An integrated approach to a teaching file linked to PACS.
To meet the educational needs of a medical imaging department with a strong teaching commitment, a teaching file that uses digital data supplied by the institutional picture archiving and communications system (PACS) was required. This teaching file had to be easily used by the end users, have a simple submission process, be able to support multiple users, be searchable on all data fields, and implementing the teaching file must not incur any additional software or hardware costs. The teaching file developed to address this problem takes advantage of the database structure and capabilities of several components included in the commercial PACS installed at the hospital. MS Access is used to seamlessly integrate with the digital imaging and communication in medicine (DICOM) database of a normal work station that is part of the PACS. This integration allows relevant patient and study demographics to be copied from images of interest and then to be stored in a separate database as the back-end of the digital teaching file. When images for a particular teaching file case need to be reviewed, they are automatically retrieved and displayed from the main PACS database using an open application programming interface (API) connection defined on the PACS web server. Utilizing this open API connection means the teaching file contains only the relevant demographic information of each teaching file case; no image data is stored locally. The open API connection allows access to imaging data usually not encountered in a teaching file, allowing more comprehensive imaging case files to be developed by the radiologist. Other advantages of this teaching file design are that it does not duplicate image data, it is small allowing simple ongoing backup, and it can be opened with multiple users accessing the database without compromising data access or integrity.


Enhancing collaborative leadership in palliative social work in oncology.
The Institute of Medicine (IOM) Report-Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs-provided recommendations for meeting the palliative care needs of our growing population of older Americans. The IOM report highlights the demand for social work leadership across all aspects of the health care delivery system. Social workers are core interdisciplinary members of the health care team and it is important for them to be well prepared for collaborative leadership roles across health care settings. The ExCEL in Social Work: Excellence in Cancer Education & Leadership education project was created as a direct response to the 2008 IOM Report. This article highlights a sampling of palliative care projects initiated by outstanding oncology social work participants in the ExCEL program. These projects demonstrate the leadership of social workers in palliative care oncology.


Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: role of interleukin 1beta.
A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. Using this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated intracervically using a micro-endoscope, at a time corresponding to 70% of average gestation. Intracervical injection of lipopolysaccharide (LPS) or Escherichia coli reliably induced premature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 36 h after inoculation. No losses were observed in mice inoculated with saline. Pregnancy loss was associated with increased uterine tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL-1beta-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss. This model using direct intracervical bacterial or LPS inoculation is useful for studying preterm pregnancy loss in genetically altered mice in order to develop novel interventions for infection-associated preterm labor.


Skin grafts 2: management of donor site wounds in the community.
Skin grafting is a surgical procedure used to quickly restore skin integrity in large wounds or those wounds which cannot be directly closed by suturing. The procedure of skin grafting necessitates the creation of a second wound; the donor site. Although often viewed as secondary importance by surgeons once skin has been harvested from the area, it is the donor site which frequently causes complications such as pain/discomfort and slow healing (Wilkinson, 1997). Because skin graft sites and donor sites are viewed as part of a specialist practice, their wound management is regarded as being 'something different'. However, the donor site is a partial-dermal thickness wound and should be seen as such, rather than a 'special' wound. This may help to lessen the anxiety felt by both patient and nurse in dealing with donor site wounds.


[Cutaneous leukocytoclastic vasculitis: about 85 cases].
Clinical manifestation, etiology and outcome of leukocytoclastic vasculitis are little studied. The aim of our study was to examine epidemiological, clinical etiological, and evolutionary characteristics of this entity. We conducted a cross-sectional data collection from medical records of 85 patients with leukocytoclastic vasculitis in the Department of Dermatology at the Farhat Hached University Hospital, Sousse between January 2000 and December 2013. Epidemiological, clinical, paraclinical, etiological data sheets had been completed for each patient. The average age of patients was 47.65 years, ranging between 10 and 78 years. Fifty-three women and 32 men were registered (sex ratio = 0.6). Cutaneous manifestations were dominated by vascular purpura (88.2%). The most common causes of leukocytoclastic vasculitis were systemic diseases (51%), infection (20%) and neutrophilic dermatoses (14.5%). Other causes were drugs (9.1%) and hematologic malignancies (5.4%). The cause of leukocytoclastic vasculitis was not detected in 30 patients (35, 3%). Two predictive factors associated with the acute outcome were retained: the presence of a recent infection (p= 0.014) and drug intake before the rash (p= 0.013). Chronic evolution was positively correlated with antinuclear antibodies (p= 0.009) and cryoglobulinemia (p=0.025). Our study highlights the multitude of causes of leukocytoclastic vasculitis. The search for an underlying disease is an imperative in order to ensure better therapeutic management.


The impact of ocular trauma during the Nepal earthquake in 2015.
Nepal was struck by a massive earthquake on the 25th April 2015 and major aftershock on the 12th of May 2015, resulting in widespread devastation with a death toll in the thousands. The burden of ocular trauma resulting from the recent earthquakes in Nepal has not been described thus far. The aim of this study was to determine the types of ocular injuries sustained in the earthquake in Nepal and its management in Tilganga Institute of Ophthalmology (TIO) in Gaushala, Kathmandu. This is a hospital-based retrospective study of patients presenting to TIO following repeated earthquake. Variables that were recorded included patients' presenting symptoms and time to presentation, visual acuities at presentation and at follow-up, diagnosis of ocular injury and surgery performed. There were 59 cases of earthquake victims visiting TIO, Gaushala, Kathmandu from April 2015 to July 2015, with 64 affected eyes due to 5 cases of bilateral involvement. The majority of patients were from the district Sindhupalchowk (14 cases, 23.7%), which was the epicenter of the main earthquake. The average duration between the earthquake and presentation was 13 · 9 days (range 1-120 days). Closed globe injury was most frequent (23 cases), followed by open globe injuries (8 cases). While 24 patients (38%) initially presented with a visual acuity <3/60 in their affected eye, 15 patients (23%) had a visual acuity of <3/60 on follow-up. A variety of surgical treatments were required including anterior and posterior segment repair. Immediate management of ocular trauma is critical in order to prevent blindness. Characterizing the burden of earthquake-related ocular trauma will facilitate planning for service provision in the event of a future earthquake in Nepal, or in countries, which are similarly at risk of having natural disasters.


Preface to the Special Issue of ChemSusChem on Organic Batteries.
All about Organic: Guest Editors Philippe Poizot, Yan Yao, Jun Chen, and Ulrich S. Schubert provide their thoughts on organic batteries-the challenges they face, their advantages and disadvantages, and what needs to be done to make them a commercially viable option-in this preface to a special issue of ChemSusChem on organic batteries, with highly interesting contributions from scientists around the world.


Embryonic Stem Cell Conditioned Medium Supports In Vitro Maturation of Mouse Oocytes.
This study aimed to investigate the maturation and fertilization rates of immature mouse oocytes using Embryonic Stem Cell Conditioned Medium (ESCM). Germinal Vesicle (GV) stage oocytes were observed in 120 NMRI mice, aged 4-6 weeks. GV oocytes with or without cumulus cells were subjected to IVM in either ESCM, Embryonic Stem Cell Growth Medium (ESGM), or α-minimum essential medium (α-MEM). After recording the Metaphase II (MII) oocyte maturation rate, the oocytes were fertilized in vitro. The fertilization success rate was recorded after 24 hr. The embryos were maintained in potassium Simplex Optimization Medium (KSOM) for 96 hr and allowed to grow until the blastocyst stage. After recording developmental competence, they were transferred into the uteri of pseudopregnant mice and their birth rates were recorded. No significant difference existed between the maturation rates in α-MEM (68.18%) and ESCM (64.67%; p>0.05), whereas this rate was significantly higher for both α-MEM and ESCM compared to ESGM (32.22%; p<0.05). A significant difference in IVF success rate existed for oocytes grown in α-MEM (69.44%), ESCM (61.53%), and ESGM (0%). A significantly higher developmental competence was observed at the blastocyst stage for oocytes grown in α-MEM (51.2%) compared to ESCM (35%; p<0.05). 17 days after embryo transfer into the uteri of pseudopregnant mice, there was a nonsignficant (p>0.05), similar birth rate between α-MEM and ESCM (47 vs. 40%). ESCM is an effective medium for preantral follicle growth, oocyte maturation, and subsequent embryo development.


[Status of malnutrition and its influencing factors in children under 5 years old in Yunnan Province from 2016 to 2017].
To analyzing the malnutrition status and influencing factors of children under 5 years in Yunnan Province. Multi-stage stratified sampling used in the national survey was performed. The subjects of the study were 2869 children under 5 years, selected from 13 counties(cities) in Yunnan Province from 2016 to 2017. The contents of the investigation included questionnaire survey and anthropometric measurement. Z-scores were calculated according to WHO growth standards by WHO Anthro V3.2.2 software. Non conditional Logistic regression model was used to analyze the multiple factors. SPSS 20.0 statistical software was used to calculate and analyze the malnutrition rate of children. A total of 2869 children under 5 years old were investigated in Yunnan Province, including 1433 boys(49.95%) and 1436 girls(50.05%). The prevalence of stunting, underweight and wasting of children under 5 years old were 3.46%, 6.37% and 3.42%. Logistic multifactor regression analysis showed that low birth weight(OR=4.368, 95% CI 2.057-9.275), rural area(OR=1.931, 95% CI 1.076-3.462), household use of unsanitary toilets(OR=1.688, 95% CI 1.022-2.790), children without supplemental food(OR=2.000, 95% CI 1.130-3.542) were the most important factors making the child more likely to become malnutrition in 6-23 month age group. Asking children for advice on food selection or cooking(OR=3.570, 95%CI 1.249-10.204) was the most important factors making the child more likely to become malnutrition in 6-23 month age group. The nutritional status of children under 5 years old in Yunnan Province has been improved, but the prevalence of malnutrition is still high.


