Neighborhood Risk Factors for Recidivism: For Whom do they Matter?
Justice-involved people vary substantially in their risk of reoffending. To date, recidivism prediction and prevention efforts have largely focused on individual-level factors like antisocial traits. Although a growing body of research has examined the role of residential contexts in predicting reoffending, results have been equivocal. One reason for mixed results may be that an individual's susceptibility to contextual influence depends upon his or her accumulated risk of reoffending. Based on a sample of 2218 people on probation in San Francisco, California, this study draws on observational and secondary data to test the hypothesis that individual risk moderates the effect of neighborhood factors on recidivism. Results from survival analyses indicate that individual risk interacts with neighborhood concentrated disadvantage and disorder-and these factors increase recidivism among people relatively low in individual risk, but not those at higher risk. This is consistent with the disadvantage saturation perspective, raising the possibility that some people classified as low risk might not recidivate but for placement in disadvantaged and disorderly neighborhoods. Ultimately, residential contexts "matter" for lower risk people and may be useful to consider in efforts to prevent recidivism.


Synergistic Genotoxic Effects and Modulation of Cell Cycle by Ginger Ethanolic Extracts in Adjunct to Doxorubicin in Human Lymphocytes In Vitro.
Several natural phytochemicals are increasingly used, as an adjunct to chemotherapy, to reduce drug adverse effects. Zingiber officinale rhizome (ginger) product has been reported to be effective against nausea and vomiting in patients receiving emetogenic chemotherapy such as cisplatin/doxorubicin (DXR). In addition, its ethanolic extract of Zingiber officinale rhizome (EEZOR) has been reported to possess anticarcinogenic properties. However, the mechanism for anticancer activity of ginger especially when used in combination with chemotherapy has not well elucidated, one of its possible mechanisms might involve its genotoxicity. To investigate genotoxic and cytotoxic potentials of EEZOR alone and EEZOR pretreatments followed by 0.1 mcg/ ml DXR, a genotoxic chemotherapeutic agent in human lymphocytes by sister chromatid exchange (SCE) assay in vitro. The effect on cell cycle kinetics was also explored. Human lymphocytes were treated with EEZOR alone at 25-500 mcg/ml and EEZOR pretreated at 12.5-200 mcg/ml followed by 0.1 mcg/ml DXR. SCE levels and cell cycle kinetics were evaluated. EEZOR significantly induced biphasic SCE at 50 and 400 mcg/ml (p < 0.05). However, cytotoxicity manifested at 500 mcg/ml. All EEZOR pretreatments at 12.5, 25, 50, and 100 mcg/ml, except at 200 mcg/ml, prior to DXR, moderately enhanced DXR-induced genotoxicity by 1.3 times (p < 0.05). Both EEZOR alone and EEZOR prior to DXR at certain concentrations delayed cell cycle. At specific doses, EEZOR could induce genotoxicity and in pretreatments could moderately enhance DXR-induced genotoxicity and delay cell cycle. This finding suggests that dosage use of EEZOR needs to be adjusted for long-term safety. In addition, EEZOR in adjunct to DXM might have potential benefits not only as an emetic agent but also in chemotherapy. Further in vivo animal and human studies to support this evidence is essentially needed.


Biological and chemical studies on mycobacteria. Relationship of colony morphology to mycoside content for Mycobacterium kansasil and Mycobacterium fortuitum.
Fregnan, G. B. (University of Wisconsin, Madison), D. W. Smith, and H. M. Randall. Biological and chemical studies on mycobacteria. Relationship of colony morphology to mycoside content for Mycobacterium kansasii and Mycobacterium fortuitum. J. Bacteriol. 82:517-527. 1961.-Using a suitable technique and an adequate medium it was possible to show a unique and uniform type of colony characteristic for Mycobacterium kansasii (photochromogen) and for Mycobacterium fortuitum strains freshly isolated either from patients, or from the soil, or kept in our stock culture collection for several years. New symbols have been proposed to represent these colony types. It was demonstrated that colony morphology is closely related to the specific mycoside present in a given strain; for example, M. kansasii strains showed in each instance colony type K and mycoside A, and M. fortuitum strains showed colony type F and mycoside F. Attention is called to the importance of the technique and the medium used. No change in colony morphology resulted from incubation in the presence of air containing 5 to 10% CO(2), although this improved growth. Better growth of mycobacteria occurred in the presence of glycerol, or lipids of a human strain of mycobacteria, or sodium bicarbonate, but the specificity of colony form was lost.


Dental caries and oral health practices among 12 year old children in Nairobi West and Mathira West Districts, Kenya.
Dental caries is a common disease in children which causes pain with resultant effect on various physiological and social functions. The main objective of the study was to determine the association between dental caries and oral health knowledge and practice among children in Nairobi West and Mathira West Districts. A cross-sectional study was conducted among 639 children aged 12 years attending public primary schools in Nairobi West and Mathira West districts between August 2009-February 2010. A questionnaire was used to determine the level of knowledge and practices employed. Oral screening was performed using World Health Organisation (WHO) recommended methods. Dental caries was measured using the Decayed, Missing, Filled Teeth (DMFT) index. Nairobi West District had significantly higher caries prevalence of 37.5% than Mathira West District (24.0%). The DMFT in Nairobi West District was 0.76 ± 1.2, while in Mathira West District it was 0.36 ± 0.7. On multivariate analysis high consumption of soda was found to be a significant risk factor for dental caries in Nairobi West District(Odds Ratio (OR) = 3.0). In Mathira West District having an illiterate mother was a significant risk factor for dental caries (OR = 4.3). Countrywide intensive oral health promotion should be carried out especially in urban areas, to reduce the higher prevalence of dental caries. The school health policy should be used to promote oral health by provision of oral health instructions and highlighting harmful dietary practices. Preventive practices such as regular dental checkups should be advocated and promoted in schools.


Rationale for the association of sulfonylurea and insulin.
Approximately 20-30% of patients with non-insulin-dependent diabetes mellitus (NIDDM) started on sulfonylureas fail to respond to treatment (primary failure); in the remaining patients, secondary failure to sulfonylurea therapy occurs at a rate of 5-10% per year. On the other hand, in insulin-treated NIDDM patients a progressive increase in insulin requirement can occur without significant improvement in glucose control. In these patients the combination of oral agents with insulin therapy may be useful. The rationale behind this therapeutic approach resides in the synergistic action of the two agents on specific mechanisms responsible for glucose intolerance and hyperglycemia. Long-acting insulin, administered as a single dose at supper or bedtime, should restrain excessive overnight hepatic glucose production, thus allowing a significant reduction in fasting glucose concentrations. A lower ambient glucose level should favor the stimulatory effect of sulfonylureas on insulin secretion. Sulfonylurea treatment should increase the portal inflow of secreted insulin with a resultant increase in insulin levels draining into liver, thus reducing postprandial hepatic glucose output. Moreover, sulfonylureas might improve insulin action on its target tissue (i.e., muscle), thus increasing overall insulin-mediated glucose metabolism. The reduction in prevailing plasma glucose levels will reduce the toxic effect of hyperglycemia on the beta-cell and on insulin-sensitive tissues. On this basis, NIDDM patients with secondary failure of monotherapy may benefit from combined therapy. Nevertheless, the effects of combined therapy should be strictly monitored and intensive insulin therapy promptly started if poor control persists.


Improved mechanical properties of antimicrobial poly(N-[3-(dimethylaminopropyl)] methacrylamide) hydrogels prepared by free radical polymerization in the presence of cetyltrimethylammonium bromide as a lyotropic liquid crystal template.
The poor mechanical strength of the poly(N-[3-(dimethylamino)propyl] methacrylamide) (PDMAPMAAm) hydrogel limits its application as a drug delivery system and antimicrobial agent. In this study, both its morphology and antibacterial effectiveness were controlled through free radical solution polymerization in the presence of cetyltrimethylammonium bromide (CTAB; cationic nonreactive surfactant), forming lyotropic liquid crystal (LLC) mesophases. All the templated reactions proceeded in four different CTAB concentrations with three different concentrations of DMAPMAAm (2.0, 3.0 and 4.0 mol L-1), which were carried out in distilled-deionized water (DDW) using potassium persulfate (KPS) and N,N'-methylenebisacrylamide (BIS) as the initiator and crosslinker, respectively. The pH-dependent phase transition temperature (34 °C at pH 14), compression moduli, antibacterial and diffusion properties, and the effect of the LLC mesophases of CTAB on the hydrogel properties were investigated by mechanical measurements, image analysis, inhibition zone tests, X-ray diffractograms and polarized optical microscopy (POM). It was found that the compression moduli of the templated (T)-PDMAPMAAm hydrogels increased by nearly ten times (from ∼3.0 to 30.0 kPa) compared to that of the isotropic (I) ones. The POM and XRD results before the removal of CTAB exhibited the formation of lamellar and hexagonal mesophases. Further, the inhibition zones showed the ability of the I-PDMAPMAAm hydrogels to reduce the activity of E. coli even in the absence of CTAB, gentamicin (GS) and ciprofloxacin (CF). This was because the quaternary ammonium (QA) groups on the DMAPMAAm units could interact with the bacterial membrane.


