Prenatal Maternal Stress and Pediatric Asthma Across Development: Adolescent Female-Specific Vulnerability.
Prenatal maternal stress (PNMS) is linked to physical sequelae in offspring, including childhood asthma. This study sought to examine the roles of objective and subjective PNMS in the development of asthma at offspring ages 5 and 15. The sample included 815 mother-child dyads from the Mater Misericordiae Mothers' Hospital-University of Queensland Study of Pregnancy. PNMS was measured via retrospective self-report during pregnancy and 3-5 days after birth. Postnatal maternal stress was measured at offspring age 5. Objective PNMS was associated with elevated asthma risk at age 5 (OR 1.21, 95% CI 1.00, 1.45, p = 0.05), albeit not above concurrent postnatal stress. Sex moderated the association between PNMS and asthma at age 15, controlling for postnatal stress. Sex stratified analyses revealed a positive association between objective PNMS and age 15 asthma in females, but not males. Results provide evidence that PNMS may impact asthma outcomes in adolescence.


Helminths of the ocelot from southern Texas.
In the USA, the ocelot (Leopardus pardalis) is a highly endangered felid found only in a few remaining vestiges of native thornshrub brushland in the Lower Rio Grande Valley (LRGV) of extreme southern Texas. From 1987-1998, carcasses of 15 adult ocelots that died of vehicular accidents or natural causes were examined for helminths. All cats had 1-8 (mean = 3) helminth species. All were infected with 1-101 (mean +/- SE = 32 +/- 7) Toxascaris leonina. Other helminths from these ocelots were Alaria marcianae, Brachylaima sp., Mesocestoides lineatus, Taenia rileyi, Oncicola canis, Dirofilaria immitis, Physaloptera rara, Ancylostoma tubaeformae, Cylicospirura chevreuxi, Vogeloides felis, and Metathelazia californica. Additionally, two cats had scarring of the aorta with lesions typical of those caused by Spriocerca lupi, although larval nematodes were not seen. A clinal variation in size of nearly three orders of magnitude was noted in the diplostomatid trematodes in the small intestine of one adult male ocelot. Despite the differences in size, all specimens appeared morphologically identical and were regarded as A. marcianae. Helminth prevalences and abundances, including those of potentially pathogenic species like D. immitis, were low. Although a single heartworm infection may have contributed to the death of one ocelot, helminth infections in general seemed to be of no great consequence to this endangered ocelot population. The helminth fauna of ocelots in the LRGV is reflective of that from wild felids in general; all have been reported previously from the bobcat (Lynx rufus) and mountain lion (Puma concolor) elsewhere in Texas.


Humor in evaluating and treating children and adolescents.
Humor can provide useful information during the psychiatric evaluation of children and adolescents and can also facilitate the therapeutic process. Clinical examples demonstrate how humor is useful as a diagnostic tool; how it can be used to shape the therapeutic relationship; and the role of humor as a therapeutic technique. Humor may help the child and adolescent patient explore feelings and may help the therapist deal with resistance. In some circumstances, the humor itself can become an agent of change. Humor has been used in the treatment of depression, aggression, social ineptitude, and conduct problems. Both the benefits and the risks of using humor are discussed.


Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine.
To elucidate inhibition of protein kinase C alpha (PKC alpha) activity by staurosporine on apoptosis of oral cancer cell line tongue squamous cell carcinoma (TSCCa) cells and to clarify the role of survivin and caspase-3 in mediating apoptosis. TSCCa cell viability was measured by MTT assay after 100 nmol/L staurosporine treatment. Apoptotic cells were identified by using phase contrast microscopy, acridine orange/ethidium bromide staining, and flow cytometry. Level of PKC alpha and its subcellular location were investigated using Western blot analysis. Expression of survivin and caspase-3 were evaluated using immunocytochemistry. Staurosporine significantly inhibited the cell viability of TSCCa cells in a dose- and time-dependent manner. Marked cell accumulation in G2/M phase was observed after 100 nmol/L staurosporine exposure for 6 h and 12 h. In addition, the percentage of apoptosis increased in a time-dependent manner, from 2.9% in control cultures to approximately 27.4% at 100 nmol/L staurosporine treatment for 24 h. Staurosporine displayed difference in inhibitory efficacy between cytosolic and membrance-derived PKC alpha. The content of PKCalpha in membrane versus cytosol decreased quickly, from 0.45 in ethanol-treated control cultures to 0.18 after staurosporine exposure for 24 h (P<0.01). After treatment with staurosporine, a time-dependent reduction of survivin and an activation of caspase-3 were observed in TSCCa cells. Staurosporine inhibited cell viability and promoted apoptosis in TSCCa cells. Inhibition of PKCalpha activity might be a potential mechanism for staurosporine to induce apoptosis in this cell line. The cleavage of survivin and activation of caspase-3 signaling pathway might contribute to PKC alpha inhibition-induced apoptosis.


Mild tricuspid regurgitation: a benign fetal finding at various stages of pregnancy.
Tricuspid regurgitation (TR) may accompany various anatomical malformations and/or dysfunction of the fetal right heart. It may also appear in an anatomically healthy heart. With improved ultrasound modalities, more cases than the previously estimated prevalence of fetal TR in the low-risk population are being diagnosed. The objective of this study was to determine the prevalence of mild fetal TR in a low-risk obstetric population. In 157 low-risk pregnant women (age range, 18-42 years) undergoing both early second-trimester and mid-trimester targeted organ scanning, including complete fetal echocardiography according to the five transverse planes technique, the apical four-chamber view was visualized using gray-scale, color Doppler and spatiotemporal image correlation (STIC) ultrasound modalities, with optimal acquisition parameters. Mild-to-moderate TR was discovered in the early second-trimester scan in 131/157 (83.4%) fetuses. No cases of cardiac malformation were found. All fetuses showed normal flow in the ductus venosus, including in one case diagnosed with moderate TR. Only in 39 (24.8%) cases was mild TR still evident at the second, mid-trimester scan. Neonatal echocardiography revealed mild TR in eight (5.1%) cases. No cases of chromosomal anomalies were detected. Mild TR is a benign finding of a temporal nature in early pregnancy.


Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors.
Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers. Histone deacetylase inhibitors (HDACi) are epigenetic modifiers that, in vitro, have been shown to induce growth arrest, apoptotic or autophagic cell death, and terminal differentiation of myeloid tumor cells. These effects were observed both at the bulk tumor level and in the most immature CD34⁺38- cell compartments containing the leukemic stem cells. Thus, there is a strong rationale supporting HDACi therapy in myeloid malignancies. However, despite initial promising results in phase I trials, HDACi in monotherapy as well as in combination with other drugs, have failed to improve responses or survival. This review provides an overview of the rationale for HDACi in myeloid malignancies, clinical results and speculations on why clinical trials have thus far not met the expectations, and how this may be improved in the future.


Isophorone Diisocyanate: An Effective Additive to Form Cathode-Protective-Interlayer and Its Influence on LiNi0.5Co0.2Mn0.3O2 at High Potential.
In this work, we propose a novel electrolyte additive, isophorone diisocyanate (IPDI), to construct the surface protective interlayer. This membrane is produced via nucleophilic addition between the IPDI's diisocyanate groups and the free-radical-onium ion oxidative intermediate of propylene carbonate (PC). In the electrolyte with IPDI added between 10-20 mM, LiNi0.5Co0.2Mn0.3O2 presents the excellent performance, demonstrating the relative wide operational window to form the optimal protective membrane. This protective membrane ameliorates the cyclic stability. Although all systems deliver ∼185 mAh g-1 under 1 C between 2.5-4.6 V (vs Li+/Li), the cells in the suitable electrolyte maintain 90.4% in the 50 cycles and 83.2% in the 200 cycles, whereas the control cells are seriously dropped to 73.4% and 69.8%. The cells in the electrolyte with the appropriate IPDI also present the good rate capability, attaining ∼143 mAh g-1 under 5 C, much higher than the cells in the control electrolyte(92.4 mAh g-1). The additive proposed in this work is helpful to augment the energy density of lithium ion battery and prolong the one-drive distance of electric vehicles.


An Adenosine Triphosphate- Dependent 5'-3' DNA Helicase From sk1-Like Lactococcus lactis F13 Phage.
Here, we describe functional characterization of an early gene (gp46) product of a virulent Lactococcus lactis sk1-like phage, vB_Llc_bIBBF13 (abbr. F13). The GP46 F13 protein carries a catalytically active RecA-like domain belonging to the P-loop NTPase superfamily. It also retains features characteristic for ATPases forming oligomers. In order to elucidate its detailed molecular function, we cloned and overexpressed the gp46 gene in Escherichia coli. Purified GP46 F13 protein binds to DNA and exhibits DNA unwinding activity on branched substrates in the presence of adenosine triphosphate (ATP). Size exclusion chromatography with multi-angle light scattering (SEC-MALS) experiments demonstrate that GP46 F13 forms oligomers, and further pull-down assays show that GP46 F13 interacts with host proteins involved in replication (i.e., DnaK, DnaJ, topoisomerase I, and single-strand binding protein). Taking together the localization of the gene and the obtained results, GP46 F13 is the first protein encoded in the early-expressed gene region with helicase activity that has been identified among lytic L. lactis phages up to date.


