A central role for intermolecular dityrosine cross-linking of fibrinogen in high molecular weight advanced oxidation protein product (AOPP) formation.
Advanced oxidation protein products (AOPPs) are dityrosine cross-linked and carbonyl-containing protein products formed by the reaction of plasma proteins with chlorinated oxidants, such as hypochlorous acid (HOCl). Most studies consider human serum albumin (HSA) as the main protein responsible for AOPP formation, although the molecular composition of AOPPs has not yet been elucidated. Here, we investigated the relative contribution of HSA and fibrinogen to generation of AOPPs. AOPP formation was explored by SDS-PAGE, under both reducing and non-reducing conditions, as well as by analytical gel filtration HPLC coupled to fluorescence detection to determine dityrosine and pentosidine formation. Following exposure to different concentrations of HOCl, HSA resulted to be carbonylated but did not form dityrosine cross-linked high molecular weight aggregates. Differently, incubation of fibrinogen or HSA/fibrinogen mixtures with HOCl at concentrations higher than 150 μM induced the formation of pentosidine and high molecular weight (HMW)-AOPPs (>200 k Da), resulting from intermolecular dityrosine cross-linking. Dityrosine fluorescence increased in parallel with increasing HMW-AOPP formation and increasing fibrinogen concentration in HSA/fibrinogen mixtures exposed to HOCl. This conclusion is corroborated by experiments where dityrosine fluorescence was measured in HOCl-treated human plasma samples containing physiological or supra-physiological fibrinogen concentrations or selectively depleted of fibrinogen, which highlighted that fibrinogen is responsible for the highest fluorescence from dityrosine. A central role for intermolecular dityrosine cross-linking of fibrinogen in HMW-AOPP formation is shown. These results highlight that oxidized fibrinogen, instead of HSA, is the key protein for intermolecular dityrosine formation in human plasma.


Liquid storage of miniature boar semen.
The effects of liquid storage at 15 degrees C on the fertilizing ability of miniature pig semen were investigated. Characterization of ejaculated semen from 3 miniature boars was carried out. Semen volume and pH were similar among these boars. In one of the boars, sperm motility was slightly low, and sperm concentration and total number of sperm were significantly lower than in the others (P < 0.01). Seminal plasma of the semen was substituted with various extenders (Kiev, Androhep, BTS and Modena) by centrifugation and semen was stored for 7 days at 15 degrees C. Sperm motility was estimated daily at 37 degrees C. For complete substitution of seminal plasma, Modena was significantly more efficient than the other extenders (P < 0.001) in retaining sperm motility. Semen from each of the 3 miniature boars that had been stored for 5 to 7 days at 15 degrees C in Modena was used for artificial insemination of 15 miniature sows. The farrowing rates were 100, 100 and 60%, and litter sizes were 6.4 +/- 1.5, 5.8 +/- 0.8 and 5.0 +/- 1.0 for each boar semen, respectively. The boar that sired the smallest farrowing rate was the same one that showed lower seminal quality with respect to sperm motility, sperm concentration and total number of sperm. These results suggest that miniature boar semen can be stored for at least 5 days at 15 degrees C by the substitution of seminal plasma with Modena extender.


Body mass index is associated with dietary patterns and health conditions in georgia centenarians.
Associations between body mass index (BMI) and dietary patterns and health conditions were explored in a population-based multiethnic sample of centenarians from northern Georgia. BMI ≤20 and ≥25 was prevalent in 30.9% and 25.3% of study participants, respectively. In a series of logistic regression analyses controlled for gender and place of residence, the probability of having BMI ≥25 was increased by being black versus white and having a low citrus fruit, noncitrus fruit, orange/yellow vegetable or total fruit and vegetable intake. The probability of having BMI ≤20 was not associated with dietary intake. When controlled for race, gender, residence, and total fruit and vegetable intake, BMI ≥25 was an independent risk factor for diabetes or having a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, whereas BMI ≤20 was a risk factor for anemia. Given the many potential adverse consequences of under- and overweight, efforts are needed to maintain a healthy weight, even in the oldest old.


A Noninvasive, Electromagnetic, Epidermal Sensing Device for Hemodynamics Monitoring.
Non-intrusive monitoring of blood flow parameters is vital for obtaining physiological and pathophysiological information pertaining to dynamic cardiovascular events and is feasible to achieve via non-invasive, conformal, wearable technologies. Here, we present a proof-of-concept of a fully integrated, high frequency (bandwidth 40 MHz), electromagnetic sensing device for monitoring limb hemodynamics and morphology associated with blood flow. The sensing architecture integrates a novel radio frequency (RF) skin patch resonator embedded with a coplanar outer loop antenna and a scalable, standalone wireless readout hardware based on standing wave ratio (SWR) bridge. The resonator itself is a copper-based open circuit planar Archimedean spiral with a rectangular cross-sectional area, chemically etched on a flexible polyimide substrate. The readout hardware is developed exploiting off-the-shelf components, fabricated on the top of a rigid FR4 substrate. The proposed readout circuit can measure resonant frequency of an RLC network. When energized by the external oscillating RF field via loop antenna, the resonator produces an electromagnetic field response which can be perturbed by dielectric variation inside its field boundary. Through leveraging this principle, the in-vitro experimental results from the benchtop models suggest that the resonator's RF attributes such as resonant frequency shift and magnitude variation of reflection coefficient due to fluid volume displacement can be successfully detected through the proposed hardware architecture. Hence, the system could be an alternative to the conventional, multimodal, non-invasive wearable sensing with an unprecedented capability of ubiquitous fluid phenomena detection from multiple sites of the human body.


Anemonefish oxygenate their anemone hosts at night.
Many stony coral-dwelling fishes exhibit adaptations to deal with hypoxia among the branches of their hosts; however, no information exists on the respiratory ecophysiology of obligate fish associates of non-coral organisms such as sea anemones and sponges. This study investigated metabolic and behavioral interactions between two-band anemonefish (Amphiprion bicinctus) and bulb-tentacle sea anemones (Entacmaea quadricolor) at night. We measured the net dark oxygen uptake ( , μmol O2 h(-1)) of fish-anemone pairs when partners were separate from each other, together as a unit, and together as a unit but separated by a mesh screen that prevented physical contact. We also measured the effects of water current on sea anemone and quantified the nocturnal behaviors of fish in the absence and presence of host anemones in order to discern the impacts of anemone presence on fish behavior. Net of united pairs was significantly higher than that of both separated pairs and united pairs that were separated by a mesh screen. Anemone increased with flow rate from 0.5 to 2.0 cm s(-1), after which remained constant up to a water flow rate of 8.0 cm s(-1). Furthermore, the percentage time and bout frequency of flow-modulating behaviors by fish increased significantly when anemones were present. We conclude that physical contact between anemonefish and sea anemones elevates the of at least one of the partners at night, and anemonefish behavior at night appears to oxygenate sea anemone hosts and to augment the metabolism of both partners.


Understanding the Mechanism of Social Attachment Role in Social Media: A Qualitative Analysis.
Qualitative research method was used to explore the formation and development of the attachment relationship between users and social media in the process of using social media. Based on the attachment theory, this study selected three representative social media platforms, namely, TikTok, WeChat, and MicroBlog, as theoretical samples, and this study adopted NVivo12.0 to root, theorize, and construct the original data. Research shows that users are stimulated by co-creation value to stimulate changes in their psychological needs and self-expression, leading to the formation of social attachment. Among them, user participation is a prerequisite for driving the occurrence of co-creation value, creating a continuous-use scenario for the attachment relationship between individuals and social media. Further, psychological needs and self-expression play mediating roles between co-creation of value and social attachment and promote the occurrence of personal belonging to software platforms. The findings of this research better our understandings about the mechanism of developing social attachment from continuous use of social media and offer practical implications for commercial uses of social media platforms.


Design of metal-dielectric grating lasers only supporting surface-wave-like modes.
We present a prototype of semiconductor lasers with plasmonic periodic structures that only support transverse-magnetic modes at telecommunication wavelengths. The structure does not sustain transverse-electric guided modes which are irrelevant to surface-wave-enhanced applications, and lasing modes must be surface-wave-like. With thin low-index dielectric buffers near the metal surface, the threshold gain is kept at a decent level around the photonic band edge. Thin windows are then opened on the metal surface to let out significant surface fields. This facilitates usages of surface waves for the spectroscopy and sensing.


Histological Correlates of Diffusion-Weighted Magnetic Resonance Microscopy in a Mouse Model of Mesial Temporal Lobe Epilepsy.
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy. It is frequently associated with abnormal MRI findings, which are caused by underlying cellular, structural, and chemical changes at the micro-scale. In the current study, it is investigated to which extent these alterations correspond to imaging features detected by high resolution magnetic resonance imaging in the intrahippocampal kainate mouse model of MTLE. Fixed hippocampal and whole-brain sections of mouse brain tissue from nine animals under physiological and chronically epileptic conditions were examined using structural and diffusion-weighted MRI. Microstructural details were investigated based on a direct comparison with immunohistochemical analyses of the same specimen. Within the hippocampal formation, diffusion streamlines could be visualized corresponding to dendrites of CA1 pyramidal cells and granule cells, as well as mossy fibers and Schaffer collaterals. Statistically significant changes in diffusivities, fractional anisotropy, and diffusion orientations could be detected in tissue samples from chronically epileptic animals compared to healthy controls, corresponding to microstructural alterations (degeneration of pyramidal cells, dispersion of the granule cell layer, and sprouting of mossy fibers). The diffusion parameters were significantly correlated with histologically determined cell densities. These findings demonstrate that high-resolution diffusion-weighted MRI can resolve subtle microstructural changes in epileptic hippocampal tissue corresponding to histopathological features in MTLE.


