Simultaneous determination of vinblastine and its monomeric precursors vindoline and catharanthine in Catharanthus roseus by capillary electrophoresis-mass spectrometry.
Catharanthus roseus is an important dicotyledonous medicinal plant that contains various anticancer components, such as vinblastine (VLB) and its monomeric precursors (vindoline and catharanthine). A capillary electrophoresis-mass spectrometry (CE-MS) approach for the simultaneous determination of three components was developed in this work. Baseline separation for three components was achieved by using a running buffer consisting of 20 mM ammonium acetate and 1.5% acetic acid in <20 min. Quantification of three components was assigned in positive-ion mode at a protonated molecular ion [M+H](+). The CE-MS method was validated for linearity, sensitivity, accuracy and precision, and then used to determine the content of the above components. The detection limits of VLB, catharanthine and vindoline are 0.8, 0.1 and 0.1 μg/mL, respectively. The precision was not more than 4.54% and the mean recovery of the analytes was 95.04-97.04%. The CE-MS method was successfully applied to determine VLB and its monomeric precursors in real sample C. roseus.


Are HLA DQB1 alleles correlated with breast cancer histopronostic parameters in Tunisia?
Tumor cells express surface structures different from normal cells. These structures may be recognized by the immune system, which ensure anti-tumoral surveillance. Antigenic presentation requires HLA molecules role. Since, these molecules are encoded by a high polymorphic system, immune response can be modulated according to HLA genotype. So, HLA polymorphism could be correlated with tumor escape from anti-tumor immunosurveillance. We have aimed to search for possible associations between HLA DQB1 alleles and the histoprognostical parameters in breast cancer in the Tunisian population. DQB1 alleles were determined by PCR-SSO molecular typing in 100 healthy matched and unrelated Tunisian female and 87 Tunisian women with breast cancer. Allelic distribution between the two studied groups showed no significant associations between this locus and the occurrence, the EE grade and the lymph node invasion of breast cancer in the Tunisian population. This result may be explained by the fact that cancer is a multifactoral disease due to several interacting factors that might change from one population to another.


PCR-restriction fragment length polymorphism analysis for detection of point mutations associated with macrolide resistance in Campylobacter spp.
A 23S rRNA gene fragment in domain V was sequenced from 30 clinical isolates of Campylobacter spp., including 22 resistant to macrolides. Two point mutations associated with erythromycin resistance were identified at positions 2074 and 2075 on the 23S rRNA gene (homologous to A2142C and A2143G mutations in Helicobacter pylori) in which an adenine residue is also replaced with a cytosine and a guanine residue, respectively. A combined PCR-restriction fragment length polymorphism technique was developed to detect these mutations by using the BsaI and BceAI enzymes.


The Influence of DHA on Language Development: A Review of Randomized Controlled Trials of DHA Supplementation in Pregnancy, the Neonatal Period, and Infancy.
This review summarizes randomized controlled trials (RCTs) assessing the effect of docosahexaenoic acid (DHA) supplementation in the first 1000 days on child language. Six databases were searched and RCTs were included if they involved supplementation with DHA during pregnancy, to preterm infants, or during the postpartum period, included a placebo group with less or no DHA, and reported a language outcome. We included 29 RCTs involving n = 10,405 participants from 49 publications. There was a total of 84 language measures at ages ranging from 3 months to 12 years. Of the 84 assessments, there were 4 instances where the DHA group had improved scores, and 2 instances where the DHA group had worse scores (with the majority of these significant effects found within one RCT). The remaining comparisons were null. A few RCTs that included subgroup analyses reported (inconsistent) effects. There was limited evidence that DHA supplementation had any effect on language development, although there were some rare instances of both possible positive and adverse effects, particularly within population subgroups. It is important that any subgroup effects are verified in future trials that are adequately powered to confirm such effects.


Single-Pill Combination to Improve Hypertension Treatment: Pharmaceutical Industry Development.
Multiple illness is an increasingly common phenomenon. Its consequence is the need for polytherapy, which is particularly common among people suffering from arterial hypertension. The development of combined preparations (containing at least two API-active pharmaceutical ingredients) dedicated to the treatment of hypertension is a response to increased compliance, especially in elderly patients. In our work, we describe in particular the possibilities of using β-adrenergic receptors blockers and angiotensin-converting enzyme inhibitors in combinations. The combinations of APIs are used as single pills in patients with arterial hypertension with concomitant diseases such as hyperlipidemia; blood coagulation problems and diabetes mellitus were also discussed successively. Pharmacoeconomic analysis for the API combinations shown is also presented. As a final conclusion, numerous benefits of using the combined preparations should be indicated, especially by the elderly and/or in patients with coexistence of other diseases.


Use and indications of cholestyramine and bile acid sequestrants.
Cholestyramine is a bile acid sequestrant, like colestipol and colesevelam. These molecules are positively charged non-digestible resins that bind to bile acids in the intestine to form an insoluble complex, which is excreted in the feces. They are used mainly for the treatment of primary hypercholesterolemia and hypercholesterolemia associated with mild hypertriglyceridemia, in patients not responding to dietary treatment as well as a second line-treatment for pruritus associated with cholestatic disease, in patients with incomplete biliary obstruction. Several data indicate that modulation of bile acid homeostasis has a good clinical effect in managing diabetes mellitus and the diarrhea from bile acid malabsorption. In this review, we present the "in label" use and indication for these compounds, revisiting the other clinical applications that may benefit from the use of bile acid sequestrants in the near future.


