An Edge Computing Based Smart Healthcare Framework for Resource Management.
The revolution in information technologies, and the spread of the Internet of Things (IoT) and smart city industrial systems, have fostered widespread use of smart systems. As a complex, 24/7 service, healthcare requires efficient and reliable follow-up on daily operations, service and resources. Cloud and edge computing are essential for smart and efficient healthcare systems in smart cities. Emergency departments (ED) are real-time systems with complex dynamic behavior, and they require tailored techniques to model, simulate and optimize system resources and service flow. ED issues are mainly due to resource shortage and resource assignment efficiency. In this paper, we propose a resource preservation net (RPN) framework using Petri net, integrated with custom cloud and edge computing suitable for ED systems. The proposed framework is designed to model non-consumable resources and is theoretically described and validated. RPN is applicable to a real-life scenario where key performance indicators such as patient length of stay (LoS), resource utilization rate and average patient waiting time are modeled and optimized. As the system must be reliable, efficient and secure, the use of cloud and edge computing is critical. The proposed framework is simulated, which highlights significant improvements in LoS, resource utilization and patient waiting time.


Survivin and pancreatic cancer.
Pancreatic cancer is estimated to be the fourth most common cancer in men and fifth in women in the world and has poor prognosis. In recent years, more and more effort has been put on the relationship between pancreatic cancer and apoptosis. As a newly discovered inhibitor of apoptosis, survivin has drawn more attention. Strong evidence has shown that survivin is expressed in pancreatic cancer cells on frozen sections. Survivin increases in the development of pancreatic ductal adenocarcinoma and its expression can be a marker in evaluating the prognosis of pancreatic cancer patients. Survivin itself may be a new target in the treatment of pancreatic cancer and a survivin DNA vaccine could generate specific antitumor effects in pancreatic carcinoma models.


PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis.
Many bacteria switch between a sessile and a motile mode in response to environmental and host-related signals. Porphyromonas gingivalis, an oral anaerobe implicated in the etiology of chronic periodontal disease, has long been described as a nonmotile bacterium. And yet, recent studies have shown that under certain conditions, P. gingivalis is capable of surface translocation. Considering these findings, this work aimed to increase our understanding of how P. gingivalis transitions between sessile growth and surface migration. Here, we show that the peptidylarginine deiminase secreted by P. gingivalis (PPAD), an enzyme previously shown to be upregulated during surface translocation and to constrain biofilm formation, promotes surface translocation. In the absence of PPAD, the production of outer membrane vesicles (OMVs) was drastically reduced. In turn, there was a reduction in gingipain-mediated proteolysis and a reduced zone of hydration around the site of inoculation. Transcriptome sequencing (RNA-Seq) and metabolomics analyses also showed that these changes corresponded to a shift in arginine metabolism. Overall, this report provides new evidence for the functional relevance of PPAD and proteases, as well as the importance of PPAD activity in OMV biogenesis and release. Our findings support the model that citrullination is a critical mechanism during lifestyle transition between surface-attached growth and surface translocation by modulating OMV-mediated proteolysis and arginine metabolism.IMPORTANCE Gram-negative bacteria produce nanosized OMVs that are actively released into their surroundings. The oral anaerobe P. gingivalis is prolific in OMV production, and many of the proteins packaged in these vesicles are proteolytic or protein-modifying enzymes. This includes key virulence determinants, such as the gingipains and PPAD (a unique peptidylarginine deiminase). Here, we show that PPAD activity (citrullination) is involved in OMV biogenesis. The study revealed an unusual mechanism that allows this bacterium to transform its surroundings. Since OMVs are detected in circulation and in systemic tissues, our study results also support the notion that PPAD activity may be a key factor in the correlation between periodontitis and systemic diseases, further supporting the idea of PPAD as an important therapeutic target.


Profiling executive dysfunction in adults with autism and comorbid learning disability.
Executive dysfunction is thought to be primary to autism. We examined differences in executive function between 20 adults with autism and learning disability and 23 individuals with learning disabilities outside the autistic spectrum. All participants were matched for chronological age and full-scale IQ, and were given a battery of tasks assessing fluency, planning, set-shifting, inhibition and working memory. Analyses of the individual tasks revealed very few significant differences between the two groups. However, analyses of composite scores derived for each executive domain revealed that the group with autism showed impaired performance on the working memory and planning tests. Together, these two measures were sufficient to classify participants into their diagnostic groups significantly better than would be expected by chance (75% of the autism group; 65% of the control group). Executive impairments were neither universal nor exclusive to the autism group, and we suggest that an alternative cognitive theory may better explain the cognitive profile we found.


Development and application of a survey instrument to measure collaboration among health care and social services organizations.
To measure strategies of interorganizational collaboration among health care and social service organizations that serve older adults. Twenty Hospital Service Areas (HSAs) in the United States. We developed and validated a novel scale to characterize interorganizational collaboration, and then tested its application by assessing whether the scale differentiated between HSAs with high vs low performance on potentially avoidable health care use and spending for Medicare beneficiaries. Health care and social service organizations (N = 173 total) in each HSA completed a 12-item collaboration scale, three questions about collaboration behaviors, and a detailed survey documenting collaborative network ties. We identified two distinguishable subscales of interorganizational collaboration: (a) Aligning Strategy and (b) Coordinating Current Work. Each subscale demonstrated convergent validity with the organization's position in the collaborative network, and with collaboration behaviors. The full scale and Coordinating Current Work subscale did not differentiate high- vs low-performing HSAs, but the Aligning Strategy subscale was significantly higher in high-performing HSAs than in low-performing HSAs (P = .01). Cross-sector collaboration-and particularly Aligning Strategy-is associated with health care use and spending for older adults. This new survey measure could be used to track the impact of interventions to foster interorganizational collaboration.


Identification of the domains of cauliflower mosaic virus protein P6 responsible for suppression of RNA silencing and salicylic acid signalling.
Cauliflower mosaic virus (CaMV) encodes a 520 aa polypeptide, P6, which participates in several essential activities in the virus life cycle including suppressing RNA silencing and salicylic acid-responsive defence signalling. We infected Arabidopsis with CaMV mutants containing short in-frame deletions within the P6 ORF. A deletion in the distal end of domain D-I (the N-terminal 112 aa) of P6 did not affect virus replication but compromised symptom development and curtailed the ability to restore GFP fluorescence in a GFP-silenced transgenic Arabidopsis line. A deletion in the minimum transactivator domain was defective in virus replication but retained the capacity to suppress RNA silencing locally. Symptom expression in CaMV-infected plants is apparently linked to the ability to suppress RNA silencing. When transiently co-expressed with tomato bushy stunt virus P19, an elicitor of programmed cell death in Nicotiana tabacum, WT P6 suppressed the hypersensitive response, but three mutants, two with deletions within the distal end of domain D-I and one involving the N-terminal nuclear export signal (NES), were unable to do so. Deleting the N-terminal 20 aa also abolished the suppression of pathogen-associated molecular pattern-dependent PR1a expression following agroinfiltration. However, the two other deletions in domain D-I retained this activity, evidence that the mechanisms underlying these functions are not identical. The D-I domain of P6 when expressed alone failed to suppress either cell death or PR1a expression and is therefore necessary but not sufficient for all three defence suppression activities. Consequently, concerns about the biosafety of genetically modified crops carrying truncated ORFVI sequences appear unfounded.


Heart work: Indigenous doulas responding to challenges of western systems and revitalizing Indigenous birthing care in Canada.
In Canada, there has been a significant increase in the training of Indigenous doulas, who provide continuous, culturally appropriate support to Indigenous birthing people during pregnancy, birth, and the postpartum period. The purpose of our project was to interview Indigenous doulas across Canada in order to document how they worked through the logistics of providing doula care and to discern their main challenges and innovations. Our paper analyzes interviews conducted with members of five Indigenous doula collectives across Canada, from the provinces of British Columbia, Manitoba, Ontario, Quebec and Nova Scotia. Semi-structured interviews were conducted with members of the five Indigenous doula collectives across Canada in 2020 as part of the project, "She Walks With Me: Supporting Urban Indigenous Expectant Mothers Through Culturally Based Doulas." Interview transcripts were approved by participants and subsequently coded by the entire research team to identify key themes. Our paper examines two themes that emerged in interviews: the main challenges Indigenous doulas describe confronting when working within western systems, and how they navigate and overcome these obstacles. Specifically, interview participants described tensions with the biomedical approach to maternal healthcare and conflicts with the practice of Indigenous infant apprehension. In response to these challenges, Indigenous doulas are working to develop Indigenous-specific doula training curricula, engaging in collective problem-solving, and advocating for the reformation of a grant program in order to fund more Indigenous doulas. Both the biomedical model of maternal healthcare and the crisis of Indigenous infant apprehension renders Canadian hospitals unsafe and uncomfortable spaces for many Indigenous birthing people and their families. Indigenous doulas are continually navigating these challenges and creatively and concertedly working towards the revitalization of Indigenous birthing care. Indigenous doula care is critical to counter systemic, colonial barriers and issues that disproportionately impact Indigenous families, as well as recentering birth as the foundation of Indigenous sovereignty and community health.