A scoping review of research on potential impact of implicit bias in healthcare settings for children with acquired brain injuries.
Acquired brain injury (ABI) is a leading cause of disability in children and adolescents. Implicit biases within pediatric ABI healthcare settings may exert negative effects on clinical interactions and medical decision-making processes. This study aimed to conduct a scoping review of current research that examines the potential impact of implicit biases in such healthcare settings for children with ABI. Following PRISMA-ScR guidelines, a search among five databases (CINAHL, Cochrane CENTRAL, PubMed, PsycArticles, and PsycInfo) was conducted, followed by abstract/full-text screening and data extraction. Main characteristics of the included studies, including research design, relevance to implicit biases, and public health impact were synthesized. The risk of bias of included studies was assessed. Out of the 203 articles returned from the literature search, a total of three studies met the inclusion criteria for the present review. All studies examined the relevance of racial/ethnic biases for evaluating abusive head trauma or nonaccidental trauma. The included studies had an overall unclear to low risk of biases. This scoping review identified scarce but emerging evidence of the presence and detrimental impact of potential implicit biases on the access and quality of care received by children with ABI. More research is needed to examine the causes, process mechanisms, and consequences of implicit biases in pediatric ABI healthcare settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective.
Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.


Severe deformational plagiocephaly: long-term results of surgical treatment.
Deformational plagiocephaly (DP), a benign infantile condition, is often thought to improve spontaneously but can in fact lead to permanent skull asymmetry if left untreated. Deformational plagiocephaly can be completely corrected by nonsurgical treatments if recognized in the first year of life. Nevertheless, efficacy of these treatments drastically diminishes after 9 months as the calvaria thickens. Beyond 15 months, if the asymmetry is severe, surgical remodeling becomes an option. In this study, we analyzed the surgical morbidities and the morphologic outcome of surgical remodeling in DP. This study was designed as a retrospective analysis of a craniofacial database combined with an outcome study. Between January 1992 and August 2006, 2363 occipital DP cases were treated by repositioning. Thirty patients were operated on, always after the age of 15 months (1.23%). Mean (SD) age at the time of the first clinic was 19.2 (± 5.8) months (range, 11-34 mo). A switch cranioplasty (A) was first used, progressively replaced since 1995 by a large occipital monobloc graft rotated 180 degrees and fixed with tongue-in-groove pillars (B). Morbidities were extracted from the database. Long-term morphologic outcomes were evaluated during a free clinic visit with a 4-point Likert-type outcome scale. Mean (SD) age at the time of surgery was 20.2 (± 5.6) months. Incidents (dural tears or venous sinus breaches) occurred in 28% (A) and 36% (B) or patients. One complication required repeat operation (extradural hematoma). No cerebrospinal fluid leaks and/or meningitis were recorded. Mean (SD) hospital stay was 5.3 (± 0.95) days. There was no statistical difference in the long-term morphologic outcome between the 2 groups (median of group A being "good but still visible"; median of group B being "excellent, unnoticeable"). Surgical correction of DP is a potentially life-threatening procedure, which should be indicated only in very severe cases, after exhaustion of all other nonsurgical methods, in a reference craniofacial center combining pediatric neurosurgery and plastic surgery.


Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.
Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.


[Liability for medical malpractice: an economic approach].
In recent years, changes in the organization of healthcare institutions and the increased number of medical malpractice claims have revealed the need to study the concept of medical responsibility and the repercussion of these changes on healthcare provision. To date, discussion has focussed on legal aspects and economic implications have been largely ignored.The present article reviews studies that have performed an economic analysis the subject. Firstly, we examine studies that gradually introduce the concepts of uncertainty, risk aversion and moral hazard. Secondly, in the healthcare environment, we pay particular attention to models that include new arguments on professionals' objective duties or to bargaining models when there is asymmetric information. Finally, we consider the medical malpractice insurance market and investigate how reputation and the possibilities of exercising defensive medicine influence healthcare provision. Our analysis suggests that, due to the characteristics of the healthcare market, the models proposed by the economy of information are very useful for performing economic analyses of liability in medical malpractice. However, alternative hypotheses also need to be formulated so that these models can be adapted to the specific characteristics of different health systems.


Improved effects of okara atomized by a water jet system on α-amylase inhibition and butyrate production by Roseburia intestinalis.
Improving the physicochemical properties of okara for various applications in foods is of great importance. Here, okara and microcrystalline cellulose (MCC) were atomized using a water jet (WJ) system. The WJ-treated okara and MCC dispersed homogeneously in water, and their median sizes in particle size distribution were 6.6 μm and 9.5 μm, respectively. The dispersions of WJ-treated okara and MCC showed high apparent viscosity and shear thinning behavior. Moreover, the inhibition of α-amylase activities by WJ-treated okara was more effective than that by untreated MCC and cellulose. Furthermore, the production of short-chain fatty acids by 32 dominant species of human gut microbes was determined. An increase in butyrate production by Roseburia intestinalis was observed in the presence of WJ-treated okara, but not in untreated okara or WJ-treated MCC. These results demonstrate that WJ system can be used on okara to increase inhibited α-amylase activities and butyrate production by gut microbiota.


Template-directed molecular assembly on silicon carbide nanomesh: comparison between CuPc and pentacene.
The template-directed assembly of two planar molecules (copper phthalocyanine (CuPc) and pentacene) on SiC nanomesh has been studied by scanning tunneling microscopy and photoelectron spectroscopy, respectively. Both molecules are trapped as single molecules in the cells of SiC nanomesh at low coverage. At high coverage, CuPc forms a highly ordered single-molecular array with identical symmetry and periodicity as the substrate, whereas pentacene forms a quasi-amorphous layer due to the random mixture of three different adsorption configurations. This difference in adsorption behavior is attributed to differences in molecular geometries. The measured changes of work functions reveal weak charge transfer between the molecules and substrate. Both molecules are preferentially adsorbed on the SiC nanomesh rather than on graphene. The CuPc single-molecular array possesses good long-range order, large area coverage, and a molecular density of over 3.0 x 10(13) molecules/cm(2).


Beneficial effects of oleuropein on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle.
Oleuropein, the main constituents of leaves and fruits of the olive tree, has been demonstrated to exert various therapeutic and pharmacological properties including antidiabetic effect. However, the effectiveness of oleuropein on glucose homeostasis in intact rat skeletal muscle ex vivo has never been explored. Therefore, our current study was carried out to investigate and confirm the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. For this purpose, soleus muscles were incubated for 12 hr without (control) or with oleuropein, in the presence or absence of AMP-activated protein kinase (AMPK) inhibitor, compound C, or wortmannin, an inhibitor of phosphatidylinositol kinase. Oleuropein-stimulated glucose transport, plasmalemmal glucose transporter 4 (GLUT4), and phosphorylation of phosphatidylinositol kinase and AMPK were examined. We observed that oleuropein treatment enhanced glucose transport, GLUT4 translocation, and AMPK phosphorylation. The oleuropein-stimulated glucose uptake and GLUT4 translocation were inhibited by compound C and were not affected by wortmannin. These results suggest that increased glucose uptake induced by oleuropein might be mediated through activation of AMPK and the subsequent increase in GLUT4 translocation in skeletal muscles.


Endoplasmic reticulum-quality control chaperones facilitate the biogenesis of Cf receptor-like proteins involved in pathogen resistance of tomato.
Cf proteins are receptor-like proteins (RLPs) that mediate resistance of tomato (Solanum lycopersicum) to the foliar pathogen Cladosporium fulvum. These transmembrane immune receptors, which carry extracellular leucine-rich repeats that are subjected to posttranslational glycosylation, perceive effectors of the pathogen and trigger a defense response that results in plant resistance. To identify proteins required for the functionality of these RLPs, we performed immunopurification of a functional Cf-4-enhanced green fluorescent protein fusion protein transiently expressed in Nicotiana benthamiana, followed by mass spectrometry. The endoplasmic reticulum (ER) heat shock protein70 binding proteins (BiPs) and lectin-type calreticulins (CRTs), which are chaperones involved in ER-quality control, were copurifying with Cf-4-enhanced green fluorescent protein. The tomato and N. benthamiana genomes encode four BiP homologs and silencing experiments revealed that these BiPs are important for overall plant viability. For the three tomato CRTs, virus-induced gene silencing targeting the plant-specific CRT3a gene resulted in a significantly compromised Cf-4-mediated defense response and loss of full resistance to C. fulvum. We show that upon knockdown of CRT3a the Cf-4 protein accumulated, but the pool of Cf-4 protein carrying complex-type N-linked glycans was largely reduced. Together, our study on proteins required for Cf function reveals an important role for the CRT ER chaperone CRT3a in the biogenesis and functionality of this type of RLP involved in plant defense.