Safety and immunogenicity of plant-produced African horse sickness virus-like particles in horses.
African horse sickness (AHS) is caused by multiple serotypes of the dsRNA AHSV and is a major scourge of domestic equids in Africa. While there are well established commercial live attenuated vaccines produced in South Africa, risks associated with these have encouraged attempts to develop new and safer recombinant vaccines. Previously, we reported on the immunogenicity of a plant-produced AHS serotype 5 virus-like particle (VLP) vaccine, which stimulated high titres of AHS serotype 5-specific neutralizing antibodies in guinea pigs. Here, we report a similar response to the vaccine in horses. This is the first report demonstrating the safety and immunogenicity of plant-produced AHS VLPs in horses.


Burning Mouth Syndrome Treated with Mandibular and Maxillary Nerve Blocks.
Burning mouth syndrome is a condition characterized by a painful burning sensation in the oral mucosa lasting at least 3-6 months with no definitive etiology. The pathophysiology is not well understood, though there appears to be a connection with other neuropsychiatric conditions such as depression, anxiety, and mood disorders. We briefly discuss our experience with a patient who suffered from this conidtion and how it was treated with mandibular and maxillary nerve blocks after failing more conservative pharmacological options.


Social Media Use Among Physicians and Trainees: Results of a National Medical Oncology Physician Survey.
Cancer management requires coordinated care from many health care providers, and its complexity requires physicians be up to date on current research. Web-based social media support physician collaboration and information sharing, but the extent to which physicians use social media for these purposes remains unknown. The complex field of oncology will benefit from increased use of online social media to enhance physician communication, education, and mentorship. To facilitate this, patterns of social media use among oncologists must be better understood. A nine-item survey investigating physician social media use, designed using online survey software, was distributed via e-mail to 680 oncology physicians and physicians in training in Canada. Responses were analyzed using descriptive statistics. A total of 207 responses (30%) were received; 72% of respondents reported using social media. Social media use was highest, at 93%, in respondents age 25 to 34 years and lowest, at 39%, in those age 45 to 54 years. This demonstrates a significant gap in social media use between younger users and mid- to late-career users. The main barrier to use was lack of free time. The identified gap in social media use between age cohorts may have negative implications for communication in oncology. Despite advancements in social media and efforts to integrate social media into medical education, most oncologists and trainees use social media rarely, which, along with the age-related gap in use, may have consequences for collaboration and education in oncology. Investigations to further understand barriers to social media use should be undertaken to enhance physician collaboration and knowledge sharing through social media.


A multimedia database system for thermal ablation therapy of brain tumors.
A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the use to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.


The occurrence of biofilm in an equine experimental wound model of healing by secondary intention.
In humans, biofilm is a well-known cause of delayed healing and low-grade inflammation of chronic wounds. In horses, biofilm formation in wounds has been studied to a very limited degree. The objective of this study was thus to investigate the occurrence of biofilm in equine experimental wounds healing by secondary intention. Tissue biopsies from non-contaminated, experimental excisional shoulder and limb wounds were obtained on day 1-2, day 7-10 and day 14-15 post-wounding. Limb wounds were either un-bandaged or bandaged to induce exuberant granulation tissue (EGT) formation and thereby impaired healing. Presence of biofilm in tissue biopsies was assessed by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and confocal laser scanning microscopy (CLSM). Bandaged limb wounds developed EGT and displayed delayed healing, while shoulder and un-bandaged limb wounds healed normally. Biofilm was detected in limb wounds only. At day 14-15 biofilm was significantly more prevalent in bandaged limb wounds than in un-bandaged limb wounds (P=0.003). Further, bandaged limb wounds had a statistically significant increase in biofilm burden from day 7-10 to day 14-15 (P=0.009). The finding that biofilm was most prevalent in bandaged limb wounds with EGT formation suggests that biofilm may be linked to delayed wound healing in horses, as has been observed in humans. The inability to clear bacteria could be related to hypoxia and low-grade inflammation in the EGT, but the interaction between biofilm forming bacteria and wound healing in horses needs further elucidation.


Atomic force microscopic observation of in vitro polymerized poly[(R)-3-hydroxybutyrate]: insight into possible mechanism of granule formation.
Atomic force microscopy (AFM) was used to study the formation and growth of poly[(R)-3-hydroxybutyrate] (PHB) structures formed in the enzymatic polymerization of (R)-3-hydroxybutyryl coenzyme A [(R)-3-HBCoA] in vitro. Poly(3-hydroxyalkanoate) (PHA) synthase (PhaC(Re)) from Ralstonia eutropha, a class I synthase, was purified by one-step purification and then used for in vitro reactions. Before the reaction, PhaC(Re) molecules were deposited on highly oriented pyrolytic graphite (HOPG) and observed as spherical particles with an average height of 2.7 +/- 0.6 nm and apparent width of 24 +/- 3 nm. AFM analysis during the initial stage of the reaction, that is, after a small amount of (R)-3-HBCoA had been consumed, showed that the enzyme molecules polymerize (R)-3-HBCoA and form flexible 3HB polymer chains that extend from the enzyme particles, resulting in the formation of an enzyme-nascent PHB conjugate. When a sufficient amount of (R)-3-HBCoA was used as substrate, the reaction rapidly increased after the first minute followed by a slow increase in rate, and substrate was completely consumed after 4 min. After 4 min, spherical granules continued to grow in size to form clusters over 10 um in width, and in later stages of cluster formation, the cluster developed small projections with a size of approximately 100-250 nm, suggesting qualitative changes of the PHB clusters. Moreover, the high-resolution AFM images suggested that globular structures of approximately 20-30 nm apparent width, which corresponds to the size of PhaC(Re), were located on the surface of the small PHB granule particles.


Bone marrow necrosis and fat embolism: an autopsy report of a severe complication of hemoglobin SC disease.
Sickle Cell Disease encompasses a group of disorders related with the hemoglobin S and other hemoglobin genotypes. The clinical manifestation and the severity of symptoms are dependent on the specific genotype. In this setting, homozygous genotype (HbSS) presents an early onset of symptoms and a low expectancy of lifetime. However, the SC genotype (HbSC), which apparently shows a less severe clinical course, may exhibit the same complications of HbSS. These complications are usually manifested late in the course of life, when compared with the HbSS patients. It is noteworthy that HbSC may present a normal hematocrit, and therefore stays unknown until the first complication, that may be disastrous. The authors report a case of an African-Descendant woman, aging 65 years, with no previous diagnosis of anemia who sought medical attention because of a thoracic back pain followed by fever and altered mental status. The clinical picture deteriorated very fast with multiple organ failure and death. The autopsy findings concluded by generalized vaso-occlusive crisis, bone marrow necrosis and bone marrow and fat embolism, mainly to the lungs and kidney. The authors call attention for the knowledge of this severe life threatening complication, mainly in a country with a high Afro-Descendant population.


Assessment of the risk posed by the antifouling booster biocides Irgarol 1051 and diuron to freshwater macrophytes.
Antifouling paints are used to reduce the attachment of living organisms to the submerged surfaces of ships, boats and aquatic structures, usually by the release of a biocide. Two 'booster' biocides in common use are the triazine herbicide Irgarol 1051 (N-2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine), and diuron (1-(3,4-dichlorophenyl)-3,3-dimethylurea), which are designed to inhibit algal photosynthesis. Previous research has been directed at the effects of these compounds in marine and estuarine environments. In 2001 we sampled the main rivers and shallow freshwater lakes (Broads) of East Anglia UK for Irgarol 1051, its metabolite GS26575 (2-methylamino-4-tert-butylamino-6-amino-s-triazine) and diuron in order to establish the baseline environmental concentrations of these compounds in freshwater systems of eastern UK and to investigate their possible effects on aquatic plants. Irgarol 1051, GS26575 and diuron were found in water samples collected from 21 locations. The highest concentrations were found in the Norfolk and Suffolk Broads in May. The rivers Great Ouse, Wissey, Bure and Yare also contained all three compounds, as did the Great Ouse Cut-off Channel. The toxicity of these biocides to three macrophyte species (Apium nodiflorum, Chara vulgaris, and Myriophyllum spicatum) was investigated. Deleterious effects on relative growth rate, the maximum quantum efficiency (Fv/Fm) of photosystem II and, for Apium, root mass production were found. C. vulgaris was generally most sensitive; growth, especially of roots, was strongly affected in A. nodiflorum; growth rate of M. spicatum was sensitive to diuron. No observed effect concentrations (NOEC) were interpolated using standard toxicological analysis. These were compared with measured environmental concentrations (MEC) to determine the ranges of risk quotients (MEC/NOEC). Both Irgarol 1051 and diuron represented significant risks to A. nodiflorum and C. vulgaris in this area.


Near-Infrared photoluminescence in the femtosecond time region in monolayer graphene on SiO₂.
We investigate the dynamical properties of photoexcited carriers in a single monolayer of graphene at room temperature in air using femtosecond time-resolved luminescence spectroscopy. The luminescence kinetics are observed in the near-infrared region of 0.7-1.4 eV and analyzed based on the two-temperature model describing the cooling of thermalized carriers via the carrier-optical phonon interaction. The observed luminescence in the range 0.7-0.9 eV is well reproduced by the model. In the range 1.0-1.4 eV, however, the luminescence, which decays in ∼300 fs, cannot be reproduced by this model. These results indicate that the carrier system is not completely thermalized in ∼300 fs. We also show the importance of the carrier-doping effect induced by the substrate and surrounding environment in the carrier cooling dynamics and the predominance of optical phonons over acoustic phonons in the carrier-phonon interactions even at a temperature of ∼400 K.


