Dislocations and vacancies in two-dimensional mixed crystals of spheres and dimers.
In colloidal crystals of spheres, dislocation motion is unrestricted. On the other hand, recent studies of relaxation in crystals of colloidal dimer particles have demonstrated that the dislocation dynamics in such crystals are reminiscent of glassy systems. The observed glassy dynamics arise as a result of dislocation cages formed by certain dimer orientations. In the current study, we use experiments and simulations to investigate the transition that arises when a pure sphere crystal is doped with an increasing concentration of dimers. Specifically, we focus on both dislocation caging and vacancy motion. Interestingly, we find that any nonzero fraction of dimers introduces finite dislocation cages, suggesting that glassy dynamics are present for any mixed crystal. However, we have also identified a vacancy-mediated uncaging mechanism for releasing dislocations from their cages. This mechanism is dependent on vacancy diffusion, which slows by orders of magnitude as the dimer concentration is increased. We propose that in mixed crystals with low dimer concentrations vacancy diffusion is fast enough to uncage dislocations and delay the onset of glassy dislocation dynamics.


Pesticide residues in adults living near a bioenergy plant with 85,000 tons of contaminated wetcake.
Neonicotinoid insecticide use is on the rise worldwide due to its broad-spectrum insecticidal action and exclusive approach of neurotoxic action. Besides application during the cultivation of several crops, all seed companies coat their seeds with neonicotinoids to have increased protection against insects during germination. Despite reduced mammalian toxicity, neonicotinoids have harmful effects on non-target non-mammalian organisms such as bees, an essential part of maintaining the ecosystem. In addition, epidemiologic studies have linked human exposure to neonicotinoids with poor developmental and neurological outcomes. Starting in 2015, the AltEn bioenergy plant near Mead, Nebraska, USA, used coated seeds for their ethanol production and failed to properly dispose of byproducts, causing environmental contamination that still exists. This pilot study reports the human urinary levels of neonicotinoids in samples collected during 2022-2023 in the population living in areas close to this now-closed bioenergy plant. Our results show that approximately 30% of the urine samples are contaminated with at least one of the targeted neonicotinoids or their transformed products. The most frequently detected parent neonicotinoid was clothianidin, which accounts for 13% of the samples. However, 5-hydroxy-imidacloprid, the transformed imidacloprid product, is detected in 27% of the samples, ranging from 1.2 to 42 ng/mL. In conclusion, the environmental contamination near Mead, Nebraska, due to improper storage and disposal of highly contaminated byproducts, puts the nearby population at risk from continuous exposure to neonicotinoids through air and dust particles and possible water contamination.


Three insulation methods to minimize intravenous fluid administration set heat loss.
To assess the effect of three methods for insulating an intravenous (IV) fluid administration set on the temperature of warmed fluid delivered rapidly in a cold environment. The three chosen techniques for insulation of the IV fluid administration set involved enclosing the tubing of the set in 1) a cotton conforming bandage, 2) a reflective emergency blanket, and 3) a combination of technique 2 followed by technique 1. Intravenous fluid warmed to 44°C was infused through a 20-drop/mL 180-cm-long fluid administration set in a controlled environmental temperature of 5°C. Temperatures in the IV fluid bag, the distal end of the fluid administration set, and the environment were continuously measured with resistance thermosensors. Twenty repetitions were performed in four conditions, namely, a control condition (with no insulation) and the three different insulation methods described above. One-way analysis of variance was used to assess the mean difference in temperature between the IV fluid bag and the distal fluid administration set under the four conditions. In the control condition, a mean of 5.28°C was lost between the IV fluid bag and the distal end of the fluid administration set. There was a significant difference found between the four conditions (p < 0.001). A mean of 3.53°C was lost between the IV fluid bag and the distal end of the fluid administration set for both the bandage and reflective emergency blanket, and a mean of 3.06°C was lost when the two methods were combined. Using inexpensive and readily available materials to insulate a fluid administration set can result in a reduction of heat loss in rapidly infused, warmed IV fluid in a cold environment.


Bacterial community structure and response to nitrogen amendments in Lake Shenandoah (VA, USA).
Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.


[Maternal mortality in the Rheinische Landesfrauenklinik Wuppertal from 1917 to 1979 (author's transl)].
From 1917 to 1979, the maternal mortality in the Rheinische Landesfrauenklinik Wuppertal has been investigated on the basis of 136084 live births. From 1917 to 1921, it was 10.1% and decreased to 0.16% in the period from 1973 to 1979. The maternal mortality in association with caesarean section, which was 11.8% in the period from 1917 to 1921 with a frequency of caesarean sections of 2.5%, decreased to zero since 1973 with a frequency of 6.3%. A caesarean section preceded more than 50% of the deaths since 1962. Most of the decreased (24.4%) were in the group of 30-34 years of age and 48.3% aged more than 30 years. 51.5% were primiparas and 14.6% of the women were at least para 4's. From 1917 to 1936, infection was the main cause of maternal mortality with 39.6%; from 1957 to 1966, however, thrombo-embolism advanced to the leading cause with 27.3%. Since 1960, 4 of 35 deaths were anaesthetic deaths. During all the examined periods, non-specific reasons of maternal mortality were an important factor with more than 30%.


Trace metal speciation in brackish water using diffusive gradients in thin films and ultrafiltration: comparison of techniques.
Diffusive gradients in thin films (DGT) and ultrafiltration were used to measure trace metal concentrations in the Baltic Sea. The results provide the first comparison of these two fundamentally different speciation methods for trace metals. Cd, Cu, Mn, Ni, and Zn were measured at two sites with different total trace metal concentrations. DGT units prepared with APA-gel as diffusive layer and Chelex 100 resin as binding agent were used throughout the study. The ultrafiltration was performed with Millipore Prep/Scale modules with cutoffs of 1 and 10 kDa. Concentration levels of Mn, Zn, and Cd measured by DGT agreed with the concentrations measured in 1 kDa ultrafiltered samples. For Cu and Ni the ultrafiltered concentrations exceeded the DGT-labile concentrations. The ability of DGT to preconcentrate metals was found to be an analytical advantage compared with ultrafiltration. DGT appears to be a good alternative to 1 kDa ultrafiltration for measurement of truly dissolved Mn, Cd, and Zn in the Baltic Sea.


Identification of Mild Cognitive Impairment Subtypes using an Interpretable Neural Network based Clustering of Gene Expression Data and Neuroimaging Markers.
In this study, an attempt is made to cluster the gene expression data and neuroimaging markers using an interpretable neural network model to identify Mild Cognitive Impairment (MCI) subtypes. For this, structural Magnetic Resonance (MR) brain images and gene expression data of early and late MCI subjects are considered from a public database. A neural network model is employed to cluster the gene expression data and regional MR volumes. To evaluate the performance of model, clustering metrics are employed and model is explained using perturbation-based method. Results indicate that the developed model is able to identify MCI subtypes. The network learns latent embeddings of disease-specific genes and MR images markers. The clustering metrics are found to be highest when both the imaging and genetic markers are employed. Volumes of lateral ventricles, hippocampus, amygdala and thalamus are found to be associated with late MCI. Significant scores suggest that genes such as StAR, CCDC108, APOO, TRMT13, RASAL2 and ZNF43 play a key role in identifying the MCI subtypes.Clinical Relevance-Identifying distinct MCI subtypes offer potential for precision diagnostics and targeted clinical recruitment.


Integrative computed tomographic imaging of cardiac structure, function, perfusion, and viability.
Recent advances in multidetector-row computed tomography (MDCT) technology have created new opportunities in cardiac imaging and provided new insights into a variety of disease states. Use of 64-slice coronary computed tomography angiography has been validated for the evaluation of clinically relevant coronary artery stenosis with high negative predictive values for ruling out significant obstructive disease. This technology has also advanced the care of patients with acute chest pain by simultaneous assessment of acute coronary syndrome, pulmonary embolism, and acute aortic syndrome ("triple rule out"). Although MDCT has been instrumental in the advancement of cardiac imaging, there are still limitations in patients with high or irregular heart rates. Newer MDCT scanner generations hold promise to improve some of these limitations for noninvasive cardiac imaging. The evaluation of coronary artery stenosis remains the primary clinical indication for cardiac computed tomography angiography. However, the use of MDCT for simultaneous assessment of coronary artery stenosis, atherosclerotic plaque formation, ventricular function, myocardial perfusion, and viability with a single modality is under intense investigation. Recent technical developments hold promise for accomplishing this goal and establishing MDCT as a comprehensive stand-alone test for integrative imaging of coronary heart disease.


