[Determination of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan for Uyghur medicine by high performance liquid chromatography].
Uyghur medicine is one important part of the national medicine system. Uyghur medicine modernization, namely the study of effective components with modern technologies, is the only way for the scientification, standardization, and industrialization of Uyghur medicine. Here we developed a selective extraction method for rutin, quercetin and kaempferol in Althaea rosea (L) Gavan. The three active species were determined by high performance liquid chromatography (HPLC) with HC-C18 column (250 mm x 4.6 mm, 5 μm) and the mobile phase of CH3OH-0.4% H3PO4 (50 :50, v/v). Rutin, quercetin and kaempferol were baseline separated with each other and the interference species with flow rate of 1.0 mL/min and column temperature of 30 degrees C. Under the optimal conditions, linear correlation were obtained in the mass concentration range of 12.5-150 μg/mL (r = 0.999 8) for rutin, 12.5-125 μg/mL (r = 0.999 9) for quercetin, and 12.5-125 μg/mL (r = 0.998 8) for kaempferol. The recoveries (n = 5) of rutin, quercetin and kaempferol were 100.25% ( RSD = 1.1%), 97.60% ( RSD = 0.47%) and 97.75% (RSD = 0.71%), respectively. The method can be used to determine the contents of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan and provide the guidance for the analysis of the flavonoids in other Uyghur medicines.


Zeta-associated protein 70 expression in chronic lymphocytic leukemia: Relevance in Indian context.
Chronic lymphocytic leukemia (CLL) is prognosticated using the Rai and the Binet's staging. In the past few years, new parameters have been considered for prognostication. One such marker that has been a subject of speculation and found useful by some western studies is zeta-associated protein 70 (ZAP-70). To investigate the prevalence of ZAP-70 and find out its association with other prognostic markers like Rai and Binet's stage and CD38 in Indian CLL patients. Twenty-nine newly diagnosed cases of CLL were selected over 1 year. Immunophenotyping was done and expression of CD38 and ZAP-70 was evaluated on gated CLL cells. Qualitative data were expressed as frequency and percentage. Differences between groups were evaluated using Student's t-test for quantitative data and Chi-square test/Fisher's exact t-test for qualitative variables. A P value less than 0.05 was considered significant. We found a lower prevalence rate of ZAP-70 (2/29, 6.89%) with no association with any of the conventional poor prognostic factors. A large number of our CLL patients fall into the good prognostic group (22/29, ZAP 70-/CD38-) with a least number in the poor prognostic group (2/29, ZAP-70 + CD38+). Also, no association was found between ZAP-70 and CD38. The findings of the present study suggest that the majority of CLL patients in India have a good prognosis, may not require treatment, and have good overall survival. Geographical variations, genetic makeup, and natural history of the CLL could be the cause of such differences from western literature.


Immunohistochemical detection of alpha 1-antitrypsin, alpha 1-antichymotrypsin, transferrin and ferritin in ameloblastoma.
An immunohistochemical study was performed to investigate the presence of alpha-1-antitrypsin (alpha 1-AT), alpha-1-antichymotrypsin (alpha 1-ACT), transferrin and ferritin in 32 ameloblastomas and to evaluate the co-expression of these antibodies. Histologically, we recognized the following 6 patterns in the series of 32 ameloblastomas and at least 2 patterns in variable proportions were present in each of our cases: follicular pattern (21 cases, 66%), plexiform pattern (17 cases, 53%), cystic pattern (21 cases, 66%), acanthomatous pattern (10 cases, 31%), granular cell type (2 cases, 6%), and hyalinized stromal pattern (20 cases, 63%). Neoplastic epithelia of cystic pattern were divided into superficial cell, basal cell and whole layer to compare the immunohistochemical localization. The results made on the various patterns of ameloblastomas were as follows: (1) alpha 1-AT positivity in plexiform, cystic and hyalinized stromal patterns was significantly higher than that of alpha 1-ACT (P < 0.05). (2) The incidence of transferrin in follicular and plexiform patterns was markedly higher than that of ferritin in the same patterns (P < 0.025 and P < 0.01). Transferrin strongly stained metaplastic squamous cells of acanthomatous pattern and basal cells of cystic epithelium. (3) Granular cells reacted with transferrin and ferritin. (4) In follicular and acanthomatous patterns, coexpression of alpha 1-AT and alpha 1-ACT, alpha 1-AT and transferrin, or alpha 1-ACT and transferrin was higher than that of another combination. On the other hand, co-expression of alpha 1-AT and transferrin in plexiform and cystic patterns was higher than that of other antibodies. These results of co-expression of 4 antibodies used in the present study, suggest that the histogenesis of follicular and acanthomatous patterns is different from that of plexiform and cystic patterns.


Drugs affecting clearance of middle ear secretions: a perspective for the management of otitis media with effusion.
Otitis media with effusion (OME) is characterized by the production and accumulation in the middle ear of mucus secretions, whose physicochemical properties are an important feature in the etiology and treatment of the disease. Many types of pharmaceutical agents, including anti-inflammatory agents, antihistamines, antibiotics, and mucolytics, have been used in attempts to improve the clinical status of patients with OME. This study critically reviews the literature from the point of view of possible changes induced by these agents in the physicochemical properties of the secretions and hence their clearance from the middle ear. In vitro studies on mucociliary clearance of respiratory (tracheobronchial) secretions and middle ear effusions are cited as the basis for analyzing the important parameters expected to govern middle ear clearance and to determine the rationale for use (or nonuse) of various classes of drugs. It is expected that this analysis will prove useful in the design of properly controlled trials of such agents.


Two-Dimensional Superconductivity at the LaAlO_{3}/KTaO_{3}(110) Heterointerface.
We report on the observation of a T_{c}∼0.9 K superconductivity at the interface between LaAlO_{3} film and the 5d transition metal oxide KTaO_{3}(110) single crystal. The interface shows a large anisotropy of the upper critical field, and its superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition. Both facts suggest that the superconductivity is two-dimensional (2D) in nature. The carrier density measured at 5 K is ∼7×10^{13} cm^{-2}. The superconducting layer thickness and coherence length are estimated to be ∼8 and ∼30 nm, respectively. Our result provides a new platform for the study of 2D superconductivity at oxide interfaces.


Antiinflammatory effect of retrovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches.
To investigate the role of interleukin-10 (IL-10) in the inflammatory response, the antiinflammatory effect of retrovirally transfected IL-10 was evaluated both in vitro and in vivo. A recombinant retrovirus containing the murine IL-10 gene was constructed using the pLXSN vector and was designated as LXSN-IL-10. Murine IL-10 was introduced into embryonic C57BL/6J fibroblast cells using LXSN-IL-10 to create C57-IL-10 cells. The effect of IL-10 in the culture supernatant of these cells was then evaluated by determining changes in the production of tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta by macrophages. The antiinflammatory effect of C57-IL-10 cells was also investigated using an in vivo model of monosodium urate monohydrate (MSU) crystal-induced acute inflammation. The IL-10 gene transcript and its product were detected by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The level of IL-10 in the culture supernatant of C57-IL-10 cells was estimated to be 50 ng/ml. The culture supernatant of these cells exerted the biologic activity of IL-10, showing inhibition of TNFalpha, MIP-1alpha, and MIP-1beta production by macrophages. Injection of C57-IL-10 cells into murine air pouches significantly inhibited MSU crystal-induced cellular infiltration (P < 0.01) and production of the mouse CXC chemokine KC (P < 0.05). These findings were consistent with the results obtained by the injection of recombinant human IL-10 into air pouches. In this murine air pouch model of MSU crystal-induced inflammation, IL-10 seemed to inhibit the recruitment of neutrophils at least partly by suppressing KC production. These findings seem to suggest that IL-10 gene therapy may be useful for inflammatory diseases.


[A Structural Equation Model of Pressure Ulcer Prevention Action in Clinical Nurses].
The purpose of this study was to construct and test a structural equation model for pressure ulcer prevention action by clinical nurses. The Health Belief Model and the Theory of Planned Behavior were used as the basis for the study. A structured questionnaire was completed by 251 clinical nurses to analyze the relationships between concepts of perceived benefits, perceived barriers, attitude, subjective norm, perceived control, intention to perform action and behavior. SPSS 22.0 and AMOS 22.0 programs were used to analyze the efficiency of the hypothesized model and calculate the direct and indirect effects of factors affecting pressure ulcer prevention action among clinical nurses. The model fitness statistics of the hypothetical model fitted to the recommended levels. Attitude, subjective norm and perceived control on pressure ulcer prevention action explained 64.2% for intention to perform prevention action. The major findings of this study indicate that it is essential to recognize improvement in positive attitude for pressure ulcer prevention action and a need for systematic education programs to increase perceived control for prevention action.


Identification and determination of propafenone and its principal metabolites in human urine using capillary gas chromatography/mass spectrometry.
The capillary gas chromatography/mass spectrometry of trimethylsilyl-trifluoroacetyl, trifluoroacetyl and pentafluoropropionyl (PFP) derivatives of the antiarrhythmic agent propafenone (Rytmonorm), as well as its main metabolites N-despropyl-propafenone and 5-hydroxy-propafenone, have been investigated. Both electron impact and positive isobutane chemical ionization mass spectrometry using the Ion Trap Detector have been evaluated. The presence of propafenone and its co-extracted metabolites in human urine at time intervals after the oral administration of 150 mg Rytmonorm to healthy volunteers was established, and the urinary excretion of propafenone and 5-hydroxy-propafenone was calculated using selective chemical ionization mass spectrometric detection. Only a few per cent of the dose was excreted unchanged in the urine. Large intersubject variabilities had been observed also. The large dynamic range of the Ion Trap Detector and the high correlation coefficients (0.92-0.99) of the calibration curves were striking.