Effects of the COVID-19 Pandemic on Patients with Concussion Presenting to a Specialty Clinic.
The purpose of this study is to examine the effects of the COVID-19 pandemic on patients presenting with concussion at a specialty clinic. This study used a retrospective cohort design to compare participants (n = 3021) with a suspected concussion, including a Pandemic cohort (n = 1139; March 2020-February 2021) and a Pre-Pandemic cohort (n = 1882; March 2019-February 2020). Concussions and patient characteristics including age, sex, days since injury, and injury mechanism were extracted from an electronic health record. There were 39.5% (n = 743) fewer concussions in Pandemic. Pandemic presented to the clinic 25.8 days later (p < 0.001) and were 1.9 years older (p < 0.001) than Pre-Pandemic. Sport-related concussions decreased 59.6% overall for Pandemic. Pandemic was associated with proportional increases of concussions involving recreational activities (odds ratio [OR] = 6.11; p < 0.001), motor vehicle collisions (OR = 1.39; p < 0.001), and falls/assaults (OR = 1.33; p < 0.001). A total of 9.4% (107/1139) of all Pandemic concussion initial clinical visits were performed using telehealth (0% in Pre-Pandemic). Concussion visit volume to a sub-specialty clinic decreased by approximately 40% during the COVID-19 pandemic and patients presented to the clinic nearly 1 month later. The increase in telehealth highlights the potential to expand clinical care outreach during the current and future pandemics or similar restrictive time periods.


Structural and Electrochemical Properties of Physisorbed and Chemisorbed Water Layers on the Ceramic Oxides Y2O3, YSZ, and ZrO2.
A combination of operando Fourier transform infrared spectroscopy, operando electrochemical-impedance spectroscopy, and moisture-sorption measurements has been exploited to study the adsorption and conduction behavior of H2O and D2O on the technologically important ceramic oxides YSZ (8 mol % Y2O3), ZrO2, and Y2O3. Because the characterization of the chemisorbed and physisorbed water layers is imperative to a full understanding of (electro-)catalytically active doped oxide surfaces and their application in technology, the presented data provide the specific reactivity of these oxides toward water over a pressure-and-temperature parameter range extending up to, e.g., solid-oxide fuel cell (SOFC)-relevant conditions. The characteristic changes of the related infrared bands could directly be linked to the associated conductivity and moisture-sorption data. For YSZ, a sequential dissociative water ("ice-like" layer) and polymeric chained water ("liquid-like") water-adsorption model for isothermal and isobaric conditions over a pressure range of 10(-5) to 24 mbar and a temperature range from room temperature up to 1173 K could be experimentally verified. On pure monoclinic ZrO2, in contrast to highly hydroxylated YSZ and Y2O3, a high surface concentration of OH groups from water chemisorption is absent at any temperature and pressure. Thus, the ice-like and following molecular water layers exhibit no measurable protonic conduction. We show that the water layers, even under these rather extreme experimental conditions, play a key role in understanding the function of these materials. Furthermore, the reported data are supposed to provide an extended basis for the further investigation of close-to-real gas adsorption or catalyzed heterogeneous reactions.


Extracellular and intracellular DNA for bacterial profiling of long-ripened cheeses.
A novel approach was developed to extract the extracellular DNA (eDNA), i.e. the free DNA outside the microbial cell, compared to the intracellular DNA (iDNA). The two DNA fractions were investigated in seven long-ripened cheeses. Among different buffer solutions tested, EDTA 0.5 M at pH 8 enabled a mild homogenization of cheese samples and the highest eDNA recovery. The extraction protocol was tested on single strains of lactic acid bacteria characterizing many Italian long-ripened cheeses, such as Streptococcus thermophilus, Lactobacillus helveticus, and Lactobacillus rhamnosus. The method resulted suitable for eDNA extraction because it minimized cell-lysis, avoiding the leakage of iDNA from the cells. The yields of eDNA, ranging from 0.01 to 0.36 µg g-1 cheese, were generally higher than the iDNA, indicating that autolytic phenomena prevailed over intact cells after 8-12 months of ripening. In four of the seven cheeses, the same LAB species were detected in the eDNA and iDNA fractions by length-heterogeneity PCR, while in the remaining three samples, a higher number of species was highlighted in the eDNA compared to the corresponding iDNA. The sequential extraction of eDNA and iDNA can be applied to obtain additional information on the composition of the bacterial community in long-aged cheeses.


The Use of Radiomic Features to Predict Human Papillomavirus (HPV) Status in Head and Neck Tumors: A Review.
Head and neck cancers represent a significant source of morbidity and mortality across the world. The individual genetic makeup of each tumor can help to determine the course of treatment and can help clinicians predict prognosis. Non-invasive tools to determine the genetic status of these tumors, particularly p16 (human papillomavirus (HPV)) status could prove extremely valuable to treating clinicians and surgeons. The field of radiomics is a burgeoning area of radiology practice that aims to provide quantitative biomarkers that can be derived from radiological images and could prove useful in determining p16 status non-invasively. In this review, we summarize the current evidence for the use of radiomics to determine the HPV status of head and neck tumors. .


Implant-Based Breast Reconstruction in the Elderly: Complications and Patient-Reported Outcomes in Women Older Than 70 Years.
Advanced age is considered by many to be a relative contraindication to breast reconstruction. However, despite increased medical comorbidities and a perception that elderly patients are less concerned with body image, more women older than 70 years are choosing to undergo breast reconstruction. There is a paucity of data to guide reconstructive decision-making and counseling in this population. The aim of this study was to evaluate patient satisfaction, complication rates, and long-term outcomes in women older than 70 years undergoing implant-based breast reconstruction. A total of 400 patients were identified at the authors' institution and divided into 2 groups: ≥70 and <70 years old. Medical comorbidities, surgical outcomes, and patient-reported outcomes as defined by the BREAST-Q were compared using the χ2 tests for categorical variables and t tests for continuous variables. The cohort of patients older than 70 years was made up of 25 women, with a mean age of 73 years, and the cohort of patients younger than 70 years was made up of 375 women, with a mean age of 50 years. There was no significant difference in body mass index (P = 0.373), smoking status (P = 0.360), or history of prior ipsilateral radiation (P = 0.508) between the 2 cohorts; however, the elderly cohort was significantly more likely to have diabetes (P = 0.026). Although elderly patients were less likely to undergo bilateral mastectomy (P < 0.001), there was no significant difference in the type of mastectomy, pathological diagnosis, or method of reconstruction. There was no significant difference in complication rates when looking at minor infection (P = 0.553) or major infection (P = 0.553). The 2 groups were equally likely to undergo secondary procedures (P = 0.192). Overall satisfaction rates were high in all BREAST-Q categories in the elderly group and not significantly different when compared with the group of patients younger than 70 years. Matched-pair analysis showed a significant difference with the group of patients older than 70 years having higher levels physical well-being (P < 0.001). Immediate breast reconstruction can be performed safely and with similar high satisfaction rates in the elderly population as their younger counterparts. Age alone should not be used as a reason for excluding women from these life-changing operations.


CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure.
The caspase recruitment domain gene (CARD15) was recently identified as the underlying gene associated with the IBD1 locus that confers susceptibility to Crohn disease (CD). CARD15 is related to the NOD1/Apaf-1 family of apoptosis regulators, and three sequence variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) in the gene were demonstrated to be associated with CD. We collected a cohort of 231 patients with CD and 71 healthy control individuals from the Canadian province of Quebec, to determine the prevalence of these sequence variants in an independent population. Clinical records of all patients were systematically reviewed, and detailed phenotypic information was obtained. All patient DNA samples were genotyped for the three variants, thus enabling an analysis of genotype-phenotype correlations. In this cohort, 45.0% of patients with CD carried at least one variant in the CARD15 gene, compared with 9.0% of control individuals (P<10-7). Allele frequencies of Arg702Trp, Gly908Arg, and Leu1007fsinsC were 12.9%, 5.2%, and 10.3% in patients with CD, compared with 4.2%, 0.7%, and 0.7% in control individuals, respectively. Importantly, CARD15 mutants were seen with equal frequency in patients with familial and sporadic CD. Analysis of the relationship between genotype and phenotype convincingly demonstrates that CARD15 variants are significantly associated with ileal disease involvement, as opposed to strictly colonic disease (P<.001). Moreover, we were able to determine the haplotype structure surrounding this disease gene by genotyping 45 single-nucleotide polymorphisms (SNPs) in a 177-kb region that contained the CARD15 gene. This structure helps clarify the history of these causal mutations. Finally, this analysis shows that CARD15 involvement with CD is detectable by use of publicly available SNPs alone.


Biological and behavioral factors influence group differences in prolactin levels among breastfeeding Nepali women.
This study of two natural fertility Nepali groups, the Tamang and Kami, identifies biological and behavioral factors associated with population differences in fertility. Previous research had established that Tamang experience longer interbirth intervals than Kami despite similarly intense nursing practices, and bear considerably higher energy expenditure due to workload. This cross-sectional study of 71 breastfeeding women includes prolactin determinations on three blood spot samples collected 5, 30, and 50 minutes following a timed nursing bout, and data on maternal age, BMI, menstrual status, previous birth interval, parity, infant age, nursing bout length, and durations of supplementation and postpartum amenorrhea. The findings show that Tamang breastfeeding mothers have higher average prolactin levels than Kami for as long as 22 months postpartum. Tamang mothers sustain average prolactin levels above those of nonpregnant, nonlactating women for nearly 2 years postpartum, whereas prolactin levels among Kami breastfeeding mothers are the same as this latter group after 1 year postpartum. Furthermore, the findings indicate that Tamang mothers have higher average prolactin levels regardless of maternal age, physical status (BMI, weight, or height), or infant age, and the rate of decline in prolactin from 5 to 50 minutes after suckling is significantly greater for Kami than Tamang. Since factors associated with prolactin levels differ by group, the findings also emphasize that populations vary not only in the strength of effects that proximate determinants have on fertility regulation, but also in the pathways by which they exert their effects (direct physiological versus indirect behavioral). Am. J. Hum. Biol. 10:191-210, 1998. © 1998 Wiley-Liss, Inc.