Evaluation of pre- and postnatally diagnosed gastrointestinal tract obstructions.
Purpose: Signs of congenital obstruction of the gastrointestinal tract (GIT) organs may present on prenatal ultrasonography. Prenatal detection is influenced by several factors, including obstruction site, lesion degree (partial or complete), the occurrence of associated malformations, and gestational week at screening. Here, we aimed to evaluate the success of prenatal diagnosis of GIT obstructions in a tertiary center in Turkey. Materials and methods: The study included 34 prenatally and 22 postnatally diagnosed babies with different GIT malformations. GIT obstructions were divided into five groups according to the level of obstruction (A. esophagus, B. stomach and proximal duodenum, C. small intestine, D. large intestine, E. multiple obstructions). Results: The prenatal detection rate among all cases was 60.7%. The associated structural malformation and aneuploidy rates were 21.4 and 5.4%, respectively. Twelve neonates died within the first day after birth due to various reasons. The remaining 43 babies underwent surgery at different times according to their clinical conditions. The mean time between birth and surgery was 4.5 days (range, 1-56 days). There were 12 postoperative deaths due to various complications, and one case died at 2 years of age. Overall, 31 of the 56 (55.4%) babies were alive during the follow-up period. The successful prenatal diagnosis rates were 57.2, 85.8, 75, 25, and 80% in groups A, B, C, D, and E, respectively. The median birth weight increased significantly in groups A through D (p = .04). However, there were no intergroup differences in the Apgar scores, associated abnormality rates, time to surgery, and number of babies operated. Conclusions: These findings demonstrate the importance of prenatal ultrasonography and success of prenatal detection especially for upper GIT abnormalities. Although there are some prenatal signs of GIT obstructions, such as double bubble, polyhydramnios, enlarged bowel, and failure to visualize the stomach, early prenatal diagnosis is difficult and can be delayed, resulting in the detection of GIT obstruction after birth. When suspecting GIT obstruction, clinicians should evaluate the fetal anatomy carefully and be aware of associated chromosomal abnormalities.


In vitro conjugation of the trichloroethylene metabolite trichloroethanol to a fatty acid.
Trichloroethanol (TCA), a major metabolite of the known carcinogen trichloroethylene (TCE), was shown to conjugate to palmitic acid in an in vitro rat liver coenzyme A fortified microsomal system. This conjugation of a fatty acid to one of its major metabolites may be the mechanism by which TCE is retained in the body and ultimately exerts its toxic or carcinogenic effect.


Adolescent self-harm and suicidal behavior and young adult outcomes in indigenous and non-indigenous people.
The aim of this study was to examine the associations between self-harm and suicidal behavior in indigenous Sami and non-Sami adolescents and mental health and social outcomes in young adulthood. Data were obtained by linking the Norwegian Patient Registry (2008-2012), the National Insurance Registry (2003-2013), and the Norwegian Arctic Adolescent Health Study, a school-based survey inviting all 10th grade students in North Norway (2003-2005). In total, 3987 (68%) of all 5877 invited participants consented to the registry linkage, of whom 9.2% were indigenous Sami. Multivariable logistic regression was used to explore the associations between self-harm only, suicidal ideation with and without self-harm, and suicide attempts in adolescence (≤16-year-old), and later mental health disorders, long-term medical, social welfare benefit receipt, or long-term unemployment in young adulthood. Self-harm and suicidal behavior in Sami and non-Sami adolescents were associated with increased risk of later mental health disorders, long-term welfare benefit receipt, and long-term unemployment. These associations were attenuated by adolescent psychosocial problems. No major differences between the indigenous Sami participants and their non-Sami peers were found. Young suicide attempters experienced the highest risk, with adolescent suicide attempts being significantly associated with all four adult outcomes after adjustment. Self-harm and suicidal behavior in adolescence are markers of mental health disorders and unfavorable social outcomes in young adulthood, mostly accounted for by adolescent psychosocial problems. In contrast to other indigenous peoples, no indigenous health disparities were found, indicating that the indigenous Sami adolescents were not worse off.


Medical methods for first trimester abortion.
Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. To compare different medical methods for first trimester abortion. The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups. Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.


Severe CSU and activation of the coagulation/fibrinolysis system: clinical aspects.
Background. About 50% of patients with severe chronic spontaneous urticaria (CSU) show signs of activation of the coagulation/fibrinolysis system, but the clinical significance of this phenomenon is unclear. Objective. The present study compared patients with severe CSU showing and not showing elevated D-dimer plasma levels. Methods. 132 adult patients (m/f 44/88; mean age 51, 5 years; range 14 - 89 years) with severe CSU (UAS-7 major 30) were included in a cross-sectional, real life study. The study group was divided based on baseline D-dimer plasma levels, and compared for age, sex, disease duration, disease activity, CRP, thyroid autoimmunity, total IgE, and atopic status. Results. Identical numbers of patients showed elevated and normal D-dimer plasma levels (50% and 50%, respectively). Patients showing elevated D-dimer levels were slightly older (p minor 0.05), were more frequently females (p minor 0.05), had a longer disease duration (p minor 0.01), and had a significantly higher prevalence of elevated PCR (26/66 vs 4/66; p minor 0.001). Conclusions. Only 50% of patients with severe CSU show elevated D-dimer plasma levels. The activation of the coagulation/fibrinolysis system is associated with a systemic inflammatory milieu, suggesting the existence of a specific phenotype. Whether this reflects the existence of different endotypes in patients showing and not showing the activation of the coagulation cascade has still to be established.


Cell-cell and cell-extracellular matrix interactions regulate embryonic stem cell differentiation.
Cell interactions with the extracellular matrix (ECM) play a critical role in their physiology. Here, we sought to determine the role of exogenous and endogenous ECM in the differentiation of nonhuman primate ESCs. We evaluated cell differentiation from expression of lineage gene mRNA and proteins using real-time polymerase chain reaction and immunohistochemistry. We found that ESCs that attached to and spread upon highly adhesive collagen do not differentiate efficiently, whereas on the less adhesive Matrigel, ESCs form aggregates and differentiate along mesoderm and especially endoderm lineages. To further decrease ESC attachment to the substrate, we cultured them either on nonadhesive agarose or in suspension. In both cases, ESCs formed aggregates and efficiently differentiated along endoderm and mesoderm lineages, most strikingly into cardiomyocytes. Aggregates formed by thus-differentiated ESCs started to beat with a frequency of 50-100 beats per minute and continued to beat for approximately a month. In spite of the presence of exogenous ECM, ESCs were dependent on endogenous ECM for their survival and differentiation, as the inhibition of endogenous collagen induced a gradual loss of ESCs and neither a simple matrix, such as type I collagen, nor the complex matrix Matrigel was able to rescue these cells. In conclusion, adhesiveness to various ECM and nonbiological substrates determines the differentiation of ESCs in such a way that efficient cell-cell aggregation, together with less efficient cell attachment and spreading, results in more efficient cell differentiation.


Composition of neutral lipids from erythrocytes of common mammals.
The neutral lipids of the erythrocytes were investigated in several common mammals: cow, dog, goat, horse, pig, rabbit, rat, and sheep. Cholesterol content was determined by gas-liquid, thin-layer, and column chromatography, the last in conjunction with the IR spectrophotometry. The three methods yielded similar results. In every species investigated, cholesterol was the major neutral lipid; cholesteryl esters, triglycerides, and free fatty acids were detected only in trace amounts. It is concluded that these substances may have been contaminants from plasma lipoproteins or leukocytes rather than true constituents of the erythrocyte. In the erythrocytes of all species, cholesterol content was close to 30% of the total lipids extracted from the cells, and the molar ratio of cholesterol to phospholipid was approximately one. The significance of the data is discussed in relation to current concepts of the structure of the cell membrane involving cholesterol-polar lipid complexes.


Identification of Novel lncRNA Markers in Glioblastoma Multiforme and Their Clinical Significance: A Study Based on Multiple Sequencing Data.
Long non-coding RNAs (lncRNAs) have been verified to have a vital role in the progression of glioblastoma multiforme (GBM). Our research was about to identify the potential lncRNAs which was closely associated with the pathogenesis and prognosis of glioblastoma multiforme. All RNA sequence profiling data from patients with GBM were obtained from The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA). Differently expressed genes identified from GBM and control samples were used to construct competing endogenous RNA (ceRNA) network and perform corresponding functional enrichment analysis. Univariate Cox regression followed by lasso regression and multivariate Cox was used to validate independent lncRNA factors and construct a risk prediction model. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression levels of potential lncRNA biomarkers in human GBM clinical specimens. A gene set enrichment analysis (GSEA) was subsequently conducted to explore potential signaling pathways in which critical lncRNAs may be involved. Moreover, nomogram plot was applied based on our prediction model and significant clinical covariates to visualize the prognosis of GBM patients. A total of 2023 differentially expressed genes (DEGs) including 56 lncRNAs, 1587 message RNAs (mRNAs) and 380 other RNAs were included. Based on predictive databases, 16lncRNAs, 32 microRNAs (miRNAs) and 99 mRNAs were used to construct a ceRNA network. Moreover, we performed a novel risk prediction model with 5 potential prognostic lncRNAs, in which 4 of them were newly identified in GBM, to predict the prognosis of GBM patients. Finally, a nomogram plot was constructed to illustrate the potential relationship between the prognosis of GBM and our risk prediction model and significant clinical covariates. In this study, we identified 4 novel potential lncRNA biomarkers and constructed a prediction model of GBM prognosis. A simple-to-use nomogram was provided for further clinical application.


Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty-year period.
To investigate time trends in the incidence and survival of giant cell arteritis (GCA) over a 50-year period in Olmsted County, Minnesota. Using the unified record system at the Mayo Clinic, we identified all incident cases of GCA first diagnosed between 1950 and 1999. Incidence rates were estimated and adjusted to the 1980 United States white population for age and sex. The annual incidence rates were graphically illustrated using a 3-year centered moving average. Survival rates were computed and compared with the expected rates in the population. There were 173 incident cases of GCA during the 50-year study period. Of these, 79% were women and the mean age at diagnosis was 74.8 years. The overall age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 18.8 (95% confidence interval [95% CI] 15.9-21.6). Incidence was higher in women (24.4; 95% CI 20.3-28.6) than in men (10.3; 95% CI 6.9-13.6). Incidence rates increased significantly over the study period (P = 0.017); in particular, a progressive increase was observed from 1950 to 1979; subsequently, no substantial increases in incidence rates were observed. A cyclic pattern of annual incidence rates was apparent, with evidence of 6 peak periods. Survival among individuals with GCA was not significantly different from that expected in the population (P = 0.80). The incidence of GCA increased over the first 3 decades of the study, then remained stable over the last 20 years. The previously observed cyclic pattern of annual incidence rates was still apparent over a 50-year period. Overall survival in GCA was similar to that in the population.