Simple synthetic receptors for aspirin.
Shallow methylene-bridged cavitands appended with simple H-bond donor/acceptor groups are shown to bind aspirin. The structural features needed in a synthetic receptor for aspirin binding are defined.


Photodynamic therapy with 5-aminolevulinic acid induces apoptosis and caspase activation in malignant T cells.
Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.


New introduction of clade 18.104.22.168 avian influenza virus (H5N1) into Bangladesh.
Since the first outbreak of highly pathogenic H5N1 avian inafluenza (HPAI) in Bangladesh in February 2007, a total of 519 disease events have been reported till 22 October 2011. Partial HA gene sequences of 11 selected H5N1 HPAI isolates of 2007 to 2011 were determined and subjected to phylogenetic analysis. The study revealed a recent introduction of clade 2.3.2 and 2.3.4 viruses into Bangladesh in 2011 in addition to clade 2.2 viruses that had been in circulation since 2007. Clade 2.3.2 virus isolates from Bangladesh are phylogenetically related to the newly designated clade 22.214.171.124 viruses, reported recently from Asia and Eastern Europe.


Multi-Target In Silico Prediction of Inhibitors for Mitogen-Activated Protein Kinase-Interacting Kinases.
The inhibitors of two isoforms of mitogen-activated protein kinase-interacting kinases (i.e., MNK-1 and MNK-2) are implicated in the treatment of a number of diseases including cancer. This work reports, for the first time, a multi-target (or multi-tasking) in silico modeling approach (mt-QSAR) for probing the inhibitory potential of these isoforms against MNKs. Linear and non-linear mt-QSAR classification models were set up from a large dataset of 1892 chemicals tested under a variety of assay conditions, based on the Box-Jenkins moving average approach, along with a range of feature selection algorithms and machine learning tools, out of which the most predictive one (>90% overall accuracy) was used for mechanistic interpretation of the likely inhibition of MNK-1 and MNK-2. Considering that the latter model is suitable for virtual screening of chemical libraries-i.e., commercial, non-commercial and in-house sets, it was made publicly accessible as a ready-to-use FLASK-based application. Additionally, this work employed a focused kinase library for virtual screening using an mt-QSAR model. The virtual hits identified in this process were further filtered by using a similarity search, in silico prediction of drug-likeness, and ADME profiles as well as synthetic accessibility tools. Finally, molecular dynamic simulations were carried out to identify and select the most promising virtual hits. The information gathered from this work can supply important guidelines for the discovery of novel MNK-1/2 inhibitors as potential therapeutic agents.


A Flexible Bayesian Model for Estimating Subnational Mortality.
Reliable subnational mortality estimates are essential in the study of health inequalities within a country. One of the difficulties in producing such estimates is the presence of small populations among which the stochastic variation in death counts is relatively high, and thus the underlying mortality levels are unclear. We present a Bayesian hierarchical model to estimate mortality at the subnational level. The model builds on characteristic age patterns in mortality curves, which are constructed using principal components from a set of reference mortality curves. Information on mortality rates are pooled across geographic space and are smoothed over time. Testing of the model shows reasonable estimates and uncertainty levels when it is applied both to simulated data that mimic U.S. counties and to real data for French départements. The model estimates have direct applications to the study of subregional health patterns and disparities.


Characteristics of extracellular cyclic AMP-dependent protein kinase as a biomarker of cancer in dogs.
Early and proper diagnosis of cancer is the most critical factor for the survival and treatment of veterinary cancer patients. In this study, we evaluated extracellular cyclic AMP-dependent protein kinase A (ECPKA) level in serum as a useful cancer biomarker in dogs. ECPKA levels were detected in sera from dogs with cancers (n = 48), benign tumours (n = 18), and non-tumour diseases (n = 102) as well as healthy control dogs (n = 54) utilizing enzyme-linked immunosorbent assay (ELISA). Sera from dogs bearing various types of cancer exhibited markedly increased levels of ECPKA by up to 7.1-, 8.8-, and 10.9-fold compared with those from dogs harbouring benign tumours, dogs with non-tumour diseases, and healthy control dogs, respectively (P < .0001). In addition, serum ECPKA level did not show statistically significant correlation with gender, breed, or age of dogs or their non-cancerous disease conditions. Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs.


Prenatal telemedicine during COVID-19: patterns of use and barriers to access.
To evaluate patient experience with a prenatal telemedicine visit and identify barriers to accessing telemedicine among rural pregnant people in northern New England during the beginning of the COVID-19 pandemic. We conducted a postvisit electronic survey of pregnant people who successfully participated in a prenatal telemedicine visit at a rural academic medical center in Northern New England. Nineteen questions were included in 5 domains: (1) engagement with prenatal care; (2) barriers to telemedicine and in person healthcare; (3) experience of prenatal care; (4) remote pregnancy surveillance tools; and (5) sources of COVID-19 information. Responses were obtained from 164 pregnant people. Forty percent of participants had participated in an audio-only telemedicine visit, and 60% in a video telemedicine visit. The visit was easy or somewhat easy for 79% of respondents and somewhat difficult or difficult for 6.8%. The most common barrier to accessing telemedicine was poor internet or phone connectivity, followed by childcare responsibilities, lack of equipment, and lack of privacy. Participants also engaged in additional remote prenatal care including phone calls with registered nurses (7.6%), communication with the obstetrics team through a secure health messaging portal (21.1%), and home health monitoring (76.3%). In this survey, evaluating the experience of pregnant people participating in a prenatal telemedicine visit during the COVID-19 pandemic, respondents had a positive experience with telemedicine overall, but also identified significant barriers to participation including issues with connectivity and lack of equipment for the visit. Most participants used telemedicine in combination with other tools for remote self-care.


PixE promotes dark oligomerization of the BLUF photoreceptor PixD.
Cyanobacteria perceive and move (phototax) in response to blue light. In this study, we demonstrate that the PixD blue light-sensing using FAD (BLUF) photoreceptor that governs this response undergoes changes in oligomerization state upon illumination. Under dark conditions we observed that PixD forms a large molecular weight complex with another protein called PixE. Stoicheometric analyses, coupled with sedimentation equilibrium and size exclusion chromatography, demonstrates that PixE drives aggregation of PixD dimers into a stable PixD(10)-PixE(5) complex under dark conditions. Illumination of a flavin chromophore in PixD destabilizes the PixD(10)-PixE(5) complex into monomers of PixE and dimers of PixD. A crystallographic structure of PixD, coupled with Gibbs free energy calculation between interacting faces of PixD, lends to a model in which a light induces a conformational change in a critical PixD-interfacing loop that results in destabilization of the PixD(10)-PixE(5) complex.


Exploring Preterm Mothers' Personal Narratives: Influences and Meanings.
In this article we report on a study exploring personal narratives of mothers of former preterm infants and the attributed meaning related to that experience over time. Using narrative inquiry as the research method, in-depth, unstructured interviews were conducted with 6 preterm mothers. Findings reveal that a preterm mother's experience is informed by contextual, intrapersonal, and interpersonal dynamics, some predating the birth often with effects that continue for years beyond it. By learning a preterm mother's unique experience and its attributed meaning, nurses can better understand the resulting effect on maternal/family health and well-being and tailor nursing interventions accordingly.


Thermal ablation of canine prostate using interstitial temperature self-regulating seeds: new treatment for prostate cancer.
An interstitial temperature self-regulating implantable thermal seed for ablation of the prostate was investigated for the treatment of cancer. The technique is analogous to brachytherapy implants with three important advantages: highly localized temperatures may reduce complications, the thermal seed can be activated for retreatment at any point in time, and the seeds pose no radiation hazard to the clinical staff. Thermal seeds were implanted in the left lobe of the prostates in four dogs; the right lobe was a control to evaluate undesired heating outside the seed array. Linear-array thermometry probes were placed in both lobes, and the induction field for heating the implants was activated for 1 hour. After treatment, biopsies were taken from both lobes at 4-hour intervals up to 28 hours to evaluate thermal damage and thermotolerance as measured by expression of heat shock protein (hsp) 70. Only 5 minutes was required to heat the left lobe to 45 degrees to 55 degrees C. The maximum and minimum cumulative equivalent minutes at 43 degrees C (CEM43) thermal doses in the treated lobe were 174 and 4.4 hours, respectively; less than a 1-minute CEM43 was observed in the control lobe. Elevated hsp70 expression was detected in tissue of the treated lobe between 12 and 24 hours after treatment; minimal increases occurred in the control lobe. The thermal seed system was effective at heating the prostatic volume without damage to normal tissues outside the implant array, and subsequent treatments were simplified in comparison with other hyperthermia devices. Expression of hsp70 implies that retreatment of the prostate at intervals as short as 48 to 72 hours may avoid thermotolerance making weekly treatment an appropriate regimen.


Radiology Medical Student Education 2020: Surveys of the Alliance of Medical Student Educators in Radiology and Medical Students.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant changes to medical student education by disrupting clinical rotations, licensing exams, and residency applications. To evaluate the pandemic's impact and required modifications of radiology medical student courses, the authors developed and administered surveys to Alliance of Medical Student Educators in Radiology (AMSER) faculty and enrolled medical students. The surveys requested feedback and insight about respondents' experiences and innovations. Anonymous twenty-question and seventeen-question surveys about the pandemic's impact on medical student education were distributed via email to AMSER members and medical students. The surveys consisted of multiple choice, ranking, Likert scale, and open-ended questions. Differences in the Likert score agreement was performed using one-sided Wilcoxon-Mann-Whitney tests. Survey data were collected using SurveyMonkey (San Mateo, California). This study was IRB exempt. The AMSER survey indicated 96% of institutions cancelled medical student courses and 92% resumed with virtual courses, typically general radiology. A total of 64% of faculty enjoyed online teaching, although 82% preferred on-site courses. A total of 62% of students felt an online radiology course was an excellent alternative to an on-site rotation, although 27% disagreed. A total of 69% of students who completed both on-site and online courses preferred the on-site format. Survey-reported innovations and free response comments have been collated as educational resources. Faculty were able to adapt radiology courses to the online environment utilizing interactive lectures, self-directed learning, flipped classroom sessions, and virtual readouts, which were effective for student respondents. Hybrid rotations with on-site and online elements may offer the best of both worlds.