The role of hippocampal dopamine receptors in prepulse inhibition.
Although it has long been realized that the hippocampal formation receives a projection from the midbrain dopaminergic cell groups and contains mRNA for all five dopamine receptors, the functional role of this dopaminergic projection has not been studied so far. The present study aimed to investigate the role of dopamine receptors in the dorsal CA1 area of the hippocampus in prepulse inhibition. The results show that local application of amphetamine reduced prepulse inhibition without affecting the baseline startle amplitude. This effect of amphetamine could be reversed by coadministration of the D1 antagonist SCH23390. Moreover, local application of the D1 agonist SKF81297 also disrupted prepulse inhibition without altering basal startle amplitude. These data clearly suggest that the hippocampal D1 receptor plays an important role in prepulse inhibition. The effects of amphetamine could not be reversed by coadministration of the D2 antagonist sulpiride. Interestingly, the D2/3 agonist quinpirole did reduce prepulse inhibition, again without affecting basal startle amplitude. Because quinpirole has a much higher affinity for the D3 receptor than does sulpiride, it is suggested that the D3 receptor might be involved in this effect.


Effectiveness of manual and rotary instrumentation techniques for cleaning flattened root canals.
The cleaning capacity of manual and rotary instrumentation techniques in mesial-distal flattened canals was studied by morphometric analysis. Twenty human mandibular incisors were divided into two groups of 10 teeth each: group 1, crown-down technique with rotary instrumentation using ProFile .04; group 2, crown-down technique with manual instrumentation using K-files. The teeth were evaluated with an optic microscope that was coupled to a computer to determine the percentage of root canal area with debris. The nonparametric Mann-Whitney U test showed a statistically significant difference at the level of 1% between the techniques. The manual technique was more efficient in cleaning mesial-distal flattened root canals than the rotary technique, although neither completely cleaned the root canal.


Similarity Measures for Quantifying Restrictive and Repetitive Behavior in Conversations of Autistic Children.
Restrictive and repetitive behavior (RRB) is a core symptom of autism spectrum disorder (ASD) and are manifest in language. Based on this, we expect children with autism to talk about fewer topics, and more repeatedly, during their conversations. We thus hypothesize a higher semantic overlap ratio between dialogue turns in children with ASD compared to those with typical development (TD). Participants of this study include children ages 4-8, 44 with TD and 25 with ASD without language impairment. We apply several semantic similarity metrics to the children's dialogue turns in semi-structured conversations with examiners. We find that children with ASD have significantly more semantically overlapping turns than children with TD, across different turn intervals. These results support our hypothesis, and could provide a convenient and robust ASD-specific behavioral marker.


Identification of a Novel TRPM8 Agonist from Nutmeg: A Promising Cooling Compound.
The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary receptor for innocuous cold stimuli (<28 °C) in humans. TRPM8 agonists such as l-(-)-menthol are widely used as flavors and additives to impart briskness, in addition to medicinal uses for inflammation and pain. Though various natural and synthetic agonists have been explored, only few natural compounds are known. We report herein the identification and characterization of the novel neolignan agonist erythro- and threo-Δ8'-7-ethoxy-4-hydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (1) with an EC50 of 0.332 μM, which was isolated from a well-known spice, nutmeg (Myristica fragrans Houtt.). Structure activity relationships are also disclosed, showing that the 7-d-menthoxy derivative is the most potent agonist (EC50 = 11 nM). The combination of 1 and l-(-)-menthol has an additive effect, suggesting that neolignan compounds interact with TRPM8 at different sites from those of l-(-)-menthol.


Detection of Cryptic taxa in the genus Leptophryne (Fitzinger, 1843) (Amphibia; Bufonidae) and the description of a new species from Java, Indonesia.
We investigated phylogenetic relationships among populations of two species within the genus Leptophryne, L. cruentata and L. borbonica, using the mitochondrial 16S rRNA gene. As a result, we identified two distinct lineages within populations currently considered Leptophryne cruentata: 1) a lineage containing L. cruentata from the type locality, and 2) a lineage from Mt. Slamet and Mt. Ciremai. On the basis of genetic and morphological differences, we describe the Mt. Slamet and Mt. Ciremai populations as a new species, L. javanica sp. nov. The new species is distinguished from L. cruentata and L. borbonica by the following combination of morphological characters: the presence of distinct yellow mottling on the dorsum; relatively small body size (SVL male 22.2-24.0 mm, female 29.6 mm); relatively short hindlimbs (HLL 37.0-40.9 mm); relatively short fourth toe (4ToeL 4.3-6.0 mm); basal webbing on the hands, but well developed on toes; very protruding snout and an indistinct tympanum. In our preliminary phylogenetic analysis, we also detected four distinct lineages within Leptophryne borbonica: 1) a lineage containing true L. borbonica from west Java, 2) a lineage from Lampung (Sumatra I), 3) a lineage from northern Borneo, and 4) a lineage from Bengkulu (Sumatra II). Further studies are needed to determine taxonomic status of these lineages.


The neural bases of feeling understood and not understood.
Past research suggests that feeling understood enhances both personal and social well-being. However, little research has examined the neurobiological bases of feeling understood and not understood. We addressed these gaps by experimentally inducing felt understanding and not understanding as participants underwent functional magnetic resonance imaging. The results demonstrated that feeling understood activated neural regions previously associated with reward and social connection (i.e. ventral striatum and middle insula), while not feeling understood activated neural regions previously associated with negative affect (i.e. anterior insula). Both feeling understood and not feeling understood activated different components of the mentalizing system (feeling understood: precuneus and temporoparietal junction; not feeling understood: dorsomedial prefrontal cortex). Neural responses were associated with subsequent feelings of social connection and disconnection and were modulated by individual differences in rejection sensitivity. Thus, this study provides insight into the psychological processes underlying feeling understood (or not) and may suggest new avenues for targeted interventions that amplify the benefits of feeling understood or buffer individuals from the harmful consequences of not feeling understood.


Isolation and fractionation of the photosynthetic membranous organelles from Rhodopseudomonas spheroides.
Molecular sieve chromatography and sucrose gradient centrifugation were used to prepare large quantities of purified chromatophores from Rhodopseudomonas spheroides. Electron micrographs of these chromatophores revealed that the final preparations were very homogeneous and free of non-chromatophore particulate material. As an additional check on purity, (14)C-l-phenylalanine-labeled aerobic cells, devoid of chromatophores, were mixed with unlabeled photosynthetic cells. The resulting preparation contained less than 1% of the radioactivity, originally located in non-chromatophore protein. The purified chromatophores were solubilized in 2-chloroethanol and separated into two fractions. Fraction P(1) contained 3 to 5% of the total chromatophore protein and could be resolved into 10 electrophoretic components. The second fraction, P(II), contained five electrophoretic components. One of these components had associated with it all of the pigment and phospholipid present in P(II). Preliminary immunochemical studies on these fractions are also reported.


Retirement outcomes in the Health and Retirement Study.
This article examines retirement outcomes in the first four waves of the 1992-1998 Health and Retirement Study (HRS). Measured retirement is seen to differ, sometimes substantially, with the definition of retirement used and among various groups analyzed. Moreover, those differences vary with the wave of the survey as respondents age. Retirement comprises a complex set of flows among states representing nonretirement, partial retirement, and complete retirement. Using the self-reported definition of retirement, 77 percent of transitions continue in the same or equivalent states between adjoining waves of the HRS, 17 percent involve a move from greater to lesser labor force participation, and 6 percent involve a move from lesser to greater labor force participation. Twenty-two percent of the sample report they were partially retired at some time in the first four waves, and by age 65, over a fifth of the population is partially retired. Altogether, 17 percent of the sample experienced a reversal in the course of the survey, moving from a state of less work to a state of more work. A comparison of retirement flows for men between the HRS and the 1969-1979 Retirement History Study (RHS) shows that the large spike in the population leaving nonretirement at age 65 observed in the 1969-1979 RHS has fallen from 18 to 11 percentage points in the HRS and that the share leaving nonretirement at 62 has increased from 13 to 20 percentage points over time. The results presented here should help researchers improve their understanding of the structure of the dependent variable in retirement studies. Incorrect or arbitrary measurement of the retirement variable may lead to a misunderstanding of how Social Security and related policies affect retirement outcomes. Thus, the improved understanding of retirement gained from this research will be helpful to those designing retirement policies as they attempt to understand the effects of those policies.


Magnetic flux emergence and associated dynamic phenomena in the Sun.
We present a review of the process of magnetic flux emergence in the Sun. We focus on observations and numerical experiments that explore the dynamical rise of magnetic fields from the solar interior to the corona. We describe the response of the highly stratified solar atmosphere on flux emergence and, consequently, we present a comprehensive picture of the coupling between solar dynamic events and flux emergence. We discuss potential applications of this process in other astrophysical environments.


A leukoencephalomyelopathy of rottweiler dogs.
Two adult rottweiler dogs were evaluated for slowly progressive ataxia and paresis of all four limbs of over seven months duration. On neurologic examination, signs referable to a lesion in the cervical spinal cord affecting motor and sensory white matter tracts were found. Both dogs were necropsied and were found to have demyelinating lesions in the spinal cord, brain stem, and deep cerebellar white matter. Primary morphologic alterations were intact naked axons and thinly myelinated axons accompanied by reactive astrogliosis. The spinal cord lesions tended to have bilateral symmetry and were found in the lateral funiculi and occasionally in the dorsal funiculi. The cause and pathogenesis of the lesion were not determined.