Type 2 segmental manifestation of Hailey-Hailey disease: poor therapeutic response to dermabrasion is due to severe involvement of adnexal structures.
In autosomal dominant skin conditions, two different types of segmental manifestation can be distinguished. Type 1 represents heterozygosity for a postzygotic mutation, resulting in a degree of severity similar to that of the nonmosaic phenotype. Type 2 reflects loss of heterozygosity and shows an excessively pronounced involvement superimposed on the ordinary nonsegmental phenotype. We describe the clinical, histopathological and therapeutic aspects of the first case of type 2 segmental manifestation of Hailey-Hailey disease (HHD). A 24-year-old woman with a family history of HHD comprising four generations, presented with lesions of erythema and blistering arranged in a unilateral pattern following the lines of Blaschko. The disorder was first noted at the age of 3 months. At the age of 24 years, additional scattered symmetrical lesions involving the axillary and inguinal folds were noted. Histopathological examination of the severely involved linear skin areas revealed pronounced acantholysis within the deep adnexal structures, whereas clinically unaffected skin showed the typical histopathological features of the heterozygous phenotype with suprabasal clefting and acantholysis sparing the adnexae. Dermabrasion was performed in the areas of segmental involvement. During a follow-up period of one year, no recurrence was noted, but 18 months after dermabrasion a recurrence was present in the left submammary and left perianal regions. This therapeutic resistance to dermabrasion may be explained by the presence of acantholysis within the adnexal structures of the skin as found in type 2 segmental HHD.


An estimate of chronic disease burden and some economic consequences among the elderly Hong Kong population.
To estimate the burden of chronic disease for an elderly Chinese population aged 70 years and over, and to illustrate the use of this information in estimating the economic consequences of disease burden using stroke as an example. A total of 1902 subjects recruited by random sampling of the old age and disability allowance schemes, which cover over 90% of the Hong Kong elderly population, stratified by sex and five year age groups from age 70 years onwards. Information was collected on 10 medical conditions at baseline: arthritis, hypertension, cardiac disease, stroke, chronic obstructive airways disease, peptic ulcer, diabetes mellitus, osteoporotic fracture, malignancy, and dementia. A follow up survey was carried out after 18 months to determine the occurrence of new disease and the number with disease who had died. Disease burden is calculated as the number with disease at baseline plus the number developing new disease minus the number who had died. Disease burden figures were highest for arthritis, hypertension, cardiac disease, and peptic ulcer, and were higher in the 70-79 age group than the 80+ age group for some diseases. For stroke, the economic cost based on a population projection for 2001 was estimated to be around HK$1,900,000,000, or US$250 million. Information on the burden of chronic disease is important. It enables the economic consequences to be estimated so that strategies can be developed to prevent diseases with high costs and known effective preventive methods.


Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases.
Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil cytoplasmic antibodies (ANCA) antigens. The objective of the present study was to investigate the presence of cross-reactivity to MPO of TMA. We studied sera from 51 patients with autoimmune thyroid diseases, all of them TMA-positive. The presence of ANCA was investigated by indirect immunofluorescence and by capture enzyme-linked immunosorbent assay. ANCA were positive in 3.9% of the TMA-positive sera and none of them reacted with MPO. In contrast, the ANCA-positive sera revealed antielastase activity. None of the ANCA-positive cases presented clinical signs of vasculitis. However, these 2 patients had been on prolonged treatment with propylthiouracil. We conclude that there is no cross-reactivity to MPO of TMA in patients with autoimmune thyroid diseases, possibly because of difference in the spatial configuration of the immunodominant region. The presence of ANCA in patients with autoimmune thyroid diseases without evidence of vasculitis might result from propyIthiouracil-induced polyclonal activation.


Identification of caveolin-1 as a fatty acid binding protein.
In an attempt to identify high affinity, fatty acid binding proteins present in 3T3-L1 adipocytes plasma membranes, we labeled proteins in purified plasma membranes with the photoreactive fatty acid analogue, 11-m-diazirinophenoxy[11-3H]undecanoate. A single membrane protein of 22 kDa was covalently labeled after photolysis. This protein fractionated with caveolin-1 containing caveolae and was immunoprecipitated by an anti-caveolin-1 monoclonal antibody. Furthermore, 2D-PAGE analysis revealed that both the alpha and beta isoforms of caveolin-1 could be labeled by the photoreactive fatty acid upon photolysis, indicating that both bind fatty acids. The saturable binding of the photoreactive fatty acid suggests caveolin-1 has a lipid binding site that may either operate during intracellular lipid traffic or regulate caveolin-1 function.


Tissue-specific localization of cytochrome P450 aromatase in the equine embryo by in situ hybridization and immunocytochemistry.
Estrogen production by the preimplantation equine embryo is presumed to be important in maternal-conceptus communication in the mare. The synthesis of C(18) estrogens from C(19) androgens requires cytochrome P450 aromatase (P450(arom)) in the conceptus, but little information is available on the specific tissue location or potential developmental patterns of expression for the horse. The goal of this research was to localize P450(arom) in the equine conceptus by immunocytochemistry and in situ hybridization. Intact blastocyst-stage embryos were collected by nonsurgical flush on Days 12-15 of pregnancy, fixed in 4% paraformaldehyde, and paraffin-embedded. Aromatase protein was localized using rabbit anti-human placental aromatase antiserum with a detection system utilizing peroxidase and 3-amino-9-ethylcarbazole. For in situ hybridization, tissue sections were incubated with sense or antisense [(35)S]UTP-labeled cRNA probes prepared from equine aromatase cDNA. Aromatase protein and transcript were abundant in the extraembryonic trophectoderm but absent from embryonic ectoderm. No P450(arom) expression was detected in abembryonic endoderm or mesoderm. Aromatase expression was demonstrated in the endoderm beneath the disc (hypoblast). This pattern of P450(arom) expression in the equine blastocyst closely resembles that seen transiently in the porcine embryo, suggesting that regulatory mechanisms conferring tissue specificity may be conserved.


Steady-state and transient-state analysis of growth and metabolite production in a Saccharomyces cerevisiae strain with reduced pyruvate-decarboxylase activity.
Pyruvate decarboxylase is a key enzyme in the production of low-molecular-weight byproducts (ethanol, acetate) in biomass-directed applications of Saccharomyces cerevisiae. To investigate whether decreased expression levels of pyruvate decarboxylase can reduce byproduct formation, the PDC2 gene, which encodes a positive regulator of pyruvate-decarboxylase synthesis, was inactivated in the prototrophic strain S. cerevisiae CEN. PK113-7D. This caused a 3-4-fold reduction of pyruvate-decarboxylase activity in glucose-limited, aerobic chemostat cultures grown at a dilution rate of 0.10 h(-1). Upon exposure of such cultures to a 50 mM glucose pulse, ethanol and acetate were the major byproducts formed by the wild type. In the pdc2Delta strain, formation of ethanol and acetate was reduced by 60-70%. In contrast to the wild type, the pdc2Delta strain produced substantial amounts of pyruvate after a glucose pulse. Nevertheless, its overall byproduct formation was ca. 50% lower. The specific rate of glucose consumption after a glucose pulse to pdc2Delta cultures was about 40% lower than in wild-type cultures. This suggests that, at reduced pyruvate-decarboxylase activities, glycolytic flux is controlled by NADH reoxidation. In aerobic, glucose-limited chemostat cultures, the wild type exhibited a mixed respiro-fermentative metabolism at dilution rates above 0.30 h(-1). Below this dilution rate, sugar metabolism was respiratory. At dilution rates up to 0.20 h(-1), growth of the pdc2Delta strain was respiratory and biomass yields were similar to those of wild-type cultures. Above this dilution rate, washout occurred. The low micro(max) of the pdc2Delta strain in glucose-limited chemostat cultures indicates that occurrence of respiro-fermentative metabolism in wild-type cultures is not solely caused by competition of respiration and fermentation for pyruvate. Furthermore, it implies that inactivation of PDC2 is not a viable option for reducing byproduct formation in industrial fermentations.


[Warfarin treatment of venous thromboembolism].
Warfarin treatment of venous thromboembolism is the most frequent cause of reported serious and fatal adverse events associated with drug therapy in Norway. We assessed quality of treatment during transfer from hospital to community-based care. 66 out of 100 consecutive patients with venous thromboembolism were studied by a retrospective survey that included data from hospital records and a questionnaire survey. Time in therapeutic range was 57% during the first four weeks. Undertreatment was the most frequent deviation. Some patients reported a long time lag from INR measurement to dose prescription in community care; 42% did not receive written treatment information. There were six recurrences, but no serious or fatal bleeding complications during one year of observation. Patient satisfaction with information and treatment organisation was high. There is room for improvement of patient information and treatment quality in outpatient care in our area.


Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition.
Glioma is the most common malignant tumor of the nervous system, which accounts for more than 45% of central nervous system tumors and seriously threatens our health. Because of high mortality rate, limitations, and many complications of traditional treatment methods, new treatment methods are urgently needed. β-Mangostin is a natural compound derived from the fruit of Garcinia mangostana L. and it has anticancer activity in several types of cancer cells. However, the antitumor effect of β-mangostin in glioma has not been clarified. Hence, this study aimed to investigate its therapeutic effects on gliomas. To study the effect of β-mangostin on glioma cells, cell viability assay, reactive oxygen species production, cell cycle, apoptosis, and mitochondrial membrane potential were evaluated in the C6 cell line in vitro. Immunofluorescence and Western blotting were used to analyze protein expression and phosphorylation to study its mechanism of action. A subcutaneous xenograft model was used to investigate the effect of β-mangostin on tumorigenesis in vivo. We found that β-mangostin can inhibit glioma cell growth and induce oxidative damage in vitro. In addition, it reduces the phosphorylated form levels of PI3K, AKT and mTOR. Furthermore, the phosphorylated form levels of PI3K, AKT and mTOR were increased after the PI3K inhibitor was added. In vivo experiments showed that β-mangostin can inhibit tumor growth as shown by its reduced size and weight. This study suggests that β-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that β-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.


Evaluation of between-line variation for within-line selection against ascites in broilers.
Within-line opportunities for selection against ascites were studied in a data set comprising a 10-line comparison. The study attempted to reveal whether contrasts between lines provide reliable candidate traits for within-line selection. Mortality was chosen as the reference trait. As no pedigree information was available, a trait was required that related mortality to the nonmortality data. By principal component analysis, such a trait (ASC_INDIC = ascites indicator) was developed from pathology data. The composite trait ASC_INDIC ranked lines well for their mortality figures (r = 0.96), from which it was concluded that ASC_INDIC represents an underlying continuous ascites trait. Between lines, blood gas traits seemed to be the most promising traits. Within lines, performance traits appeared to be highly correlated to ascites. Comparison of within-line variation to between-line contrasts revealed considerable differences. The high correlation of the blood gas traits with mortality was not present within lines. However, although the magnitude was considerably reduced, the nature of the blood gas traits in their relationship to ascites was similar within and between lines. The study primarily demonstrates that contrasts between lines carry systematic but limited information for within-line coherence. Therefore, line contrasts must be interpreted with care when aiming to study genetic variation and coherence within lines.


[Effect of folliculin and estradiol-dipropionate on the phagocytic properties of the blood neutrophils of the female white rat].
In the female rat blood, prior to and 5, and 50 days after bilateral ovarectomy with the substitutional administration of 50 units of folliculin and estradiol--dipropionate subcutaneously every 48 hrs for 50 days, a progressing decrease of the phagocytic activity was observed. Under the effect of estradiol--dipropionate the phagocytic activity reduced after ovarectomy was gradually returning to the initial level, whereas under the effect of folliculin the phagocytic activity increased proportionally to the time of incubation of blood with Staphylococcus aureus bacterial areas. The phagocytic activity of the blood neutrophiles seems to depend on estrogens.


Tactic-specific differences in seminal fluid influence sperm performance.
Seminal fluid often makes up a large part of an ejaculate, yet most empirical and theoretical studies on sperm competition have focused on how sperm characteristics (number and quality) affect fertilization success. However, seminal fluid influences own sperm performance and may potentially influence the outcome of sperm competition, by also affecting that of rivals. As a consequence males may be expected to allocate their investment in both sperm and seminal fluid in relation to the potential level of competition. Grass goby (Zosterisessor ophiocephalus) is an external fertilizer with guard-sneaker mating tactics, where sperm competition risk varies according to the tactic adopted. Here, we experimentally manipulated grass goby ejaculates by separately combining sperm and seminal fluid from territorial and sneaker males. While sperm of sneaker and territorial males did not differ in their performance when they interacted with their own seminal fluid only, sperm of sneakers increased their velocity and fertilization rate in the presence of territorial males' seminal fluid. By contrast, sneaker males' seminal fluid had a detrimental effect on the performance of territorial males' sperm. Sperm velocity was unaffected by the seminal fluid of males employing the same tactic, suggesting that seminal fluid's effect on rival-tactic sperm is not based on a self/non-self recognition mechanism. Our findings show that cross interactions of sperm and seminal fluid may influence the fertilization success of competing ejaculates with males investing in both sperm and seminal fluid in response to sperm competition risk.


Supporting resident well-being on and outside the ICU during the COVID-19 pandemic: the use and value of institutional interventions and individual strategies.
During the COVID-19 pandemic, resident well-being has been shown to be at risk, which may interfere with residents' process of professional development during their educational trajectory. Therefore, we developed a well-being program for residents, aimed to help residents maintain their well-being during the COVID-19 pandemic. We explored residents' perceptions of their well-being as well as their perceived support of the well-being program during the COVID-19 pandemic. We invited all internal medicine residents and residents working in the ICU (N = 203) of one academic medical center to participate. The well-being program included a combination of (1) well-being measurements and (2) organizational support. The repeated well-being measurements involved a well-being survey on six measurement points from April to June 2020, and organizational support combined the provision of institutional interventions and promotion of individual strategies to help residents maintain their well-being during a pandemic. In total, 103 residents (50.1%) participated, showing that residents working in the ICU reported significantly lower levels of mental well-being than residents not working on the ICU. Furthermore, residents did not perceive the institutional interventions to benefit their well-being, while residents' reported engagement in individual strategies was significantly positively associated with their well-being. As ICU residents reported lower levels of mental well-being, well-being programs need to address ICU-specific stressors while enhancing supervision and peer support. Furthermore, the individual strategies of the well-being program should be tailored to residents' well-being needs as these were positively associated with resident well-being.


Systematic review of the effect of the psychosocial working environment on cognition and dementia.
The high incidence of cognitive impairment in the ageing population, together with the challenges it imposes to health systems, raises the question of what affect working life has on cognitive abilities. The study, therefore, reviews recent work on the longitudinal impact of psychosocial work conditions on cognitive functioning and on dementia. Relevant articles were identified by a systematic literature search in PubMed and PsycINFO using a standardised search string and specific inclusion and exclusion criteria. We included articles reporting longitudinal effects that were investigated in cohort studies, case-control studies or randomised controlled trials in the working population. Two independent reviewers evaluated the studies in three subsequent phases: (i) title-abstract screening, (ii) full-text screening and (iii) checklist-based quality assessment.Methodical evaluation of the identified articles resulted in 17 studies of adequate quality. We found evidence for a protective effect of high job control and high work complexity with people and data on the risk of cognitive decline and dementia. Moreover, cognitively demanding work conditions seem to be associated with a decreased risk of cognitive deterioration in old age.Psychosocial work conditions can have an impact on cognitive functioning and even on the risk of dementia. As the world of work is undergoing fundamental changes, such as accelerated technological advances and an ageing working population, optimising work conditions is essential in order to promote and maintain cognitive abilities into old age.


[Defining priorities for the management of health science and technology].
An urgent need for the management of science and technology production in the health field has been recognised in Brazil since 1994, when the Federal Government called a National Conference on the subject. The present study presents a methodology for the identification of items of priority in planning such management. A survey was conducted in the research institutes belonging to the S. Paulo State Health Department among a sample of research professionals with a view to collecting data on two different scenarios: present and expected situation. Eighteen concepts, assembled in four different groups, were assessed is terms of an average percentage approval or disapproval, for each scenario. Consistency for the measurement of each of these groups was examined by the use of Cronbach's alpha coefficient and inconsistent concepts were disregarded in the analysis. The average percentage of approval/disapproval was further calculated as scenario co-ordinates for each concept and institute entering the study so that priority maps for concepts and institutes could be constructed. Results suggest that the present situation meets with disapproval, though not strongly so, while a high degree of expectation is expressed with significant emphasis as regards research infrastructure management. The main priorities are given as: acknowledgement of performance, support for publication, resource allocation by research project and methodological advice for research analysis. It is concluded that the study methodology was helpful in eliciting management priorities and could be applied elsewhere with due adjustment of content regarding selection of concept and their grouping.


Evaluating the Effectiveness of Fatigue Management Training to Improve Police Sleep Health and Wellness: A Pilot Study.
To evaluate the effectiveness of an intervention for improving sleep health in a sample of employees from the Royal Canadian Mounted Police (RCMP). Using a pre- and post-design we exposed 61 RCMP members to a fatigue-management training program. Pre- and post-intervention surveys included the Pittsburg Sleep Quality Index (PSQI), the World Health Organization Quality of Life (WHOQOL) instrument, and the six item index of psychological distress (Symptom Checklist-90). We found the training improved member satisfaction with sleep (Wald = 2.58; df = 1; P = 0.03) and reduced symptoms of insomnia (Wald = 5.5; df = 1; P = 0.02). Furthermore, the training reduced the incidence of headaches (Wald = 6.5; df = 1; P = 0.01). Our findings suggest that a fatigue management training program resulted in positive sleep health benefits for police. We stress the importance of continued evaluation to inform the large-scale implementation of fatigue-management programs.


