strains, and serotype 4 included Microtus-derived strains. Serotypic classification of hantavirus infections was possible for humans and rodents in widely varied geographical areas, but in a few instances, sera from patients with HFRS did not conform to any of the four serotypes, suggesting the existence of as yet unidentified serotypes. A definitive serological classification of hantaviruses must await analysis of additional virus isolates.


Complementary and Alternate Management of Glaucoma: The Verdict so Far.
Complementary and alternative medicine deserves scientific scrutiny as patients with glaucoma often lose vision despite adequate medical or surgical treatment. Most glaucomatologists abstain from recommending alternative medicine as there is little evidence to support most of the recommendations for complementary and alternate management (CAM) use in glaucoma. Megavitamin supplementation has not been shown to have a long-term beneficial effect on glaucoma. In a glaucomatous eye, a very modest benefit of IOP-lowering may be offset by the temporary elevation in IOP that accompanies exercise. There is little evidence to support the use of special diets, acupuncture, relaxation techniques, or therapeutic touch for the treatment of glaucoma. Marijuana can have a profound lowering of IOP, but the low response rate, short half-life, and significant toxicity are strong indicators that it is not an appropriate therapeutic agent. Future research must be carried out to document the effect of CAM not only on IOP, but also on perimetric tests or other objective parameters, such as ocular blood fow and nerve fiber layer thickness. How to cite this article: Bhartiya S, Ichhpujani P. Complementary and Alternate Management of Glaucoma: The Verdict so Far. J Curr Glaucoma Pract 2014;8(2):54-57.


Mitochondrial RNA processing defect caused by a SUPV3L1 mutation in two siblings with a novel neurodegenerative syndrome.
SUPV3L1 encodes a helicase that is mainly localized in the mitochondria. It has been shown in vitro to possess both double-stranded RNA and DNA unwinding activity that is ATP-dependent. Here we report the first two patients for this gene who presented with a homozygous preliminary stop codon resulting in a C-terminal truncation of the SUPV3L1 protein. They presented with a characteristic phenotype of neurodegenerative nature with progressive spastic paraparesis, growth restriction, hypopigmentation, and predisposition to autoimmune disease. Ophthalmological examination showed severe photophobia with corneal erosions, optic atrophy, and pigmentary retinopathy, while neuroimaging showed atrophy of the optic chiasm and the pons with calcification of putamina, with intermittent and mild elevation of lactate. We show that the amino acids that are eliminated by the preliminary stop codon are highly conserved and are predicted to form an amphipathic helix. To investigate if the mutation causes mitochondrial dysfunction, we examined fibroblasts of the proband. We observed very low expression of the truncated protein, a reduction in the mature ND6 mRNA species as well as the accumulation of double-stranded RNA. Lentiviral complementation with the full-length SUPV3L1 cDNA partly restored the observed RNA phenotypes, supporting that the SUPV3L1 mutation in these patients is pathogenic and the cause of the disease.


Genetic diversity of Ichthyophthirius multifiliis (Fouquet, 1876) infecting farmed rainbow trout (Oncorhynchus mykiss Walbaum, 1792) in Turkey.
We assessed genetic diversities among Ichthyophthirius multifiliis (Ich) field isolates collected from farmed rainbow trout (Oncorhynchus mykiss) in Turkey. The overall prevalence of Ich was 35.3% (634/1798). Five novel Ich genotypes (ImulTR1 and ImulTR3-ImulTR6) were described based on mitochondrial cox-1 and nad1_b genes. The remaining genotype ImulTR2 was identical to the previously reported NY3 (or Ark9 and TW7) genotype from the United States and South Asia. Phylogenetic analysis indicated Turkish Ich isolates separated genetically into at least four distinct groups. Our study presents the first data on the genotypes of Ich in Turkey. We also provide evidence for the wide distribution of the NY3 genotype (or Ark9 and TW7) from the United States and South Asia to Turkey. Genetic diversities within the mitochondrial genes provided adequate resolution for describing novel genotypes and identifying the known genotype within Turkish Ich isolates. Description of the Ich genotypes allows for tracking of pathogen genotypes worldwide. Thus, we can better understand the connections between Ich outbreaks in the fisheries aquaculture.