Dominant negative effects of a carboxy-truncated Jak2 mutant on Epo-induced proliferation and Jak2 activation.
Members of the Janus family of protein tyrosine kinases are emerging as primary, receptor-associated transducing factors among numerous cytokine systems. However, little is understood regarding mechanisms of recruitment of these kinases to receptor complexes and their ligand-dependent activation. To initially address these questions, we have assessed effects of ectopically expressing a carboxy-truncated form of Jak2 (Jak2-829) in Epo-responsive DAER cells. Expression of this truncation mutant at low levels efficiently inhibited both Epo-dependent activation of endogenous Jak2 and Epo-induced mitogenesis (10% to 39% of parental DAER cells). These results suggest that amino-terminal domains of Jak2 may mediate the assembly of Jak2/Epo receptor complexes and that integration of Jak2-829 into receptor complexes may effectively inhibit the activity of oligomeric Jak2/receptor assemblages.


Dressing ignition and facial burns following orbital exenteration.
A 49-year-old woman with type II diabetes mellitus and a history of smoking underwent partial eyelid-sparing exenteration of the right orbit and antifungal therapy for zygomycosis. The medial orbital wall healed with a 7-mm fistula to the ethmoid sinus and a moist granulating apex required daily dressing changes for several months. Eighteen weeks following surgery, the patient cleaned her face with an alcohol wipe and then lit a cigarette, igniting the dressing covering the exenterated eye socket. This caused severe burns to the periorbital regions of both eyes requiring debridement, allografts, and then split-thickness skin grafting. Factors predisposing to this unusual and serious complication of orbital exenteration are reviewed and the subjects of treatment and prevention are discussed. To our knowledge, this is the first reported case of dressing ignition with serious facial burns in a postexenteration patient.


Oncogene expression detected by in situ hybridization in human primary lung cancer.
By means of in situ hybridization using biotinylated oncogene probes and the immunohistochemical reaction of avidin-biotin complex-alkaline phosphatase with substrate, we investigated expression of c-myc oncogene in the formalin-fixed, paraffin-embedded tissue sections from seven patients with squamous cell carcinoma (six cases) and small cell carcinoma (one case) of primary lung origin. The expression of c-myc oncogene was greatly enhanced in all cases studied, with individual and cell-to-cell variation. In contrast, all of the specimens incubated with deoxyribonuclease after the standard pretreatment with ribonuclease T1 were negative for the expression of c-myc oncogene. The in situ hybridization permits estimation of a heterogeneous amplification of c-myc oncogene that may be related to secondary alterations occurring during the progression of the malignant lung tumors.


Conditional love? Co-occurrence patterns of drought-sensitive species in European grasslands are consistent with the stress-gradient hypothesis.
The stress-gradient hypothesis (SGH) postulates that species interactions shift from negative to positive with increasing abiotic stress. Interactions between species are increasingly being recognized as important drivers of species distributions, but it is still unclear whether stress-induced changes in interactions affect continental-to-global scale species distributions. Here, we tested whether associations of vascular plant species in dry grasslands in Europe follow the SGH along a climatic water deficit (CWD) gradient across the continent. Dry grasslands in Europe. Present. Vascular plants. We built a context-dependent joint species distribution model (JSDM) to estimate the residual associations (i.e., associations that are not explained by the abiotic environment) of 161 plant species as a function of the CWD based on community data from 8,660 vegetation plots. We evaluated changes in residual associations between species for pairs and on the community level, and we compared responses for groups of species with different drought tolerances. We found contrasting shifts in associations for drought-sensitive and drought-tolerant species. For drought-sensitive species, 21% of the pairwise associations became more positive with increasing CWD, whereas 17% became more negative. In contrast, only 17% of the pairwise associations involving drought-tolerant species became more positive, whereas 27% became more negative in areas with a high CWD. Additionally, the incidence of positive associations increased with drought for drought-sensitive species and decreased for drought-tolerant species. We found that associations of drought-sensitive plant species became more positive with drought, in line with the SGH. In contrast, associations of drought-tolerant species became more negative. Additionally, changes in associations of single species pairs were highly variable. Our results indicate that stress-modulated species associations might influence the distribution of species over large geographical extents, thus leading to unexpected responses under climate change through shifts in species associations.


Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3.
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the ataxin-3 protein. SCA3 symptoms include progressive motor decline caused by an atrophy of the cerebellum and brainstem. However, it was recently reported that SCA3 patients also suffer from the cerebellar cognitive affective syndrome. The majority of SCA3 patients exhibit cognitive decline and approximately half of them suffer from depression and anxiety. The necessity to find a combined therapy for both motor and cognitive deficits in a SCA3 mouse model is required for the development of SCA3 treatment. Here, we demonstrated that the SCA3-84Q transgenic mice exhibited anxiety over the novel brightly illuminated environment in the open field, novelty suppressed feeding, and light-dark place preference tests. Moreover, SCA3-84Q mice also suffered from a decline in recognition memory during the novel object recognition test. SCA3-84Q mice also demonstrated floating behavior during the Morris water maze that can be interpreted as a sign of low mood and aversion to activity, i. e. depressive-like state. SCA3-84Q mice also spent more time immobile during the forced swimming and tail suspension tests which is also evidence for depressive-like behavior. Therefore, the SCA3-84Q mouse model may be used as a model system to test the possible treatments for both ataxia and non-motor symptoms including depression, anxiety, and memory loss.


Calcium modulated signaling site in type 2 rod outer segment membrane guanylate cyclase (ROS-GC2).
The ROS-GC subfamily of membrane guanylate cyclases is at present represented by two members: ROS-GC1 and ROS-GC2. A unique functional feature of this subfamily is that it is intracellularly modulated in low Ca2+ concentration by calmodulin-like Ca(2+)-binding proteins termed GCAPs, 1 and 2, and the modulation is consistent with its linkage to phototransduction. The present study shows that: (1) GCAP2 is a specific modulator of ROS-GC2; (2) through systematic remodeling of ROS-GC modules, the study also shows that the modulated domain resides within the amino acid segment 736-1020. This domain is distinct form the corresponding GCAP1-modulated ROS-GC1 domain. Thus, GCAP1 and GCAP2 act through different ROS-GCs and through two different cyclase domains.


Modulation of calcium-activated non-specific cation currents by cyclic AMP-dependent phosphorylation in neurones of Helix.
1. Currents through calcium-activated non-specific cation (CAN) channels were studied in the fast burster neurone of Helix aspersa and Helix pomatia. CAN currents were activated by reproducible intracellular injections of small quantities of Ca2+ utilizing a fast, quantitative pressure injection technique. 2. External application of forskolin (10-25 microM), an activator of adenylate cyclase, caused the endogenous bursting activity of the cells to be replaced by beating activity. These same concentrations of forskolin reduced CAN currents reversibly to about 50%. 3. External application of IBMX (3-isobutyl-1-methylxanthine, 100 microM), an inhibitor of phosphodiesterase, the enzyme which breaks down cyclic AMP, reduced CAN currents reversibly to about 40%. 4. External application of the membrane-permeable cyclic AMP analogues 8-bromo-cyclic AMP and dibutyryl-cyclic AMP (100 microM) caused almost complete block of the CAN current. A marked reduction in the CAN current was also observed following quantitative injections of cyclic AMP (internal concentrations up to 50 microM) directly into the cells from a second pressure injection pipette. 5. Similar results were obtained with quantitative injections of the catalytic subunit (C-subunit) of the cyclic AMP-dependent protein kinase (internal concentrations 10(-4) units of enzyme) directly into the cells from a second pressure injection pipette. 6. Injection of the non-hydrolysable GTP analogue, GTP-gamma-S (internal concentrations 100 microM), which stimulates G-proteins, produced a prolonged increase in CAN current amplitude by as much as 300%. 7. External application of serotonin (100-200 microM) caused a transition from bursting to beating activity of the neurones and mimicked cyclic AMP's effects on CAN currents. Two other neurotransmitters, dopamine and acetylcholine, were not significantly effective in reducing CAN currents. 8. Injection of a peptide inhibitor of cyclic AMP-dependent protein kinase suppressed serotonin's action on bursting and on CAN current. 9. Our results indicate that CAN currents in Helix burster neurones are modulated by cyclic AMP-dependent membrane phosphorylation. They suggest that the physiological transmitter that induces this second messenger action is serotonin. The dual control of CAN channels by two second messengers, namely Ca2+ and cyclic AMP, has important functional implications. While Ca2+ activates these channels which generate the pacemaker current in these neurones, cyclic AMP-dependent phosphorylation down-regulates them, thereby resulting in modulation of neuronal bursting activity.