Diversity of locations for Bacillus thuringiensis crystal protein genes.
The location of crystal protein genes in 22 crystalliferous Bacillus thuringiensis strains representing 14 subspecies was investigated by hybridization of an intragenic restriction fragment from a cloned crystal protein gene to whole plasmid preparations. Hybridization was found to a single plasmid in eight strains, to more than one plasmid in seven strains, and to one or both of two large, unresolved plasmids in two strains. The sizes of the hybridized plasmids ranged from 33 to over 150 megadaltons. In one additional subspecies, hybridization was only to linear DNA fragments, suggesting a chromosomal crystal protein gene, and for four other subspecies, not reported to be toxic to lepidopteran insects, no hybridization was found to either plasmids or to total cell DNA. Hybridization to restriction digests of plasmids and total cell DNA of several strains of subspecies thuringiensis and kurstaki revealed that all homology to the cloned crystal protein gene was plasmid associated and that several of these strains contained multiple regions of homology, implying the presence of multiple crystal protein genes.


"Ready-to-Recruit" or "Ready-to-Consent" Populations?: Informed Consent and the Limits of Subject Autonomy.
This paper queries the pharmaceutical industry's concept of "ready-to-recruit" populations by examining its recruitment strategies for clinical trials and the types of human subjects who participate in these drug studies. The argument is that the pharmaceutical industry has profited from a system comprised of what can more aptly be characterized as ready-to-consent populations, meaning populations who do not have better alternatives than participation in clinical trials. Further, through qualitative research, this paper aims to highlight some of the limitations of current U.S. federal regulation and to show how these limits signal problems that are not normally discussed in the medical ethics literature about research on human subjects. It does this by examining the impotence of informed consent - both as a concept and as a practice - in light of recruitment strategies and the structural reasons motivating individuals to participate in clinical trials.


Attributes that differentiate children who sip alcohol from abstinent peers.
Sipping alcohol during childhood may be a marker of differentiation as regards children's future risk of underage drinking; yet very little is known about alcohol use when it occurs among elementary school-aged children. The purpose of the present study is to examine alcohol sipping behavior in a sample of third-grade school children to learn whether sipping is associated with attributes that could increase children's likelihood of further underage drinking. We collected telephone interview data from 1,050 mothers and their third grade children (mean age 9.2 years; 48.2% male) residing in the Southeastern United States. The majority of mothers were White non-Hispanic (69.02%) or Black non-Hispanic (21.3%); most (85%) lived in households shared with fathers or other adult caretakers. We hypothesized that children who sip alcohol would score lower than abstinent peers on indicators of competence and score higher on indicators of exposure to alcohol-specific socialization by parents and peers. A multivariate model controlling for frequency of parent alcohol use and demographic covariates showed that children who had sipped alcohol were significantly less likely than abstinent peers to affirm indicators of competence and significantly more likely to affirm indicators of exposure to alcohol specific socialization by parents and by same age peers. These preliminary findings suggest that developmental attributes associated with risk of underage drinking begin to differentiate at least as young as middle childhood. Research is needed to test prospectively for continuity between alcohol risk attributes present in middle childhood and future alcohol use.


Sexual adjustment of men who have had strokes.
Fifty men who had suffered moderate to severe strokes were interviewed approximately six months later and asked about their sexual adjustment. Interest in sex had returned in most cases, although the level of interest was reduced in some. Nearly all the men had regained their erectile capacity, usually after a delay of approximately seven weeks following the stroke. Of those sexually active with their partner before their strokes, over half had resumed sexual intercourse by the time of the interview. Most of these men had encountered difficulties because of the physical consequences of their strokes, but two-thirds had tried new sexual positions to compensate for this. Whether or not a couple resumed sexual activity after the man's stroke was largely predictable on the basis of the frequency of their previous sexual activity, rather than the man's age or the severity of physical disability. For patients who are sexually active before suffering strokes, subsequent rehabilitation should include brief counselling on sexual readjustment for both the patients and their partners.


Transcriptional, translational and metabolic regulation of glycolysis in Lactococcus lactis subsp. cremoris MG 1363 grown in continuous acidic cultures.
The physiological behaviour of Lactococcus lactis subsp. cremoris MG 1363 was characterized in continuous culture under various acidic conditions (pH 4.7-6.6). Biomass yield was diminished in cultures with low pH and the energy dedicated to maintenance increased due to organic acid inhibition and cytoplasmic acidification. Under such acidic conditions, the specific rate of glucose consumption by the bacterium increased, thereby enhancing energy supply. This acceleration of glycolysis was regulated by both an increase in the concentrations of glycolytic enzymes (hierarchical regulation) and the specific modulation of enzyme activities (metabolic regulation). However, when the inhibitory effect of intracellular pH on enzyme activity was taken into account in the model of regulation, metabolite regulation was shown to be the dominant factor controlling pathway flux. The changes in glycolytic enzyme concentrations were not correlated directly to modifications in transcript concentrations. Analyses of the relative contribution of the phenomena controlling enzyme synthesis indicated that translational regulation had a major influence compared to transcriptional regulation. An increase in the translation efficiency was accompanied by an important decrease of total cellular RNA concentrations, confirming that the translation apparatus of L. lactis was optimized under acid stress conditions.


Laplace regression with censored data.
We consider a regression model where the error term is assumed to follow a type of asymmetric Laplace distribution. We explore its use in the estimation of conditional quantiles of a continuous outcome variable given a set of covariates in the presence of random censoring. Censoring may depend on covariates. Estimation of the regression coefficients is carried out by maximizing a non-differentiable likelihood function. In the scenarios considered in a simulation study, the Laplace estimator showed correct coverage and shorter computation time than the alternative methods considered, some of which occasionally failed to converge. We illustrate the use of Laplace regression with an application to survival time in patients with small cell lung cancer.


Porous hydrated ammonium vanadate as a novel cathode for aqueous rechargeable Zn-ion batteries.
Development of suitable cathodes for use in aqueous rechargeable zinc ion batteries has attracted extensive interest. Herein, the electrochemical and structural changes of a novel porous hydrated ammonium vanadate (AVO) cathode in an aqueous ZnSO4-based electrolyte are reported. The AVO/Zn system exhibits a high reversible capacity of 418 mA h g-1, excellent long-term cyclability, and outstanding storage performance. Moreover, an interesting insertion mechanism with ternary carriers in a Zn/AVO aqueous rechargeable zinc-ion battery has been demonstrated for the first time.


Application of transport phenomena analysis technique to cerebrospinal fluid.
The study of hydrocephalus and the modeling of cerebrospinal fluid flow have proceeded in the past using mathematical analysis that was very capable of prediction phenomenonologically but not well in physiologic parameters. In this paper, the basis of fluid dynamics at the physiologic state is explained using first established equations of transport phenomenon. Then, microscopic and molecular level techniques of modeling are described using porous media theory and chemical kinetic theory and then applied to cerebrospinal fluid (CSF) dynamics. Using techniques of transport analysis allows the field of cerebrospinal fluid dynamics to approach the level of sophistication of urine and blood transport. Concepts such as intracellular and intercellular pathways, compartmentalization, and tortuosity are associated with quantifiable parameters that are relevant to the anatomy and physiology of cerebrospinal fluid transport. The engineering field of transport phenomenon is rich and steeped in architectural, aeronautical, nautical, and more recently biological history. This paper summarizes and reviews the approaches that have been taken in the field of engineering and applies it to CSF flow.


Management of regional hidradenitis suppurativa with vacuum-assisted closure and split thickness skin grafts.
Hidradenitis suppurativa can be a debilitating chronic illness. The underlying cause of the disease is still not clear, but effective treatment of widespread regional disease relies on resection of all the involved skin and subcutaneous tissue. Closure of the resulting large wound is dependent on either flap or skin graft coverage. Many of the resulting wounds are too large for flap closure or result in unacceptable flap donor site deficits. We present a series of 11 patients with 24 regional disease sites treated with a protocol of excision, followed by wound vacuum-assisted closure (VAC; KCI, San Antonio, TX) therapy to stimulate angiogenesis of exposed fat, and then skin grafting with the use of VAC to support the grafts on the recipient sites. Only 3 of the patients required regrafting. One patient had a VAC failure because of poor patient compliance, and 1 patient had 4 sites that each required regrafting as the epithelium would not fill in the residual open areas as it usually did in other patients. All patients were cured of their local disease. Massive regional hidradenitis suppurativa can be successfully managed with wide excision, VAC therapy, and skin grafting to allow these patients to live normal and productive lives.


Effects of Osteoporosis-Inducing Drugs on Vitamin D-Related Gene Transcription and Mineralization in MG-63 and Saos-2 Cells.
Vitamin D3 is important for calcium and phosphate homeostasis. To exert its effects, vitamin D3 has to be enzymatically activated into 1,25D3 (1,25-dihydroxyvitamin D3 ). Regulation by endogenous vitamin D metabolites of the activation and inactivation of 1,25D3 is important to maintain adequate amounts of active vitamin D3 . Vitamin D deficiency and low bone mineral density have been linked to treatments with antiretroviral drugs and glucocorticoids. However, the causes of drug-induced osteoporosis remain unclear. The antiretroviral drugs efavirenz and ritonavir as well as the glucocorticoid dexamethasone were included in this study. Their effects on transcription of vitamin D-regulating enzymes in MG-63 cells were investigated. Ritonavir and dexamethasone both induced transcription of CYP27B1, the enzyme responsible for the formation of 1,25D3 . Efavirenz, however, suppressed CYP27B1 expression. When administered together with endogenous vitamin D metabolites, dexamethasone and efavirenz counteracted the 1,25D3 -mediated up-regulation of CYP24A1, which inactivates 1,25D3 . This suggests that the drugs may interfere with local regulation of the vitamin D metabolizing system in osteoblasts. Studies on mineralization were performed in MG-63 cells and Saos-2 cells by measuring calcium concentrations accumulated over time. The effects of efavirenz, ritonavir and dexamethasone and/or vitamin D metabolites were examined. 1,25D3 induced mineralization in both cell lines. Efavirenz administered alone did not affect mineralization but suppressed the inducing effects of 1,25D3 on mineralization in both MG-63 cells and Saos-2 cells. In summary, the results suggest that antiretroviral drugs and glucocorticoids may adversely affect bone by interference with the vitamin D system in osteoblasts.