HLA-B*5701 clinical testing: early experience in the United States.
HLA-B*5701 testing to provide risk stratification for abacavir hypersensitivity has the potential to reduce incidence of hypersensitivity reactions in susceptible individuals. Early experience with clinical HLA-B*5701 testing of the first 100 specimens, from a large clinical reference laboratory in the United States, is presented. Patient samples were tested using a two-step approach. The first step allowed rapid identification of most HLA-B*5701-negative samples in a high throughput mode. The second step involved resolution of putative positives by DNA sequencing to identify B*5701 specifically as well as other B57 subtypes. Test reporting included a phone call from a genetic counselor to obtain the ethnic background and indication for testing and to provide a patient-specific interpretation. The patients population was comprised of Caucasians, 84%; Hispanics, 13%; and African Americans, 3%. Among the 100 samples tested, 92% were HLA-B*5701-negative and 8% were positive for the HLA-B*5701 allele. All HLA-B*5701 allele positives were identified in Caucasian patients. Where the indication for testing was obtainable (57 patients), pre-abacavir therapy screening was the indication 67% of the time. Clarification of previous suspected history of hypersensitivity was the indication 33% of the time. Among samples tested to help clarify a previous history of hypersensitivity, 16/19 or 84% did not carry the HLA-B*5701 allele whereas 3/19 (16%) were carriers of the HLA-B*5701 allele. Early utilization of HLA-B*5701 testing in community practice was not always consistent with the clinical indications for testing. Post-test communication assisted in providing physician education and interpretation of patient-specific results.


[The proteomics research on relational expressed serum proteins among the recovered SARS patients complicating avascular necrosis of femoral head].
To seek differentially expressed serum proteins in recovered SARS patients complicating avascular necrosis of femoral head (AVNFH). 2-DE and MALDI-TOF MS were used to study the comparative serum proteomics among female SARS AVNFH group, female SARS non-AVNFH group and female healthy group. ELISA method was used to detect serum amyloid P component in individual serum; specificity and sensitivity of serum amyloid P component were analyzed. Average protein points on 2-DE of 3 groups were 632 +/- 28, 671 +/- 55, 688 +/- 42 respectively, and the matching rate of protein points was ranged from 85% to 95%; eighteen differentially expressed proteins were discovered including transthyretin, serpin peptidase inhibitor, alpha-1-antitrypsin precursor, serum amyloid P components, etc. Compared to healthy group and SARS non-AVNFH group, transthyretin, C4B3, fibrinogen gamma, apolipoprotein L, apolipoprotein A-IV precursor, albumin and prealbumin showed lower expression, inversely serpin peptidase inhibitor, alpha-1-antitrypsin precursor and serum amyloid P components showed higher expression in serum in the SARS AVNFH necrosis group. The serum amyloid P component in 3 groups were 0.54 +/- 0.30 ng/ml, 0.83 +/- 0.39 ng/ml, 1.21 +/- 0.29 ng/ml respectively. The areas under the ROC curve on serum amyloid P component was 0.854, the specificity was 77.8% and the sensitivity was 85.2%. There were differentially expressed serum proteins in three groups. Serum amyloid P components might be one of the potential biomarkers in serum of recovered SARS patients complicating avascular necrosis of femoral head.


Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats.
berrant immune responses have been identified in obesity; however, immune cells of lymph nodes residing in the inflammatory environment of visceral adipose tissue have been largely overlooked. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce inflammation and modify T-cell function and therefore may improve immune function in obesity. Thus, we determined the effects of feeding fish oil (FO) containing EPA and DHA on mesenteric lymph node (MLN) immune cell function. In this study, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp) (n=10 per group) were randomized to one of three nutritionally adequate diets for 3 weeks: control (ctl, 0% EPA+DHA), low FO (LFO, 0.8% w/w EPA+DHA) or high FO (HFO, 1.4% w/w EPA+DHA). Lean JCR:LA-cp (Cp/cp or Cp/Cp) rats (n=5) were fed ctl diet. MLN cell phospholipid (PL) fatty acid composition, phenotypes and cytokine production were measured. Obese ctl rats produced more IL-1beta, IL-4 and IL-10, despite a higher proportion of (n-3) polyunsaturated fatty acids (PUFAs) and a lower (n-6):(n-3) PUFA ratio in MLN PL compared with lean ctl rats (P<0.05). Concanavalin A-stimulated IL-2 production did not differ from lean rats even though obese ctl rats had a lower proportion of CD4(+)CD25(+) cells (P<0.05). Feeding FO to obese rats increased the incorporation of (n-3) PUFA into MLN PL and normalized production of IL-1beta (HFO only), IL-4 and IL-10 to the levels similar to lean ctl rats (P<0.05). We demonstrate for the first time that obese JCR:LA-cp rats have impaired responses of MLN immune cells to mitogen stimulation and altered PL fatty acid composition. Feeding FO lowered the ex vivo inflammatory response (HFO only) and production of Th2 cytokines, without changing IL-2 production from ConA-stimulated splenocytes, which may occur independent of leptin signalling.


Dental-Derived Mesenchymal Stem Cells: State of the Art.
Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs' functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.


Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.
Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD.


Esophageal atresia and tracheo-esophageal fistula. 25 years' experience and current management.
A review of the experience with esophageal atresia and tracheoesophageal fistula over a 25-year period appears to lead to the advisability of the following procedures in surgical management:* Emergency gastrostomy under local anesthesia in all patients.* Extrapleural interruption of tracheo-esophageal fistula and end-to-end esophago-esophagostomy in patients who have the common type of upper esophageal atresia with distal tracheo-esophageal fistula.* Upper esophageal stretching and eventual esophago-esophagostomy in patients with proximal and distal esophageal atresia with or without proximal tracheo-esophageal fistula.


Analysis of the VH3 repertoire among genetically disparate individuals.
It has been shown that a conserved but highly biased subset of the germline VH complement is utilized in the peripheral VH repertoire of Caucasians. To distinguish between VH-autonomous effects and background genetic effects, we have now assessed the incidence of rearrangement of eight VH3 gene segments in preimmune CD19+IgD+B cells from genetically disparate subjects of diverse ethnic backgrounds. Results indicate that the set of gene segments utilized for rearrangements by these subjects is similar, and predominantly reflects the bias previously observed in Caucasians. The preimmune repertoire of each subject is dominated by two or three gene segments, with a predominant expression of V3-23 in all the subjects. Variation in the use of individual gene segments, including V3-23, was observed among the subjects. These results indicate that the processes that favor the preferential use of particular genes is largely independent of genes outside the VH locus. The minor variation in utilization of VH segments, however, is probably influenced by the genetic background of the individual.


[Unwanted pregnancy: impact on health and society in Latin America and the Caribbean].
Engaging in sexuality and reproduction should always be something that is wanted and planned. Unfortunately, when that is not the case, one result can be unwanted pregnancy. Unwanted pregnancies have consequences for women, their families, and their countries. This document reviews the causes and results of unwanted pregnancy, emphasizing the impact that this problem has on Latin America and the Caribbean (LAC). Four reasons why unwanted pregnancy is a continuing problem in LAC are: 1) people's growing desire to have smaller families, 2) the unmet need for family planning, 3) the fact that contraceptive methods are not 100% effective, and 4) unwanted sexual relations. Unwanted pregnancies especially affect adolescent women, single women, and women over 40 years of age. Given their desperate situation with an unwanted pregnancy, some women opt for an unsafe abortion, which can lead to their death. Other women can go so far as to commit suicide, or be murdered by a family member or other person who is unhappy that the pregnancy has occurred. It has been found that women who decide to continue with the pregnancy have higher risks of suffering an illness, and the same is true for the child. Reducing unwanted pregnancies and treating post-abortion complications are key to lowering maternal mortality and morbidity. This necessitates developing mass communication programs that address gender issues, education programs for girls, and sex education programs. It is also vital to make available to all persons reproductive health services that include family planning methods. In the countries of LAC with laws that specify grounds for legally ending a pregnancy, it is necessary that health care be organized to actually provide this service, and that health care programs obtain the safest, most effective technologies now available for ending a pregnancy.


Influence of physical, mental and intellectual development on disability in young Norwegian men.
Few studies have examined the effects of educational level, intellectual performance, mental function, body mass index and height as well as their interrelationship on the risk of disability pension (DP), taking other life course factors into account. We linked several national registers, comprising the Medical Birth Registry, the Central Population Register, the Education Register, the Norwegian Labour and Welfare Organisation and the Norwegian Armed Forces Personnel Data Base, providing personal data on biological and social variables from childhood to young adult age. Participants were all males live born during the period 1967-76, followed up through 2003. Men were excluded who died, emigrated or were granted a DP until age 23 years (when follow-up started) and persons who did not become gainfully employed during the study period. Thus, the study population comprised 302 330 men, and the study outcome was being granted a DP after age 23 years. 3651 men (1.2%) were granted a DP. The DP rate was inversely associated with both educational level and intellectual performance. The adjusted population attributable risks (PAR) values for these two variables were 47% and 35%, respectively. The effect of the other variables was modest. Over- and underweight and short stature were associated with DP, but the effect was largely reduced after adjusting for intellectual performance. Impaired mental function seemed to have an independent effect. Receiving an early DP is dependent on several factors acting at different stages of life, above all educational level and intellectual performance. High education can modify some of the effects of low intellectual performance.


Racial and sexual identities as potential buffers to risky sexual behavior for Black gay and bisexual emerging adult men.
Emerging adult Black gay and bisexual men represent intersections of social groups that are greatly impacted by the HIV epidemic (i.e., young, Black, gay/bisexual). Given their vulnerability to HIV, it is imperative to understand how these social identities may also promote resilience, and point to protective factors that may aid in our development of population-specific HIV prevention interventions. An online survey of the experiences of Black lesbian, gay, and bisexual young adults was administered. The current study assessed the intersection of identities and sexual risk behavior for a subsample of this population; 120 Black gay and bisexual young men (Mage = 21.79, SD = 3.08). Using hierarchical linear regression, higher levels of racial centrality (degree to which being Black is central to ones identity) and racial public regard (perceptions of societal views toward Black Americans) predicted decreases in risky sexual behavior (total anal sex acts and unprotected anal sex acts). Researchers and interventionist should consider the ways in which racial centrality may be a critical tool in our efforts to decrease the HIV epidemic among young Black gay and bisexual men in America.


