Disparities in mothers' healthcare seeking behavior for common childhood morbidities in Ethiopia: based on nationally representative data.
Childhood morbidities such as diarrhea and pneumonia are the leading causes of death in Ethiopia. Appropriate healthcare-seeking behavior of mothers for common childhood illnesses could prevent a significant number of these early deaths; however, little nation-wide research has been conducted in Ethiopia to assess mothers' healthcare-seeking behavior for their under five children. The study used the Ethiopian Demographic and Health Surveys (EDHS) data. The EDHS is a cross sectional survey conducted in 2016 on a nationally representative sample of 10,641 respondents. The main determinants of care-seeking during diarrhea and acute respiratory infection (ARI) episodes were assessed using multiple logistic regression analyses while adjusting for complex survey design. Only 43% and 35% of households sought medical attention for their children in episodes of diarrhea and ARI, respectively, during a reference period of 2 weeks before the survey. The odds of seeking care for diarrhea are lower for non-working mothers versus working mothers. The likelihood of seeking care for diarrhea or ARI is higher for literate fathers compared to those with no education. The place of delivery for the child, receiving postnatal checkup and getting at least one immunization in the past determined the likelihood of seeking care for ARI, but not for diarrhea. The odds of seeking care are higher for both diarrhea and ARI among households that are headed by females and where mothers experienced Intimate Partner Violence (IPV) violence. Religion and types of family structure are also significant factors of seeking care for diarrhea episodes, but not for ARI. The findings call for more coordinated efforts to ensure equitable access to health care services focusing on mothers living in deprived household environment. Strengthening partnerships with public facilities, private health care practitioners, and community-based organizations in rural areas would help further improve access to the services.


Metabolic syndrome and endocrine status in HIV-infected transwomen.
HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.


Loss of growth factor dependence and conversion of transforming growth factor-beta 1 inhibition to stimulation in metastatic H-ras-transformed murine fibroblasts.
Cell lines with varying tumorigenic and metastatic potentials have been obtained by transformation of 10T 1/2 fibroblasts using radiation or transfection with T-24 H-ras. We have observed an inverse relationship between metastatic potential and dependence on serum for growth. The effects of basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta 1 (TGF-beta 1) on these lines were then examined to determine if the changes in the serum dependence of metastatic cells may be due to altered responsiveness to specific growth factors (GFs). Cells were grown in monolayer culture and DNA synthesis was measured by [CH3-3H]thymidine incorporation experiments. Both metastatic and nonmetastatic cells were shown to be equivalent in their diminished responsiveness to basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor as compared to their nontransformed, parental 10T 1/2 cells. However, a unique response of metastatic cells to TGF-beta 1 was identified. While TGF-beta 1 inhibited DNA synthesis in 10T 1/2 cells and a nonmetastatic tumor, cells with intermediate to high metastatic ability were stimulated up to 5.8-fold by TGF-beta 1. Interestingly, epidermal growth factor abrogated the TGF-beta 1 inhibition of the parental 10T 1/2 cells, but had no effect on the TGF-beta 1 response of any metastatic line. Therefore, metastatic but not nonmetastatic cells, demonstrated a dramatically altered sensitivity to TGF-beta 1, a response which may be important in determining metastatic potential.


Telomere alterations and genomic instability in long-term cultures of normal human fibroblasts irradiated with X rays and protons.
Telomeres are the end of linear chromosomes, responsible for chromosome stability and cell viability. It is well known that radiations are able to induce chromosome instability but it has not yet been investigated whether telomere structure is affected by the radiation exposure and if radiations with different quality act in a different way on telomeres. The effect of radiations with different quality on telomere structure and chromosome instability was analysed in human primary fibroblasts exposed to X rays or low-energy protons (28.5 keV μm(-1)). Telomere length was evaluated at different harvesting times from 24 h up to 360 h (15 days), whereas chromosome instability was evaluated in terms of sister chromatid exchanges (SCEs) (48 h from irradiation) and chromosome painting (360 h from irradiation). Results indicated a delayed telomere lengthening 360 h after X-ray treatment, whereas protons were able to induce such a lengthening shortly from irradiation as well as at longer harvesting times. Data obtained from chromosome instability analysis indicated an increase of SCE frequency only after proton irradiation, but, on the contrary, at the longer harvesting time chromosome painting analysis displayed a higher frequency of aberrations after X-ray treatment, suggesting a role of selective process against highly damaged cells.


Endothelium-dependent vasodilatory and hypotensive effects of Crotalaria sessiliflora L. in rats.
The aim of the present study was to investigate the vasoactive effect of Crotalaria sessiliflora L. extract (CSE) on rats and its mechanism when combining in vivo and in vitro approaches. CSE (0.5-5 mg/ml) induced concentration-dependent relaxation on endothelium-intact thoracic aortic rings precontracted with phenylephrine (PE, 10(-5) M). This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic strips with either N(G)-nitro-L-arginine (L-NNA, 10(-5) M) or methylene blue (10(-5) M) significantly reduced the relaxation induced by CSE. The endothelium-dependent relaxation caused by CSE was associated with production of cGMP. CSE (5 mg/ml) increased the production of cGMP in endothelium-intact aortic rings and this effect was significantly attenuated by L-NNA (10(-5) M) and methylene blue (10(-5) M). Relaxation in response to CSE in strips precontracted with PGF2alpha (3x10(-5) M) was eliminated by removing extracellular Ca2+ and significantly reduced by pretreatment with ruthenium red (10(-5) M). In in vivo tests, injection of 40 mg/kg of CSE induced an increase in plasma NO production, and this effect was blocked by L-NNA. Furthermore, CSE produced dose-dependent and transient decrease in blood pressure in normotensive rats and this effect was blocked by atropine as well as L-NNA. These findings suggest that CSE induces endothelium-dependent relaxation via NO/cGMP signaling by promoting extracellular Ca2+ influx and the release of Ca2+ from intracellular stores of endothelium, probably due to endothelial muscarinic receptor activation.


Mitral valve prolapse and Marfan syndrome.
Marfan syndrome is a multisystemic genetic condition affecting connective tissue. It carries a reduced life expectancy, largely dependent on cardiovascular complications. More common cardiac manifestations such as aortic dissection and aortic valve incompetence have been widely documented in the literature. Mitral valve prolapse (MVP), however, has remained poorly documented. This article aims at exploring the existing literature on the pathophysiology and diagnosis of MVP in patients with Marfan syndrome, defining its current management and outlining the future developments surrounding it.


Virus-neutralizing monoclonal antibody to a conserved epitope on the duck hepatitis B virus pre-S protein.
In this study we used duck hepatitis B virus (DHBV)-infected Pekin ducks and heron hepatitis B virus (HHBV)-infected heron tissue to search for epitopes responsible for virus neutralization on pre-S proteins. Monoclonal antibodies were produced by immunizing mice with purified DHBV particles. Of 10 anti-DHBV specific hybridomas obtained, 1 was selected for this study. This monoclonal antibody recognized in both DHBV-infected livers and viremic sera a major (36-kilodalton) protein and several minor pre-S proteins in all seven virus strains used. In contrast, pre-S proteins of HHBV-infected tissue or viremic sera did not react. Thus, the monoclonal antibody recognizes a highly conserved DHBV pre-S epitope. For mapping of the epitope, polypeptides from different regions of the DHBV pre-S/S gene were expressed in Escherichia coli and used as the substrate for immunoblotting. The epitope was delimited to a sequence of approximately 23 amino acids within the pre-S region, which is highly conserved in four cloned DHBV isolates and coincides with the main antigenic domain as predicted by computer algorithms. In in vitro neutralization assays performed with primary duck hepatocyte cultures, the antibody reduced DHBV infectivity by approximately 75%. These data demonstrate a conserved epitope of the DHBV pre-S protein which is located on the surface of the viral envelope and is recognized by virus-neutralizing antibodies.


Polymer extension under flow: A path integral evaluation of the free energy change using the Jarzynski relation.
The Jarzynski relation (and its variants) has provided a route to the experimental evaluation of equilibrium free energy changes based on measurements conducted under arbitrary non-equilibrium conditions. Schroeder and co-workers [Soft Matter 10, 2178 (2014) and J. Chem. Phys. 141, 174903 (2014)] have recently exploited this fact to determine the elastic properties of model DNA from simulations and experiments of chain extension under elongational flow, bypassing the need to make these measurements mechanically using sophisticated optical trapping techniques. In this paper, motivated by these observations, we investigate chain elasticity analytically, using the Jarzynski relation and a finitely extensible nonlinear elastic-type Rouse model within a path integral formalism to calculate (essentially exactly) both the flow-induced free energy change between chain conformations of definite average end-to-end distance, as well as the force-extension curve that follows from it. This curve, based on a new analytic expression, matches the trends in the corresponding curve obtained from a model of chain stretching developed by Marko and Siggia [Macromolecules 28, 8759 (1995)], which itself is in very satisfactory agreement with the numerical and experimental data from the work of Schroeder et al.


Evaluation of math anxiety and its remediation through a digital training program in mathematics for first and second graders.
Math anxiety severely impacts individuals' learning and future success. However, limited is understood about the profile in East Asian cultures where students genuinely show high-level math anxiety, despite that they outperform their Western counterparts. Here, we investigate the relation between math anxiety and math achievement in children as young as first and second graders in Taiwan. Further, we evaluate whether intensive exposure to digital game-based learning in mathematics could ameliorate math anxiety. The study first evaluated a group of 159 first and second graders' math anxiety and its correlation with math performance. Subsequently, a quasi-experimental design was adopted: 77 of the children continued and participated in multi-component digital game training targeting enumeration, speeded calculation, and working memory. Post-assessment was administered afterward for further evaluation of training-associated effects. Results confirmed that math anxiety was negatively associated with school math achievement, which assessed numerical knowledge and arithmetic calculation. Furthermore, children's math anxiety was remarkably reduced via digital training in mathematics after 6-week intensive remediation. Crucially, this math anxiety relief was more prominent in those with high-level math anxiety. Although the children who underwent the training showed training-induced math achievement and working memory enhancement, this cognitive improvement appeared to be independent of the math anxiety relief. Our findings demonstrate that students can show highly negative emotions and perceptions toward learning even in high-achieving countries. Auspiciously, the feeling of distress toward learning has the feasibility to be relieved from short-term intensive training. Our study suggests a new approach of early treatments to emotional disturbance that can lead to permanent consequences in individuals.


