Comparing neural response to painful electrical stimulation with functional MRI at 3 and 7 T.
Progressing from 3T to 7 T functional MRI enables marked improvements of human brain imaging in vivo. Although direct comparisons demonstrated advantages concerning blood oxygen level dependent (BOLD) signal response and spatial specificity, these mostly focused on single brain regions with rather simple tasks. Considering that physiological noise also increases with higher field strength, it is not entirely clear whether the advantages of 7T translate equally to the entire brain during tasks which elicit more complex neuronal processing. Therefore, we investigated the difference between 3T and 7 T in response to transcutaneous electrical painful and non-painful stimulation in 22 healthy subjects. For painful stimuli vs. baseline, stronger activations were observed at 7 T in several brain regions including the insula and supplementary motor area, but not the secondary somatosensory cortex (p<0.05 FWE-corrected). Contrasting painful vs. non-painful stimulation limited the differences between the field strengths to the periaqueductal gray (PAG, p<0.001 uncorrected) due to a similar signal increase at 7 T for both the target and specific control condition in most brain regions. This regional specificity obtained for the PAG at higher field strengths was confirmed by an additional spatial normalization strategy optimized for the brainstem. Here, robust BOLD responses were obtained in the dorsal PAG at 7 T (p<0.05 FWE-corrected), whereas at 3T activation was completely missing for the contrast against non-painful stimuli. To summarize, our findings support previously reported benefits obtained at ultra-high field strengths also for complex activation patterns elicited by painful electrical stimulation. However, this advantage depends on the region and even more on the contrast of interest. The greatest gain at 7 T was observed within the small brainstem region of the PAG, where the increased field strength offered marked improvement for the localization of activation foci with high spatial specificity.


Loss of heterozygosity and transcriptome analyses of a 1.2 Mb candidate ovarian cancer tumor suppressor locus region at 17q25.1-q25.2.
Loss of heterozygosity (LOH) analysis was performed in epithelial ovarian cancers (EOC) to further characterize a previously identified candidate tumor suppressor gene (TSG) region encompassing D17S801 at chromosomal region 17q25.1. LOH of at least one informative marker was observed for 100 (71%) of 140 malignant EOC samples in an analysis of 6 polymorphic markers (cen-D17S1839-D17S785-D17S1817-D17S801-D17S751-D17S722-tel). The combined LOH analysis revealed a 453 kilobase (Kb) minimal region of deletion (MRD) bounded by D17S1817 and D17S751. Human and mouse genome assemblies were used to resolve marker inconsistencies in the D17S1839-D17S722 interval and identify candidates. The region contains 32 known and strongly predicted genes, 9 of which overlap the MRD. The reference genomic sequences share nearly identical gene structures and the organization of the region is highly collinear. Although, the region does not show any large internal duplications, a 1.5 Kb inverted duplicated sequence of 87% nucleotide identity was observed in a 13 Kb region surrounding D17S801. Transcriptome analysis by Affymetrix GeneChip and reverse transcription (RT)-polymerase chain reaction (PCR) methods of 3 well characterized EOC cell lines and primary cultures of normal ovarian surface epithelial (NOSE) cells was performed with 32 candidates spanning D17S1839-D17S722 interval. RT-PCR analysis of 8 known or strongly predicted genes residing in the MRD in 10 EOC samples, that exhibited LOH of the MRD, identified FLJ22341 as a strong candidate TSG. The proximal repeat sequence of D17S801 occurs 8 Kb upstream of the putative promoter region of FLJ22341. RT-PCR analysis of the EOC samples and cell lines identified DKFZP434P0316 that maps proximal to the MRD, as a candidate. While Affymetrix technology was useful for initially eliminating less promising candidates, subsequent RT-PCR analysis of well-characterized EOC samples was essential to prioritize TSG candidates for further study.


Clinical and immunological profiles of anti-BP230-type bullous pemphigoid: Restriction of epitopes to the C-terminal domain of BP230, shown by novel ELISAs of BP230-domain specific recombinant proteins.
To confirm that sera from some BP patients reactive exclusively to the BP230 and to study the clinical and immunological characteristics of this condition. BP patients were divided into three groups: BP reactive only to BP230 (BP230-BP), BP reactive to both BP180 and BP230 (BP180-BP230-BP) and BP reactive only to BP180 (BP180-BP), based on the results of standard ELISAs for BP180 and BP230. Clinical features were statistically analyzed among the three groups. Then, targeted epitopes in each group were studied by immunoblotting and novel ELISAs using three domain-specific BP230 recombinant proteins. Forty-one, 65 and 47 of 153 BP patients were categorized as BP230-BP, BP180-BP230-BP and BP180-BP, respectively. Clinically, BP230-BP patients showed significantly lower severity, less need of systemic steroids and better responses to various treatments, suggesting that BP230-BP is a milder condition. Immunoblotting and ELISAs of domain-specific BP230 recombinant proteins indicated that, while BP180-BP230-BP sera reacted with all three domains of BP230, BP230-BP sera reacted more frequently with epitopes in the BP230 C-terminal domain. We propose a new disease entity, named anti-BP230-type BP, in which anti-BP230 antibodies might be pathogenic and react specifically with the BP230 C-terminal domain. While anti-BP230 antibodies in BP180-BP230-BP seem to be produced via intermolecular epitope spreading, anti-BP230 antibodies in BP230-BP are considered to be produced by different mechanisms.


Evaluation of virological quality of sewage from four biological treatment plants by a nested-PCR technique.
In order to determine the virological quality of sewage from four biological treatment plants in Greece (two in the city of Athens and two in the city of Patras), 92 raw sewage samples were analysed for the presence of enteroviruses and adenoviruses during the period from October 2000 to February 2003. A nested-PCR method was used in order to increase the sensitivity of virus detection. Enteroviruses were detected in 43 samples (47%) and adenoviruses in 75 samples (81.5%) of raw sewage by nested PCR. The more frequent isolation of adenoviruses in raw sewage indicated their stability as virological indicators of the pollution of the environment and their increased persistence in sewage.


Whole blood transcriptomic investigation identifies long non-coding RNAs as regulators in sepsis.
Sepsis is a fatal disease referring to the presence of a known or strongly suspected infection coupled with systemic and uncontrolled immune activation causing multiple organ failure. However, current knowledge of the role of lncRNAs in sepsis is still extremely limited. We performed an in silico investigation of the gene coexpression pattern for the patients response to all-cause sepsis in consecutive intensive care unit (ICU) admissions. Sepsis coexpression gene modules were identified using WGCNA and enrichment analysis. lncRNAs were determined as sepsis biomarkers based on the interactions among lncRNAs and the identified modules. Twenty-three sepsis modules, including both differentially expressed modules and prognostic modules, were identified from the whole blood RNA expression profiling of sepsis patients. Five lncRNAs, FENDRR, MALAT1, TUG1, CRNDE, and ANCR, were detected as sepsis regulators based on the interactions among lncRNAs and the identified coexpression modules. Furthermore, we found that CRNDE and MALAT1 may act as miRNA sponges of sepsis related miRNAs to regulate the expression of sepsis modules. Ultimately, FENDRR, MALAT1, TUG1, and CRNDE were reannotated using three independent lncRNA expression datasets and validated as differentially expressed lncRNAs. The procedure facilitates the identification of prognostic biomarkers and novel therapeutic strategies of sepsis. Our findings highlight the importance of transcriptome modularity and regulatory lncRNAs in the progress of sepsis.


Influence of smoking and snuff cessation on risk of preterm birth.
The mechanisms by which antenatal smoking exposure increases the risk of preterm birth remain unknown. Swedish oral moist snuff contains quantities of nicotine comparable to those typically absorbed from cigarette smoking, but does not result in exposure to the products of combustion, for example carbon monoxide. In a nation-wide study of 776,836 live singleton births in Sweden from 1999 to 2009, the authors used multiple logistic regression models to examine associations between cessation of smoking and Swedish snuff use early in pregnancy and risk of preterm birth (before 37 weeks). Compared with non-tobacco users both before and in early pregnancy, the adjusted odds ratios (OR), 95% confidence interval (CI) were OR=0.92, 95% CI 0.84-1.01, for women who stopped using snuff, and OR=0.90, 95% CI 0.87-0.94, for women who stopped smoking. In contrast, continued snuff use and smoking were associated with increased risks of preterm birth (adjusted OR=1.29, 95% CI 1.17-1.43, adjusted OR=1.30, 95% CI 1.25-1.36, respectively). The snuff and smoking-related risks were, if anything, higher for very (before 32 weeks) than moderately (32-36 weeks) preterm birth, and also higher for spontaneous than induced preterm birth. These findings suggest that antenatal exposure to nicotine is involved in the mechanism by which tobacco use increase the risk of preterm birth.


Milk and meat iodine content: relation to human health.
The amount of iodine consumed by human beings in the United States has increased over the past 10 to 15 years. Although there is no direct evidence of an increased human iodine toxicity problem because of the increased intake, there is some concern that if this trend continues, the greater iodine concentration may contribute to an increase in thyroid disorders. Because iodine content in milk has increased by 300% to 500% over the past 10 to 15 years, factors contributing to this increase have been studied. Organic iodine additions to the feed supply have contributed to large increases in iodine content in milk from some farms, and are considered the main factor contributing to the large increase in iodine content in milk values. Iodine teat dips and udder washes contribute to the increased iodine content of milk but generally do not result in increases of more than 150 micrograms/L. Iodine-sanitizing agents used on milking equipment or in milk transfer and storage equipment can contribute large amounts if improperly used, but the frequency of this problem is small. Iodine content in meat does increase with increased iodine intake, but the transfer of iodine to meat is relatively lower than it is to milk.