Characterizing Reactivity to Onchocerca volvulus Antigens in Multiplex Bead Assays.
Multiplex bead assays (MBAs) may provide a powerful integrated tool for monitoring, evaluation, and post-elimination surveillance of onchocerciasis and co-endemic diseases; however, the specificity and sensitivity of Onchocerca volvulus antigens have not been characterized within this context. An MBA was developed to evaluate three antigens (OV-16, OV-17, and OV-33) for onchocerciasis. Receiver operating characteristics (ROC) analyses were used to characterize antigen performance using a panel of 610 specimens: 109 O. volvulus-positive specimens, 426 non-onchocerciasis controls with filarial and other confirmed parasitic infection, and 75 sera from patients with no other parasitic infection. The IgG and IgG4 assays for OV-16 demonstrated sensitivities of 95.4% and 96.3%, and specificities of 99.4% and 99.8%, respectively. The OV-17 IgG and IgG4 assays had sensitivities of 86.2% and 76.1% and specificities of 79.2% and 82.8%. For OV-33, the IgG and IgG4 assays had sensitivities of 90.8% and 96.3%, and specificities of 96.8% and 98.6%. The OV-16 IgG4-based MBA had the best assay characteristics, followed by OV-33 IgG4. The OV-16 IgG4 assay would be useful for monitoring and evaluation using the MBA platform. Further evaluations are needed to review the potential use of OV-33 as a confirmatory test in the context of program evaluations.


[Low-grade MALT-type non-Hodgkin lymphoma of the stomach with local recurrence 14 years following resection. Demonstration of clonal identity using polymerase-chain-reaction (PCR)].
So-called low grade B-cell lymphomas of MALT type occurring mainly in the gastrointestinal tract but also in the salivary glands, the thyroid and the lungs are indolent neoplasms with a prolonged clinical course and persistent localized disease at the site of origin. This behaviour sets them apart from their nodal counterparts, which are frequently generalized from onset. Their recognition within and their separation from accompanying reactive processes (e.g. chronic gastritis) is important but may be difficult on morphology alone. In the immediate past there have been reports on regression of gastric MALT type lymphomas after eradication of Helicobacter pylori. We observed a 68-year-old male patient who underwent partial gastric resection for persistent ulcer disease in 1979. A histological diagnosis of pseudolymphoma was established at that time. In 1993 he again had gastrointestinal bleeding. Endoscopy revealed ulcerations at the anastomosis. Biopsies showed a monoclonal infiltrate of centrocytoid B-cells with typical lymphoepithelial lesions, suggesting the diagnosis of low grade B-cell lymphoma of MALT type which was seen focally in multiple biopsies randomly taken from the gastric remnant. Review of the 1979 specimen revealed identical lesions. Polymerase chain reaction (PCR) on both specimens demonstrated identical products of rearranged Ig-heavy chain genes, thus confirming the monoclonality and establishing the clonal relationship of both lesions. Staging revealed no extragastric disease. Two courses of chemotherapy did not affect the mucosal infiltrates. Although the patient had been under antacid medication and the presence of Helicobacter pylori could not be demonstrated, antimicrobial treatment was given, after which follow-up biopsies were free of tumor and bacteria after 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)


[The institutionalization of health care in Russia: actual trends].
Since XX century, health care is a first-rate social institution. The analysis of tendencies of functioning of institution of health care in modern Russia is presented by the article in methodological plane of the system of social structural functions (AGIL) proposed by T. Parsons. The patient is the main participant of medical organizational process. The activity of other participants of process of organization of medical care is to be focused primarily on satisfaction of needs of patient during medical care rendering. The society implements training of subjects for executing their professional roles that determines professionalization of executed functions. The most important purpose of modern training programs in medical education is determined by leading level of cognition, forecasting and achievement of socially significant aftermaths of future during structuring of educational process. In the context of integrative function the coordination of activities of participants of interaction is implemented. In conditions of actual tendencies of market economy the interaction of participants of the process of medical care rendering and the process of quality control of medical care is developed on the basis of implementation of standards of medical care. In Russia, the institutionalization of health care presupposes cooperation and interaction of subjects of system differing by degree and amount of collaborative work. The latent function (maintenance of value pattern) determines regularity, predictability, stability of functioning of social relationships. The social control supports expedient behavior of participants of process of medical care rendering. The dysfunctional practices of modern Russian health care are considered in the context of concept of effective interaction of participants of medical organizational process targeted to maintenance of rights of patients for accessible and qualitative medical care. As a result of applied analysis, the problems were revealed decreasing effectiveness of functioning of system of organization of medical care of population. The minimization of risks of development of social inequity and increasing of accessibility of qualified medical care are considered in the context of verification and overcoming of dysfunctions during organization of medical care of population.


Ionization energies of LinX (n = 2, 3; X = Cl, Br, I) molecules.
Molecules of Li(n)X (n = 2, 3; X = Cl, Br, I) were examined with a magnetic sector mass spectrometer by surface ionization using a triple rhenium filament impregnated with fullerene (C60). The ionization energies obtained for Li(2)Cl, Li(2)Br and Li(2)I molecules are 3.8 +/- 0.1, 3.9 +/- 0.1 and 4.0 +/- 0.1 eV, respectively. The first ionization energy of Li(2)Cl is documented, while there are no literature data for the ionization energies of Li(2)Br and Li(2)I. The molecules of Li(3)Cl, Li(3)Br and Li(3)I were detected experimentally for the first time with ionization energies of 4.0 +/- 0.1, 4.1 +/- 0.1 and 4.1 +/- 0.1 eV, respectively. The ionization energies of Li(n)X (n = 2, 3; X = Cl, Br, I) are in correlation with the theoretical prediction of their hyperlithiated configurations.


Inverse Rendering and Relighting From Multiple Color Plus Depth Images.
We propose a novel relighting approach that takes advantage of multiple color plus depth images acquired from a consumer camera. Assuming distant illumination and Lambertian reflectance, we model the reflected light field in terms of spherical harmonic coefficients of the bi-directional reflectance distribution function and lighting. We make use of the noisy depth information together with color images taken under different illumination conditions to refine surface normals inferred from depth. We first perform refinement on the surface normals using the first order spherical harmonics. We initialize this non-linear optimization with a linear approximation to greatly reduce computation time. With surface normals refined, we formulate the recovery of albedo and lighting in a matrix factorization setting, involving second order spherical harmonics. Albedo and lighting coefficients are recovered up to a global scaling ambiguity. We demonstrate our method on both simulated and real data, and show that it can successfully recover both illumination and albedo to produce realistic relighting results.


Revised model needs high level buy-in.
In late January this year the Department of Health (DH) released a revised and updated version of its NHS Premises Assurance Model (NHS PAM), a software-based tool originally launched in 2010 to enable estates and facilities managers to more easily gauge the condition of their built assets, provide premises assurance to their management Boards, and assure commissioners that healthcare is being delivered in fit-for-purpose buildings. Having, in the March 2013 HEJ, described some of the key features and benefits of the latest Model, here, in the first half of a two-part article, we report on the morning session of the first in a series of IHEEM and DH-organised roundtable discussion events planned for coming months to help promote the Model, explain its benefits, and encourage wider, NHS take-up. The next HEJ (August 2013) will cover the afternoon's debate.


Binary mixtures of ionic liquids: Ideal, non-ideal, or quasi-ideal?
The mixing of ILs provides an opportunity for fine tuning the physiochemical properties of ILs for various applications. However, a suitable mixture having desired properties can only be designed when the physiochemical properties of the mixtures of ILs along with their spectroscopic properties are well understood. With an aim to achieve this objective, three different mixtures with a common anion, namely, [C2C1im][C4C1im][NTf2], [C3C1pyr][C4C1pyr][NTf2], and [C3C1im][C3C1pyr][NTf2], have been investigated in the current study. Investigations have been carried out at the macroscopic level by observing the thermophysical properties, such as molar volume and thermal expansion coefficient, and at the microscopic level with time-resolved fluorescence measurements and the pulse field gradient nuclear magnetic resonance (NMR) technique. The results obtained from the thermophysical study have indicated that excess molar volume for imidazolium-based IL-IL mixtures may be linked to the free volume created by the alkyl chain of the imidazolium cation whereas for the mixture of pyrrolidinium ILs, lowering of density can give rise to free volume. Analysis of time-resolved fluorescence anisotropy data has provided clear evidence in favor of the presence of free volume in the binary mixture of ILs. NMR studies have also supported the fluorescence anisotropy data. The outcome of the present investigation reveals that the mixtures show appreciable deviation from ideal behavior and the deviation from the ideal behavior is caused due to the generation of free volume in the resultant mixture, describing these IL mixtures as quasi-ideal rather than ideal or non-ideal.


Using a short-pulse diffraction-limited laser beam to probe filamentation of a random phase plate smoothed beam.
A short pulse (few picoseconds) laser probe provides high temporal resolution measurements to elucidate details of fast dynamic phenomena not observable with typical longer laser pulse probes and gated diagnostics. Such a short pulse laser probe (SPLP) has been used to measure filamentation of a random phase plate (RPP) smoothed laser beam in a gas-jet plasma. The plasma index of refraction due to driven density and temperature fluctuations by the RPP beam perturbs the phase front of a SPLP propagating at a 90 degree angle with respect to the RPP interaction beam. The density and temperature fluctuations are quasistatic on the time scale of the SPLP (approximately 2 ps). The transmitted near-field intensity distribution from the SPLP provides a measure of the phase front perturbation. At low plasma densities, the transmitted intensity pattern is asymmetric with striations across the entire probe beam in the direction of the RPP smoothed beam. As the plasma density increases, the striations break up into smaller sizes along the direction of the RPP beam propagation. The breakup of the intensity pattern is consistent with self-focusing of the RPP smoothed interaction beam. Simulations of the experiment using the wave propagation code, PF3D, are in qualitative agreement demonstrating that the asymmetric striations can be attributed to the RPP driven density fluctuations. Quantification of the beam breakup measured by the transmitted SPLP could lead to a new method for measuring self-focusing of lasers in underdense plasmas.