Digital family histories for data mining.
As we move closer to ubiquitous electronic health records (EHRs), genetic, familial, and clinical information will need to be incorporated into EHRs as structured data that can be used for data mining and clinical decision support. While the Human Genome Project has produced new and exciting genomic data, the cost to sequence the human personal genome is high, and significant controversies regarding how to interpret genomic data exist. Many experts feel that the family history is a surrogate marker for genetic information and should be part of any paper-based or electronic health record. A digital family history is now part of the Meaningful Use Stage 2 menu objectives for EHR reimbursement, projected for 2014. In this study, a secure online family history questionnaire was designed to collect data on a unique cohort of Vietnam-era repatriated male veterans and a comparison group in order to compare participant and family disease rates on common medical disorders with a genetic component. This article describes our approach to create the digital questionnaire and the results of analyzing family history data on 319 male participants.


Knowledge, attitudes and practices of local inhabitants about insecticide treated nets (ITNs) for malaria control in an endemic area of Ethiopia.
The present study was conducted to assess the knowledge, attitudes and practices of local residents about insecticide treated nets (ITNs) for malaria control in an endemic area of Ethiopia. A descriptive cross-survey was conducted from July 2008 to September 2008. A structured questionnaire collecting sociodemographic, ITNs and malaria-related KAP information was administered to the representatives of households. Azendabo town, Ethiopia. 84% of the inhabitants had awareness about malaria transmission; mosquito bites were identified correctly as the cause of malaria. 85.2% respondents indicated that mosquitoes bite at night. ITNs awareness level of inhabitants was 92.4%; however, just 57.8% of them own ITNs. 96.2% and 91.5% of the inhabitants indicated the foremost reasons for nonpossession of ITNs were due to unaffordability and nonavailability. Inhabitants average monthly income significantly associated with the ITNs ownership at p<0.05 and, however educational status of the respondents and ITNs ownership was not significant (p=0.1). Indeed, respondents had adequate knowledge regarding ITNs and malaria related information. However, inhabitants had poor attitude and practice towards the ITNs utilization due to lack of availability and affordability. Therefore, besides health education campaign, distribution and promotion of ITNs to entire rural residents at free of charge may possibly bring constructive outcome in the near future.


Cholinergic modulation of spatial learning in mice in a Morris-type water maze.
Injection of the centrally active muscarinic antagonist scopolamine i.p. 20 min pre-test at 3 mg/kg but not at 1 mg/kg, impaired spatial learning of a Morris-type water maze adapted for mice. Both doses caused hyperactivity. D-amphetamine (3 mg/kg, i.p.), which also caused hyperactivity, did not impair spatial learning nor did methylscopolamine (3 mg/kg, i.p.). In a cued version of the water maze, apart from a temporary disturbance on day 1, scopolamine (3 mg/kg) and control groups behaved similarly, indicating that scopolamine-induced place learning deficits are not due to changes in swimming ability, motivation or ability to use proximal cues. Physostigmine (0.1 and 0.2 mg/kg, i.p.) and oxotremorine (0.02 mg/kg but not 0.01 mg/kg, i.p.) antagonized the deficits in the swimming maze. Neither drug affected the scopolamine hyperactivity despite causing hypoactivity per se. In contrast, the peripherally acting cholinergic drug neostigmine was inactive against scopolamine in either test at 0.1 mg/kg. THA (2-8 mg/kg, i.p.), RS86 (0.25-1 mg/kg, i.p.) and nicotine (1 and 3 mg/kg, i.p.) were also unable to antagonize the scopolamine effect. These studies show that scopolamine disrupts acquisition of spatial rather than cued learning in mice in a Morris-type water maze and that this effect appears to be mediated centrally and can be dissociated from drug-induced hyperactivity. Moreover, this deficit can be reversed with certain cholinergic agents.


Utility and validity of the self-administered SF-36: findings from an older population.
The objectives of this study were to assess the utility and validity of the self-administered SF-36 and the effect of visual or cognitive impairment on these measures in an older population. Attempt rates, completion rates and internal consistency (Cronbach alpha) were compared within the second cross-sectional, population-based Blue Mountains Eye Study (n = 3509, mean age 66.7 years, 57% women). The SF-36 was attempted by 3162 (90.1%) participants, of which 2470 (78.1%) completed all items and 2873 (90.9%) completed sufficient items for calculation of all dimensions. In a multivariate model adjusting for age, sex, and presenting visual and cognitive impairments, women (P = 0.011) and participants with visual or cognitive impairments (P < 0.0001) were less likely to attempt the questionnaire. Completion rates were significantly lower with increasing age (P < 0.0001), in men (P < or = 0.0005) and in those with cognitive impairment (P < 0.0001). A high level of internal consistency (Cronbach alpha > 0.85 for all dimensions) and construct validity was demonstrated, the latter distinguishing between those with and without medical conditions, disabilities or recent hospital admissions (P < 0.01). As the prevalence of visual or cognitive impairment was relatively low in this population, we found no apparent effect of these impairments on the validity of SF-36. Attempt and completion rates, but not internal consistency and construct validity, of the SF-36 were influenced by age, gender, and presenting visual and cognitive impairments. The overall high attempt and completion rates, internal consistency and construct validity suggest that the self-administered SF-36 is a suitable healthrelated quality of life (HRQOL) measure in similar older community-living populations.


The biosynthesis of gap junctions.
This brief presentation is designed to review the descriptive information available on the formation of gap junctions between cells, and to discuss the recent progress that has been made on studying the biosynthesis of junctional polypeptides in both cell-free systems and intact tissue.


Overcoming barriers in online workshop development: an ELITE experience.
The Emerging Learning and Integrated Technologies Education (ELITE) Faculty Development Program created eight online workshops to assist nurse educators in using technology within their organization's nurse education program. Continuing education units were provided for completion of the individual online workshops. The ELITE program worked through several barriers to transform content that was previously presented during face-to-face workshops into standalone online offerings. Barriers and implementation strategies for the on-site to online transition included restructuring workshop objectives, keeping current with rapid technology changes, altering a course management system to meet the needs of the program and the learner, and crafting independent practice opportunities for the online learner. The online workshop development experience of the ELITE program may assist other continuing education and staff development professionals who are updating their program offerings or pursuing online education for the first time.


Purification and initial characterization of a protein which facilitates assembly of nucleosome-like structure from mammalian cells.
A protein, which facilitates assembly of a nucleosome-like structure in vitro, was previously partially purified from mouse FM3A cells [Ishimi, Y. et al. (1983) J. Biochem. (Tokyo) 94, 735-744]. The protein has been purified to approximately 80% from FM3A cells by using histone-Sepharose column chromatography. It sedimented at 4.6 S and had a molecular mass of 53kDa. A preincubation of core histones with the 53-kDa peptide before DNA addition was necessary for the nucleosome assembly. The 53-kDa peptide bound to core histones and formed a 12-S complex. This complex contained stoichiometrical amounts of the 53-kDa peptide and core histones, and the core histones in this complex were composed of equal amounts of H2A, H2B, H3 and H4 histones. The nucleosomes were assembled by adding pBR322 DNA to the 12-S complex. When mononucleosome DNA and core histones were mixed in the presence of the 53-kDa peptide, formation of a 10.5-S complex was observed. The complex contained DNA and core histones in equal amounts, while no 53-kDa peptide was detected in the complex. From above results it is suggested that the 53-kDa peptide facilitates nucleosome assembly by mediating formation of histone octamer and transferring it to DNA. Rat antibody against the 53-kDa peptide did not bind to nucleoplasmin from Xenopus eggs. The relationship between the 53-kDa peptide and nucleoplasmin is discussed.


Human Toxocariasis in Portugal-An Overview of a Neglected Zoonosis over the Last Decade (2010-2020).
Toxocariasis is one of the most widespread and important zoonotic parasitic diseases, although neglected. Data regarding human Toxocara infection in Portugal are almost absent. This article gives an overview of the situation of toxocariasis in Portugal over the last decade based on casuistic data. A total of 846 serum samples from individuals suspected of toxocariasis, collected from 2010 to 2020, were analyzed at the Institute of Hygiene and Tropical Medicine. Sera were tested for IgG antibodies to Toxocara canis excreted-secreted larval antigens by enzyme-linked immunosorbent assay and counterimmunoelectrophoresis. Positivity was detected in 18.8% (159/846) [CI 95%: 16.3-21.6], with positives detected throughout continental Portugal. Overall, 59.7% of the positives were diagnosed in younger than 20 years (35.2% aged 0-9 years and 24.5% aged 10-19 years). Eosinophilia was the most frequent feature reported (27.7%). Pediatrics (41.5%) and Infectiology (25.8%) were the specialties with the highest number of positives. An average of 77 samples/year were received, recording a maximum positivity in 2012 (41.5%, n = 27/65) and a minimum in 2020 (6.4%, n = 3/47). These numbers may reflect the effectiveness of current preventive measures, highlighting the need to maintain public awareness to control this helminthozoonosis and promote a higher public health standard.