The importance of cardiovascular pathology contributing to maternal death: Confidential Enquiry into Maternal Deaths in South Africa, 2011-2013.
Cardiac disease is emerging as an important contributor to maternal deaths in both lower-to-middle and higherincome countries. There has been a steady increase in the overall institutional maternal mortality rate in South Africa over the last decade. The objectives of this study were to determine the cardiovascular causes and contributing factors of maternal death in South Africa, and identify avoidable factors, and thus improve the quality of care provided. Data collected via the South African National Confidential Enquiry into Maternal Deaths (NCCEMD) for the period 2011-2013 for cardiovascular disease (CVD) reported as the primary pathology was analysed. Only data for maternal deaths within 42 days post-delivery were recorded, as per statutory requirement. One hundred and sixty-nine cases were reported for this period, with 118 complete hospital case files available for assessment and data analysis. Peripartum cardiomyopathy (PPCM) (34%) and complications of rheumatic heart disease (RHD) (25.3%) were the most important causes of maternal death. Hypertensive disorders of pregnancy, HIV disease infection and anaemia were important contributing factors identified in women who died of peripartum cardiomyopathy. Mitral stenosis was the most important contributor to death in RHD cases. Of children born alive, 71.8% were born preterm and 64.5% had low birth weight. Seventy-eight per cent of patients received antenatal care, however only 33.7% had a specialist as an antenatal care provider. Avoidable factors contributing to death included delay in patients seeking help (41.5%), lack of expertise of medical staff managing the case (29.7%), delay in referral to the appropriate level of care (26.3%), and delay in appropriate action (36.4%). The pattern of CVD contributing to maternal death in South Africa was dominated by PPCM and complications of RHD, which could, to a large extent, have been avoided. It is likely that there were many CVD deaths that were not reported, such as late maternal mortality (up to one year postpartum). Infrastructural changes, use of appropriate referral algorithm and training of primary, secondary and tertiary staff in CVD complicating pregnancy is likely to improve the outcome. The use of simple screening equipment and point-of-care testing for early-onset heart failure should be explored via research projects.


A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants.
A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo). Preterm infants 500 to 1250 g birth weight and ≤48 hours of age were randomized to Darbe (10 μg/kg, 1 time per week subcutaneously), Epo (400 U/kg, 3 times per week subcutaneously) or placebo (sham dosing) through 35 weeks' gestation. All received supplemental iron, folate, and vitamin E, and were transfused according to protocol. Transfusions (primary outcome), complete blood counts, absolute reticulocyte counts (ARCs), phlebotomy losses, and adverse events were recorded. A total of 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation, 51 ± 25 hours of age at first dose) were enrolled. Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and were exposed to fewer donors (P = .044) than the placebo group (Darbe: 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo: 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo: 2.4 ± 2.9 transfusions and 1.2 ± 1.3 donors per infant). Hematocrit and ARC were higher in the Darbe and Epo groups compared with placebo (P = .001, Darbe and Epo versus placebo for both hematocrit and ARCs). Morbidities were similar among groups, including the incidence of retinopathy of prematurity. Infants receiving Darbe or Epo received fewer transfusions and fewer donor exposures, and fewer injections were given to Darbe recipients. Darbepoetin and Epo successfully serve as adjuncts to transfusions in maintaining red cell mass in preterm infants.


[Medical-psychologic study of somatic patients].
An attitude towards the disease in patients with chronic somatic disturbances is determined by three factors: the nature of the disease, personality type and the attitude to this particular disease in the microsocial environment to which the patient belongs. Three main types of attitudes towards their disease in patients with chronic somatic disturbances are described: anxious-depressive, melancholic, obsessive-phobic, hypochondriacal, neurasthenical, dysphoric, euphoric, anozognosic, apathetic, egopathic (a fanatic preoccupation with work), sensitive, egocentric, paranoiac. These types may be mixed as well. A knowledge of the above-mentioned types is useful for psychotherapeutic approaches.


[Myringoplasty in chronic simple otitis media. Comparative analysis of underlay and overlay techniques].
Myringoplasty is a surgical procedure that has been routinely performed by otological surgeons for more than 40 years. Underlay and overlay are the most commonly used tympanoplastic techniques. A comparison was made of anatomic and functional results, and the year of intervention, for 97 myringoplasties, 54 using the underlay technique and 43 using the overlay technique. Selection of the overlay or underlay technique was guided by specific indications. Results were evaluated at least 1 year after surgery. No significant differences were found in anatomic success (88.8% for underlay and 97.6% for overlay). Favorable functional results (average gap of 0 to 20 dB for frequencies of 500, 1000, 2000, and 4000 Hz) were obtained in 88.4% of patients treated with the overlay technique and in 83% of those treated with the overlay technique, with no significant difference. We believe that the high percentage of good results was due to careful preoperative selection.


Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands.
The study aimed at probing the possible role of human papillomavirus (HPV) infection in squamous cell carcinomas of the upper aerodigestive tract, with a special reference to tonsillar cancer. We used the Swedish Family Cancer Database to analyse second cancers in the upper aerodigestive tract of women first diagnosed with in-situ or invasive cervical cancer. First cancers of their husbands were also analysed. Standardized incidence ratios (SIRs) were calculated for female and male cancers, adjusted for age at diagnosis, period, sex, socio-economic status and residential area. Among women, increases were observed at many sites, but tonsillar cancers were increased only among women aged 50 years or more at diagnosis of in-situ cervical cancer (SIR 2.58). The increases at these sites are probably ascribed to the effects HPV, smoking, alcohol or their interaction. Husbands of cervical cancer patients developed an excess (SIR over 2.00) of both tonsillar cancer (SIR 2.39 when wife with in-situ cancer and SIR 2.72 when wife with invasive cervical cancer) and cancer of the tongue. The excess of tonsillar cancer among husbands of women with HPV-associated neoplastic lesions of the cervix supports the a priori hypothesis that HPV may be involved in tonsillar carcinogenesis.


Screening for cognitive and behavioral change in amyotrophic lateral sclerosis/motor neuron disease: a systematic review of validated screening methods.
Cognitive and behavioral change in Amyotrophic Lateral Sclerosis (ALS) is well-accepted. Several screening tools have been developed to detect such changes. Further guidance on their use may come from a consideration of the rigor with which they were validated. This systematic review set out to critically appraise and present published data pertaining to the validation of six screening tools used to diagnose cognitive and/or behavioral change in patients with ALS. The screening tools considered in this search included: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS), The ALS Cognitive Behavioural Screen (ALS-CBS), The Motor Neuron Disease Behavioural Scale (MiND-B), The Frontal Behavioural Inventory ALS Version, The ALS Frontotemporal Dementia Questionnaire (ALS-FTD-Q), and The Beaumont Behavioural Inventory (BBI). MEDLINE, EMBASE, and PsycINFO were searched until 4th week of June 2017. Fourteen eligible studies were included in the review. Papers either reported data concerning convergent validity or clinical validity. Validation data concerning the ECAS showed this screening tool to have strong clinical validity, although further work needs to consider how its use will affect diagnosis rates according to current diagnostic guidelines. When screening for behavioral change only, more limited information is available; the BBI may offer greater potential than the ALS-FTD-Q for detecting mild impairment as it assesses a wider range of behavioral changes. Scores of sensitivity, specificity, positive predictive values, and negative predictive values should be given considerable importance when considering which screening tools to incorporate into current clinical practice.


High resolution spatial distribution of neuropeptides by MALDI imaging mass spectrometry in the terrestrial snail, Helix pomatia.
Imaging mass spectrometry (IMS) is a powerful technique that combines the chemical and spatial analysis of surface materials. It allows spatial localization of peptides, proteins or lipids that are recorded in parallel without the need of a label. It is currently one of the most rapidly developing techniques in the proteomics toolbox. In the present study, accurate mass matrix-assisted laser desorption/ionization imaging mass spectrometry (MALD IMS) was used for direct molecular mapping of nervous tissue at micrometer spatial resolution. Cryosections of the whole brain of the terrestrial snail, Helix pomatia, were placed on indium-tin-oxide (ITO)-coated conductive glass slides and covered with a thin layer of α-cyano-4-hydroxycinnamic acid (CHCA) matrix by electro spray deposition. High-resolution molecular ion maps of well-known neuropeptides, such as FMRFamide were constructed. FMRFamide is known to exert powerful modulatory effect on synaptic transmission in molluscs. FMRFamide was predominantly localized in the cluster of neurons in the pro-, meso- and postcerebral regions of cerebral ganglia, pedal ganglia and right parietal ganglia of the central nervous system. Our present study, using MALDI IMS confirmed the distribution of FMRFamide containing cells in the Helix central nervous system previously detected by antibody dependent immunohistochemistry.