Impact of an early mobilization protocol on the reduction of medical complications after surgery for chronic subdural hematoma: the GET-UP Trial.
Timing of mobilization after chronic subdural hematoma (cSDH) surgery is highly heterogeneous among neurosurgical centers. Past studies have suggested that early mobilization may reduce medical complications without increasing recurrence, but evidence remains scarce. The purpose of this study was to compare an early mobilization protocol with a 48-hour bed rest practice, with a focus on the occurrence of medical complications. The GET-UP Trial is a prospective, randomized, unicentric, open-label study with an intention-to-treat primary analysis designed to evaluate the impact of an early mobilization protocol after burr hole craniostomy for cSDH on the occurrence of medical complications and functional outcomes. A total of 208 patients were recruited and randomly assigned to either an early mobilization group where they began head-of-bed elevation within the first 12 hours after surgery and proceeded to sedestation, orthostatism, and/or walking as rapidly as tolerated, or to a bed rest group where they remained recumbent with a head-of-bed angle inferior to 30° for 48 hours after surgery. The primary outcome was the occurrence of a medical complication (defined as either an infection, seizure, or thrombotic event) after surgery and until clinical discharge. Secondary outcomes included length of stay measured from randomization to clinical discharge, surgical hematoma recurrence at clinical discharge and 1 month after surgery, and Glasgow Outcome Scale-Extended (GOSE) assessment at clinical discharge and 1 month after surgery. A total of 104 patients were randomly assigned to each group. No significant baseline clinical differences were observed before randomization. The primary outcome occurred in 36 (34.6%) patients included in the bed rest group and 20 (19.2%) in the early mobilization group (p = 0.012). At 1 month after surgery, a favorable functional outcome (defined as GOSE score ≥ 5) was observed in 75 (72.1%) patients in the bed rest group and 85 (81.7%) in the early mobilization group (p = 0.100). Surgical recurrence occurred in 5 (4.8%) patients in the bed rest group and 8 (7.7%) in the early mobilization group (p = 0.390). The GET-UP Trial is the first randomized clinical trial to assess the impact of mobilization strategies on medical complications after burr hole craniostomy for cSDH. Early mobilization was associated with a reduction in medical complications without a significant effect on surgical recurrence, compared with a 48-hour bed rest protocol.


Intracellular trafficking of begomoviruses in the midgut cells of their insect vector.
Begomoviruses are exclusively transmitted by whiteflies in a persistent circulative manner and cause considerable economic losses to crop production worldwide. Previous studies have shown that begomoviruses accumulate in vesicle-like structures in whitefly midgut cells and that clathrin-mediated endocytosis is responsible for their internalization. However, the process by which begomoviruses are trafficked within whitefly midgut cells remains largely unknown. In this study, we investigated the roles of vesicle trafficking in the transport of Tomato yellow leaf curl virus (TYLCV), a begomovirus that has spread to over 50 countries and caused extensive damage to a range of important crops, within midgut cells of whitefly (Bemisia tabaci). By disrupting vesicle trafficking using RNA silencing and inhibitors, we demonstrated that the early steps of endosomal trafficking are important for the intracellular transport of TYLCV in the whitefly midgut. In addition, our data show that, unlike many animal viruses, TYCLV is trafficked within cells in a manner independent of recycling endosomes, late endosomes, lysosomes, the Golgi apparatus and the endoplasmic reticulum. Instead, our results suggest that TYLCV might be transported directly from early endosomes to the basal plasma membrane and released into the hemolymph. Silencing of the sorting nexin Snx12, which may be involved in membrane tubulation, resulted in fewer viral particles in hemolymph; this suggests that the tubular endosomal network may be involved in the transport of TYLCV. Our results also support a role for the endo-lysosomal system in viral degradation. We further showed that the functions of vector early endosomes and sorting nexin Snx12 are conserved in the transmission of several other begomoviruses. Overall, our data indicate the importance of early endosomes and the tubular endosomal network in begomovirus transmission.


Changes in Synaptic Plasticity and Glutamate Receptors in Type 2 Diabetic KK-Ay Mice.
In the present study, the progressive alteration of cognition and the mechanisms of reduction in long-term potentiation (LTP) in spontaneous obese KK-Ay type 2 diabetic mice were investigated. In the study, 3-, 5-, and 7-month-old KK-Ay mice were used. The results indicated that KK-Ay mice showed cognitive deficits in the Morris water maze test beginning at the age of 3 months. LTP was significantly impaired in KK-Ay mice during whole study period (3 to 7 months). The above deficits were reversible at an early stage (3 to 5 months old) by diet intervention. Moreover, we found the underlying mechanisms of LTP impairment in KK-Ay mice might be attributed to abnormal phosphorylation or expression of postsynaptic glutamate receptor subunits instead of alteration of basal synaptic transmission. The expression levels of NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptors (NMDARs) were unchanged while the Tyr-dependent phosphorylation of both NR2A and NR2B subunits were significantly reduced in KK-Ay mice. The level of p-Src expression mediating this process was decreased, and the level of αCaMKII autophosphorylation was also reduced. Meanwhile, the GluR1 of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) was decreased, and GluR2 was significantly increased. These data suggest that deficits in synaptic plasticity in KK-Ay mice may arise from the abnormal phosphorylation of the NR2 subunits and the alteration of subunit composition of AMPARs. Diet intervention at an early stage of diabetes might alleviate the cognitive deficits and LTP reduction in KK-Ay mice.


Association of weight change, weight control practices, and weight cycling among women in the Nurses' Health Study II.
To assess the association of weight cycling with weight change, weight control practices, and bulimic behaviors. A nested study of 2476 young and middle-aged women in the Nurses' Health Study II who provided information on intentional weight losses between 1989 and 1993. In total, 224 women who were severe cyclers, 741 women who were mild cyclers, 967 age- and BMI-matched controls (noncyclers), and 544 women who did not weight cycle and maintained their weight between 1989 and 1993 completed a questionnaire in 2000-2001 assessing recent intentional weight losses, weight control practices, and weight concerns. After controlling for age and body mass index (BMI) in 1993, when weight cycling was initially assessed, mild cyclers gained an average of 6.7 pounds (lbs) more and severe cyclers gained approximately 10.3 lbs more than noncyclers between 1993 and 2001. Weight cyclers preferred to change their diet rather than to exercise to control their weight. Severe weight cyclers were less likely than noncyclers to use frequent exercise as a weight control strategy (odds ratio [OR]=0.8, 95% confidence interval (CI) 0.6-1.1). Cyclers were also more likely than noncyclers to engage in binge eating (mild cyclers: OR=1.8, 95% CI 1.4-2.4; and severe cyclers: OR=2.5, 95% CI 1.7-3.5). Independent of weight cycling status, age, and BMI, women who engaged in binge eating gained approximately 5 lbs more than their peers (P<0.001). Weight cycling was associated with greater weight gain, less physical activity, and a higher prevalence of binge eating. Low levels of activity and binge eating may be partially responsible for the large amount of weight regained by weight cyclers.


Family healthcare with King's theory of goal attainment.
King's conceptual system and theory of goal attainment provide a systematic approach to the thought and action of nursing that has stood the test of time with continuing utility for organizing the complex factors of healthcare. Following a brief overview of the conceptual system and theory of goal attainment, application to family healthcare is discussed and illustrated with the programs of research of three exemplar King scholars: family healthcare with a mentally-ill child, family healthcare with children with type 1 diabetes or asthma, and family healthcare when a family member has chronic obstructive pulmonary disease. The scientific benefit and developmental progression of a theory-driven program of research for practice is noted. Future studies are presented as well as additional sources for King's conceptual system and theory of goal attainment.


An integrative approach to detect epigenetic mechanisms that putatively mediate the influence of lifestyle exposures on disease susceptibility.
There is mounting evidence that our environment and lifestyle has an impact on epigenetic regulatory mechanisms, such as DNA methylation. It has been suggested that these molecular processes may mediate the effect of risk factors on disease susceptibility, although evidence in this regard has been challenging to uncover. Using genetic variants as surrogate variables, we have used two-sample Mendelian randomization (2SMR) to investigate the potential implications of putative changes to DNA methylation levels on disease susceptibility. To illustrate our approach, we identified 412 CpG sites where DNA methylation was associated with prenatal smoking. We then applied 2SMR to investigate potential downstream effects of these putative changes on 643 complex traits using findings from large-scale genome-wide association studies. To strengthen evidence of mediatory mechanisms, we used multiple-trait colocalization to assess whether DNA methylation, nearby gene expression and complex trait variation were all influenced by the same causal genetic variant. We identified 22 associations that survived multiple testing (P < 1.89 × 10-7). In-depth follow-up analyses of particular note suggested that the associations between DNA methylation at the ASPSCR1 and REST/POL2RB gene regions, both linked with reduced lung function, may be mediated by changes in gene expression. We validated associations between DNA methylation and traits using independent samples from different stages across the life course. Our approach should prove valuable in prioritizing CpG sites that may mediate the effect of causal risk factors on disease. In-depth evaluations of findings are necessary to robustly disentangle causality from alternative explanations such as horizontal pleiotropy.


Registers of in-vitro fertilization and assisted conception.
Many countries now have registers of assisted conception that were initially set up to evaluate the effectiveness of treatment, to monitor pregnancy outcomes and the health of treated women, and to assess any immediate risks for the women and their children. World reports, based on information from national registers, have enabled international comparisons of the extent to which the various techniques of assisted conception are used to treat infertile couples, as well as comparisons of pregnancy outcome. The reports also provide comparative data on pregnancy rates in populations rather than in single in-vitro fertilization (IVF) centres. To determine whether newly introduced techniques such as intracytoplasmic sperm injection are associated with any increased risks of birth defects or other adverse outcomes, information notified to registers will often need to be supplemented by clinical reports or by linkage of data in IVF registers and other health data systems. Further efforts to improve the quality of information on assisted conception within each country and internationally need to be well supported so that the effectiveness of treatment and the outcomes of treated couples and their children can be evaluated properly.