Enhanced Characterization of Cardiolipins via Hybrid 193 nm Ultraviolet Photodissociation Mass Spectrometry.
Cardiolipins (CLs) constitute a structurally complex class of glycerophospholipids with a unique tetraacylated structure accompanied by distinctive functional roles. Aberrations in the composition of this lipid class have been associated with disease states, spurring interest in the development of new approaches to differentiate the structures of diverse CLs in complex mixtures. The structural characterization of these complex lipids using conventional methods, however, suffers from limited resolution and frequently proves unable to discern subtle yet biologically significant features such as unsaturation sites or acyl chain position assignments. Here, we describe the synergistic use of chemical derivatization and hybrid dissociation techniques to characterize CL from complex biological mixtures with both double bond and sn positional isomer resolution in a shotgun mass spectrometry strategy. Utilizing (trimethylsilyl)diazomethane (TMSD), CL phosphate groups were methylated to promote positive-mode ionization by the production of metal-cationized lipids, enabling structural interrogation via hybrid higher-energy collisional activation/ultraviolet photodissociation (HCD/UVPD). This combination of TMSD derivatization and HCD/UVPD fragmentation results in diagnostic product ions that permit distinction and relative quantitation of sn-stereoisomers and the localization of double bonds. Applying this strategy to a total lipid extract from a thyroid carcinoma revealed a previously unreported 18:2/18:1 motif, elucidating a structural feature unique to the lipid class.


The cucurbit images (1515-1518) of the Villa Farnesina, Rome.
The gorgeous frescoes organized by the master Renaissance painter Raphael Sanzio (1483-1520) and illustrating the heavenly adventures of Cupid and Psyche were painted between 1515 and 1518 to decorate the Roman villa (now known as the Villa Farnesina) of the wealthy Sienese banker Agostino Chigi (1466-1520). Surrounding these paintings are festoons of fruits, vegetables and flowers painted by Giovanni Martini da Udine (1487-1564), which include over 170 species of plants. A deconstruction and collation of the cucurbit images in the festoons makes it possible to evaluate the genetic diversity of cucurbits in Renaissance Italy 500 years ago. The festoons contain six species of Old World cucurbits, Citrullus lanatus (watermelon), Cucumis melo (melon), Cucumis sativus (cucumber), Ecballium elaterium (squirting cucumber), Lagenaria siceraria (bottle gourd) and Momordica balsamina (balsam apple), and two or three species of New World cucurbits, Cucurbita maxima, C. pepo and, perhaps, C. moschata (pumpkin, squash, gourd). The images of C. maxima are the first illustrations of this species in Europe.


Results of Extracorporeal Membrane Oxygenation (ECMO) Support before Coronary Reperfusion in Cardiogenic Shock with Acute Myocardial Infarction.
Despite aggressive treatment, the mortality rate of cardiogenic shock with acute myocardial infarction (AMI) is high. We performed extracorporeal membrane oxygenation (ECMO) prior to coronary reperfusion, and evaluated the early clinical results and risk factors. From May 2006 to November 2009, we reviewed the medical records of 20 patients in cardiogenic shock with AMI (mean age 67.7±11.7 yrs, M : F 14 : 6). After initially performing ECMO using the CAPIOX emergency bypass system (EBS®Terumo, Tokyo, Japan), patients underwent coronary reperfusion (coronary artery bypass grafting, 13; percutaneous coronary intervention, 7). All patients were in a cardiogenic shock state, cardiopulmonary resuscitations (CPR) were performed for fourteen patients (mean CPR time 20.8±26.0 min). The mean time from vascular access to the initiation of ECMO was 17.2±9.4 min and mean support time was 3.8±4.0 days. Fourteen patients were able to be weaned from ECMO and ten patients were discharged (mean admission duration 50.1±31.6 days). Patients survived on average 476.6±374.6 days of follow-up. Longer CPR and support time, increased cardiac enzyme, lower ejection fraction, lower albumin, and major complications were the risk factors of mortality (p<0.05). The early application of ECMO prior to coronary reperfusion and control of risk factors allowed for good clinical results in cardiogenic shock with AMI.


High nasal burden of methicillin-resistant Staphylococcus aureus increases risk of invasive disease.
In a retrospective cohort study of 1,140 patients harboring methicillin-resistant Staphylococcus aureus, the nasal burden was low in 31%, category 1+ to 2+ in 54%, and category 3+ to 4+ in 15%. There was a significant trend in infection risk with increasing nasal burden (P = 0.007). In multivariate models, high nasal burden remained significantly associated with invasive infection.


Functional Importance of Arginine 64 in Chlamydomonas reinhardtii Phosphoribulokinase.
Phosphoribulokinase (EC 220.127.116.11) was investigated in wild-type Chlamydomonas reinhardtii and in mutant strains deficient in this enzyme activity. Immunoblot analysis revealed substantial amounts of phosphoribulokinase in mutant 12-2B but none in mutant F-60. The pH optimum of the wild-type enzyme was 8.0 and that of the 12-2B enzyme was 6.5. The mutant kinase possessed a K(m) value for ribulose 5-phosphate of about 45 millimolar, nearly three orders of magnitude greater than the wild-type value of 56 micromolar. K(m) values for ATP in the range of 36 to 72 micromolar were observed with both wild-type and mutant enzymes. The V(max) of the wild-type enzyme was about 450 micromoles per minute per milligram of protein, and values for the mutant enzyme were 140 micromoles per minute per milligram at pH 6.5 and 36 micromoles per minute per milligram at pH 7.8. Thermal stabilities of the wild-type and mutant kinases were similar. Sequence analysis of the 12-2B phosphoribulokinase gene revealed a C to T transition that caused an arginine to cysteine change at position 64 of the enzyme. This arginine residue is conserved in phosphoribulokinases from vascular plants, algae, and photosynthetic bacteria and appears to function in binding ribulose 5-phosphate.


Improvement in the quality of heterotopic allotransplanted mouse ovarian tissues with basic fibroblast growth factor and fibrin hydrogel.
Does basic fibroblast growth factor (bFGF) in combination with fibrin hydrogel improve follicle development and revascularization of heterotopically transplanted mouse ovarian tissues? Treatment of transplanted ovarian tissues with higher concentrations (75, 100 and 150 μg/ml), but not lower concentrations (25 and 50 μg/ml), of bFGF significantly improved primordial follicle survival and angiogenesis, while apoptosis of follicles and stromal cells was significantly decreased. Use of transplanted ovarian tissues in female fertility preservation is limited by the massive loss of follicles and ischemia-reperfusion injury due to the expected delay in revascularization. Ovarian tissues from 18-day-old ICR mice were encapsulated in fibrin hydrogel mixed with different concentrations of bFGF, then transplanted under the skin of adult female mice for 1 week. The ovarian tissues treated without fibrin hydrogels and bFGF were designated as Control group I, and the ovarian tissues treated with fibrin hydrogels but without bFGF were designated as Control group II. The ovarian tissues treated with 25 and 50 μg/ml bFGF were designated as the lower concentration group, and the ovarian tissues treated with 75, 100 and 150 μg/ml bFGF were designated as the higher concentration group. Assessment of follicular quantity and follicle classification was carried out by histologic analysis. Follicle proliferation was evidenced by immunostaining with proliferating cell nuclear antigen and apoptosis was verified by anti-active caspase-3 staining. Epithelial cells of new blood vessels were stained using CD31 antibody to evaluate neoangiogenesis, and the blood vessel density was analyzed by immunohistochemistry. The ovarian tissues were recovered 1 week post-transplantation. Compared with the control group, the survival and proliferation of the follicles was significantly increased, the apoptosis of follicles and stromal cells was significantly decreased, and angiogenesis was significantly enhanced when the transplanted ovarian tissues were treated with a higher concentration of bFGF. Treatment with a lower concentration of bFGF did not improve follicle survival and blood revascularization. The results obtained may not be fully extrapolated to humans because of the physiologic differences between mice and humans. For the first time, the present study investigated the role of bFGF in transplanted ovarian tissues and demonstrated that bFGF might significantly improve the quality of transplanted ovarian tissues by increasing follicle quantity and promoting neoangiogenesis. This study sets the stage for further study and application of ovarian tissue transplantation in clinics, and may eventually benefit females for fertility preservation. This work was partially supported by the Ministry of Science and Technology of China Grants (973 Program; 2011CB944503 to Q.J.), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (30825038 to Q.J.), and the National Natural Science Funds for Young Scholar (81200470 to Y.J. and 81000275 to Y.L.Y.). None of the authors have any conflicts of interest.


Ru(II) glycodendrimers as probes to study lectin-carbohydrate interactions and electrochemically measure monosaccharide and oligosaccharide concentrations.
We describe a novel platform on which to study carbohydrate-protein interactions based on ruthenium(II) glycodendrimers as optical and electrochemical probes. Using the prototypical concanavalin A (ConA)-mannose lectin-carbohydrate interaction as an example, oligosaccharide concentrations were electrochemically monitored. The displacement of the Ru(II) complex from lectin-functionalized gold surfaces was repeatedly regenerated. This new platform presents a method to monitor many different complex sugars in parallel.