Role of Ultrasound Lung Comets in the Diagnosis of Acute Heart Failure in Emergency Department: A Systematic Review and Meta-analysis.
A new technique of transthoracic lung ultrasonography (TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung comets (ULCs) for acute heart failure (AHF) performed in busy emergency department (ED) is uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of ULCs in AHF. We conducted a search on online journal databases to collect the data on TLS performed for diagnosing AHF published up to the end of July 2017. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curve were calculated. The post-test probability of AHF was calculated by using Bayes analysis. We enrolled a total of 15 studies involving 3,309 patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026, respectively. We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis. Results suggest that the time interval between patient's admission to bedside TLS examination was closely related to TLS accuracy. This meta-analysis demonstrated that detecting ULCs is a convenient bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be recommended to be applied for early diagnosis of AHF in ED.


[Improvement of sensoneurinal hearing loss in a patient with Muckle-Wells syndrome treated with anakinra].
Muckle Wells syndrome is an autoinflammatory disease in the group of cryopyrin associated periodic syndromes (CAPS). We report the case of an 8 year old girl with MWS who presented with remitting fever, urticaria, remitting coxitis, osteitis, bilateral uveitis anterior, elevated levels of C-reactive protein (CRP) and Serum amyloid A (SAA) and progressive sensoneurinal hearing loss. After starting treatment with anakinra, clinical symptoms dissolved almost completely for about two years now. CRP and SAA levels normalized quickly and sustained and as a consequence the risk of amyloidosis may be minimized. Notable is the complete recovery from sensoneurinal hearing loss merely two months after start of treatment. This brings up questions about pathophysiology of sensoneurinal hearing loss in MWS and emphasizes the benefits of an early diagnosis, as an early start of treatment possibly reduces long-term damage.


METTL3 inhibits inflammation of retinal pigment epithelium cells by regulating NR2F1 in an m6A-dependent manner.
N6-metyladenosine (m6A) RNA methylation has been proven to be involved in diverse biological processes, but its potential roles in the development of lipopolysaccharide (LPS) induced retinal pigment epithelium (RPE) inflammation have not been revealed. In this study, we explored the effects and underlying mechanisms of methyltransferase-like 3 (METTL3) in LPS stimulated RPE cells. Proliferation of METTL3-silenced RPE cells was examined by Cell counting kit-8 (CCK8) and 5-Ethynyl-2´-Deoxyuridine (Edu). Expression of tight junction proteins ZO-1 and Occludin, and secretion of inflammatory factors interleukins (IL)-1, 6 and 8 were detected by Western blotting or Enzyme-linked immunosorbent assay (ELISA). RNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing were used to analyze the target gene nuclear receptor subfamily 2 group F member 1 (NR2F1) of METTL3. Our results showed that both human RPE (hRPE) cells and ARPE19 cells exhibited inhibited proliferation, tight junction protein expression, and increased inflammatory factor secretion after METTL3 silencing. Mechanistically, we found that NR2F1, as a METTL3-methylated target gene, inhibits Occludin level and promotes IL-6 secretion of RPE cells in an m6A-dependent manner. Interestingly, NR2F1 deficiency reversed the decreased Occludin expression and increased IL-6 secretion in METTL3-defective RPE cells. In conclusion, our study revealed that METTL3 attenuates RPE cell inflammation by methylating NR2F1, suggesting the critical role of METTL3 in RPE cells.


What is Health Level 7?
HL7 is a huge undertaking and continues to grow. We talked about certain main themes of the spec that I've found interesting and thought you might too. You can always find additional information-especially from the HL7 website itself at www.hl7.org or www.altisinc.com/ IE/hl7.html. The main thing to remember is that HL7 is a specification for describing, formatting, encoding, and sharing of clinical and administrative data in healthcare. An easy way to remember that is that the 7 in HL7 refers to the Application layer in the OSI model. The next time someone talks about their HL7 software or application, you'll know that they really mean their HL7 compliant software or application. Then be sure to ask them how many composites are in their OBX segments!


Expression and regulation of the osteoarthritis-associated protein asporin.
Asporin (ASPN) is a small leucine-rich proteoglycan that is involved in pathological processes of osteoarthritis. Previously, we showed that asporin can inhibit transforming growth factor-beta1 (TGF-beta1)-mediated expression of cartilage matrix genes and chondrogenesis in vitro (Kizawa, H., Kou, I., Iida, A., Sudo, A., Miyamoto, Y., Fukuda, A., Mabuchi, A., Kotani, A., Kawakami, A., Yamamoto, S., Uchida, A., Nakamura, K., Notoya, K., Nakamura, Y., and Ikegawa, S. (2005) Nat. Genet. 37, 138-144). However, details about regulation of asporin itself are not yet known. Here, we examined ASPN expression in skeletal tissue and potential regulation of ASPN by TGF-beta. In situ hybridization revealed the presence of ASPN mRNA in the perichondrium/periosteum of long bones, but its absence in articular cartilage and growth plates. Immunohistochemical analysis also showed ASPN protein expression predominantly in the perichondrium/periosteum. TGF-beta1 induced endogenous ASPN mRNA expression over time in vitro, and this induction was suppressed by the TGF-beta type I receptor kinase inhibitor SB431542. Inhibition of Smad3 significantly reduced TGF-beta1-induced ASPN expression, whereas overexpression of Smad3 augmented the induction. Characterization of the human ASPN promoter region revealed a region from -126 to -82 that is sufficient for full promoter activity; however, TGF-beta1 failed to increase activity through the ASPN promoter. Our findings indicate that TGF-beta1 induces ASPN through Smad3 but that this induction is indirect.