Identifying proteins that can form tyrosine-cysteine crosslinks.
Protein cofactors represent a unique class of redox active posttranslational protein modifications formed in or by metalloproteins. Once formed, protein cofactors provide a one-electron oxidant, which is tethered to the protein backbone. Twenty-five proteins are known to contain protein cofactors, but this number is likely limited by the use of crystallography as the identification technique. In order to address this limitation, a search of all reported protein structures for chemical environments conducive to forming a protein cofactor through tyrosine and cysteine side chain crosslinking yielded three hundred candidate proteins. Using hydrogen bonding and metal center proximity, the three hundred proteins were narrowed to four highly viable candidates. An orphan metalloprotein (BF4112) was examined to validate this methodology, which identifies proteins capable of crosslinking tyrosine and cysteine sidechains. A tyrosine-cysteine crosslink was formed in BF4112 using copper-dioxygen chemistry, as in galactose oxidase. Liquid chromatography-MALDI mass spectrometry and optical spectroscopy confirmed tyrosine-cysteine crosslink formation in BF4112. This finding demonstrates the efficacy of these predictive methods and the minimal constraints, provided by the BF4112 protein structure, in tyrosine-cysteine crosslink formation. This search method, when coupled with physiological evidence for crosslink formation and function as a cofactor, could identify additional protein-derived cofactors.


Preferential release of tri-iodothyronine following stimulation by thyrotrophin or thyrotrophin-releasing hormone in sheep of different ages.
The influence of TRH and TSH injections on plasma concentrations of tri-iodothyronine (T3) and thyroxine (T4) was investigated in neonatal (injection within 0.5 h after delivery) and growing lambs and in normal, pregnant and lactating adult ewes (all 2 years old and originating from Suffolk, Milksheep and Texal crossbreeds). Neonatal lambs had higher levels of T3, T4 and GH compared with all other groups, whereas prolactin and TSH were higher in lactating ewes. In all animals, injections of TRH increased plasma concentrations of prolactin and TSH after 15 min but not of GH at any time. Small increases in T3 and T4 were observed in neonatal lambs, without any effect on the T3 and T4 ratio, after prolactin administration, whereas prolactin did not influence plasma concentrations of T3 or T4 in all other experimental groups. Similar results for thyroid hormones were obtained after TRH or TSH injections. It was therefore concluded that the effects observed after TRH challenge were mediated by the release of TSH. With the possible exception of neonatal lambs, plasma concentrations of T3 after administration of TRH or TSH were always increased before those of T4; the increase in T3 occurred within 0.5-1 h compared with 2-4 h for T4 in all experimental groups. This resulted in an increased ratio of plasma T3 to T4 up to 4 h after injection. It is concluded that, in sheep, TRH and TSH preferentially release T3 from the thyroid gland probably by a stimulatory effect of TSH on the intrathyroidal conversion of T3 to T4.


RtsA and RtsB coordinately regulate expression of the invasion and flagellar genes in Salmonella enterica serovar Typhimurium.
Salmonella enterica serovar Typhimurium encounters numerous host environments and defense mechanisms during the infection process. The bacterium responds by tightly regulating the expression of virulence genes. We identified two regulatory proteins, termed RtsA and RtsB, which are encoded in an operon located on an island integrated at tRNA(PheU) in S. enterica serovar Typhimurium. RtsA belongs to the AraC/XylS family of regulators, and RtsB is a helix-turn-helix DNA binding protein. In a random screen, we identified five RtsA-regulated fusions, all belonging to the Salmonella pathogenicity island 1 (SPI1) regulon, which encodes a type III secretion system (TTSS) required for invasion of epithelial cells. We show that RtsA increases expression of the invasion genes by inducing hilA expression. RtsA also induces expression of hilD, hilC, and the invF operon. However, induction of hilA is independent of HilC and HilD and is mediated by direct binding of RtsA to the hilA promoter. The phenotype of an rtsA null mutation is similar to the phenotype of a hilC mutation, both of which decrease expression of SPI1 genes approximately twofold. We also show that RtsA can induce expression of a SPI1 TTSS effector, slrP, independent of any SPI1 regulatory protein. RtsB represses expression of the flagellar genes by binding to the flhDC promoter region. Repression of the positive activators flhDC decreases expression of the entire flagellar regulon. We propose that RtsA and RtsB coordinate induction of invasion and repression of motility in the small intestine.


Values as predictors of judgments and behaviors: the role of abstract and concrete mindsets.
This research makes strides toward reconciling mixed findings in the value-behavior relation by positing that values are abstract representations of ideal end states that are more likely to influence behavior when individuals think abstractly (vs. concretely) and focus on high- (vs. low-) level motivations for interpreting their actions. In 6 experiments, the authors measured the importance of values (or made them salient via a priming procedure) and simultaneously manipulated accessible mindsets (abstract vs. concrete), and assessed their effect on judgments and behaviors. An abstract (and not a concrete) mindset led participants to engage in judgments or behaviors that were consistent with a broad range of values, including power, benevolence, universalism, self-direction, individualism, and collectivism. These results support the notion that values are more likely to be expressed through value-congruent judgments and behaviors when individuals think abstractly about their actions, and not when they think concretely. Two of the experiments examined the process underlying these effects.


ROS1 Rearrangement in Thyroid Cancer.
Aberrations involving the ROS1 gene have not been reported in thyroid cancer. Here, a case of ROS1-associated thyroid cancer with unique and aggressive characteristics is presented. A 24-year-old athlete presented with a 3.5 cm left paramedian upper neck mass. Open biopsy demonstrated a papillary thyroid carcinoma arising in the pyramidal lobe. Additional imaging revealed involvement of her cricothyroid membrane, thyroid laryngeal cartilage, and left vocal cord. Complete en bloc surgical resection of the thyroid with cricothyroid membrane and endolarynx was performed with negative surgical margins. Microscopically, the tumor was largely solid with microfollicular architecture with focal cytoplasmic clearing and nodular invasion with rare true papillae, extending posteriorly through the cricothyroid membrane into the deep soft tissue of the left anterior vocal cord (pT4a). Metastases were present in 5/11 lateral neck and pretracheal lymph nodes with a size up to 0.4 cm (pN1b) with perinodal lymphatic involvement. She was staged according to her age (<45 years) as stage I. The solid-variant histology and locally aggressive behavior triggered oncologic genotyping, which was performed using massive parallel sequencing and anchored multiplexed next-generation sequencing for gene fusion detection on formalin-fixed paraffin embedded tissue. Targeted genotyping did not reveal a panel-specific point mutation. However, gene fusion assessment demonstrated a gene fusion involving ROS1. Mapping of the fusion and sequence analysis identified CCDC30 as the ROS1 fusion partner. Sequence-based prediction of the fusion product revealed the coiled-coil domain 30 (CCDC30) gene fused to the N-terminal ROS1 kinase domain, with CCDC30 as the postulated driver of ROS1-kinase constitutive activation. ROS1 rearrangement was confirmed using fluorescent in situ hybridization as an orthogonal method. A review of all currently reported ROS1 fusions in >7000 samples (The Cancer Genome Atlas) showed no prior report of ROS1-CCDC30, ROS1 fusions, or presence of ROS1 aberrations in thyroid cancer. Herein, the first case of a ROS1 rearrangement in a papillary thyroid carcinoma with a locally aggressive presentation is reported. A review of additional patients with solid-variant papillary thyroid carcinoma and similar clinical characteristics with undetermined tumor genetics is needed, especially in light of the availability of ROS1-targeted therapeutics.


The pathogenesis of radiation injury in complex tissues: an overview of problems and probes.
The evaluation of radiation injury in complex organs has tended to lag behind comparable areas of investigative interest. This observation is somewhat surprising in view of the increased use of radiotherapy as a primary or adjuvant mode of therapy for malignant disease. In part, this problem appears to relate to the difficulty of identifying and quantifying the morphologic consequences of radiation injury in complex organs, in which the various component tissues exhibit a broad spectrum of radiosensitivities. Two approaches have been employed to address this problem: (1) utilization of sophisticated probes to evaluate the functional and morphologic sequelae of radiation injury and (2) segmentation of complex tissues into their component parts, which are then evaluated individually. Both approaches are illustrated in the papers presented in this issue. The purpose of this overview is to call attention to some of the attendant difficulties of the former approach, as seen in an ongoing investigative program concerned with radiation injury of the kidney.