Abdominal pain, indigestion, anorexia, nausea and vomiting.
Non-specific abdominal complaints are a very frequent cause of discomfort. Even if only comparatively few are brought to the attention of the physician, they account for a considerable portion of the reasons for seeking medical care, both in acute and chronic conditions. On the other hand, few drugs are free of the suspicion of causing abdominal complaints, which make up between one-tenth and one-third of reported adverse reactions. A wide variety of possible alternative or concomitant causes makes a clear causative attribution to suspected drugs very difficult. This holds especially true for the ill-defined conditions of indigestion and anorexia. For nausea and vomiting, specific scales have been developed which facilitate differentiation between drugs causing these effects most frequently and most intensively. They have been applied in cytostatic therapy, where this is one of the most frequently encountered problems, but nausea and vomiting can seriously affect compliance in many other treatments. Somatic abdominal pain results in most instances from the irritation of the parietal peritoneum and is usually the effect of a lesion. This may or may not be caused by a drug, but this cause should be the first consideration. Visceral pain may result from functional disturbance of secretory glands or of the muscular coat, from drug action on bowel content or from irritation of the mucosa, all of which are frequently interrelated. Most frequently suspected pharmacological causes are drugs with anticholinergic action, antibiotics, potassium supplements and non-steroidal, anti-inflammatory agents. Drug-induced hyperinsulinism and porphyria are rare cases. Abuse of laxatives should always be considered because of its prevalence. A great number of other untoward drug effects have been described in the literature, but rarely merit first consideration. With the exception of promptly occurring or persistent emesis, gastrointestinal symptoms usually are not pathognomonic for drug effects and are the result of several factors. The usual approach to identifying an adverse drug effect is to delineate the functional or structural disorder, and to associate this diagnosis with possible pharmacodynamic aetiologies.


Controllable water permeation on a poly(N-isopropylacrylamide)-modified nanostructured copper mesh film.
Water permeation is important for various applications in industry, agriculture, and daily life. However, most research mainly focuses on the static wettability on different surfaces, and the dynamic properties of the micro- and nanostructure-enhanced responsive wettability is lacking. And the relevant application research is rare, which still remains a challenge. Herein we report the temperature-controllable water permeation on a poly(N-isopropylacrylamide)-modified nanostructured copper mesh film. At low temperatures (below 25 degrees C), the film shows good water permeability because of the highly hydrophilic nature, and as a result, the water can easily penetrate through the film. At high temperatures (above 40 degrees C), it is impermeable to water because of the superhydrophobicity and the large negative capillary effect induced by the micro- and nanostructures. The excellent controllability of water permeation on this film may be convenient for use in many processes including filtration, water/oil separation, and so on. A detailed investigation indicates that the special nanostructures and the appropriate size of the microscale mesh pores not only influence the static contact angles of the mesh film, but also, more importantly, greatly improve the dynamic properties of wettability at different temperatures simultaneously, which plays a crucial role in the excellent controllability over water permeation on this film. This work may also provide interesting insight into the design of novel functional devices that are relevant to surface wettability.


Lung dose analysis in loco-regional hypofractionated radiotherapy of breast cancer.
To report the ipsilateral lung dosimetry data of breast cancer (BC) patients treated with loco-regional hypofractionated radiotherapy (HFRT). Treatment plans of 150 patients treated in the Radiotherapy Unit, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January 2012 and March 2015 by HFRT for BC were retrospectively reviewed. All patients received 42.4 Gy in 16 fractions by tangential and supra-clavicular fields with 6 MV, 18 MV, or mixed energies. Ipsilateral lung dosimetric data V20Gy and mean lung dose (MLD) were recorded. Correlations between lung dose, patient characteristics, and treatment delivery parameters were assessed by a logistic regression test. The mean ipsilateral lung V20Gy was 24.6% and mean MLD was 11.9 Gy. A weak, but statistically significant correlation was found between lung dose and lung volume (p=0.043). The lung dose was significantly decreasing with patient separation and depth of axillary lymph node (ALN) and supra-claviculary lymph nodes (SCLN) (p less than 0.0001), and increasing with ALN (p=0.001) and SCLN (p=0.003) dose coverage. Lung dose significantly decreased with beam energy (p less than 0.0001): mean V20Gy was 27.8%, 25.4% for 6 MV, mixed energy, and 21.2% for 18 MV. The use of a low breast-board angle correlates with low lung dose. Our data suggest that the use of high energy photon beams and low breast-board angulation can reduce the lung dose.


Establishment of a foreign antigen secretion system in mycobacteria.
In order to develop recombinant Mycobacterium bovis BCG into a useful multivaccine vehicle, we established a foreign antigen secretion system in mycobacteria in which an extracellular alpha antigen of Mycobacterium kansasii was utilized as a carrier. By using this system, a B-cell epitope (Glu-12-Leu-Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 p17gag, which was identified by a fusion protein-based method, has been successfully obtained from BCG along with the alpha antigen. This is the first report of expression and secretion of a foreign viral antigen from BCG. It is possible that the system can become a universal vaccination vehicle applicable to protection against various infectious diseases.


Gestational Weight Gain in the First Two Pregnancies and Perinatal Outcomes in the Second Pregnancy.
Gestational Weight Gain (GWG) below or above the Institute of Medicine (IOM) recommendations increases the risk of adverse pregnancy outcomes. However, it remains unknown whether the risk of adverse outcomes is affected by GWG in a previous pregnancy. We examined associations between GWG in the index (second) pregnancy and pregnancy outcomes, including preterm delivery and small for gestational age (SGA), while taking into consideration GWG in the first pregnancy. In a population-based cohort study (n = 210 564), using the Missouri maternally-linked birth registry (1989-2005), we used multivariable Poisson regression with robust error variance stratified by prepregnancy body mass index (BMI) to evaluate associations between GWG in the index pregnancy and a composite indicator of GWG in the first and second pregnancies and our outcomes of interest, after controlling for sociodemographic and pregnancy-related confounders. Associations between GWG in the index pregnancy and pregnancy outcomes were moderated by GWG in the first pregnancy. Despite having GWG within recommendations in the index pregnancy, women had increased risk of preterm delivery and SGA if they had suboptimal GWG in their first pregnancy. Also, women having suboptimal GWG in the index pregnancy had increased risk of preterm delivery only if their GWG in the first pregnancy was also suboptimal. The observation that women who have GWG within recommendations in a current pregnancy may still have increased risk of adverse outcomes if they had suboptimal GWG in the first pregnancy has considerable clinical and public health implications.


The Psychosocial Impact of Cleft Lip and/or Palate on Unaffected Siblings.
Sibling relationships are among the most unique social connections, significantly affecting psychosocial adjustment. Previous reviews in the fields of chronic illness and disability have concluded that unaffected siblings of children with long-term conditions are at risk of poorer psychological functioning as a consequence. Much research has investigated the psychosocial impact of CL/P on affected individuals and their parents, yet comparatively little is known about the impact on other close family members. To gain a better understanding of the experience of unaffected siblings of children born with CL/P, with a view to informing service provision and support. Individual qualitative interviews conducted over the telephone/Internet with five siblings and eight parents, including five sibling-parent pairs from the same family. Thematic analysis identified three key themes applicable across both parent and sibling interviews: perceptions of positive and negative impacts, factors affecting the degree of impact, and support for families. This study provides insight into a population that is often overlooked in the context of cleft care. The analysis identified a number of sibling support and information needs, along with suggestions of how to incorporate support for siblings in practice. The findings suggest that an inclusive approach to health care encompassing all members of the family is essential for optimal familial adjustment.


Understanding patterns of immunoglobulin gene rearrangements.
When immunoglobulin (Ig) gene rearrangements are analyzed, several patterns emerge. The rearrangements at the various loci generally appear in a specific temporal order. In addition, within a given locus the frequency of rearrangement of the various gene segments is not equal but is skewed towards preferential rearrangement of particular gene segments. Understanding the reasons for these patterns will shed light on the mechanism of recombination, the regulation of rearrangement, and the relationship between Ig gene rearrangement and B cell development. In this review, we discuss evidence that the observed patterns of Ig gene rearrangement are due to a combination of factors including the recombination signal sequences, sequences in the coding termini, the accessibility of genetic elements to V(D)J recombinase, and cellular selection.


Elevated levels of mannan-binding lectin in patients with type 1 diabetes.
The hepatic protein mannan-binding lectin (MBL) activates the complement system on binding to carbohydrate patterns and is involved in first-line defense against invading microorganisms. Emerging evidence indicates that in some situations MBL may cause inexpedient complement activation and tissue injury through binding to endothelial glycosylations. MBL levels are suppressed by insulin treatment in critically ill patients, and, hypothetically, hepatic portal hypoinsulinemia could lead to increased levels of MBL in patients with type 1 diabetes. We measured MBL and C-reactive protein (CRP) levels in 132 normoalbuminuric type 1 diabetic patients and 66 healthy age- and sex-matched controls. The median MBL concentration was higher in diabetic patients than in healthy controls [1290 micro g/liter (interquartile range, IQR 354-2961 micro g/liter) vs. 970 micro g/liter (IQR 277-1607 micro g/liter), P = 0.025], whereas CRP concentrations were similar among patients and controls [1.42 mg/liter (IQR 0.95-2.21) vs. 1.21 mg/l (IQR 0.74-2.13), NS]. In diabetic subjects, CRP levels correlated with poor glycemic control as indicated by hemoglobin A(1c) and daily insulin dose, which was not the case with MBL. MBL concentrations were positively correlated with urinary albumin excretion (r = 0.22; P = 0.013) and increased with increasing urinary albumin excretion tertile (P = 0.036). In conclusion, our data demonstrate that circulating MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes.


Regular-to-chaotic tunneling rates: from the quantum to the semiclassical regime.
We derive a prediction of dynamical tunneling rates from regular to chaotic phase-space regions combining the direct regular-to-chaotic tunneling mechanism in the quantum regime with an improved resonance-assisted tunneling theory in the semiclassical regime. We give a qualitative recipe for identifying the relevance of nonlinear resonances in a given variant Planck's over 2pi regime. For systems with one or multiple dominant resonances we find excellent agreement to numerics.