The disparity of the size of the liver as determined by physical examination and by hepatic gammascanning in 504 patients.
The liver extended a minimum of 5 cm inferior to the right costal margin in 51% of the 504 patients studied. In 53% of these patients, experienced, mature physicians declared that the liver was not palpable on physical examination. In 3% of the cases, a mass was palpated which was believed to be liver by the examining physician but was found to be extrahepatic upon scanning and laparotomy. The unreliability of physical examination in determining whether or not the liver extends inferior to the costal margin in many instances is demonstrated.


Number of cells from Plasmodium falciparum-immune donors that produce gamma interferon in vitro in response to Pf155/RESA, a malaria vaccine candidate antigen.
Secretion of gamma interferon (IFN-gamma) in response to stimulation of Plasmodium falciparum-primed T cells by specific antigens may be a useful indicator of cellular immunity to malaria. An enzyme-linked immunospot (ELISPOT) assay designed to detect IFN-gamma at the single-cell level was used to study IFN-gamma-producing cells from P. falciparum-primed donors from The Gambia after in vitro stimulation with various malarial antigens. IFN-gamma secreted into the culture supernatant was measured by conventional enzyme-linked immunosorbent assay (ELISA). There was a good correlation in individual donors between the level of IFN-gamma secreted into the culture supernatant and the number of IFN-gamma-secreting cells. However, the ELISPOT assay was apparently more sensitive in demonstrating low levels of IFN-gamma production than the ELISA was. Thus after stimulation with crude P. falciparum antigen from infected erythrocytes, 72% of the primed donors responded positively in the ELISPOT assay but only 55% responded positively in the ELISA. When stimulated with synthetic peptides representing immunodominant epitopes of the malarial antigen Pf155/RESA, a vaccine candidate, 31 to 55% responded in the ELISPOT assay and 21 to 36% responded in the ELISA. Unprimed Europeans did not respond positively to these antigens in either of the assays, and background in antigen-free controls was generally low. These results indicate that measurement of IFN-gamma by the ELISPOT assay or ELISA should have wide applications in large-scale epidemiological studies of malaria immunity. In addition, the ELISPOT assay makes it possible to analyze the T cells responding to malarial antigens in terms of both numbers and functional heterogeneity.


Injuries associated with electronic nicotine delivery systems: A systematic review.
Since its introduction on the market in 2007, the number of reports on injuries caused by the overheating, ignition, or explosion of electronic nicotine delivery systems (ENDSs) has increased significantly. These injuries appear to have different causes, the most important one being lithium-ion battery overheating to the point of ignition or explosion. A literature search for all relevant studies concerning ENDS-related traumatic injuries of all kinds was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol. The search started with the first introduction of ENDSs in 2007 and ended February 2020. Articles included were reports on patients who sustained flame, chemical, or traumatic injuries of the skin, soft tissue, and/or bone, related to the use of ENDSs. This systematic review includes 180 patients from 41 case series and reports, published between 2016 and 2020. The mean age was 30.8 years (range, 17-59 years) with an overall male predominance (168 of 180 patients, 93%). In most injuries, multiple anatomical sites were affected, with the thigh/lower limb being the most commonly injured area (77%) followed by the upper limb/hand (43%). Eighty-two patients (51%) required a surgical treatment, 70 patients (43%) were managed conservatively with dressings or ointments, and 9 patients (6%) underwent enzymatic debridement. Thirty-five percent of all patients underwent skin grafting. Injuries from overheating, ignition, or explosion of ENDSs are an emerging, underreported, and underresearched issue. There is a need for increased regulation of ENDSs and improved surveillance of related injuries. Both health care providers and consumers should be made aware of the risks and be advised about how to safely handle these devices. In contrast to other articles, this systematic review includes all types of injuries related to ENDS overheating, ignition, and explosion. To our knowledge, this is the most extensive systematic review performed to date. Review article, level III.


Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More.
Butyrophilins (BTN) are relatives of the B7 family (e.g., CD80, PD-L1). They fulfill a wide range of functions including immunomodulation and bind to various receptors such as the γδ T cell receptor (γδTCR) and small molecules. One intensively studied molecule is BTN3A1, which binds via its cytoplasmic B30.2 domain, metabolites of isoprenoid synthesis, designated as phosphoantigen (PAg), The enrichment of PAgs in tumors or infected cells is sensed by Vγ9Vδ2 T cells, leading to the proliferation and execution of effector functions to remove these cells. This article discusses the contribution of BTNs, the related BTNL molecules and SKINT1 to the development, activation, and homeostasis of γδ T cells and their immunomodulatory potential, which makes them interesting targets for therapeutic intervention.


Low-voltage, high-speed and compact electro-absorption modulator laterally integrated with 980-nm VCSEL.
We present a compact electro-absorption slow-light modulator laterally-integrated with a 980-nm VCSEL. We figured out the small signal modulation response for different modulator lengths. While the 3-dB small-signal modulation bandwidth of conventional directly modulated VCSELs on the same epi-wafer structure was limited below 10 GHz, we obtained a modulation bandwidth over 21 GHz for a 30 µm long modulator. We also demonstrated large signal modulation up to 25 Gbps with a low driving voltage below 600 mV(pp) and an extinction ratio of 4 dB for the modulator length of 50 µm. Prospects of much higher speed (> 40 Gbps) were examined with reducing the size of the modulator. Also, the tapered waveguide coupling structure enables "quasi-unidirectional coupling", which reduces the optical feedback in a VCSEL from the integrated modulator.


Local to global: Working together to meet the needs of vulnerable communities.
Since 2012, the University of Wisconsin-Milwaukee (UWM) faculty from nursing and physical therapy (PT) have been working together towards a common goal: to meet the healthcare needs of vulnerable populations in Malawi and Milwaukee. Sharing valuable knowledge and understanding one another's professions have allowed us to develop interprofessional education (IPE) learning experiences for students to help identify how quality of life could be improved or enhanced for children and their families across two different geographic spaces, one in rural Malawi and the other in urban Milwaukee. IPE learning modules were implemented in UWM's community health-focused short-term study abroad programmes to Malawi. IPE learning modules were also piloted at one of UWM's nurse-managed community health centres, located in a low-income, African American community in the inner city of Milwaukee, Wisconsin. Based on survey data collected from 10 participating IPE students in Milwaukee, from nursing, occupational therapy, PT, and speech and language pathology, a pilot study yielded a statistically significant change in a positive direction for increased understanding of three interprofessional collaborative practice core competencies: values and ethics, roles and responsibilities, and teams and teamwork. In this article, we discuss the processes used to develop, implement, and evaluate IPE experiences for UWM students, which may enable other professionals to envision the various projects they can embark upon from an interprofessional perspective.


Analyzing the pathways enriched in genes associated with nicotine dependence in the context of human protein-protein interaction network.
Nicotine dependence is the primary addictive stage of cigarette smoking. Although a lot of studies have been performed to explore the molecular mechanism underlying nicotine dependence, our understanding on this disorder is still far from complete. Over the past decades, an increasing number of candidate genes involved in nicotine dependence have been identified by different technical approaches, including the genetic association analysis. In this study, we performed a comprehensive collection of candidate genes reported to be genetically associated with nicotine dependence. Then, the biochemical pathways enriched in these genes were identified by considering the gene's propensity to be related to nicotine dependence. One of the most widely used pathway enrichment analysis approach, over-representation analysis, ignores the function non-equivalence of genes in candidate gene set and may have low discriminative power in identifying some dysfunctional pathways. To overcome such drawbacks, we constructed a comprehensive human protein-protein interaction network, and then assigned a function weighting score to each candidate gene based on their network topological features. Evaluation indicated the function weighting score scheme was consistent with available evidence. Finally, the function weighting scores of the candidate genes were incorporated into pathway analysis to identify the dysfunctional pathways involved in nicotine dependence, and the interactions between pathways was detected by pathway crosstalk analysis. Compared to conventional over-representation-based pathway analysis tool, the modified method exhibited improved discriminative power and detected some novel pathways potentially underlying nicotine dependence. In summary, we conducted a comprehensive collection of genes associated with nicotine dependence and then detected the biochemical pathways enriched in these genes using a modified pathway enrichment analysis approach with function weighting score of candidate genes integrated. Our results may provide insight into the molecular mechanism underlying nicotine dependence.


Fatty Acid Percentage Distribution in Complex Lipids of Breast Milk From Mothers on a Low Docosahexaenoic Acid Diet.
The aim of this study was to assess the fatty acid (FA) percentage distribution in complex lipids of breast milk from mothers on a low docosahexaenoic acid (DHA) diet. We performed a descriptive, cross-sectional study of milk samples (n = 14) collected 90 days after delivery and analyzed them using gas chromatography, thin-layer chromatography, and the Fiske-Subbarow method. Complex lipid distribution was 40.70 ± 5.11% sphingomyelin (SM), 26.03 ± 5.98% phosphatidylethanolamine (PE), 21.12 ± 2.32% phosphatidylcholine, 7.94 ± 1.96% phosphatidylserine, and 4.22 ± 1.25% phosphatidylinositol. Median DHA and arachidonic acid values were 0.13% (0.12; 0.18) and 0.42% (0.33; 0.53), respectively. Mean FA percentage in SM and PE was as follows: palmitic acid, 34.45 ± 1.94% and 5.38 ± 0.94%; oleic acid, 16.50 ± 4.07% and 9.43 ± 4.05%; linoleic acid, 5.91 ± 4.69% and 9.05 ± 4.5%. DHA was not detectable in SM, but it was found in PE (55.33 ± 14.46). In conclusion, breast milk of mothers on a low DHA diet contained 55% DHA in PE, but no DHA in SM.