Racial/ethnic disparities in time to follow-up after an abnormal mammogram.
Although non-Hispanic white women have an increased risk of developing breast cancer, the disease-specific survival is lower for African American and Hispanic women. Little is known about disparities in follow-up after an abnormal mammogram. The goal of this study was to investigate potential disparities in follow-up after an abnormal mammogram. A retrospective cohort study of 6722 women with an abnormal mammogram and documented follow-up from January 2000 through December 2002 was performed at an academic medical center in New York City. The outcome was the number of days between the abnormal mammogram and follow-up imaging or biopsy. Cox proportional hazards models were used to assess the effect of race/ethnicity and other potential covariates. The median number of days to diagnostic follow-up after an abnormal mammogram was greater for African American (20 days) and Hispanic (21 days) women compared with non-Hispanic white (14 days) women (p < 0.001). Racial/ethnic disparities remained significant in a multivariable model controlling for age, Breast Imaging Reporting and Data System (BIRADS) category, insurance status, provider practice location, and median household income. After an abnormal mammogram, African American and Hispanic women had longer times to diagnostic follow-up compared with non-Hispanic white women. Future efforts will focus on identifying the barriers to follow-up so that effective interventions may be implemented.


[The combined treatment of locally disseminated stomach cancer with intra-arterial regional chemotherapy].
The method of a long-term celiac artery catheterization through the lumbar transaortic access is proposed. In 56 patients with a 3d stage gastric cancer regional intraarterial chemotherapy with 5-fluorouracil was used pre- and postoperatively. There was a decrease of postoperative complications from 47.8 + 6% in surgical treatment to 16.0 +/- 4% in combined treatment. Metastases and recurrence were observed in 11 (21.2 + 5%) patients with regional chemotherapy and in 34 (58.6 + 6%) patients with surgical treatment only.


Binocular interaction in the cat's superior colliculus.
1. Binocularly driven neurones with small receptive fields near the area centralis were recorded in the cat's superior colliculus. 2. Binocular interaction was tested by stimulating both eyes simultaneously with a single moving stimulus at various retinal disparities. 3. Collicular cells in general showed strong summation or even facilitation when the images of the stimulus were in exact correspondence on the receptive fields, sometimes with occlusion when they were out of register. The range of retinal disparity over which there was additive interaction could be as little as 1 or 2 deg, almost as narrow as for the most precisely tuned neurones in the visual cortex. Even cells with large receptive fields sometimes showed a narrow range of binocular interaction. 4. Non-directional cells generally exhibited weaker summation and broader disparity selectivity than did direction-selective cells. 5. Some neurones with virtually no response to a stimulus in one of the eyes can exhibit marked binocular interaction. Other apparently monocular cells show little or no binocular interaction. 6. The disparity of the centres of the receptive fields was measured after correcting for small eye movements, which were assessed by two different techniques. For 132 cells the measured distribution of horizontal disparity (range 4.5 deg; S.D. 0.93 deg) was significantly broader than that of vertical disparity (range 2.2 deg; S.D. 0.52 deg). Sources of error in these measurements are considered. 7. The results are discussed in relation to the known connexions between visual cortex and superior colliculus and the possible role of the latter in the regulation of eye movements.


Evolution of response dynamics underlying bacterial chemotaxis.
The ability to predict the function and structure of complex molecular mechanisms underlying cellular behaviour is one of the main aims of systems biology. To achieve it, we need to understand the evolutionary routes leading to a specific response dynamics that can underlie a given function and how biophysical and environmental factors affect which route is taken. Here, we apply such an evolutionary approach to the bacterial chemotaxis pathway, which is documented to display considerable complexity and diversity. We construct evolutionarily accessible response dynamics starting from a linear response to absolute levels of attractant, to those observed in current-day Escherichia coli. We explicitly consider bacterial movement as a two-state process composed of non-instantaneous tumbling and swimming modes. We find that a linear response to attractant results in significant chemotaxis when sensitivity to attractant is low and when time spent tumbling is large. More importantly, such linear response is optimal in a regime where signalling has low sensitivity. As sensitivity increases, an adaptive response as seen in Escherichia coli becomes optimal and leads to 'perfect' chemotaxis with a low tumbling time. We find that as tumbling time decreases and sensitivity increases, there exist a parameter regime where the chemotaxis performance of the linear and adaptive responses overlap, suggesting that evolution of chemotaxis responses might provide an example for the principle of functional change in structural continuity. Our findings explain several results from diverse bacteria and lead to testable predictions regarding chemotaxis responses evolved in bacteria living under different biophysical constraints and with specific motility machinery. Further, they shed light on the potential evolutionary paths for the evolution of complex behaviours from simpler ones in incremental fashion.


Can Sex-hormone Binding Globulin Considered as a Predictor of Response to Pharmacological Treatment in Women with Polycystic Ovary Syndrome?
This study aims to evaluate the sex hormone binding globulin (SHBG) level as a predictor of response to pharmacological treatment in women with polycystic ovary syndrome (PCOS). This study was conducted in 2009-2012 in Isfahan, Iran. Anovulatory women with a diagnosis of PCOSwere studied. Metformin was started at 500 mg three times a day. If no ovulation occurred, Clomiphene citrate was added. The study comprised273 infertile women with PCOS completed the study, 75 (28%) of them became pregnant 6 months after treatment (7.36% with metformin and 20.14% with metformin and clomiphene citrate). Patients who responded to metformin treatment had significantly lower mean SHBG levels compared to those who did not (0.88+0.32vs. 0.2642+0.44 nmol/L, respectively, P<0.0001). The area under the ROC curve (AUC) for prediction the response to treatment was 0.85. The baseline level of 27was the most appropriate cut of point HSBG for the prediction of conception. HSBG had a sensitivity of 88%, and specificity of 73.6%. It had a false positive level of 26.4% and false negative level of 12%. Its positive predictive value was 56.4% and its negative predictive value was 94%. The chance of conception increased for reducing a unit of fpg (OR = 0.69; 95% CI = 0.54-0.86; P = .002), as well as reducing of every unit of HSBG (OR = 0.47; 95% CI = 0.39-0.56; P <0.001), and for reducing each unit of insulin in (OR = 0.082; 95% CI = 1.021-0.33; P <0.001). HSBG test is suggested as an appropriate test for predicting pregnancy achievement of PCOs women after pharmacological treatment.


Shear wave elasticity of breast lesions: would it be correlated with the extracellular matrix components?
Malignant breast lesions have higher shear wave elasticity than benign lesions, and the occurrence of breast lesions is accompanied by changes in extracellular matrix (ECM) components which are related to invasion and metastasis of breast lesions. Therefore, the purpose of this study was to analyze the relationship between shear wave elasticity and ECM components in breast lesions. From March 2012 to March 2013, 69 consecutive breast lesions in 65 patients were eventually included in this study. The shear wave elasticity features of the lesions and their diagnostic performance were analyzed. ECM components of the specimens were analyzed by Van Gieson (VG) dye, Aldehyde Fuchsin dye and immunohistochemical staining, respectively. Image-Pro Plus 5.1 software was used for quantitative analysis of the areas of the components of ECM. The elasticity ratio of lesions to peripheral parenchyma, maximum elasticity and mean elasticity of malignant lesions were significantly higher than those of benign lesions (3.5±0.7 vs. 2.3±0.9, 112.5±27.2 vs. 45.0±20.5, 44.0±10.3 vs. 26.0±14.0 kPa, respectively; P=0.014, P=0.000, P=0.000, respectively). The contents of collagen fiber and elastic fiber of benign lesions were significantly lower than those of malignant lesions (9,717.2±2,548.1 vs. 13,757.2±2,926.6, 9,257.5±2,392.8 vs. 14,384.4±2,853.7, P<0.001, P<0.001). Multiple linear regression analysis showed that collagen fiber and elastic fiber were independent variables correlated to the maximum elasticity of breast lesions (r2 =0.564, P=0.014). The contents of collagen fiber and elastic fiber are positively correlated with the elasticity of breast lesions, which suggested that further study of the mechanism of ECM might provide a new method for the study of the elasticity of breast carcinoma.


[Complaints caused by episiotomy. Study of 413 women with spontaneous complication-free labor].
In 413 women following normal spontaneous delivery the short and long term complaints due to the episiotomy were studied. Every fifth woman found the cutting of the episiotomy painful. Episiotomies done by specialist's or chief residents were found to be less-painful. The suturing of the episiotomy was found to be painful by 4 of 10 women. The more experienced the surgeon the less was the pain. Only every tenth woman had no pain in the episiotomy immediately post-partum independent of the experience of the obstetrician. Medilateral episiotoma were twice as often very painful (21%) as median episiotomies (11%). Every fifth woman had pain in the perineum for more than one month. A third of these women had more pain with sexual intercourse than prior to delivery. Every tenth woman had infections in the episiotomy, half of these required treatment. Following medio-lateral episiotomy there were twice as many complication with the episiotomy than following median-episiotomy. Every fifth woman though that her vagina and perineum was disfigured by the episiotomy scar. This impression was independent of the type of episiotomy and of the experience of the obstetrician. More dyspareunia than prior to delivery was reported by twice as many primipara (20%) as multipara (11%). 18% of the women reported that the vaginal introitus appeared to be narrower than prior to the delivery.


Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.
During skeletal development most bones are first formed as cartilage templates, which are gradually replaced by bone. If later in life those bones break, temporary cartilage structures emerge to bridge the fractured ends, guiding the regenerative process. This bone formation process, known as endochondral ossification (EO), has been widely studied for its potential to reveal factors that might be used to treat patients with large bone defects. The extracellular matrix of cartilage consists of different types of collagens, proteoglycans and a variety of non-collagenous proteins that organise the collagen fibers in complex networks. Thrombospondin-5, also known as cartilage oligomeric matrix protein (TSP-5/COMP) is abundant in cartilage, where it has been described to enhance collagen fibrillogenesis and to interact with a variety of growth factors, matrix proteins and cellular receptors. However, very little is known about the skeletal distribution of its homologue thrombospondin-4 (TSP-4). In our study, we compared the spatiotemporal expression of TSP-5 and TSP-4 during postnatal bone formation and fracture healing. Our results indicate that in both these settings, TSP-5 distributes across all layers of the transient cartilage, while the localisation of TSP-4 is restricted to the population of hypertrophic chondrocytes. Furthermore, in fractured bones we observed TSP-4 sparsely distributed in the periosteum, while TSP-5 was absent. Last, we analysed the chemoattractant effects of the two proteins on endothelial cells and bone marrow stem cells and hypothesised that, of the two thrombospondins, only TSP-4 might promote blood vessel invasion during ossification. We conclude that TSP-4 is a novel factor involved in bone formation. These findings reveal TSP-4 as an attractive candidate to be evaluated for bone tissue engineering purposes.


Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol.
Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-κB translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-κB signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-κB translocation into the nucleus that resulted in high NF-κB transcription activity. The overall magnitude of NF-κB transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-κB translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-κB transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-κB transcription factor.


Androgen receptor down-regulation in prostate cancer with phosphorodiamidate morpholino antisense oligomers.
Androgen receptor (AR) has a pivotal role in the growth and proliferation of prostate cancer (PCa). Even in advanced stages of PCa AR continues to be expressed and appears to be functional. Since the mechanisms of AR activation in androgen independent PCa have yet to be clearly defined, the decrease in AR protein by antisense compounds is an attractive therapeutic option. In this study we evaluated a novel antisense phosphorodiamidate morpholino oligomer (PMO) targeting the translational start site of AR mRNA in vitro and in vivo in a PCa xenograft and murine prostate. AR antisense PMOs targeting the AR initiation AUG were tested in vitro and in LNCaP cells, and in vivo in LAPC-4 xenografts and normal mouse prostate. Effects on AR protein and PSA expression were assessed. AR antisense PMOs specifically down-regulated AR protein levels in a plasmid based screening system and also decreased endogenous AR levels in androgen responsive LNCaP cells in culture compared to control nonspecific PMOs. Pretreatment and posttreatment biopsies in the LAPC-4 xenograft model demonstrated that the antisense AR PMO administered intraperitoneally specifically decreased AR protein levels and serum PSA. Analysis of tissue distribution of the AR PMO by high performance liquid chromatography based methodology showed significant PMO levels in tumor tissue and mouse prostate, and there was a dose dependent decrease in AR protein levels in murine AR antisense PMO treated mouse prostates. An AR antisense PMO with unique chemical properties administered once daily can decrease AR protein levels and PSA in vivo. The reduction of AR protein with an antisense PMO may be an effective method of interfering with AR mediated growth in advanced human PCa.


Thermocouple-tip-exposing temperature assessment technique for evaluating photothermal conversion efficiency of plasmonic nanoparticles at low laser power density.
A new thermocouple (TC) tip-exposing temperature assessment technique that combines experimental temperature measurements with a numerical model of the photothermal conversion efficiency η is presented. The proposed technique is designed to evaluate η for a gold-coated superparamagnetic iron oxide nanoparticle (SPIO-Au NP) solution (26 nm, 12-70 ppm) at low continuous wave laser power (103 mW, 532 nm) irradiation in a convenient manner under ambient conditions. The TC tip temperature is measured during the first 30 s of the laser exposure, and the results are combined with a finite element model to simulate the temperature rise of the NP solution for a given concentration. The value of η is adjusted in the model until the model agrees with the measured transient TC temperature rise. Values of η = 1.00 were observed for all concentrations. Theoretical predictions of η derived by Mie theory confirmed the near unity conversion efficiency of the as-synthesized SPIO-Au NPs. Advantages of the current technique include co-locating the TC tip in the geometric center of the laser-heated region, rather than outside of this region. In addition, the technique can be done under ambient room conditions using unmodified commercially available hardware.


Management of Terminal Osseous Overgrowth of the Humerus With Simple Resection and Osteocartilaginous Grafts.
Osseous overgrowth is a common complication in children after humeral transcortical amputation. Capping tibial overgrowth with the proximal fibula has been shown to be the most effective treatment. However, best treatment practices are not clear for the humerus. We compared patients treated surgically for humeral osseous overgrowth with simple resection or autologous osteocartilaginous graft to determine if this treatment were as effective in the humerus as it has been in the tibia. A retrospective review of humeral amputees from 1987 to 2011 at a pediatric hospital was performed. Patients with 2 years follow-up who underwent surgical treatment for established humeral overgrowth were included. Patients initially managed with simple resection were compared with those managed with autologous osteocartilaginous grafts. Descriptive statistics were calculated for demographic and outcome variables. T tests and χ tests were used to compare differences between groups. Eighteen humeri in 16 patients met inclusion criteria. Mean age at surgery was 8.3 (2.6 to 13.6) years and mean follow-up was 6.3 (1.5 to 10.4) years. Thirteen humeri underwent simple resection, with recurrent overgrowth in 9, and revision surgery in 8 at a mean 2.6 years. Five humeri were primarily managed with autologous osteocartilaginous grafts. Two developed non-overgrowth-related complications at 1 and 42 months. Including revision procedures after simple resection, 10 humeri were managed with autologous osteocartilaginous grafts. Thirty percent (3/10) required revision surgery; however, there were no cases of recurrent overgrowth. χ comparison showed lower rates of complications (P=0.004) and reoperation (P=0.012) with capping as compared with simple resection. Autologous osteocartilaginous capping of the humerus has a significantly lower rate of complications and reoperation compared with simple resection. However, the capping procedure has the potential for other complications related to difficulty with graft fixation. Surgeons should be aware that the outcomes are not as consistent as when the technique is applied to osseous overgrowth of the tibia and anticipate the possibilities of hardware prominence and difficulty with fixation. Level 3-therapeutic-retrospective comparative.


Dietary patterns and attention deficit hyperactivity disorder among Iranian children.
This study was conducted to assess the relation of major dietary patterns identified by factor analysis to attention-deficit/hyperactivity disorder (ADHD) in a group of Iranian school-age children. This cross-sectional study was conducted in 375 school-age children in Tehran, Iran. We assessed usual dietary intakes by a semiquantitative food-frequency questionnaire. The presence of ADHD was diagnosed using the questionnaire of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Major dietary patterns were identified by factor analysis. The prevalence of ADHD was 9.7% in this population. We identified four major dietary patterns: "healthy," "Western," "sweet," and "fast food." After controlling for potential confounders, children in the top quintile of the sweet dietary pattern score had greater odds for having ADHD compared with those in the lowest quintile (odds ratio 3.95, 95% confidence interval 1.16-15.31, P for trend = 0.03). Greater adherence to the fast-food dietary pattern was significantly associated with a higher risk of having ADHD (odds ratio 3.21, 95% confidence interval 1.05-10.90, P for trend = 0.03). No overall significant associations were seen between the healthy or Western dietary pattern and ADHD. We found significant independent associations between the sweet and fast-food dietary patterns and the prevalence of ADHD. Prospective studies are required to confirm these findings.


A case report of pedigree of a homozygous mutation of the steroidogenic acute regulatory protein causing lipoid congenital adrenal hyperplasia.
Lipoid congenital adrenal hyperplasia (LCAH) is extremely rare, but is the most fatal form of congenital adrenal hyperplasia resulting from mutations in the steroidogenic acute regulatory protein (STAR) gene. LCAH arises from severe defects in the conversion of cholesterol to pregnenolone, the precursor of all steroids. A case was reported that an 11-month-old Chinese girl who presented with a sex development disorder and hyponatremia. The clinical and genetic tests were carried out to confirm the diagnosis. The genogram of this case was also explored and analyzed. The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular-like tissue in the bilateral inguinal regions were detected with abdominal ultrasound. She was suspected of having LCAH, and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT (p.Lys236Thrfs*47) on exon 6 of the STAR gene. LCAH. She was prescribed hydrocortisone 10 to 12 mg/m2 and 9a- fludrocortisone 100 mg/d. Her skin hyperpigmentation and vomiting disappeared, and she had normal growth and development without adrenal crisis attacks. Her hormone and electrolyte levels remained normal, except for a persistently elevated ACTH level throughout 2 years of follow-up. At follow-up for 2 years, the patient is now 104.5 cm tall and weighs 23.3 kg at the age of 4 years old. Her plasma sodium and potassium concentration were normal. Her ACTH level is still elevated (1176 pg/mL). Her baseline sex hormone levels are testosterone <0.1 ng/dL and progesterone <0.08 ng/dL. The level of PRA (1.06 ng/mL per h) is within normal range. This mutation was in accordance with previously reported gene mutations. The patient's parents were nonconsanguineous; her parents, paternal grandfather, and maternal grandmother were all found to be carriers of a STAR gene mutation. This 46 XY disorders of sex development case presented with adrenal insufficiency and female phenotype initially. The diagnosis was complicated depending on the clinical hormone workup. LCAH was confirmed by genetic tests and genogram of the family.