Assessment and refinement of intra-bone marrow transplantation in mice.
Intra-bone marrow transplantation (IBMT) may improve the seeding efficiency of transplanted hematopoietic stem cells compared to the routinely used intravenous injection. Current IBMT protocols are optimized for ease of use and to improve experimental results. However, there have been no investigations to assess the impact of IBMT on animal welfare. Here, we report the results of pain assessment after IBMT and the effects of refinements to the current standard procedure. IBMT was performed in either the tibia or the femur of a recipient mouse under general anesthesia. Impact was determined using clinical scoring of different parameters (lameness, grip capacity, body weight loss, footprint analysis), behavioural tests (burrowing, open-field), monitoring of stress hormones and post-mortem histology. The results revealed that IBMT definitely induces severe post-operative distress. Although IBMT in the tibia is technically easier, the degree of impairment and the distress observed were consistently higher than for transplantation in the femur. A refinement for IBMT in the tibia was achieved by using 30- instead of 26-gauge needles and by sparing the patellar tendon. Consequently, for IBMT, we recommend either using the femur, or if the tibia is required due to its better feasibility, using our refined protocol. Furthermore, IBMT should definitely be limited to one leg per animal.


Role of steroid injection for skin thickness and edema in rhinoplasty patients.
The aim of this study was to observe the effect of the triamcinolone acetonide injections in thick skinned patients with ultrasonographic measurements and to compare these results with the postoperative nasal skin thickness of patients that were not injected with steroids. A prospective study was planned with 42 thick nasal skinned rhinoplasty candidates in our clinic. Skin thickness of specific points along nose was measured and documented. On the 10th day after surgery, triamcinolone acetonide injections were performed into the supratip region of 21 patients in the study group. No injections were made for the control group. Nasal ultrasonographic measurements were repeated 40 days after the surgery for all 42 patients by the same radiologist and results were evaluated. Seventeen women (40.5%) and 25 men (59.5%) were included in the study. Patients' ages ranged from 18 to 53 with an average age of 27.9. In study group, all injections sites showed thinning on the 40th day after surgery. These findings were statistically significant at B (rhinion), D (middle of supratip), and G (middle of the tip). In the control group, all injection sites except A (nasion) displayed thickening on the 40th day after surgery. These findings were statistically significant at B (rhinion), D (middle of supratip), H (left side of the tip), and J (left alar region). Triamcinolone acetonide injections are effective in the prevention of edema and provide thinning of the post-rhinoplasty skin envelope.


New roles of reactive astrocytes in the brain; an organizer of cerebral ischemia.
The brain consists of neurons and much higher number of glial cells. They communicate each other, by which they control brain functions. The brain is highly vulnerable to several insults such as ischemia, but has a self-protective and self-repairing mechanisms against these. Ischemic tolerance or preconditioning is an endogenous neuroprotective phenomenon, where a mild non-lethal ischemic episode can induce resistance to a subsequent severe ischemic injury in the brain. Because of its neuroprotective effects against cerebral ischemia or stroke, ischemic tolerance has been widely studied. However, almost all studies have been performed from the viewpoint of neurons. Glial cells are structurally in close association with synapses. Recent studies have uncovered the active roles of astrocytes in modulating synaptic connectivity, such as synapse formation, elimination and maturation, during development or pathology. However, glia-mediated ischemic tolerance and/or neuronal repairing have received only limited attention. We and others have demonstrated that glial cells, especially astrocytes, play a pivotal role in regulation of induction of ischemic tolerance as well as repairing/remodeling of neuronal networks by phagocytosis. Here, we review our current understanding of (1) glial-mediated ischemic tolerance and (2) glia-mediated repairing/remodeling of the penumbra neuronal networks, and highlight their mechanisms as well as their potential benefits, problems, and therapeutic application.


[Behçet's syndrome and the digestive tract].
Gastrointestinal involvement represents only 14% of the anatomical sites of Behçet's syndrome in France. The various segments of the gastrointestinal tract may be affected. Episodes of mucosal aphthae are more frequent in the oesophagus than in the stomach or duodenum. Intestinal involvement constitutes the major gastrointestinal localisation. Colonic or ileo-colonic lesions may appear after several years of recurrent aphthosis and present in the form of acute complications (perforation, massive haemorrhage) or by prolonged haemorrhagic diarrhoea with marked deterioration in the general state. The radiological and endoscopic signs are similar to those observed in various forms of severe acute colitis such as haemorrhagic proctocolitis or Crohn's disease. The diagnosis of an intestinal localisation of Behçet's syndrome is based on the richness of the extra-intestinal signs and moreover on the presence of deep colonic ulcerations frequently situated in healthy mucosa, the presence of an adjacent non-specific inflammatory infiltrate affecting all of the colonic wall, lesions of vasculitis and perivasculitis with signs of leukocytoclasis and fibrinoid necrosis. Surgical treatment is frequently necessary. The high incidence of ulcerative recurrences in the anastomoses, in which fistulae may also develop, requires extensive intestinal resections or diversions by long-term ileostomies.


Effects of soil organic matter and ageing on remediation of diesel-contaminated soil.
Bioremediation of diesel-contaminated soil was investigated for the effects of soil organic matter (SOM) and ageing time in two sets of experiments (Batch I and II, respectively). This study examined degradation efficiency in soil artificially contaminated with diesel oil (maximum total petroleum hydrocarbons (TPH) concentration of 9000 mg/kg soil). Batch I data showed that the values of the first-order degradation rate, k, were relatively high in the low-SOM soil batches. The quantity of SOM negatively correlated with the TPH degradation rates and with the total TPH degradation efficiency (%). Introduction of rhamnolipid to the soil proved to be a useful solution to resolve the problem of the residual TPH in the soil with high SOM. In Batch II, the k values decreased with the length of ageing time: 0.0245, 0.0128 and 0.0090 l/d in samples ST0 (freshly contaminated), ST38 (aged for 38 days) and ST101 (aged for 101 days), respectively. The TPH degradation efficiency (%) also decreased along with the ageing time. The research also applied molecular technology to analyse the bacterial community dynamics during the bioremediation course. Multivariate statistics based on terminal-restriction fragment length data indicated: 1) the soils with different SOM resulted in separate bacterial community structures, 2) ageing time created a variety of bacterial communities, 3) the bacterial community dynamics was associated with the hydrocarbon consumption. The SOM content in soils affected the TPH degradation rate and efficiency and the bacterial community structures. Aged soil is more difficult to remediate than freshly contaminated soil, and the resulting bacterial community was less dynamic and showed a lack of succession.


Structure and function of intact photosystem 1 monomers from the cyanobacterium Thermosynechococcus elongatus.
Until now, the functional and structural characterization of monomeric photosystem 1 (PS1) complexes from Thermosynechococcus elongatus has been hampered by the lack of a fully intact PS1 preparation; for this reason, the three-dimensional crystal structure at 2.5 A resolution was determined with the trimeric PS1 complex [Jordan, P., et al. (2001) Nature 411 (6840), 909-917]. Here we show the possibility of isolating from this cyanobacterium the intact monomeric PS1 complex which preserves all subunits and the photochemical activity of the isolated trimeric complex. Moreover, the equilibrium between these complexes in the thylakoid membrane can be shifted by a high-salt treatment in favor of monomeric PS1 which can be quantitatively extracted below the phase transition temperature. Both monomers and trimers exhibit identical posttranslational modifications of their subunits and the same reaction centers but differ in the long-wavelength antenna chlorophylls. Their chlorophyll/P700 ratio (108 for the monomer and 112 for the trimer) is slightly higher than in the crystal structure, confirming mild preparation conditions. Interaction of antenna chlorophylls of the monomers within the trimer leads to a larger amount of long-wavelength chlorophylls, resulting in a higher photochemical activity of the trimers under red or far-red illumination. The dynamic equilibrium between monomers and trimers in the thylakoid membrane may indicate a transient monomer population in the course of biogenesis and could also be the basis for short-term adaptation of the cell to changing environmental conditions.


The presence of the Ii blood group system on human platelets.
To examine platelets for the Ii antigens, high-titer human IgM anti-I and anti-i antibodies were affinity purified, radiolabeled with 125I, and incubated with adult and cord platelets. Saturation binding curves were performed by incubating adult platelets with serial dilutions of concentrated 125I-anti-I. Inhibition binding curves were performed by incubating adult platelets with doubling dilutions of concentrated unlabeled anti-I mixed with 125I-labeled anti-I. Adult platelets bound significantly more anti-I than anti-i, while cord platelets bound more anti-i than anti-I (P less than 0.025). Both anti-I and anti-i show a temperature-dependent dose-response curve of maximum binding at 4 degrees C. Binding of 125I-labeled anti-I was inhibited by preincubation with 100-fold concentration of unlabeled anti-I. The authors conclude that platelets express I/i antigens in parallel with that of red blood cells.


Comparison of molecular and cytogenetic methods in the evaluation of engraftment following allogeneic bone marrow transplantation.
Cytogenetic evaluation of patients after bone marrow transplantation (BMT) has provided a standard method of documentation of hematopoietic engraftment. More recently, recombinant DNA technology has also been applied to determine engraftment status. In order to establish the relative utility of these methods in clinical practice we have directly compared the data from cytogenetic and recombinant DNA methods, evaluating engraftment status in 68 BMT recipients. Patients were evaluated pre-transplant, 30, 60, 90, and 180 days after BMT, and yearly thereafter for 1) the presence or absence of the Y chromosome in sex-mismatched allogeneic transplant recipients, 2) the presence or absence of the Philadelphia chromosome [t(9;22)] in patients transplanted for chronic myelogenous leukemia (CML), 3) restriction fragment length polymorphism (RFLP) profiles, and/or 4) clonal rearrangement of the bcr gene. Cytogenetic examination of unstimulated bone marrow and recombinant DNA tests of nucleated peripheral blood or bone marrow cells produce qualitatively similar data in the identification of patient and donor cells and/or normal and tumor cells. Differences in the results obtained by the two analytic methods were most often due to the restricted cell populations evaluable by cytogenetic studies of PHA-stimulated peripheral blood specimens. DNA analyses could frequently be applied at earlier intervals after transplantation and, in cases of graft rejection, when cell counts were low. Although recombinant DNA methods required fewer cells and demonstrated greater sensitivity in detection of minor cell populations in the majority of instances, the cytogenetic evaluation may complement the DNA studies and allow detection of additional chromosomal anomalies.