The energy dependence of CO(v,J) produced from H2CO via the transition state, roaming, and triple fragmentation channels.
The dynamics of CO production from photolysis of H2CO have been explored over a 8000 cm-1 energy range (345 nm-266 nm). Two-dimensional ion imaging, which simultaneously measures the speed and angular momentum distribution of a photofragment, was used to characterise the distribution of rotational and translational energy and to quantify the branching fraction of roaming, transition state (TS), and triple fragmentation (3F) pathways. The rotational distribution for the TS channel broadens significantly with increasing energy, while the distribution is relatively constant for the roaming channel. The branching fraction from roaming is also relatively constant at 20% of the observed CO. Above the 3F threshold, roaming decreases in favour of triple fragmentation. Combining the present data with our previous study on the H-atom branching fractions and published quantum yields for radical and molecular channels, absolute quantum yields were determined for all five dissociation channels for the entire S1←S0 absorption band, covering almost 8000 cm-1 of excitation energy. The S0 radical and TS molecular channels are the most important over this energy range. The absolute quantum yield of roaming is fairly constant ∼5% at all energies. The T1 radical channel is important (20%-40%) between 1500 and 4000 cm-1 above the H + HCO threshold, but becomes unimportant at higher energy. Triple fragmentation increases rapidly above its threshold reaching a maximum of 5% of the total product yield at the highest energy.


Gonadal- and sex-chromosome-dependent sex differences in the circadian system.
Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.


Can Subacute Thyroiditis Be a Cause of Fever of Unknown Origin?
Subacute thyroiditis (SAT) is a self-limiting, painful, non-suppurative thyroid gland inflammation, which usually develops two to eight weeks after viral upper respiratory tract infections, accompanied by pain and fever. The thyroid gland is large, painful, and tender. It presents with fever, myalgia, arthralgia, weakness, and sore throat. A 37-year-old male presented to medical ward with a history of fever for three weeks along with swelling of neck and difficulty in swallowing. The patient had features of hyperthyroidism. High-resolution ultrasonography (HRUSG) and thyroid scan were suggestive of thyroiditis. Later on, on follow-up, the patient developed hypothyroidism. He was managed with antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids, and he responded well to the above treatment. The index patient presented as a case of fever which on workup was found to be secondary to subacute thyroiditis (SAT).


[Determination of elastase 1 in plasma or serum by latex turbidometric immunoassay with automatic analyzer].
We developed a latex turbidometric immunoassay(LTIA) for elastase 1. The precisions were 1.0-2.8% intra-run and 1.2-2.9% inter-day. The dilution test showed good linearity between 80-4000 ng/dl. There was interference by bilirubin, hemoglobin, lipemia or rheumatoid factor. Serum and plasma elastase 1 measured by LTIA(y) showed significant correlations with those by RIA(x) (serum: y = 0.98x--18, r = 0.980, n = 64, plasma: y = 0.96x--19, r = 0.976, n = 61). It was confirmed that the values were elevated in patients with pancreatic disease compared to the normal level. These results demonstrate that the determination of elastase 1 in plasma or serum by this method is useful, simple and time-saving, when compared with that by RIA.


Effects of Platinum Nanocolloid in Combination with Gamma Irradiation on Normal Human Esophageal Epithelial Cells.
Our previous study demonstrated that platinum nanocolloid (Pt-nc), combined with lower-dose gamma irradiation at 3, 5, and 7 Gy significantly decreased proliferation and accelerated apoptosis of the human esophageal squamous cell carcinoma-derived cell line KYSE-70. The aim of the present study was to determine, under the same conditions as our previous study where gamma rays combined with Pt-nc were carcinostatic to KYSE-70 cells, if we could induce a radioprotective or the radiation-sensitizing effect on the human normal esophageal epithelial cells (HEEpiC). HEEpiC were treated with various Pt-nc concentrations and then irradiated with various gamma-ray doses. The proliferative status of HEEpiC was evaluated using trypan blue dye-exclusion and WST-8 assays. The cellular and nucleic morphological features were determined using crystal violet and Hoechst 33342 stainings, respectively. The intracellular level of reactive oxygen species (ROS) in HEEpiC was evaluated with a nitro blue tetrazolium (NBT) assay. The apoptotic status was detected with caspase-3, Bax, and Bcl-2 by Western blotting. Either Pt-nc or gamma irradiation could inhibit the growth of HEEpiC; however, their combined use exerted a significant proliferation-inhibitory effect in a Pt-nc dose-dependent manner than gamma irradiation alone. Pt-nc resulted in radiation sensitization rather than radiation protection on HEEpiC in vitro similar to KYSE-70 cells, when Pt-nc was administrated alone or combined with gamma irradiation. Thus, Pt-nc has an inhibitory effect on cell proliferation, a facilitative effect on apoptosis, and a certain degree of toxicity against HEEpiC.


Quantitative structure-activity relationships: analysis of interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2-substituted analogues with rat, mouse, guinea pig, and hamster cytosolic receptor.
The competitive receptor binding affinities of thirteen 2-substituted 3,7,8-trichlorodibenzo-p-dioxins to hepatic cytosol from rat, mouse, guinea pig, and hamster were determined with [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin as the radioligand. Multiple parameter linear regression analysis of the binding data from the four species gave the following equations: pEC50 (rat) = 7.196 + 0.600 pi - 0.255 delta Es - 1.683 HB pEC50 (mouse) = 6.365 + 1.641 pi + 1.206 sigma 0 pEC50 (hamster) = 7.416 + 1.026 pi + 0.509 delta Es + 0.748 sigma 0 pEC50 (guinea pig) = 6.892 + 1.035 pi where pi, delta Es, HB, sigma 0, and Vw are physicochemical parameters for substituent lipophilicity, steric effect, hydrogen bonding capacity, electronegativity, and van der Waals volume (relative to H), respectively. These equations demonstrate that there are important species differences in the receptor protein binding site interactions with the substituted analogues. These data, coupled with the known species differences in the molecular properties of the receptor proteins, are evidence for a heterologous nature of the receptor between mammalian species. Multiple parameter linear regression analysis of the relative aryl hydrocarbon hydroxylase (AHH) induction potencies of these analogues in rat hepatoma H-4-II E-cells in culture gave the following equation. The correlation pEC50 (AHH induction) = 3.208 + 0.950 pEC50 (rat binding) - 0.955 delta B5 between receptor binding and AHH induction was dependent on a steric parameter (delta B5, STERIMOL) and the results suggest that an additional substituent-dependent process (e.g., an activation step) may be required after initial ligand-receptor binding for the ultimate expression of the receptor-mediated response (i.e., AHH induction).


Hypnosis in the clinical setting.
Therapeutic hypnosis has been in use for hundreds of years, yet it is still is still relatively unknown as a therapeutic modality and underutilized by health care professionals. Nurse practitioners are in a unique position to bring hypnosis into the forefront of our work with patients and clients in most clinical settings. The author aims to introduce nurse practitioners to the potential and possibilities of incorporating hypnosis into individual treatment plans.


Improving health care: national policy and local practice.
Attention to quality and patient safety in health care has grown substantially over recent years. From 1982, I have been involved in advocating for efforts to improve quality and safety. Four years ago, I was given the opportunity to lead an academic health system - hospitals, doctors, and a medical school. This article recounts the shift in perspective, from a focus solely on national policy, to one now of changing local practice. Both are important and needed. The past 25 years have seen a large scale shift in the way the public at large and especially the medical community view the state of quality and safety in health care. I have been privileged to participate in this transformation at the national level in several roles, and I would like to describe that evolution. Now, however, I have the job of leading an academic medical enterprise, and am challenged by the task of putting lofty national ideas into practice at the local level. I am very committed to this effort, but am sobered by the challenges we face.


Priming of motion direction and area V5/MT: a test of perceptual memory.
Presentation of supraliminal or subliminal visual stimuli that can (or cannot) be detected or identified can improve the probability of the same stimulus being detected over a subsequent period of seconds, hours or longer. The locus and nature of this perceptual priming effect was examined, using suprathreshold stimuli, in subjects who received repetitive pulse transcranial magnetic stimulation over the posterior occipital cortex, the extrastriate motion area V5/MT or the right posterior parietal cortex during the intertrial interval of a visual motion direction discrimination task. Perceptual priming observed in a control condition was abolished when area V5/MT was stimulated but was not affected by magnetic stimulation over striate or parietal sites. The effect of transcranial magnetic stimulation (TMS) on priming was specific to site (V5/MT) and to task - colour priming was unaffected by TMS over V5/MT. The results parallel, in the motion domain, recent demonstrations of the importance of macaque areas V4 and TEO for priming in the colour and form domains.


Public Perception Toward COVID-19 Disease Nature, Susceptibility to Complication, and Relationship to Influenza: A Cross-Sectional Study from Yemen.
Following the coronavirus disease (COVID-19) declaration as a pandemic, Yemen has started applying preventive measures to prevent its spread. This study aims to identify the perception regarding the nature of the COVID-19 disease, susceptibility to severe forms of the disease, and its relationship to seasonal influenza among the population of Yemen. This was a cross-sectional study of the public in Yemen. The relationship between participants' sociodemographic factors and their responses was assessed by the chi-square test. A total of 748 participants agreed to participate in the study. Regarding the nature of the diseases, nearly half of the participants (48.8%, n=352) believed that COVID-19 is a naturally occurring human virus that is a serious and fatal disease (61.2%, n=448). The majority (74.9%; n=518) did not agree that bacteria cause COVID-19. More than half of the participants (57.5%, n=423) believed this disease is transmitted to humans through a host animal. Regarding the vulnerable groups to develop severe COVID-19 infection, most of the participants pointed out that the elderly (94.3%, n=705), people with chronic diseases (89.9%, n=669), and pregnant women (53%, n=365) were more susceptible to severe diseases. Regarding symptoms, the majority (61.9%, n=458) of the participants agreed that the symptoms of COVID-19 are similar to those of seasonal influenza. Additionally, the majority (81.9%, n=579) agreed that some individuals develop more severe symptoms than seasonal influenza, particularly those with chronic illness. Gender, age, and education were found to be associated with participants' perceptions regarding the nature of the virus and susceptibility to severe disease. Participants demonstrate a good understanding of the nature and susceptibility to complications associated with COVID-19 disease and its relationship to influenza. However, the respondents with a lower level of education might require additional educational campaigns to improve their awareness of the disease.