[Biochemical study of testicular biopsy in infertility].
Basic semen tests nowadays contain no variables that may allow to certify that a man is fertile. Starting from this premise it could be clinically very useful, for the diagnosis of male infertility, to evaluate a parameter that may be related to sexual maturity and be specific of the germinal tissue, such as the C4-lactate dehydrogenase isoenzyme (C4-LDH), which could indicate the activity of the germinal epithelium and the quality of the spermatozoa. In our experience, C4-LDH activity in seminal plasma discriminates between fertile and non-fertile males; also, their testicular study has a good correlation both with histologically diagnosed disease and the seminal plasma levels. All of which suggest the diagnostic validity of plasma C4-LDH in male infertility, as a routine test which thus precludes the use of invasive techniques in the patient.


A survey of pregnant women using isotretinoin.
Isotretinoin is a known human teratogen, causing birth defects and/or subnormal cognitive performance in prenatally-exposed children. A survey was conducted among women who called teratology information services throughout North America. Using a structured questionnaire, women with an isotretinoin-exposed pregnancy were prospectively interviewed before the outcome of the pregnancy was known. Almost 1/4 of the women surveyed (24%; 8/34) did not recall having contraception counseling before starting their medications. Once therapy was initiated, 62% (21/34) recalled using a birth control method, but only 29% (6/21) recalled using 2 forms of birth control, as specified by the voluntary pregnancy prevention programs. Monthly pregnancy tests were not always conducted during treatment, as recalled by the surveyed women (56%; 19/34). As many as 24% (8/34) of the women surveyed recalled that they were not screened using 2 pregnancy tests before receiving a prescription, another recommendation of the programs. Only a small number of the women (30%; 6/20) in the United States recalled being enrolled in any manufacturers' voluntary pregnancy prevention survey. Results demonstrate that essential components of voluntary pregnancy prevention programs were not consistently followed, which resulted in fetal exposures.


A SEX DIFFERENCE IN THE PROPENSITY TO ENTER DIRECT/DIAPAUSE DEVELOPMENT: A RESULT OF SELECTION FOR PROTANDRY.
In monandrous mating systems with discrete nonoverlapping generations males should maximize the expected number of matings by starting to emerge before females. This is known as protandry. Moreover, Evolutionarily Stable Strategies (ESS) models show that the male emergence curve should be abruptly truncated before female emergence has ceased. In temperate areas where many insects have partial second generations, we accordingly predict that males should enter diapause development at an earlier date than should females, as a result of late-emerging males being penalized in terms of fewer mating opportunities. The decision to diapause or to develop directly is usually mediated by response to environmental stimuli of which day length is the most important. Hence we predict that the mechanism by which males enter diapause at an earlier date than females will be that of the male reaction norm for diapause development being shifted towards longer day lengths when compared to that of females. As a result of the greater tendency of males to enter diapause development, partial second generations that develop directly should be female biased. As a corollary, first generations should be male biased because some males of the first generation are from the previous year. The prediction that males should enter diapause development earlier in the season, i.e., at longer day lengths, as compared to females was corroborated by rearing Pieris napi under a variety of critical day length regimes producing mixed broods of directly developing and diapausing individuals, and by outdoor rearings of cohorts of larvae of P. napi and P. rapae initiated throughout the season. The prediction that partial second generations should be female biased was corroborated by laboratory rearings at constant temperature of P. napi (Pieridae), Polygonia c-album (Nymphalidae), and Pararge aegeria (Satyridae) under critical day length conditions, producing female-biased sex ratio under direct, and male-biased sex ratio under diapause development.


Detection of New Delhi metallo-beta-lactamase and extended-spectrum beta-lactamase genes in Escherichia coli isolated from mastitic milk samples.
In this study, eight Escherichia coli isolates were obtained from milk samples of dairy cattle suffering from clinical/subclinical mastitis. Isolates were characterized for antimicrobial resistance traits and virulence genes. Results revealed that one isolate was harbouring New Delhi metallo-beta-lactamase gene (blaNDM ). Cloning and sequencing of the PCR amplicon confirmed the identity of the gene (GenBank accession no. KC769583) having 100% homology with blaNDM-5 (GenBank accession no. JN104597.1), and this isolate was susceptible to colistin, chloramphenicol and tetracycline only. Moreover, another isolate carried extended-spectrum beta-lactamase (ESBL) gene - blaCTX-M , and all isolates possessed blaTEM gene. Of the eight isolates, only one isolate was positive for shiga toxin gene (stx2), and none were harbouring stx1 gene. Occurrence of New Delhi metallo-beta-lactamase (blaNDM ) in one E. coli isolate and ESBL genes in other isolates poses a potential threat to human health following possible entry and spread through food chain.


Child Holocaust survivors as parents: a transgenerational perspective.
Children of Holocaust survivors frequently point out problems associated with having been raised by survivor parents. However, large-scale studies demonstrate that both Holocaust survivors and their children function within the normal range. This study addresses relationship issues between the younger survivors and their children. It does not compare them with nonsurvivor families, who may exhibit similar patterns. We found wide gaps between how child survivor parents and their children viewed parental expectations and behaviors. These discrepancies are described as 4 paradoxes.


Single-dose mRNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Including Alpha and Gamma Variants: A Test-negative Design in Adults 70 Years and Older in British Columbia, Canada.
Randomized-controlled trials of messenger RNA (mRNA) vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included relatively few elderly participants. We assess single-dose mRNA vaccine effectiveness (VE) in adults ≥ 70 years old in British Columbia, Canada, where second doses were deferred by up to 16 weeks and where a spring 2021 wave uniquely included codominant circulation of Alpha (B.1.1.7) and Gamma (P.1) variants of concern (VOC). Analyses included community-dwelling adults ≥ 70 years old with specimen collection between 4 April (epidemiological week 14) and 1 May (week 17) 2021. Adjusted VE was estimated by test-negative design. Cases were reverse-transcription polymerase chain reaction (RT-PCR) test-positive for SARS-CoV-2, and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥ 21 days before specimen collection, but a range of intervals was assessed. Variant-specific VE was estimated against viruses genetically characterized as Alpha, Gamma or non-VOC lineages. VE analyses included 16 993 specimens: 1226 (7%) test-positive cases and 15 767 test-negative controls. Of 1131 (92%) genetically characterized viruses, 509 (45%), 314 (28%), and 276 (24%) were Alpha, Gamma, and non-VOC lineages, respectively. At 0-13 days postvaccination, VE was negligible at 14% (95% confidence interval [CI], 0-26) but increased from 43% (95% CI, 30-53) at 14-20 days to 75% (95% CI, 63-83) at 35-41 days postvaccination. VE at ≥ 21 days postvaccination was 65% (95% CI, 58-71) overall: 72% (95% CI, 58-81), 67% (95% CI, 57-75), and 61% (95% CI, 45-72) for non-VOC, Alpha, and Gamma variants, respectively. A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 by about two-thirds in adults ≥ 70 years old, with protection only minimally reduced against Alpha and Gamma variants.


Childhood liposarcoma. Report of a case and review of the literature.
A case of liposarcoma presenting in an adolescent black male is described. Features unique to this case include a mediastinal primary site (the fourth to be documented in a pediatric patient), a demonstrable response to radiotherapy and chemotherapy allowing complete surgical excision of an initially inoperable tumor, and the apparent histologic maturation of the tumor following multimodal therapy. A review of previously published accounts of pediatric liposarcoma revealed the following: (1) peak incidences during infancy and in early adolescence; (2) the extremities to be the most common site of origin (51%); (3) a predominance of myxoid histology (76%); and (4) a lower overall recurrence rate when compared with adult cases (37% versus 72%, respectively). The influence of histology, location of the tumor, and completeness of surgical excision on the prognosis of adult liposarcoma was confirmed in this limited pediatric experience. While the use of radiotherapy and chemotherapy cannot be advocated in all instances of liposarcoma, our experience and that from other reports would support the incorporation of these modalities of treatment in selected patients where the tumor is surgically inaccessible due to size.


Comparison of the Quality of Life and Depression in the Elderly with and without a History of COVID-19 Infection in Shiraz, Iran.
COVID-19 causes many physical and mental complications. The elderly, as one of the vulnerable groups, were more exposed to the problems caused by this pandemic. The aim of this study was to compare the quality of life and depression in the elderly with and without a history of COVID-19 infection. This is a cross-sectional descriptive study conducted on 404 elderly people (202 from the affected group and 202 from the nonaffected group) aged over 60 years old in Shiraz city. The elderly participants were selected based on simple random sampling from the elderly list. In order to collect information, the quality of life questionnaire of the World Health Organization and Beck's depression questionnaire were used. Data analysis was done through SPSS software version 22 using statistical tests of chi-square, t-test, analysis of variance, and Pearson's correlation coefficient. An alpha level under 0.05 was considered the significant level. The average score of depression in the elderly with a history of COVID-19 (14.66 ± 13.17) was significantly higher than that of the elderly without a history of COVID-19 (9.71 ± 10.12) (p < 0.001). The average score of the quality of life in the elderly with a history of COVID-19 (80.15 ± 14.85) was significantly lower than that of the elderly without a history of COVID-19 (85.25 ± 14.09) (p < 0.001). Elderly people with a history of COVID-19 had more depression and lower quality of life compared to people without a history of COVID-19. It is suggested that planners and health policymakers should pay special attention to the use of effective psychological interventions in order to reduce the problems of the elderly.