Cells in microfluidics.
Microfluidic devices offer a realistic environment for cell cultures as it is related to scales found in biological systems. The aim is to create more in vivo like systems, in comparison to 2D plate cultures. Creating 3D cell culture constructs increase the cell's functionality. By controlling the microenvironment (e.g., cell matrix, flow rate, temperature) cell functionality can be increased even more. As microfluidic devices allow for precise control of the microenvironment, they are a paramount tool to study stem cells and their differentiation caused by external factors. We will give an overview of the use of microfluidic devices for some biological problems, and especially as a cell culture platforms. We focus on 3D cell cultures and stem cells and their microenvironment.


Status of complementary and alternative medicine in the osteopathic medical school curriculum.
Reflecting society's interest in complementary and alternative medicine (CAM), most allopathic medical schools in the United States offer instruction in CAM. Pertinent information about the teaching of CAM at osteopathic medical schools is lacking. The authors therefore sought to document the form and content of CAM instruction at osteopathic medical schools and compare their findings with those reported for allopathic medical schools in a recently published survey. Phone conversations with academic officials at each of the 19 colleges of osteopathic medicine revealed that only one school did not teach CAM. With the help of these officials, the authors identified 25 CAM instructors at 18 osteopathic medical schools and sent them questionnaires. All returned a completed form with details about CAM instruction at their schools. The authors found that CAM material was usually presented in required courses sponsored by clinical departments, was most likely taught in the first 2 years of medical school, and involved fewer than 20 contact hours of instruction. The topics most often taught were acupuncture (68%), herbs and botanicals (68%), spirituality (56%), dietary therapy (52%), and homeopathy (48%). Most (72%) CAM instructors were also practitioners of CAM modes of therapy. Few (12%) of the instructors taught CAM from an evidence-based perspective. The authors conclude that the form and content of CAM instruction at osteopathic medical schools is similar to that offered at allopathic medical schools and that both osteopathic and allopathic medical schools should strive to teach CAM with less advocacy and more reliance on evidence-based medicine.


Human insulinoma hybrids produce proinsulin-like material.
We have established somatic cell hybrids by fusing cells from two human insulinomas with an established murine cell line LMTK- Cl1D. After selection of the hybrids, the media were analyzed and found to contain insulin and human C-peptide immunoreactive material. The newly synthesized material was further characterized by pulse labeling and immunoprecipitation, and shown in five hybrid lines on Sephadex G-50 chromatography to have a size similar to proinsulin. The hybrids produced the apparent proinsulin-like material for up to 7 mo. Chromosome composition of the hybrids was determined by isozyme analysis and banding techniques. Chromosome 11, which previously has been assigned the insulin gene using cDNA probes, was identified in the hybrids producing proinsulin-like material. However, the retention of this chromosome did not always assure the production of hormone. This independent technique has confirmed the localization of the insulin gene to chromosome 11 and offers the opportunity of studying insulin processing and developing continuous insulin-producing cell lines.


Vascular permeability increase and plasma volume loss induced by endotoxin was attenuated by hypertonic saline with or without dextran.
Endotoxin given intravenously is known to cause plasma leakage and subsequent loss of circulating plasma volume. Hypertonic saline resuscitation has been successfully applied in hemorrhagic and traumatic shock, but its application for the treatment or prevention of septic or endotoxin shock is less well studied. Our aim was to investigate the effects of endotoxin on plasma leakage in hamsters when administered in two different ways: applied locally to the hamster cheek pouch microcirculation or systemically by i.v. injection. The cheek pouch was studied by intravital microscopy using FITC-labeled dextran as a tracer of plasma leakage. Escherichia coli lipopolysaccharide (LPS) was continuously added into the superfusion buffer of the cheek pouch preparation during 120 min in two control groups (each n = 6) and two further groups (each n = 6) treated with either hypertonic saline (HS) or hypertonic saline and dextran (HSD). Treatment was given as an i.v. injection 0.35 mL NaCl 7.5%/100 g b.w. during 4 min starting 15 min prior to the start of endotoxin application. Endotoxin caused a reversible increase in the number of postcapillary venular leaks with a maximal response at 70 min after start of endotoxin application. The maximal responses were reduced to 36% in the HS-treated and to 37% in the HSD-treated group in comparison to what was seen in the control groups. In the second part of the study endotoxin was given i.v. 0.3 mg/kg to anesthetized hamsters (n = 41) and arterial blood samples were collected at 0, 60, 120, and 180 min after endotoxin injection for measurement of hematocrit and plasma FITC-dextran concentration. Hamsters were divided into seven groups: untreated control group (n = 6); HSC control group given only an i.v. injection of hypertonic saline (n = 6); LPS group given endotoxin 0.3 mg/kg during 1 min (n = 9); HSp group given hypertonic saline (NaCl 7.5%) 10 min prior to i.v. endotoxin (n = 6); HSa group given hypertonic saline 10 min after i.v. endotoxin (n = 6); HSD group given hypertonic saline with dextran 40, 10 min prior to i.v. endotoxin (n = 6); HSD control group given only i.v. hypertonic saline + dextran and no endotoxin (n = 2). Injection of endotoxin caused a significant increase in hematocrit, which was counteracted by hypertonic saline treatment, with or without dextran, probably due to reduced extravasation of plasma in postcapillary venules.


Invited commentary: meta-physical activity and the search for the truth.
Measurement error in self-reported data from questionnaires is a well-recognized challenge in studies of physical activity and health. In this issue of the Journal, Lim et al. (Am J Epidemiol. 2015;181(9):648-655) used data from accelerometers in a small measurement study to correct self-reported physical activity data from a larger study of adults from New York City and to develop an error correction model. They showed that correction of measurement error in self-reported physical activity levels strengthened the associations of physical activity with both obesity and diabetes by 30%-50% compared with using the self-reported questionnaire data alone. Thus, Lim et al. demonstrated a method to improve potentially biased estimates of the association between self-reported physical activity and disease. However, as this field develops, we feel it is important to call attention to a sometimes overlooked problem that occurs when comparing these instruments: Questionnaires and accelerometers are often calibrated (i.e., designed) to measure different types of physical activity, and accelerometers are still subject to measurement error. Thus, physical activity estimates corrected with an imperfect accelerometer measurement might over- or undercorrect the strength of the associations. We take this opportunity to further comment on physical activity measurement in epidemiologic studies and the implications for research.


Effectiveness of cognitive behavioral therapy: An evaluation of therapies provided by trainees at a university psychotherapy training center.
At the psychotherapy training center at Karlstad University, a study was carried out to examine the levels of symptom change and satisfaction with therapy in a heterogeneous population of clients treated using cognitive behavioral therapy (CBT) by less experienced trainee therapists with limited theoretical education. The clients received an average of 11 therapy sessions. The results suggested that CBT performed by less experienced trainee therapists can be effective. According to client estimations, a statistically significant reduction in symptoms, measured using the Symptoms Checklist, was achieved for seven of nine variables (p ≤ .006), as well as a significant increase in satisfaction with life (p ≤ .001). Also, the pre- and posttherapy measurements using the Montgomery-Åsberg Depression Rating Scale showed a statistically significant improvement in the clients' condition. According to the therapists' estimations, 64% (SD = 32.01) of the clients experienced a significant improvement in their condition. In addition, the results of a survey of client satisfaction demonstrated that the clients were very pleased with the therapy received. Also the therapists were, to a great extent, satisfied with the treatment process itself, including the supervision received, and very satisfied with the client alliance. A correlation analysis between the clients' perceived level of improvement and therapist satisfaction showed a strong correlation between the two variables (r = .50, p < .005). By including the Comparative Psychotherapy Process Scale (CPPS) in our study it was possible to measure trueness to therapy form. An analysis of the CPPS results confirmed that the form of therapy used at the training site was more strongly CBT than psychodynamic interpersonal treatment (p ≤ .001). The CBT subscale score indicated that the therapy was characteristic of CBT, confirming that the interventions used in the therapy belong to the CBT genre.


Proteomics, Transcriptomics, and Phosphoproteomics Reveal the Mechanism of Talaroconvolutin-A Suppressing Bladder Cancer via Blocking Cell Cycle and Triggering Ferroptosis.
Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng. Whether TalaA exerts anticancer activity in bladder cancer remains unknown. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and Western blotting, we studied the anticancer activity of TalaA in vitro. Moreover, we performed xenograft tumor implantation. The antitumor effects were evaluated through H&E and immunohistochemistry staining. Proteomics was conducted to detect changes in the protein profile; transcriptomics was performed to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 μM, respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and AURKB and upregulating p21/CIP. TalaA also elevated intracellular reactive oxygen species and upregulated transferrin and heme oxygenase 1 to induce ferroptosis. Moreover, TalaA was able to bind to MAPKs (MAPK1, MAPK8, and MAPK14) to inhibit the phosphorylation of ∗SP∗ motif of transcription regulators. This study revealed that TalaA inhibited bladder cancer by arresting cell cycle to suppress proliferation and triggering ferroptosis to cause cell death. Conclusively, TalaA would be a potential candidate for treating bladder cancer by targeting MAPKs, suppressing the cell cycle, and inducing ferroptosis.