Greater vulnerability to warming of marine versus terrestrial ectotherms.
Understanding which species and ecosystems will be most severely affected by warming as climate change advances is important for guiding conservation and management. Both marine and terrestrial fauna have been affected by warming1,2 but an explicit comparison of physiological sensitivity between the marine and terrestrial realms has been lacking. Assessing how close populations live to their upper thermal limits has been challenging, in part because extreme temperatures frequently drive demographic responses3,4 and yet fauna can use local thermal refugia to avoid extremes5-7. Here we show that marine ectotherms experience hourly body temperatures that are closer to their upper thermal limits than do terrestrial ectotherms across all latitudes-but that this is the case only if terrestrial species can access thermal refugia. Although not a direct prediction of population decline, this thermal safety margin provides an index of the physiological stress caused by warming. On land, the smallest thermal safety margins were found for species at mid-latitudes where the hottest hourly body temperatures occurred; by contrast, the marine species with the smallest thermal safety margins were found near the equator. We also found that local extirpations related to warming have been twice as common in the ocean as on land, which is consistent with the smaller thermal safety margins at sea. Our results suggest that different processes will exacerbate thermal vulnerability across these two realms. Higher sensitivities to warming and faster rates of colonization in the marine realm suggest that extirpations will be more frequent and species turnover faster in the ocean. By contrast, terrestrial species appear to be more vulnerable to loss of access to thermal refugia, which would make habitat fragmentation and changes in land use critical drivers of species loss on land.


Insights into the precursor effect on the surface structure of γ-Al2O3 and NO + CO catalytic performance of CO-pretreated CuO/MnOx/γ-Al2O3 catalysts.
NO reduction by CO was investigated over CO-pretreated CuO/MnOx/γ-Al2O3 catalysts with different metal precursors (nitrate and acetate). It was found that the catalyst prepared from acetate salts (Cu/Mn/Al-A) exhibited significantly higher activity than counterpart catalyst from nitrate precursors (Cu/Mn/Al-N). XRD, XPS and in situ DRIFT were carried out to approach the nature for the different catalytic performance. For both catalysts, copper mainly existed as CuO, but the status of manganese oxide was markedly different. Mn(IV) was predominant in Cu/Mn/Al-N and Mn(III) was enriched in Cu/Mn/Al-A. As a result, different dispersion behaviors of manganese oxide on γ-Al2O3 were displayed, which induced inconsistent Cu-Mn contact. The catalyst obtained from acetate precursor exhibited enriched Cu-Mn contact and thus more Cu+-□-Mn3+/2+ entities would be produced after CO pretreatment, leading to promoted NO dissociation and favorable performance in NO reduction by CO. The present study sheds light on the effective tuning of Cu-O-Mn interfacial sites in CuO/MnOx/γ-Al2O3 via modulating the dispersion behaviors of surface components.


Pharmacogenomics in the intensive care unit: focus on potential implications for clinical practice.
Critically ill patients often are at high-risk for adverse drug reactions (ADRs), mainly due to alterations in pharmacokinetic and pharmacodynamic (PK/PD) parameters. These PK/PD differences in can also lead to inadequate therapeutic response to many commonly used drugs in this patient population. Frequently in the critically ill patient, medications are utilized based on a "trial-and-error" approach. Furthermore, drug dosing in the critically ill largely remains a "one-size-fits-all" phenomenon, utilizing dosing based on PK studies in healthy volunteers. Known differences in gene variation among the general population can greatly alter response to drug therapy. The use of pharmacogenomics (PGX) to aid in the development of individualized pharmacotherapeutic regimens, potentially may reduce ADRs and increase therapeutic efficacy. Potential uses of PGX include: identification of patients who are particularly susceptible to ADRs; and patients whom are more likely to benefit from a particular drug therapy, based on the patient's own genetic profile. This review will focus on potential applications of PGX in the critically ill, including management of acute coronary syndromes (ACS), invasive fungal infections, and pain management. Current barriers to PGX-guided therapy in the critically ill and recent patent developments in the clinical application of PGX will also be discussed.


The convergent and discriminant validity of burnout measures in sport: a multi-trait/multi-method analysis.
Athlete burnout research has been hampered by the lack of an adequate measurement tool. The Athlete Burnout Questionnaire (ABQ) and the Maslach Burnout Inventory General Survey (MBI-GS) are two recently developed self-report instruments designed to assess burnout. The convergent and discriminant validity of the ABQ and MBI-GS were assessed through multi-trait/multi-method analysis with a sporting population. Overall, the ABQ and the MBI-GS displayed acceptable convergent validity with matching subscales highly correlated, and satisfactory internal discriminant validity with lower correlations between non-matching subscales. Both scales also indicated an adequate discrimination between the concepts of burnout and depression. These findings add support to previous findings in non-sporting populations that depression and burnout are separate constructs. Based on the psychometric results, construct validity analysis and practical considerations, the results support the use of the ABQ to assess athlete burnout.