Effect of ovarian involvement on the frequency of luteinized unruptured follicle in endometriosis.
When we review the current literature on endometriosis and luteinized unruptured follicle (LUF), we see that most of the studies deal with only the association between LUF frequency and the severity of endometriosis. Our purpose was to evaluate the effect of ovarian involvement on LUF frequency in endometriosis and assess the relationship between endometriosis and LUF in infertile women. This study is a prospective analysis covering a total of 126 infertile women between 22 and 35 years of age who underwent diagnostic laparoscopy from September 1995 to August 1997 in the Department of Obstetrics and Gynecology at Süleyman Demirel University, Isparta, Turkey. Endometriosis was diagnosed in 58 of these patients. All had received a revised American Fertility Society staging score at the time of the laparoscopic diagnosis. Diagnosis of LUF was made when the following criteria were fulfilled: absence of ultrasonic signs of ovulation, and absence of an ovulation ostium on the follicle by laparoscopy, despite increased serum progesterone. Statistical evaluation was performed using chi2 test and Fisher's exact test where appropriate. The prevalence of LUF in mild, moderate and severe endometriosis cases was 13.3, 41.2 and 72.7%, respectively. The LUF frequencies were 45.9% in 37 endometriosis patients with ovarian involvement, 9.5% in 21 cases without ovarian involvement, and 5.9% in 68 cases without endometriosis. A statistically significant difference was observed between the LUF rate in the group with ovarian involvement and that without involvement (chi(2) = 8.06, p < 0.001). In summary, in this study we noted a significant increase in LUF frequency in endometriosis patients with ovarian involvement.


Functional foods as a formulation ingredients in beverages: technological advancements and constraints.
As a consequence of expanded science and technical research, the market perception of consumers has shifted from standard traditional to valuable foods, which are furthermore nutritional as well as healthier in today's world. This food concept, precisely referred to as functional, focuses on including probiotics, which enhance immune system activity, cognitive response, and overall health. This review primarily focuses on functional foods as functional additives in beverages and other food items that can regulate the human immune system and avert any possibility of contracting the infection. Many safety concerns must be resolved during their administration. Functional foods must have an adequate amount of specific probiotic strain(s) during their use and storage, as good viability is needed for optimum functionality of the probiotic. Thus, when developing novel functional food-based formulations, choosing a strain with strong technological properties is crucial. The present review focused on probiotics as an active ingredient in different beverage formulations and the exerting mechanism of action and fate of probiotics in the human body. Moreover, a comprehensive overview of the regulative and safety issues of probiotics-based foods and beverages formulations.


Lightning-induced myocardial injury. A case report with management.
A young patient of lightning induced myocardial injury with chest pain is described. Electro-cardiogram mimicked true myocardial infarction (due to coronary artery disease). Practical aspects of case management is discussed. Use of short course of steroid helped in early recovery.


Greenhouse tests on resistance management of Bt transgenic plants using refuge strategies.
Experimental evaluation of the effectiveness of resistance management tactics is vital to help provide guidelines for the deployment of transgenic insecticidal crops. Transgenic broccoli expressing a Cry1Ac gene of Bacillus thuringiensis (Bt) and the diamondback moth, Plutella xylostella (L.), were used in greenhouse tests to evaluate the influence of size and placement of nontransgenic refuge plants on changes in resistance allele frequency and pest population growth. In the first test with an initial Cry1Ac-resistance (R) allele frequency of 0.007, P. xylostella were introduced into cages with the following treatments: 0, 3.3, 10, 20, and 100% refuge plants. Results after four generations showed that resistance could be delayed by increasing the proportion of refuge plants in the cage. Population growth was also influenced by refuge size with the highest populations occurring in treatments that had either no refuge plants or all refuge plants. In the second test, we evaluated the effect of refuge placement by comparing 20% separate and 20% mixed refuges. P. xylostella with an initial frequency of resistant alleles at 0.0125 were introduced into cages and allowed to cycle; later generations were evaluated for resistance and population growth. Separating the refuge had a pronounced effect on delaying resistance and slowing establishment of resistant larvae on Bt plants. Combining information from both trials, we found a strong negative correlation between the number of larvae on Bt plants and the mortality of the population in leaf dip bioassays. Results from larval movement studies showed that separate refuges delayed resistance better than mixed refuges because they conserved relatively more susceptible alleles than R alleles and did not increase the effective dominance of resistance.