High Infection Fatality Rate Among Elderly and Risk Factors Associated With Infection Fatality Rate and Asymptomatic Infections of COVID-19 Cases in Hong Kong.
Background: Since the emergence in December 2019, the COVID-19 pandemic has become one of the greatest global public health threats in history. However, asymptomatic infections have increased the challenges of providing accurate estimates for the infection fatality rate (IFR) of COVID-19. Methods: We calculated the asymptomatic case ratios based on the reported COVID-19 cases in Hong Kong where intensive testing has been conducted in close contacts and high-risk populations. We estimated the IFR using both symptomatic and asymptomatic cases as denominator. The boosted regression tree (BRT) and multivariable logistic regression models were used to identify relative contribution and effect size of the risk factors associated with the asymptomatic cases and IFRs. Results: The ratio of the asymptomatic patients in Hong Kong was higher than many other regions over the world. Imported cases had a higher asymptomatic proportion than local cases. Older age and male were associated with a higher IFR than younger age and females. Conclusion: Policymakers should consider the potential risk factors for the asymptomatic infections and IFRs by the Hong Kong surveillance data to mitigate the diseases and reduce the case mortality of COVID-19.


Molecular-genetic and chemotaxonomic studies on Actinomadura and Nocardiopsis.
The relationships of 24 strains of 13 species of Actinomadura and 4 strains of Nocardiopsis dassonvillei were determined by nucleic acid hybridization studies. DNA-rRNA cistron similarity and DNA homology values reveal that Actinomadura is genetically heterogeneous. One cluster contained the type species Actinomadura madurae, Actinomadura pelletieri, Actinomadura verrucosospora, Actinomadura malachitica, Actinomadura citrea and 'Actinomadura kijaniata'. A second cluster embraced Actinomadura pusilla, Actinomadura roseoviolacea, Actinomadura libanotica, Actinomadura roseola and Actinomadura ferruginea. The internal homogeneity of the two Actinomadura clusters was demonstrated by a high similarity in the menaquinone and fatty acid composition of the strains enclosed. Actinomadura spadix, Actinomadura spiralis, and two strains of Actinomadura madurae were found to be unrelated to each other and could not be allocated to one of the two major Actinomadura clusters. Nocardiopsis dassonvillei was genetically and phenotypically clearly separated from all Actinomadura species investigated.


Perinatal mental healthcare in Northern Ireland: challenges and opportunities.
Perinatal mental health is a vital component of public mental health. The perinatal period represents the time in a woman's life when she is at the highest risk of developing new-onset psychiatric disorders or relapse of an existing mental illness. Optimisation of maternal mental health in the perinatal period is associated with both short- and long-term benefits not only for the mother, but also for her infant and family. However, perinatal mental health service provision remains variable across the world. At present in Northern Ireland, 80% of women do not have access to specialist community perinatal mental health services, and without access to a mother and baby unit, mothers who require a psychiatric admission in the postnatal period are separated from their baby. However, following successful campaigns, funding for development of specialist perinatal mental health community teams has recently been approved. In this article, we discuss the importance of perinatal mental health from a public health perspective and explore challenges and opportunities in the ongoing journey of specialist service development in Northern Ireland.


Results of reoperation for failed ulnar nerve surgery at the elbow: a systematic review and meta-analysis.
The clinical results of reoperation for recurrent or persistent ulnar nerve compression at the elbow have not been clearly determined. The aim of this review was to determine overall improvement, residual pain, and sensory and motor deficits following reoperation regardless of the type of primary surgery performed for this condition. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a systematic review and meta-analysis of studies was performed. An independent librarian performed a literature search using Ovid MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). The Newcastle-Ottawa Scale and the quality appraisal tool described by Moga et al. were used to assess the quality of included case series. Of the 278 retrieved studies, 16 were eligible for analysis and included a total of 290 patients with failed surgery for ulnar nerve entrapment at the elbow. Relief of symptoms after reoperation was reported in 85% of patients. A decrease in pain was noted in 85% of the patients (95% CI 75%-93%). Only 2.4% of patients with preoperative pain experienced worse pain after reoperation. Motor and sensory function improvement was noted in 77% (95% CI 63%-88%) and 77% (95% CI 61%-90%) of cases, respectively. Complete recovery from signs and symptoms at the final follow-up was noted in 23% of elbows (95% CI 16%-31%). Although the level of evidence of the included studies was low, the majority of patients had relief from their complaints after reoperation for recurrent or persistent ulnar nerve compression at the elbow following a previous surgery. The success rate of surgical treatment for a failed surgery was quite remarkable since almost a quarter of the patients completely recovered. Therefore, the authors recommend reoperation as a serious option for patients with this condition.


Psychosurgery: a retrospective.
Of the 56 patients within the Yakovlev collection who had undergone psychosurgery 11 (20%) improved, 18 (32%) were either worse or without improvement, and 27 (48%) were without any clinical follow-up. Thus, in retrospect, psychosurgery was perhaps not as successful as once envisioned.


Dermal drug delivery: Revisited.
The unique histological and molecular organization of skin poses a formidable barrier to drug delivery into and across skin. Due to the severe restrictions on molecular transport, only potent and lipophilic drug candidates have been able to successfully enter the market. New drug discovery programs based on high-throughput screening and combinatorial chemistry have lead to synthesis of potent but highly lipophilic molecules, and yet these molecules are difficult to deliver by conventional routes of administration. (trans)dermal delivery offers an attractive route of administration for these lipophilic molecules. Further, the diverse opportunities offered by genomics and proteomics cannot be effectively utilized without an equally diverse delivery approach. Skin offers a convenient and effective route for those genes and proteins due to the presence of the stem cell compartment in the epidermis.


Laser-induced breakdown spectroscopy (LIBS) of a high-pressure CO2-water mixture: application to carbon sequestration.
Geologic carbon storage in deep saline aquifers is considered a feasible and possible approach of mitigating the problem of increasing greenhouse gas emissions. However, there are latent risks in which carbon dioxide (CO2) could migrate from the deep saline formations to shallower aquifers. In the event of a significant CO2 leakage to an underground source of drinking water, CO2 will dissolve in the water, thereby increasing its acidity, which could potentially enhance the solubility of various aquifer constituents, including hazardous compounds, subsequently compromising groundwater quality due to increased concentration of aqueous metals. In this paper we explore the possibility of detecting such leakage by the use of laser-induced breakdown spectroscopy (LIBS). The experiments were conducted in calcium chloride solution at three pressures of 10, 50, and 120 bar. To evaluate the direct effect of elevated CO2 on the intensity of calcium emission lines (422.67 and 393.37 nm), we also performed experiments with pure nitrogen (N2) gas, offering large water solubility contrast. We found that when performed in presence of CO2, LIBS showed only a modest decrease in Ca emission intensity from 10 to 120 bar compared to N2. These results indicate that LIBS is a viable tool for measuring brine/water contents in high-pressure CO2 environment and can be applied for monitoring CO2 leakage and displaced brine migration.


5-HT1 and 5-HT2 binding characteristics of some quipazine analogues.
Arylpiperazines, such as 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and its chloro analogue mCPP, are 5-HT1 agonists, whereas quipazine, i.e., 2-(1-piperazino)quinoline, appears to be a 5-HT2 agonist. Radioligand binding studies using rat cortical membrane homogenates and drug discrimination studies using rats trained to discriminate a 5-HT1 agonist (i.e., TFMPP) or a 5-HT2 agonist (i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)) from saline reveal that quipazine and its 1-deaza analogue 2-naphthylpiperazine (2-NP) bind at 5-HT1 and 5-HT2 sites but produce stimulus effects similar to those of DOM. A structurally related compound, 1-naphthylpiperazine (1-NP), possesses a high affinity for 5-HT1 (Ki = 5 nM) and 5-HT2 (Ki = 18 nM) sites. 1-NP produces stimulus effects similar to those of TFMPP and is able to antagonize the stimulus effects produced by DOM. The present results suggest that the unsubstituted benzene ring of quipazine, and of its 1-deaza analogue 2-naphthylpiperazine, makes a significant contribution to the binding of these agents to 5-HT2 sites and, more importantly, may account for their 5-HT2 agonist properties.