Research and scholarship of clinical laboratory science faculty members.
To describe the research and scholarly productivity of faculty in four-year college and university clinical laboratory science (CLS) programs. To identify hours spent in research, numbers of presentations and publications, and external funding. In 2008, a national study involving 106 college and university CLS programs was conducted to determine whether faculty were participating in research. A questionnaire, in electronic format, was distributed to 448 faculty members. Data from 2001 to 2008, and from 275 respondents (61% response) representing 93 of 106 (88%) CLS programs were analyzed. The study took place at The Ohio State University with collaboration from the University of Minnesota. All CLS faculty within a four-year university or college sponsoring a NAACLS-accredited CLS program were invited to participate. To determine whether CLS faculty scholarly activities have been strengthened in the past decade. To quantitate scholarship productivity. To assess faculty perceptions of their employment environments. Data indicate that faculty who possess earned doctorates have higher levels of research productivity. While 52% of CLS faculty hold doctorates and 45% are tenured, 36% of all CLS faculty members have not published a research paper or abstract since 2001. On the other hand, 19% have published 11 or more times. CLS faculty were also awarded a total of $62 million in external funding, 83% from government sources. Teaching remains a primary responsibility of many faculty members. In the past decade, and generally speaking, CLS faculty have made some progress in scholarship including highest degree obtained, publications, presentations, and grantsmanship.


Historical perspective on folic acid and challenges in estimating global prevalence of neural tube defects.
Neural tube defects (NTD) are major congenital malformations affecting births worldwide. NTD are associated with life-long disability, significant medical care costs, and child mortality. Their prevalence varies worldwide. We conducted a review of published literature and surveillance systems to examine challenges in estimating an overall global prevalence estimate for NTD. Our review showed that most low- and middle-income countries do not track NTD and indicate a high prevalence of these malformations where data are available. Challenges in global NTD prevalence estimation include (1) quality of surveillance methods, (2) existing risk factors (including geographic or socioeconomic factors, availability and use of folic acid, and racial-ethnic and genetic factors), and (3) limitations in education and access to care. We recommend population-based surveillance systems tracking all pregnancy outcomes and major risk factors. Countries should invest in sustainable, multisource surveillance systems, in parallel to folic acid interventions, for gaining a more accurate knowledge of global prevalence of NTD than we currently have. Such efforts will assist in both global prevention of NTD and periodic evaluation of folic acid interventions for NTD reduction. Global NTD prevalence data can drive political will and accelerate the implementation and evaluation of NTD prevention programs.


Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.
To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations.


Predicting patterns of interaction between children with cerebral palsy and their mothers.
Children with cerebral palsy (CP) have often been described as passive communicators. Their familiar conversation partners tend to direct and control interaction. Such conversation patterns may have various precursors: children's motor impairment, their intelligibility difficulties, and/or their level of cognitive development. To test the comparative influence of these factors, measures of motor function, speech, communication, cognitive and language skills were applied in 40 children (18 males, 22 females) with CP who were aged from 2 years 8 months to 10 years. These variables were correlated with measures relating to interaction patterns to investigate whether individual features predicted communication style. In this group, poor speech intelligibility was the main predictor of restrictive communication patterns, such as fewer child-initiated conversation exchanges, more simple child communicative acts such as yes/no answers and acknowledgements of the other partner's messages. Results support the provision of therapy to increase children's intelligibility, whether spoken or augmented, such as the introduction of communication aids and training programmes for parents.


Comparative effectiveness of surgery in traumatic acute subdural and intracerebral haematoma: study protocol for a prospective observational study within CENTER-TBI and Net-QuRe.
Controversy exists about the optimal treatment for patients with a traumatic acute subdural haematoma (ASDH) and an intracerebral haematoma/contusion (t-ICH). Treatment varies largely between different regions. The effect of this practice variation on patient outcome is unknown. Here, we present the protocol for a prospective multicentre observational study aimed at comparing the effectiveness of different treatment strategies in patients with ASDH and/or t-ICH. Specifically, the aims are to compare (1) an acute surgical approach to an expectant approach and (2) craniotomy to decompressive craniectomy when evacuating the haematoma. Patients presenting to the emergency room with an ASDH and/or an t-ICH are eligible for inclusion. Standardised prospective data on patient and injury characteristics, treatment and outcome will be collected on 1000 ASDH and 750 t-ICH patients in 60-70 centres within two multicentre prospective observational cohort studies: the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Neurotraumatology Quality Registry (Net-QuRe). The interventions of interest are acute surgery, defined as surgery directly after the first CT at presentation versus late or no surgery and craniotomy versus decompressive craniectomy. The primary outcome measure is the Glasgow Outcome Score-Extended at 6 months. Secondary outcome measures include in-hospital mortality, quality of life and neuropsychological tests. In the primary analysis, the effect of treatment preference (eg, proportion of patients in which the intervention under study is preferred) per hospital will be analysed with random effects ordinal regression models, adjusted for casemix and stratified by study. Such a hospital-level approach reduces confounding by the indication. Sensitivity analyses will include propensity score matching, with treatment defined on patient level. This study is designed to determine the best acute management strategy for ASDH and t-ICH by exploiting the existing between-hospital variability in surgical management. Ethics approval was obtained in all participating countries. Results of surgical management of ASDH and t-ICH/contusion will separately be submitted for publication in a peer-reviewed journal. NCT02210221 and NL 5761.


Mortality after low-energy fractures in patients aged at least 45 years old.
Fractures sustained in low-energy injuries are recognized as a major public health issue, although, with the exception of proximal femoral fractures, little is known about the subsequent mortality rates. The aim of this study was to compare the survival rates of a population of individuals who sustained 3 types of low-energy fractures with age-matched cohorts from within the same population. Between January 1988 and December 1999, data were prospectively gathered from all inpatient and outpatient fracture cases at a single trauma unit. During this time, 18,019 patients sustained low-energy fractures of the proximal femur, proximal humerus, or wrist. Survival analysis using the life table method was performed and hazard ratios calculated for risk of mortality when compared to general population controls within the first year postinjury, between the second and fifth years postinjury, and between the sixth and tenth years postinjury. The effects of various social, physical, and mental health parameters on survival were also analyzed using a Cox proportional hazards model. The patients who sustained proximal femoral fractures were older and significantly more physically and mentally impaired than the patients who sustained wrist fractures. The demographic features of the proximal humeral fracture cohort were intermediate between these 2 groups. The mortality was high in all age groups following proximal femoral and proximal humeral fractures, though the relative risk of death, when compared to age-matched population controls, decreased with increasing age at fracture. The risk of death in these groups was greatest in younger individuals and in the first year postinjury. The wrist fracture population had similar or enhanced survival when compared to age-matched population controls. The mortality after fracture was independently predicted by age at fracture, male gender, and use of walking aids, for all 3 fracture groups (P < 0.05), and additionally by level of social dependence in the proximal femoral fracture group (P < 0.05). level one, prospective cohort study. There is prolonged risk of premature mortality seen in both proximal femoral and proximal humeral fracture groups in the younger age cohorts, possibly as a result of concomitant medical comorbidities contributing to their premature deaths. Elderly patients sustaining proximal femoral fractures, despite high risk of mortality in the first year after injury, have survival approaching those of the general population in the longer term. Elderly patients who sustain wrist fractures have consistently better survival rates than the general population. This group of patients may be physiologically more robust than their age-matched peers in the general population.


Synergistic effects of urban tributary mixing on dissolved organic matter biodegradation in an impounded river system.
Dams and wastewater may greatly perturb riverine fluxes of dissolved organic matter (DOM) and CO2, yet little is known about the relationships between altered DOM quality and CO2 emission in eutrophic impounded river systems. A basin-wide field survey of surface water CO2 and dissolved organic carbon (DOC) was combined with laboratory incubations to examine how dams and urban tributaries delivering treated wastewater influence longitudinal patterns in DOM properties and CO2 along the impounded Han River traversing Seoul metropolitan area. Fluorescent DOM indices including parallel factor analysis (PARAFAC) components were used to characterize DOM in relation to biodegradable DOC (BDOC). Compared with distinct downstream increases in DOC and CO2, BDOC concentration and its proportion in DOC (%BDOC) were highly variable along the mainstem and peaked at urban tributaries. Longitudinal increases in fluorescence index (FI), biological index (BIX), and two PARAFAC components (C2 and C3) contrasted with general decreases in humification index (HIX) and C1, reflecting increasing downstream inputs of anthropogenic DOM. During a 5-day incubation employing continuous CO2 measurements, the cumulative production of CO2 in the mainstem water mixed with urban tributary water was significantly higher than the level expected for conservative mixing of the two samples, indicating a synergistic enhancement of DOM biodegradation. Molecular formulas identified by Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS) revealed more consumed molecules in the mainstem water and more newly produced molecules in the tributary water over the 5-day incubation, implying abundant labile components in the mainstem water discharged from the upstream dam and highly processed tributary DOM limited in immediately biodegradable organic materials. Downstream increases in CO2 and DOC along the Han River, combined with the synergistic effect observed in the mixed water, suggest that mixing wastewater-derived DOM with labile autochthonous DOM can enhance CO2 production in the river system perturbed by impoundment and wastewater.