QTL mapping for fruit quality in Citrus using DArTseq markers.
Citrus breeding programs have many limitations associated with the species biology and physiology, requiring the incorporation of new biotechnological tools to provide new breeding possibilities. Diversity Arrays Technology (DArT) markers, combined with next-generation sequencing, have wide applicability in the construction of high-resolution genetic maps and in quantitative trait locus (QTL) mapping. This study aimed to construct an integrated genetic map using full-sib progeny derived from Murcott tangor and Pera sweet orange and DArTseq™ molecular markers and to perform QTL mapping of twelve fruit quality traits. A controlled Murcott x Pera crossing was conducted at the Citrus Germplasm Repository at the Sylvio Moreira Citrus Centre of the Agronomic Institute (IAC) located in Cordeirópolis, SP, in 1997. In 2012, 278 F1 individuals out of a family of 312 confirmed hybrid individuals were analyzed for fruit traits and genotyped using the DArTseq markers. Using OneMap software to obtain the integrated genetic map, we considered only the DArT loci that showed no segregation deviation. The likelihood ratio and the genomic information from the available Citrus sinensis L. Osbeck genome were used to determine the linkage groups (LGs). The resulting integrated map contained 661 markers in 13 LGs, with a genomic coverage of 2,774 cM and a mean density of 0.23 markers/cM. The groups were assigned to the nine Citrus haploid chromosomes; however, some of the chromosomes were represented by two LGs due the lack of information for a single integration, as in cases where markers segregated in a 3:1 fashion. A total of 19 QTLs were identified through composite interval mapping (CIM) of the 12 analyzed fruit characteristics: fruit diameter (cm), height (cm), height/diameter ratio, weight (g), rind thickness (cm), segments per fruit, total soluble solids (TSS, %), total titratable acidity (TTA, %), juice content (%), number of seeds, TSS/TTA ratio and number of fruits per box. The genomic sequence (pseudochromosomes) of C. sinensis was compared to the genetic map, and synteny was clearly identified. Further analysis of the map regions with the highest LOD scores enabled the identification of putative genes that could be associated with the fruit quality characteristics. An integrated linkage map of Murcott tangor and Pera sweet orange using DArTseq™ molecular markers was established and it was useful to perform QTL mapping of twelve fruit quality traits. The next generation sequences data allowed the comparison between the linkage map and the genomic sequence (pseudochromosomes) of C. sinensis and the identification of genes that may be responsible for phenotypic traits in Citrus. The obtained linkage map was used to assign sequences that had not been previously assigned to a position in the reference genome.


Histologic studies of islets of Langerhans in transplanted pancreata from marginal donors in Japan.
The serious shortage of brain-dead donors leads to the use of pancreata from marginal donors, including cardiac death in Japan. We studied the islet histology of pancreas graft biopsies to investigate the adequacy of using pancreata from marginal donors. Pancreas allograft biopsy was performed originally to diagnose acute rejection (Drachenberg grade I-III) at a mean of 6 months after transplantation. The percentage of beta cells showing oxidative DNA changes, replication, and apoptosis was investigated in 7 recipients of simultaneous pancreas-kidney transplantations with good graft function from marginal donors. Their causes of death were cerebrovascular with donor ages >44 years (n = 3), cardiac (n = 2), and cerebrovascular (n = 2). The percentage of beta cells per islet in the transplanted pancreas (71.9 +/- 3.3%) did not correlate with glycemic control or insulin secretion, but did correlated inversely with donor age (r = -0.81; P < .05). Oxidative DNA changes as revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present in islet cells as well as in the exocrine cells of the transplanted pancreas. The percentage of 8-OHdG-positive cells per pancreas (71.8 +/- 4.5%) did not correlate with glycemic levels, insulin secretion, donor age, or ischemic time. There were no Ki67-positive replicating cells or terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive apoptotic islet cells. Transplanted pancreata from marginal donors showed preserved beta cells and function despite diffuse oxidative changes.