Physiochemical properties, safety and pharmacokinetics of bimosiamose disodium after intravenous administration.
Bimosiamose is a novel synthetic panselectin antagonist being developed for the treatment of acute and chronic inflammatory disorders. Therefore, we have studied the pharmacokinetics and tolerability and determined the pharmacokinetically relevant physicochemical characteristics of bimosiamose. A randomized, double-blind, placebo-controlled dose-escalation trial in healthy male subjects has been carried out. The subjects received intravenous infusions of 0.5-30 mg/kg bimosiamose disodium. The maximum plasma concentration (Cmax) was 675 +/- 11 microg/ml with a tmax of 0.36 +/- 0.13 h (mean +/- SD). The elimination half-life t1/2 was 4.1 +/- 1.0 h, and the AUC(o-inf) was 1,360 +/- 393 h microg/ml after the 30 mg/kg dose. The clearance and the apparent volume of distribution decreased with increasing dose to 22 +/- 6 ml/kg/h and 40 +/- 13 ml/kg/h at the highest dose, respectively, and the mean residence time increased to 1.8 +/- 0.35 h. Bimosiamose was safe and well-tolerated.


Regulation of fatty acid synthase gene expression: an approach for reducing fat accumulation.
Fatty acid synthase (FAS) catalyzes the last step in the fatty acid biosynthetic pathway. The tissue concentration of FAS, which is affected by a number of hormonal and dietary factors, is a key determinant for the maximal capacity of a tissue to synthesize fatty acids by the de novo pathway. The complete nucleotide sequence of the avian and rat FAS transcripts has been cloned. In addition, a 1.5-kb cDNA that represents the thioesterase domain of the pig FAS protein plus the entire 3'-untranslated region of the transcript was isolated from a porcine liver cDNA library. Using these FAS cDNA tools, FAS mRNA transcripts have been found in most tissues, including adipose, liver, lung, brain, kidney, and small intestine. Moreover, the abundance of FAS mRNA in a tissue determines the rate of FAS protein synthesis, and ultimately the tissue content of FAS protein. In the liver, the rate of FAS gene transcription dictates the level of FAS mRNA, whereas the FAS mRNA content of adipose tissue seems to be determined by factors that affect gene transcription and mRNA stability. Adaptive changes in the abundance of FAS mRNA seem to occur primarily in hepatic and adipose tissues, whereas FAS expression in other tissue types is resistant to nutritional and hormonal manipulations. This review presents the concept that the tissue-specific adaptation in FAS gene expression can be exploited to develop a tissue-specific inhibitor of FAS gene expression and, hence, reduce the tissue capacity for fat accretion through the de novo biosynthetic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].
To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.


Effect of lower limb kinetic on carrying infant by hip seat carrier during high heel gait.
While common characteristics between wearing of high heel between carrying an infant elevate height of center of gravity, it is not known what interaction effect influence to leg stiffness. The aim of the study is to investigate the effect of carrying infant by hip seat carrier on leg mechanics during high heel gait. Adult female (n=9) and infant (n=9) participated as subjects. Infant was positioned on rear of trunk as of wearing 6 cm of high heel shoe. Change of leg mechanics was analyzed with ground reaction force variables (1st peak vertical force [PVF], 2nd PVF, center of pressure [medial-lateral, anterior-posterior]), extrapolated center of mass (XCoM) theta, and leg stiffness. While carrying infant with wearing of high heel more increased 1st PVF, 2nd PVF, and leg stiffness than normal gait, and more decreased medial-lateral center of pressure and XCoM theta. High heel and carrying infant showed potential transformation of posture for securement of stability, which related with mechanism to decrease an impulse type. In conclusion, it is suggest that gait for long time in the condition may accumulate fatigue on leg and increase falling injury, so experts of clinics and exercise rehabilitation should understand the mechanism that could recommend guideline for exercise prescription on several problems.


The role of Gβ5 in vision.
Recent advances in our understanding of R7RGS proteins have benefited from studies involving the fifth member of the Gβ family (Gβ5) that is found throughout the visual system. Unlike conventional Gβsthat form dimers with Gγ, Gβ5 partners with R7RGS proteins, which contain the G-protein gamma-like (GGL) domain, to act as a GTPase accelerating protein (GAP) complex on certain Gα subunits. Recent studies in the retina underscore the necessity of Gβ5 for normal recovery in photoreceptors and light responses in ON-bipolar cells. Gβ5 may also be important for the generation and propagation of spontaneous retinal waves in retina and proper synapse formation in lateral geniculate nucleus (LGN). Here, we review these findings and discuss future investigative directions concerning Gβ5's function in vision.


Simulathon 2020: Integrating Simulation Period Prevalence Methodology Into the COVID-19 Disaster Management Cycle in India.
The disaster management cycle is an accepted model that encompasses preparation for and recovery from large-scale disasters. Over the past decade, India's Pediatric Simulation Training and Research Society has developed a national-scale simulation delivery platform, termed the Simulathon , with a period prevalence methodology that integrates with core aspects of this model. As an exemplar of the effectiveness of this approach, we describe the development, implementation, and outcomes of the 2020 Simulathon, conducted from April 20 to May 20 in response to the nascent COVID-19 pandemic disaster. We conclude by discussing how aspects of the COVID-19 Simulathon enabled us to address key aspects of the disaster management cycle, as well as challenges that we encountered. We present a roadmap by which other simulation programs in low- and middle-income countries could enact a similar process.


Development of a purity control strategy for pemetrexed disodium and validation of associated analytical methodology.
Stability-indicating reversed phase HPLC methods have been developed and validated for the determination of 13 potential process and degradation impurities in pemetrexed disodium drug substance (DS) and pemetrexed for injection drug product (DP). This paper describes the development of HPLC-UV impurity methods for drug substance and drug product. Relative response factors (RRF) have been determined using HPLC-UV in tandem with CAD or by NMR detection. Conditions for the generation of system suitability solutions are described and assure adequate chromatographic resolution and peak identification without the need for impurity reference standards. The methods were fully validated and demonstrated to have acceptable specificity, linearity, accuracy, repeatability, intermediate precision, detection/quantitation limit, and robustness.


A traumatic central cord syndrome occurring after adequate decompression for cervical spondylosis: biomechanics of injury: case report.
Case report with review of the literature. To present the first case of a central cord syndrome occurring after adequate decompression, and review the mechanics of the cervical spinal cord injury and postoperative biomechanical and anatomic changes occurring after cervical decompressive laminectomy. Cervical spondylosis is a common pathoanatomic occurrence in the elderly population and is thought to be one of the primary causes for a central cord syndrome. Decompressive laminectomy with or without fusion has been a primary treatment for spondylotic disease and is thought to be protective against further injury. To our knowledge, there are no cases of a central cord syndrome occurring after adequate decompression reported in the literature. Case study with extensive review of the literature. The patient underwent C3-C7 cervical laminectomy without complications. After surgery, the patient's spasticity and gait difficulties improved. She was discharged to inpatient rehabilitation for further treatment of upper extremity weakness. The patient fell in the rehabilitation center, with a central cord syndrome despite adequate decompression of her spinal canal. The patient was treated conservatively for the central cord and had minimal improvement. Decompressive laminectomy provides an immediate decompressive effect on the spinal cord as seen by the dorsal migration of the cord, however, the biomechanics of the cervical spine after decompressive laminectomy remain uncertain. This case supports the ongoing research and need for more intensive research on postoperative cervical spine biomechanics, including decompressive laminectomies, decompressive laminectomy and fusion, and laminoplasty.


Leg position learning by an insect: II. Motor strategies underlying learned leg extension.
The patterns of myographic activity in the flexor and extensor tibiae muscles of the locust which accompany learned tibial extension were examined. Three distinct motor strategies were identified: (1) repeated flexion-extension movements, each of which resulted in a momentary excursion beyond the required, pre-set joint angle (demand angle) and in sum met the criterion for learning; (2) changes in basic muscle tonus, which resulted in maintained shifts in tibial position without discernible myographic activity; (3) tonic activity in the single slow excitatory motoneuron of the extensor tibiae ( SETi ) which produced maintained tibial extension. These strategies were selectively employed depending on the particular range of joint angle required. These strategies were compared and their effectiveness evaluated using a variety of behavioral criteria. Neuronal mechanisms which might underlie each of these strategies are discussed.


Identification of Differentially Expressed Genes In Deltamethrin-Resistant Culex pipiens quinquefasciatus.
Culex quinquefasciatus is one of China's major house-dwelling mosquito species and an important vector of filariasis and encephalitis. Chemical treatments represent one of the most successful approaches for comprehensive mosquito prevention and control. However, the widespread use of chemical pesticides has led to the occurrence and development of insecticide resistance. Therefore, in-depth studies of resistance to insecticides are of vital importance. In this study, we performed a gene expression analysis to investigate genes from Cx. quinquefasciatus that may confer pyrethroid resistance. We aimed to understand the mechanisms of Cx. quinquefasciatus resistance to pyrethroid insecticides and provide insights into insect resistance management. Using a resistance bioassay, we determined the deltamethrin LC50 values (lethal concentration required to kill 50% of the population) for Cx. quinquefasciatus larvae in the F21, F23, F24, F26, F27, and F30 generations. The 7 tested strains exhibited pesticide resistance that was 25.25 to 87.83 times higher than that of the SanYa strain. Moreover, the expression of the OBPjj7a (odorant-binding protein OBPjj7a), OBP28 (odorant-binding protein OBP28), and E2 (ubiquitin-conjugating enzyme) genes was positively correlated with deltamethrin resistance ( R2 = 0.836, P = 0.011; R2 = 0.788, P = 0.018; and R2 = 0.850, P = 0.009, respectively) in Cx. quinquefasciatus. The expression of 4 additional genes, H/ACA, S19, SAR2, and PGRP, was not correlated with deltamethrin resistance. In summary, this study identified 3 Cx. quinquefasciatus genes with potential involvement in deltamethrin resistance, and these results may provide a theoretical basis for the control of mosquito resistance and insights into resistance detection.


Vertical transmission of dengue 1 virus by Haemagogus equinus mosquitoes.
Vertical transmission of dengue type 1 virus was demonstrated by a strain of Haemagogus equinus mosquitoes from Panama. Parental females were infected by intrathoracic inoculation and egg production was stimulated by feeding on mice. Dengue 1 virus was detected in fourth instar larval progeny obtained from two installment hatches of eggs. Minimum filial infection rates ranged up to 1:495.