Superhydrophobic highly flexible doubly cross-linked aerogel/carbon nanotube composites as strain/pressure sensors.
We report novel superhydrophobic highly flexible composites based on a doubly cross-linked (DCL) aerogel and carbon nanotubes (CNTs) for strain/pressure sensing. The DCL aerogel/CNT composite is prepared by radical polymerization of vinylmethyldimethoxysilane and vinyldimethylmethoxysilane, respectively, followed by hydrolytic co-polycondensation of the obtained polyvinylmethyldimethoxysilane and polyvinyldimethylmethoxysilane, combined with the incorporation of CNTs. Benefiting from the flexible methyl-rich DCL structure of the aerogel and conductive CNTs, the resultant DCL aerogel/CNT composite combines superhydrophobicity, high compressibility, high bendability, high elasticity, and strain- and pressure-sensitive conductivity. We demonstrate that the composite can be applied as a high-performance strain/pressure sensor for the detection of arterial pulse waves and joint bending with high sensitivity and high durability against humidity.


Rhodococcus fascians infection after haematopoietic cell transplantation: not just a plant pathogen?
Rhodococcus spp. have been implicated in a variety of infections in immunocompromised and immunocompetent hosts. Rhodococcus equi is responsible for the majority of reported cases, but Rhodococcus erythropolis, Rhodococcusgordoniae and Rhodococcusruber infections have been described. There are no prior reports of human infection with Rhodococcus fascians. We describe the unexpected finding of R. fascians in liver lesions incidentally noted at autopsy in an immunosuppressed patient status after bone-marrow transplant for acute lymphoblastic leukaemia who died of unrelated causes (septic shock due to Clostridium difficile colitis). At autopsy, an otherwise unremarkable liver contained several dozen well-demarcated sclerotic-appearing lesions measuring 0.1-0.3 cm in size. The absence of other bacterial or fungal DNA in the setting of histologically visible organisms argues against its presence as a contaminant and raises the consideration that R. fascians represents a human pathogen for the immunocompromised. Whether it represents the sole infectious agent responsible for the miliary lesions or a partially treated co-infection is impossible to determine, but our finding continues to reinforce the importance of molecular techniques in associating organisms with sites of infection and optimizing treatment of infectious diseases.


PVDF shock sensors: applications to polar materials and high explosives.
Ferroelectric polymers (PVDF) with well-defined and precisely known electrical properties are now routinely available from commercial sources. Electrical processing with the Bauer cyclic poling method can produce individual films with well-defined remanent polarization up to 9 /spl mu/C/cm/sup 2/. These polymers provide an unusual opportunity to study the structure and physical properties of materials subjected to shock loading. The behavior of PVDF has been studied over a wide range of pressures using high-pressure shock loading and has yielded well-behaved, reproducible data up to 25 GPa in inert materials. The application of PVDF gauges for recording shock waves induced in polar materials such as Kel-F, PMMA, or in reactive materials is hampered by observations of anomalous responses due to shock-induced polarization or an electrical charge released inside a shock-compressed explosive. A solution using an appropriate electrical shielding has been identified and applied to PVDF for shock measurement studies of Kel-F, and for Hugoniot measurements of high explosives (PH). Furthermore, shock pressure profiles obtained with in situ PVDF gauges in porous HE (Formex) in a detonation regime have been achieved. Typical results of shock pressure profile versus time show a fast superpressure of a few nanoseconds followed by a pressure release down to a plateau level and then by a pressure decay. More accurate measurements are reported with electrically improved PVDF gauges as well as with 0.25 mm/sup 2/ active area PVDF gauges.


SHP-2 Phosphatase Prevents Colonic Inflammation by Controlling Secretory Cell Differentiation and Maintaining Host-Microbiota Homeostasis.
Polymorphisms in the PTPN11 gene encoding for the tyrosine phosphatase SHP-2 were described in patients with ulcerative colitis. We have recently demonstrated that mice with an intestinal epithelial cell-specific deletion of SHP-2 (SHP-2(IEC-KO) ) develop severe colitis 1 month after birth. However, the mechanisms by which SHP-2 deletion induces colonic inflammation remain to be elucidated. We generated SHP-2(IEC-KO) mice lacking Myd88 exclusively in the intestinal epithelium. The colonic phenotype was histologically analyzed and cell differentiation was determined by electron microscopy and lysozyme or Alcian blue staining. Microbiota composition was analyzed by 16S sequencing. Results show that innate defense genes including those specific to Paneth cells were strongly up-regulated in SHP-2-deficient colons. Expansion of intermediate cells (common progenitors of the Goblet and Paneth cell lineages) was found in the colon of SHP-2(IEC-KO) mice whereas Goblet cell number was clearly diminished. These alterations in Goblet/intermediate cell ratio were noticed 2 weeks after birth, before the onset of inflammation and were associated with significant alterations in microbiota composition. Indeed, an increase in Enterobacteriaceae and a decrease in Firmicutes were observed in the colon of these mice, indicating that dysbiosis also occurred prior to inflammation. Importantly, loss of epithelial Myd88 expression inhibited colitis development in SHP-2(IEC-KO) mice, rescued Goblet/intermediate cell ratio, and prevented NFκB hyperactivation and inflammation. These data indicate that SHP-2 is functionally important for the maintenance of appropriate barrier function and host-microbiota homeostasis in the large intestine. J. Cell. Physiol. 231: 2529-2540, 2016. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.


Modification of lymph by lymph nodes. III. Effect of increased lymph hydrostatic pressure.
Previous studies have shown that lymph nodes function as fluid exchange chambers in which the protein concentration of lymph is changed in the direction required to establish equilibrium of the Starling forces acting across the nodal blood-lymph barrier. We examined the effect of increased lymph hydrostatic pressure on efferent lymph by use of an isolated dog popliteal node preparation in which lymph having a protein concentration averaging 27.6 +/- 1.2% (SD) of that of plasma was infused into the node at a flow rate averaging 45.6 +/- 0.2 (SD) microliter/min. We compared steady-state values of prenodal and postnodal lymph flow and protein concentration following step increases in efferent lymph pressure from 0 to over 15 mmHg. Increasing efferent lymph pressure to values less than about 8 mmHg caused the efferent lymph protein concentration to increase; however, further increases in lymph pressure caused the lymph protein concentration to decrease to values approaching those attained at very low lymph pressures. We suggest that the failure of high lymph pressure to increase lymph protein concentration might be caused by blood vessel collapse within the node, a condition believed to increase nodal blood capillary pressure and to decrease blood-lymph barrier filtration coefficient. An important finding was that increasing efferent lymph pressure caused significant amounts of lymph proteins to be lost during nodal transit. Therefore, it appears that increasing efferent lymph pressure to very high values has little effect on lymph protein concentration but has great effect on postnodal lymph protein flux.


Management of behavioural and psychological symptoms of dementia by an aroma-massage with acupressure treatment protocol: A randomised clinical trial.
This study evaluates the clinical effectiveness of a multicomponent aroma-massage with an acupressure treatment protocol and compared it to cognitive training for the management of behavioural and psychological symptoms of dementia. Pharmacological interventions have been unsatisfactory in managing behavioural and psychological symptoms of dementia; thus, complementary and alternative medicine has been extensively researched to identify an adjunct safe and cost-effective intervention. This randomised clinical trial utilised a three-arm parallel group design. Cognitive training was used as a conventional intervention to manage behavioural and psychological symptoms of dementia, whereas exercise was considered "treatment as usual" in this study; both were used as comparisons with the experimental protocol. There were three treatment groups: Group 1: aroma-massage with acupressure + exercise, Group 2: cognitive training + exercise and Group 3: aroma-massage with acupressure + cognitive training. Sixty older adults were recruited and randomly assigned to the three groups (20 each). Using the 29-item Chinese Version of the Cohen-Mansfield Agitation Inventory, Neuropsychiatric Inventory, Mini-mental State Examination and Barthel Index-20, the outcome measures were assessed at preintervention, postintervention and the 3-month follow-up to assess behaviour, Activities of Daily Living, cognition, and behavioural and psychological symptoms of dementia severity and distress. Multiple comparisons performed through repeated measures were analysed to detect between-group differences and within-subject differences, as well as the interaction effects between groups and times. The Group 1 and 3 participants showed a significant reduction in the severity and distress caused by behavioural and psychological symptoms of dementia, whereas Group 2 did not demonstrate similar effects. This clinical study suggests that aroma-massage with acupressure is as effective as cognitive training and can enhance cognitive training in reducing the severity and distress of behavioural and psychological symptoms of dementia. Aroma-massage with acupressure may serve as an adjunct therapy to reduce behavioural and psychological symptoms of dementia. This therapy is safe, cost-effective and can be implemented by caregivers and family members who are not professionally trained.