Advances in immunology.
Much was accomplished in the last decade in understanding how the adaptive immune system evolved to combat pathogens. Essential features of antigen presentation and T lymphocyte recognition were deciphered, setting the stage for further studies that elucidated basic elements of lymphocyte differentiation (including positive and negative selection during lymphocyte ontogeny) and the major interactions that occur among cells in secondary lymphoid organs in an ongoing immune response. The major challenges of today are found in the burgeoning fields of programmed cells death, enzymology of recombination and somatic mutation, development of memory, and the recognition of pathogens by unconventional lymphocytes.


The role of non-viraemic transmission on the persistence and dynamics of a tick borne virus--Louping ill in red grouse ( Lagopus lagopus scoticus) and mountain hares ( Lepus timidus).
There exist many tick borne infections that are of either economic or public health interest. Mathematical models have previously been used to describe the dynamics of these infections. However it has recently come to light that there is an alternative mechanism for the transmission of these diseases that has not been considered in a modelling framework. This is transmission through ticks co-feeding on non-viraemic hosts. This paper extends a simple mathematical model to include this alternative transmission mechanism. The model is used to describe the dynamics of Louping ill virus in red grouse (the viraemic host) and hares (the non-viraemic host). However, these results are applicable to many other systems. The model is analysed using joint threshold density curves. It is found that the presence of a non-viraemic host allows the virus to persist more readily than it would in the presence of a host that simply amplified the tick population. More importantly, if the level of non-viraemic transmission is high enough the virus can persist in the absence of the viraemic host. This result has important implications for the control of tick borne diseases.


AKXD recombinant inbred strains: models for studying the molecular genetic basis of murine lymphomas.
We analyzed the lymphoma susceptibility of 13 AKXD recombinant inbred mouse strains derived from AKR/J, a highly lymphomatous strain, and DBA/2J, a weakly lymphomatous strain. Of the 13 strains used, 12 showed a high incidence of lymphoma development. However, the average age at onset of lymphoma varied considerably among the different AKXD strains, suggesting that they have segregated several loci that affect lymphoma susceptibility. A relatively unambiguous classification of lymphomas was made possible by using histopathology in addition to detailed molecular characterization of rearrangements in immunoglobulin heavy and kappa light genes and in T-cell receptor beta-chain genes. Among the 12 highly lymphomatous strains, only 2 were identified that, like the parental AKR/J strain, died primarily of T-cell lymphomas. Three strains died primarily of B-cell lymphomas, and one strain primarily of myeloid lymphomas. Six strains were susceptible to both T-cell and B-cell lymphomas. Thus, these strains have segregated genes that affect both lymphoma susceptibility and lymphoma type and should prove to be useful models for studying the molecular genetic basis of murine lymphomas.


Azelaic acid--biochemistry and metabolism.
Medium chain length dicarboxylic acids (DA) from C8 to C13 are competitive inhibitors of tyrosinase in vitro. The introduction of electron acceptor groups or electron donor groups into the 2 and/or the 8 position of the molecule enhances or reduces respectively the inhibitory effects of DA. In addition to tyrosinase, DA can reversibly inhibit thioredoxin reductase, NADPH cytochrome P450 reductase, NADH dehydrogenase, succinic dehydrogenase and H2CoQ-Cytochrome C oxidoreductase. Among DA, azelaic acid (AA, C9 dicarboxylic acid) is extensively used because: 1) it is much cheaper than other DA; 2) it has no apparent toxic or teratogenic or mutagenic effect; 3) when administered perorally to humans, at the same concentrations as the other DA, it reaches much higher serum and urinary concentrations. Serum concentrations and urinary excretion obtained with intravenous or intra-arterial infusions of AA are significantly higher than those achievable by oral administration. Together with AA, variable amounts of its catabolites, mainly pimelic acid, are found in serum and urine, indicating an involvement of mitochondrial beta-oxidative enzymes. Short-lived serum levels of AA follow a single 1 h intravenous infusion, but prolonging the period of infusion with successive doses of similar concentration produces sustained higher levels during the period of administration. These levels are consistent with the concentrations of AA capable of producing a cytotoxic effect on tumoral cells in vitro. AA is capable of crossing the blood-brain barrier: its concentration in the cerebrospinal fluid is normally in the range of 2-5% of the values in the serum.


Body fat percentage as a marker of new-onset diabetes mellitus after kidney transplantation.
New-onset diabetes after transplantation (NODAT) is a serious metabolic complication that can follow kidney transplantation. Several risk factors, including obesity, have been related to NODAT development. Obesity is defined as an excessive accumulation of body fat, and body fat percentage (BF%) has been commonly measured by different techniques, including bioelectrical impedance analysis. However, the correlation between an increase in BF% and the development of NODAT during outpatient follow-up has not yet been explored. We aimed to elucidate the association between BF% changes and the development of NODAT. We performed a retrospective study involving 45 patients without diabetes who underwent kidney transplantation in our hospital between March 2008 and December 2010. We compared the BF% and demographic variables of patients who did and did not develop NODAT during follow-up. Four patients (8.9%) developed NODAT during a mean follow-up period of 30.3 months. The post-transplantation increase in BF% was much higher in NODAT+ patients than the NODAT- patients. Univariate analysis indicated that the rate of increase in BF% was a risk factor for NODAT (hazard ratio [HR], 1.08 [1.02-1.18]; P < .005). A large increase in BF% may be a risk factor for NODAT. These findings underline the importance of routine BF% measurements in medical practice.


From scores to face templates: a model-based approach.
Regeneration of templates from match scores has security and privacy implications related to any biometric authentication system. We propose a novel paradigm to reconstruct face templates from match scores using a linear approach. It proceeds by first modeling the behavior of the given face recognition algorithm by an affine transformation. The goal of the modeling is to approximate the distances computed by a face recognition algorithm between two faces by distances between points, representing these faces, in an affine space. Given this space, templates from an independent image set (break-in) are matched only once with the enrolled template of the targeted subject and match scores are recorded. These scores are then used to embed the targeted subject in the approximating affine (non-orthogonal) space. Given the coordinates of the targeted subject in the affine space, the original template of the targeted subject is reconstructed using the inverse of the affine transformation. We demonstrate our ideas using three, fundamentally different, face recognition algorithms: Principal Component Analysis (PCA) with Mahalanobis cosine distance measure, Bayesian intra-extrapersonal classifier (BIC), and a feature-based commercial algorithm. To demonstrate the independence of the break-in set with the gallery set, we select face templates from two different databases: Face Recognition Grand Challenge (FRGC) and Facial Recognition Technology (FERET) Database (FERET). With an operational point set at 1 percent False Acceptance Rate (FAR) and 99 percent True Acceptance Rate (TAR) for 1,196 enrollments (FERET gallery), we show that at most 600 attempts (score computations) are required to achieve a 73 percent chance of breaking in as a randomly chosen target subject for the commercial face recognition system. With similar operational set up, we achieve a 72 percent and 100 percent chance of breaking in for the Bayesian and PCA based face recognition systems, respectively. With three different levels of score quantization, we achieve 69 percent, 68 percent and 49 percent probability of break-in, indicating the robustness of our proposed scheme to score quantization. We also show that the proposed reconstruction scheme has 47 percent more probability of breaking in as a randomly chosen target subject for the commercial system as compared to a hill climbing approach with the same number of attempts. Given that the proposed template reconstruction method uses distinct face templates to reconstruct faces, this work exposes a more severe form of vulnerability than a hill climbing kind of attack where incrementally different versions of the same face are used. Also, the ability of the proposed approach to reconstruct actual face templates of the users increases privacy concerns in biometric systems.


Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer.
MAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). The expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics. MAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC. MAP4K5 expression is decreased or lost in majority of PDACs. The strong associations between low MAP4K5 expression and loss of E-cadherin, reduced CES2 expression and decreased overall survival may suggest an important role of MAP4K5 in epithelial-to-mesenchymal transition, chemotherapy resistance and tumor progression in pancreatic cancer. Targeting impaired MAP4K5 signaling may represent a new therapeutic strategy for pancreatic cancer.


Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity.
A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets-both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.