Nanostructured Au Electrode with 100 h Stability for Solar-Driven Electrochemical Reduction of Carbon Dioxide to Carbon Monoxide.
Solar-to-chemical energy conversion is a potential alternative to fossil fuels. A promising approach is the electrochemical (EC) reduction of CO2 to value-added chemicals, particularly hydrocarbons. Here, we report on the selective EC reduction of CO2 to CO on a porous Au nanostructure (pAu) cathode in 0.1 M KHCO3. The pAu cathode anodized at 2.6 V exhibited maximum Faradaic efficiency (FE) for conversion of CO2 to CO (up to 100% at -0.75 V vs reversible hydrogen electrode (RHE)). Furthermore, commercial Si photovoltaic cells were combined with EC systems (PV-EC) consisting of pAu cathodes and IrO2 anodes. The triple-junction cell and EC system resulted in a solar-to-CO conversion efficiency (SCE) of 5.3% under 1 sun illumination and was operated for 100 h. This study provides a PV-EC CO2 reduction system for CO production and indicates the potential of the PV-EC system for the EC reduction of CO2 to value-added chemicals.


Integrating research into the culture of allied health professions: the background and a review of issues in the United Kingdom.
This article reviews the challenges and barriers to change associated with development of a research culture in allied health professions within the higher education sector. We address the cultural upheaval and alterations in ways of working experienced by higher education and the health professions in recent times as a result of government policy as it applies to education and the National Health Service in the United Kingdom. Cooperation between higher education and the National Health Service in developing a culture of research in the health professions is fundamental to achieving evidence-based practice in health care. Improving research capability is hampered, however, by lack of funding and institutional barriers to change and barriers within individuals. Engendering a sense of identity and ownership in relation to change and a strategic approach to the next Research Assessment Exercise are essential if allied health professional programs are to survive within higher education.


Predictors of physical activity in older adults in an independent living retirement community.
This study was undertaken to examine potential predictors of physical activity in older adults in an independent living retirement community. Participants received a self-developed questionnaire that included questions regarding age, gender, educational attainment, physical activity habits, and physicians' physical activity counseling habits. One hundred nine of 150 questionnaires (72.7%) were completed and returned. Multivariate regression analyses revealed that younger age (p=0.013), higher educational attainment (p=0.003), positive attitude toward physical activity (p=0.030), and receiving advice from a physician to be physically active (p=0.001) were all positive predictors of increased physical activity. The results demonstrate that younger age, higher educational attainment, a positive attitude toward physical activity, and receiving advice from a physician to be physically active result in increased physical activity levels of older adults in an independent living retirement community.


Newton's cradle versus nonbinary collisions.
Newton's cradle is a classical example of a one-dimensional impact problem. In the early 1980s the naive perception of its behavior was corrected: For example, the impact of a particle does not exactly cause the release of the farthest particle of the target particle train, if the target particles have been just in contact with their own neighbors. It is also known that the naive picture would be correct if the whole process consisted of purely binary collisions. Our systematic study of particle systems with truncated power-law repulsive force shows that the quasibinary collision is recovered in the limit of hard core repulsion, or a very large exponent. In contrast, a discontinuous steplike repulsive force mimicking a hard contact, or a very small exponent, leads to a completely different process: the impacting cluster and the targeted cluster act, respectively, as if they were nondeformable blocks.


Flexible Electronic Substrate Film Fabricated Using Natural Clay and Wood Components with Cross-Linking Polymer.
Requirements for flexible electronic substrate are successfully accomplished by green nanocomposite film fabricated with two natural components: glycol-modified biomass lignin and Li+ montmorillonite clay. In addition to these major components, a cross-linking polymer between the lignin is incorporated into montmorillonite. Multilayer-assembled structure is formed due to stacking nature of high aspect montmorillonite, resulting in thermal durability up to 573 K, low thermal expansion, and oxygen barrier property below measurable limit. Preannealing for montmorillonite and the cross-linking formation enhance moisture barrier property superior to that of industrial engineering plastics, polyimide. As a result, the film has advantages for electronic film substrate. Furthermore, these properties can be achieved at the drying temperature up to 503 K, while the polyimide films are difficult to fabricate by this temperature. In order to examine its applicability for substrate film, flexible electrodes are finely printed on it and touch sensor device can be constructed with rigid elements on the electrode. In consequence, this nanocomposite film is expected to contribute to production of functional materials, progresses in expansion of biomass usage with low energy consumption, and construction of environmental friendly flexible electronic devices.


HPTLC - Bioautographic methods for selective detection of the antioxidant and α-amylase inhibitory activity in plant extracts.
A high-performance thin-layer chromatography (HPTLC) method was developed for quantification of α-amylase inhibitory activity and stigmasterol content in ant plant extracts. An improved HPTLC method for the determination of total free radical scavenging activity in samples using DPPH• is also reported. For quantification of α-amylase inhibitory activity, the developed HPTLC plate is dipped into an α-amylase solution, and the bioautogram is then incubated at 25 °C for 30 min under humid conditions. For visualization of enzyme inhibitory activity, the starch test with an iodine indicator solution is used. The blue zone observed comes from the starch-iodine complex formed from starch that was not hydrolyzed by the amylase due to enzyme inhibition by the compound(s) present in the sample. The area of the blue zones was used to compare and quantify relative α-amylase inhibitory activity in different extracts. Location of the blue zones (hRF) on the plate was used to detect compounds that are responsible for the α-amylase inhibitory activity. Relative α-amylase activity was not related to the antioxidant activity, but was highly correlated with the stigmasterol content in the sample extracts (R = 0.95). Therefore, plant sterols present in the extracts might be responsible for α-amylase inhibitory activities in the extracts. •The developed method for quantification of α-amylase inhibitory activity provides an efficient and effective tool that can be used to screen, detect and quantify α-amylase inhibitory activity in plant extracts.•The proposed protocol is easy to run, involves minimal sample preparation, with multiple samples able to be analyzed in parallel on the same chromatographic plate, in a short time.•There were significant differences in α-amylase inhibitory activity, stigmasterol content, and total free radical scavenging activity between methanol, ethanol, dichloromethane, and ethyl acetate ant plant extracts.


Trypanosoma cruzi dysregulates expression profile of piRNAs in primary human cardiac fibroblasts during early infection phase.
Trypanosoma cruzi, the etiological agent of Chagas Disease, causes severe morbidity, mortality, and economic burden worldwide. Though originally endemic to Central and South America, globalization has led to increased parasite presence in most industrialized countries. About 40% of infected individuals will develop cardiovascular, neurological, and/or gastrointestinal pathologies. Accumulating evidence suggests that the parasite induces alterations in host gene expression profiles in order to facilitate infection and pathogenesis. The role of regulatory gene expression machinery during T. cruzi infection, particularly small noncoding RNAs, has yet to be elucidated. In this study, we aim to evaluate dysregulation of a class of sncRNAs called piRNAs during early phase of T. cruzi infection in primary human cardiac fibroblasts by RNA-Seq. We subsequently performed in silico analysis to predict piRNA-mRNA interactions. We validated the expression of these selected piRNAs and their targets during early parasite infection phase by stem loop qPCR and qPCR, respectively. We found about 26,496,863 clean reads (92.72%) which mapped to the human reference genome. During parasite challenge, 441 unique piRNAs were differentially expressed. Of these differentially expressed piRNAs, 29 were known and 412 were novel. In silico analysis showed several of these piRNAs were computationally predicted to target and potentially regulate expression of genes including SMAD2, EGR1, ICAM1, CX3CL1, and CXCR2, which have been implicated in parasite infection, pathogenesis, and various cardiomyopathies. Further evaluation of the function of these individual piRNAs in gene regulation and expression will enhance our understanding of early molecular mechanisms contributing to infection and pathogenesis. Our findings here suggest that piRNAs play important roles in infectious disease pathogenesis and can serve as potential biomarkers and therapeutic targets.


Oral tolerance: overview and historical perspectives.
Oral tolerance was first detailed almost 100 years ago, and since then, it has been shown repeatedly that feeding a wide variety of nonpathogenic antigens can inhibit subsequent systemic immune responses. All systemic immune responses are susceptible, but the degree and scope of the suppression depends on the nature and dose of the fed antigen. Oral tolerance has been described in most mammals, including humans, and it may be the homeostatic mechanism that prevents hypersensitivity to food antigens, as is found in celiac disease. A similar process may prevent the aberrant immune responses to commensal bacteria that occur in inflammatory bowel disease. The ability of oral tolerance to modulate experimental models of autoimmune and inflammatory disease has led to clinical trials in such diseases as rheumatoid arthritis, multiple sclerosis, and type I diabetes, with only variable success. Despite intense research, the exact mechanisms responsible for the systemic tolerance and the reasons why tolerance is the default response to many fed antigens remain controversial. Early studies suggested that CD8(+) "suppressor" T cells were important, but it is now accepted that it may involve either anergy/deletion of CD4(+) T cells, or the induction of regulatory CD4(+) T cells that produce IL-10 and/or TGFbeta. There may also be a role for CD4(+) CD25(+) T(reg), but how and when all these different mechanisms operate is still unclear. The ability of fed antigens to induce tolerance probably reflects their uptake by "quiescent" antigen-presenting cells in the intestine, with presentation to specific CD4(+) T cells in the absence of costimulation, or with the involvement of inhibitory costimulatory molecules. Dendritic cells in the Peyer's patches or mucosal lamina propria are the most likely APCs involved, but it remains to be determined exactly where these interactions occur and what the precise nature of the relevant dendritic cells is.