A qualitative evaluation of the effects of Metacognitive Reflection and Insight Therapy: 'Living more consciously'.
Extensive research showed that one of the major difficulties that people with schizophrenia spectrum disorders are struggling with involves their ability to reflect on their own and others' mental activities, also defined as metacognition. Several new psychotherapies have been developed to assist patients (re)gain metacognitive capacity, including Metacognitive Reflection and Insight Therapy (MERIT). The current study investigated the client's subjective experience of psychotherapy, to determine whether service users found MERIT effective and whether these gains align with quantitative findings, which processes they considered responsible for these benefits, in which ways participants found MERIT similar or different from other interventions, and whether they experienced non-desirable factors and outcomes. All participants who had participated in a randomized controlled trial investigating the efficacy of MERIT were offered a structured post-therapy interview by an independent assessor. Fourteen out of 18 (77%) participants, all of whom had completed therapy, responded. Most participants (10/14) indicated that they had experienced the therapy as beneficial to their recovery, and in general contributed to their understanding of their own thinking, which maps closely onto the quantitative findings reported elsewhere. They mainly attributed these changes to their own active role in therapy, the intervention letting them vent and self-express, and forming an alliance with the therapist. Participants reports of change map closely onto the quantitative findings from the randomized controlled trial. Findings are discussed in the frameworks of the metacognitive model of psychosis and the integrative intersubjective model of psychotherapy for psychosis emphasizing the role of the clients as active agent of change. The use of a systematic, qualitative interview at the conclusion of therapy may yield important information regarding process and outcome. Analysis of the interview revealed that clients' perceptions regarding change within themselves closely maps onto quantitative findings. MERIT may not be the appropriate intervention for all clients; some may prefer a more solution-oriented approach such as CBTp or Metacognition-Oriented Social Skills training. Self-expressing with a trained clinician may be therapeutic in itself.


An abattoir survey of caprine liver diseases in the sultanate of Oman.
The examination of 675 caprine livers from a slaughterhouse in the Greater Muscat area in the Sultanate of Oman revealed that 63 (9.3%) exhibited gross pathological changes leading to condemnation of this organ. Forty of these livers (71.4%) exhibited one major abnormality, whereas the remaining 28.6% had two or more lesions. The most frequently occurring disorder was diffuse hepatic lipidosis (4.0%), followed by bacterial associated abscesses (2.4%), cysticercosis (1.9%), and eosinophilic granulomata (1%). Although the cause for the hepatic lipidosis was not determined it appeared to be a reversible condition based on the absence of degenerative nuclei within the affected hepatocytes. Conditions observed in only a single liver were subcapsular (non-parasitic) cysts, focal necrosis, micronodular cirrhosis, extensive bile duct proliferation and diffuse haemorrhage.


Genetic research with Indigenous Peoples: perspectives on governance and oversight in the US.
Indigenous Peoples are increasingly exerting governance and oversight over genomic research with citizens of their nations, raising questions about how best to enforce research regulation between American Indian, Alaska Native, and Native Hawaiian peoples and researchers. Using a community-engaged research approach, we conducted 42 semi-structured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members about their perspectives on ethical issues related to genetics research with Indigenous Peoples in the US. We report findings related to (1) considerations for Indigenous governance, (2) institutional relationships upholding sovereignty, (3) expectations for research approvals, and (4) agreements enacting Indigenous governance. Participants described concerns about different ways of exerting oversight, relationships and agreements between Indigenous Peoples and researchers, and gaps that need to be addressed to strengthen existing governance of genomic data. The results will ultimately guide policy-making and development of new strategies for Indigenous Peoples to enforce oversight in research to promote ethically and culturally appropriate research.


Establishment and lineage replacement of H6 influenza viruses in domestic ducks in southern China.
Domestic ducks in southern China act as an important reservoir for influenza viruses and have also facilitated the establishment of multiple H6 influenza virus lineages. To understand the continuing evolution of these established lineages, 297 H6 viruses isolated from domestic ducks during 2006 and 2007 were genetically and antigenically analyzed. Phylogenetic analyses showed that group II duck H6 viruses had replaced the previously predominant group I lineage and extended their geographic distribution from coastal to inland regions. Group II H6 virus showed that the genesis and development of multiple types of deletions in the neuraminidase (NA) stalk region could occur in the influenza viruses from domestic ducks. A gradual replacement of the N2 NA subtype with N6 was observed. Significant antigenic changes occurred within group II H6 viruses so that they became antigenically distinguishable from group I and gene pool viruses. Gene exchange between group II H6 viruses and the established H5N1, H9N2, or H6N1 virus lineages in poultry in the region was very limited. These findings suggest that domestic ducks can facilitate significant genetic and antigenic changes in viruses established in this host and highlight gaps in our knowledge of influenza virus ecology and even the evolutionary behavior of this virus family in its aquatic avian reservoirs.


Income inequalities in multimorbidity prevalence in Ontario, Canada: a decomposition analysis of linked survey and health administrative data.
The burden of multimorbidity is a growing clinical and health system problem that is known to be associated with socioeconomic status, yet our understanding of the underlying determinants of inequalities in multimorbidity and longitudinal trends in measured disparities remains limited. We included all adult respondents from four cycles of the Canadian Community Health Survey (CCHS) (between 2005 to 2011/12), linked at the individual-level to health administrative data in Ontario, Canada (pooled n = 113,627). Multimorbidity was defined at each survey response as having ≥2 (of 17) high impact chronic conditions, based on claims data. Using a decomposition method of the Erreygers-corrected concentration index (CErreygers), we measured household income inequality and the contribution of the key determinants of multimorbidity (including socio-demographic, socio-economic, lifestyle and health system factors) to these disparities. Differences over time are described. We tested for statistically significant changes to measured inequality using the slope index (SII) and relative index of inequality (RII) with a 2-way interaction on pooled data. Multimorbidity prevalence in 2011/12 was 33.5% and the CErreygers was - 0.085 (CI: -0.108 to - 0.062), indicating a greater prevalence among lower income groups. In decomposition analyses, income itself accounted more than two-thirds (69%) of this inequality. Age (21.7%), marital status (15.2%) and physical inactivity (10.9%) followed, and the contribution of these factors increased from baseline (2005 CCHS survey) with the exception of age. Other lifestyle factors, including heavy smoking and obesity, had minimal contribution to measured inequality (1.8 and 0.4% respectively). Tests for trends (SII/RII) across pooled survey data were not statistically significant (p = 0.443 and 0.405, respectively), indicating no change in inequalities in multimorbidity prevalence over the study period. A pro-rich income gap in multimorbidity has persisted in Ontario from 2005 to 2011/12. These empirical findings suggest that to advance equality in multimorbidity prevalence, policymakers should target chronic disease prevention and control strategies focused on older adults, non-married persons and those that are physically inactive, in addition to addressing income disparities directly.


Biphasic Supramolecular Self-Assembly of Ferric Ions and Tannic Acid across Interfaces for Nanofilm Formation.
Cell nanoencapsulation provides a chemical tool for the isolation and protection of living cells from harmful, and often lethal, external environments. Although several strategies are available to form nanometric films, most methods heavily rely on time-consuming multistep processes and are not biocompatible. Here, the interfacial supramolecular self-assembly and film formation of ferric ions (FeIII ) and tannic acid (TA) in biphasic systems is reported, where FeIII and TA come into contact each other and self-assemble across the interface of two immiscible phases. The interfacial nanofilm formation developed is simple, fast, and cytocompatible. Its versatility is demonstrated with various biphasic systems: hollow microcapsules, encasing microbial or mammalian cells, that are generated at the water-oil interface in a microfluidic device; a cytoprotective FeIII -TA shell that forms on the surface of the alginate microbead, which then entraps probiotic Lactobacillus acidophilus; and a pericellular FeIII -TA shell that forms on individual Saccharomyces cerevisiae. This biphasic interfacial reaction system provides a simple but versatile structural motif in materials science, as well as advancing chemical manipulability of living cells.


Mapping regional funding for COVID-19 research in the Asia-Pacific region.
The Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) is a network of funders supporting research on infectious diseases of epidemic/pandemic potential. GloPID-R is establishing regional hubs to strengthen stakeholder engagement particularly among low-income and middle-income countries. The first pilot hub, led from Republic of Korea (South Korea), has been launched in the Asia-Pacific region, a region highly prone to outbreaks of emerging infectious diseases. We present findings of mapping research undertaken in support of the hub's development. We analysed five COVID-19 research databases in September 2022 to identify research funders and intermediary funding sources supporting research in infectious diseases in the Asia-Pacific region. This was complemented with an in-depth analysis of the UK Collaborative on Development Research (UKCDR) and GloPID-R COVID-19 Research Project Tracker to assess the alignment of funded projects in the region to the WHO COVID-19 research priorities. We identified 453 funders and funding sources supporting COVID-19 research in the Asia-Pacific Region including public, private and philanthropic organisations and universities. However, these organisations were clustered in few countries in the region. The in-depth analysis of the UKCDR and GloPID-R COVID-19 Research project Tracker found limited research involving Asia-Pacific countries with the 117 funders supporting these projects investing at least US$604m in COVID-19 research in the region. Social Sciences was the dominant theme on which funded projects focused whereas the priority areas with the least number of projects were research on 'animal and environmental health' and 'ethics considerations for research'. Our analyses show the diversity of funding sources for research on infectious diseases in the Asia-Pacific region. Engagement between multiple actors in the health research system is likely to promote enhanced coordination for greater research impact. GloPID-R's Asia-Pacific regional hub aims to support activities for the enhancement of preparedness for outbreaks of emerging infectious diseases in the region.