EEG slow (approximately 1 Hz) waves are associated with nonstationarity of thalamo-cortical sensory processing in the sleeping human.
Intracellular studies reveal that, during slow wave sleep (SWS), the entire cortical network can swing rhythmically between extremely different microstates, ranging from wakefulness-like network activation to functional disconnection in the space of a few hundred milliseconds. This alternation of states also involves the thalamic neurons and is reflected in the EEG by a slow (<1 Hz) oscillation. These rhythmic changes, occurring in the thalamo-cortical circuits during SWS, may have relevant, phasic effects on the transmission and processing of sensory information. However, brain reactivity to sensory stimuli, during SWS, has traditionally been studied by means of sequential averaging, a procedure that necessarily masks any short-term fluctuation of responsiveness. The aim of this study was to provide a dynamic evaluation of brain reactivity to sensory stimuli in naturally sleeping humans. To this aim, single-trial somatosensory evoked potentials (SEPs) were grouped and averaged as a function of the phase of the ongoing sleep slow (<1 Hz) oscillation. This procedure revealed a dynamic profile of responsiveness, which was conditioned by the phase of the spontaneous sleep EEG. Overall, the amplitude of the evoked potential changed sistematically, increasing and approaching wakefulness levels along the negative slope of the EEG oscillation and decaying below SWS average levels along the positive drift. These marked and fast changes of stimulus-correlated electrical activity involved both short (N20) and long latency (P60 and P100) components of SEPs. In addition, the observed short-term response variability appeared to be centrally generated and specifically related to the evolution of the spontaneous oscillatory pattern. The present findings demonstrate that thalamo-cortical processing of sensory information is not stationary in the very short period (approximately 500 ms) during natural SWS.


Preparation of cationized polysaccharides as gene transfection carrier for bone marrow-derived mesenchymal stem cells.
The objective of this study is to prepare a non-viral carrier of gene transfection from various polysaccharides and evaluate the feasibility in gene expression for mesenchymal stem cells (MSCs). Various amounts of spermine were chemically introduced into pullulan, dextran and mannan with a molecular weight of around 40 000 or pullulan with different molecular weights to prepare cationized polysaccharides with different extents of spermine introduced (spermine-polysaccharide). Each cationized polysaccharide was complexed with a plasmid DNA at various ratios and in vitro gene transfection was investigated for rat bone marrow-derived MSCs. The level of gene expression depended on the type of cationized polysaccharide. The highest level was observed for the complex of spermine-pullulan and plasmid DNA. Additionally, the level also depended on the molecular weight of pullulan and the extent of spermine introduced to pullulan. Suppression of gene expression with chlorpromazine and methyl-beta-cyclodextrin of endocytosis inhibitors demonstrated that the cellular uptake of spermine-pullulan-plasmid DNA complexes was mediated by clathrin- and raft/caveolae-dependent endocytic pathways. The cationized pullulan is a promising non-viral carrier of plasmid DNA for MSCs.


IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform.
The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4(+) T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4(+) T cell production of interferon (IFN) gamma, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-gamma(+)IL-2(+)TNF(+) Th1 cells, a high frequency of IL-10-producing CD4(+) T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4(+) T cells.


A comparative study of partial dealcoholisation versus early harvest: Effects on wine volatile and sensory profiles.
Two Verdelho and Petit Verdot wines were produced from sequential harvests of grapes. The alcohol concentration of early harvest (EH) and late harvest (LH) wines were respectively 9% and 13.5% v/v for Verdelho, and 10.5% and 13% v/v for Petit Verdot. LH wines were dealcoholised to match the same alcohol level of EH samples using a combined reverse osmosis-evaporative perstraction process. In dealcoholised wines, there was a decrease in volatile compounds (esters particularly) compared to LH treatments. For both varieties, the sensory attribute ratings for overall aroma intensity and alcohol mouthfeel also decreased following dealcoholisation. Dealcoholised wines were distinctively different from both LH and EH wines even though these wines had similar alcohol level to EH wines. When dealcoholisation is considered for high-alcohol wines, it is important to consider that membrane effects can significantly change depending on the wine non-volatile matrix composition and the level of alcohol reduction required.


Identification of the key genes and characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC).
This study aimed to investigate the key genes and immune microenvironment involved in different TNM stages of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The gene expression and clinical characteristics data were downloaded from the genomic data commons (GDC) database. After initial data processing, the characteristics of the immune microenvironment were analyzed. The differentially expressed genes (DEGs) in tumor vs. normal, and in early vs. advanced stages were screened, followed by Spearman correlation test for tumor infiltrating immune cells (TIICs) to identify immune-related genes. Finally, functional enrichment, protein-protein interaction, and survival analyses were performed. In LUAD, early stage was with higher immune scores, greater number of memory B cells and M0 macrophages compared to advanced stage. M0 and M2 macrophages, and resting memory CD4+ T cells accounted for a large proportion of TIICs in LUAD. The abundance of M0 macrophage infiltration was significantly correlated with the TNM stage and survival. In LUSC, early stage was with higher cytolytic activity and neoantigen burden compared to advanced stage. M0 and M2 macrophages, and plasma cells accounted for a large proportion of TIICs in LUSC. The abundance of resting and activated mast cells was significantly correlated with TNM stage, while resting dendritic cells, eosinophils, activated memory CD4 T cells, and mast cells were significantly correlated with prognosis. Tumor mutation burden analysis revealed that the median of variants per sample decreased from stage I to IV in LUAD, while it increased in LUSC. Further, 83 and 9 immune-related DEGs were identified in LUAD and LUSC, respectively, of which 23 genes in LUAD and 2 genes in LUSC correlated with survival. In conclusion, we identified the key genes, and characterized the tumor immune microenvironment in LUAD and LUSC which may provide therapeutic targets for the treatment of NSCLC.


Impact of Patient-Engaged Video Surveillance on Nursing Workforce Safety: Patient Aggression/Violence.
Health care workers are 4 times more likely to suffer violence than workers in other industries. The aim was to examine types of patients' verbal/physical abuse against the nursing workforce observed through patient-engaged video surveillance (PEVS) and interventions initiated by monitor technicians. A descriptive study was conducted to analyze all types of patient-initiated abuse, physical and verbal, reported from 73 hospitals and patient response to PEVS. Of 150 434 patients whom RNs enrolled into 24-hour PEVS, 5034 patients (3%) were identified by RNs as at risk for aggressive/violent behavior as their primary or secondary reason for PEVS enrollment, and 32 (0.60%) patients exhibited such behavior. A total of 221 patients demonstrated aggressive/violent behaviors, 32 (15%) were identified as at risk, and 189 (85%) were not. However, 5002 (99%; 5002/5034) of the patients identified as a risk for aggressive/violent behaviors did not exhibit these behaviors. Patient-engaged video surveillance is an effective method to track and trend patient aggression toward nursing staff, increasing patient and nursing workforce safety. Because 99% of the patients who exhibited aggressive/violent behavior were not identified by RNs as at risk, organizations should consider adding violence risk tools as part of patients' admission assessment.


Increased Ki-67 immunoreactivity in the white matter in hemimegalencephaly.
Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged unilateral hemisphere with cortical malformation comprising abnormal hypertrophic cells. To address the proliferative status of HMG, Ki-67 immunoreactivity was investigated in HMG specimens obtained during epilepsy surgery. Nine HMG tissues were stained with a Ki-67 antibody and Ki-67 labeling index in the malformed cortex, and the underlying white matter was measured separately and compared with tissues from focal cortical dysplasias and normal brains from autopsy. In HMG tissues, Ki-67-positive cells were scattered in both the gray and white matter, with a significantly higher Ki-67 labeling index in the white matter compared with gray matter. No dysmorphic neuron or balloon cell was stained for Ki-67. As Ki-67 immunoreactivity overlapped with that of ionized calcium-binding adaptor protein-1, Ki-67-positive cells were identified as microglia. In HMG, microglia were activated and entered into a proliferative status with higher distribution in the white matter, implying an ongoing neuroinflammatory process involving the white matter.


Mineralization of aromatics in water by sunlight-assisted electro-fenton technology in a pilot reactor.
The viability of the degradation of aqueous solutions of aniline, nitrobenzene, and 4-chlorophenol by the so-called Photoelectro-Fenton process in a pilot reactor is reported. The Electro-Fenton process stage, based on the flow of oxygen through a gas diffusion cathode to produce H2O2, allows mineralization of about a half of the TOC content in ca. 1 h, because anodic oxidation is coupled with Fenton reaction in the presence of Fe2+ catalyst. An intensity of 20 A was applied in a flow cell comprising a Ti/Pt anode and a carbon-PTFE cathode. After electrolysis, samples of the effluent were exposed to sunlight, and almost complete mineralization was reached after ca. 50 min. Effect of parameters such as electrolysis time, pH, initial concentration, and solar or UVA irradiation on the process efficiencies and the running costs are studied. The Photoelectro-Fenton process using sunlight effectively diminishes these costs. The analogous behavior of the three aromatics suggests similar degradation pathways, regardless of the different groups attached to the ring.


Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-S6 kinase.
We have investigated the involvement of phosphoinositide (PI) 3-kinase and p70 ribosomal protein-S6 kinase (p70s6k) in mediating insulin stimulation of glycogen synthesis in 3T3-L1 adipocytes using specific inhibitors. Wortmannin inhibited PI 3-kinase activity (IC50 approximately 10 nM), inhibition being complete at 100 nm. Wortmannin (100 nM) completely blocked the ability of insulin to activate glycogen synthase in 3T3-L1 adipocytes and the ability of insulin to stimulate glucose incorporation into glycogen in 3T3-L1 fibroblasts. Rapamycin, which blocks insulin-stimulated activation of p70s6k, decreased insulin activation of glycogen synthase in a dose-dependent manner (IC50 approximately 0.8 ng/ml), with a maximum approx. 75% inhibition of insulin's stimulatory effect. Rapamycin inhibited insulin-stimulated glucose incorporation into glycogen to a similar extent and with similar dose-dependency, while having no effect on insulin-stimulated glucose transport. We conclude that PI 3-kinase and p70s6k are involved in the signalling pathways by which insulin stimulates glycogen synthase in 3T3-L1 adipocytes.


Mask Reuse in the COVID-19 Pandemic: Creating an Inexpensive and Scalable Ultraviolet System for Filtering Facepiece Respirator Decontamination.
As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.


An Unbiased Drug Screen for Seizure Suppressors in Duplication 15q Syndrome Reveals 5-HT1A and Dopamine Pathway Activation as Potential Therapies.
Duplication 15q (Dup15q) syndrome is a rare neurogenetic disorder characterized by autism and pharmacoresistant epilepsy. Most individuals with isodicentric duplications have been on multiple medications to control seizures. We recently developed a model of Dup15q in Drosophila by elevating levels of fly Dube3a in glial cells using repo-GAL4, not neurons. In contrast to other Dup15q models, these flies develop seizures that worsen with age. We screened repo>Dube3a flies for approved compounds that can suppress seizures. Flies 3 to 5 days old were exposed to compounds in the fly food during development. Flies were tested using a bang sensitivity assay for seizure recovery time. At least 40 animals were tested per experiment, with separate testing for male and female flies. Studies of K+ content in glial cells of the fly brain were also performed using a fluorescent K+ indicator. We identified 17 of 1280 compounds in the Prestwick Chemical Library that could suppress seizures. Eight compounds were validated in secondary screening. Four of these compounds regulated either serotonergic or dopaminergic signaling, and subsequent experiments confirmed that seizure suppression occurred primarily through stimulation of serotonin receptor 5-HT1A. Additional studies of K+ levels showed that Dube3a regulation of the Na+/K+ exchanger ATPα (adenosine triphosphatase α) in glia may be modulated by serotonin/dopamine signaling, causing seizure suppression. Based on these pharmacological and genetic studies, we present an argument for the use of 5-HT1A agonists in the treatment of Dup15q epilepsy.


Epstein-Barr virus nuclear antigen EBNA3C/6 expression maintains the level of latent membrane protein 1 in G1-arrested cells.
The Epstein-Barr virus in the Burkitt lymphoma-derived cell line Raji has a deletion in the EBNA3C gene. When Raji cells are allowed to grow to high density and most of the cells become growth arrested in the G1 phase of the cell cycle, the level of detectable latent membrane protein 1 (LMP1) is substantially reduced. After dilution of the cells with fresh growth medium, within 8 h, there is a large increase in LMP1 mRNA, and by 12 h, LMP1 is expressed to a high level (H. Boos, M. Stoehr, M. Sauter, and N. Mueller-Lantzch, J. Gen. Virol. 71:1811-1815, 1990). Here we show that in Raji cells which constitutively express a transfected EBNA3C gene, the down-regulation of LMP1 in growth-arrested cells does not take place. Furthermore, we show that in wild-type Raji cells, low-level LMP1 expression occurs when most of the cells are arrested at a point(s) early in G1 (or G0) when the product of the retinoblastoma gene, pRb, is hypophosphorylated. The dramatic synthesis of LMP1 coincides with the progression of these cells to late G1 when pRb becomes hyperphosphorylated. Thus, in Raji cells, the LMP1 gene is apparently regulated in a cell cycle- or proliferation-dependent manner, but when EBNA3C is present, sustained LMP1 expression occurs as it does in a lymphoblastoid cell line. EBNA3C appears to either relieve the apparent repression of LMP1 in cells progressing through early G1 or possibly alter the stage at which the cells growth arrest to one where they are permissive for LMP1 expression.


Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs.
Hyperoxia and hypoxia influence morbidity and mortality of preterm infants. Automated closed-loop control of the fraction of inspired oxygen (FiO(2)) has been shown to facilitate oxygen supplementation in the neonatal intensive care unit (NICU), but has not yet been tested during preterm resuscitation. We hypothesized that fully automated FiO(2) control based on predefined oxygen saturation (SpO(2)) targets was applicable in both preterm resuscitation and ventilation. Twenty-two preterm lambs were operatively delivered and intubated in a modified EXIT procedure. They were randomized to receive standardized resuscitation with either automated or manual FiO(2) control, targeting SpO(2) according to the Dawson curve in the first 10 min and SpO(2) 90-95% hereafter. Automated FiO(2) control also was applied during surfactant replacement therapy and subsequent ventilation. Time within target range did not differ significantly between manual and automated FiO(2) control during resuscitation, however automated FiO(2) control significantly avoided hyperoxia. Automated FiO(2) control was feasible during surfactant replacement and kept SpO(2) within target range significantly better than manual control during subsequent ventilation. In our model, fully automated FiO(2) control was feasible in rapidly changing physiologic conditions during postnatal resuscitation and prevented hyperoxia. We conclude that closed loop FiO(2) control is a promising tool for the delivery room.


Preventing rapid repeat births among latina adolescents: the role of parents.
Latina adolescent parents are at increased risk for rapid repeat births (second birth ≤ 24 months after the first), sexually transmitted infections, and negative educational and social outcomes. Although several effective parent-based interventions have been developed to prevent Latino youths' sexual risk taking, little research has explored the development of interventions to prevent repeat births that involve the parents of these adolescents. Existing preventative interventions involving parents suffer from important methodological limitations. Additional research is needed to advance theories of behavior, identify the causal pathways of parental influence, and specify appropriate behavioral targets. Future parent-based interventions to prevent repeat births should target pregnancy intentions, age of partners, contraceptive use, integrated prevention of pregnancies and sexually transmitted infections, educational attainment, and future orientations.


Fast numerical optimization for genome sequencing data in population biobanks.
Large-scale and high-dimensional genome sequencing data poses computational challenges. General-purpose optimization tools are usually not optimal in terms of computational and memory performance for genetic data. We develop two efficient solvers for optimization problems arising from large-scale regularized regressions on millions of genetic variants sequenced from hundreds of thousands of individuals. These genetic variants are encoded by the values in the set {0,1,2,NA}. We take advantage of this fact and use two bits to represent each entry in a genetic matrix, which reduces memory requirement by a factor of 32 compared to a double precision floating point representation. Using this representation, we implemented an iteratively reweighted least square algorithm to solve Lasso regressions on genetic matrices, which we name snpnet-2.0. When the dataset contains many rare variants, the predictors can be encoded in a sparse matrix. We utilize the sparsity in the predictor matrix to further reduce memory requirement and computational speed. Our sparse genetic matrix implementation uses both the compact two-bit representation and a simplified version of compressed sparse block format so that matrix-vector multiplications can be effectively parallelized on multiple CPU cores. To demonstrate the effectiveness of this representation, we implement an accelerated proximal gradient method to solve group Lasso on these sparse genetic matrices. This solver is named sparse-snpnet, and will also be included as part of snpnet R package. Our implementation is able to solve Lasso and group Lasso, linear, logistic and Cox regression problems on sparse genetic matrices that contain 1 000 000 variants and almost 100 000 individuals within 10 min and using less than 32GB of memory. https://github.com/rivas-lab/snpnet/tree/compact.


Large artery stiffness is associated with gamma-glutamyltransferase in young, healthy adults: The African-PREDICT study.
Increased arterial stiffness is linked to cardiovascular disease development, particularly in black populations. Since detrimental health behaviors in young adults may affect arterial stiffness, we determined whether arterial stiffness associates with specific health behaviors, and whether it is more pronounced in young healthy black compared to white adults. We included 373 participants (49% black, 42% men) aged 20-30 years. Mean arterial pressure was higher for blacks than whites (P < .001), but carotid-femoral pulse wave velocity was similar (6.37 vs. 6.36 m/s; P = .89) after adjustment for mean arterial pressure. The black group had higher gamma-glutamyltransferase (GGT) (P < .001), cotinine, reactive oxygen species, interleukin-6, and monocyte-chemoattractant protein-1 (all P ≤ .017). Pulse wave velocity related positively and independently to GGT in both groups before and after multiple adjustments (both β = 0.15; P ≤ .049). Blacks had an unfavorable vascular profile and higher GGT, possibly indicating a higher vulnerability to cardiovascular disease development, including changes in arterial stiffness. However, this observation needs confirmation.