Intra-abdominal pulmonary sequestration: a case report and literature review.
Pulmonary sequestration is a rare congenital malformation mostly located in the thorax, while intra-abdominal pulmonary sequestration is an extremely rare type of pulmonary sequestration usually diagnosed during the first 6 months of life. Only 1 case of intra-abdominal pulmonary sequestration in a patient older than 60 years has been reported in the current literature. It is difficult to differentiate an intra-abdominal pulmonary sequestration from other retroperitoneal tumors. A definitive diagnosis is always made by histological examination. Intra-abdominal pulmonary sequestration commonly responds well to surgical resection and is associated with excellent results and prognosis. The authors present the case of a 74-year-old asymptomatic man with a retroperitoneal mass which was completely excised and revealed by histopathological study to be an intra-abdominal pulmonary sequestration.


Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis.
Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired driving skills and increased risk of motor vehicle accidents (MVAs). Detection and treatment of MHE has the potential to reduce costs and morbidity associated with MVAs. We conducted a cost-effectiveness analysis to assess the benefits of different strategies of MHE diagnosis and treatment for reducing MVA-related societal costs. The analyses compared five MHE management strategies: (1) presumptive treatment of all cirrhosis patients; (2) diagnosis by neuropsychological exam (NPE) with treatment; (3) diagnosis by standard psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or treatment (status quo). Treatments considered were lactulose or rifaximin, which were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis patients with benefit adjusted for treatment compliance. A Markov model followed a simulated cohort of 1,000 cirrhosis patients without overt hepatic encephalopathy (OHE), from entry into treatment, through MHE development, and later OHE, when they exited the modeled cohort. Follow-up was for 5 years and included biannual MHE testing. The societal cost of a single MVA was estimated at $42,100. All four strategies with lactulose were cost-saving compared with the status quo. Diagnosis with ICT and lactulose was the most cost-effective approach (cost/MVA prevented: $24,454 ICT; $25,470 SPT; $30,469 presumptive treatment and $33,742 NPE). Net program savings over 5 years ranged from $1.7 to 3.6 million depending on the strategy. Rifaximin therapy was not cost-saving at current prices but would become so at a monthly cost of <$353. Detection of MHE, especially using the ICT, and subsequent treatment with lactulose could substantially reduce societal costs by preventing MVAs.


[Responsibilities and importance of tumor centers for interdisciplinary tumor therapy].
Early diagnosis, therapy and follow-up of tumor patients rest on the three pillars of medical care: tumor centers, hospitals and physicians. The tumor centers are the pace makers and coordinators in the following functions: definition of primary treatment and additional therapies and their standard of quality; implementation of primary multimodal therapies and treatment of rare tumors; development of improved treatment methods for tumor metastases and local recurrence, including surgical treatment; improvement of diagnostic and therapeutic (surgical) potential through interdisciplinary research, especially in the fields of tumor biology and tumor immunology; and establishment of a standardized follow-up and new care and treatment strategies for the improvement of the patients' quality of life.


Feeding Problems in Typically Developing Young Children, a Population-Based Study.
Feeding problems have been estimated to occur in approximately 25-45% of normally developing children. The aim of this study was to investigate the prevalence of feeding problems in typically developing young children in Greece. Child feeding behavior, parents' feelings about their child's feeding patterns, and parental feeding practices were also explored. Parents completed the Greek version of the Behavioral Pediatrics Feeding Assessment Scale (BPFAS). Data on 742 healthy, typically developing children aged two to seven years are presented. Overall, the majority of children in the sample showed high frequency of desirable mealtime behaviors and low frequency of undesirable mealtime behaviors. However, a significant proportion of the cohort presented with food neophobia and low consumption of vegetables. When applying test cut-off scores, it was found that 8.2% of the sample had abnormal Total Frequency Score (TFS) and 26.6% had abnormal Total Problem Score (TPS). The study showed that parent-reported feeding problems are quite common in children of typical development in Greece. Moreover, while the majority of the sample displayed a high frequency of favorable behaviors, specific child feeding behaviors are amenable to improvement.


Microbiome derived acidity protects against microbial invasion in Drosophila.
Microbial invasions underlie host-microbe interactions that result in microbial pathogenesis and probiotic colonization. While these processes are of broad interest, there are still gaps in our understanding of the barriers to entry and how some microbes overcome them. In this study, we explore the effects of the microbiome on invasions of foreign microbes in Drosophila melanogaster. We demonstrate that gut microbes Lactiplantibacillus plantarum and Acetobacter tropicalis improve survival during invasion of a lethal gut pathogen and lead to a reduction in microbial burden. Using a novel multi-organism interactions assay, we report that L. plantarum inhibits the growth of three invasive Gram-negative bacteria, while A. tropicalis prevents this inhibition. A series of in vitro and in vivo experiments revealed that inhibition by L. plantarum is linked to its ability to acidify both internal and external environments, including culture media, fly food, and the gut itself, while A. tropicalis diminishes the inhibition by quenching acids. We propose that acid produced by the microbiome serves as an important gatekeeper to microbial invasions, as only microbes capable of tolerating acidic environments can colonize the host. The methods described herein will add to the growing breadth of tools to study microbe-microbe interactions in broad contexts.