Influence of Ultrasonic and Chemical Pretreatments on Quality Attributes of Dried Pepper (Capsicum annuum).
This study investigates the effects of ultrasound, in combination with chemical pretreatments, on the quality attributes (total phenolic and carotenoid content, antioxidant activity (2,2-Diphenyl-1-picrylhydrazyl assay (DPPH)), ferric-reducing ability (FRAP), CIE L* a* b* color, non-enzymatic browning, rehydration ratio, textural and morphological properties) of red pepper subjected to drying (hot air drying or freeze drying). The fractional factorial design was used to assess the impact of factors. The global Derringer desirability function was used to determine the optimal conditions for the best quality attributes of dried pepper. The drying method influenced total phenolic content, a* (redness), and initial rehydration ratio; pretreatment time significantly affected FRAP antiradical activity, a*, chroma and non-browning index, while pH-value had a significant effect on the texture of dried pepper. Non-enzymatic browning was reduced to 72.6%, while the DPPH antioxidant capacity of freeze-dried peppers was enhanced from 4.2% to 71.9%. Ultrasonic pretreatment led to changes in the pepper morphology, while potassium metabisulfite (KMS) was a more effective additive than citric acid.


A Roundtable Discussion: Combination Products: Twice the Challenge?
Combination products are therapeutic or diagnostic medical products that combine drugs, devices, and/or biological products with one another. FDA developed a regulation (final rule) on Current Good Manufacturing Practices (CGMP) for combination products that became effective July 22, 2013 (21 CFR Part 4). AAMI recently developed a technical information report (TIR) that provides information on how to effectively implement FDA's regulation. The overall goal of the TIR is to aid informed, risk-based decisions in establishing CGMP operating systems that support development, manufacture, premarket regulatory evaluation, and ultimately commercialization of combination products. This article, a result of an discussion with industry and FDA representatives, explores the landscape of combination products, highlights important considerations in developing and seeking marketing clearance for these innovative products, and provides insight on trends in the area.


Postoperative analgesia by infusion of local anesthetic into the surgical wound after modified radical mastectomy: a randomized clinical trial.
There is no consensus on the efficacy of postoperative infusion of local anesthetics after radical mastectomy. A randomized, double-blind, placebo-controlled, parallel-groups clinical trial was conducted in a tertiary hospital. Eighty consecutive women with operable breast cancer with indications for modified radical mastectomy without breast reconstruction were assigned randomly to receive infusion of levobupivacaine (0.5%) or saline at 2 ml/hour for 48 hours through a wound catheter. Seventy-three women finished the study (intervention group, n = 34; control group, n = 39). During surgery, all patients received 0.25% levobupivacaine (30 ml). The levobupivacaine group reported less pain (p < 0.001) than controls in the postanesthesia care unit (1.6 ± 1.3 versus 6.7 ± 1.8) and on the ward at 24 (0.8 ± 0.9 versus 4.2 ± 1.9) and 48 (0.4 ± 0.7 versus 3.3 ± 2.3) hours. In the postanesthesia care unit, the levobupivacaine group consumed less metamizole (0.4 ± 0.5 versus 0.8 ± 0.4; p < 0.001) and dexketoprofen (0.1 ± 0.3 versus 0.7 ± 0.4; p < 0.001), with differences in paracetamol use being insignificant (0.8 ± 0.4 versus 0.9 ± 0.3; p = 0.140). On the ward, the levobupivacaine group used significantly less paracetamol (0.5 ± 0.7 versus 2.0 ± 2.0; p < 0.001) and metamizole (0.2 ± 0.4 versus 1.2 ± 1.4; p < 0.001), but differences in dexketoprofen were not significant (0.03 ± 0.2 versus 0.2 ± 0.6; p = 0.074). In the postanesthesia care unit, the levobupivacaine and control groups consumed 0 ± 0 and 0.7 ± 1.2 doses of opioids (p = 0.001), respectively. The authors observed no differences in nausea and vomiting at any stage in the postanesthesia care unit (0.2 ± 0.4 versus 0.4 ± 0.5; p = 0.081) or on the ward (0.3 ± 0.5 versus 0.4 ± 0.5; p = 0.563). All participants reported high levels of satisfaction. Continuous infusion of local anesthetic reduces pain and analgesic consumption, with high satisfaction, but does not affect rates of nausea and vomiting.


Organization and expression of the 16S, 23S and 5S ribosomal RNA genes from the archaebacterium Thermoplasma acidophilum.
To elucidate the organization of the transcription units encoding the 16S, 23S and 5S rRNAs in the archaebacterium Thermoplasma acidophilum, the nucleotide sequences flanking the three rRNA genes were determined, and the 5' and 3' termini of the rRNA transcripts were mapped by primer extension and nuclease S1 protection. The results show that each of the rRNAs is transcribed separately, consistent with the lack of physical proximity among them in the T. acidophilum genome. The transcription initiation sites are preceded at an interval of approximately 25 base pairs by conserved A + T-rich sequences of the form CTTATATA, which strongly resemble the archaebacterial promoter consensus, TTTAT/AATA. In all three cases, transcription termination occurs within T-rich tracts just downstream from inverted repeats which can be folded into relatively stable stem-loop structures. While no partially processed intermediates of the 16S or 5S rRNA transcripts were detected, the 23S rRNA transcript appears to be processed by a RNase III-like activity prior to final maturation. This is the only organism known in the prokaryotic world in which the 16S, 23S and 5S rRNAs are all expressed from separate transcription units.


Integrin β1 Gene Therapy Enhances in Vitro Creation of Tissue-Engineered Cartilage Under Periodic Mechanical Stress.
Periodic mechanical stress activates integrin β1-initiated signal pathways to promote chondrocyte proliferation and matrix synthesis. Integrin β1 overexpression has been demonstrated to play important roles in improving the activities and functions of several non-chondrocytic cell types. Therefore, in the current study, we evaluated the effects of integrin β1 up-regulation on periodic mechanical stress-induced chondrocyte proliferation, matrix synthesis and ERK1/2 phosphorylation in chondrocyte monolayer culture, and evaluated the quality of tissue-engineered cartilage constructed in vitro under periodic mechanical stress combined with integrin β1 up-regulation. Our results revealed that under periodic mechanical stress, pre-treatment with integrin β1-wild type vector significantly enhanced chondrocyte proliferation and matrix synthesis and promoted ERK1/2 phosphorylation in comparison to mock transfectants. Furthermore, when chondrocytes were seeded in PLGA scaffolds, more accumulated GAG and type II collagen tissue were detected after Lv-integrin β1 transfection compared with sham controls exposed to periodic mechanical stress. In contrast, in the Lv-shRNA-integrin β1 group, the opposite results were observed. Our findings collectively suggest that in addition to periodic mechanical stress, integrin β1 up-regulation in chondrocytes could further improve the quality of tissue-engineered cartilage.


Developing a two-step heat treatment for inactivating desiccation-adapted Salmonella spp. in aged chicken litter.
The effectiveness of a two-step heat treatment for eliminating desiccation-adapted Salmonella spp. in aged chicken litter was evaluated. The aged chicken litter with 20, 30, 40, and 50% moisture contents was inoculated with a mixture of four Salmonella serotypes for a 24-h adaptation. Afterwards, the inoculated chicken litter was added into the chicken litter with the adjusted moisture content for a 1-h moist-heat treatment at 65 °C and 100% relative humidity inside a water bath, followed by a dry-heat treatment in a convection oven at 85 °C for 1 h to the desired moisture level (<10-12%). After moist-heat treatment, the populations of Salmonella in aged chicken litter at 20 and 30% moisture contents declined from ≈6.70 log colony-forming units (CFU)/g to 3.31 and 3.00 log CFU/g, respectively. After subsequent 1-h dry-heat treatment, the populations further decreased to 2.97 and 2.57 log CFU/g, respectively. Salmonella cells in chicken litter with 40% and 50% moisture contents were only detectable by enrichment after 40 and 20 min of moist-heat treatment, respectively. Moisture contents in all samples were reduced to <10% after a 1-h dry-heat process. Our results demonstrated that the two-step heat treatment was effective in reducing >5.5 logs of desiccation-adapted Salmonella in aged chicken litter with moisture content at or above 40%. Clearly, the findings from this study may provide the chicken litter processing industry with an effective heat treatment method for producing Salmonella-free chicken litter.


Stress fracture of the radius following a fracture of the ulna diaphysis.
A 70-year-old woman incurred a stress fracture of the radius following a fracture of the ulna. The patient had osteomalacia secondary to a Billroth II procedure. The primary reasons for the development of osteomalacia following a Billroth II procedure are: decreased transit time through the gut, which causes less Vitamin D and calcium absorption, and bypassing of the duodenum, where calcium absorption is highest. After treatment of the osteomalacia with calcium and Vitamin D, the fracture healed uneventfully. The present case report emphasizes the need to identify and treat diseases associated with fractures. Patients with severe osteomalacia and ulnar shaft fractures should have the forearm immobilized because motion at the fracture site may lead to a stress fracture of the radius.