Examining the effects of remote-video confederates on young women's food intake.
One's decisions about eating are at times, largely based on the observations of other people's eating behavior. Previous studies have shown that modeling of eating is a robust effect. The current research examined the impact of a video remote confederate on young women's food intake. Experiment 1 examined the effect of an eating or non-eating video confederate. Participants (N=77 female undergraduate students, M age=20.29) were exposed to a same-sex video confederate (i.e., a 25 year old woman) who was modeling eating (i.e., 4 winegums; pastille-type sweets) or not eating (i.e. no food visible). Results indicated that participants exposed to the eating confederate did not eat more than participants exposed to the non-eating confederate. Experiment 2 was conducted to address some of the limitations of Experiment 1. In this experiment, participants (N=51, M age=20.43) were exposed to one of three intake conditions: No-eating (i.e. food visible but not consumed), Small portion-size condition (i.e., 8 M&Ms) or Large portion-size condition (i.e., 20 M&Ms). The same video confederate as in Experiment 1 modeled these three conditions. Results indicated that participants did not adjust their intake to that of a video model. The current findings provide preliminary evidence for the assumption that modeling only exists if people have clear indications about how much others have consumed in the same context (as was the case in previous modeling studies). Future research is needed to further examine this proposition.


An infant presenting with Kawasaki disease following immunization for influenza: A case report.
Kawasaki disease (KD) is a childhood vascular disorder of unknown etiology. Concerns have recently been raised regarding vaccinations as a potential risk factor for KD. In addition, various forms of vasculitis have been reported as adverse events following administration after various vaccines. Patients exhibiting post vaccination KD have previously been described; however, thus far, to the best of our knowledge, only one patient exhibiting post influenza vaccination KD has been reported in Japan. The present study describes a case of KD 24 h after immunization with influenza in an infant (age, 18 months) following 6 days of high fever, a body rash that had persisted for 2 days and nonsuppurative bilateral conjunctivitis. To the best of the authors' knowledge, this is the first reported case in Korea and the present study reviews various recent studies regarding vasculitis following vaccination and the causal association between them.


Bone induction in subcutaneous tissue in rats by a newly developed DNA-coated atelocollagen and bone morphogenetic protein.
A unique biomaterial, a mixture of DNA and collagen (DNA/collagen), was developed and its efficacy as a carrier matrix for bone morphogenetic protein (BMP) was evaluated histologically. The material was prepared as a composite of DNA from salmon milt and pepsin-digested type I collagen (atelocollagen) from bovine dermis. Phase-contrast and fluorescence microscopy showed atelocollagen fibres with DNA coating. The dose-response and time-course of bone induction by BMP in DNA/collagen (5 x 10 x 1 mm) in the subcutaneous tissue was investigated in 20 male Wistar rats. The BMP/DNA/collagen induced new bone in a dose-dependent manner (0, 25, 50 or 100 micrograms of BMP). Histological examination in the time-course study showed that the BMP (100 micrograms)/DNA/collagen induced bone formation, while the DNA/collagen alone resulted in the accumulation of fibroblasts. These results indicate that the DNA/collagen is effective as a carrier matrix for BMP. It provides a cell anchorage for differentiation of osteoblasts and is absorbed as bone matures.


Relationship between brachial-ankle pulse wave velocity and invasively measured aortic pulse pressure.
Although brachial-ankle pulse wave velocity (baPWV) has been widely used as an index of arterial stiffness, no consensus exists about whether baPWV can reflect central aortic stiffness. The authors investigated the association between baPWV and invasively measured aortic pulse pressure (APP) in a total of 109 consecutive patients (mean age, 62.3 ± 11.3 years; 67.9% men). Most patients (91%) had obstructive coronary artery disease, and mean baPWV and APP values were 1535 ± 303 cm/s and 66.8 ± 22.5 mm Hg, respectively. In univariate analysis, there was a significant linear correlation between baPWV and APP (r = .635, P < .001). The correlation between baPWV and APP remained significant even after controlling for potential confounders (β = 0.574, P < .001; R2 = .469). Arterial stiffness measured by baPWV showed a strong positive correlation with invasively measured APP, independent of clinical confounders. Therefore, baPWV can be a good marker of central aortic stiffness.


The Impact of Different Sources of Fluctuations on Mutual Information in Biochemical Networks.
Stochastic fluctuations in signaling and gene expression limit the ability of cells to sense the state of their environment, transfer this information along cellular pathways, and respond to it with high precision. Mutual information is now often used to quantify the fidelity with which information is transmitted along a cellular pathway. Mutual information calculations from experimental data have mostly generated low values, suggesting that cells might have relatively low signal transmission fidelity. In this work, we demonstrate that mutual information calculations might be artificially lowered by cell-to-cell variability in both initial conditions and slowly fluctuating global factors across the population. We carry out our analysis computationally using a simple signaling pathway and demonstrate that in the presence of slow global fluctuations, every cell might have its own high information transmission capacity but that population averaging underestimates this value. We also construct a simple synthetic transcriptional network and demonstrate using experimental measurements coupled to computational modeling that its operation is dominated by slow global variability, and hence that its mutual information is underestimated by a population averaged calculation.


Oral health behaviour of schoolchildren and parents in Jordan.
The objectives of the study were: (i) to assess the level of dental knowledge and attitudes towards child dental care among parents in Jordan, (ii) to analyse the oral health care habits of schoolchildren and parents, and (iii) to evaluate the oral hygiene habits and use of professional dental services of children in relation to socio-demographic conditions. Cross-sectional, self-administered questionnaires for parents. National representative sample of 6-16-year-olds living in urban areas (n = 1556, children and parents, response rate 92%, 48.7% boys, 51.3% girls). In all, 80% of the parents knew about the harmful effect of sugar and 79% thought that poor oral hygiene may induce dental caries. In addition to proper oral hygiene (79%) and restriction of sugar/sweets (42%), 36% of the parents emphasized regular dental visits for the prevention of dental disease in children. However, most children saw a dentist for symptomatic reasons only (86%), while 11% attended for dental check-ups. At their last visit to the dentist, 49% of the children had tooth extraction and only 8% had preventive services (fissure sealing). Toothbrushing at least twice a day was reported for 31% of the children; 14% of children aged 6-9 years had assistance from adults in brushing. Dental care habits of children were highly affected by dental visiting habits of parents, and variations by level of education of parents were also found. The discrepancy between dental knowledge and attitudes of parents and oral health care practices indicate the need for oral health education. School-based oral health promotion programmes should be established in Jordan to influence the oral health behaviour of children and parents and to avoid further deterioration in their oral health.


Tongue to palate contact during speech in subjects with and without a tongue thrust.
The aims of this study were to determine the location and movements of the tongue on the palate during pronunciation of Persian consonants and selected words in subjects with and without a tongue thrust (TT). Ten patients with a TT and 10 control subjects, 9-13 years of age, matched for age, gender, ethnicity, type and severity of malocclusion, with no history of orthodontic treatment, surgery, or systemic disease were selected. Maxillary alginate impressions were taken to construct upper removable appliances with 12 electrodes. Fine wires connected the electrodes to a specially designed electropalatovision (EPU) device. The removable appliance was inserted in the upper arch and then the Persian consonants and some selected words were pronounced by both groups. An electromechanical marker was included on each electrode which showed the tongue movements on the palate. Tongue movements, the quantity of the tongue contacts, and the location of the tongue were compared using t- and Chi-square tests. In the TT group, the tongue had more contact with the palate on six electrodes (P < 0.001). When pronouncing the consonants, the tongue made contact anteriorly on the palate in the TT group. The quantity of tongue contacts with the palate was similar in both groups. During pronunciation of selected words, the contact points of the tongue to the palate were similar in both groups.


Comparison of the use of fresh-frozen canine cadavers and a realistic composite ex vivo simulator for training in small animal flexible gastrointestinal endoscopy.
OBJECTIVE To compare the usefulness of fresh-frozen canine cadavers (FFCCs) and a validated canine simulator model for training veterinary students in basic gastrointestinal endoscopic procedures. DESIGN Randomized trial. SAMPLE 48 veterinary students in their final year of training. PROCEDURES Students were randomly assigned to receive basic gastrointestinal endoscopic training on a canine simulator or FFCC. All students were trained as assigned in esophagogastroduodenoscopy, endoscopic gastric biopsy, and gastric foreign body removal for 2 h/d for 5 days. They then performed each procedure on a live dog, and procedure completion time and performance ability were compared between groups. Two experienced endoscopists used a validated Likert-type procedural rating scale to rate the students' performance. Students completed a survey to rate their training model. RESULTS No significant differences were identified between groups in quality of performance of the 3 endoscopic procedures on a live dog. Students required significantly less time to complete the procedures on a live dog when trained on an FFCC versus canine simulator. Although both training models were considered equally useful by students, training on the simulator was significantly more stimulating. CONCLUSIONS AND CLINICAL RELEVANCE Students showed the same skill level in performing basic endoscopic procedures on live dogs regardless of the training model used, although students who trained on the FFCC completed these procedures faster than students trained on the canine simulator. Use of the simulator appeared to be a viable alternative to use of FFCCs for veterinary endoscopic training, providing students with a good level of proficiency before performing endoscopic procedures on live dogs.