The inter-tester repeatability of a model for analysing elbow flexion-extension during overhead sporting movements.
This study investigates the inter-tester repeatability of an upper limb direct kinematic (ULDK) model specifically for the reporting of elbow flexion-extension (FE) during overhead sporting movements, such as cricket bowling. The ULDK model consists of an upper arm and a forearm connected with a 6° of freedom elbow joint. The ULDK model was assessed for inter-tester repeatability by calculating elbow FE during cricket bowling in two sessions, with unique testers applying the kinematic marker set in each session. Analysis of both elbow FE time-varying waveforms (statistical parametric mapping = 0% time different) and extracted discrete events (no statistical differences, strong correlations > 0.9) support that this model is inter-tester repeatable at assessing elbow FE within the context of cricket bowling. This model is recommended as a framework in future studies for measuring elbow kinematics during other overhead sporting tasks, with recommendations for further participant-specific considerations. Graphical abstract .


Assessment of anxiety in dementia: an investigation into the association of different methods of measurement.
The objectives were to compare patient and caregiver ratings of anxiety for individuals with Alzheimer's disease and investigate their association with ratings of patient depression. Participants were 95 community-dwelling Alzheimer's disease patients and their caregivers. Measurements included caregiver proxy ratings: Rating Anxiety in Dementia, the NeuroPsychiatric Inventory, the Revised Memory and Behavior Problems Checklist, and the Cornell Scale for Depression in Dementia. Patient self-assessments included the Clinical Anxiety Scale (adapted) and the Geriatric Depression Scale. Correlations among anxiety measures ranged from rho = .16 to .40, whereas correlations between anxiety and depression scales ranged from rho = .03 to .66. Overlap among items across both anxiety and depression scales appeared to be the most important factor in determining these associations. Current scales for anxiety in dementia differ in their construction of symptoms and can overlap considerably with depression scales. Because of this, measures inadequately distinguish anxiety from depression in individuals with Alzheimer's disease. The measurement of anxiety in dementia needs additional refinement.


A Giant Solid-Cystic Gastric Inflammatory Myofibroblastic Tumor: A Case Report and Literature Review.
An inflammatory myofibroblastic tumor (IMT) is a very rare tumor of mesenchymal origin with unclear etiopathogenesis, no unique diagnostic features, and no specific management protocol. It is often confused with inflammatory pseudotumor in literature, and the distinction needs further study. The average size, recurrence risk, and metastatic potential differ as per the site of origin. The abdomen is a very rare site for IMTs. Hepatic IMTs (H-IMTs) are reported to be solid tumors with sizes ranging from 1 cm to 20 cm in literature, and gastric IMTs (G-IMTs) range from 3 cm to 10 cm in size and can be solid-cystic. We report here a case of a 36-year-old gentleman with a 34x27x17 cm solid-cystic lesion in the lesser sac with loss of fat planes with stomach and left hemi-liver. The patient was managed by complete surgical resection of the lesion with wedge gastrectomy and wedge hepatectomy and recovered uneventfully. To our knowledge and based on our literature review, this case presents the largest reported and solid-cystic G-IMT with the involvement of left hemi-liver in a young gentleman and discusses its management as well as the relevant literature on this rare entity. This clinical presentation of G-IMT should be kept in the differential diagnosis in a relevant case presenting in the future. Immunohistochemistry is a must to establish the diagnosis, and surgical resection to negative margins is the management option of choice in resectable cases.


Do dental educators need to improve their approach to teaching rubber dam use?
Most dentists are educated in rubber dam use in dental school, but there is often disparity between what is taught for various restorative procedures and what is practiced in the private sector. It is a common, although undocumented, belief that few practicing dentists routinely use rubber dam isolation. This study repeated a survey conducted in 1985 evaluating U.S. general dentists' attitudes toward rubber dam usage to see if improvement is needed in current dental educators' approach to this topic. Four hundred dentists were selected randomly from ten major geographically diverse cities using the website YellowPages.com. Each was mailed a letter requesting survey participation, which included a pre-stamped, pre-addressed postcard with the survey printed on the back. The target population, general dentists, returned 164 surveys (41 percent). Their responses can be summarized as follows: 71 percent do amalgams-of those, 53 percent never use a rubber dam whereas 12 percent always use a rubber dam; 100 percent do anterior direct resin composites-of those, 45 percent never use a rubber dam whereas 17 percent always use a rubber dam; 98 percent do posterior direct resin composites-of those, 39 percent never use a rubber dam and 18 percent always use a rubber dam; and 78 percent do endodontic procedures-of those, 11 percent never use a rubber dam whereas 58 percent always use a rubber dam. Most (74 percent) felt that their dental school rubber dam training was adequate; 42 percent felt that its use has an effect on the quality of restorative dentistry. Their most common reasons for not using a dam were the following: inconvenience (40 percent); unnecessary (28 percent); other (12 percent); patient refusal (11 percent); and time (9 percent). No respondent indicated that "cost" was a reason for not using rubber dams. This study indicates that many general dentists in this country continue to ignore the rubber dam for many restorative and some endodontic procedures. It indicates that predoctoral dental educators need to look for opportunities for improvement to reduce the discrepancy between what is taught and the general practice of dentistry.