The endogenous Mtv-8 provirus resides within the V kappa locus.
The endogenous Mtv-8 provirus previously has been mapped within approximately 0.52 centimorgan from several V kappa markers on mouse chromosome 6. Using Southern blotting and DNA from a recombinant backcross mouse from the C57BL/6 (Mtv-8 positive) and C58 (Mtv-8 negative) strains, Mtv-8 was localized to the same side of the crossover point as immunoglobulin kappa (Ig kappa)-V24 but on the opposite side of the crossover from Ig kappa-V10 and Ig kappa-V21. Molecular cloning and characterization of cellular DNA adjacent to Mtv-8 revealed a functional V kappa 9 gene approximately 4.6 kb downstream and in the same transcriptional orientation as the provirus. These data suggest that Mtv-8 is within the centromere-proximal portion of the V kappa locus.


The role of Earth Observation (EO) technologies in supporting implementation of the Ramsar Convention on Wetlands.
Over one hundred wetland specialists and Earth Observation experts from around the world gathered at the European Space Agency's 'GlobWetland Symposium: Looking at wetlands from space' in Frascati, Italy, from 19 to 20 October, 2006. The aim of the Symposium was to stimulate discussion between the two communities by reviewing the latest developments in Earth Observation (EO) for the inventory, assessment and monitoring of wetlands and identify key scientific, technical and policy-relevant challenges for the future. The results provide an overview of the key areas of current research in the use of EO for mapping and managing wetlands, while also pointing out gaps that could hinder global inventory, assessment and monitoring of wetlands. This paper provides a summary of the main outputs with a focus on the role of EO technologies in supporting the implementation of the Ramsar Convention on Wetlands. The summary contains a qualitative analysis of the state of the art and considers possible directions and priorities for future research, development and application of EO-based technologies in wetland management. In this context we: 1) highlight those applications where EO technologies are ready for wider uptake by wetland managers, and provide suggestions for supporting such uptake; 2) indicate where EO technologies and applications currently in the research and development stages could potentially be useful in wetland management; and 3) provide recommendations for new research and development of EO technologies, that can be utilized to address aspects of wetland management not covered by the range of current EO applications.


Indirubin inhibits cell proliferation, migration, invasion and angiogenesis in tumor-derived endothelial cells.
Hepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC). Td-EC were derived from human umbilical vein endothelial cells (HUVEC) by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay. Td-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin's effects were weaker on HUVEC than Td-EC. Indirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis.


Methotrexate suppresses inflammatory agonist induced interleukin 6 synthesis in osteoblasts.
Interleukin 6 (IL-6) is a pleiotropic cytokine that plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). In bone metabolism, it is known that IL-6 is produced and secreted by osteoblasts, and that IL-6 induces osteoclast formation and stimulates bone resorption. Various bone inflammatory agonists such as tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, prostaglandin D2 (PGD2), PGE2, and PGF2alpha, which play important roles in the pathogenesis of RA, induce IL-6 synthesis in osteoblast-like MC3T3-E1 cells. Low dose methotrexate (MTX) is currently used for treatment of patients with RA. We investigated the effect of MTX on IL-6 synthesis induced by these agents in MC3T3-E1 cells. Cultured cells were pretreated with various doses of MTX, and then stimulated by these inflammatory agonists. The IL-6 in the conditioned medium was measured by IL-6 enzyme immunoassay. MTX significantly suppressed IL-6 synthesis stimulated by these agonists in a dose-dependent manner, although MTX alone had no effect on the levels of IL-6. In addition, MTX significantly inhibited the enhancement by IL-17 of TNF-alpha-stimulated IL-6 synthesis. MTX reduced the levels of IL-6 induced by 12-O-tetradecanoylphorbol 13-acetate, a direct activator of protein kinase C (PKC), suggesting that MTX inhibits PKC signals for IL-6 synthesis. MTX suppresses IL-6 synthesis stimulated by various inflammatory agonists in osteoblasts.


Effects of a drink containing creatine, amino acids, and protein combined with ten weeks of resistance training on body composition, strength, and anaerobic performance.
The purpose of this study was to examine the effects of a drink containing creatine, amino acids, and protein vs. a carbohydrate placebo on body composition, strength, muscular endurance, and anaerobic performance before and after 10 weeks of resistance training. Fifty-one men (mean +/- SD; age: 21.8 +/- 2.9 years) were randomly assigned to either the test drink (TEST; n = 23) or the placebo (PLAC; n = 28) and performed two 30-second Wingate Anaerobic Tests for determination of peak power (PP) and mean power (MP), were weighed underwater for percent body fat (%fat) and fat-free mass (FFM), and were tested for 1 repetition maximum (1RM) dynamic constant external resistance strength and muscular endurance (END; number of repetitions performed with 80% of 1RM) on the bilateral leg extension (LE) and free-weight bench press (BP) exercises. The testing was conducted before (PRE) and after (POST) 10 weeks of resistance training (3 sets of 10 repetitions with 80% of the subject's 1RM performed 3 times per week) on the LE and BP exercises. Body weight, FFM, LE 1RM, LE END, BP 1RM, and BP END increased (p < 0.05), whereas %fat decreased (p < 0.05) from PRE to POST for both the TEST and PLAC groups. Peak power and MP, however, increased for the TEST group, but not for the PLAC group. These results suggested that the creatine-, amino acid-, and protein-containing drink provided no additional benefits when compared with carbohydrates alone for eliciting changes in body composition, strength, and muscular endurance after a 10-week resistance training period. The TEST drink was, however, more effective than carbohydrates alone for improving anaerobic power production.


Action of the efferent vestibular system on primary afferents in the toadfish, Opsanus tau.
Spinalized toadfish were held in a lucite chamber and perfused through the mouth with running seawater. Primary vestibular afferents and vestibular efferent axons and somas were studied with glass microelectrodes. Vestibular semicircular canal afferent and efferent axons were visually identified and penetrated with glass microelectrodes. Afferents responded to pulses of injected current with trains of action potentials, whereas efferents responded with only a single spike. This differential response to injected current served to further distinguish these two classes of nerve fibers that share the same canal nerve for part of their course. When current pulses were injected into efferent somadendritic recording sites, cells responded with trains of action potentials similar to those seen in other central nervous system neurons. Semicircular canal afferents were spontaneously active and occupied the same spectrum of regularity as vestibular afferents recorded in other species. Behavioral arousal evoked by lightly touching the fish on the snout or over the eye resembled spontaneous arousal observed in the field and consisted of eye withdrawal, fin erection, and attempted swimming. Efferent vestibular neurons were spontaneously active and increased their frequency of discharge when the fish was behaviorally aroused. Most efferents were briskly activated by behavioral arousal, but the time constant of the decay of their responses was variable ranging from 100 to 600 ms. Not only touch, but multimodal stimuli were capable of increasing the level of spontaneous activity of efferent vestibular neurons. The shortest latency to behavioral activation was 160 ms. Vestibular primary afferents also manifested increase in neuronal activity with behavioral activation. Irregularly discharging afferents were much more responsive than regularly discharging afferents. One rare case of transient inhibition in a regularly discharging afferent is illustrated. Severing the efferent vestibular nerve blocked behavioral activation in vestibular primary afferents. Electrical stimulation of the efferent vestibular nerve produced excitatory postsynaptic potentials (EPSPs) at latencies within the monosynaptic range in vestibular primary afferents. These monosynaptic EPSPs could produce action potentials in primary afferents or could sum with subthreshold depolarizations produced by current passed through the microelectrode to initiate impulses.(ABSTRACT TRUNCATED AT 400 WORDS)


Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.
To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata. We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families. Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years; p < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years; p = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males. Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.


Role of self-efficacy and behaviour change.
Behaviour change is an important concept in relation to health promotion and disease prevention. Self-efficacy has been identified as an important determinant of health behaviour, future health behaviour and health behaviour change. In order to effectively facilitate behaviour change, it is essential that interventions are research based, and emphasize the utility of theory in practice. The effective practice of health promotion and disease prevention requires a full understanding of the processes of patient behaviour. This article presents the role of the nurse in influencing health-related behaviour change. Self-efficacy and related but distinct theories that underpin behaviour change are discussed. The empirical evidence that supports the link between self-efficacy and predictions of health behaviours is also examined.


The epidemiology of prostate cancer part I: descriptive epidemiology.
The incidence and mortality of prostate cancer is highly varied among populations and especially among blacks and whites. The incidence rates of all American populations have dramatically changed over the past 25 years. The recent increase in incidence has been attributed to prostate cancer screening. Although the incidence has increased over the past 25 years, the mortality rates although vastly different between populations have remained rather stable within populations. Prostate cancer is still a disease that primarily afflicts older men. The median age at diagnosis is 71 years for whites and 69 years for blacks. More than 80% are over the age of 65 years. Screening for prostate cancer has dramatically increased the number of men with local disease at diagnosis, but it is unclear whether screening and aggressive treatment have caused a decrease in mortality.