Efficacy of vincristine administered via convection-enhanced delivery in a rodent brainstem tumor model documented by bioluminescence imaging.
Brain stem gliomas account for 20% of childhood brain tumors. Presently, there is no effective treatment for these tumors, and the prognosis remains poor. One reason for this is that chemotherapeutic drugs cannot cross the blood-brain barrier. In this study, we used a rodent brainstem tumor model, monitored both qualitatively and quantitatively, to examine the effectiveness of vincristine (VCR) administered via convection-enhanced delivery (CED). C6 rat glioblastoma cells, transduced with an oncoretroviral plasmid containing a luciferase coding sequence, were inoculated into Fischer 344 rat brainstems. Tumor growth was monitored by bioluminescence intensity (BLI), and tumor volume was calculated from serial histopathologic sections. Therapeutic efficacy of VCR delivered via CED was assessed. Intravenous (I.V.) and intraperitoneal (I.P.) drug administration were used as a comparison for CED efficacy. BLI monitoring revealed progressive tumor growth in inoculated rats. Symptoms caused by tumor burden were evident 16-18 days after inoculation. BLI correlated quantitatively with tumor volume (r(2) = 0.9413), established by histopathological analysis of tumor growth within the pons. VCR administered through CED was more effective than I.V. or I.P. administration in reducing tumor size and increasing survival times. TUNEL assay results suggest that VCR induced glioblastoma cell apoptosis. VCR administered by CED was effective in reducing tumors and prolonging survival time.


A holomorph approach to xiphosuran evolution--a case study on the ontogeny of Euproops.
Specimens of Euproops sp. (Xiphosura, Chelicerata) from the Carboniferous Piesberg quarry near Osnabrück, Germany, represent a relatively complete growth series of 10 stages. Based on this growth sequence, morphological changes throughout the ontogeny can be identified. The major change affects the shape of the epimera of the opisthosoma. In earlier stages, they appear very spine-like, whereas in later stages the bases of these spine-like structures become broader; the broadened bases are then successively drawn out distally. In the most mature stage known, the epimera are of trapezoidal shape and approach each other closely to form a complete flange around the thoracetron (=fused tergites of the opisthosoma). These ontogenetic changes question the taxonomic status of different species of Euproops, as the latter appear to correspond to different stages of the ontogenetic series reconstructed from the Piesberg specimens. This means that supposed separate species could, in fact, represent different growth stages of a single species. It could alternatively indicate that heterochrony (=evolutionary change of developmental timing) plays an important role in the evolution of Xiphosura. We propose a holomorph approach, i.e., reconstructing ontogenetic sequences for fossil and extant species as a sound basis for a taxonomic, phylogenetic, and evolutionary discussion of Xiphosura.


The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin.
Bacteria initially respond to nutrient starvation by eliciting large-scale transcriptional changes. The accompanying changes in gene expression and metabolism allow the bacterial cells to effectively adapt to the nutrient-starved state. How the transcriptome subsequently changes as nutrient starvation ensues is not well understood. We used nitrogen (N) starvation as a model nutrient starvation condition to study the transcriptional changes in Escherichia coli experiencing long-term N starvation. The results reveal that the transcriptome of N-starved E. coli undergoes changes that are required to maximize chances of viability and to effectively recover growth when N starvation conditions become alleviated. We further reveal that, over time, N-starved E. coli cells rely on the degradation of allantoin for optimal growth recovery when N becomes replenished. This study provides insights into the temporally coordinated adaptive responses that occur in E. coli experiencing sustained N starvation.IMPORTANCE Bacteria in their natural environments seldom encounter conditions that support continuous growth. Hence, many bacteria spend the majority of their time in states of little or no growth due to starvation of essential nutrients. To cope with prolonged periods of nutrient starvation, bacteria have evolved several strategies, primarily manifesting themselves through changes in how the information in their genes is accessed. How these coping strategies change over time under nutrient starvation is not well understood, and this knowledge is important not only to broaden our understanding of bacterial cell function but also to potentially find ways to manage harmful bacteria. This study provides insights into how nitrogen-starved Escherichia coli bacteria rely on different genes during long-term nitrogen starvation.


Malpractice and the National Practitioner Data Bank: what OR nurses need to know.
The National Practitioner Data Bank will record any payments made for any reason related to a malpractice suit in a central data bank available to a number of designated parties. Hospitals will be required to request this information to screen applicants and at least every 2 years for appointment renewals. The data bank may also be consulted by hospitals and state licensing boards as they deem necessary and by professional societies when reviewing membership applications. It is in the best interests of all malpractice defendants to insist on adequate representation of their personal, professional, and financial interests, which may necessitate insurance carriers providing each defendant with individual counsel.


[The relevance of duplex Doppler sonography in pediatrics].
Since the introduction of duplex Doppler sonography the noninvasive assessment of hemodynamic changes in children has become possible. The clinical application comprises the depiction of cerebral hemodynamics in infants, where characteristic flow patterns can be found in patent ductus arteriosus, hypoxic-ischemic encephalopathy, cerebral hemorrhage, hydrocephalus or in brain death. Moreover, Duplex Doppler Sonography play an important role in the evaluation of renal hemodynamics, especially in kidney transplants. Finally, the examination of the portal venous system can demonstrate thrombosis of the portal vein, portosystemic collaterals or a hepatofugal flow in severe portal hypertension. Thus, invasive investigative procedures may become unnecessary in certain cases. The future potential of this technique lies in the development of quantitative measurements of volume flow and in Doppler color flow imaging.


Can cultural consumption increase future earnings? Exploring the economic returns to cultural capital.
Cultural consumption is often viewed as a form of embodied cultural capital which can be converted into economic rewards (e.g., earnings) because such practices increase the likelihood of moving into more advantaged social positions. However, quantitative evidence supporting this theory remains uncertain because it is often unable to rule out alternative explanations. Cultural consumption appears to influence hiring decisions in some elite firms, in both the US and the UK, but it is unclear whether these processes are applicable to other professional occupations and other labour market processes, such as promotions. We examine these processes using data from Understanding Society, an individual-level panel survey conducted in the UK, allowing us to explore whether cultural consumption predicts future earnings, upward social mobility and promotions. People who consume a larger number of cultural activities are more likely to earn higher wages in the future, to be upwardly socially mobile, and to be promoted. Cultural consumption, then, can function as cultural capital in some labour market settings, potentially contributing to the reproduction of income inequality between generations.


Analysis of murine lymphocyte subpopulations by dual-color flow cytometry: technical considerations and specificities of monoclonal antibodies directed against surface markers.
We performed detailed phenotypic analysis of murine lymphocytes from thymus, spleen, lymph node, and peripheral blood using commercially available monoclonal antibodies, each with specificities for membrane surface markers and dual-color flow cytometry. Erythrocyte lysis techniques were utilized for lymphocyte preparation so that inherent difficulties with gradient techniques would be avoided, such as the potential for loss of abnormally sized cells. These studies demonstrated that the specificities of each monoclonal must be carefully determined; for example, the Lyt-1 monoclonal, frequently utilized to identify helper/inducer T cells, also reacts with suppressor/cytotoxic (Lyt-2+) cells; helper/inducer cells are better studied with a more recently available monoclonal, L3T4. Cells from different tissues may differ greatly not only in the presence of surface markers, but also in the surface density of each marker; this density can be studied and quantitated using appropriate analytic software. We also show that larger and more granular lymphocytes appear to be enriched for surface Ia antigen, indicating that these cells may be activated or regulatory subsets; these large, Ia+ T-cells will be lost from analysis if standard, narrow gate settings are used for analyzing forward and side-scatter characteristics or for cell sorting.


The World Trade Center disaster and the health of workers: five-year assessment of a unique medical screening program.
Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. To characterize WTCrelated health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Longterm medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters.


[The importance of clinical case reports in research].
Clinical case reports correspond to articles that have the lowest level of evidence within different research trials. However, not only are they common and significant in the medical field, but they have often been the basis the generation of research. The purpose of their publication can be scientific or educational. In general terms, the discovery of new diseases, the presentation of rare diseases, unusual forms of common diseases, the complications of a common treatment, or the effect (beneficial or adverse) of a treatment, among other things, are narrated in these documents. Clinical case reports continue to be one of the most important sources of knowledge. The advent of a standardized guideline for the creation of this type of reports allows homogenizing the form and content of the cases intended to be described in the near future and, furthermore, will enable authors to have a reference when preparing this type of publications. Case reports are valuable resources of new and unusual information that can encourage and serve to conduct future research studies with a higher level of evidence.