Anaerobic biodegradation of BTEX by original bacterial communities from an underground gas storage aquifer.
BTEX biodegradation by an indigenous deep subsurface microbial community was evaluated in a water sample collected in the area of an underground gas storage. Five different sulfate-reducing microbial communities able to use at least either benzene, toluene, ethylbenzene, or xylene (BTEX) compounds were studied. A total of 21 different bacterial phylotypes were identified, each community containing three to nine bacterial phylotypes. Archaeal phylotypes were retrieved from only three communities. The analysis of 16S rRNA gene sequences showed that i) these consortia were mainly composed of novel species, some of which belonging to bacterial groups not previously suspected to be involved in BTEX anaerobic degradation, ii) three consortia were dominated by an uncultured Pelobacter sp. previously detected in biodegraded oil reservoirs, iii) a deeply branching species distantly affiliated to Thermotogales was abundant in two consortia, and that iv) Firmicutes related to the Desulfotomaculum and Carboxydocella genera represented the only three detectable phylotypes in a toluene-degrading consortium. This work shows that subdominant microbial populations present in a deep subsurface aquifer used for seasonal underground gas storage could be involved in the natural attenuation of the traces of BTEX coinjected with methane in the deep subsurface.


Assessment of vitamin A deficiency indicators in urban slum communities of National Capital Territory of Delhi.
A study was conducted to assess the magnitude of Vitamin A deficiency in two urban slum communities of Delhi. Biological and ecological indicators suggested by WHO/UNICEF 1992, were used. Five hundred and fifty two children in the age group of 0-5 years were studied. Data was collected on socio- economic status, breastfeeding pattern, immunisation, morbidity profile and presence of vitamin A deficiency. Height and weight were recorded using standard techniques. Vitamin A intake of subjects was assessed using food frequency and 24 hr recall methods. It was found that 63.9% children >1 year of age were fully immunised. Colostrum was received by only 28.1% of children. Only 32% infants <4 months of age were exclusively breastfed. Breast milk was being received by 93.5% children <6 months old. 18.1% children had diarrhoea within last 15 days of survey. 7.1% children gave history of helminthic infestations. 47.8% children <3 yrs were stunted while 26.9% were wasted. None of the children had Bitot's spots but nightblindness was observed in 1.2% children. 35.7% children (12-24 months) consumed vitamin A rich foods less than once A week. The frequency of consumption of vitamin A rich foods was significantly higher in winter as compared to summer and rainy seasons (p<0.05). The mean daily vitamin A intake for 6-11 months and 12-71 months old children was 1187±755 m g and 847±111m g respectively. It was concluded that moderate vitamin A deficiency was present in the study area.


Clinical manifestations of acute rejection in renal allograft recipients receiving cyclosporin-A therapy.
Cyclosporin-A-treated renal allograft recipients have demonstrated an improved graft survival rate, when compared to that of patients treated with conventional azathioprine and steroid therapy. Cyclosporin-A has been used for immunosuppressive therapy after renal transplantation at the National Taiwan University Hospital since November 1985. Since then, the one-year graft survival rate has been 78%, and the patient survival rate is 91%. At our service, acute rejection is confirmed mainly by an increase in the serum creatinine level of 0.5 mg% per day and a subsequent return of kidney function to normal after pulse steroid therapy. Twenty patients receiving cyclosporin-A and suffering from acute rejection episodes were chosen for comparison with 18 patients receiving conventional azathioprine and steroid therapy. Compared to conventional therapy, the classical systemic manifestations of rejection, such as malaise, lethargy, apathy, general weakness, vague discomfort, increase in body weight, swelling of graft with tenderness, were all more mild and less frequent in the cyclosporin-A-treated group. Episodes of rejection appeared earlier and the duration of rejection was shorter than in those of the conventional group. The urinary sodium concentration and the ratio of urine urea nitrogen to blood urea nitrogen were reliable references during the acute rejection episode in the conventional group, but it cannot be used as indices in the cyclosporine group. These findings can help us understand the changes which occurred in acute rejection in patients who receive renal transplantation during the cyclosporine era.


Electrospinning Directly Synthesized Porous TiO2 Nanofibers Modified by Graphitic Carbon Nitride Sheets for Enhanced Photocatalytic Degradation Activity under Solar Light Irradiation.
We report a direct approach to the fabrication of a composite made of porous TiO2 nanofibers (NFs) and graphitic carbon nitride (g-C3N4) sheets, by means of an angled two-nozzle electrospinning combined with calcination process. Different wt % amounts of g-C3N4 particles in a polymer solution from one nozzle and TiO2 precursors containing the same polymer solution from another nozzle were electrospun and deposited on the collector. Structural characterizations confirm a well-defined morphology of the TiO2/g-C3N4 composite in which the TiO2 NFs are uniformly attached on the g-C3N4 sheet. This proper attachment of TiO2 NFs on the g-C3N4 sheets occurred during calcination. The prepared composites showed the enhanced photocatalytic activity over the photodegradation of rhodamine B and reactive black 5 under natural sunlight. Here, the synergistic effect between the g-C3N4 sheets and the TiO2 NFs having anisotropic properties enhanced the photogenerated electron-hole pair separation and migration, which was confirmed by the measurement of photoluminescence spectra, cyclic voltammograms, and electrochemical impedance spectra. The direct synthesis approach that is established here for such kinds of sheetlike structure and porous NFs composites could provide new insights for the design of high-performance energy conversion catalysts.


Expression and regulation of drug transporters in vertebrate neutrophils.
There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans. We anticipate that this will be a valuable resource to the field of inflammation biology and will be an important asset in future anti-inflammatory drug design.


[Cytoprotective action of guanylate cyclase stimulators on human leukocytes].
An original experimental model has been presented for studying of cytoprotection of non-stimulated leukocytes. The model consists in determining of a degree of inhibition of the release of lactic acid dehydrogenase (LDH) by isolated human neutrophils (PMNs) in the course of their "ageing" at the room temperature (22 degrees C). Using this model for the first time, cytoprotective action was pointed-out of following compounds: NO (EDRF) in aqueous solution; natrium nitroprusside; active metabolite of molsidomine--SIN-1; N-acetyl-S-nitroso-penicillamine (SNAP) which are believed to owe their anti-platelet and vasodilatory activity to stimulation of cyclic-GMP--and iloprost (a stable prostacyclin analogue) and prostaglandin E2 (PGE2) which activate cyclic AMP. Effectiveness of cytoprotective action of these compounds increased as follows: NO (IC50 = 58.4) less than PGE2 (IC50 = 38) less than SIN-1 (IC50 = 9.2) less than SNAP (IC50 = 3.2) less than natrium nitroprusside (IC50 = 1.2) less than iloprost (IC50 = 0.2)(nmoles/5 x 10(6) PMNs; moreover, iloprost and SIN-1 showed a synergic action. Among ++nitroso-vasodilators, nitroglycerin had no cytoprotective action; it may indicate that to achieve cytoprotection in leukocytes a nitro- vasodilator should contain in its chemical structure -NO group and not -NO3 group, as it is in nitroglycerin. In neutrophils stimulated with calcium ionophore, arachidonic acid or FMLP, nitro-vasodilators are of no influence on production of superoxide anions O2-, hydroxyeicosatetraenoic acids (5-HETE and 12-HETE) and leukotriene B4. A hypothesis has been put forward on the relationship of function of c-GMP and c-AMP in the mechanism of cytoprotection of human leukocytes.


Glasses-free 3-D visualization with multi-layered transparent cholesteric films.
Fabrication of a three-dimensional (3D) device with volume-filling autostereoscopic imagery provides a unique solution to the accommodation-convergence mismatch problem in a conventional stereoscopic 3D display. We demonstrate a volumetric 3D display consisting of a stack of sequentially-driven transparent cholesteric films that illuminate every point in the display volume to generate a synthetic 3D image. Transparent cholesteric films comprise of the reverse-mode polymer-stabilized cholesteric texture (R-PSCT) that exhibits > 85% transmittance in its off-state (Grandjean texture) and <15% transmittance in its on-state (focal-conic texture). The polymer network in the R-PSCT is formed with the mixture of reactive monomers: RM6 and RM257. The electro-optical measurements show a strongly influence of concentration of each reactive monomer in the total mixture on the optical contrast and driving voltage of R-PSCT films. Hence, we optimize the composition of reactive monomers in R-PSCT to achieve a low driving voltage, high optical contrast and high electro-mechanical stability. Furthermore, we fabricate a multi-surface and a see-through volumetric 3D display prototype that consists an optical element with 15 R-PSCT films that are sequentially-switched with a microcontroller and operated at 250 Hz. A high-speed DLP projector is used to project a time-multiplexed series of two-dimensional images that are used to build the multi-planar volumetric images.


Ultrastructure of a cardiac rhabdomyoma.
Electron microscopic study of a cardiac rhabdomyoma removed at open heart operation revealed large rounded or polygonal cells that contained large amounts of monoparticulate glycogen. Myofibrils in these cells were few and located either subjacent to the plasma membranes or radiating from central areas. Leptofibrils and masses of anomalous Z band material were abundant. Shallow tubular sarcolemmal invaginations and elements of free and junctional sarcoplasmic reticulum were associated with the myofibrils. Desmosomes and nexuses were evident in intercellular junctions, which were extensive and randomly distributed throughout the cell surfaces. It is concluded that cardiac rhabdomyomas probably are hamartomas.