Adolescents' Perceptions of Harmfulness of Tobacco and Tobacco-like Products in Finland.
During the recent years, new tobacco and tobacco-like products, e.g., e-cigarettes, have emerged on the market. Adolescents often underestimate health risks in general, including those concerning tobacco. Little is known of adolescents' perceptions of health risks of the newer products. Our paper compares adolescents' perceptions of harmfulness of cigarettes, e-cigarettes, snus, water pipes, and nicotine in Finland, a country with a long history of strict tobacco control policy. Online surveys to nationally representative samples of 12-18-year-olds were conducted in 2017 and 2019, with 7578 answering the surveys. Only 3% of boys and 2% of girls did not agree that cigarettes are harmful to health. The percentages were slightly higher for snus (6% and 3%, respectively) and nicotine (12%, 8%) but much higher for e-cigarettes (30%, 22%) and water pipes (36%, 38%). Those who used the product, whose parents were smokers or had lower education, and whose school performance was lower, less often agreed with the harmful health effects of the products. Our results showed that adolescents understood the harmfulness of older tobacco products better than the harmfulness of the newer ones. Our results also showed the need to strengthen health education and fix adolescents' misperceptions of the health effects of the newer products.


Genetic nature of individual frailty: comparison of two approaches.
The traditional frailty models used in genetic analysis of bivariate survival data assume that individual frailty (and longevity) is influenced by thousands of genes, and that the contribution of each separate gene is small. This assumption, however, does not have a solid biological basis. It may just happen that one or a small number of genes makes a major contribution to determining the human life span. To answer the questions about the nature of the genetic influence on life span using survival data, models are needed that specify the influence of major genes on individual frailty and longevity. The goal of this paper is to test the nature of genetic influences on individual frailty and longevity using survival data on Danish twins. We use a new bivariate survival model with one major gene influencing life span to analyse survival data on MZ (monozygotic) and DZ (dizygotic) twins. The analysis shows that two radically different classes of model provide an equally good fit to the data. However, the asymptotic behaviour of some conditional statistics is different in models from different classes. Because of the limited sample size of bivariate survival data we cannot draw reliable conclusions about the nature of genetic effects on life span. Additional information about tails of bivariate distribution or risk factors may help to solve this problem.


Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance.
POT1 is a single-copy gene in yeast and humans that encodes a single-strand telomere binding protein required for chromosome end protection and telomere length regulation. In contrast, Arabidopsis harbors multiple, divergent POT-like genes that bear signature N-terminal OB-fold motifs, but otherwise share limited sequence similarity. Here, we report that plants null for AtPOT1 show no telomere deprotection phenotype, but rather exhibit progressive loss of telomeric DNA. Genetic analysis indicates that AtPOT1 acts in the same pathway as telomerase. In vitro levels of telomerase activity in pot1 mutants are significantly reduced and are more variable than wild-type. Consistent with this observation, AtPOT1 physically associates with active telomerase particles. Although low levels of AtPOT1 can be detected at telomeres in unsynchronized cells and in cells arrested in G2, AtPOT1 binding is significantly enhanced during S-phase, when telomerase is thought to act at telomeres. Our findings indicate that AtPOT1 is a novel accessory factor for telomerase required for positive telomere length regulation, and they underscore the coordinate and extraordinarily rapid evolution of telomere proteins and the telomerase enzyme.


Hypoxia-induced endothelial progenitor cell function is blunted in angiotensinogen knockout mice.
Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout (AGT(+/-)) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of AGT(+/-) EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in AGT(+/-) EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-1α and -2α were downregulated in AGT(+/-) early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-1α were suppressed in AGT(+/-) EPCs. In AGT(+/-) mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.


Quantifying the colour loss of green field pea (Pisum sativum L.) due to bleaching.
Post-harvest change in the colour of green field pea (Pisum sativum L.) is undesirable as this impacts the visual quality and market value of the seed. To date, there is no standard, objective method to determine bleaching. Therefore, the aim of this study was to develop an objective method for scoring bleaching based on colour reflectance spectra, measured both by spectrophotometer and multispectral Image Analysis (IA). Green field pea seeds were sorted into samples of uniform colour and these were used to train the model. Spectra calculated from multispectral images (with colour bands at 405,470,530,590,660 and 850nm) were matched to the spectrophotometer output through multiple linear regression. All spectra were transformed to emphasize the wavelength regions most impacted during bleaching, following which two critical reflectance values were scaled to a single bleaching score. The bleaching assessment method was tested in a time-course experiment comprising seeds from five green-pea genotypes stored for six months. Each sample was divided into two so that half of the seeds were stored in the dark and the remainder were exposed to controlled light to exaggerate bleaching. Throughout this period, the samples were imaged at six-weekly intervals. Assessment of bleaching by the IA method agreed well with spectrophotometer measurements, achieving a Lin's concordance statistic of 0.99 and 0.96 for the calibration and time-course samples respectively. The IA method proved more versatile because assessments could be made on individual seeds enabling the computation of bleaching uniformity within each sample. This method captured differences between genotypes in the extent, rate and uniformity of bleaching. All genotypes exhibited susceptibility to bleaching when stored under the controlled light conditions. Excell was observed to be the most susceptible genotype with the greatest bleaching-rate and OZB1308 displayed the most colour-stability.


Guidelines for the treatment of gout: a Swiss perspective.
Gout is a common condition and its management is suboptimal. A number of guidelines on the management of gout have been published in the last decade by professional societies with the aim of informing the physician of the recommended therapeutic strategies and the treatment options. We have tried to synthesize the current recommendations and to highlight some challenges that still need to be resolved in clinical practice in Switzerland.


Inoperable non-small-cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Report to the Medical Research Council by its Lung Cancer Working Party.
Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a randomised multicentre controlled trial. A total of 369 patients with inoperable, histologically or cytologically confirmed disease, too advanced for radical 'curative' radiotherapy, and with their main symptoms related to the primary intrathoracic tumour even if metastases were present, were studied. They were allocated at random either to a regimen of 17 Gy given in two fractions of 8.5 Gy 1 week apart (F2 regimen), or to a conventional multifractionated regimen of either 30 Gy in ten fractions or 27 Gy in six fractions (a biologically equivalent dose), given daily except at weekends (FM regimen). On admission, 93% of the patients had cough, 47% haemoptysis, 57% chest pain, 58% anorexia, and 11% dysphagia. As assessed by the clinicians, palliation of the main symptoms was achieved in high proportions of patients ranging in the F2 group from 65% for cough to 81% for haemoptysis and in the FM group from 56% for cough to 86% for haemoptysis. Haemoptysis, chest pain, and anorexia disappeared for a time in well over half the patients with these symptoms, and cough in 37%. For all the main symptoms, the median duration of palliation was 50% or more of survival. Performance status improved in approximately half of the patients with a poor status on admission. All these results were similar in the two treatment groups. As assessed daily by the patients using a diary card, the quality of life deteriorated slightly during treatment but then improved steadily during the next 5 weeks. The proportion of patients with dysphagia increased considerably during treatment, but fell to the pretreatment level during the next 2 weeks. The results were similar in the two groups. Radiation myelopathy was suspected in one (F2) patient. There was no difference in survival between the two groups (log-rank test), the median survival time from the date of allocation being 179 days in the F2 and 177 days in the FM group. In the light of all the findings, the regimen of two fractions of 8.5 Gy given 1 week apart is recommended.


Robotic thyroidectomy by a gasless unilateral axillo-breast or axillary approach: our early experiences.
Various endoscopic thyroidectomy procedures have been designed to minimize visible scarring. However, endoscopic thyroidectomies have some limitations in obtaining adequate surgical views and in the precise manipulations of the endoscopic instrument. Recently, robotic technology has been applied to thyroid surgery. The aim of this study was to determine the technical feasibility, intraoperative safety, and efficacy of robotic thyroidectomy. We analyzed 41 patients with thyroid nodules who underwent robot-assisted endoscopic thyroidectomy from October 2008 to August 2009 using a gasless unilateral axillo-breast or axillary approach with a da Vinci S Surgical System robot at Hanyang University Hospital, Seoul, Korea. We also compared the early surgical outcomes of robotic thyroidectomies with those of 167 patients who underwent conventional open thyroidectomies during the same period. In the robotic group, there were more female patients (P = 0.001) and the mean age was younger than that of the open thyroidectomy group (P < 0.001). The robotic thyroidectomy surgical procedure was completed successfully in all patients. Unilateral lobectomy was performed in 29 patients and total thyroidectomy was performed in 10 patients. The rate of central compartment neck dissection (CCND) for thyroid cancer was not different between the two groups (P = 0.127). The operative time was longer and the amount of drainage was higher in the robotic group than the open group (P < 0.001 and P = 0.002, respectively). The complication rate was not different between the two groups. The postoperative pain score of the neck and anterior chest was not different between the two groups except the anterior chest pain score at postoperative week 1. The cosmetic satisfaction was greater in the robotic group (P < 0.001). Robot-assisted endoscopic thyroidectomy by a gasless unilateral axillo-breast or axillary approach using a da Vinci S Surgical System robot is a safe, feasible, and cosmetically excellent procedure. It can be a promising alternative to endoscopic thyroidectomy or conventional open thyroidectomy.


Genetics of age-related macular degeneration: current concepts, future directions.
Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways.