Mucinous gastric carcinoma with abdominal carcinomatosis and hypergastrinemia in a dog.
A 12-year-old, spayed female Australian cattle dog was evaluated for a 5-month history of progressive vomiting. Abdominal radiographs and ultrasound revealed significant gastric wall thickening and a peripancreatic mass, and serum gastrin concentration was increased (127 pg/mL, reference range 10 to 40 pg/mL). Surgical exploration of the abdomen revealed a thickened, firm, and irregular gastric fundus, pylorus, and antrum; nodules were present throughout the spleen and mesentery adjacent to the left limb of the pancreas. Mucinous gastric carcinoma with carcinomatosis was diagnosed by histopathological examination of surgically excised tissues. Unfortunately, severe postoperative complications resulted in euthanasia 10 days after surgery, and a necropsy was not performed. This case is significant, because it is the first report of a mucinous gastric carcinoma associated with hypergastrinemia in a dog.


Rapid analysis of amphetamines in blood using head space-solid phase microextraction and selected ion monitoring.
A simple and rapid method for analysis of methamphetamine (MA) and amphetamine (AP) in blood was developed using head space-solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry/electron impact ionization-selected ion monitoring (GC-MS/EI-SIM). A vial containing a blood sample, sodium hydroxide, and pentadeuterated methamphetamine as an internal standard, was heated at 80 degrees C for 20 min. The extraction fiber of the SPME was exposed for 5 min in the head space of the vial. First, heptafluorobutyric anhydride solution was injected into the injection port of the GC-MS to make heptafluorobutyramide (HFB) derivatives of amphetamines, and compounds absorbed on the fiber were detached by exposing the fiber in the injection port. Straight calibration curves of MA and AP were obtained from 0.01 to 2 micrograms/g in blood, respectively. No interfering substances were found, and the time for analysis was 30 min for one sample.


High-Resolution MRI Microscopy Coil Assessment of Parotid Masses.
The goal of this study was to determine whether high-resolution magnetic resonance imaging (MRI) microscopy coil imaging can improve the depiction parotid masses. A total of 14 parotid masses, including 7 salivary neoplasms, 2 abnormal lymph nodes, and 5 benign cystic lesions were imaged with T2-weighted and fat-suppressed postcontrast T1-weighted sequences using a 47-mm diameter microscopy coil in addition to conventional MRI sequences acquired with a conventional head and neck neurovascular coil. Compared to conventional parotid MRI sequences, microscopy coil images provided better definition of the margins of neoplasms, provide more detailed definition of lymph node morphology, and better depict certain cyst contents in the superficial portions of the parotid gland. The microscopy coil images provided significantly better definition of lesions and surrounding tissues within the superficial parotid gland with resptect to the deep parotid gland structures due to loss of signal. Furthermore, the fat-suppressed postcontrast T1-weighted microscopy coil images were significantly better than the corresponding T2-weighted images for delineating the superficial parotid gland. Ultimately, the microscopy coil sequences added over 10 minutes to the examination time.


Smoking and the risk of suicide.
To estimate the relationship between cigarette smoking and the risk of suicide. The mortality of 36527 adult men and women was monitored for the mean 14.4 years. Information on deaths caused by suicide was obtained from the National Mortality Register. Suicides were subclassified by the level of violence used. Current smokers of 1-20 cigarettes per day were considered light/moderate smokers and heavy smokers were defined as those smoking > or =21 cigarettes per day. There were 134 suicides among 17798 men and 31 suicides among 18729 women. The most common suicide methods were hanging, firearms and drug overdose. According to the Cox model the adjusted relative risk of both violent and non-violent suicide was significantly and linearly increased among light/moderate and heavy smokers compared with non-smokers. Smoking was associated with an increased risk of suicide irrespective of the level of violence used.


Influence of cholesterol and lovastatin on alpha-form of secreted amyloid precursor protein and expression of alpha7 nicotinic receptor on astrocytes.
The influence of cholesterol and the lovastatin (cholesterol-lowering drug) on secretion of alpha-secretase cleavage product of amyloid precursor protein (APP) and expression of nicotinic acetylcholine receptors (nAChRs) was investigated in human HTB-15 astrocytes. The results showed that exposure of cholesterol to astrocytes inhibited the secretion of alpha-form of secreted APP (alphaAPPs) and reduced cell viability, while lovastatin enhanced the alpha-secretase processing on astrocytes; cholesterol treatment decreased expression of alpha7 nAChR, whereas lovastatin induced an up-regulation of the receptor; the increase in alphaAPPs resulted from lovastatin was partially inhibited by the alpha7 nAChR antagonists, alpha-bungarotoxin or methyllycaconitine; cholesterol or lovastatin did not influence either whole APP level or expression of alpha4 nAChR. We suggest that high dose of cholesterol may inhibit both the activity of alpha-secretase in APP metabolic processing and the expression of alpha7 nAChR, while lovastatin may stimulate alpha-secretase cleavage processing that might be regulated by alpha7 nAChR.


Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on allogeneic bone marrow transplantation in mice.
The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) was examined. Specific pathogen-free (SPF) C3H mice, kept in a flexible isolator for germ-free animals, received 10Gy of total body irradiation (TBI), and an allogeneic BMT 24 hours later. The 14 day survival rate was 33%. When the mice were received rhG-CSF (30 micrograms/kg/day subcutaneously) daily for 2 weeks following BMT, the 14 day survival rate rose to 79%. The effect of rhG-CSF treatment on hemopoiesis in BMT mice resulted in higher neutrophil counts in the peripheral blood by day 14 post-BMT. Administration of rhG-CSF after allogeneic BMT benefited survival rate and neutrophil recovery without any apparent complications.


Measure Dx: Implementing pathways to discover and learn from diagnostic errors.
Despite the high frequency of diagnostic errors, multiple barriers, including measurement, make it difficult learn from these events. This article discusses Measure Dx, a new resource from the Agency for Healthcare Research and Quality that translates knowledge from diagnostic safety measurement research into actionable recommendations. Measure Dx guides healthcare organizations to detect, analyze, and learn from diagnostic safety events as part of a continuous learning and feedback cycle. Wider adoption of Measure Dx, along with the implementation of solutions that result, can advance new frontiers in reducing preventable diagnostic harm to patients.


Accuracy of exercise 201Tl myocardial scintigraphy in asymptomatic young men.
Little is known about the diagnostic usefulness of 201Tl scintigraphy for detecting asymptomatic coronary artery disease in apparently healthy men. We thus evaluated planar 201Tl exercise myocardial scintigraphy in 845 asymptomatic male military aircrew undergoing coronary arteriography because of abnormal noninvasive tests suggesting possible myocardial ischemia. Patients were stratified by prior disease risk into six subgroups using age (< 45 and > or = 45 years) and ratio of total to high density lipoprotein cholesterol (< 4.5, 4.5-6.0, and > 6.0). Significant coronary artery disease (> or = 50% diameter stenosis in any major coronary artery) was present in 143 (16.9% prevalence). Overall sensitivity and specificity of 201Tl scintigraphy adjusted for verification bias were estimated to be 45 +/- 4% and 78 +/- 1%, respectively. These values are lower than corresponding values accepted for clinical populations. Positive and negative predictive values varied across subgroups. A normal thallium scan indicated low risk of disease, but an abnormal test was likely to be a false-positive result. A logistic equation was retrospectively fit to the data for estimating the probability of disease given age, cholesterol ratio, and thallium results. Within each quintile of estimated risk, the average risk did not differ significantly from the observed disease prevalence. Exercise 201Tl scintigraphy is limited by the frequent occurrence of false-positive tests in detecting asymptomatic, anatomic coronary artery disease in young men in accordance with Bayesian probability theory.


The sex hormone receptors in the bladder in childhood - I: preliminary report in male subjects.
The sex hormone receptors (oestrogen, androgen, progesterone) in the bladder were demonstrated in clinical studies by various authors in adult patients. But the presence of these receptors in childhood had not been investigated. The aim of this study was to assess the presence of sex hormone receptors in the bladder of male subjects in childhood. The study included 20 bladder biopsies from a total of 15 children. Biopsies were taken during open surgery and/or cystoscopic procedures for various indications from the bladder dome, trigonum and in the region of the bladder neck. All biopsies were routinely fixed and processed for histopathological assessment and investigated immunohistochemically to determine the sex hormone receptors in the bladder. The sex hormone receptors were demonstrated with different densities and locations. In particular, sex hormone receptors were found very frequently in biopsies taken from the bladder neck. Overall receptor positivity in the specimens was 90 % for progesterone, 65 % for androgen and 25 % for oestrogen. There was no receptor expression in the deeper tissues of the bladder wall. This preliminary study demonstrated: 1. Sex hormone receptors are present in children; 2. There was a female sex hormone (progesterone, oestrogen) receptor expression in male subjects; 3. The receptors are mainly localised at the bladder neck and in transitional epithelium of the bladder wall. We think that the sex hormone receptor map may be useful in the evaluation of lower urinary tract and specially bladder neck disorders in childhood in the future.


Choline distribution and metabolism in pregnant rats and fetuses are influenced by the choline content of the maternal diet.
Choline supplementation of pregnant rats between d 12 and 17 of pregnancy permanently enhances the spatial memory of offspring; however, the mechanism is unknown. We examined the effect of choline supplementation on metabolism of orally ingested choline by nonmated rats and pregnant rats and their fetuses. We studied the metabolism of an acute oral dose of 14C-choline chloride in pregnant and nonmated rats with and without choline supplementation (25 mmol/L choline chloride in water) on d 12-17 of pregnancy. During the first 2 h after oral dosing, plasma radiolabeled choline was detectable, whereas plasma choline metabolites contributed little to total radioactivity at any time. The pattern of accumulation of label in placentas was similar in all groups. Fetal tissues (i.e., brain, liver and carcass remnant) contained primarily 14C-phosphatidylcholine and 14C-phosphorylcholine. Also, we examined the fetal tissue distribution of isotopically labeled (deuterated) choline derived from the diet and from the dietary choline supplement. The distribution patterns for radiolabeled choline metabolites in fetuses of supplemented dams accumulated significantly (P < 0.01) more of their total choline and its metabolites than fetuses of control dams during d 12-17 of gestation (50 vs. 20%). In fetuses from supplemented dams, betaine concentrations were greater than in fetuses from control dams in all organs assayed (by 36-57%). Phosphorylcholine concentrations in brain of fetuses from supplemented dams were also greater. These experiments identify potential metabolites of choline that might mediate the observed effects on brain development in the rats.