Covalently bound conjugates of albumin and heparin: synthesis, fractionation and characterization.
Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10-16 weight % of heparin) were obtained by a condensation reaction between albumin and heparin using 1-ethyl-3-(dimethylaminopropyl)-carbodiimide. Unreacted albumin and heparin were removed by diethyl-aminoethyl (DEAE)-cellulose and Cibacron Blue Sepharose chromatography respectively. The activity of the heparin component incorporated in the albumin-heparin conjugates (Ac) was compared with that of the heparin used for the synthesis of the conjugates (Anat) by thrombin time, inhibition of Factor Xa and the activated partial thromboplastin time (APTT) assays. The Ac/Anat ratio for the above assays was as follows: Thrombin time 1.25, Factor Xa inhibition 0.5. and APTT 0.5. Gel filtration chromatography showed broad-molecular weight distributions. The conjugates were fractionated using immobilized antithrombin III (ATIII). High ATIII and low ATIII affinity conjugate fractions showed the same behavior as ATIII fractionated heparin with respect to thrombin times and Factor Xa inhibition.


Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells.
Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.


Individual boron nanowire has ultra-high specific Young's modulus and fracture strength as revealed by in situ transmission electron microscopy.
Boron nanowires (BNWs) may have potential applications as reinforcing materials because B fibers are widely known for their excellent mechanical performance. However until now, there have been only few reports on the mechanical properties of individual BNW, and in situ transmission electron microscopy (TEM) investigations shining a light on their fracture mechanism have not been performed. In this paper, we applied in situ high-resolution TEM (HRTEM) technique to study the mechanical properties of individual BNWs using three loading schemes. The mean fracture strength and the maximum strain of individual BNWs were measured to be 10.4 GPa and 4.1%, respectively, during the tensile tests. And the averaged Young's modulus was calculated to be 308.2 GPa under tensile and compression tests. Bending experiments for the first time performed on individual BNWs revealed that their maximum bending strain could reach 9.9% and their ultimate bending stress arrived at 36.2 GPa. These figures are much higher than those of Si and ZnO nanowires known for their high bending strength. Moreover, the BNWs exhibited very high specific fracture strength (3.9 (GPa·cm(3))/g) and specific elastic modulus (130.6 (GPa·cm(3))/g), which are several dozens of times larger compared to many nanostructures known for their superb mechanical behaviors. At last, the effect of surface oxide layer on the Young's modulus, fracture strength and maximum bending strength of individual BNWs was elucidated to extract their intrinsic mechanical parameters using calculated corrections. All experimental results suggest that the present BNW are a bright promise as lightweight reinforcing fillers.


Methylmercury in Industrial Harbor Sediments in Taiwan: First Observations on its Occurrence, Distribution, and Measurement.
The distribution of methylmercury (MeHg) and total mercury (T-Hg) in sediments of the estuaries and the basin in Kaohsiung Harbor (Taiwan) is studied. MeHg in the sediment samples was determined using gas chromatography-mass spectrometry. The certified reference material of sediments with respect to the method showed the recovery efficiency between 97.4 and 103.6% which confirmed the applicability of analysis method. The T-Hg and MeHg concentrations were between 149 to 9035 μg/kg and <0.31 to 17.7 μg/kg, respectively. The T-Hg and MeHg concentrations in the estuaries of Kaohsiung Harbor were relatively high. Results suggest that Hg in this studied area was likely contributed from the catchments of the rivers. The MeHg level was <0.01 to 2.66% of the T-Hg in the sediments. A positive correlation is obtained between MeHg, T-Hg, and total organic carbon in the sediments, whereas a negative correlation is observed between pH, oxidation-reduction potential, and MeHg concentration. The results further suggest that sediment characteristics contribute mainly to the distribution of MeHg.


Selection for weaning weight in Targhee sheep in two environments. II. Correlated effects.
Targhee sheep were selected for 120-d weight under irrigated pasture-drylot conditions at Davis (DW) and under range conditions at Hopland (HW). Unselected control lines were maintained in both environments (DC, HC1 and HC2). At Hopland, a line (DH) was maintained in which ewes were mated to Davis (DW) rams. Selection for 120-d weight was successful in both environments, with more improvement made in the drylot environment. The genetic improvement made in the drylot environment was expressed, although to a lesser degree, under range conditions. Correlated responses were analyzed. Birth weight increased significantly in all three selected lines; the increase was less in line DH than in the other two lines. In all selected lines, weights of ewes of all ages at mating increased significantly compared with their respective controls. Proportion of ewes lambing decreased (P less than .05) in line DH; the trend was negative but nonsignificant in line DW. Differences in litter size between lines within location were not significant. Lamb survival to weaning decreased in lines DW (P less than .05) and DH (P less than .01), compared with their respective controls; and the trend in HW was negative but nonsignificant. Fertility and survival data indicated that, under range conditions, the line selected under drylot conditions (DH) was less fit than the line selected under range conditions (HW). As a result of the decreases in lamb survival and fertility, none of the selected lines produced more total lamb weight weaned per ewe than the controls, in spite of the significant direct response to selection. Mature ewes of lines DH and DW produced less total lamb weight weaned per ewe (P less than .001 and P less than .05) than their respective controls. The results indicate that while single trait selection for growth rate to weaning results in heavier lambs, it does not increase and may decrease total lamb production per ewe.


Abundance and Diversity of Mosquito Species Collected From a Rural Area of Central Mississippi: Implications for West Nile Virus Transmission in Mississippi.
To determine abundance and seasonality of potential West Nile virus (WNV) mosquito vectors in a forested area of central Mississippi, mosquitoes were collected weekly from a wildlife management area located approximately 10 mi from a local urban area known to have numerous human WNV cases. We were particularly interested in the presence or absence of Culex quinquefasciatus, the primary vector of WNV in Mississippi, although other Culex species were assayed. Two Centers for Disease Control and Prevention light traps baited with CO2 were set once a week from 2005 through 2006 in the Pearl River Wildlife Management Area (PRWMA), which consists of 6,925 acres primarily composed of bottomland hardwood forest with wetland areas. Traps were placed midafternoon and picked up the following morning. A total of 199,222 mosquitoes were collected during the 2-year study. No Cx. quinquefasciatus were collected throughout the entire study, although other health department surveys have indicated they are abundant just a few miles away. As for other potential WNV vectors, 1,325 (0.6%) Cx. nigripalpus, 1,804 (0.9%) Cx. restuans, and 6,076 (3.1%) Cx. salinarius were collected in the PRWMA over the 2-year period. These data suggest that Cx. quinquefasciatus is not usually found in remote forested environments, but is more associated with human habitation.


Features for non-targeted cross-sample analysis with comprehensive two-dimensional chromatography.
This review surveys different approaches for generating features from comprehensive two-dimensional chromatography for non-targeted cross-sample analysis. The goal of non-targeted cross-sample analysis is to discover relevant chemical characteristics (such as compositional similarities or differences) from multiple samples. In non-targeted analysis, the relevant characteristics are unknown, so individual features for all chemical constituents should be analyzed, not just those for targeted or selected analytes. Cross-sample analysis requires matching the corresponding features that characterize each constituent across multiple samples so that relevant characteristics or patterns can be recognized. Non-targeted, cross-sample analysis requires generating and matching all features across all samples. Applications of non-targeted cross-sample analysis include sample classification, chemical fingerprinting, monitoring, sample clustering, and chemical marker discovery. Comprehensive two-dimensional chromatography is a powerful technology for separating complex samples and so is well suited for non-targeted cross-sample analysis. However, two-dimensional chromatographic data is typically large and complex, so the computational tasks of extracting and matching features for pattern recognition are challenging. This review examines five general approaches that researchers have applied to these difficult problems: visual image comparisons, datapoint feature analysis, peak feature analysis, region feature analysis, and peak-region feature analysis.


Inhibition of vitamin D2-induced arteriosclerosis in rats by depletion of complement with cobra venom factor.
Widespread calcerous deposits developed in the aorta, heart and kidneys of rats fed for 4 days with purina chow and high doses of vitamin D2 (200,000 IU/kg body wt/day). Decomplementation of rats with highly purified cobra venom factor (CoF) prior to vitamin D2 feeding, almost completely prevented calcium deposition in the aorta and arteritis. The mortality rate in the CoF-treated vitamin D2-fed rats was much lower than in untreated rats. These findings suggest that the complement system may be recruited in the pathogenesis of vitamin D2-induced arteriosclerosis.


Norepinephrine turnover in obese mice and rats.
The possibility that sympathetic nervous system activity, as assessed by measurement of norepinephrine turnover, in brown adipose tissue of animals with a predisposition for development of obesity is altered has been examined. Evidence is provided to indicate that ob/ob mice, fa/fa rats and rats with hypothalamic lesions all exhibit some abnormalities of norepinephrine kinetics in brown adipose tissue. Data are needed to evaluate the contribution of these abnormalities to development of obesity in these animals.