Blood-brain, blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers in a marsupial (Macropus eugenii) during development.
1. The blood-brain, blood-CSF and CSF-brain barriers to protein have been studied in post-natal tammar wallabies (newborn to 70 days) using morphological and physiological techniques. 2. Endogenous and exogenous plasma proteins, and in some experiments horseradish peroxidase, were used as indicators of barrier integrity or permeability. 3. Immunocytochemical studies of endogenous tammar proteins showed that these (e.g. albumin) were present in the lumen of vessels in the brain, in cerebrospinal fluid (CSF) and within some cells in the choroid plexus and brain. No staining of the brain extracellular space was obtained; in particular there was no perivascular staining. Possible artifacts that could account for this lack of staining are discussed. 4. Ultrastructural studies showed the presence of well-formed tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells, even as early as the day of birth. A membrane specialization between adjacent neuropendymal cells that had the same ultrastructural appearance as the 'strap junction' previously described in human and sheep fetuses was observed. These junctions may act as a barrier (CSF-brain barrier) to the passage of protein from CSF into brain in these immature animals, as has previously been described in eutherian fetuses. 5. In experiments in which exogenous plasma proteins or horseradish peroxidase were injected intravenously, care was taken to limit both the volume and protein load injected. These proteins penetrated into CSF. The naturally occurring steady-state CSF/plasma ratio for several proteins was approached by several of the injected (human) proteins within a few hours of I.V. injection, suggesting that much of the protein in CSF, at least when sampled from the hindbrain, originates from plasma in this species. No penetration across cerebral vessels was observed. Uptake of some proteins (e.g. albumin), occurred into neuroependymal cells at some ages. 6. These results suggest that the very immature brain of the newborn tammar is protected from protein present in the circulating plasma even at an embryonic stage of development by a combination of a well-formed blood-brain barrier to protein in the cerebral vessels and a CSF-brain barrier to protein at the level of the neuroependyma. The adult-type blood-CSF barrier to protein (tight junctions between adjacent choroid plexus epithelial cells) is present but appears to be bypassed in the immature brain, probably by a transcellular route across the choroid plexus.


Nonsteroidal anti-inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell-cycle arrest.
Therapeutic options to inhibit growth of human NETs of the GEP system are limited. Since NSAIDs might provide an antiproliferative treatment alternative with acceptable toxicity, we examined the effects of different NSAIDs on growth and survival in a representative set of human GEP NET cell lines. Growth and apoptosis were determined based on cell numbers, cell-cycle analyses, kinase assays, DNA fragmentation and PARP cleavage. Expression of COX and cell cycle-regulatory molecules was examined by immunoblotting and reporter gene assays. Depending on the drug and cell line investigated, NSAID treatment resulted in profound growth inhibition of GEP NET cells. Growth-inhibitory effects were achieved with either COX-2 selective (NS398) or unselective (indomethacin, sulindac) compounds. Cell-cycle analyses documented a G1 arrest in NSAID-treated GEP NET populations. In addition, 100 microM sulindac or indomethacin induced apoptosis. All 3 COX inhibitors prevented CDK-2 activation. In parallel to the NSAID-mediated reduction of CDK-2 activity, p21(cip-1) promoter activity and cellular p21(cip-1) levels increased and p21(cip-1) was sequestered into CDK-2 complexes. Thus, the G1 arrest likely resulted from p21(cip-1)-dependent inhibition of CDK-2 activity. At therapeutically relevant concentrations, sulindac significantly reduced GEP NET cell numbers, whereas IFN-alpha and octreotide remained ineffective. The extent of growth inhibition in GEP NETs was comparable to the antiproliferative effects of sulindac in established NSAID-sensitive cell models. NSAIDs acted as potent antiproliferative agents in GEP NET cells via G1 cell-cycle arrest and might therefore offer a therapeutic alternative to current treatment modalities.


Origin of Somatic Mutations in β-Catenin versus Adenomatous Polyposis Coli in Colon Cancer: Random Mutagenesis in Animal Models versus Nonrandom Mutagenesis in Humans.
Wnt signaling is compromised early in the development of human colorectal cancer (CRC) due to truncating nonsense mutations in adenomatous polyposis coli (APC). CRC induced by chemical carcinogens, such as heterocyclic aromatic amines and azoxymethane, in mice also involves dysregulation of Wnt signaling but via activating missense mutations in the β-catenin oncogene despite the fact that genetically modified mice harboring an inactive APC allele efficiently develop CRC. In contrast, activating mutations in β-catenin are rarely observed in human CRC. Dysregulation of the Wnt signaling pathway by the two distinct mechanisms reveals insights into the etiology of human CRC. On the basis of calculations related to DNA adduct levels produced in mouse CRC models using mutagens, and the number of stem cells in the mouse colon, we show that two nonsense mutations required for biallelic disruption of APC are statistically unlikely to produce CRC in experiments using small numbers of mice. We calculate that an activating mutation in one allele near the critical GSK3β phosphorylation site on β-catenin is >105-times more likely to produce CRC by random mutagenesis due to chemicals than inactivating two alleles in APC, yet it does not occur in humans. Therefore, the mutagenesis mechanism in human CRC cannot be random. We explain that nonsense APC mutations predominate in human CRC because of deamination at 5-methylcytosine at CGA and CAG codons, coupled with the number of human colonic stem cells and lifespan. Our analyses, including a comparison of mutation type and age at CRC diagnosis in U.S. and Chinese patients, also indicate that APC mutations in CRC are not due to environmental mutagens that randomly damage DNA.


Acute nephropathy of organotin compounds.
Three patients who developed acute nephropathy following ingestion of triphenyltin acetate (TPTA) are described. All of them had significant proteinuria, azotemia, and polyuria. Mild neurological manifestations in all patients were also noted. Hematuria and pyuria were noted in 1 severely poisoned patient. Evidence for hepatitis was present in 2 patients, and for pancreatitis in 1. Renal biopsy showed focal fusion of glomerular cell processes and proximal tubular damage with cellular necrosis. Two patients survived with complete recovery of renal functions. One old patient died of aspiration pneumonia. Acute nephropathy following organotin intoxication appears to result mainly from proximal renal tubular damage with a benign and reversible clinical course.


Fast Pairwise Approximation of Solvent Accessible Surface Area for Implicit Solvent Simulations of Proteins on CPUs and GPUs.
We propose a pairwise and readily parallelizable SASA-based nonpolar solvation approach for protein simulations, inspired by our previous pairwise GB polar solvation model development. In this work, we developed a novel function to estimate the atomic and molecular SASAs of proteins, which results in comparable accuracy as the LCPO algorithm in reproducing numerical icosahedral-based SASA values. Implemented in Amber software and tested on consumer GPUs, our pwSASA method reasonably reproduces LCPO simulation results, but accelerates MD simulations up to 30 times compared to the LCPO implementation, which is greatly desirable for protein simulations facing sampling challenges. The value of incorporating the nonpolar term in implicit solvent simulations is explored on a peptide fragment containing the hydrophobic core of HP36 and evaluating thermal stability profiles of four small proteins.


Meta-phosphoric acid-its use in the selective extraction of RNA from fixed tissue sections.
This communication presents a new quick method for selective extraction of RNA from formalin-fixed tissues, such as kidney, intestine, ovary and testis of white rat and liver of rodents, Tatera indica and Millardia meltada and of the frog, Rana tigrina as well as of human wart. Sections of pancreas and kidney fixed in acetic acid-alcohol were also tried. The method is to treat deparaffinised sections in 20% and 15% meta-phosphoric acid at 5 degrees C for 10-20 and 20-30 min, respectively, and then to stain nuclear DNA with 0.5% aqueous solution of methyl green, methylene green, Giemsa, toluidine blue O or 0.125% pyronin G for 2 min, rinsed with water, treated with n-butanol for 2-3 min, cleared in xylene and mounted. It has been found that liver sections of rodents require 24 hours of treatment in 15% cold meta-phosphoric acid for complete removal of RNA, whereas those of the frog require only 20 min at 20% acid. It has been concluded that following treatment of sections in cold meta-phosphoric acid, RNA is extracted selectively leaving DNA in a native state. Therefore, staining of DNA in tissue sections from which RNA has been extracted is due to binding of its negatively charged phosphate groups with the positively charged dye molecules.


Thermal adjustment to cold-water exposure in exercising men and women.
Thermoregulatory responses were studied in 10 men and 8 women during 36-W exercise for 1 h in air and water at 20, 24, and 28 degrees C. Men were classified as high (27.6%; n = 2), average (16.8%; n = 4), and low (9.2%; n = 4) percent body fat, whereas women were classified as average (25.2%; n = 4) and low (18.5%; n = 4) fat. For both men and women, exercise of about 1.7 l O2 X min-1 was beneficial in either preventing or retarding the fall in rectal temperature (Tre) observed in a previous study for the same subjects at rest. The greatest thermal strain was noted for the leanest subjects. However, in no instance did exercise facilitate a drop in Tre compared with resting conditions. Despite a larger surface area-to-mass ratio (P less than 0.05) and less effective thermoregulation for women at rest compared with men, essentially similar thermoregulatory responses were observed for both sexes during exercise at each water temperature. For both the men and women, the thermoregulatory benefits of exercise were due largely to the added heat production from physical activity. For the female, an additional benefit of exercise may in part be derived from a more favorable distribution of subcutaneous fat over the active musculature.


[Sneddon syndrome with anti-mitochondrial type M5 antibodies].
Antimitochondrial type M5 antibodies (AMA-M5) are among the immunological abnormalities associated with Sneddon syndrome. A 45 year-old woman, hospitalized for diplopia and with a 20-year history of obstetrical accidents, internuclear ophthalmoplegia and livedo, was diagnosed with Sneddon syndrome associated with primary antiphospholipid syndrome (APS) aggravated by the presence of AMA-M5. AMA-M5 are immunological markers of APS to the same extent as antiphospholipid antibodies. This case demonstrates the interest of screening for AMA-M5 in cases of strong clinical suspicion of APS when the anticoagulant lupus test is normal and no anti-cardiolipin, anti-b2 glycoprotein I or antiprothrombin antibodies are found.