Anti-cariogenic properties of a water-soluble extract from cacao.
The addition of a water-soluble extract from cacao-extracted powder (CEPWS) to a cariogenic model food, a white chocolate-like diet that contains 35% sucrose, significantly reduced caries scores in SPF rats infected with Streptococcus sobrinus 6715, compared to control rats fed a white chocolate-like diet. CEPWS markedly inhibited water-insoluble glucan (WIG) synthesis through crude glucosyltransferases (GTFs) from Streptococcus sobrinus B13N in vitro. GTF-inhibitor(s) in CEPWS was prepared through three-step fractionation, and was termed CEPWS-BT, which is a high molecular weight (>10 kDa) heat-stable matrix of sugar, protein, and polyphenol. When the inhibitory effect of CEPWS-BT on glucan synthesis was examined using the purified GTF-I, GTF-T, and GTF-U enzymes from S. sobrinus B13N, significant reduction in GTF-I and GTF-T activity as a result of adding CEPWS-BT at low concentrations was observed. These results suggest that the addition of CEPWS to cariogenic food could be useful in controlling dental caries.


The role of ultrasonography in diagnosing hourglass-like fascicular constriction(s) of the anterior interosseous nerve.
In the past, the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve mostly depended on electrophysiological examination, by which the location could not be diagnosed. There are few studies on the evaluation of hourglass-like fascicular constriction(s) by ultrasonography. To evaluate the role of ultrasonography in the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve. A retrospective analysis of 12 patients with hourglass-like fascicular constriction(s) of the anterior interosseous nerve was carried out, and the characteristics of the high-frequency ultrasonographic images were summarized and compared with surgical exploration. The 12 cases of hourglass-like fascicular constriction(s) of the anterior interosseous nerve were all located in the median nerve of the distal upper arm, including nine cases of single hourglass-like fascicular constriction and three cases of multiple hourglass-like fascicular constrictions. High-frequency ultrasonography can accurately locate the hourglass-like fascicular constriction(s) of the anterior interosseous nerve and the extent of neuropathy. The ultrasonographic images of hourglass-like fascicular constriction(s) of the anterior interosseous nerve showed single or multiple hourglass-like change(s) in the median nerve of the distal upper arm. The nerve fascicles on both sides of the affected nerve with hourglass-like change thickened. High-frequency ultrasonography could be a reliable, convenient, and non-invasive diagnostic imaging method for hourglass-like fascicular constriction(s) of the anterior interosseous nerve.


Traditional and new prognosticators in breast cancer: Nottingham index, Mib-1 and estrogen receptor signaling remain the best predictors of relapse and survival in a series of 289 cases.
Histopathological and immunohistochemical findings on tissue microarrays, overall survival (OS), disease-free survival (DFS) and incidence of relapses (R) were recorded and statistically analyzed in 289 breast cancers. A higher R and a shorter DFS were significantly related to larger tumors, lymph node invasion, higher tumor grade, absence of estrogen receptors (ER), triple negative tumors, and presence of lymphovascular invasion (LVI). Longer OS was observed to be significantly associated with smaller tumor size (T), lymph node negativity, lower tumor grade, absence of LVI, lower Mib-1 expression and with the presence of ER. At multivariate analysis, only T for DFS and lymph node status and triple negativity either for DFS or OS had independent prognostic value. In the 194 lymph node-negative women DFS and OS were inversely related to tumor grade, absence of ER, Mib-1 expression in more than 15% of neoplastic cells and, only for DFS, presence of LVI. In the 95 lymph node-positive the number of involved nodes was the most discriminating parameter either for DFS or OS; T, Her-2 status and presence of LVI were significantly related to DFS. ER negativity was related to higher grade, progesterone receptors (PR) negativity, Her-2 negativity, hence to triple negativity, to basal-like type, Mib-1expression over 15% of neoplastic cells. Her-2 positivity was related to higher grade, ER positivity and PR positivity. Basal-like type was not an independent prognosticator, while triple negative type has a significant relation to shorter OS. The Nottingham prognostic index accurately identifies prognostic groupings and Mib-1 expression and ER signaling are the key biological predictors even in single cases.


[Hemorrhagic fever with renal syndrome in Penza Province].
The evidence of the existence of natural foci of HFRS in Penza region has first been presented on the basis of serological examinations of patients and normal population as well as HFRS virus antigen demonstration in the lung tissue of small mammals. An outbreak of HFRS among children in a pioneer camp is described. Aerogenic infection of the children contracted from HFRS virus-infected bank voles (Clethrionomys glareolus) living near the camp is assumed. The detection of HFRS antigen in 5 species of small mammals indicates the polyhostal nature of HFRS foci existing in the region.


Effects of potato peels inclusion with exogenous enzymes in broiler diet on growth performance, nutrients digestibility and carcass characteristics.
The purpose of the research was to investigate the effects of including potato peels (PP) in broilers diet with exogenous enzymes supplementation on feed intake (FI), body weight gain (BWG), nutrient digestibility and carcass parameters. For this purpose, five iso-caloric and iso-nitrogenous rations were formulated with different levels of PP (0, 5, 10, 15 and 20%). Experimental diets were supplemented with a blend of exogenous enzymes (Xylanase, Mannanase, Protease, Cellulase). A total of four hundred male broiler chicks (day old) of 38 ± 3 gram were randomly distributed into 5 experimental groups in such a way that each group had 8 replicates and each replicate had 10 birds. Results revealed that the inclusion of PP @ 5% with exogenous enzymes had similar FI, BWG and nutrients digestibility with control. However, the inclusion of P @ of 10, 15, and 20% with exogenous enzymes in the broiler diet adversely affected the BWG, feed conversion ratio and nutrient digestibility (p < 0.05). Results of carcass parameters were not affected (p > 0.05) by dietary treatments. Based on findings, it is concluded that 5% addition of PP with exogenous enzymes could be practiced in broiler diet without any adverse effect on the performance of commercial broilers.


Seeing gene expression in cells: the future of structural biology.
Although much is known about the machinery that executes fundamental processes of gene expression in cells, much also remains to be learned about how that machinery works. A recent paper by O'Reilly et al. reports a major step forward in the direct visualization of central dogma processes at submolecular resolution inside bacterial cells frozen in a native state. The essential methodologies involved are cross-linking mass spectrometry (CLMS) and cryo-electron tomography (cryo-ET). In-cell CLMS provides in vivo protein interaction maps. Cryo-ET allows visualization of macromolecular complexes in their native environment. These methods have been integrated by O'Reilly et al. to describe a dynamic assembly in situ between a transcribing RNA polymerase (RNAP) and a translating ribosome - a complex known as the expressome - in the model bacterium Mycoplasma pneumoniae 1. With the application of improved data processing and classification capabilities, this approach has allowed unprecedented insights into the architecture of this molecular assembly line, confirming the existence of a physical link between RNAP and the ribosome and identifying the transcription factor NusA as the linking molecule, as well as making it possible to see the structural effects of drugs that inhibit either transcription or translation. The work provides a glimpse into the future of integrative structural cell biology and can serve as a roadmap for the study of other molecular machineries in their native context.


Ruptured infected popliteal artery aneurysm treated with endovascular therapy: A case report.
An 86-year-old woman was admitted for a ruptured popliteal artery aneurysm (rPAA, 26 × 28 mm). Due to the patient's age and comorbidities, emergency endovascular repair was performed. After the failed antegrade guidewire crossing, a retrograde approach from the anterior tibial artery and snaring was performed for lesion crossing, and stentgraft (5 × 50 mm) was deployed from antegrade fashion. At the 14-month follow-up, computed tomography angiogram demonstrated stentgraft patency and reduced aneurysmal size. Although open surgery remains the first-line treatment for infected rPAA, our approach adds to the evidence and can be applied to emergency cases or high-risk surgical patients.


Croceivirga litoralis sp. nov., isolated from coastal surface water, and reclassification of Muricauda lutea as Croceivirga lutea comb. nov.
A novel Gram-stain-negative, aerobic, yellow-pigmented bacterium was isolated from seawater of Aoshan Bay, and designated as strain ASW18T. Strain ASW18T was a long-rod-shaped bacterium without flagellum and lacked gliding ability. Based on 16S rRNA gene phylogeny, strain ASW18T showed the closest relationship to Croceivirga radicis MCCC 1A06690T, with a sequence similarity of 97.0 %. Strain ASW18T was able to grow at 25-40 °C, at pH 5.5-9.5 and with 0.5-9 % (w/v) NaCl. The genomic DNA G+C content of strain ASW18T was 37.3 %. The predominant cellular fatty acids of strain ASW18T were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The major polar lipids were phosphatidylethanolamine, phosphatidyldimethylethanolamine, an aminolipid and three unidentified lipids. The respiratory quinone of strain ASW18T was menaquinone with six isoprene units (MK-6). Based on the present polyphasic analysis, strain ASW18T represents a novel species of the genus Croceivirga, for which the name Croceivirga litoralis sp. nov. is proposed; the type strain is ASW18T (=MCCC 1K04203T=KCTC 72852T). In addition, it is also proposed that Muricauda lutea should be reclassified as Croceivirga lutea comb. nov.; the type strain is CSW06T (=CGMCC 1.15761T=JCM 31455T=KCTC 52375T=MCCC 1K03195T).