Validity and psychometric properties of the Self-Identification as Having a Mental Illness Scale (SELF-I) among currently untreated persons with mental health problems.
Conceptualizing own symptoms as potential signs of a mental illness is an important, yet under-researched step towards appropriate help. Few validated measures address recognition and identification of own mental illness. Aim of this study is to investigate performance and correlates of the 'Self-Identification as Having a Mental Illness' scale (SELF-I) in a group of 229 currently untreated individuals with mental health problems, predominantly depression. Measures included: self-identification with having a mental illness (SELF-I), depressive and somatic symptom severity (PHQ-9 and PHQ-15), illness perceptions (B-IPQ-R-C), and sociodemographic variables. Principal-component analysis revealed in a unidimensional factor structure. The SELF-I showed good reliability in terms of internal consistency (Cronbach's alpha, 0.85-0.87) and re-test reliability over three months (Intraclass correlation coefficient, 0.74). Associations with depressive symptoms, previous treatment experiences and self-labelling demonstrated construct and criterion validity. Low associations with somatic symptoms and with illness-perceptions as measured by the B-IPQ-R-C indicated discriminant validity. We did not observe any floor or ceiling effects. The SELF-I scale is a brief, unidimensional and reliable measure of self-identification as having a mental illness that offers useful research perspectives.


HOCl-Activated Aggregation of Gold Nanoparticles for Multimodality Therapy of Tumors.
Tumor microenvironment-responsive nanodrugs offer promising opportunities for imaging-guided precision therapy with reduced side effects. Considering that the antitumor effect is closely related to the size of the nanodrugs, it is particularly important to develop a therapeutic system with size adjustability in the tumor microenvironment, which is still a great challenge in the field of nanotheranostics. Herein, a reactive oxygen species (ROS)-activated aggregation strategy is reported for imaging-guided precision therapy of tumors. The ROS-activated nanoplatform is constructed based on gold nanoparticles (AuNPs) coated with an HOCl probe on its surface (namely, Au-MB-PEG NPs). The Au-MB-PEG NPs show high sensitivity toward HOCl, resulting in the modulation of surface charge and rapid aggregation of AuNPs, and simultaneous release of methylene blue as a photosensitizer for photodynamic therapy (PDT). In the tumor environment, the aggregated AuNPs ensure higher tumor accumulation and retention. Furthermore, the redshift of the absorption of aggregated AuNPs leads to activated photoacoustic imaging signals and photothermal therapy (PTT) under near-infrared irradiation. Au-MB-PEG NPs thus efficiently inhibit the tumor growth through combined PTT-PDT therapy. This work contributes to the design of stimuli-induced size-aggregation nanodrugs, thereby attaining advanced performance in cancer diagnosis and treatment.


Early versus delayed single-stage laparoscopic eradication for both gallstones and common bile duct stones in mild acute biliary pancreatitis.
Several studies addressed that preoperative endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct (CBD) clearance, followed by interval laparoscopic cholecystectomy (two-stage approach), constitutes the most common practice in cases of uncomplicated mild acute biliary pancreatitis. Between June 1998 and December 2002, 44 patients (35 females and 9 males with a median age of 62 years) suffering from uncomplicated mild acute biliary pancreatitis were treated in our unit. All patients were electively submitted to surgery after subsidence of the acute symptoms, and for definitive treatment we favored the single-stage laparoscopic management, avoiding preoperative ERCP. All patients underwent laparoscopic cholecystectomy plus fluoroscopic intraoperative cholangiogram (IOC). If filling defect(s) were detected in the IOC, a finding suggestive of concomitant choledocholithiasis, laparoscopic common bile duct exploration (LCBDE) was added in the same sitting. Twenty patients were operated upon within 2 weeks since the attack of the acute symptoms and constitute the early group (n=20), whereas 24 patients underwent an operation later on and constitute the delay group (n=24). We retrospectively compare the safety, effectiveness, and outcome after the single-stage laparoscopic management between the two groups of patients. Laparoscopic cholecystectomy alone constituted the definitive treatment in 38 patients, while an additional LCBDE was performed in the remaining 6 patients (14%), and all operations were achieved laparoscopically. There was no statistically significant difference between the groups in terms of operative time, incidence of concomitant choledocholithiasis, morbidity rate, and postoperative hospital stay. During the follow-up, none of the patients experienced recurrent pancreatitis. In uncomplicated mild acute biliary pancreatitis cases, a single-stage definitive laparoscopic management, avoiding preoperative ERCP, can be safely performed during the same admission, after the improvement of symptoms and local inflammation. Postoperative ERCP should be selectively used in patients in whom the single-stage method failed to resolve the problem.


Highly Selective Synthesis of cis-Enediynes on a Ag(111) Surface.
Cis-enediyne-type compounds have received much attention as potent antitumor antibiotics. The conventional synthesis of cis-enediynes in solution typically involves multiple steps and various side reactions. For the first time, selective one-step synthesis of cis-enediyne from a single reactant is reported on a Ag(111) surface with a yield up to 90 %. High selectivity for the formation of cis-enediyne originates from the steric effect posed by weak intermolecular interactions, which protect the cis-enediyne from further reaction. A series of comparative experiments and DFT-based transition-state calculations support the findings. The described synthetic approach for directing reaction pathways on-surface may illuminate potential syntheses of other unstable organic compounds.


Molecular Characteristics of the Equine Periodontal Ligament.
The equine periodontal ligament (PDL) is a fibrous connective tissue that covers the intra-alveolar parts of the tooth and anchors it to the alveolar bone-it, therefore, provides a similar function to a tendinous structure. While several studies have considered the formation and structure of tendons, there is insufficient information particularly on the molecular composition of the PDL. Especially for the equine PDL, there is limited knowledge concerning the expression of genes commonly regarded as typical for tendon tissue. In this study, the gene expression of, e.g., collagen type 1 alpha 1 (COL1), collagen type 3 alpha 1 (COL3), scleraxis (SCX), and fibrocartilage markers was examined in the functional mature equine PDL compared with immature and mature equine tendon tissue. PDL samples were obtained from incisor, premolar, and molar teeth from seven adult horses. Additionally, tendon samples were collected from four adult horses and five foals at different sampling locations. Analyses of gene expression were performed using real-time quantitative polymerase chain reaction (qRT-PCR). Significantly higher expression levels of COL1 and 3 were found in the mature equine PDL in comparison with mature tendon, indicating higher rates of collagen production and turnover in the mature equine PDL. The expression levels of SCX, a specific marker for tenogenic-differentiated cells, were on a similar level in functional mature PDL and in mature tendon tissue. Evidence of chondrogenic metaplasia, often found in tendon entheses or in pressurized regions of tendons, was not found in the mature equine PDL. The obtained results justify further experiments focused on the possible use of equine PDL cells for cell-based regenerative therapies.


Bis(ammonium) fluorophosphate at room temperature.
The title room-temperature phase of (NH(4))(2)(PO(3)F) is orthorhombic (Pna2(1)) and is related to the beta-K(2)SO(4) structure family. The title structure consists of ammonium cations, NH(4)(+), and fluorophosphate anions, (PO(3)F)(2-). These ions are connected by N-H.O hydrogen bonds. Two-centre N-H.F hydrogen bonds are not present in the structure. Phase transitions were detected at 251+/-2 and 274+/-2 K during cooling and heating, respectively.


RORα inhibits adipocyte-conditioned medium-induced colorectal cancer cell proliferation and migration and chick embryo chorioallantoic membrane angiopoiesis.
Lipid metabolic disturbances are related to many diseases, such as obesity, diabetes, and certain cancers. Notably, lipid metabolic disturbances have been reported to be a risk factor for colorectal cancer. Nuclear receptors act as ligand-dependent transcription regulators and play key roles in the regulation of body lipid metabolism and the development of many cancers. Retinoic acid receptor-related orphan receptor α (RORα) is a nuclear receptor and can regulate several lipid metabolism genes in certain cancers. Herein, we demonstrate that the conditioned medium from adipocytes has a proproliferative and promigratory effect on colorectal cancer cells and enhances angiogenesis in chicken embryonic chorioallantoic membranes. In addition, the conditioned medium leads to a decrease in the expression of RORα and its target genes. Meanwhile, RORα and its target gene expressions are lower in human colorectal tumor tissue compared with control colorectal tissue. Activation of RORα inhibits the effect of conditioned medium on the proliferation and migration of colorectal cancer cells as well as the angiogenesis in chicken embryonic allantoic membranes. In colorectal cancer cells, the putative ligand of RORα, cholesterol sulfate (CS), prevents cell cycle progression at the G1/S boundary and concurrently modulates the expression of cell cycle-regulatory genes in colorectal cancer cell. CS inhibits angiogenesis in chicken embryonic chorioallantoic membranes and concurrently decreases the mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α as well as the secretion of VEGF. In addition, lipogenic gene expression is higher in human colorectal tumor tissue compared with control colorectal tissue. CS inhibits the expression of lipogenic genes in colorectal cancer cells. These results suggest that RORα could represent a direct link between local lipid metabolism of colorectal tissue and colorectal cancer. Therefore, the reduction of the expression of RORα could represent a potential warning sign of colorectal cancer.


Go.Data as a digital tool for case investigation and contact tracing in the context of COVID-19: a mixed-methods study.
A manual approach to case investigation and contact tracing can introduce delays in response and challenges for field teams. Go.Data, an outbreak response tool developed by the World Health Organization (WHO) in collaboration with the Global Outbreak Alert and Response Network, streamlines data collection and analysis during outbreaks. This study aimed to characterize Go.Data use during COVID-19, elicit shared benefits and challenges, and highlight key opportunities for enhancement. This study utilized mixed methods through qualitative interviews and a quantitative survey with Go.Data implementors on their experiences during COVID-19. Survey data was analyzed for basic univariate statistics. Interview data were coded using deductive and inductive reasoning and thematic analysis of categories. Overarching themes were triangulated with survey data to clarify key findings. From April to June 2022, the research team conducted 33 interviews and collected 41 survey responses. Participants were distributed across all six WHO regions and 28 countries. While most implementations represented government actors at national or subnational levels, additional inputs were collected from United Nations agencies and universities. Results highlighted WHO endorsement, accessibility, adaptability, and flexible support modalities as main enabling factors. Formalization and standardization of data systems and people processes to prepare for future outbreaks were a welcomed byproduct of implementation, as 76% used paper-based reporting prior and benefited from increased coordination around a shared platform. Several challenges surfaced, including shortage of the appropriate personnel and skill-mix within teams to ensure smooth implementation. Among opportunities for enhancements were improved product documentation and features to improve usability with large data volumes. This study was the first to provide a comprehensive picture of Go.Data implementations during COVID-19 and what joint lessons could be learned. It ultimately demonstrated that Go.Data was a useful complement to responses across diverse contexts, and helped set a reproducible foundation for future outbreaks. Concerted preparedness efforts across the domains of workforce composition, data architecture and political sensitization should be prioritized as key ingredients for future Go.Data implementations. While major developments in Go.Data functionality have addressed some key gaps highlighted during the pandemic, continued dialogue between WHO and implementors, including cross-country experience sharing, is needed ensure the tool is reactive to evolving user needs.