Patient and Provider Experiences With Virtual Care in a Large, Ambulatory Care Hospital in Ontario, Canada During the COVID-19 Pandemic: Observational Study.
Virtual care use increased during the COVID-19 pandemic. The impact of that shift on patient and provider experiences is unclear. We evaluated patient and provider experiences with virtual visits across an academic, ambulatory hospital in Toronto, Canada and assessed predictors of positive experience with virtual care. Survey data were analyzed from consenting patients who attended at least one virtual visit (video or telephone) and from consenting providers who delivered at least one virtual visit. Distributions for demographic variables and responses to survey questions are reported, with statistical significance assessed using chi-square tests and t tests. Ordinal logistic regression analysis was used to identify any patient predictors of responses. During the study period, 253 patients (mean age 45.1, SD 15.6 years) completed 517 video visit surveys, and 147 patients (mean age 41.6, SD 16.4 years) completed 209 telephone visit surveys. A total of 75 and 94 providers completed the survey in June 2020 and June 2021, respectively. On a scale from 1 to 10 regarding likelihood to recommend virtual care to others, fewer providers rated a score of 8 or above compared with patients (providers: 62/94, 66% for video and 49/94, 52% for telephone; patients: 415/517, 80% for video and 150/209, 72% for telephone). Patients of non-White ethnicity had lower odds of rating a high score of 9 or 10 compared with White patients (odds ratio 0.52, 95% CI 0.28-0.99). Patient experiences with virtual care were generally positive, but provider experiences were less so. Findings suggest potential differences in patient experience by ethnicity, warranting further investigation into equity concerns with virtual care.


Achieving sub-nanometer roughness on aspheric optical mold by non-contact polishing using damping-clothed tool.
The surface quality of optical lenses is highly required in imaging functions. Normally, ultra-precision turning is employed to fabricate the optical lenses. However, ultra-precision turning cannot meet the surface quality demands due to the tool marks. In this study, a new damping-clothed (DC) tool and chemical enhanced non-Newtonian ultrafine (CNNU) slurry for non-contact polishing are proposed to achieve sub-nanometer roughness on aspherical optical molds. A material removal model based on the hydrodynamic pressure and velocity simulation was established to calculate the dwell time in curved surface machining. The formation mechanism of sub-nanometer roughness is clarified. The proposed method and slurry were verified by the experiments in processing NiP alloy aspheric optical mold. After the process, surface roughness Sa achieved 0.54 nm and the form accuracy is less than PV 600 nm.


Safety and efficacy of direct oral anticoagulants for venous thromboembolism and stroke prophylaxis in patients with hematologic malignancies.
Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.


NURR1 Alterations in Perinatal Stress: A First Step towards Late-Onset Diseases? A Narrative Review.
Perinatal life represents a delicate phase of development where stimuli of all sorts, coming to or from the mother, can influence the programming of the future baby's health. These stimuli may have consequences that persist throughout adulthood. Nuclear receptor related 1 protein (NURR1), a transcription factor with a critical role in the development of the dopaminergic neurons in the midbrain, mediates the response to stressful environmental stimuli in the perinatal period. During pregnancy, low-grade inflammation triggered by maternal obesity, hyperinsulinemia or vaginal infections alters NURR1 expression in human gestational tissues. A similar scenario is triggered by exposure to neurotoxic compounds, which are associated with NURR1 epigenetic deregulation in the offspring, with potential intergenerational effects. Since these alterations have been associated with an increased risk of developing late-onset diseases in children, NURR1, alone, or in combination with other molecular markers, has been proposed as a new prognostic tool and a potential therapeutic target for several pathological conditions. This narrative review describes perinatal stress associated with NURR1 gene deregulation, which is proposed here as a mediator of late-onset consequences of early life events.


[Relationship between body mass index and clinicopathological characteristics and prognosis of gastric cancer patients].
Objective: To investigate the relationship between body mass index (BMI) and clinicopathological characteristics and prognosis of gastric cancer patients. Methods: The clinical data of 788 patients with advanced gastric cancer were retrospectively analyzed. According to WHO weight standard, BMI<18.5 kg/m(2) was the low weight group, BMI 18.5~< 25.0 kg/m(2) was the normal weight group, BMI ≥ 25.0 kg/m(2) was the overweight group. The low weight group included 127 cases, the normal weight group included 540 cases and the overweight group included 121 cases. The relationship between different BMI groups and clinicopathological characteristics of patients was analyzed. Cox multivariate regression model was used to analyze the independent factor of the prognosis of patients. Results: The average BMI of 788 patients was 21.70 kg/m(2). The patients' BMI was significantly correlated with depth of invasion, maximum diameter of tumors, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (all P<0.05). BMI was marginally correlated with gender, age, smoking, alcohol consumption, TNM stage, lymph node metastasis and histological type (all P>0.05). Furthermore, BMI was significantly correlated with prealbumin, prognostic nutritional index, total protein, albumin and hemoglobin levels (all P<0.05). BMI was also significantly correlated with intraoperative bleeding volume, operation time, number of lymph node resection, number of lymph node metastasis and lymph node metastatic ratio (all P<0.05). The median survival time of the entire group was 35.3 months. The median survival time of patients in low weight group, normal weight group, and overweight group was 21.0 months, 26.3 months, and 31.2 months, respectively, the differences were statistically significant (P<0.001). Cox multivariate analysis showed that TNM stage, depth of tumor invasion, lymph node metastasis, PLR and BMI were independent risk factors of the prognosis of patients with gastric cancer (all P<0.05). Conclusions: BMI is associated with the nutritional status, intraoperative blood loss, operative time, and lymph node metastatic ratio of patients with gastric cancer. BMI is an independent risk factor of the prognosis of patients with gastric cancer. The overall survival time of patients with low body weight is shorter than those of normal weight and overweight patients.