Fasting Ramadan in chronic kidney disease patients: clinical and biochemical effects.
Fasting of the month of Ramadan is a pillar of Islam. Muslim patients with chronic kidney disease (CKD) usually fast this month. To determine the effects of fasting on renal function in CKD patients, we prospectively studied 31 (19 males and mean age 54 ± 14.2 years) CKD patients during the month of Ramadan 1426 Hijra (4th October - 4th November 2005); 14 patients were in stage III CKD, 12 had stage IV and 5 had stage V. The mean estimated glomerular filtration rate (e-GFR) was 29 ± 16.3 mL/min. Diabetes was the main cause of CKD (19 (61%) patients), and hypertension was present in 22 (71%) patients. Clinical assessment and renal function tests were performed one month prior to fasting then during and a month later. Medications were taken in two divided doses at sunset (time of breaking the fast) and pre dawn (before starting the fast). All patients fasted the whole month of Ramadan with a good tolerance, tendency to weight reduction, and lower systolic and diastolic blood pressure. eGFR showed a significant improvement during the fast and the month after. The blood sugar was high during fasting with an increment in the Hb A1c. There was better lipid profile, reduction of the proteinuria and urinary sodium. We conclude that this study demonstrates a good tolerance and safety of fasting Ramadan in CKD patients.


Bridging two translation gaps: a new informatics research agenda for telemonitoring of chronic disease.
To propose a research agenda that addresses technological and other knowledge gaps in developing telemonitoring solutions for patients with chronic diseases, with particular focus on detecting deterioration early enough to intervene effectively. A mixed methods approach incorporating literature review, key informant, and focus group interviews to gain an in-depth, multidisciplinary understanding of current approaches, and a roadmapping process to synthesise a research agenda. Counter to intuition, the research agenda for early detection of deterioration in patients with chronic diseases is not only primarily about advances in sensor technology but also much more about the problems of clinical specification, translation, and interfacing. The ultimate aim of telemonitoring is not fully agreed between the actors (patients, clinicians, technologists, and service providers). This leads to unresolved issues such as: (1) How are sensors used by patients as part of daily routines? (2) What are the indicators of early deterioration and how might they be used to trigger alerts? (3) How should alerts lead to appropriate levels of responses across different agencies and sectors? Attempts to use telemonitoring to improve the care of patients with chronic diseases over the last two decades have so far failed to lead to systems that are embedded in routine clinical practice. Attempts at implementation have paid insufficient attention to understanding patient and clinical needs and the complex dynamics and accountabilities that arise at the level of service models. A suggested way ahead is to co-design technology and services collaboratively with all stakeholders.


A cost analysis of physician assistants in primary care.
Acute medical conditions commonly seen by physician assistants (PAs) or physicians were assigned costs for all resources used to treat an episode of illness. Included in the analysis were data on the provider of record for the episode, patient characteristics, health status, diagnosis, treatment, referrals, medication, imaging, laboratory studies, and return visits. In every medical condition managed by PAs, the total episode cost was less than a similar episode managed by a physician, regardless of patient age, gender, health status, and department. Few differences emerged in the use of resources and the rate of return visits for a diagnosis between physicians and PAs. In this setting PAs appear to be cost-effective from an employment standpoint.


Superconducting silver brazing alloy (silver solder).
A superconducting transition has been observed in a type BAg-3 silver brazing alloy (silver solder) with T(c)=96.(6) mK and H(c)=4.7 Oe. The associated diamagnetism indicates that approximately 1/3 of the sample volume displays the Meissner effect. This property dictates caution in its use at very low temperatures, particularly near sensitive magnetic devices such as ac and SQUID magnetometers.


Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.
The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease.


Biocide Selective TolC-Independent Efflux Pumps in Enterobacteriaceae.
Bacterial resistance to biocides used as antiseptics, dyes, and disinfectants is a growing concern in food preparation, agricultural, consumer manufacturing, and health care industries, particularly among Gram-negative Enterobacteriaceae, some of the most common community and healthcare-acquired bacterial pathogens. Biocide resistance is frequently associated with antimicrobial cross-resistance leading to reduced activity and efficacy of both antimicrobials and antiseptics. Multidrug resistant efflux pumps represent an important biocide resistance mechanism in Enterobacteriaceae. An assortment of structurally diverse efflux pumps frequently co-exist in these species and confer both unique and overlapping biocide and antimicrobial selectivity. TolC-dependent multicomponent systems that span both the plasma and outer membranes have been shown to confer clinically significant resistance to most antimicrobials including many biocides, however, a growing number of single component TolC-independent multidrug resistant efflux pumps are specifically associated with biocide resistance: small multidrug resistance (SMR), major facilitator superfamily (MFS), multidrug and toxin extruder (MATE), cation diffusion facilitator (CDF), and proteobacterial antimicrobial compound efflux (PACE) families. These efflux systems are a growing concern as they are rapidly spread between members of Enterobacteriaceae on conjugative plasmids and mobile genetic elements, emphasizing their importance to antimicrobial resistance. In this review, we will summarize the known biocide substrates of these efflux pumps, compare their structural relatedness, Enterobacteriaceae distribution, and significance. Knowledge gaps will be highlighted in an effort to unravel the role that these apparent "lone wolves" of the efflux-mediated resistome may offer.


The nucleotide sequence at the 3'-end of Neurospora crassa 25S-rRNA and the location of a 5.8S-rRNA binding site.
The sequence of 110 nucleotides adjacent to the 3'-end of Neurospora crassa 25S-rRNA has been derived by chemical sequencing methods. Sequences present between 40 and 85 nucleotides of the 3'-end were found to complement sequences at the 3'- and 5'-ends of 5.8S-rRNA. Interaction was shown to occur between 5.8S-rRNA and a specific 3'-terminal fragment of 85 nucleotides derived from 25S-rRNA. We have also demonstrated that the nucleotide sequence at the 3'-end of N. crassa 5.8S-rRNA (-UCAUUOH) is different from the published sequence (-UUUUOH) which was derived from rDNA.


[Sampling of airborne allergens: practical experience].
The availability of specific monoclonal and policlonal antibodies and the standardization of allergen extracts enables to quantify the exposure to airborne allergens in the domestic environment and at the workplace. In this article we report our experience coming from three studies based upon the measurement of airborne allergens in different environments. In a pharmaceutical factory we measured levels of laboratory animals allergens and evaluated the prevalence of sensitization to the same allergens among the workers. Airborne latex allergens and latex allergens content in latex gloves were measured in hospitals. In bakeries we evaluated the prevalence of sensitization to flour and measured flour allergens levels. The results of our studies give information useful to improve methods of prevention, diagnosis, and therapy of occupational allergic diseases.


[Pediatric complex regional pain syndrome affecting an upper limb: 7 cases and a brief review of the literature].
To review the clinical, psychiatric, and social characteristics of complex regional pain syndrome in children and adolescents treated in the last 4 years at our pediatric pain clinic. We analyzed the specialty of the initial treating physician, age, sex, initial diagnosis, pain intensity, degree of disability, fear of movement, clinical stage, history of trauma, time between onset and diagnosis, psychiatric illness, family support and behavior, chronic pain in near relatives, school grades and attendance, treatment given at the pediatric pain clinic, recurrences, and course of disease. The cases of 7 patients (4 female, 3 male) between the ages of 8 and 15 years were analyzed. Four had been referred by the child psychiatry department. The initial diagnosis was erroneous in all but 1 case. Pain intensity and associated disability were severe in 5 patients and 4 expressed intense fear of moving the limb. Five patients had initial stage I disease, 5 had a history of trauma, and 5 had been previously treated by immobilization of the limb and prescription of nonsteroidal anti-inflammatory drugs. The time between onset and diagnosis ranged from 2 to 18 months (mean [SD], 6.4 [3.5] months). In most cases psychiatric disease and concomitant social disability were present. Treatment prescribed at the pediatric pain clinic consisted of a combination of oral medication, psychologic and psychiatric counseling, and intensive physiotherapy for all but 2 children, who required regional nerve blocks. The clinical course was satisfactory for all but 1 patient, who developed severe disability. Complex regional pain syndrome affecting an upper limb is uncommon in children but not rare.


Is genotype 3 of the hepatitis C virus the new villain?
Genotype 3 of the hepatitis C virus (HCV) has been long considered an easy-to-treat infection, with higher cure rates (∼70%) than other viral genotypes with the standard combination of pegylated interferon-α and ribavirin. However, the relative insensitivity of this genotype to most protease inhibitors and the recent unexpected data on decreased effectiveness of sofosbuvir have raised questions on how to achieve universal cure, a goal that seems reasonable for other genotypes. In addition, increasing clinical and experimental data show that HCV genotype 3 may be associated not only with severe steatosis, but also with accelerated fibrosis progression rate and increased oncogenesis. Currently available data suggest that we should increase our efforts to understand the virology and pathogenesis of HCV genotype 3, aiming at better and more potent, genotype-targeted treatments.


Human tissue preservation for disaster victim identification (DVI) in tropical climates.
Disaster victim identification (DVI) poses unique challenges for forensic personnel. Typical scenarios may involve many bodies or body parts to identify in remote locations with limited access to laboratory facilities and in extreme temperatures. Transportation of tissue samples to a forensic laboratory for DNA profiling can take weeks without refrigeration. As well as protecting DNA for subsequent analysis, tissue preservation methods ideally should be safe, readily available and easy to transport to the scene at relatively low cost. We examined eight tissue preservatives (salt, DMSO, ethanol, ethanol with EDTA, TENT buffer, RNAlater(®), DNA Genotek Tissue Stabilising Kit and DNAgard(®)) and compared the quantity and quality of DNA recovered from human tissue and preservative solution stored at 35°C. Salt, DMSO, ethanol solutions, DNA Genotek and DNAgard(®) produced full Identifiler(®) genotypes up to one month from DNA extracts. In addition, DMSO, DNA Genotek and DNAgard(®) produced full profiles from aliquots of the liquid preservative.