HIV prevalence and associated risk factors among men who have sex with men in three regions of Paraguay, 2020.
Our study aimed to measure HIV prevalence and associated risk factors among men who have sex with men (MSM) in three regions of Paraguay in 2020. MSM were recruited for cross-sectional surveys in three regions of Paraguay using respondent-driven sampling. Interview were conducted face-to-face to collect demographic characteristics and risk and preventive behaviors. The analysis assessed HIV prevalence and associated risk factors in the three samples of MSM within each region. A total of 1,207 MSM were recruited, including 559 in Asunción-Central, 245 in Alto Paraná, and 403 in Caaguazú. HIV prevalence was 24.2% (95% CI 20.6-27.9) in Asunción-Central, 10.2% (95% CI 6.7-14.6) in Alto Paraná, and 3.2% (95% CI 1.7-5.4) in Caaguazú. In Asunción-Central, associations with HIV were age ≥25 years (1.86, 95% CI 1.15-3.00), being employed (1.82, 95% CI 1.07-3.11), self-reporting as homosexual (1.90, 95% CI 1.06-3.43), having sex with a known HIV-positive partner acquisition (4.19, 95% CI 2.37-7.43), self-perceived as being at higher risk for HIV acquisition (4.15, 95% CI 2.54-6.77), and able to access condoms and lubricants (1.82, 95% CI 1.08-3.05). In Alto Paraná, associations with HIV were self-reporting as homosexual (4.33, 95% CI 1.19-15.65) and having higher HIV knowledge (2.53, 95% CI 0.97-6.61). In Caaguazú, associations with HIV were self-reporting as homosexual (7.06, 95% CI 1.53-32.46) and being diagnosed with depression (4.68, 95% CI 0.89-24.43). HIV prevalence among MSM in Paraguay varied by region, being highest in the capital and major metropolitan area of Asunción-Central, followed by the border area of Alto Paraná. While being self-identified as homosexual was associated with HIV in all three regions, other associations differed, indicating prevention programs need to be tailored to the locale.


Pediatric Wilson's disease: presentation and management.
Eleven patients (4 males, 7 females) with Wilson's disease who presented before 18 years of age are described. The mean age onset of symptoms was 11.2 +/- 3.9 (SD) years. The mean age at diagnosis was 13.3 +/- 3.4 (SD) years. All patients had hepatic manifestations of the disease when diagnosed: cirrhosis (6 patients), chronic hepatitis (2) and fulminant hepatic failure (3). Three patients were asymptomatic at diagnosis. Two of the symptomatic patients presented with new undescribed manifestations: one with blurred vision and the other with acalculous cholecystitis. At diagnosis, 6 patients had Kayser Fleischer rings and 5 had hemolytic anemia. The three patients with fulminant hepatic failure had hemolysis with relatively low serum aminotransferase and alkaline phosphatase levels, possibly helpful findings for rapid diagnosis of Wilson's disease in such presentation. Ten patients were treated with penicillamine. Liver transplantation was performed in 4 patients, 2 of which presented with fulminant hepatic failure. One patient died while waiting for liver transplantation, the remainder of the patients live free of symptoms. It is important to be aware of the different manifestations of Wilson's disease in the pediatric population, in order to make appropriate evaluations in a timely manner to facilitate early diagnosis and appropriate treatment.


Hot flashes, core body temperature, and metabolic parameters in breast cancer survivors.
To examine core body temperature, energy expenditure, and respiratory quotient among breast cancer survivors experiencing hot flashes and compare these data to published studies from healthy women. In an observational study, nine breast cancer survivors with daily hot flashes who met specified criteria spent 24 hours in a temperature- and humidity-controlled whole-room indirect calorimeter (ie, metabolic room). Demographic and disease/treatment information were obtained and the following were measured: hot flashes via sternal skin conductance monitoring (sampled every second); core body temperature via an ingested radiotelemetry pill (sampled every 10 seconds); and energy expenditure and respiratory quotient via a whole-room indirect calorimeter (calculated every minute). Circadian analysis of core temperature indicated wide variability with disrupted circadian rhythm noted in all women. Core temperature began to rise 20 minutes pre-flash to 7 minutes pre-flash (0.09 degrees C increase). Increases in energy expenditure and respiratory quotient increased with each hot flash. Findings are comparable to published data from healthy women and warrant replication in larger, more diverse samples of women treated for breast cancer.


Blue emissive dimethylmethylene-bridged triphenylamine derivatives appending cross-linkable groups.
Five new dimethylmethylene-bridged triphenylamine (DTPA) derivatives 4a-e bearing peripheral cross-linkable vinyl and trifluorovinyl groups were synthesized. The chemical structure of these compounds was characterized by 1H NMR, 13C NMR and HRMS. Their optical properties were studied by UV/Vis spectroscopy and fluorescence spectroscopy. Based on these studies, blue-coloured fluorescence and high fluorescence quantum yields were obtained for 4a-e. The electrochemical properties of these compounds were studied by cyclic voltammetry and the results were further elucidated by DFT calculations. Furthermore, the thermotropic properties of the new DTPAs were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Compounds 4a-d exhibit high thermal stability and thermal cross-linkable properties. These results provide an effective strategy for the design and synthesis of thermally stable and cross-linkable DTPA derivatives with tunable optical and electrochemical properties.


Clustering Enhancement of Noisy Cryo-Electron Microscopy Single-Particle Images with a Network Structural Similarity Metric.
The reconstruction of a three-dimensional model from cryo-electron microscopy (cryo-EM) two-dimensional images is currently a mainstream technology for revealing the structure of biomacromolecules. In this structure solution protocol, an important step is to identify each particle's projection orientation. Because the obtained single-particle images are often too noisy, clustering is an important step to mitigate noise by averaging images within the same class. The core of clustering is to place similar cryo-EM images into the same class; hence, measurement of similarity between data samples is an essential element in any clustering algorithm. As the cryo-EM images are highly noisy, directly measuring the similarity of two images will be easily biased by the hidden noise. In this study, we propose a new network structural similarity metric-based clustering protocol NCEM for clustering the noisy cryo-EM images. We first construct an image complex network for all of the cryo-EM single-particle images, where each image is represented as a node in the network. Then the similarity between two images is refined from the network structural geometry. By extending the similarity measurement from two independent images to their corresponding neighboring sets in the network, this new NCEM has typical advantages over direct measurement of two images for its noise resistance by using the structural information on the network. Our experimental results for both synthetic and real data sets demonstrate the efficacy of the protocol.


The whole-genome molecular epidemiology of sequential isolates of Acinetobacter baumannii colonizing the rectum of patients in an adult intensive care unit of a tertiary hospital.
Acinetobacter baumannii is a nosocomial multidrug-resistant pathogen that specifically colonizes and infects patients in intensive care units (ICUs). Genome plasticity of A. baumannii may contribute to the rapid development of A. baumannii resistance during patient treatment. There is little clarity on the dynamics of colonization of A. baumannii in humans. We studied 269 serial isolates of A. baumannii colonizing the rectum of 32 adult patients in an ICU; 5 to 16 isolates were obtained from each patient over a period of weeks to months. The isolates were sequenced using the Illumina platform. Multi-locus sequence typing revealed genetic diversity with 13 sequence types (STs); the dominant ST2 accounted for 202 of the 269 isolates and was isolated from each patient. A core genome comparison of isolates was used to elucidate a detailed understanding of the relationship among isolates within an ST and the genomic relationship among STs. One to three STs were observed in the isolates from each patient. Instances of unchanged colonization, sequential lineage colonization, and colonization with multiple lineages of A. baumannii were seen. The number of resistance genes carried by the isolates varied from 2 to 17. The predominant genes corresponded to those encoding resistance to β-lactam and aminoglycoside antibiotics. Generally, there was a strong correlation between ST and a particular antimicrobial resistance gene profile. This study makes an important baseline contribution to information that will help us understand the role of A. baumannii colonization in the development of opportunistic infections in ICU patients. IMPORTANCE Acinetobacter baumannii is a multidrug-resistant nosocomial pathogen that colonizes and infects debilitated patients in the ICU. There is very little information on the genomic characteristics of colonizing strains. This information is important to understand the evolution of lineages of A. baumannii that develop resistance while patients receive antibiotic treatment in the ICU. Our study demonstrated different patterns of colonization of the rectum of ICU patients with different STs of A. baumannii while one ST colonized all patients. Some STs carried more antibiotic resistance genes compared to others. However, there was a correlation between ST and a particular resistance gene profile. Our results further elucidate the dynamics of enteric colonization of this opportunistic pathogen.


Effect of growth hormone on muscle and liver protein synthesis in septic rats receiving glutamine-enriched parenteral nutrition.
Administration of recombinant human growth hormone (rhGH) to critically ill adults in an attempt to attenuate catabolism was associated with increased morbidity and mortality. Possible explanations included inhibition of glutamine release from skeletal muscle and consequent restriction of splanchnic glutamine supply. In this study, we examined the effects of rhGH on plasma glutamine levels and on muscle and liver glutamine concentrations and protein synthesis rates in sepsis. We investigated the possibility that administration of supplemental glutamine might ameliorate any adverse effects of rhGH. Prospective study in rats rendered septic by cecal ligation and puncture. University hospital laboratory. A total of 78 male Wistar rats in six groups. Animals received 6-hr tail vein infusions, commencing 18 hrs after cecal ligation and puncture, of either (a) 0.9% sodium chloride, (b) a standard parenteral nutrition (PN) solution without glutamine, or (c) an isocaloric, isonitrogenous PN solution with glutamine. PN groups received 400 microg rhGH or equivolume 0.9% sodium chloride vehicle in a divided subcutaneous and intravenous dose at PN commencement. Sacrifice was at the end of the infusion period. A further group was unoperated and uninfused and killed at 24 hrs as baseline controls. Glutamine concentrations were measured by fluorometry. Protein synthesis in muscle and liver was measured by a "flooding-dose" technique employing L-[4-H]phenylalanine. Plasma glutamine was increased after cecal ligation and puncture except in the saline and glutamine with rhGH animals. Muscle glutamine was reduced after cecal ligation and puncture and was significantly lower in animals receiving standard PN with rhGH vs. saline alone. Liver glutamine was increased in animals receiving saline and those receiving standard PN with rhGH. PN, with or without glutamine, increased muscle protein synthesis, and the administration of rhGH tended to further increase this effect. Neither PN, glutamine, nor rhGH had an effect on the increased liver protein synthesis characteristic of sepsis. In sepsis, increased muscle protein synthesis with PN and rhGH administration is not associated with increased muscle glutamine levels. Administration of rhGH does not result in reduced liver glutamine levels or rates of hepatic protein synthesis. PN containing glutamine was no more efficacious than standard PN at increasing muscle protein synthesis.