A new 5-HT3 receptor ligand. II. Structure-activity analysis of 5-HT3 receptor agonist action in the gut.
Several modified 2-piperazinyl benzoxazole derivatives, which exhibit an agonistic effect on gastrointestinal motility, were synthesized and their effects on the contraction of guinea-pig ileum were examined. The quaternary piperazinyl benzoxazole structure has a restricted conformation and stereostructure compared to those of the other 5-HT3 receptor agonists, serotonin and meta-chlorophenylbiguanide. The mutual positions of the aromatic ring, nitrogen atom and terminal amine are considered to form the pharmacophore of the 5-HT3 receptor agonist in the gut. In the serotonin-evoked reflex bradycardia [Bezold-Jarisch (B-J) reflex] inhibition test using rats the B-J reflex-inducing ratio was different for each synthesized compound. These results suggest that, in these 5-HT3 receptor agonists, the substituents of the benzoxazole ring influence the B-J reflex-inducing activity in rats.


NMDA receptor modulation by the neuropeptide apelin: implications for excitotoxic injury.
Excitotoxic neuronal damage via over-activation of the NMDA receptor has been implicated in many neurodegenerative diseases. In vitro modeling of excitotoxic injury has shown that activation of G-protein coupled receptors (GPCRs) counteracts such injury through modulation of neuronal pro-survival pathways and/or NMDA receptor signaling. We have previously demonstrated that the GPCR APJ and its endogenous neuropeptide ligand apelin can protect neurons against excitotoxicity, but the mechanism(s) of this neuroprotection remain incompletely understood. We hypothesized that apelin can promote neuronal survival by activating pro-survival signaling as well as inhibiting NMDA receptor-mediated excitotoxic signaling cascades. Our results demonstrate that (i) apelin activates pro-survival signaling via inositol trisphosphate (IP(3) ), protein kinase C (PKC), mitogen-activated protein kinase kinase 1/2 (MEK1/2), and extracellular signal-regulated kinase-1/2 (ERK1/2) to protect against excitotoxicity, and (ii) apelin inhibits excitotoxic signaling by attenuating NMDA receptor and calpain activity, and by modulating NMDA receptor subunit NR2B phosphorylation at serine 1480. These studies delineate a novel apelinergic signaling pathway that concurrently promotes survival and limits NMDA receptor-mediated injury to protect neurons against excitotoxicity. Defining apelin-mediated neuroprotection advances our understanding of neuroprotective pathways and will potentially improve our ability to develop therapeutics for excitotoxicity-associated neurodegenerative disorders.


Whole exome sequencing of a family revealed a novel variant in the CHM gene, c.22delG p.(Glu8Serfs*4), which co-segregated with choroideremia.
Choroideremia is a complex form of blindness-causing retinal degeneration. The aim of the present study was to investigate the pathogenic variant and molecular etiology associated with choroideremia in a Chinese family. All available family members underwent detailed ophthalmological examinations. Whole exome sequencing, bioinformatics analysis, Sanger sequencing, and co-segregation analysis of family members were used to validate sequencing data and confirm the presence of the disease-causing gene variant. The proband was diagnosed with choroideremia on the basis of clinical manifestations. Whole exome sequencing showed that the proband had a hemizygous variant in the CHM gene, c.22delG p. (Glu8Serfs*4), which was confirmed by Sanger sequencing and found to co-segregate with choroideremia. The variant was classified as likely pathogenic and has not previously been described. These results expand the spectrum of variants in the CHM gene, thus potentially enriching the understanding of the molecular basis of choroideremia. Moreover, they may provide insight for future choroideremia diagnosis and gene therapy.


Health system strengthening: Integration of breast cancer care for improved outcomes.
The adoption of the goal of universal health coverage and the growing burden of cancer in low- and middle-income countries makes it important to consider how to provide cancer care. Specific interventions can strengthen health systems while providing cancer care within a resource-stratified perspective (similar to the World Health Organization-tiered approach). Four specific topics are discussed: essential medicines/essential diagnostics lists; national cancer plans; provision of affordable essential public services (either at no cost to users or through national health insurance); and finally, how a nascent breast cancer program can build on existing programs. A case study of Zambia (a country with a core level of resources for cancer care, using the Breast Health Global Initiative typology) shows how a breast cancer program was built on a cervical cancer program, which in turn had evolved from the HIV/AIDS program. A case study of Brazil (which has enhanced resources for cancer care) describes how access to breast cancer care evolved as universal health coverage expanded. A case study of Uruguay shows how breast cancer outcomes improved as the country shifted from a largely private system to a single-payer national health insurance system in the transition to becoming a country with maximal resources for cancer care. The final case study describes an exciting initiative, the City Cancer Challenge, and how that may lead to improved cancer services.


Role of cyclic AMP in insulin release evoked by glucose and other secretagogues.
A close coupling in time-course and dose-dependency exists between cyclic AMP and insulin responses to glucose as tested in isolated islets of Langerhans from the rate and other species. Other secretagogues are also capable of inducing a cyclic AMP response. Under circumstances where the insulin response is reduced, secretion can, however, proceed without a measurable increase in cyclic AMP. "Classical" cyclic AMP-raising agents such as the methylxanthines are unable to induce substantial insulin release in the absence of glucose; however, short-term previous exposure to 27.7 mM glucose transforms 3-isobutyl-1-methylxanthine into a potent insulin-releasing agent. It is concluded that 1) all secretagogues share the stimulation of cyclic AMP as part of the insulinogenic signal; 2) a cyclic AMP response may be needed only for optimal secretory responsiveness of the B-cell; 3) whether a rise in cyclic AMP is solely sufficient to trigger insulin secretion depends on the extent to which a "memory" of exposure to glucose is present in the B-cell.


The Effects of Twitter Users' Gender and Weight on Viral Behavioral Intentions Toward Obesity-Related News.
In this study, male and female participants were exposed to identical news stories covering obesity topics paired with tweets from Twitter users. Our study aimed at understanding how obesity-related news combined with user-generated social media posts (i.e., tweets) affect consumers' evaluations of online content and viral behavioral intentions (the intentions to like, share, and comment). An experiment (N = 316) explored how gender and weight of a Twitter user (tweeter) affect participants' evaluations and viral behavioral intentions toward news stories. Participants differed in their evaluations of and viral behavioral intentions for news stories as a function of Twitter users' gender and weight, as well as participants' gender. While participants expressed more favorable attitudes toward news stories paired with tweets by overweight than healthy females (with the opposite true for tweets by male users), participants expressed greater viral behavioral intentions for news stories paired with tweets by healthy weight than overweight user. These effects were more pronounced among male than female participants. Findings are discussed within the context of social media posts and their persuasive effects in relation to attitude and behavior changes.


Highly Efficient Single-Layer Phosphorescent Organic Light-Emitting Diodes Based on Co-Host Structure.
High-efficiency single-layer organic light-emitting diodes (OLEDs) based on a simple structure doped with iridium(III) bis(4-phenylthieno[3,2-c]pyridinato-N,C2') acetylacetonate (PO-01) as emission dyes are realized, achieving maximum current efficiency (CE) and power efficiency (PE) of 37.1 cd A-1 and 33.3 lm W-1 as well as low turn-on voltage of 3.31 V. Such superior performance is mainly attributed to the employment of a uniform co-host structure and assisted charge transport property of phosphors dyes, which were in favor of the balance of charge carrier injection and transport in the single emitting layer (EML). Moreover, systematic researches on the position of exciton recombination region and the dopant effect on charge carriers were subsequently performed to better understand the operational mechanism. It could be experimentally found that the orange emitting dopants promoted the acceleration of the charge carriers transport and raised the exciton recombination efficiency, eventually leading to an excellent performance of single-layer OLEDs.


Isokinetic Robotic Device to Improve Test-Retest and Inter-Rater Reliability for Stretch Reflex Measurements in Stroke Patients with Spasticity.
Measuring spasticity is important in treatment planning and determining efficacy after treatment. However, the current tool used in clinical settings has been shown to be limited in inter-rater reliability. One factor in this poor inter-rater reliability is the variability of passive motion while measuring the angle of catch (AoC) measurements. Therefore, an isokinetic device has been proposed to standardize the manual joint motion; however, the benefits of isokinetic motion for AoC measurements has not been tested in a standardized manner. This protocol investigates whether isokinetic motion itself can improve inter-rater reliability for AoC measurements. For this purpose, a robotic isokinetic device was developed that is combined with surface electromyography (EMG). Two conditions, manual and isokinetic motions, are compared with the standardized method to measure the angle and subjective feeling of catch. It is shown that in 17 stroke patients with mild elbow flexor spasticity, isokinetic motion improved the intraclass correlation coefficient (ICC) for inter-rater reliability of AoC measurements to 0.890 [95% confidence interval (CI): 0.685-0.961] by the EMG criteria, and 0.931 (95% CI: 0.791-0.978) by the torque criteria, from 0.788 (95% CI: 0.493-0.920) by manual motion. In conclusion, isokinetic motion itself can improve inter-rater reliability of AoC measurements in stroke patients with mild spasticity. Given that this system may provide greater standardized angle measurements and catch of feeling, it may be a good option for the evaluation of spasticity in a clinical setting.


Specific and differential prediction of health anxiety by disgust sensitivity and propensity.
Current models of health anxiety suggest that fear resulting from false alarms to perceived threats to one's health results in the development of hypochondriasis and related disorders. Disgust has been proposed as an affective response that may function as an etiological and maintenance mechanism in health anxiety. Moreover, the way in which an individual perceives the disgust response (disgust sensitivity) may affect health anxiety, separately from their likelihood of experiencing disgust (disgust propensity). The present study utilized multiple hierarchical regression analysis to investigate the degree to which self-reported disgust sensitivity and disgust propensity differentially predict elevated health anxiety in a sample of 620 non-treatment-seeking undergraduates. Further, this effect is tested in comparison to that of anxiety sensitivity, a construct demonstrated to be strongly related to health anxiety. Analyses indicate that disgust sensitivity, rather than disgust propensity, is primarily responsible for this relation. An additional analysis tested the specificity of disgust sensitivity relative to anxiety sensitivity. Disgust sensitivity was no longer significant after including anxiety sensitivity in the model. Suggestions for further evaluation of this relation are provided. These results suggest that although disgust sensitivity may appear related to health anxiety, this relation may be confounded by anxiety sensitivity.