Computer-assisted fracture reduction of pelvic ring fractures: an in vitro study.
A newly developed software module for computer-assisted surgery based on a commercially available navigation system allows simultaneous, independent registration of two fragments and real-time navigation of both fragments while reduction occurs. To evaluate the accuracy three fracture models were used: geometric foam blocks, a pelvic ring injury with disruption of the symphysis and the sacroiliac joint, and a pelvic ring fracture with symphysis disruption and a transforaminal sacral fracture. One examiner did visual and navigated reduction and in all experiments the end point was defined as anatomic reduction. Residual displacement was measured with a magnetic motion tracking device. The results revealed a significantly increased residual displacement with navigated reduction compared with visual control. The differences were low, averaging 1 mm for residual translation and 0.7 degrees for the residual rotation, respectively. Residual displacement was small in both set-ups and may not be clinically relevant. Additional development of the software prototype with integration of surface registration may lead to improved handling and facilitated multifragment tracking. Use in the clinical setting should be possible within a short time.


Sleep and partner-specific quality of life in partners of men with lower urinary tract symptoms compared with partners of men from the general population.
The aims of this study were to examine differences between partners of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) and partners of men from the population regarding sleep and two aspects of quality of life, partner-specific quality of life and health-related quality of life (HRQoL), and to identify factors related to the partner-specific quality of life and the parameter sleep efficiency. The design was descriptive and comparative. The subjects were partners of men with LUTS suggestive of BPO (n = 126) and partners of randomly selected men from the general population (n = 131). Self-administered questionnaires about demography, comorbidity, sleep, sexuality, partner-specific quality of life and HRQoL were used. Partners of men with LUTS suggestive of BPO were significantly more affected in all variables measuring partner-specific quality of life compared with partners from the population. The most impaired aspects were compassion and worry about an operation or cancer. In logistic regression, the only explanatory factors were having a partner belonging to the LUTS group for impaired partner-specific quality of life and having a bed partner for high sleep efficiency. There were no significant differences between the two groups regarding the quantity and quality of sleep or the HRQoL. The partner-specific quality of life was impaired in partners of men with LUTS suggestive of BPO. Sleep and HRQoL did not differ between partners of men with LUTS and partners from the population.


Differential interactions of phytochrome A (Pr vs. Pfr) with monoclonal antibodies probed by a surface plasmon resonance technique.
Phytochromes are red- and far-red light-reversible photoreceptors for photomorphogenesis in plants. Phytochrome A is a dimeric chromopeptide that mediates very low fluence and high irradiance responses. To analyze the surface properties of phytochrome A (phyA), the epitopes of 21 anti-phyA monoclonal antibodies were determined by variously engineered recombinant phyA proteins and the dissociation constants of seven anti-phyA monoclonal antibodies with phyA were measured using a surface plasmon resonance (SPR)-based resonant mirror biosensor (IAsys). Purified oat phyA was immobilized on the sensor surface using a carboxymethyl dextran cuvette in advance, and the interactions of each chosen monoclonal antibody against phyA in either red light absorbing form (Pr) or far-red light absorbing form (Pfr) at different concentrations were monitored. The binding profiles were analyzed using the FAST Fit program of IAsys. The resultant values of dissociation constants clearly demonstrated the differential affinities between the phyA epitopes and the monoclonal antibodies dependent upon Pr vs. Pfr conformations. Monoclonal antibody mAP20 preferentially recognized the epitope at amino acids 653-731 in the Pr form, whereas mAA02, mAP21 and mAR07/mAR08 displayed preferential affinities for the Pfr's surfaces at epitopes 494-601 (the hinge region between the N- and C-terminal domains), 601-653 (hinge in PASI domain), and 772-1128 (C-terminal domain), respectively. The N-terminal extension (1-74) was not recognized by mAP09 and mAP15, suggesting that the N-terminal extreme is not exposed in the native conformation of phyA. On the other hand, the C-terminal domain becomes apparently exposed on Pr-to-Pfr phototransformation, suggesting an inter-domain cross-talk. The use of surface plasmon resonance spectroscopy offers a new approach to study the surface properties of phytochromes associated with the photoreversible structural changes, as well as for the study of protein-protein interactions of phytochromes with their interacting proteins involved in light signaling events in plants.


Effects of an educational bereavement program on health care professionals' perceptions of perinatal loss.
The purpose of this study was to examine the differences in health care professionals' perceptions of perinatal loss situations before and after an educational program on perinatal bereavement. A quasi-experimental design was used in a pretest and posttest format. Scores were significantly higher (p = .000) on each of the posttest vignettes. Overall scores were lowest for the miscarriage pretest, whereas scores for the pretest vignettes for the stillbirth and neonatal loss were similar. A similar pattern occurred in the posttest vignette scores. Health care professionals' perceptions of the emotional care needs of families experiencing perinatal loss were significantly increased after an educational program. The miscarriage vignette had the largest change score and the lowest mean scores on the pretest and posttest, which indicates professionals do not view miscarriage as significant a loss as stillbirth and neonatal loss.


Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.
To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) < PP2A < GAPDH. For local infection by TMV, the most stable genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH < PP2A < UCE. Using two of the most stable and the two least stable validated reference genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus.


Postintubation tracheal injuries--case series and literature review.
SUMMARY - Post-intubation tracheal injury is a rare and potentially fatal complication. The most common causes are overinflation ofendotracheal tube cuffs and multiple intubation attempts in emergency cases. The diagnosis is based on clinical and radiological suspicion of tracheal injury confirmed by fiberoptic bronchoscopy. Decision between conservative and surgical management of the injury depends on clinical presentation (respiratory instability, concomitant diseases), lesion characteristics (lesion site, size, and number), and time elapsed from injury to diagnosis. We present three cases ofpost-intubation tracheal injury. In two cases, the patients were treated conservatively; in the third case, the patient died from asphyxia caused by thrombus occlusion of the trachea after a longitudinal tracheal lesion. Pre-anesthetic examination did not indicate any possibility of difficult intubation in any of the patients; however, in one of the patients admitted through the emergency department, emergency intubation was performed.


Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern.
To investigate the efficacy of long-term lamivudine (3TC) and adefovir dipivoxil (ADV) combination therapy in 3TC-resistant chronic hepatitis B virus (HBV) infected patients, we analysed 28 3TC-resistant patients treated with the combination therapy during 47 months (range, 9-75). At 12, 24, 36, and 48 months, the rates of virological response with undetectable HBV DNA (≤ 2.6 log copies/mL) were 56, 80, 86, and 92%, respectively. Among 17 hepatitis B e antigen (HBeAg)-positive patients, HBeAg disappeared in 24% at 12 months, 25% at 24 months, 62% at 36 months, and 88% at 48 months. When HBV genotypes were compared, patients with genotype B achieved virological response significantly more rapidly than those with genotype C (P=0.0496). One patient developed virological breakthrough after 54 months, and sequence analysis of HBV obtained from the patient was performed. An rtA200V mutation was present in the majority of HBV clones, in addition to the 3TC-resistant mutations of rtL180M+M204V. The rtN236T ADV-resistant mutation was observed in only 25% clones. In vitro analysis showed that the rtA200V mutation recovered the impaired replication capacity of the clone with the rtL180M+M204V mutations and induced resistance to ADV. Moreover, rtT184S and rtS202C, which are known entecavir-resistant mutations, emerged in some rtL180M+M204V clones without rtA200V or rtN236T. In conclusion, 3TC+ADV combination therapy was effective for most 3TC-resistant patients, especially with genotype B HBV, but the risk of emergence of multiple drug-resistant strains with long-term therapy should be considered. The mutation rtA200V with rtL180M+M204V may be sufficient for failure of 3TC+ADV therapy.


The Value and Impacts of Academic Public Health Departments.
The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic-practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic-practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these partnerships matter regarding the outputs, outcomes, and impacts of the units that comprise them. This review also considers the most recent perspectives on how AHDs have responded to the COVID-19 pandemic and how they might advance public health's efforts to address structural racism and promote health equity.


Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics.
Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs. In this work, the relation between the solvent evaporation rate and the kinetic stabilization of highly drug-loaded ASDs was investigated. Accordingly, thermal gravimetric analysis (TGA) was employed to study the evaporation kinetics of seven organic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen (NAP), on the evaporation behavior. At 10 °C below the boiling point of the respective solvent, methanol (MeOH) had the lowest evaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effect was more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNB increased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and the solvent or NAP and PVPVA, which was further investigated using Fourier transform-InfraRed (FT-IR) spectroscopy. Based on these findings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOH and DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP. Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited, demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantly determined by the API-polymer-solvent combination rather than the process parameters applied.


Drug- and/or trauma-induced hyperthermia? Characterization of HSP70 and myoglobin expression.
Heat shock protein 70 (HSP70) expression could be discussed as an adaption that promotes repair and counteracts cell damage. Myoglobin is released upon muscle damage of several pathways. The purpose of the present study was to determine whether the expression of HSP70 in kidney, heart and brain and of myoglobin in the kidney were associated with the cause of death and the survival times after lethal intoxications with three of the drugs most widely used in our local area (Saxony, Germany) as well as after fatal traumatic brain injury (TBI). We retrospectively collected kidney, heart and brain samples of 50 autopsy cases with toxicological proved lethal intoxication (main drugs methamphetamine, morphine, alcohol), 14 TBI cases and 15 fatalities with acute myocardial injury in age- and gender-matched compilations. Our main findings suggest that HSP70 is associated with hyperthermal and other stress factors of most cell populations. HSP70 expressions in kidney and heart muscle are useful for a differentiation between fatal intoxications and cases without toxicological influence (p < 0.05). There were significant differences in the cerebral expression patterns between methamphetamine- and morphine-associated deaths compared to alcohol fatalities (p < 0.05). An intensive staining of HSP70 in the pericontusional zone and the hippocampus after TBI (especially neuronal and vascular) was shown even after short survival times and may be useful as an additional marker in questions of vitality or wound age. A relevant myoglobin decoration of renal tubules was only shown for methamphetamine abuse in the study presented. In sum, the immunohistochemical characteristics presented can be supportive for determining final death circumstances and minimal trauma survival times but are not isolated usefully for the detection of drug- or trauma-induced hyperthermia.