How Different Electrolytes Can Influence the Aqueous Solution Behavior of 1-Ethyl-3-Methylimidazolium Chloride: A Volumetric, Viscometric, and Infrared Spectroscopy Approach.
The density, sound velocity, and viscosity of 1-ethyl-3-methylimidazolium chloride [C2mim]Cl in pure water and aqueous solutions of some electrolytes such as potassium chloride, potassium carbonate, and potassium phosphate (weight fraction of salt fixed at w s = 0. 11) have been measured over a wide range of temperatures from 298.15 to 318.15 K. The obtained experimental data have been used to compute various volumetric, compressibility, and viscometric parameters, e.g., apparent molar properties, limiting apparent molar and transfer properties. The co-sphere overlap model was employed to describe the dominant intermolecular interactions in the ternary solutions. Additionally, the structure making/breaking nature of the [C2mim]Cl in the ternary solutions has been discussed in terms of Hepler's constant and the temperature derivative of viscosity B-coefficient (dB/dT). The activation free energy of solvent and solute, activation enthalpy, and activation entropy have been calculated by the application of transition state theory. The calculated parameters have been interpreted in the sense of solvent-solute and solute-solute interactions. The Fourier transform infrared (FTIR) studies also have been done for the studied systems. Volumetric, acoustic, viscometric, and spectroscopic studies can render some evidence and help to understand the aqueous solution behavior of ionic liquids.


High-resolution three-dimensional imaging of red blood cells parasitized by Plasmodium falciparum and in situ hemozoin crystals using optical diffraction tomography.
We present high-resolution optical tomographic images of human red blood cells (RBC) parasitized by malaria-inducing Plasmodium falciparum (Pf)-RBCs. Three-dimensional (3-D) refractive index (RI) tomograms are reconstructed by recourse to a diffraction algorithm from multiple two-dimensional holograms with various angles of illumination. These 3-D RI tomograms of Pf-RBCs show cellular and subcellular structures of host RBCs and invaded parasites in fine detail. Full asexual intraerythrocytic stages of parasite maturation (ring to trophozoite to schizont stages) are then systematically investigated using optical diffraction tomography algorithms. These analyses provide quantitative information on the structural and chemical characteristics of individual host Pf-RBCs, parasitophorous vacuole, and cytoplasm. The in situ structural evolution and chemical characteristics of subcellular hemozoin crystals are also elucidated.


Risks, Benefits, and Effects on Management for Biopsy of the Papilla in Patients With Familial Adenomatous Polyposis.
Ampullary and duodenal cancer are the leading causes of death in patients with familial adenomatous polyposis (FAP) after colectomy has been performed. Risk of duodenal cancer is determined based on Spigelman stage (SS) of duodenal polyposis. Guidelines recommend endoscopic surveillance of the duodenum and visualization of the papilla to stage duodenal polyposis. There is no consensus on whether biopsies should be routinely collected from duodenal papilla and findings included in SS. Additionally, there are no data on the risk of pancreatitis after biopsy collection from papilla of patients with FAP. We studied the incidence of pancreatitis after biopsy of the papilla in patients with FAP and effects of biopsy findings on SS. We identified consecutive patients with FAP at a single center from January 2011 through December 2018 with ≥1 endoscopy with biopsy of the papilla. Patients with history of foregut surgery were excluded. We identified 273 patients with FAP who had biopsies collected from papilla over 792 EGDs, with 1-8 independent exams with biopsy per patient. We collected demographic, endoscopic, and histology data from patients and calculated SS with vs without biopsy findings. Post-procedural pancreatitis was defined by 2 of the following: abdominal pain, lipase level 3-fold the upper limit of normal, or radiography findings consistent with pancreatitis within 7 days of esophagogastroduodenoscopy (EGD). Pancreatitis developed in 2 patients (0.73%): 1 after biopsy of a normal-appearing papilla and 1 after biopsy of an abnormal appearing papilla. Inclusions of biopsy data increased SS in 36 patients (13.2%), with consideration of prophylactic duodenectomy for 3.3%. Pancreatitis after biopsy of the duodenal papilla is rare. Histology data obtained from biopsy of the papilla in patients with FAP can change SS and affect patient management.


Management considerations in the care of elderly heart failure patients in long-term care facilities.
Heart failure, a condition that affects up to 20% of older persons residing in long-term care facilities, is an important cause of morbidity, health service utilization and death. Effective and interprofessional heart failure care processes could potentially improve care, outcomes and quality of life and delay decline or hospital admission. This article reviews the clinical aspects of heart failure, and the challenges to the diagnosis and management of this condition in long-term care residents who are frail and are affected by multiple comorbidities.


Atypical retinitis proliferans, retinal telangiectasis, and vitreous hemorrhage in a patient with tuberous sclerosis.
This report describes an unusual case of recurrent vitreous hemorrhage and atypical retinal neovascularization in a patient with tuberous sclerosis. During three years of observation, the patient also developed retinal telangiectasis with macular edema and lipid exudation. Although the patient did not have an obvious astrocytic hamartoma, a diffuse, flat retinal hamartoma within the nerve fiber layer was suspected.


Minimally invasive costotransversectomy for the resection of large thoracic dumbbell tumors.
Due to their important size and complex localization, the management of thoracic dumbbell tumors is challenging, frequently requiring the need for an anterior approach. Our study aims to first report the feasibility and safety of a single-stage posterior minimally invasive procedure in achieving complete resection of voluminous thoracic dumbbell tumors. We retrospectively reviewed the medical records of five consecutive patients, who underwent the minimally invasive resection of a type III thoracic dumbbell tumor in our institution between March 2007 and March 2012. There were two men and three women, with a mean age at diagnosis of 57 years (range 41-68 years). After the placement of a non-expandable tubular retractor under fluoroscopic control, a costotransversectomy was achieved. By moving the retractor in all directions, the tumor was largely exposed and resected with the cavitron ultrasonic surgical aspirator. Clinical and radiological monitoring was performed before discharge, at 6 months, 1 year and 2 years. No major intraoperative complication was reported. Gross total resection was achieved in four patients. The mean operative time was 219 mins (range 75-540 mins) and the mean estimated blood loss was 230 ml (range 50-500 ml). No postoperative complication was reported. The mean length of hospital stay was 3.6 days (range 2-6 days) and all patients were discharged home. Histological analysis confirmed the diagnosis of grade 1 schwannoma in four patients and revealed a hemangiopericytoma in one patient. No tumor recurrence was noted with a mean follow up period of 46 months (range 32-54 months). Thoracic dumbbell tumors can be safely and completely resected using a single-stage minimally invasive procedure. The costotransversectomy can be performed through a non-expandable retractor allowing sufficient access to all parts of the tumor.


Investigating the Heterogeneous Ice Nucleation of Sea Spray Aerosols Using Prochlorococcus as a Model Source of Marine Organic Matter.
Sea spray is the largest aerosol source on Earth. Bubble bursting mechanisms at the ocean surface create smaller film burst and larger jet drop particles. This study quantified the effects of particle chemistry on the depositional ice nucleation efficiency of laboratory-generated sea spray aerosols under the cirrus-relevant conditions. Cultures of Prochlorococcus, the most abundant phytoplankton species in the global ocean, were used as a model source of organic sea spray aerosols. We showed that smaller particles generated from lysed Prochlorococcus cultures are organically enriched and nucleate more effectively than larger particles generated from the same cultures. We then quantified the ice nucleation efficiency of single component organic molecules that mimic Prochlorococcus proteins, lipids, and saccharides. Amylopectin, agarose, and aspartic acid exhibited similar critical ice saturations, fractional activations, and ice nucleation active site number densities to particles generated from Prochlorococcus cultures. These findings indicate that saccharides and proteins with numerous and well-ordered hydrophilic functional groups may determine the ice nucleation abilities of organic sea spray aerosols.


FertDish: microfluidic sperm selection-in-a-dish for intracytoplasmic sperm injection.
The selection of high quality sperm is critical for intracytoplasmic sperm injection (ICSI), a prevalent assisted reproduction technology. However, standard selection methods are time-consuming and fail to recover the most viable sperm, thereby limiting the ICSI success rate. Microfluidics enables rapid selection of viable sperm in a manner representing in vivo processes, however, existing platforms lack clinical applicability. Here, we present FertDish, which integrates the clinically established ICSI Petri dish with a film featuring an array of sperm-selecting microchannels for selection of sperm directly from semen. The FertDish format mimics the clinician-familiar ICSI dish setup, and provides rapid (<10 min) single stage sperm preparation that circumvents standard labour-intensive multi-stage sperm processing steps. Tests with human donor and patient semen samples show that FertDish enables the selection of a high quality sperm sub-population, featuring improvements in DNA fragmentation index of more than 91% (donor) and 74% (patient) versus raw semen and 50% (donor) and 63% (patient) versus standard methods, and a distribution of more than 97% sperm with viable and high level DNA. The FertDish enables a high sperm recovery rate (>3.3 × 105 sperm per mL), and is readily adaptable to the clinical workflow with potential to improve ICSI outcomes.


Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth.
The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese medicine, were separately discovered in pathological intestinal tissues. However, whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the present study, we found that berberine effectively inhibited colitis-associated tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium (DSS)-treated ApcMin/+ mice. A mechanistic study identified that these inhibitory effects of berberine occurred through blocking interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression in colonic macrophages. An in vitro study on cell lines identified that berberine treatment of Raw 264.7 macrophages resulted in conditioned media with fewer proliferative effects on a cell line with a heterozygous Apc mutation (Immorto-Min colonic epithelium, IMCE). EGFR-ERK signaling act downstream of berberine/pro-inflammatory cytokines axis to regulate CACRC cell proliferation. Furthermore, in vivo administration of IL-6 to DSS-treated ApcMin/+ mice effectively weakened the inhibitory effects of berberine on tumorigenesis and EGFR-ERK signaling in colon tissues. Altogether, the results of our studies have revealed that berberine inhibits the development of CACRC by interfering with inflammatory response-driven EGFR signaling in tumor cell growth. The findings of this study support the possibility that berberine and other anti-inflammatory drugs may be beneficial in the treatment of CACRC.