Civic engagement and mental health system strengthening in Indonesia: a qualitative examination of the views of health professionals and national key stakeholders.
Mental health services in Indonesia are developing rapidly in response to national and global health policy to support people living with psychosis. This presents a unique opportunity for civic engagement, the active involvement of patients, carers and communities in mental health care, to shape emergent services. In-depth explorations of the views of professionals and other key stakeholders in mental health care on the use of civic engagement in Indonesia are lacking which contributes to a limited understanding of its potential in this regard. The study aimed to explore contemporary professionals' and other key stakeholders' perspectives on the current use of and potential for civic engagement to strengthen mental health systems in Indonesia. Qualitative interviews were undertaken and analysed using thematic analysis underpinned by a critical realist approach. Eighteen multi-disciplinary professionals and lay health workers involved in mental health care in Jakarta and Bogor and 10 national key stakeholders were recruited. Despite high levels of awareness of and support for civic engagement amongst mental health professionals and policy makers combined with a nascent grass roots movement, analysis revealed unstructured and insufficient mechanisms for civic engagement which resulted in ad-hoc and mostly superficial levels of involvement activity. Civic engagement was thought to require a marked shift in existing practices as well as organisational and societal cultures. Challenging stigma is a key feature of civic engagement and our analysis highlights the relevance of social contact methods which are locally and culturally contextualised in this regard. Our findings point to a need to expand current definitions of civic engagement which focus on indivdiual enablement to ones that also encompass environmental and organisational enablement to optimise the future use of civic engagement in mental health settings. Key mental health stakeholders have identified that central aspects of Indonesian culture are well aligned to the ethos of civic engagement which has the potential to facilitate the enactment of recent global health policy. However, full realisation is likely to be impeded by prevailing paternalistic cultures in mental health services and high levels of stigma and discrimination towards those with mental illness in Indonesia without intervention.


Actin polymerization does not provide direct mechanical forces for vesicle fission during clathrin-mediated endocytosis.
Actin polymerization is important for vesicle fission during clathrin-mediated endocytosis (CME), and it has been proposed that actin polymerization may promote vesicle fission during CME by providing direct mechanical forces. However, there is no direct evidence in support of this hypothesis. In the present study, the role of actin polymerization in vesicle fission was tested by analyzing the kinetics of the endocytic tubular membrane neck (the fission-pore) with cell-attached capacitance measurements to detect CME of single vesicles in a millisecond time resolution in mouse chromaffin cells. Inhibition in dynamin GTPase activity increased the fission-pore conductance (Gp), supporting the mechanical role of dynamin GTPase in vesicle fission. However, disruptions in actin polymerization did not alter the fission-pore conductance Gp, thus arguing against the force-generating role of actin polymerization in vesicle fission during CME. Similar to disruptions of actin polymerization, cholesterol depletion results in an increase in the fission-pore duration, indicating a role for cholesterol-dependent membrane reorganization in vesicle fission. Further experiments suggested that actin polymerization and cholesterol might function in vesicle fission during CME in the same pathway. Our results thus support a model in which actin polymerization promotes vesicle fission during CME by inducing cholesterol-dependent membrane reorganization.


Desonide: a review of formulations, efficacy and safety.
Desonide is a low-potency topical corticosteroid that has been used for decades in the treatment of steroid-responsive dermatoses. The favorable safety profile of this topical agent makes it ideal for patients of all ages. This article provides a review of desonide's history, pharmacodynamic properties, vehicle technology, efficacy and safety. Randomized controlled trials, as well as open-label and non-comparative studies, case series and reports, experimental models, and data from the Galderma pharmacovigiliance program were reviewed in order to address the clinical efficacy and safety of desonide. Clinical efficacy and safety have been proven in multiple clinical trials. In addition to cream, lotion and ointment formulations, the recently developed hydrogel and foam preparations have increased desonide's versatility and patient tolerability.


[Anti-ulcer effect of gamma-aminobutyric acid and its mechanisms of action].
It has been shown in experiments on white rats with chronic gastric ulcer induced according to the method of Takashi and coworkers that intramuscular administration of gamma-aminobutyric acid (GABA) exerts a pronounced antiulcerous effect. As compared with ganglerone, GABA reduces the content of free physiologically active histamine in the gastric mucosa to a far greater extent. The relationship has been disclosed between the therapeutic effect of GABA and the decreased content of histamine in the gastric mucosa.


Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study.
Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides. Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy. There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79). There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.


Table-top combined scanning X-ray small angle scattering and transmission microscopies of lipid vesicles dispersed in free-standing gel.
A mm thick free-standing gel containing lipid vesicles made of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) was studied by scanning Small Angle X-ray Scattering (SAXS) and X-ray Transmission (XT) microscopies. Raster scanning relatively large volumes, besides reducing the risk of radiation damage, allows signal integration, improving the signal-to-noise ratio (SNR), as well as high statistical significance of the dataset. The persistence of lipid vesicles in gel was demonstrated, while mapping their spatial distribution and concentration gradients. Information about lipid aggregation and packing, as well as about gel density gradients, was obtained. A posteriori confirmation of lipid presence in well-defined sample areas was obtained by studying the dried sample, featuring clear Bragg peaks from stacked bilayers. The comparison between wet and dry samples allowed it to be proved that lipids do not significantly migrate within the gel even upon drying, whereas bilayer curvature is lost by removing water, resulting in lipids packed in ordered lamellae. Suitable algorithms were successfully employed for enhancing transmission microscopy sensitivity to low absorbing objects, and allowing full SAXS intensity normalization as a general approach. In particular, data reduction includes normalization of the SAXS intensity against the local sample thickness derived from absorption contrast maps. The proposed study was demonstrated by a room-sized instrumentation, although equipped with a high brilliance X-ray micro-source, and is expected to be applicable to a wide variety of organic, inorganic, and multicomponent systems, including biomaterials. The employed routines for data reduction and microscopy, including Gaussian filter for contrast enhancement of low absorbing objects and a region growing segmentation algorithm to exclude no-sample regions, have been implemented and made freely available through the updated in-house developed software SUNBIM.


The method of bladder cuff excision during laparoscopic radical nephroureterectomy does not affect oncologic outcomes in upper tract urothelial carcinoma.
To determine whether the method of bladder cuff excision (BCE) during laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma is associated with rates of disease recurrence or metastases. We performed a retrospective review of all laparoscopic radical nephroureterectomies performed at our institution over 10 years. Three methods of BCE were used: transurethral incision (TUI) with Collins knife and a single intravesical port, open extravesical, and open intravesical via cystotomy. Logistic regression analyses were performed to determine whether BCE method was associated with recurrence or metastases. Laparoscopic radical nephroureterectomy was performed in 110 patients. BCE was performed via TUI in 61 patients, open extravesical in 29, and open intravesical in 20. After a median follow-up of 22 months, 36 patients (32.7 %) developed recurrences. Metastases were observed in 18 patients (16.4 %). Recurrence rates were 32.8, 27.6, and 40.0 % in the TUI, extravesical, and intravesical groups, respectively (p = 0.69). Positive surgical margins occurred in nine patients with no significant difference between groups. Factors associated with recurrence or metastases in a multivariate regression analysis were stage, positive surgical margins and carcinoma in situ (CIS). The method of BCE was not associated with oncologic outcomes. The three methods of bladder cuff excision (TUI, extravesical, and intravesical) are oncologically valid with similar recurrence and metastases rates when performed during laparoscopic radical nephroureterectomy. Stage, positive margin status and CIS are predictive of adverse oncologic outcomes and can facilitate postoperative prognostication.


Service Bundle Recommendation for Person-Centered Care Planning in Cities.
Providing appropriate support for the most vulnerable individuals carries enormous societal significance and economic burden. Yet, finding the right balance between costs, estimated effectiveness and the experience of the care recipient is a daunting task that requires considering vast amount of information. We present a system that helps care teams choose the optimal combination of providers for a set of services. We draw from techniques in Open Data processing, semantic processing, faceted exploration, visual analytics, transportation analytics and multi-objective optimization. We present an implementation of the system using data from New York City and illustrate the feasibility these technologies to guide care workers in care planning.


A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.
Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE) gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser) in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203) containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.


Increased Risk of Optic Neuritis in Patients With Fibromyalgia: Nationwide Population-Based Cohort Study in South Korea.
To estimate the risk of incidence of optic neuritis and identify the high-risk group among patients with fibromyalgia (FM). Population-based cohort study. A nationwide, population-based study was conducted using data from the Korean National Health Claims database from 2012 to 2021. This study included all the patients with FM from the entire South Korean population aged 20-79 years (FM group). Moreover, those with pain but not diagnosed with FM were considered as the non-FM group. A cohort was established by classifying it into the FM and non-FM groups during the recruitment period. A log-rank analysis was used to compare the risk of optic neuritis incidence between the FM group and non-FM group. Cox proportional hazards regression analysis was performed to calculate the adjusted hazard ratio (HR). The cohort was analyzed by stratifying according to age and sex. The FM and non-FM groups included 479,892 and 479,892 participants, respectively. The incidence rate of optic neuritis was 35.65/100,000 person-years in the FM group; the HR was significantly higher in the FM group than in the non-FM group (HR 2.11, 95% CI 1.84-2.41; P < .001). The mean interval between the onset of FM and incident optic neuritis was 2.4 ± 1.8 years. The risk increased significantly in men aged 60-79 years (HR 3.37, 95% CI 2.54-4.48) and in women aged 20-39 years (HR 2.07, 95% CI 1.38-3.22). We quantified the risk of optic neuritis through a long-term follow-up, which could contribute to understanding the pathophysiology and estimating the general health care burden associated with FM in a practical setting. Great attention should be paid to its risk in older men and younger women.


Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET.
The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.


Differential effects of dopaminergic drugs on spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine.
The differential effects of dopaminergic drugs with different pharmacological profiles were investigated with respect to spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine (6-OHDA). Three marmosets received infusions of 6-OHDA (either 30 or 40 μg/side) into the bilateral dopamine-rich area running from the substantia nigra to the striatum. The motor activity of the 6-OHDA marmosets was compared with that of three intact marmosets. Following the administration of apomorphine (0.5 and 1 mg/kg, subcutaneously), the 6-OHDA group showed a tendency toward a brief increase in activity counts, suggesting denervation supersensitivity at the dopamine receptors. After the administration of methamphetamine (1 and 2 mg/kg, subcutaneously), the 6-OHDA group showed a significant decrease in activity counts, indicating limited dopamine release from the degenerated neurons. After the administration of L-3,4-dihydroxyphenylalanine (10 and 20 mg/kg, orally), the 6-OHDA group showed a significant increase in activity counts without hyperexcitation, consistent with the contribution of exogenous L-3,4-dihydroxyphenylalanine toward dopamine synthesis in the degenerated neurons. The present findings indicate that bilateral brain infusion of 6-OHDA in the marmoset may have preclinical utility as a primate model for investigating the behavioral properties of dopaminergic drugs in brains with dopaminergic neural deficits.


Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.
Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis associated with tumors and other pathological conditions, including proliferative diabetic retinopathy and age-related macular degeneration. The murine anti-human VEGF monoclonal antibody (muMAb VEGF) A.4.6.1 has been shown to potently suppress angiogenesis and growth in a variety of human tumor cells lines transplanted in nude mice and also to inhibit neovascularization in a primate model of ischemic retinal disease. In this report, we describe the humanization of muMAb VEGF A.4.6.1. by site-directed mutagenesis of a human framework. Not only the residues involved in the six complementarity-determining regions but also several framework residues were changed from human to murine. Humanized anti-VEGF F(ab) and IgG1 variants bind VEGF with affinity very similar to that of the original murine antibody. Furthermore, recombinant humanized MAb VEGF inhibits VEGF-induced proliferation of endothelial cells in vitro and tumor growth in vivo with potency and efficacy very similar to those of muMAb VEGF A.4.6.1. Therefore, recombinant humanized MAb VEGF is suitable to test the hypothesis that inhibition of VEGF-induced angiogenesis is a valid strategy for the treatment of solid tumors and other disorders in humans.


Cloning and Characterization of Two Novel PR4 Genes from Picea asperata.
Pathogenesis-related (PR) proteins are important in plant pathogenic resistance and comprise 17 families, including the PR4 family, with antifungal and anti-pathogenic functions. PR4 proteins contain a C-terminal Barwin domain and are divided into Classes I and II based on the presence of an N-terminal chitin-binding domain (CBD). This study is the first to isolate two PR4 genes, PaPR4-a and PaPR4-b, from Picea asperata, encoding PaPR4-a and PaPR4-b, respectively. Sequence analyses suggested that they were Class II proteins, owing to the presence of an N-terminal signal peptide and a C-terminal Barwin domain, but no CBD. Tertiary structure analyses using the Barwin-like protein of papaya as a template revealed structural similarity, and therefore, functional similarity between the proteins. Predictive results revealed an N-terminal transmembrane domain, and subcellular localization studies confirmed its location on cell membrane and nuclei. Real-time quantitative PCR (RT-qPCR) demonstrated that PaPR4-a and PaPR4-b expression levels were upregulated following infection with Lophodermium piceae. Additionally, PaPR4-a and PaPR4-b were induced in Escherichia coli, where the recombinant proteins existed in inclusion bodies. The renatured purified proteins showed antifungal activity. Furthermore, transgenic tobacco overexpressing PaPR4-a and PaPR4-b exhibited improved resistance to fungal infection. The study can provide a basis for further molecular mechanistic insights into PR4-induced defense responses.


Dark pulses affect the circadian rhythm of activity in hamsters kept in constant light.
We compared the effects of light pulses in constant darkness (DD) and dark pulses in constant light (LL) on the free-running rhythm of locomotor activity in male golden hamsters. Light pulses yielded advances, delays, or no change in the rhythm of activity. These data conform to a typical phase-response curve; this curve was unaffected by pinealectomy. Dark pulses occurring either late in the subjective night or early in the subjective day had little effect. In contrast, dark pulses occurring either late in the subjective day or early in the subjective night altered the rhythm in one of three ways: advance of the rhythm; splitting into two components; or induction of a new component, in phase with the pulse. Because dark pulses in LL perturb the circadian system in a different manner than do light pulses in DD, they may have value in identifying heretofore unknown aspects of circadian systems. As such, the use of dark pulses to perturb circadian rhythmicity will be a useful tool in examining the formal properties of circadian systems.


Ameloblastic fibro-odontoma of the maxilla: case report.
A 7-year-old girl presenting with proptosis was referred for management of a partially ossified mass occupying the right maxillary sinus. A complete enucleation was performed after the histological diagnosis given in frozen section as ameloblastic fibro-odontoma. Ameloblastic fibro-odontomas occur predominantly in children and young adults. The mandibular molar-ramus area is the favored location and radiographically, these lesions are well circumscribed and lucent-opaque. The tumor mass is composed of a myxoid connective tissue with strands of odontogenic epithelium and differentiated tissues such as enamel and dentin. The treatment is a conservative surgical procedure due to benign biological behavior.


One-year health and care costs after hip fracture for home-dwelling elderly patients in Norway: Results from the Trondheim Hip Fracture Trial.
The aim of this study was to estimate the one-year health and care costs related to hip fracture for home-dwelling patients aged 70 years and older in Norway, paying specific attention to the status of the patients at the time of fracture and cost differences due to various patient pathways after fracture. Data on health and care service provision were extracted from hospital and municipal records and from national registries; data on unit costs were collected from the municipalities, hospital administrations and previously published studies. Four different patient pathways were identified and the total costs for subgroups of patients according to age, sex, fracture type and instrumental activity of daily living at fracture incidence were calculated. Descriptive statistics were used to identify cost estimates. The mean total one-year costs per patient were EUR 68,376 and the costs for patients alive one year after hip fracture were EUR 71,719. The patients' age and pre-fracture functional status contributed most to the total cost. On average, care costs accounted for more than 50% of the total cost; even for patients with good functional status before hip fracture, care costs accounted for 40% of the total cost compared with hospital costs of 38%. To reduce the financial costs of hip fractures in the care sector, the results point to the importance of preventive programmes to reduce the risk of hip fracture, but also to the importance of comprehensive geriatric care in the initial phase after a hip fracture.


Patterns of death among avalanche fatalities: a 21-year review.
Avalanches are a significant cause of winter recreational fatalities in mountain regions. The purpose of this study was to determine the relative contributions of trauma and asphyxia to avalanche deaths. We reviewed all avalanche fatalities between 1984 and 2005 that had been investigated by the offices of the British Columbia Coroners Service and the Chief Medical Examiner of Alberta. In addition, we searched the database of the Canadian Avalanche Centre for fatal avalanche details. We calculated injury severity scores for all victims who underwent autopsy. There were 204 avalanche fatalities with mortality information over the 21-year study period. Of these, 117 victims underwent autopsy, and 87 underwent forensic external examination. Asphyxia caused 154 (75%) deaths. Trauma caused 48 (24%) deaths, with the rate of death from trauma ranging from 9% (4/44) for snowmobilers to 42% (5/12) for ice climbers. In addition, 13% (12/92) of the asphyxia victims who underwent autopsy had major trauma, defined as an injury severity score of greater than 15. Only 48% (23/48) of victims for whom trauma was the primary cause of death had been completely buried. Asphyxia and severe trauma caused most avalanche fatalities in western Canada. The relative rates differed between snowmobilers and those engaged in other mountain activities. Our findings should guide recommendations for safety devices, safety measures and resuscitation.


Attitudes of primary care physicians and specialists about cancer clinical trials: a survey of Texas physicians.
A one-page questionnaire assessing physicians' prior involvement in and attitudes about clinical trials was distributed to primary care physicians (PCPs) and specialists practicing in Texas. The survey form was completed and returned by 57 PCPs and 80 specialists. The two physician groups agreed strongly about the value of what can be learned in clinical trials, and agreed that the greatest barriers to participation were paperwork requirements, time constraints, and concern for patient welfare. Both PCPs and specialists were concerned about enrolling patients if they felt that the patients did not understand what was involved. Because PCPs report only a limited experience with clinical trials, a realistic strategy to increase patient accrual involves developing effective educational outreaches to this group of physicians. In general, PCPs are trusted by their patients and can play an important role in providing information and in encouraging participation in appropriate trials.


Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner.
Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.


Pathophysiology of cancer cachexia: current understanding and areas for future research.
Weight loss and failure to gain weight normally in cancer patients are attributable to negative energy balance and altered metabolism. Energy balance is negative because of decreased intake, increased expenditure, or both. Changes in carbohydrate metabolism include glucose uptake and lactate production by tumor, relative hypoinsulinism, and relative insulin resistance. Alterations in protein metabolism include preferential uptake of amino acids by the tumor, decreased synthesis of some host tissue proteins such as muscle tissue, and increased synthesis of other host proteins. Lipid metabolism is seemingly less affected. These metabolic changes result in muscle wasting in adult cancer patients and growth failure in pediatric cancer patients. Host tissues are catabolized to meet the nutritional demands of tumor, and nutritional death may ensue.


Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites.
Previous studies have suggested that Lycium barbarum (L. barbarum) has a radioprotective function, although more in-depth investigation is still required. We investigated the radioprotective efficacy of extract of the fruits of L. barbarum (LBE) and its radioprotective mechanisms. Mice were exposed to 8.5 Gy, 5.5 Gy, or 6.0 Gy total body irradiation (TBI), and the survival rate, lymphocyte percentage, amount of cytokines, and viability of the irradiated cells, as well as the gut microbiome and fecal metabolomics were studied. LBE enhanced the survival of the mice exposed to 8.5 Gy γ-ray TBI or 5.5 Gy X-ray TBI. After 6.0 Gy γ-ray TBI, LBE exhibited good immunomodulatory properties, mainly characterized by the accelerated recovery of lymphocyte percentages, and the enhanced expression of immune-related cytokines. LBE reconstituted the gut microbiota of irradiated mice, increased the relative abundance of potentially beneficial genera (e.g., Turicibacter, Akkermansia), and decreased the relative abundance of potentially harmful bacterial genera (e.g., Rikenellaceae_RC9_gut_group). Beneficial regulatory effects of LBE on the host metabolites were also noted, and the major upregulated metabolites induced by LBE, such as Tetrahydrofolic acid and N-ornithyl-L-taurine, were positively correlated with the immune factor interleukin (IL)-6. In vitro, LBE also increased the vitality of rat small intestinal epithelial cells (IEC-6) after 4.0 Gy γ-ray irradiation and promoted the growth of Akkermansia muciniphila. These results confirmed a radioprotective function of LBE and indicated that the radioprotective mechanism may be due to immunomodulation and the synergistically modulating effect on the gut microbiota and related metabolites.


Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion.
Human immunodeficiency virus type 1 (HIV-1) entry is governed by the interaction of the viral envelope glycoprotein (Env) with its receptor. The HIV-1 receptor is composed of two molecules, the CD4 binding receptor and a coreceptor. The seven-membrane-spanning chemokine receptor CCR-5 is one of the coreceptors used by primary isolates of HIV-1. We demonstrate that the mouse homolog of CCR-5 (mCCR-5) does not function as an HIV-1 coreceptor. A set of chimeras of human CCR-5 and mCCR-5 was studied for Env-induced cell fusion and HIV-1 infection. Using the HIV-1ADA envelope glycoprotein in a syncytium formation assay, we show that replacement of any fragment containing extracellular domains of mCCR-5 by its human counterparts is sufficient to allow Env-induced fusion. Conversely, replacement of any fragment containing human extracellular domains by its murine counterpart did not lead to coreceptor function loss. These results show that several domains of CCR-5 participate in coreceptor function. In addition, using a panel of primary nonsyncytium-inducing and syncytium-inducing isolates that use CCR-5 or both CXCR-4 and CCR-5 as coreceptors, we show that the latter dual-tropic isolates are less tolerant to changes in CCR-5 than strains with a more restricted coreceptor use. Thus, different strains are likely to have different ways of interacting with the CCR-5 coreceptor.


Histological, immunohistochemical and biochemical effects of bee bread on stomach tissue of obese rats.
Obesity is a major health problem threatening humanity in medical, social and psychological dimensions. In this study, we aimed to determine the histological, immunohistochemical and biochemical effects of bee bread, added to diets of obese rats in different doses, on leptin and ghrelin expression. In the study, 40 female Sprague‒Dawley (200‒250 g) rats were randomly divided into 5 equal groups and then assigned to control and obesity groups. The obesity group consisted of four subgroups: high‑fat diet group, 100 and 200 mg/kg/bw groups, and metformin group. Histopathological evaluation revealed structural deterioration and necrotic areas in the epithelium and glands of the obese rats' stomach tissue, while in their serum and gastric tissues, the MDA level was significantly higher than in the other groups. There was a negative correlation between leptin and ghrelin levels. Apoptotic cells increased with obesity, but the application of beebread was similarly effective as metformin administration in reducing this increase (Tab. 5, Fig. 4, Ref. 51). Keywords: bee bread, leptin, ghrelin, stomach, obesity, rat.


Suprapatellar nailing in proximal third tibial fractures - Clinicoradiological outcome.
To evaluate the clinical and radiological outcome of proximal third tibia fractures managed by suprapatellar nailing with a minimum follow-up of 12 months. In our retrospective cohort study of 43 consecutive proximal third tibia fractures from January 2015 to September 2018 treated with intramedullary nailing through suprapatellar approach in semiextended knee position were included. The patients were followed up regularly at 6 weeks, 3 months, 4.5 months, 6 months, 12 months and every 6 months thereafter. At each visit patients were assessed for union, shortening and rotational alignment. The clinical outcome was analysed using Lower Extremity Functional Scale (LEFS) and anterior knee pain. The radiological outcomes are analysed by evaluating the radiographs for progression of fracture union and tibial alignments. After fulfilling the exclusion and inclusion criteria, 43 out of 60 consecutive proximal third tibia fracture were included in the study with an average age of 38.4 years (20-71 years), follow up of 20.4 months (12-45 months) after the index procedure. The radiological union was achieved in 7.3 months (4-13 months). At the end of 1 year follow up, the average LEFS was 89.4% (60%-95%). 4 patients had Malunion - with 1 valgus and 3 anterior angulations, 8 delayed unions and 1 non-union (with bone loss- which required bone grafting). All the fractures united eventually. No incidence of anterior knee pain. We recommend suprapatellar nailing in proximal third tibial fractures when meticulously performed using the current surgical principles and techniques with proper implant selection. It results in excellent clinical and radiological outcomes with minimal complications when compared to other modalities of management. Suprapatellar nailing is a viable option for proximal third tibia fractures due to its inherent advantages of positioning, perfect nail entry and placement. Additionally, noteworthy absence of anterior knee pain is an additional benefit of this technique.


Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system.
The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.


Artificial light at night causes conflicting behavioural and morphological defence responses in a marine isopod.
Encroachment of artificial light at night (ALAN) into natural habitats is increasingly recognized as a major source of anthropogenic disturbance. Research focussed on variation in the intensity and spectrum of ALAN emissions has established physiological, behavioural and population-level effects across plants and animals. However, little attention has been paid to the structural aspect of this light, nor how combined morphological and behavioural anti-predator adaptations are affected. We investigated how lighting structure, background reflectance and the three-dimensional properties of the environment combined to affect anti-predator defences in the marine isopod Ligia oceanica. Experimental trials monitored behavioural responses including movement and background choice, and also colour change, a widespread morphological anti-predator mechanism little considered in relation to ALAN exposure. We found that behavioural responses of isopods to ALAN were consistent with classic risk-aversion strategies, being particularly exaggerated under diffuse lighting. However, this behaviour was disconnected from optimal morphological strategies, as diffuse light caused isopods to become lighter coloured while seeking out darker backgrounds. Our work highlights the potential for the structure of natural and artificial light to play a key role in behavioural and morphological processes likely to affect anti-predator adaptations, survival, and ultimately wider ecological effects.


Assay for human matrix gla protein in serum: potential applications in the cardiovascular field.
Matrix Gla protein (MGP) is synthesized in a vitamin K-dependent way in smooth muscle cells of the healthy vessel wall, and its mRNA transcription is substantially upregulated in atherosclerotic lesions. Here we report the preparation of a monoclonal antibody against human MGP and its use in an enzyme-linked immunosorbent assay. The intra-assay and interassay coefficients of variation in serum samples were 5.4% and 12.6%, respectively, and the lower detection limit was 8.5% of the normal serum value. Individual within-day variations were <11% and did not show a distinct circadian pattern. Day-to-day variations in fasting morning samples were <8%. In a first explorative survey, serum MGP concentrations were found to be significantly increased in patients with severe atherosclerosis, whereas these values were normal in those with low bone mass and osteoporosis. This finding is consistent with the high MGP mRNA expression observed in atherosclerotic vessels and plaques. More elaborate studies are required to assess the potential clinical utility of this newly developed assay.