The HLA class I immunopeptidomes of AAV capsid proteins.
Cellular immune responses against AAV vector capsid represent an obstacle for successful gene therapy. Previous studies have used overlapping peptides spanning the entire capsid sequence to identify T cell epitopes recognized by AAV-specific CD8+ T cells. However, the repertoire of peptides naturally displayed by HLA class I molecules for CD8 T cell recognition is unknown. Using mRNA transfected monocyte-derived dendritic cells (MDDCs) and MHC-associated peptide proteomics (MAPPs), we identified the HLA class I immunopeptidomes of AAV2, AAV6 and AAV9 capsids. MDDCs were isolated from a panel of healthy donors that have diverse alleles across the US population. mRNA-transfected MDDCs were lysed, the peptide:HLA complexes immunoprecipitated, and peptides eluted and analyzed by mass spectrometry. We identified 65 AAV capsid-derived peptides loaded on HLA class I molecules of mRNA transfected monocyte derived dendritic cells. The HLA class I peptides are distributed along the entire capsid and more than 60% are contained within HLA class II clusters. Most of the peptides are organized as single species, however we identified twelve clusters containing at least 2 peptides of different lengths. Only 9% of the identified peptides have been previously identified as T cell epitopes, demonstrating that the immunogenicity potential for the vast majority of the AAV HLA class I immunopeptidome remains uncharacterized. In contrast, 12 immunogenic epitopes identified before were not found to be naturally processed in our study. Remarkably, 11 naturally presented AAV peptides were highly conserved among the three serotypes analyzed suggesting the possibility of cross-reactive AAV-specific CD8 T cells. This work is the first comprehensive study identifying the naturally displayed HLA class I peptides derived from the capsid of AAVs. The results from this study can be used to generate strategies to assess immunogenicity risk and cross-reactivity among serotypes during gene therapies.


Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.
The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis".


Role of lncRNA BANCR in Human Cancers: An Updated Review.
Being located in a gene desert region on 9q21.11-q21.12, BRAF-activated non-protein coding RNA (BANCR) is an lncRNA with 693 bp length. It has been discovered in 2012 in a research aimed at assessment of gene expression in the melanocytes in association with BRAF mutation. Increasing numbers of studies have determined its importance in the tumorigenesis through affecting cell proliferation, migration, invasion, apoptosis, and epithelial to mesenchymal transition. BANCR exerts its effects via modulating some tumor-related signaling pathways particularly MAPK and other regulatory mechanisms such as sponging miRNAs. BANCR has been up-regulated in endometrial, gastric, breast, melanoma, and retinoblastoma. Conversely, it has been down-regulated in some other cancers such as those originated from lung, bladder, and renal tissues. In some cancer types such as colorectal cancer, hepatocellular carcinoma and papillary thyroid carcinoma, there is no agreement about BANCR expression, necessitating the importance of additional functional studies in these tissues. In the present manuscript, we review the investigations related to BANCR expression changes in cancerous cell lines, clinical samples, and animal models of cancer. We also discuss the outcome of its deregulation in cancer progression, prognosis, and the underlying mechanisms of these observations.


Improved confidence estimation for the binomial proportion with applications to clinical studies.
In this paper, we establish a frequentist framework that incorporates all confidence sets with guaranteed frequentist coverage probability for the binomial proportion, where different confidence sets are completely characterized by their tail functions. Based on measures of precision in the form of interval length, probability of false coverage, and a new evaluation criterion utilizing prior information, we construct the optimal confidence set for the binomial proportion. The newly proposed methodology is applied to clinical studies. It is shown that confidence intervals obtained via the tail functions are often better than prevailing confidence intervals in view of precision.


Use of evidence-based management for acute coronary syndrome.
This study compared the management of acute coronary syndrome (ACS) for patients admitted to Dunedin Coronary Care with evidence-based recommendations from the American College of Cardiology / American Heart Association in 1999 and 2002 and with management reported in international and local registries. All patients with ACS from 2001-2002 were included. Guidelines stated that aspirin, beta-blockers, statins, and ACE-inhibitors/angiotensin-II-blockers are appropriate treatment for acute coronary syndrome. These medications were prescribed respectively in 98%, 80%, 70% and 55% of patients on discharge. In patients with documented dyslipidaemia, Statins was prescribed in 80% on discharge. The use of ACE inhibitors was 73% in patients with impaired left ventricular function, 79% in patients with clinical heart failure and 84% in patients with anterior ST-elevation myocardial infarction (STEMI). For patients with STEMI, 67% received coronary angiography, 50% had PCI and 7% underwent inpatient coronary artery bypass grafting. For Non-ST-elevation myocardial infarction (NSTEMI), the respective numbers were 73%, 38% and 21%. Our use of evidence-based medications was consistent with published guidelines and comparable to results of international registries (CRUSADE, EUROESPIRE II, GRACE) in 2001-2002. There is good adherence to the use of evidence-based management for acute coronary syndrome in Dunedin Coronary Care Unit.


Immunological studies on the localization of phosphatidylglycerol in the membranes of Mycoplasma hominis.
Phosphatidylglycerol is the main component (87%) of the membrane phospholipids of Mycoplasma hominis. It is immunologically active. Antibodies directed against phosphatidylglycerol were detected in rabbits intravenously immunised with native M. hominis or isolated M. hominis membranes. The intravenous method of immunisation was chosen in order to select for a response to surface antigenic determinants. Anti-phosphatidylglycerol antibodies were induced in rabbits by intravenously injecting the flocculated complexes of methylated bovine serum albumin and a phosphatidylglycerol/phosphatidylcholine/cholesterol mixture. These antibodies were specifically bound to intact M. hominis, as shown by complement fixation and Coombs tests. Native M. hominis were not agglutinated by anti-phosphatidylglycerol antibodies; but after partial digestion of the membrane proteins with Pronase, the mycoplasmas were heavily agglutinated by the anti-phosphatidylglycerol antibodies. The same amount of anti-phosphatidylglycerol antibodies was bound to intact M. hominis, containing 600 mug of phosphatidylglycerol as to 6 mug of phosphatidylglycerol in the optimal configurational arrangement of a mixed phosphatidylglycerol/phosphatidylcholine/cholesterol micelle. It is concluded that the major part of the phosphatidylglycerol in native M. hominis membranes is masked, probably by membrane proteins, and is not accessible to the anti-phosphatidylglycerol antibodies.


[Study of T lymphocyte subpopulations in patients with leprosy, using incubation with theophylline].
T cells and the theophylline resistant cells (the-r, helper cells) in peripheral blood of patients with different forms of leprosy were studied. Active lepromatous patients (LL+) showed a significant decrease in T lymphocytes and the-r cells. Nevertheless, in LL+ developing a reactional episode of erythema nodosum (LL-ENL) a restoration in the level of the-r cells was observed. It is concluded that in LL+ patients the depression of T cells and the-r cells represents an imbalance in the T-T cellular cooperation with a defective cellular immune response. On the other hand, the recovery of the-r cells in LL-ENL support the hypothesis of a cell mediated immune mechanism in the immunopathology of this reactional episode.


Evidence of allopolyploidy in Brachiaria brizantha (Poaceae: Paniceae) through chromosome arrangement at metaphase plate during microsporogenesis.
In the hexaploid (2n = 6x = 54) accession B176 of Brachiaria brizantha, one cytological characteristic differentiated it from the other accessions previously analyzed with the same ploidy level. Nearly 40% of meiocytes displayed the chromosome set arranged at two metaphase plates at the poles of the cell, close to the membrane. In these cells, both metaphase plates were arranged in an angle to form a typical tripolar spindle. Therefore, cells did not show normal chromosome segregation at anaphase I. Only nine univalent chromosomes migrated from each plate to the opposite pole with the remainder staying immobile on the plate. As a result of such spindle orientation and chromosome behavior, trinucleate telophases I were recorded. After telophase, cytokinesis eliminated the small nuclei into a microcyte. The second division proceeded normally, with the presence of microcytes in all phases. The origin of such an abnormality was explained on the hexaploid level of the accession which could have resulted by chromosome doubling of a triploid derived from species that did not display the same behavior for spindle organization. The high percentage of meiotic abnormalities recorded in this accession compromises fertility and renders it inadequate for the breeding program.


Development of Bruton's Tyrosine Kinase Inhibitors for Rheumatoid Arthritis.
Rheumatoid Arthritis (RA) is a chronic autoimmune disease and becomes one of the major causes of disability and work force loss. The presence of abnormal B cell and autoantibodies produced by most RA patients, primarily ACPA and RF, indicate that the function of B cell was involved in the development of RA disease. Accordingly, the drug targeting B cell has become a hot spot in the treatment of RA. Studies have shown that Bruton's tyrosine kinase (BTK) is involved in the regulation of B cell proliferation and activation process. Some small molecule BTK inhibitors have shown excellent inhibition in biological activity analysis and animal models. Therefore, this review will briefly introduce BTK and its role in cell signaling and overview recent progress of BTK inhibitors for RA treatment.