Cloning and transcriptional expression of a leucokinin-like peptide receptor from the southern cattle tick, Boophilus microplus (Acari: Ixodidae).
Leucokinins are invertebrate neuropeptides that exhibit myotropic and diuretic activity. Only one leucokinin-like peptide receptor is known, the lymnokinin receptor from the mollusc Lymnaea stagnalis. A cDNA encoding a leucokinin-like peptide receptor was cloned from the Southern cattle tick, Boophilus microplus, a pest of cattle world-wide. This is the first neuropeptide receptor known from the Acari and the second known in the subfamily of leucokinin-like peptide G-protein-coupled receptors. The deduced amino acid sequence exhibits 40% identity to the lymnokinin receptor. The receptor transcript is present in all tick life stages as determined by semiquantitative reverse transcription polymerase chain reaction. We also propose that the sequence AAF50775.1 from the Drosophila melanogaster genome (CG10626) encodes the first identified insect leucokinin receptor.


Neurologic Injury in Patients Treated With Extracorporeal Membrane Oxygenation for Postcardiotomy Cardiogenic Shock.
To investigate the frequency, predictors, and outcomes of neurologic injury in adults treated with postcardiotomy extracorporeal membrane oxygenation (PC-ECMO). A retrospective multicenter registry study. Twenty-one European institutions where cardiac surgery is performed. A total of 781 adult patients who required PC-ECMO during 2010 to 2018 were divided into patients with neurologic injury (NI) and patients without neurologic injury (NNI). Baseline and operative data, in-hospital outcomes, and long-term survival were compared between the NI and the NNI groups. Predictors of neurologic injury were identified. A subgroup analysis according to the type of neurologic injury was performed. Overall, NI occurred in 19% of patients in the overall series, but the proportion of patients with NI ranged from 0% to 65% among the centers. Ischemic stroke occurred in 84 patients and hemorrhagic stroke in 47 patients. Emergency procedure was the sole independent predictor of NI. In-hospital mortality was higher in the NI group than in the NNI group (79% v 61%, p < 0.001). The one-year survival was lower in the NI group (17%) compared with the NNI group (37%). Long-term survival did not differ between patients with ischemic stroke and those with hemorrhagic stroke. Neurologic injury during PC-ECMO is common and associated with a dismal prognosis. There is considerable interinstitutional variation in the proportion of neurologic injury in PC-ECMO-treated adults. Well-known risk factors for stroke are not associated with neurologic injury in this setting.


Rapid Body Color Change Provides Lizards with Facultative Crypsis in the Eyes of Their Avian Predators.
AbstractColor change serves many antipredator functions and may allow animals to better match environments or disrupt outlines to prevent detection. Rapid color change could potentially provide camouflage to animals that frequently move among microhabitats. Determining the adaptiveness of whole-animal rapid color changes in natural habitats with respect to predator visual systems would greatly broaden our fundamental understanding of the evolution of rapid color change. We tested whether whole-body color change provides water anoles (Anolis aquaticus) with camouflage against avian predators and whether these rapid changes allow them to shift between environment matching and edge disruption. We manipulated A. aquaticus placement in natural microhabitats and used digital image analysis to quantify color matching, pattern matching, and edge disruption produced by microhabitat-induced color change. Color change reduced lizard detectability to predators in microhabitat-specific ways. Environment matching was favored when lizards were in solid-colored microhabitats, regardless of exposure to predators. Edge disruption was instead induced by high exposure and varied by body region. We provide the first evidence that rapid color change permits a tetrapod to flexibly employ the most optimal camouflaging strategy by form (e.g., color matching vs. edge disruption) to minimize detection in the eyes of its predators.


Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study.
Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies. To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects. A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed. The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25-1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses. The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT. Chinese Clinical Trial Registry: ChiCTR1900026294.


Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells by inducing a neuronal nitric oxide synthase.
Nitric oxide (NO) has been considered to play an important role in the regulation of blood flow, mucosal integrity, and mucus production in the stomach. We investigated the stimulatory actions of epidermal growth factor (EGF) and a cytoprotective compound, geranylgeranylacetone (GGA), on mucin synthesis in guinea pig gastric pre-pit cells, maintained in a serum-free culture system. GGA increased [3H]glucosamine uptake and the accumulation of mucus granules positive for galactose oxidase-Schiff reaction in the cells. This stimulatory action of GGA was equivalent to that of EGF, but GGA did not stimulate the cell growth. Both EGF and GGA increased the release of NO degeneration products, NO2- and NO3-. The [3H]glucosamine uptake was completely inhibited by the non-selective NO synthase (NOS) inhibitors, N(G)-nitro-L-arginine and N(G)-monomethyl-L-arginine, and it was only partially inhibited by a more selective inhibitor for inducible NOS isoform (iNOS), aminoguanidine. Northern blotting with a cDNA probe for rat iNOS, and Western blotting with a polyclonal antibody against iNOS, demonstrated that GGA did not up-regulate the iNOS mRNA expression nor induce its protein. In contrast, GGA and EGF induced neuronal NOS, but not endothelial NOS, which was confirmed by immunoblot analyses with antibodies against these constitutive NOS isoforms. Thus, the present experiments suggests that GGA, as well as EGF, stimulates mucin synthesis at least in part through an NO-dependent pathway, leading to an increase in the integrity of the gastric mucosa.


Burnout in US hematologists and oncologists: impact of compensation models and advanced practice provider support.
Burnout is prevalent throughout medicine. Few large-scale studies have examined the impact of physician compensation or clinical support staff on burnout among hematologists and oncologists. In 2019, the American Society of Hematology conducted a practice survey of hematologists and oncologists in the AMA (American Medical Association) Masterfile; burnout was measured using a validated, single-item burnout instrument from the Physician Work-Life Study, while satisfaction was assessed in several domains using a 5-point Likert scale. The overall survey response rate was 25.2% (n = 631). Of 411 respondents with complete responses in the final analysis, 36.7% (n = 151) were from academic practices and 63.3% (n = 260) from community practices; 29.0% (n = 119) were female. Over one-third (36.5%; n = 150) reported burnout, while 12.0% (n = 50) had a high level of burnout. In weighted multivariate logistic regression models incorporating numerous variables, compensation plans based entirely on relative value unit (RVU) generation were significantly associated with high burnout among academic and community physicians, while the combination of RVU + salary compensation showed no significant association. Female gender was associated with high burnout among academic physicians. High advanced practice provider utilization was inversely associated with high burnout among community physicians. Distinct patterns of career dissatisfaction were observed between academic and community physicians. We propose that the implementation of compensation models not based entirely on clinical productivity increased support for women in academic medicine, and expansion of advanced practice provider support in community practices may address burnout among hematologists and oncologists.


An overview of gibberellin metabolism enzyme genes and their related mutants in rice.
To enhance our understanding of GA metabolism in rice (Oryza sativa), we intensively screened and identified 29 candidate genes encoding the following GA metabolic enzymes using all available rice DNA databases: ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA 20-oxidase (GA20ox), GA 3-oxidase (GA3ox), and GA 2-oxidase (GA2ox). In contrast to the Arabidopsis genome, multiple CPS-like, KS-like, and KO-like genes were identified in the rice genome, most of which are contiguously arranged. We also identified 18 GA-deficient rice mutants at six different loci from rice mutant collections. Based on the mutant and expression analyses, we demonstrated that the enzymes catalyzing the early steps in the GA biosynthetic pathway (i.e. CPS, KS, KO, and KAO) are mainly encoded by single genes, while those for later steps (i.e. GA20ox, GA3ox, and GA2ox) are encoded by gene families. The remaining CPS-like, KS-like, and KO-like genes were likely to be involved in the biosynthesis of diterpene phytoalexins rather than GAs because the expression of two CPS-like and three KS-like genes (OsCPS2, OsCPS4, OsKS4, OsKS7, and OsKS8) were increased by UV irradiation, and four of these genes (OsCPS2, OsCPS4, OsKS4, and OsKS7) were also induced by an elicitor treatment.


Measles immunity and immunization in developing countries of Africa: a review.
Although an effective vaccine against measles has been available for several years, the disease is still prevelant in Africa. The disease is characterized by its occurrence in younger age groups and high morbidity and mortality. The African child is born with a high transplacentally acquired measles antibody level. However, the antibody declines rapidly, so that it is virtually absent after the age of 6 months. The measles vaccine with which the African child is immunized is of reduced potency because of poor storage and transportation facilities and the adverse effect of tropical climate on the vaccine. The pattern of measles immunity in Africa is different from that in developed countries. Measles immunization schedule in Africa, as in any other part of the world, must be based on sound epidemiological and serological data.