B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.
The duration of signaling through the MAP kinase (or ERK pathway) cascade has been implicated in thymic development, particularly positive and negative selection. In T cells, two isoforms of the MAP kinase kinase kinase Raf function to transmit signals from the T-cell receptor to ERK: C-Raf and B-Raf. In this study, we conditionally ablated B-Raf expression within thymocytes to assess the effects on ERK activation and thymocyte development. The complete loss of B-Raf is accompanied by a dramatic loss of ERK activation in both the double positive (DP) and single positive (SP) thymocytes, as well as peripheral splenocytes. There was a significant decrease in the cellularity of KO thymi, largely due to a loss of pre-selected DP cells, a decrease in DP cells undergoing positive selection, and a defect in SP maturation. B-Raf plays significant roles in survival of DP thymocytes and function of SP cells in the periphery. Surprisingly, we saw no effect of B-Raf deficiency on negative selection of autoreactive SP thymocytes, despite the greatly reduced ERK activation in these cells.


Cluster beam deposition of lead sulfide nanocrystals into organic matrices.
Lead sulfide nanocrystals (PbS NCs) were codeposited into two organic films, titanyl phthalocyanine (TiOPc) and alpha-sexithiophene, using cluster beam deposition (CBD). NCs of average diameters of approximately 3-4 nm were evenly distributed in these organic films with average particle spacings of approximately 4 nm, as determined by transmission electron microscopy. The film composition and NC surface chemistry were monitored by X-ray photoelectron spectroscopy (XPS) and other methods. Pb:S stoichiometry in the NC/TiOPc film was determined by XPS to correspond to the PbS cubic rock salt structure. Soft-XPS using 200 eV energy photons determined the NC-organic surface chemistry by resolving the S 2p core level into four distinct components for sulfur. The soft-XPS results found that the PbS NC surface chemistry could be tuned by varying the H(2)S/Ar gas ratio within the CBD source.


Nosocomial spread of armA-mediated high-level aminoglycoside resistance in Enterobacteriaceae isolates producing CTX-M-3 beta-lactamase in a cancer hospital in Bulgaria.
1,310 Enterobacteriaceae, 242 Pseudomonas aeruginosa and 97 Acinetobacter baumannii clinical isolates collected at a cancer hospital in Bulgaria were screened for the presence of 16S rRNA methylases. The armA methylase gene was identified in 20 (1.5%) Enterobacteriaceae (7 Klebsiella pneumoniae, 3 Escherichia coli, 3 Serratia marcescens, 3 Citrobacter freundii , 3 Enterobacter cloacae and 1 Klebsiella oxytoca). ArmA-mediated aminoglycoside resistance was transferable by conjugation and carried by closely related IncL/M plasmids which also carried ant3"9, dfrXII, sul1, bla(TEM-1), and bla(CTX-M-3) genes encoding resistance to streptomycin-spectinomycin, trimethoprim, sulfonamides, and ss-lactams, respectively. Most of the isolates were genetically different according to PFGE but shared similar restriction patterns of the armA -encoding plasmids. Our findings highlight the strong association of armA and bla(CTX-M-3) extended-spectrum ss-lactamase genes across various species in the family Enterobacteriaceae . The spread of multiresistant isolates expressing 16S rRNA methylases and ESBLs is a worrisome development requiring continuous monitoring.


A family with the branchio-oto-renal syndrome: clinical and genetic correlations.
The branchio-oto-renal (BOR) syndrome is an autosomal dominant disease characterized by hearing loss of early onset, preauricular pits, branchial clefts, and early progressive chronic renal failure in up to 40% of family affected members. So far, it has not received due attention in the adult European nephrology literature and because of the combination of deafness with chronic renal failure it may be confused with the Alport syndrome. The BOR syndrome is caused by mutations in the EYA1 gene that maps on chromosome 8q13.3. A three-generation, 20-member large BOR Greek-Cypriot family has been studied and followed up clinically over a 27-year period. The findings in four individuals who developed early onset renal failure are described in detail. Genetic DNA linkage studies have also been carried out. Of the 15 family members at risk, 14 were tested with DNA linkage analysis. Ten members were genetically affected and four were normal. All 10 affected members developed early-onset deafness. Some had different ear lobe abnormalities. Nine affected members had preauricular pits. In some of the patients these pits were deep and prominent while in others they were minor and superficial. Eight affected members had early-onset branchial clefts that needed early corrective surgery without the correct familial diagnosis ever being made. End-stage renal disease (ESRD) developed in four members at ages 36, 14, 17, and 17 with minimal proteinuria, if any. This was due to unilateral renal agenesis with contralateral hypodysplasia or bilateral, severe renal hypodysplasia. The BOR syndrome is an infrequent but well-described entity that combines early-onset renal failure and deafness together with branchial clefts and preauricular pits. Renal agenesis and dysplasia are the causes of ESRD in these individuals. Other renal abnormalities include bifid kidneys with double ureters, vesico-ureteric reflux and pelvi-ureteric stenoses. The BOR syndrome should be included in the differential diagnosis of deafness and chronic renal failure in childhood and adolescence.


The adrenal chromaffin cells of Salmo gairdneri Richardson (Teleostei, Salmonidae).
The chromaffin cells of the adrenal homologue of Salmo gairdneri R. have been studied by light and electron microscopy. The chromaffin tissue was localised in the head kidney adjacent to the wall of the proximal part of the cardinal veins and their main branches. Specific histochemical techniques failed to demonstrate different types of chromaffin cells. With the electron microscope two different types of chromaffin cells were observed. The first type, characterised by numerous dense cytoplasmic granules of average diameter 90 nm, was interpreted as a noradrenalin cell; the second type was characterised by the presence of moderately electron-dense granules of average diameter of 85 nm, and was interpreted as an adrenalin cell. The reaction for acetylcholinesterase activity was present on nerve terminals and sometimes in the vacuolar membrane systems of both chromaffin cells.


Sexual experience increases nitric oxide synthase in the medial preoptic area of male rats.
Nitric oxide in the medial preoptic area (MPOA) is important for the expression and sensitization of male sexual behavior. In this article, the authors report that repeated sexual experience (mating for 2 hr on each of 3 days) increased levels of nitric oxide synthase (NOS) in the MPOA of male rats, regardless of whether they mated on the day they were given an overdose of sodium phenobarbital. This effect resulted from the previous experience and not acute mating, as NOS was not increased 2 hr after the first mating in previously naive males. Experience-induced increases in NOS in the MPOA may be one mechanism through which sexual experience facilitates sexual behavior in male rats.


Hymenolepis microstoma: a change in susceptibility to resistance with increasing age of the parasite.
Hymenolepis microstoma from secondary infections in mice were found to grow initially more slowly than H. microstoma from primary infections. Eventually a similar rate of growth was attained by both kinds of worm. After transplantation, young worms (less than or equal to 4 days old) grew more slowly in previously infected than in naive mice. In contrast, 10-day-old worms grew equally well in naive or resistant mice. The administration of cortisone to mice during a secondary infection of H. microstoma inhibited the stunting of growth in young worms which were able to grow as well as those in a primary infection. The effects of the cortisone persisted for less than 4 days. Worms in a secondary infection given 4 days after cortisone treatment were stunted in growth. These experiments suggest that the susceptibility of the worms to the resistance of the mouse applies to the first 4 days within the host. The loss or reduction of this susceptibility might be associated with the worm's entry into the bile duct which occurs 3--4 days after infection.


[The "pneumoneck" in videocervicoscopy: operative technique and anatomic limits].
The aim of this study was to describe a technic in order to create a gas space "pneumoneck" during videoendoscopic surgery of the neck and to determine the anatomical limits of this space. Data were based on a surgical experience and on the dissection of two corpses. This space was located between the two layers of the pre-tracheal lamina of the cervical fascia. This space was enclosed and favourable to detachment with insufflated gas without subcutaneous emphysema. This approach can be used for parathyroid and thyroid surgery.


Small cell carcinoma of the ovary of the hypercalcemic type presenting in a 5-year-old girl.
Small cell carcinoma of the ovary, hypercalcemic type is a very rare, highly aggressive tumor associated with a poor prognosis. Diagnosis is typically challenging secondary to undifferentiated cells and the rarity of the tumor. We report our experience with a 5-year-old girl who presented with stage IV disease.