Differential effect of acute and permanent heat shock protein 70 overexpression in tumor cells on lysability by cytotoxic T lymphocytes.
We have shown previously that acute heat shock protein (Hsp) 70 induction in a human melanoma cell line containing a doxycycline-inducible Hsp70 expression construct increases lysability of these tumor cells by cytotoxic T lymphocyte (CTL) without interfering with MHC class I expression and antigen presentation. The same parental melanoma cell line has now been transduced retrovirally to overexpress Hsp70 permanently. Here we demonstrate that MHC class I cell surface expression is again not altered and that these cells, in contrast with acutely Hsp70 overexpressing cells, do not show augmentation of CTL-mediated apoptosis. Also, long-term induction of Hsp70 in cells with the doxycycline-inducible Hsp70 construct leads to abrogation of increased lysability. Because, furthermore, after heat shock the same permanently Hsp70 overexpressing cells show Hsp70 induction and increased lysability, it is hypothesized that acutely available Hsp70 is able to chaperone proteins that are involved in CTL-mediated apoptosis of target cells and to thereby improve their lysability. We also observed that permanent but not acute Hsp70 overexpression resulted in decreased levels of Hsc70, the constitutively expressed member of the Hsp70 family. Down-regulation of Hsc70 occurs at the post-transcriptional level and can be observed also after long-term induction of Hsp70 in cells containing the doxycycline-inducible expression system. Hsc70 down-regulation might reflect a functional integration of the overexpressed Hsp70 on the basis of a chaperone network so that only acute induction will provide Hsp70 that can improve tumor cell lysability. The implications of the differential effect of acute versus permanent Hsp70 overexpression for tumor therapy are discussed.


Lodgement of the equine blastocyst in the uterus from fixation through endometrial cup formation.
The equine blastocyst becomes fixed in position in the uterus on approximately Day 16 of gestation, but allantochorionic villi are not formed until about Day 50. The purpose of this study was to examine evidence that the blastocyst is orientated during this time period, and to determine what morphological features might assist retention of the position of the blastocyst within the uterus. Implantation sites were collected on Days 10-42 of gestation, and the reproductive tracts perfused with fixative for light and electron microscopic examination. The conceptus is found at the bend of a uterine horn near the junction with the body of the uterus. As the conceptus expands, the ventral antimesometrial aspect of the horn is dilated, forming a distinct chamber. Despite the prescence of the capsule around the conceptus through Day 20, the conceptus is orientated with the embryo situated anti-mesometrially. The endometrial folds at the ends of the chamber are closely apposed and exhibit cross ridges that may aid in stabilizing the chamber. After displacement of the capsule, the trophoblast is closely apposed to the endometrium over most of the surface of the conceptus. As the expanding allantois pushes the embryo and yolk sac toward the mesometrial side, the sinus terminalis region of the yolk sac becomes progressively modified. A ridge or annulus of trophoblast indents the endometrium prior to the stage of girdle cell migration. The structure of the sinus terminalis complex is consistent with a role in prevention of rotation of the conceptus within the chamber. Close association of vascularized trophoblast and uterine epithelium, underlain by dilated subepithelial capillaries, is present as early as Day 25 in the allantochorion. Orientation of the blastocyst is important for apposition of vascularized trophoblast to the flattened antimesometrial surface and for proper sitting of the endometrial cups in the mesometrial area.


Cross-sectional imaging of nontraumatic peritoneal and mesenteric emergencies.
Multiple nontraumatic peritoneal and mesenteric emergencies are encountered at imaging of patients in the emergency department. Peritoneal and mesenteric emergencies are usually detected in patients in the emergency department during evaluation of nonspecific abdominal pain. A high index of suspicion is required for the establishment of early diagnosis and aversion of life-threatening complications in cases of peritoneal carcinomatosis, nontraumatic hemoperitoneum, and peritonitis. A correct diagnosis of omental infarction, mesenteric adenitis, and mesenteric panniculitis helps patients primarily by avoiding unnecessary surgery. In this review article, we illustrate the cross-sectional imaging appearance of various nontraumatic peritoneal and mesenteric emergencies by emphasizing the role of the emergency radiologist in detecting and managing these entities.


Video equipment recommendations for slit lamp videography.
Current developments in video technology have made videotaping through a slit lamp a useful capability available at a more reasonable cost. The technical basis of equipment needed to select or design an apparatus for slit lamp videography is reviewed. As an overview, the optimum slit lamp video apparatus would have the following criteria; the slit lamp should have zoom optics and rheostat illumination, the beam splitter should be a mirror or 70/30 type, the camera should have maximal light sensitivity (101ux) with reasonable resolution (greater than 300 lines). The recorder should be SP-Umatic or Super VHS for documentation, or consumer VHS for patient education, and the monitor should be a professional 13- or 15-inch monitor.


Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice.
Staphylococcus aureus is a significant cause of hospital and community acquired pneumonia and causes secondary infection after influenza A. Recently, patients with hyper-IgE syndrome, who often present with S. aureus infections of the lung and skin, were found to have mutations in STAT3, required for Th17 immunity, suggesting a potential critical role for Th17 cells in S. aureus pneumonia. Indeed, IL-17R(-/-) and IL-22(-/-) mice displayed impaired bacterial clearance of S. aureus compared with that of wild-type mice. Mice challenged with influenza A PR/8/34 H1N1 and subsequently with S. aureus had increased inflammation and decreased clearance of both virus and bacteria. Coinfection resulted in greater type I and II IFN production in the lung compared with that with virus infection alone. Importantly, influenza A coinfection resulted in substantially decreased IL-17, IL-22, and IL-23 production after S. aureus infection. The decrease in S. aureus-induced IL-17, IL-22, and IL-23 was independent of type II IFN but required type I IFN production in influenza A-infected mice. Furthermore, overexpression of IL-23 in influenza A, S. aureus-coinfected mice rescued the induction of IL-17 and IL-22 and markedly improved bacterial clearance. These data indicate a novel mechanism by which influenza A-induced type I IFNs inhibit Th17 immunity and increase susceptibility to secondary bacterial pneumonia.


Kinetic mechanism of glutaryl-CoA dehydrogenase.
Glutaryl-CoA dehydrogenase (GCD) is a homotetrameric enzyme containing one noncovalently bound FAD per monomer that oxidatively decarboxylates glutaryl-CoA to crotonyl-CoA and CO2. GCD belongs to the family of acyl-CoA dehydrogenases that are evolutionarily conserved in their sequence, structure, and function. However, there are differences in the kinetic mechanisms among the different acyl-CoA dehydrogenases. One of the unanswered aspects is that of the rate-determining step in the steady-state turnover of GCD. In the present investigation, the major rate-determining step is identified to be the release of crotonyl-CoA product because the chemical steps and reoxidation of reduced FAD are much faster than the turnover of the wild-type GCD. Other steps are only partially rate-determining. This conclusion is based on the transit times of the individual reactions occurring in the active site of GCD.


Nanostructured Lipid-Based Delivery Systems as a Strategy to Increase Functionality of Bioactive Compounds.
Acquisition of a healthy lifestyle through diet has driven the food manufacturing industry to produce new food products with high nutritional quality. In this sense, consumption of bioactive compounds has been associated with a decreased risk of suffering chronic diseases. Nonetheless, due to their low solubility in aqueous matrices, high instability in food products during processing and preparation as well as poor bioavailability, the use of such compounds is sometimes limited. Recent advancements in encapsulation and protection of bioactive compounds has opened new possibilities for the development of novel food products. In this direction, the present review is attempting to describe encapsulation achievements, with special attention to nanostructured lipid-based delivery systems, i.e., nanoemulsions, multi-layer emulsions and liposomes. Functionality of bioactive compounds is directly associated with their bioavailability, which in turn is governed by several complex processes, including the passage through the gastrointestinal tract and transport to epithelial cells. Therefore, an overview of recent research on the properties of these nanostructured lipid-based delivery systems with a strong impact on the functionality of bioactive compounds will be also provided. Nanostructured lipid-based delivery systems might be used as a potential option to enhance the solubility, stability, absorption and, ultimately, functionality of bioactive compounds. Several studies have been performed in this line, modifying the composition of the nanostructures, such as the lipid-type or surfactants. Overall, influencing factors and strategies to improve the efficacy of encapsulated bioactive compounds within nanostructures have been successfully identified. This knowledge can be used to design effective targeted nanostructured lipid-based delivery systems for bioactive compounds. However, there is still a lack of information on food interactions, toxicity and long-term consumption of such nanostructures.


The impacted lower wisdom tooth: to remove or to leave alone?
The management of impacted third molars, particularly the indications for their removal, is judged against a constantly changing climate of professional opinion, public attitudes to treatment and the funding of healthcare. These changes highlight the practitioner's dilemma: to remove an impacted wisdom tooth or to leave well alone? This article discusses the indications for and risks of wisdom tooth removal, and suggests guidelines for dealing with the dilemma.


External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration.
An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.


Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons.
Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20-min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABAB agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABAB and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.