Chromosomes trapped in micronuclei are liable to segregation errors.
DNA in micronuclei is likely to get damaged. When shattered DNA from micronuclei gets reincorporated into the primary nucleus, aberrant rearrangements can take place, a phenomenon referred to as chromothripsis. Here, we investigated how chromatids from micronuclei act in subsequent divisions and how this affects their fate. We observed that the majority of chromatids derived from micronuclei fail to establish a proper kinetochore in mitosis, which is associated with problems in chromosome alignment, segregation and spindle assembly checkpoint activation. Remarkably, we found that, upon their formation, micronuclei already display decreased levels of important kinetochore assembly factors. Importantly, these defects favour the exclusion of the micronucleus over the reintegration into the primary nucleus over several divisions. Interestingly, the defects observed in micronuclei are likely overcome once micronuclei are reincorporated into the primary nuclei, as they further propagate normally. We conclude that the formation of a separate small nuclear entity represents a mechanism for the cell to delay the stable propagation of excess chromosome(s) and/or damaged DNA, by inducing kinetochore defects.


Pathogen prevalence predicts human cross-cultural variability in individualism/collectivism.
Pathogenic diseases impose selection pressures on the social behaviour of host populations. In humans (Homo sapiens), many psychological phenomena appear to serve an antipathogen defence function. One broad implication is the existence of cross-cultural differences in human cognition and behaviour contingent upon the relative presence of pathogens in the local ecology. We focus specifically on one fundamental cultural variable: differences in individualistic versus collectivist values. We suggest that specific behavioural manifestations of collectivism (e.g. ethnocentrism, conformity) can inhibit the transmission of pathogens; and so we hypothesize that collectivism (compared with individualism) will more often characterize cultures in regions that have historically had higher prevalence of pathogens. Drawing on epidemiological data and the findings of worldwide cross-national surveys of individualism/collectivism, our results support this hypothesis: the regional prevalence of pathogens has a strong positive correlation with cultural indicators of collectivism and a strong negative correlation with individualism. The correlations remain significant even when controlling for potential confounding variables. These results help to explain the origin of a paradigmatic cross-cultural difference, and reveal previously undocumented consequences of pathogenic diseases on the variable nature of human societies.


Differential loss of components of traditional ecological knowledge following a primate extinction event.
Traditional ecological knowledge (TEK), an important component of the modern conservation toolkit, is being eroded in indigenous communities around the world. However, the dynamics of TEK loss in response to ecosystem change and disruption to social-ecological systems, and patterns of variation in vulnerability and resilience of different components of TEK, remain poorly understood. The Hainan gibbon (Nomascus hainanus), a culturally significant primate, was formerly distributed across Hainan Island, China, but became extinct across most of this range within living memory and is now restricted to a single landscape, Bawangling National Nature Reserve. Gibbon-specific TEK (including folktales, natural history information and methods of gibbon exploitation) is still present in indigenous communities across seven Hainanese landscapes, but statistically significant differences in TEK content exist between landscapes with different histories of gibbon persistence: respondents from Bawangling and most landscapes that have recently lost gibbons report more gibbon-related folktales compared with landscapes from which gibbons have been absent for several decades. Species-specific folktales might have been lost more rapidly compared with other components of TEK because older community members are typically the 'cultural repositories' of stories, whereas knowledge about practical interactions with biodiversity might be shared more widely with younger community members.


Dual Myelomeningoceles in Twins: Case Report, Review, and Insights for Etiology.
Despite folate supplementation, neural tube defects (NTDs) still occur in 0.5-1.0/1,000 pregnancies, with 30-50% not preventable with folate. Twinning has increased due to artificial fertilization and in itself predisposes to NTDs at a rate of 1.6/1,000. The contributions of genetic and environmental factors to myelomeningocele development remain poorly understood. Expression patterns of congenital pathologies in twins can sometimes provide etiological insight. Concordance of NTDs in twins is 0.03/1,000, with dual myelomeningocele reported in only 23 pairs, only one of which survived. We present the 24th pair, the 1st to maintain lower extremity motor function. We review all prior cases and discuss implications of twin concordance on the interplay of genetic and environmental influences. Case Report and Review: A new case of female monozygotic twins born to a well-nourished 24-year-old female is reported with details of perioperative care. Prenatal ultrasound showed L3-S4 and L5-S4 myelomeningoceles, Chiari II malformations, and ventriculomegaly. Copy number microarray was unrevealing. Each underwent uncomplicated repair on day of life 1, and ventriculoperitoneal shunt placement on days of life 10 and 16. Both had movement in the legs upon 6-week follow-up. All prior reported cases of concordant twin myelomeningoceles were abstracted and analyzed, revealing persistence of occurrence despite folate supplementation and a majority occurring in dizygotic pairs. The literature is also reviewed to summarize current knowledge of myelomeningocele pathophysiology as it relates to genetic and environmental influences. Meticulous surgical and perioperative care allowed for early positive outcomes in each twin. However, etiopathogenesis remains elusive. In general, only of a minority of cases have underlying genetic lesions or clear environmental triggers. Concordance in monozygotic twins argues for a strong genetic influence; yet, literature review reveals a higher rate of concordant dizygotic twins. This, along with the observation of differing resultant phenotypes in monozygotic twins as seen in this case, prompts further investigation into nonfolate environmental influences. While efforts in genetic investigation should continue, the role of teratogens and exposures should not be minimized in research efforts, public health, and family counseling. Clinical genetic testing remains of limited utility in the majority of patients until more is known.


Chirally-coupled-core Yb-fiber laser delivering 80-fs pulses with diffraction-limited beam quality warranted by a high-dispersion mirror based compressor.
We demonstrate a high-energy femtosecond laser system that incorporates two rapidly advancing technologies: chirally-coupled-core large-mode-area Yb-fiber to ensure fundamental-mode operation and high-dispersion mirrors to enable loss-free pulse compression while preserving the diffraction-limited beam quality. Mode-locking is initiated by a saturable absorber mirror and further pulse shortening is achieved by nonlinear polarization evolution. Centered at 1045 nm with 39-MHz repetition rate, the laser emits 25-nJ, positively chirped pulses with 970-mW average power. 6 bounces from double-chirped-mirrors compress these pulses down to 80 fs, close to their transform-limited duration. The loss-free compression gives rise to a diffraction-limited optical beam (M2 = 1.05).


SOX9 as a Predictor for Neurogenesis Potentiality of Amniotic Fluid Stem Cells.
Preclinical studies of amniotic fluid-derived cell therapy have been successful in the research of neurodegenerative diseases, peripheral nerve injury, spinal cord injury, and brain ischemia. Transplantation of human amniotic fluid stem cells (AFSCs) into rat brain ventricles has shown improvement in symptoms of Parkinson's disease and also highlighted the minimal immune rejection risk of AFSCs, even between species. Although AFSCs appeared to be a promising resource for cell-based regenerative therapy, AFSCs contain a heterogeneous pool of distinct cell types, rendering each preparation of AFSCs unique. Identification of predictive markers for neuron-prone AFSCs is necessary before such stem cell-based therapeutics can become a reality. In an attempt to identify markers of AFSCs to predict their ability for neurogenesis, we performed a two-phase study. In the discovery phase of 23 AFSCs, we tested ZNF521/Zfp521, OCT6, SOX1, SOX2, SOX3, and SOX9 as predictive markers of AFSCs for neural differentiation. In the validation phase, the efficacy of these predictive markers was tested in independent sets of 18 AFSCs and 14 dental pulp stem cells (DPSCs). We found that high expression of SOX9 in AFSCs is associated with good neurogenetic ability, and these positive correlations were confirmed in independent sets of AFSCs and DPSCs. Furthermore, knockdown of SOX9 in AFSCs inhibited their neuronal differentiation. In conclusion, the discovery of SOX9 as a predictive marker for neuron-prone AFSCs could expedite the selection of useful clones for regenerative medicine, in particular, in neurological diseases and injuries.


Human Leukocyte Antigen Class II associations in late-onset Myasthenia Gravis.
Genetic factors predisposing to late-onset myasthenia gravis (LOMG) have not been clearly defined yet. However, genome-wide association studies identified Human Leukocyte Antigen (HLA) Class II alleles as a hotspot in this disease subtype. The aim of this study was to analyze the correlations of HLA Class II alleles with clinical data and titin antibodies in this patient subgroup. This study consecutively enrolled anti-acetylcholine receptor antibody-positive, non-thymoma patients with generalized LOMG. All patients were of Italian ancestry. HLA-DRB1 and -DQB1 genotyping and serum titin antibody testing were performed in this population. A total of 107 patients (females: 28/107, 26.2%; median age of onset: 68 years, range: 50-92) were included. We found a positive association with HLA-DRB1*07 (P = 1.1 × 10-5 ), HLA-DRB1*14 (P = 0.0251) and HLA-DQB1*02 (P = 0.0095). HLA-DRB1*03, HLA-DRB1*11, and HLA-DQB1*03 were protective alleles (P = 7.9 × 10-5 , P = 0.0104, and P = 0.0067, respectively). By conditional haplotype analysis, HLA-DRB1*07-DQB1*02 was found to be the major risk haplotype (OR = 4.10; 95% C.I.: 2.80-5.99; P = 6.01 × 10-11 ). The mean age at onset was 73.4 years in DRB1*07 homozygotes, 69.7 years in heterozygotes, and 66.6 in non-carriers (P = 0.0488). DRB1*07 carriers and non-carriers did not differ in disease severity and response to therapy. Titin antibodies were detected in 61.4% of the cases, having no association with HLA alleles or specific clinical characteristics. In our study, we identified the HLA DRB1*07-DQB1*02 haplotype as a predisposing factor for the development of generalized LOMG in the Italian population.