Synthesis of Gold Nanoparticles from Au(I) Ions That Shuttle To Solidify: Application on the Sensor Array Design.
Metal-mediated interlocking rings won the 2016 Nobel Prize in Chemistry. The metal-directed interlocking rings in macromolecular systems (e.g., proteins) may be similar to the form of Maxwell's electromagnetic waves; the metal ions may shuttle among the rings in the special environment. To verify this hypothesis, we designed a general approach to synthesize the multicolored gold nanoparticles (GNPs) mediated by Au(I)-directed interlocking rings in proteins. The Au(I) ions shuttled among these interlocking rings in the strong alkaline solution. Through the rapid nucleation method, the multicolored GNPs of different morphology and sizes were synthesized in the multiple honeycombed templates. On the basis of the "three-color" principle of Thomas Young, we extracted the red, green, and blue (RGB) alterations of GNPs to fabricate a visual sensor array for protein discrimination. The fingerprints (ΔRGB) were obtained from the target proteins and fed into computer programs. The proposed sensing platform was also applied to detect lysozyme in human tears with satisfactory results. Importantly, we forecasted that lysozyme could be the effective drug for curing dacryocystitis and nasolacrimal duct obstruction diseases.


Parasite Specific Antibody Levels, Interferon-γ and TLR2 and TLR4 Transcripts in Blood from Dogs with Different Clinical Stages of Leishmaniosis.
Canine leishmaniosis has a wide range of disease severity from mild (stage I), to severe (stages II-III), or very severe disease (stage IV). The objective of the study was to evaluate and compare serum antibody levels, Leishmania infantum specific IFN-γ production and TLR2 and TLR4 transcripts in non-stimulated blood from dogs with different clinical stages at the time of diagnosis as well as blood parasitemia. Enzyme-Linked ImmunoSorbent Assay (ELISAs) were performed to determine serum antibody levels and IFN-γ production and quantitative polymerase chain reaction (qPCRs) in order to determine blood parasite load and TLR2 and TLR4 transcripts. Older dogs were significantly affected by more severe disease with higher antibody levels and blood parasitemia than dogs with mild disease. IFN-γ production was significantly higher in dogs with stage I disease when compared to dogs with more severe disease. Relative quantification of TLR2 in dogs with mild disease was similar to that of control dogs. On the other hand, TLR2 transcripts were significantly higher in dogs with severe disease as compared with that from control healthy dogs. No differences were found in TLR4 relative quantification between groups. This study demonstrates that dogs with different clinical stages of leishmaniosis present different levels of biological markers indicative of different immune responses.


Association Between Body Mass Index and Functional Dyspepsia in Young Japanese People.
Evidence regarding the association between body mass index (BMI) and functional dyspepsia (FD) in the Asian population is limited. Further, no study has evaluated this issue in young people in Asian and Western populations. Thus, we aim to investigate this issue among young Japanese people. The study subjects comprised of 8923 Japanese university students. BMI was divided into 4 categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, overweight, and obese was BMI < 18.5 kg/m2, 18.5 ≤ BMI < 25 kg/m2 (reference), 25 kg/m2 ≤ BMI < 30 kg/m2, and 30 kg/m2 ≤ BMI, respectively. The definition of FD was based on the Rome III criteria. The prevalence of FD was 1.9% in this cohort. The lowest BMI was independently associated with FD after adjustment (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.46-3.67); P for trend = 0.001). The lowest BMI was independently associated with FD in women but not in men (OR, 2.94; 95% CI, 1.59-5.77; P for trend = 0.001). Leanness was independently associated with FD in total and in women but not in men (total: adjusted OR, 2.01; 95% CI, 1.40-2.86) and women (OR, 2.19; 95% CI, 1.35-3.45). However, interaction analysis showed no significant difference for sex. Among young Japanese people, BMI may be independently inversely associated with FD. Leanness may be an independent associated factor for FD in the young Japanese women.


New strategies to prevent Staphylococcus aureus infections in peritoneal dialysis patients.
The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.


Effectiveness of an mHealth Intervention for Infant Sleep Disturbances.
Bedtime problems and night wakings are highly prevalent in infants. This study assessed the real-world effectiveness of an mHealth behavioral sleep intervention (Customized Sleep Profile; CSP). Caregivers (83.9% mothers) of 404 infants (age 6 to 11.9 m, M = 8.32 m, 51.2% male) used the CSP (free and publicly available behavioral sleep intervention delivered via smartphone application, Johnson's® Bedtime® Baby Sleep App). Caregivers completed the Brief Infant Sleep Questionnaire-Revised (BISQ-R) at baseline and again 4 to 28 days later. Changes in sleep patterns were analyzed, based on sleep problem status (problem versus no problem sleepers; PS; NPS). Sleep onset latency improved in both groups. Earlier bedtimes, longer continuous stretches of sleep, as well as decreased number and duration of night wakings, were evident in the PS group only. The BISQ-R Total score, total nighttime sleep, and total 24-hour sleep time improved for both groups, with a greater change for the PS group. Further, caregivers of infants in the PS group decreased feeding (bedtime and overnight) and picking up overnight, and perceived better sleep. Bedtime routine regularity, bedtime difficulty, sleep onset difficulty, and caregiver confidence improved for both groups, with the PS group showing a greater magnitude of change. Thus, a real-world, publicly available, mHealth behavioral sleep intervention was associated with improved outcomes for older infants. Intervention recommendations resulted in changes in caregivers' behavior and improvements in caregiver-reported sleep outcomes in infants, in as few as 4 days.


Ameloblastin expression during craniofacial bone formation in rats.
Based on previous results showing the expression of ameloblastin (Ambn; amelin) in the formation of mesenchymal dental hard tissues, we investigated its presence during bone development. Immunohistochemistry (IHC), in situ hybridization (ISH), and reverse transcription-polymerase chain reaction (RT-PCR) were used to investigate the expression of ameloblastin protein and mRNA during craniofacial development in rats. Tissue samples were collected on embryonic day 18 and from days 2-28 postnatally. IHC revealed the expression of ameloblastin during bone formation at embryonic and early postnatal stages with different patterns of expression in intramembranous and endochondral ossification. In intramembranous ossification, ameloblastin expression was detected in the superficial layer of the condensed vascularized primitive connective tissue and in the cellular layer covering the surface of the newly formed woven bone. In endochondral ossification, ameloblastin was expressed within the extracellular matrix of the cartilage templates and in the perichondrium. Between days 2 and 28 the expression decreased markedly, concordant with the maturation of the bone, and disappeared after completion of bone remodeling. The results obtained by IHC were confirmed by ISH and RT-PCR, showing the expression of ameloblastin mRNA during craniofacial bone formation. This study indicates the expression of the putative dental protein ameloblastin during craniofacial bone development in rats.


Impact of steam explosion on the wheat straw lignin structure studied by solution-state nuclear magnetic resonance and density functional methods.
Chemical changes of lignin induced by the steam explosion (SE) process were elucidated. Wheat straw was studied as the raw material, and lignins were isolated by the enzymatic mild acidolysis lignin (EMAL) procedure before and after the SE treatment for analyses mainly by two-dimensional (2D) [heteronuclear single-quantum coherence (HSQC) and heteronuclear multiple-bond correlation (HMBC)] and (31)P nuclear magnetic resonance (NMR). The β-O-4 structures were found to be homolytically cleaved, followed by recoupling to β-5 linkages. The homolytic cleavage/recoupling reactions were also studied by computational methods, which verified their thermodynamic feasibility. The presence of the tricin bound to wheat straw lignin was confirmed, and it was shown to participate in lignin reactions during the SE treatment. The preferred homolytic β-O-4 cleavage reaction was calculated to follow bond dissociation energies: G-O-G (guaiacyl) (69.7 kcal/mol) > G-O-S (syringyl) (68.4 kcal/mol) > G-O-T (tricin) (67.0 kcal/mol).


[Fibrillary glomerulonephritis. Case report for differential nephrotic syndrome diagnosis].
A 67-year-old male patient presented with a nephrotic syndrome. Biopsy of the kidney revealed the characteristic of fibrillary glomerulopathy on light and electron microscopy. Other non-nephritic causes of a nephrotic syndrome (e.g. amyloidosis, immunotactoid glomerulopathy, light-chain glomerulopathy, cryoglobulinaemia, collagen-III glomerulopathy, fibronectin glomerulopathy) could be excluded. Besides the case report, differential diagnosis of fibrillary glomerulopathies is presented.


Use of fibrin glue in obstetrics and gynecology: a review of the literature.
Most authors consider the principal advantage of FG anastomoses (compared to microsurgical anastomoses) to be shorter operating time, reduced surgical trauma to oviduct stumps, and absence of tissue ischemia. These features promote reparative regeneration and decrease adhesion formation, resulting in complete recanalization of fallopian tubes. To date, the majority of work on FG is confined to the experimental development of surgical techniques. Investigations in reconstructive gynecological surgery are quite uncommon. The physical properties of FG and the positive results of available experimental studies suggest that further development of surgical techniques using FG in obstetrics and gynecology is worthwhile.


Management of high-output chylous ascites after D2-lymphadenectomy in patients with gastric cancer: a multi-center study.
This study aimed to propose treatment strategies for high-output chylous ascites (CA) developed after gastric cancer surgery. The data of patients with CA after gastric cancer surgery in three high volume Training and Research Hospitals between 2005 and 2015 were retrospectively evaluated. Nine patients out of 436 gastrectomies were detected with CA. The mean amount of daily fistula output was 939 mL. Treatment consisted of cessation of oral feeding, total parenteral nutrition (TPN), somatostatin analogs administration, clamping and/or removal of the drainage tube, diuretic administration and diet therapy with medium-chain triglycerides (MCTs) alone or in combination. The mean fistula closure time and length of hospital stay were 23 and 24 days respectively. Hemopneumothorax developed during right subclavian vein catheterisation for TPN implementation in one patient. There was no mortality. Combined cessation of oral feeding and TPN are usually used for treatment of CA as first-line treatment. However, TPN is no harmless. Although our data are limited they do allow us to conclude that diet with MCT's may use for medical treatment of CA as first-line.


HEPARIN BONDING ON COLLOIDAL GRAPHITE SURFACES.
Experiments on clotting, both in vitro and in vivo, showed that a colloidal graphite surface, when rinsed with a cationic, surface-active agent, was capable of bonding heparin. The resistance of this graphite-heparin surface to the formation of clots was far greater than plastic or silicone surfaces in comparable studies.