Dual-Gate Modulation of Carrier Density and Disorder in an Oxide Two-Dimensional Electron System.
Carrier density and disorder are two crucial parameters that control the properties of correlated two-dimensional electron systems. In order to disentangle their individual contributions to quantum phenomena, independent tuning of these two parameters is required. Here, by utilizing a hybrid liquid/solid electric dual-gate geometry acting on the conducting LaAlO3/SrTiO3 heterointerface, we obtain an additional degree of freedom to strongly modify the electron confinement profile and thus the strength of interfacial scattering, independent from the carrier density. A dual-gate controlled nonlinear Hall effect is a direct manifestation of this profile, which can be quantitatively understood by a Poisson-Schrödinger sub-band model. In particular, the large nonlinear dielectric response of SrTiO3 enables a very wide range of tunable density and disorder, far beyond that for conventional semiconductors. Our study provides a broad framework for understanding various reported phenomena at the LaAlO3/SrTiO3 interface.


Membrane permeabilization by poliovirus proteins 2B and 2BC.
Poliovirus infection leads to drastic alterations in membrane permeability late during infection. Transient expression of each nonstructural protein of poliovirus by means of recombinant vaccinia virus encoding the T7 RNA polymerase indicates that proteins 2B and 2BC strongly enhance membrane permeability to hygromycin B in HeLa cells. Almost no effect on expression of proteins 2C, 3A, 3AB, and 3C was found. Deletions and point mutations in 2B and 2BC have identified sequences in 2B involved in membrane permeabilization. Regions located at both ends of 2B are necessary to bring about these permeability alterations. A deletion of 11 amino acids of 2BC at the junction between 2B and 2C, as well as long deletions in 2C encompassing the GTPase motifs of this protein, do not impair the capacity of 2BC to modify the permeability of the membrane. The release of compounds such as choline or uridine from preloaded cells is also augmented by 2B and 2BC expression.


High density electromyography data of normally limbed and transradial amputee subjects for multifunction prosthetic control.
Pattern recognition based control of powered upper limb myoelectric prostheses offers a means of extracting more information from the available muscles than conventional methods. By identifying repeatable patterns of muscle activity across multiple muscle sites rather than relying on independent EMG signals it is possible to provide more natural, reliable control of myoelectric prostheses. The purposes of this study were to (1) determine if participants can perform distinctive muscle activation patterns associated with multiple wrist and hand movements reliably and (2) to show that high density EMG can be applied individually to determine the electrode location of a clinically acceptable number of electrodes (maximally eight) to classify multiple wrist and hand movements reliably in transradial amputees. Eight normally limbed subjects (five female, three male) and four transradial amputee subjects (two traumatic and congenital) subjects participated in this study, which examined the classification accuracies of a pattern recognition control system. It was found that tasks could be classified with high accuracy (85-98%) with normally limbed subjects (10-13 tasks) and with amputees (4-6) tasks. In healthy subjects, reducing the number of electrodes to eight did not affect accuracy significantly when those electrodes were optimally placed, but did reduce accuracy significantly when those electrodes were distributed evenly. In the amputee subjects, reducing the number of electrodes up to 4 did not affect classification accuracy or the number of tasks with high accuracy, independent of whether those remaining electrodes were evenly distributed or optimally placed. The findings in healthy subjects suggest that high density EMG testing is a useful tool to identify optimal electrode sites for pattern recognition control, but its use in amputees still has to be proven. Instead of just identifying the electrode sites where EMG activity is strong, clinicians will be able to choose the electrode sites that provide the most important information for classification.


Parental Experiences Caring for Their Hospitalized Medically Fragile Infants: A Description of Grief, Stress, and Coping.
Advances in care have increased survival and improved outcomes of infants with complex and chronic diseases. These medically fragile infants require long-term hospitalization and depend on technology for survival. Parents of these infants experience stress and difficulties adapting to their parental role. To present an account of parental experiences as they provided care for their hospitalized medically fragile infant. This study was part of a larger constructivist grounded theory study to provide a holistic understanding of the processes of care for medically fragile infants. For this sub-study, 21 parents of hospitalized medically fragile infants were recruited from a pediatric hospital in Western Canada. Parents participated in face-to-face, semi-structured interviews, which were transcribed and analyzed using initial and focused coding. Parents of hospitalized medically fragile infants grieved the loss of parenting a healthy infant, and they experienced multiple stressors. Parents utilized various coping strategies to manage their grief and stressors. Some parents were unable to cope, which exacted a heavy toll on their physical and mental health. Parents recommended psychological support, access to physical activity, primary nursing, and health system navigators. Parental recommendations can inform the design of interventions for parents of hospitalized medically fragile infants.


Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis: Analysis of Follow-up Data From the Measure Up 1 and Measure Up 2 Randomized Clinical Trials.
Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown. To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis. Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2). Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner. Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed. Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals. In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks. ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).


Catalytic properties of hairpin ribozymes derived from Chicory yellow mottle virus and arabis mosaic virus satellite RNAs.
Regions of the negative strands of the satellite RNAs of chicory yellow mottle virus (sCYMV1) and arabis mosaic virus (sArMV) have similarity in sequence and predicted secondary structure compared to the tobacco ringspot virus satellite RNA (sTRSV) hairpin ribozyme, suggesting that they may also be catalytic RNAs of a similar type. Our experiments show that the hairpin ribozyme-like sequences derived from sCYMV1 and sArMV have high phosphodiesterase activity. The Kcat values determined are similar to that of the highly active native sTRSV hairpin ribozyme under the same conditions, although the Km values are much higher. The Km of the sArMV ribozyme was reduced 3-fold, with no change in kcat, by extending substrate hybridization in helix 2. Additionally, the three hairpin ribozymes prefer different GUX sequences on the immediate 3'-side of the cleavage site. The sTRSV hairpin ribozyme cleaves GUX substrates with catalytic efficiencies in the relative order GUC >> GUU > GUG = GUA. The sCYMV1 ribozyme cleaves GUA > GUC, GUG, GUU. The sArMV ribozyme prefers GUA > GUG > GUU > GUC. The functional domain, regulating substrate selection at this position, must reside in the nucleotides that vary between the ribozyme--substrate complexes. The sTRSV ribozyme is most efficient at cleaving GUC complexes, while the sCYMV1 and sArMV ribozymes are most efficient for cleaving GUA-containing sequences.


STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma.
We sought to identify genes associated with the progression and metastasis of esophageal squamous-cell cancer by comparing the expression profiles of normal, primary cancer, and metastatic cancer cells isolated with laser microdissection. Oligo microarray analysis identified several lymph node-specific, metastasis-related genes. STC2 (stanniocalcin 2), which was overexpressed in esophageal cancer cases, was chosen for further characterization. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to explore the clinicopathologic significance of STC2 expression status in 70 cases. Additionally, the functional role of STC2 in esophageal cancer was studied by the attenuation of STC2 in an esophageal cancer cell line. Laser microdissection and oligo microarray analysis identified 63 candidate genes. Among them, STC2 showed higher expression in cancer tissue than in corresponding normal tissue (P < 0.001). STC2 expression was significantly correlated with lymph node metastasis, lymphatic invasion, and distant metastasis (P = 0.005, 0.007, and 0.038, respectively). Patients whose tumors had high STC2 expression had a worse 5-year survival rate than patients whose tumors had a low STC2 expression level (P = 0.016). STC2 transfected cells had a significantly higher proliferation rate than control cells (P < 0.001). Additionally, STC2 transfected cells were more invasive in vitro (P < 0.001) than control cells. These findings were validated by means of RNA interference assays. We identified lymph node-specific, metastasis-related genes in esophageal cancer cells. One of these, STC2, may be associated with lymph node metastasis, making it a potential prognostic marker for esophageal cancer patients.


Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma.
Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.


Psychological adjustment to hospitalization: factorial structure, antecedents, and outcome.
Using various methods of observation, the psychological status of 211 patients of both sexes was assessed after the surgery or treatment justifying their hospitalization. Intercorrelations of scores on 40 variables obtained to describe the state of the patients were submitted to a principal components analysis. The latter yielded a factor of maladjustment to hospitalization associated with various psychosociological antecedents of the patients and a short-term unfavorable development of their physical health. This dimension seems to correspond not just with personal characteristics but to involve the interaction of medical staff members and patients in a manner detrimental to patients' recovery.


Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model.
Francisella tularensis causes a serious and often fatal infection, tularemia. We compared the efficacy of moxifloxacin formulated as free drug vs disulfide snap-top mesoporous silica nanoparticles (MSNs) in a mouse model of pneumonic tularemia. We found that MSN-formulated moxifloxacin was more effective than free drug and that the intramuscular and subcutaneous routes were markedly more effective than the intravenous route. Measurement of tissue silica levels and fluorescent flow cytometry assessment of colocalization of MSNs with infected cells revealed that the enhanced efficacy of MSNs and the intramuscular route of delivery was not due to better delivery of MSNs to infected tissues or cells. However, moxifloxacin blood levels demonstrated that the nanoparticle formulation and intramuscular route provided the longest half-life and longest time above the minimal inhibitory concentration. Thus, improved pharmacokinetics are responsible for the greater efficacy of nanoparticle formulation and intramuscular delivery compared with free drug and intravenous delivery.