QTL analysis of the developmental response to L-glutamate in Arabidopsis roots and its genotype-by-environment interactions.
Primary root growth in Arabidopsis and a number of other species has previously been shown to be remarkably sensitive to the presence of external glutamate, with glutamate signalling eliciting major changes in root architecture. Using two recombinant inbred lines from reciprocal crosses between Arabidopsis accessions C24 and Col-0, we have identified one large-effect quantitative trait locus (QTL), GluS1, and two minor QTLs, GluS2 and GluS3, which together accounted for 41% of the phenotypic variance in glutamate sensitivity. The presence of the GluS1 locus on chromosome 3 was confirmed using a set of C24/Col-0 isogenic lines. GluS1 was mapped to an interval between genes At3g44830-At3g46880. When QTL mapping was repeated under a range of environmental conditions, including temperature, shading and nitrate supply, a strong genotype-by-environment interaction in the controls for the glutamate response was identified. Major differences in the loci controlling this trait were found under different environmental conditions. Here we present evidence for the existence of loci on chromosomes 1 and 5 epistatically controlling the response of the GluS1 locus to variations in ambient temperature, between 20°C and 26°C. In addition, a locus on the long arm of chromosome 1 was found to play a major role in controlling the ability of external nitrate signals to antagonize the glutamate effect. We conclude that there are multiple loci controlling natural variation in glutamate sensitivity in Arabidopsis roots and that epistatic interactions play an important role in modulating glutamate sensitivity in response to changes in environmental conditions.


[Differences in the course of depressive disorders among women and men measured by MMPI-2].
The aim of the study is to assess the differences between clinical scales of MMPI-2 among women and men suffering from depressive disorders. 36 patients were examined (aged 23-62 years, average age = 51.27, SD = 8.84): 19 women (52.77%, aged 23-59, average age = 51.16, SD = 4.74) and 17 men (47.23%, aged: 23-61, average age = 51.41, SD = 12.07). All patients were hospitalised in the Clinic of Adult Psychiatry Medical University of Łódź. The Minnesota Multiphasic Personality Inventory (MMPI-2, adapted by T. Kucharski) and Hamilton Depression Rating Scale (HDRS, consisting of 21-items) were used. MMPI-2 is used in psychological diagnostic and HDRS is used to assess the intensity of depressive disorders. Relevant statistical differences between women and men in the several clinical scales of MMPI-2 were observed. There were no relevant statistical differences between the examined groups in the HDRS. (1). The characteristic symptoms of depressive disorders for women are: the excessive concentration on physical health, numerous complaints about physical disabilities, lack of energy, insomnia, diminishing of attention concentration and low self-esteem, diffidence and pessimism (2). Examined men achieved statistically lower results than women in the following scales: hypochondria, hysteria and D1, D3, D4 subscales of the depression scale. (3). MMPI-2 is one of the psychological methods which allow for a specific diagnosis of depressive disorders symptoms among women and men.


A dental technician with pulmonary fibrosis: a case of chromium-cobalt alloy pneumoconiosis?
A 45 yr old male developed pulmonary fibrosis after 29 yrs of employment as a dental technician. He subsequently developed adenocarcinoma of the lung. Diffuse interstitial fibrosis was seen using light microscopy. Neutron activation analysis of non-neoplastic lung tissue demonstrated high levels of chromium and cobalt suggesting the possibility of a chromium-cobalt alloy pneumoconiosis.


Early developmental gene enhancers affect subcortical volumes in the adult human brain.
Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.