Solar-Driven H2 O2 Generation From H2 O and O2 Using Earth-Abundant Mixed-Metal Oxide@Carbon Nitride Photocatalysts.
Light-driven generation of H2 O2 only from water and molecular oxygen could be an ideal pathway for clean production of solar fuels. In this work, a mixed metal oxide/graphitic-C3 N4 (MMO@C3 N4 ) composite was synthesized as a dual-functional photocatalyst for both water oxidation and oxygen reduction to generate H2 O2 . The MMO was derived from a NiFe-layered double hydroxide (LDH) precursor for obtaining a high dispersion of metal oxides on the surface of the C3 N4 matrix. The C3 N4 is in the graphitic phase and the main crystalline phase in MMO is cubic NiO. The XPS analyses revealed the doping of Fe(3+) in the dominant NiO phase and the existence of surface defects in the C3 N4 matrix. The formation and decomposition kinetics of H2 O2 on the MMO@C3 N4 and the control samples, including bare MMO, C3 N4 matrix, Ni- or Fe-loaded C3 N4 and a simple mixture of MMO and C3 N4 , were investigated. The MMO@C3 N4 composite produced 63 μmol L(-1) of H2 O2 in 90 min in acidic solution (pH 3) and exhibited a significantly higher rate of production for H2 O2 relative to the control samples. The positive shift of the valence band in the composite and the enhanced water oxidation catalysis by incorporating the MMO improved the light-induced hole collection relative to the bare C3 N4 and resulted in the enhanced H2 O2 formation. The positively shifted conduction band in the composite also improved the selectivity of the two-electron reduction of molecular oxygen to H2 O2 .


NF2/merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations.
Inactivating germline mutations in the tumor suppressor gene NF2 cause the hereditary syndrome neurofibromatosis 2, which is characterized by the development of neoplasms of the nervous system, most notably bilateral vestibular schwannoma. Somatic NF2 mutations have also been reported in a variety of cancers, but interestingly these mutations do not cause the same tumors that are common in hereditary neurofibromatosis 2, even though the same gene is involved and there is overlap in the site of mutations. This review highlights cancers in which somatic NF2 mutations have been found, the cell signaling pathways involving NF2/merlin, current clinical trials treating neurofibromatosis 2 patients, and preclinical findings that promise to lead to new targeted therapies for both cancers harboring NF2 mutations and neurofibromatosis 2 patients.


Grasshopper (Orthoptera: Acridomorpha) diversity in response to fallow-land use in southern Cameroon with recommendations for land management.
The sensitivity of grasshoppers to disturbance makes them useful bioindicators for land management. The current study compared the grasshopper communities of three fallow-lands at different levels of human pressure: heavily used land (Ongot), moderately used land (Zamakoe), and least-used land (Ngutadjap). Grasshoppers were sampled by nets, pitfall traps, and box quadrats. Their species composition was analyzed using species-richness, abundance, abundance distribution-model, occurrence, and diversity indexes. Species number was not very different between localities. However, the opening up of forests by human activities offers suitable environment for the development or proliferation of the pest grasshopper populations such as Zonocerus variegatus (Linnaeus, 1758), Eyprepocnemis plorans (Charpentier, 1825), and Catantops sylvestrisJago, 1984, which are adapted to the very common Asteraceae found in fallow lands. Native forest species [such as Mazaea granulosa Stål, 1876, Holopercna gerstaeckeri (Bolívar, 1890), Digentia fasciataRamme, 1929] were, generally absent or rare and were collected in only forest/fallow-land ecotones. Low abundance and low occurrence of ecotone species fitted the log-normal abundance distribution model. The grasshopper communities of the less degraded localities were quite similar, but different from the Ongot community. Forest management by reforestation, reduction of slash-and-burn agriculture, and wood cutting, would restore the original grasshopper assemblages and general environmental health.


Berenil complexation with a nucleic acid triple helix.
The interaction of berenil molecule, a minor groove binding drug, with T-A-T triple helix and A-T double helix was studied using circular dichroism spectroscopy and thermal denaturation. The triple helix was made by an oligonucleotide (dA)12-X-(dT)12-X-(dT)12, where x is a hexaethylene glycol chain bridged between the 3' phosphate of one strand and the 5' phosphate of the following strand. This oligonucleotide is able to fold back on itself to form a very stable triplex. Circular dichroism spectroscopy demonstrates that berenil can bind to the triple helical structure. Spectral analysis shows that in the same ionic strength the drug bound to a double-stranded structure exhibits a conformation and an environment close to those observed in triple-stranded structure. The influence of the ionic strength on the interaction between the berenil molecule and the 36-mer is clearly demonstrated. We showed that when no NaCl salt is added in the buffer the triplex form of (dA)12-X-(dT)12-X-(dT)12 is stabilized by berenil whereas it is destabilized slightly by the dye when NaCl concentration is 1 M.


Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide.
A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a SRN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH2, amide, ester).


The risk of coronary bypass surgery for patients with postinfarction angina.
Three hundred consecutive patients who developed unstable postinfarction angina requiring isolated coronary artery bypass from 1982 through 1987 were analyzed. Hospital mortality was 5%; 15 (5.5%) additional late deaths occurred during the 69-month follow-up period (mean follow-up, 23.3 months). Significant independent predictors of perioperative mortality by univariate analysis were ejection fraction (p = 0.004); existence of an anterior, transmural infarction (p = 0.0001); and the requirement for preoperative intra-aortic balloon counterpulsation (p = 0.001). By multivariate analysis, only the occurrence of an anterior, transmural infarction (p = 0.001) and the preoperative use of an intra-aortic balloon pump (p = 0.004) were significant independent predictors of mortality. Actuarial survival in this group ranged from 96 +/- 1% at 1 year to 88 +/- 4% at 5 years.


Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.


Staphylococcus aureus and Pseudomonas aeruginosa infectious keratitis: key bacterial mechanisms that mediate pathogenesis and emerging therapeutics.
Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate broad-spectrum antibiotics are essential to adequately treat this disease. However, rising antibiotic resistance continues to accelerate, rendering many commonly used therapeutics increasingly ineffective. As such, there is a significant effort to understand the basic pathogenesis of common causative organisms implicated in keratitis in part, to fuel the development of novel therapies to treat this blinding disease. This review explores two common causes of bacterial keratitis, Staphylococcus aureus and Pseudomonas aeruginosa, with regards to the bacterial mediators of virulence as well as novel therapies on the horizon.


ALD Al2O3-Coated TiO2 Nanotube Layers as Anodes for Lithium-Ion Batteries.
The utilization of the anodic TiO2 nanotube layers, with uniform Al2O3 coatings of different thicknesses (prepared by atomic layer deposition, ALD), as the new electrode material for lithium-ion batteries (LIBs), is reported herein. Electrodes with very thin Al2O3 coatings (∼1 nm) show a superior electrochemical performance for use in LIBs compared to that of the uncoated TiO2 nanotube layers. A more than 2 times higher areal capacity is received on these coated TiO2 nanotube layers (∼75 vs 200 μAh/cm2) as well as higher rate capability and coulombic efficiency of the charging and discharging reactions. Reasons for this can be attributed to an increased mechanical stability of the TiO2 nanotube layers upon Al2O3 coating, as well as to an enhanced diffusion of the Li+ ions within the coated nanotube layers. In contrast, thicker ALD Al2O3 coatings result in a blocking of the electrode surface and therefore an areal capacity decrease.


Role of skeletal muscle-fibre type in regulation of glucose metabolism in middle-aged subjects with impaired glucose tolerance during a long-term exercise and dietary intervention.
The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance (IGT) during a 2-year exercise and dietary intervention. Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGT(slow) (n=10) with a high proportion of MHC I isoforms and IGT(fast) (n=12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1+/-2.7 h/week in the IGT(slow) and 5.1+/-2.8 h/week in the IGT(fast) group. Fasting glucose (p<0.05), 2-h glucose (p<0.05), fasting insulin (p<0.05), haemoglobin A1c (HbA(1c)) (p<0.01) and insulin resistance (p<0.05) [homeostasis model assessment for insulin resistance (HOMA-IR)] decreased in the IGT(fast) group, whereas only the 2-h glucose and HbA(1c) concentrations decreased in the IGT(slow) group. The amount of the glycogen synthase kinase-3-alphabeta (GSK-3-alphabeta) decreased in the IGT(fast) group (p<0.05). Exercise training increased the lactate dehydrogenase (LDH) (p<0.01), LDH-1 (p<0.05) and citrate synthase (CS) (p<0.05) activities in the vastus lateralis muscle in the IGT(slow) group, but only the CS activity (p<0.05) in the IGT(fast) group. The glucose metabolism improved both in the IGT(slow) and IGT(fast) group during the 2-year exercise and dietary intervention. The change was more prominent in the IGT(fast) group than in the IGT(slow) group, associated with the decrease of the GSK-alphabeta protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGT(slow) group and the oxidative capacity in both groups.


Induction of chromosome aberrations and specific locus mutation but not sister chromatid exchanges in Chinese hamster ovary cells by neocarzinostatin.
The induction of chromosome aberrations, sister chromatid exchanges (SCE), cytotoxicity, and 6-thioguanine-resistant mutation by neocarzinostatin (NCS) in Chinese hamster ovary cells was analyzed. It was observed that within the same concentration range of 0.01-0.1 mu/ml NCS, the drug induced a significant increase in all analyzed end-points except in SCE frequencies. There was no increase in SCE frequencies even when the cells were treated at the G1/S border in the first cell cycle and when aberrations were observed in the same cell showing a second cycle differential staining pattern. Our study indicates that the cellular damage induced by NCS leads to expression in chromosome aberrations, cytotoxicity, and mutagenicity but not in sister chromatid exchanges.