Assessment of captopril and nicardipine effects on chronic occlusive arterial disease of the lower extremity using Doppler ultrasound.
The effects of two potent vasodilating drugs, captopril (C) (25 mg tid), nicardipine (N) (20 mg tid), and placebo (P) were evaluated and compared, in 10 men (mean age of sixty-five years) with intermittent claudication from moderate to severe multilevel chronic occlusive arterial disease (COAD) of the lower extremity, by use of the Doppler ultrasonic method, at rest and after Carter's exercise test. All the examined subjects were normotensive, without diabetes or cardiopathy; all have been smokers. The eight-week total protocol consisted of an initial two-week placebo run-in period followed by two active drug phases and a two-week placebo phase, according to a double-blind, randomized, crossover design. At the end of each two-week period, ankle-arm index (AAI) and, following exercise, onset of lower extremity discomfort time (ODT), duration of exercise (ET), decrease of ankle systolic pressure after test (APD), and recovery time (RT) were determined. Moreover, at rest, just after exercise, and after recovery, simultaneous common femoral artery velocity waves were recorded and analyzed by a quantitative approach to detect the peripheral vasomotor adjustments. None of the patients required the withdrawal of the active treatments. Compared with P, C significantly reduced APD and RT, and N reduced RT and AAI; furthermore N caused a significant decrease in ODT, whereas C showed a trend, although not statistically significant, to increase ODT. Neither active therapy modified ET. These results suggest that C and N have different short-term effects on peripheral circulation in COAD. During exercise, C induces hemodynamic improvement in the ischemic lower extremity probably by inhibition of the sympathetic system and consequent reduction in collateral vessel vasoconstriction.


FAMILIAL HYPERCHOLESTEROLAEMIA - A DIAGNOSIS THAT EVERY PLASTIC SURGEON CAN EXPERIENCE.
Familial hypercholesterolaemia (FH) is the most common autosomal dominant inheritable disease caused by a defective catabolism of LDL particles. Their subsequent accumulation in circulation accelerates atherosclerotic vascular disease. Untreated FH increases the risk of premature manifestation of atherosclerosis (myocardial infarction - MI- or stroke); it is known that homozygous patients, if not adequately treated, are usually affected by atherothrombotic complications of the underlying disease before 20 years of age and often do not live longer than 30 years. Patients with FH are asymptomatic for a long period of time; their elevated blood lipid levels are often a random laboratory finding. The cardiovascular complications (MI or stroke) may be the primary manifestation of this disease. Clinical signs (xanthomas, xanthelasma or arcus corneae lipoides) occur rarely in these patients but are pathognomic, so at least basal awareness of these findings is necessary. Upon detection of such findings, a diagnostic procedure of FH including blood lipid measuring, careful personal and family history of cardiovascular disease (CVD) and subsequent referral to GPs or to MEDPED specialist is crucial. MEDPED (Make Early Diagnosis to Prevent Early Deaths in MEDical PEDigrees) project associates physicians specializing in patients with severe lipid metabolism disorders including FH. Treatment is based on statins, often in combination with ezetimibe. A great benefit in the treatment of these patients was the discovery of PCSK9 inhibitors, which are very effective and represent a therapeutic option especially for patients with very severe dyslipidaemia or with intolerance of statin therapy. The FH awareness of a plastic surgeon as a first-contact physician, who may be confronted with typical skin or eye manifestations of FH, is essential for the early detection of FH patients, who can then be internally examined and followed-up.


Protective ventilation during anaesthesia reduces major postoperative complications after lung cancer surgery: A double-blind randomised controlled trial.
Thoracic surgery for lung resection is associated with a high incidence of postoperative pulmonary complications. Controlled ventilation with a large tidal volume has been documented to be a risk factor for postoperative respiratory complications after major abdominal surgery, whereas the use of low tidal volumes and positive end-expiratory pressure (PEEP) has a protective effect. To evaluate the effects of ventilation with low tidal volume and PEEP on major complications after thoracic surgery. A double-blind, randomised controlled study. A multicentre trial from December 2008 to October 2011. A total of 346 patients undergoing lobectomy or pneumonectomy for lung cancer. The primary outcome was the occurrence of major postoperative complications (pneumonia, acute lung injury, acute respiratory distress syndrome, pulmonary embolism, shock, myocardial infarction or death) within 30 days after surgery. Patients were randomly assigned to receive either lung-protective ventilation (LPV group) [tidal volume 5 ml kg ideal body weight + PEEP between 5 and 8 cmH2O] or nonprotective ventilation (control group) (tidal volume 10 ml kg ideal body weight without PEEP) during anaesthesia. The trial was stopped prematurely because of an insufficient inclusion rate. Major postoperative complications occurred in 23/172 patients in the LPV group (13.4%) vs. 38/171 (22.2%) in the control group (odds ratio 0.54, 95% confidence interval, 0.31 to 0.95, P = 0.03). The incidence of other complications (supraventricular cardiac arrhythmia, bronchial obstruction, pulmonary atelectasis, hypercapnia, bronchial fistula and persistent air leak) was also lower in the LPV group (37.2 vs. 49.4%, odds ratio 0.60, 95% confidence interval, 0.39 to 0.92, P = 0.02).The duration of hospital stay was shorter in the LPV group, 11 [interquartile range, 9 to 15] days vs. 12 [9 to 16] days, P = 0.048. Compared with high tidal volume and no PEEP, LPV combining low tidal volume and PEEP during anaesthesia for lung cancer surgery seems to improve postoperative outcomes. ClinicalTrials.gov number: NCT00805077.


Transgender and Gender Diverse Community Perspectives on Barriers and Benefits of the Psychosocial Assessment for Gender-Affirming Medical Care.
Transgender and gender diverse (TGD) individuals often must undergo a psychosocial assessment and receive a letter of support from a mental health care provider to access gender-affirming medical care (GAMC). This study describes TGD individuals' perceptions of barriers and benefits of the assessment process and uses thematic analysis to explore TGD individuals' opinions on how mental health care should or should not be related to gender-affirming medical care. Two hundred and eighteen TGD participants completed an online survey. Participants endorsed benefits and negative impacts associated with the psychosocial assessment and provided qualitative responses to explain their support or opposition to involvement of mental health care and assessment in accessing GAMC. Nearly all participants identified both benefits (e.g., "experienced validation") and barriers (e.g., "experienced an increase in psychological distress") to the psychosocial assessment. Results are considered in the context of the historical marginalization and gatekeeping of TGD people by the medical system.


SyConn2: dense synaptic connectivity inference for volume electron microscopy.
The ability to acquire ever larger datasets of brain tissue using volume electron microscopy leads to an increasing demand for the automated extraction of connectomic information. We introduce SyConn2, an open-source connectome analysis toolkit, which works with both on-site high-performance compute environments and rentable cloud computing clusters. SyConn2 was tested on connectomic datasets with more than 10 million synapses, provides a web-based visualization interface and makes these data amenable to complex anatomical and neuronal connectivity queries.


Repulsion between oppositely charged macromolecules or particles.
The interaction of two oppositely charged surfaces has been investigated using Monte Carlo simulations and approximate analytical methods. When immersed in an aqueous electrolyte containing only monovalent ions, two such surfaces will generally show an attraction at large and intermediate separations. However, if the electrolyte solution contains divalent or multivalent ions, then a repulsion can appear at intermediate separations. The repulsion increases with increasing concentration of the multivalent salt as well as with the valency of the multivalent ion. The addition of a second salt with only monovalent ions magnifies the effect. The repulsion between oppositely charged surfaces is an effect of ion-ion correlations, and it increases with increasing electrostatic coupling and, for example, a lowering of the dielectric permittivity enhances the effect. An apparent charge reversal of the surface neutralized by the multivalent ion is always observed together with a repulsion at large separation, whereas at intermediate separations a repulsion can appear without charge reversal. The effect is hardly observable for a symmetric multivalent salt (e.g., 2:2 or 3:3).


Evaluation of an in vitro model with a novel statistical approach to measure differences in bacterial survival of extended-spectrum β-lactamase-producing Escherichia coli on an inanimate surface.
The role of environmental contamination in the transmission of Enterobacteriaceae is increasingly recognized. However, factors influencing the duration of survival in the environment have not yet been extensively studied. In this study, we developed and evaluated an in vitro model with a novel statistical approach to accurately measure differences in bacterial survival, that can be used to model the effects of multiple factors/conditions in future experiments. Two extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) isolates were used for this in vitro experiment: a CTX-M-15-producing E. coli sequence type (ST) 131 and a CTX-M-1-producing E. coli ST10 isolate. Each strain was 1:1 diluted in sterile water, sterile saline or sheep blood. Cover glasses (18 × 18 mm) were inoculated with the dilution and subsequently kept at room temperature. Bacterial survival on the glasses was determined hourly during the first day, once daily during the following 6 days, and from day 7 on, once weekly up to 100 days. The experiment was repeated six times for each strain, per suspension fluid. Viable bacteria could be detected up to 70 days. A biphasic survival curve for all suspension fluids was observed, whereby there was a rapid decrease in the number of viable bacteria in the first 7 h, followed by a much slower decrease in the subsequent days. We found a difference in survival probability between E. coli ST10 and ST131, with a higher proportion of viable bacteria remaining after 7 h for ST131, particularly in sheep blood.