Assessment of teaching to predict gains in student achievement in urban schools.
We examined the degree to which assessment of teachers' instructional and behavior management practices, as measured by the Classroom Strategies Assessment System (CSAS; Reddy & Dudek, 2014), relates to gains in student achievement as measured by the Measures of Academic Progress (Northwest Evaluation Association [NWEA], 2011). Two-level hierarchical linear modeling was applied to achievement scores from 2,771 students in 130 kindergarten through 8th-grade classrooms in 13 urban schools serving students in communities with high concentrations of poverty. Results suggest that teachers' use of evidence-based instructional and behavior management strategies, as measured by the CSAS, were associated with reading and mathematics gains. In general, students in classrooms with higher quality use of evidence-based teaching strategies exhibited greater gains, whereas students in classrooms with lower quality use of effective strategies exhibited lesser gains. Implications of these findings for research and educational practice are presented. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Radioimmunoassay of rat leptin: sexual dimorphism reversed from humans.
Adipose tissue secretes leptin, which interacts with receptors in the hypothalamus. In rodent models of obesity, leptin increases metabolism and decreases food intake, which helps to maintain normal body composition. Accurate and precise methods to quantitate circulating leptin concentrations are needed for physiological studies. We developed an RIA to measure leptin in rat plasma, serum, or adipocyte culture fluids. The working range of the assay, defined by the detection limit and the highest calibrator, was 0.5-50 micrograms/L. Recovery of 1.6-11.6 micrograms/L leptin added to serum was 92-103%. The rat leptin RIA correlated well with a previously developed mouse RIA when rat plasma was assayed with both methods (r = 0.94), but the mouse leptin assay underestimated rat leptin in plasma. Within- and between-run CVs were 2.4% to 5.7%. Plasma leptin concentrations correlated directly with percentage of body fat, and correlation improved when the results were separated by gender (r = 0.796, P < 0.001 for males; r = 0.710, P < 0.001 for females). Leptin concentrations were generally higher in male rats than in females; plasma leptin increased 0.60 microgram/L for each percentage of increase in body fat for males but only 0.22 microgram/L for females. We conclude that rat serum/plasma leptin concentrations are accurately and precisely measured with this new RIA.


All anxiety is not created equal: Correlates of parent/youth agreement vary across subtypes of anxiety.
Research has examined patterns and correlates of parent/youth informant discrepancies in the reporting of youth anxiety. However, little work has examined whether it is better to conceptualize patterns and correlates of informant disagreement across anxiety broadly, or more useful to consider disagreement on specific symptom clusters. Using data from the Child Adolescent/Anxiety Multimodal Study (CAMS; N = 488; Walkup et al., 2008), the current study applied the most recent recommended analytic strategies to study informant discrepancies and examined differences in the magnitude and patterns of disagreement for: (a) broadband anxiety symptoms, versus (b) symptoms of specific anxiety diagnoses (or anxiety subtypes; e.g., separation, social anxiety). Correlates of informant discrepancies were also examined. Results indicated that there was variability in agreement across anxiety subtypes, with parent/youth agreement higher on separation anxiety and school refusal symptoms relative to other domains. Parental psychopathology was associated with disagreement on broadband anxiety symptoms, such that parental psychopathology was highest when parents reported higher symptoms than their children; however, this finding was largely driven by a relationship between parental psychopathology and disagreement on separation anxiety symptoms. Age was associated with disagreement on total and separation anxiety symptoms. Gender was not associated with disagreement. Clinical implications are discussed.


On the origin of surface imposed anisotropic growth of salicylic and acetylsalicylic acids crystals during droplet evaporation.
In this paper droplet evaporative crystallization of salicylic acid (SA) and acetylsalicylic acid (ASA) crystals on different surfaces, such as glass, polyvinyl alcohol (PVA), and paraffin was studied. The obtained crystals were analyzed using powder X-ray diffraction (PXRD) technique. In order to better understand the effect of the surface on evaporative crystallization, crystals deposited on glass were scraped off. Moreover, evaporative crystallization of a large volume of solution was performed. As we found, paraffin which is non-polar surface promotes formation of crystals morphologically similar to those obtained via bulk evaporative crystallization. On the other hand, when crystallization is carried out on the polar surfaces (glass and PVA), there is a significant orientation effect. This phenomenon is manifested by the reduction of the number of peaks in PXRD spectrum recorded for deposited on the surface crystals. Noteworthy, reduction of PXRD signals is not observed for powder samples obtained after scraping crystals off the glass. In order to explain the mechanism of carboxylic crystals growth on the polar surfaces, quantum-chemical computations were performed. It has been found that crystal faces of the strongest orientation effect can be characterized by the highest surface densities of intermolecular interactions energy (IIE). In case of SA and ASA crystals formed on the polar surfaces the most dominant faces are characterized by the highest adhesive and cohesive properties. This suggests that the selection rules of the orientation effect comes directly from surface IIE densities.


The Mutual Support Model of Mindfulness and Character Strengths.
Numerous studies have confirmed robust relationships between general well-being and mindfulness or character strengths, respectively, but few have examined associations between mindfulness and character strengths. Two studies were carried out to explore these relationships comprehensively in the framework of the Values in Action (VIA) classification of character strengths. In study 1, participants (N = 1335) completed validated assessments of mindfulness and character strengths, and the relationship between the two was investigated in a broad online sample. In study 2, the effect of a mindfulness training on specific character strengths was investigated using a randomized-control design (N = 42). The results of study 1 confirmed positive relationships between mindfulness and character strengths and further identified a list of character strengths that might overlap with mindfulness-i.e., creativity, curiosity, open-mindedness, love of learning, perspective, bravery, perseverance, zest, love, social intelligence, forgiveness, self-regulation, appreciation of beauty, gratitude, hope, and spirituality. The findings of study 2 provided further support for the hypothesis that mindfulness training could help cultivate certain character strengths. Compared with participants in the waitlist control condition, those who attended an 8-week mindfulness-based training program showed significant increases in the strengths of love, appreciation of beauty, gratitude, and spirituality, and a trend toward significant increases in the strengths of zest and bravery. The results provide initial evidence for a mutual support model of mindfulness and character strengths.


Two Rare Cases of Paratubal Leydig Cell Nodules: Clinical Relevance and Debated Terminology of a Noteworthy Incidentaloma.
Cells with cytologic and immunohistochemical features of Leydig cells are normally present in the ovary and the ovarian hilum, are testosterone-producing, and have been referred to as ovarian hilus cells. Rarely these cells form nests or nodules in extraovarian sites such as the mesovarium or mesosalpinx. Because they are so rare, these nodules can present a diagnostic challenge when first encountered. This report describes 2 such incidental nodules in the mesosalpinx associated with a small paratubal cyst and suggests that the term Leydig cell nodule be preferred over the nonspecific and confusing historical term ovarian hilus cell nest.


EEG sedation for children with autism.
Seizures are reported to occur more frequently among children with diagnoses of autism and pervasive developmental disorder (PDD), and some reports indicate a frequency as high as 30%. Sedation is often necessary to perform diagnostic electroencephalograms (EEGs) in these children, who are known to be difficult to sedate with current available pediatric sedating agents, including chloral hydrate. We used clonidine as a sedative agent in children with autism and PDD, and our findings are presented. In a prospective study, 27 children with autism and PDD diagnoses underwent conscious sedation for EEG recording. Informed consents were obtained, and clonidine was administered orally as a sedating agent in a dose ranging from 0.05 mg to 0.2 mg. Subjects were monitored for pulse rate, respiration rate, blood pressure, and oxygen saturation on a continuous basis by a registered nurse. Study parameters included time to induction, time to recovery, changes in vital signs, and technical quality of EEGs. Sedation was achieved in 23 of 27 patients (85%) per our sedation criteria, and this included five patients who had previously failed to be sedated with chloral hydrate. Two patients did not satisfy the sedation criteria but cooperated enough to allow acceptable EEG tracings, increasing the success rate to 93% (25/27). The mean time to achieve sedation was 58 minutes, and the mean time to recovery was 105 minutes. Two patients (0.07%) experienced an asymptomatic heart rate reduction up to 40%, which was not sustained and recovered promptly without any intervention. Two patients (0.07%) experienced systolic blood pressure reductions of 30% and 40%. They remained asymptomatic, had no changes in other cardiorespiratory parameters, and required no intervention. All EEGs were of good technical quality without any "drug effect." Clonidine is a viable alternative for sedation in children with autism and PDD. It is well tolerated without any significant side effects and is efficacious in children with autism and PDD. The advantages of clonidine include ease of administration, shorter duration of total sedation, lack of EEG drug effect, and high overall success rate.