Does the molecular electrostatic potential reflect the effects of substituents in aromatic systems?
A detailed analysis of the molecular electrostatic potential (MEP) at selected positions in molecular space was performed for a series of substituted benzene derivatives. We show that appropriately selected MEP values can quantitatively reflect the regiospecific effects of substituents on the aromatic ring. Theoretically evaluated electrostatic potentials in close proximity to the ring carbon atoms reflect well both through-space and resonance effects and excellent correlation is established between the MEP values and substituent constants. The best descriptor of the local properties at different ring positions is the electrostatic potential at nuclei (EPN).


A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands.
The most common genetic risk factor for Parkinson's disease known is a damaging variant in the GBA1 gene. The entire GBA1 gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire GBA1 gene in Parkinson's disease from a single large population. The GBA1 gene was assessed in 3402 Dutch Parkinson's disease patients using next-generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers. Fifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; P < 0.001). The rarely reported complex allele p.D140H + p.E326K appears to likely be a Dutch founder variant, found in 2.4% of patients and 0.9% of controls (OR, 2.7; P = 0.012). The number of first-degree relatives (excluding children) with Parkinson's disease was higher in p.D140H + p.E326K carriers (5.6%, 21 of 376) compared with p.E326K carriers (2.9%, 29 of 1014); OR, 2.0; P = 0.022, suggestive of a dose effect for different GBA1 variants. Dutch Parkinson's disease patients display one of the largest frequencies of GBA1 variants reported so far, consisting in large part of the mild p.E326K variant and the more severe Dutch p.D140H + p.E326K founder allele. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.


Synthesis of Sulfilimines via Selective S-C Bond Formation in Water.
Sulfilimines are valuable compounds both in organic synthesis and in pharmaceuticals. Here we developed a mild and simplified method for preparation of sulfilimines via selective S-C bond formation rather than traditional S-N bond formation. The method is both attractive and useful for the following reasons: it uses a readily available alkylation reagent such alkyl bromide or alkyl iodide, it uses water as solvent, it is easy to perform, and it is convenient for late-stage diversification of drugs.


Bifacial DNA origami-directed discrete, three-dimensional, anisotropic plasmonic nanoarchitectures with tailored optical chirality.
Discrete three-dimensional (3D) plasmonic nanoarchitectures with well-defined spatial configuration and geometry have aroused increasing interest, as new optical properties may originate from plasmon resonance coupling within the nanoarchitectures. Although spherical building blocks have been successfully employed in constructing 3D plasmonic nanoarchitectures because their isotropic nature facilitates unoriented localization, it still remains challenging to assemble anisotropic building blocks into discrete and rationally tailored 3D plasmonic nanoarchitectures. Here we report the first example of discrete 3D anisotropic gold nanorod (AuNR) dimer nanoarchitectures formed using bifacial DNA origami as a template, in which the 3D spatial configuration is precisely tuned by rationally shifting the location of AuNRs on the origami template. A distinct plasmonic chiral response was experimentally observed from the discrete 3D AuNR dimer nanoarchitectures and appeared in a spatial-configuration-dependent manner. This study represents great progress in the fabrication of 3D plasmonic nanoarchitectures with tailored optical chirality.


Antigenic diversity among Onchocerca volvulus in Nigeria, and immunological differences between onchocerciasis in the savanna and forest of Cameroon.
Onchocerciasis is a remarkably chronic infection and, in West Africa, there are distinct clinical and pathological differences between the disease in the savanna and in the forest. Experiments were carried out to see whether antigenic diversity among Ochocerca volvulus worms might contribute to these features. Extracts of adult worms and or microfilariae were analysed by disc electrophoresis on polyacrylamide gels and showed a remarkable diversity of protein patterns but no consistent savanna/forest or Nigeria/Cameroon differences. Indirect haemagglutination using cross-absorbed sera was used to look for antigenic diversity or identity between different O. volvulus worms. Sera of patients were absorbed with antigens extracted from worms taken from those paitents and then titrated against sheep erythrocytes coated with the same antigens. It was shown that an adult Onchocerca volvulus could be either antigenically identical with, or distinct from, another worm taken from the same patient. In one Nigerian village identity was shown in two instances nad diversity in five. Microfilariae lack some antigens possessed by adult worms. This test has shown consistent savanna/forest differences in worm antigen patterns and antibody responses. In order to explain the pattern of these differences it was necessary to postulate that forest patients possessed antibodies to another worm which had antigens in common with savanna Onchocerca. The relevance of these findings to the pathology and prevention of onchocerciasis is discussed.


Evidence based health care in old age psychiatry.
The purpose of this article is to present the current status and future needs of old age psychiatry in relation to evidence-based health care. The opportunities and difficulties of evidence-based medicine as applied to old age psychiatry are described. Depression is used as a specific example. The role of the Cochrane Collaboration and of clinical guidelines in dealing with these difficulties are discussed. There has been a tendency for drug studies to focus on younger age groups and to exclude patients with comorbidity or polypharmacy. Aspects of clinical management separate from drugs are given insufficient attention. The generalizability of current studies is a problem in old age psychiatry. Psychiatry is no less part of medicine than any other specialty. Increased attention to studies of effectiveness, as opposed to efficacy, is indicated. The Cochrane Collaboration is an international network which promotes and conducts systematic reviews of the effectiveness of health care. Systematic reviews can increase the generalizability of the current knowledge base and better define the needs for future research.


In vitro and in vivo evaluation of doxorubicin conjugates with the divalent peptide E-[c(RGDfK)2] that targets integrin alphavbeta3.
Integrins, especially integrin alpha vbeta3, are attractive receptors for vascular targeting strategies. Recently, a divalent RGD peptidomimetic, E-[c(RGDfK)2], has been described that demonstrates increased uptake in human ovarian carcinoma OVCAR-3 xenograft tumors. Inspired by these results, we set out to develop doxorubicin conjugates with E-[c(RGDfK)2] by binding two different maleimide derivatives of doxorubicin to E-[c(RGDfK)2] that was thiolated with iminothiolane. In this way, two water-soluble derivatives were obtained, E-[c(RGDfK)2]-DOXO-1 and E-[c(RGDfK)2]-DOXO-2. In E-[c(RGDfK)2]-DOXO-1, doxorubicin was bound to the peptide through a stable amide bond, and in E-[c(RGDfK)2]-DOXO-2, a MMP-2/MMP-9 cleavable octapeptide was introduced between doxorubicin and the peptide. The rationale for a MMP-2/MMP-9-cleavable linker was that MMP-2 and MMP-9 bind to integrin alpha vbeta3 and both are overexpressed in tumor vasculature. In addition, analogous control doxorubicin-containing peptides bearing c(RADfK) that does not bind to integrin alpha vbeta3 were synthesized, i.e., c(RADfK)-DOXO-1 and c(RADfK)-DOXO-2. Whereas E-[c(RGDfK) 2]-DOXO-2 was cleaved effectively by MMP-2 and in OVCAR-3 tumor homogenates releasing a doxorubicin-tetrapeptide or doxorubicin as the final cleavage product, no release of doxorubicin was observed for E-[c(RGDfK)2]-DOXO-1. Proliferation of HUVEC in the presence of MMP-2-cleavable doxorubicin-containing peptides exhibited 6- to 10-fold increased inhibition compared to the amide-linked doxorubicin-containing peptides. In addition, inhibition of HUVEC sprouting during a 24 h exposure was approximately 3-fold stronger for E-[c(RGDfK) 2]-DOXO-2 and 20-fold stronger for the reference peptide conjugate c(RADfK)-DOXO-2 than for doxorubicin alone. In vivo studies in an OVCAR-3 xenograft model demonstrated no or only moderate antitumor efficacy for either E-[c(RGDfK)2], E-[c(RGDfK)2]-DOXO-1, E-[c(RGDfK)2]-DOXO-2, or c(RADfK)-DOXO-2, even at doses of 3 x 24 mg/kg doxorubicin equivalents, compared to an improved antitumor effect for doxorubicin at 2 x 8 mg/kg.


A Case of Recurrent Pneumoperitoneum and Pneumatosis Intestinalis After Bilateral Lung Transplant.
We report a case of a 60-year-old male patient with recurrent episodes of free gas in the peritoneal and the retroperitoneal cavities as well as pneumatosis intestinalis 3 months after bilateral lung transplant. Interestingly, despite staged laparotomy within the scope of the first episode, no cause for free gas could be found. In a second episode of symptomatically pneumatosis, a conservative treatment with metro_nidazole was performed successfully. Despite several case reports on patients with pneumatosis intestinalis after lung transplant, an effective treatment strategy has not yet been proposed.


Do MRPS18-2 and RB proteins cooperate to control cell stemness and differentiation, preventing cancer development?
In childhood tumors, including retinoblastoma, osteosarcoma, and neuroblastoma, the RB-E2F1 pathway is inactivated, as a rule. These tumors arise from precursor cells that fail to undergo the terminal differentiation. Noteworthy, the RB1-encoded protein (RB) does not control the cell cycle in embryonic stem cells. It has not been yet well understood how RB controls cell stemness and differentiation. The question arises why "inactive" RB is required for the survival and stemness of cells? Recently, we have found that overexpression of the RB-binding protein MRPS18-2 (S18-2) in primary fibroblasts leads to their immortalization, which is accompanied by the induction of embryonic stem cell markers and, eventually, malignant transformation. We suggest that cell stemness may be associated with high expression levels of both proteins, RB and S18-2. There must be a strict regulation of the expression levels of S18-2 and RB during embryogenesis. Disturbances in the expression of these proteins would lead to the abnormalities in development. We think that the S18-2 protein, together with the RB, plays a crucial role in the control on cell stemness and differentiation. We hope to uncover the new mechanisms of the cell fate determination. The S18-2 may serve as a new target for anticancer medicines, which will help to improve human health.