Degradation of recalcitrant compounds by catechol-driven Fenton reaction.
Dihydroxybenzenes are able to reduce Fe(III) and promote the Fenton reaction in the presence of H2O2. The catechol/Fe(III)/H2O2 system has been successfully used to degrade different compounds, being more efficient than the Fe(II)-Fenton reaction. In this paper the possibilities for using the catechol-driven Fenton reaction to degrade recalcitrant compounds such as the Fe(III)-EDTA complex and veratryl alcohol are reviewed.


Reduced arteriolar responses to skeletal muscle contraction after ingestion of a high salt diet.
We previously reported that in skeletal muscle arterioles of rats fed a very high salt (HS; 7%) diet, the bioavailability of endothelium-derived nitric oxide (NO) is reduced through scavenging by reactive oxygen species. Because arteriolar NO can play an important role in local blood flow control, we investigated whether arteriolar responses to increased tissue metabolism become compromised in skeletal muscle of salt-fed rats. Consumption of a HS (4%) diet for 4 weeks had no effect on arteriolar diameters, volume flow or shear stress in resting spinotrapezius muscle. Arteriolar responses to a modest elevation in metabolic demand (0.5 Hz contraction) were not different from those in rats fed a normal diet, but diameter responses to a greater elevation in metabolic demand (4 Hz contraction) were significantly less in HS rats than in rats fed a normal diet. In both groups, the NO synthase inhibitor N(G)-monomethyl-L-arginine reduced resting arteriolar diameters and flow by a similar amount and had little or no effect on arteriolar diameter or flow responses to muscle contraction. Arterioles in HS rats exhibited an increase in overall oxidant activity (tetranitroblue tetrazolium reduction) but not in superoxide activity (dihydroethidine oxidation). Reactive oxygen species scavengers (2,2,6,6-tetramethylpiperidine-N-oxyl and catalase) did not normalize the reduced arteriolar responses to muscle contraction in HS rats. These findings suggest that increased oxidant activity in the arteriolar network of salt-fed rats is not due to accumulation of superoxide anion and that neither this oxidant activity nor reduced NO availability can account for the blunted active arteriolar dilation in rats fed a 4% salt diet.


Meta-analysis of the safety of home birth.
The safety of planned home birth is controversial. This study examined the safety of planned home birth backed up by a modern hospital system compared with planned hospital birth in the Western world. A meta-analysis of six controlled observational studies was conducted, and the perinatal outcomes of 24,092 selected and primarily low-risk pregnant women were analyzed to measure mortality and morbidity, including Apgar scores, maternal lacerations, and intervention rates. Confounding was controlled through restriction, matching, or in the statistical analysis. Perinatal mortality was not significantly different in the two groups (OR = 0.87, 95% Ci 0.54-1.41). The principal difference in the outcome was a lower frequency of low Apgar scores (OR = 0.55; 0.41-0.74) and severe lacerations (OR = 0.67; 0.54-0.83) in the home birth group. Fewer medical interventions occurred in the home birth group: induction (statistically significant ORs in the range 0.06-0.39), augmentation (0.26-0.69), episiotomy (0.02-0.39), operative vaginal birth (0.03-0.42), and cesarean section (0.05-0.31). No maternal deaths occurred in the studies. Some differences may be partly due to bias. The findings regarding morbidity are supported by randomized clinical trials of elements of birth care relevant for home birth, however, and the finding relating to mortality is supported by large register studies comparing hospital settings of different levels of care. Home birth is an acceptable alternative to hospital confinement for selected pregnant women, and leads to reduced medical interventions.