Composite motion in cervical disc segments.
This study of composite motion in cervical motion segments used biplanar radiography and the principles of rigid body mechanics to determine the relationship of the axes of motion to the planes of the discs and zygapophyseal joints. Each cervical disc has an uniinate process posterolaterally on each side and the zygapophyseal joints are orientated at approximately 45° to the long axis of the spine. When considering the full range of composite motion from left to right the axis of motion lies in the mid-sagittal plane, but when unilateral movements to the left or right are studied the axes are eccentrically situated. When viewed in the lateral projection the line of the axis passes obliquely upwards and backwards through the front of the disc, then through the posterior part of the moving vertebral body, to cross the plane of the zygapophyseal joints approximately at right-angles. The orientation varies depending on whether the moment is applied in axial rotation or lateral flexion. The range of variation of the axis is small in the upper two disc segments where the superior articular facets have a slightly medial inclination, and larger in the lower cervical motion segments where the facets are inclined slightly laterally. The position and inclination of the axes of composite motion suggest that the anterior part of each cervical disc acts like a pivot, while the posterior part of the disc with the uncinate process on each side acts like a socket within which the upper vertebral body rolls.


Stress and diurnal cortisol among Latino/a college students: A multi-risk model approach.
The transition to college is a time of increased opportunity and stress spanning multiple domains. Adolescents who encounter significant stress during this transition may be vulnerable to adverse outcomes due to a "wear and tear" of the hypothalamic pituitary adrenal (HPA) axis. Latino/a students may be particularly at-risk for heightened stress exposure due to experiences of both minority-specific and general life stress. Despite this, little is known regarding the cumulative impact of multiple stressors on Latino/a students' HPA axis functioning. The present study employed a "multi-risk model" approach to examine additive, common, and cumulative effects of multiple stress forms (general, academic, social, financial, bicultural, ethnic/racial discrimination) on diurnal cortisol in a sample of first-year Latino/a college students (N = 196; 64.4% female; Mage = 18.95). Results indicated that no stress forms were additively associated with the cortisol awakening response (CAR), but general stress was associated with a flatter diurnal cortisol slope (DCS) and bicultural stress was linked with a steeper DCS. A college stress latent factor was associated with a lower CAR, whereas a latent factor of discrimination was not associated with diurnal cortisol. Cumulative risk was linked with a lower CAR. Findings highlight the physiological correlates of various stressors experienced by Latino/a college students.


A meta-analysis of the relationships between body checking, body image avoidance, body image dissatisfaction, mood, and disordered eating.
Body checking (BC) and body image avoidance (BIA) have been proposed as etiological and maintaining mechanisms for eating disorder (ED) pathology. To date, no comprehensive review summarizes the relationships of BC and BIA with ED pathology, body image dissatisfaction, or mood/affect. Meta-analyses examined the relationships of BC and BIA with ED pathology, body image dissatisfaction, and mood/affect. Gender, publication status, and presence or absence of ED diagnoses were examined as potential moderators. Results showed strong relationships between BC and ED pathology (ρ = 0.588) and BC and body image dissatisfaction (ρ = 0.631) and a moderate relationship between BC and mood/affect (ρ = 0.385). Similarly, results showed strong relationships between BIA and ED pathology (ρ = 0.553) and BIA and body image dissatisfaction (ρ = 0.543) and a moderate relationship between BIA and mood/affect (ρ = 0.392). Overall, limited evidence supported publication bias; however, publication bias may exist in the relationship between BIA and body image dissatisfaction in the literature. Subgroup moderator analyses suggested that gender moderates the strength of the relationships between BC and ED pathology, body image dissatisfaction, and mood/affect and between BIA and body image dissatisfaction. Results are consistent with cognitive-behavioral models of ED pathology that suggest BC and BIA are behavioral expressions of overvaluation of weight and shape. Notably, more published research has investigated BC than BIA. Future studies, incorporating methods such as meta-analytic structural equation modeling, should examine these variables to further test cognitive-behavioral models of ED development and maintenance.


Gray Matter Volume Changes over the Whole Brain in the Bulbar- and Spinal-onset Amyotrophic Lateral Sclerosis: a Voxel-based Morphometry Study.
Objective To investigate cerebral structural signatures of the bulbar- and spinal-onset amyotrophic lateral sclerosis (ALS) using voxel-based morphometry on magnetic resonance imaging. Methods The MR structural images of the brain were obtained from 65 ALS patients (15 bulbar-onset, 50 spinal-onset) and 65 normal controls (NC) on a 3.0T MRI system. Gray matter (GM) volume changes were investigated by voxel-based morphometry, and the distribution of the brain regions with volume changes was compared between ALS and normal controls, as well as between bulbar-onset and spinal-onset ALS based on Neuromorphometrics atlas. Result On voxel-level the decreased volume of brain regions in ALS patients was located in the right precentral gyrus (rPrcGy) and right middle frontal gyrus compared with that in NC. The bulbar-onset ALS presented extra-motor cortex atrophy (fronto-temporal pattern), including left medial orbital gyrus, left inferior temporal gyrus and right middle temporal gyrus; the spinal-onset ALS suffered from motor cortex atrophy (rPrcGy dominance) and extra-motor cortex atrophy (fronto-temporal and extra-fronto-temporal pattern) compared with NC. The spinal-onset ALS featured by GM volume loss of left postcentral gyrus and bulbar-onset ALS featured by GM volume loss of left middle temporal gyrus compared with each other. Conclusions The asymmetric GM atrophy of the motor cortex and extra-motor cortex represents the common MRI structural signatures of spinal-onset ALS, and sole extra-motor cortex atrophy represents the structural signatures of bulbar-onset ALS. The present study also demonstrated that the pattern of GM damage is likely to distribute wider in spinal-onset ALS than in bulbar-onset ALS.


Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson's disease.
There is a growing number of clinical studies that revealed a variety of behavioral and physiological desynchronies in patients with Parkinson's disease (PD). However, these desynchronies have not been defined at the molecular level. Using real-time RT-PCR assay, we analyzed the expression profiles of two principle clock genes, PER1 and BMAL1, in total leukocytes for 12 h during the evening, overnight and morning in subjects with PD and age/sex-matched healthy controls. A difference in the expression pattern of BMAL1 but not PER1 was apparent during the dark span, where the relative abundance of BMAL1 was significantly lower in PD patients versus control subjects at 21:00, 00:00 and 06:00 h. Furthermore, expression levels of BMAL1 in PD patients correlated with their United Parkinson's Disease Rating Scale score at 06:00, 09:00 h, and with Pittsburgh Sleep Quality Index score at 06:00 h. These results suggest that a peripheral molecular clock, as reflected in the dampened expression of the clock genes BMAL1 in total leukocytes, is altered in PD patients. In addition, the relative BMAL1 levels correlate positively with PD severity, which could provide a molecular basis to help monitor disease progression and response to investigational drugs.


Barriers to using research evidence in nursing practice.
Barriers to using research evidence in nursing practice The nursing profession has long recognized the importance of research as an essential basis for its development. More recently, the movement supporting evidence-based practice has brought this point into focus. However, relatively little research has been conducted to identify factors that interfere with the ability of nurses to base their practice on research evidence. Using factor analysis procedures, barriers to the use of research evidence in practice which were perceived to be present by 400 registered nurses working in an Australian hospital, were grouped under four main factors. These were accessibility of research findings, anticipated outcomes of using research, organizational support to use research and support from others to use research. The most important factor was perceived to be organizational support, particularly in relation to providing time to use and conduct research.


[Types of neurons in the visual cortex of the rat, identified in Nissl- and deimpregnated Golgi preparations].
Neuronal types of the rat's visual cortex were identified in Nissl stained and deimpregnated Golgi sections (rapid Golgi method modified by Fairén et al. 1977, Golgi-Bubenaite, Golgi-Kopsch and modified by Braitenberg; deimpregnation after FAIREN et al. 1977 and Braak and Braak 1982, respectively). Cytoplasm and nucleus become visible in deimpregnated neurons and can then be counter-stained with methylene blue or toluidin blue. Somal and nuclear features of Nissl stained and deimpregnated neurons were compared. Provided that these features as well as the specific localization, the relative size and the shape of the soma agree the neurons are identical. We could find that the following neuronal types are identical in Golgi and Nissl stained sections: pyramidal cells of layers II-VI, pyramid-like neurons of layers VI and VII (VIa, b, c) (type C, Werner et al. 1982), multiangular neurons of layer I (type A, Werner et al. 1982), spiny stellate cells of layer IV, sparsely spined neurons with ascending axons (Martinotti cells) (type H, Werner et al. 1982), large and medium-sized spine-free, multipolar neurons (basket cells) (type B, Werner et al. 1982). Bipolar neurons and chandelier cells are identical with neurons poor in cytoplasm (types E, F, G, Werner et al. 1982). Until today two neuronal types could not be identified: type D of L I (Werner et al. 1982) and small, sparsely-spined neurons of layer IV with variable axons (Hedlich and Winkelmann 1982; Hedlich et al. 1984). Characteristics of somata, dendrites and axons of neurons identified in this paper are summarized in table 1. In most cases, these findings confirm earlier suppositions concerning the identity of neuronal types of the rat's visual cortex in Golgi and Nissl stained sections (Werner et al. 1979) and verify the values of their frequency and distribution pattern (Werner et al. 1982).


Baseline Functional Connectivity Features of Neural Network Nodes Can Predict Improvement After Sound Therapy Through Adjusted Narrow Band Noise in Tinnitus Patients.
Previous resting-state functional magnetic resonance imaging (fMRI) studies have shown neural connectivity alterations after the treatment of tinnitus. We aim to study the value of the baseline functional connectivity features of neural network nodes to predict outcomes of sound therapy through adjusted narrow band noise. The fMRI data of 27 untreated tinnitus patients and 27 matched healthy controls were analyzed. We calculated the graph-theoretical metric degree centrality (DC) to characterize the functional connectivity of the neural network nodes. Therapeutic outcomes are determined by the changes in the Tinnitus Handicap Inventory (THI) score after a 12-week intervention. The connectivity of 10 brain nodes in tinnitus patients was significantly increased at baseline. The functional connectivity of right insula, inferior parietal lobule (IPL), bilateral thalami, and left middle temporal gyrus was significantly modified with the sound therapy, and such changes correlated with THI changes in tinnitus patients. Receiver operating characteristic curve analyses revealed that the measurements from the five brain regions were effective at classifying improvement after therapy. After age, gender, and education correction, the adjusted area under the curve (AUC) values for the bilateral thalami were the highest (left, 0.745; right, 0.708). Our study further supported the involvement of the fronto-parietal-cingulate network in tinnitus and found that the connectivity of the thalamus at baseline is an object neuroimaging-based indicator to predict clinical outcome of sound therapy through adjusted narrow band noise.


T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease.
T helper (Th)1 cells were considered responsible for the induction of graft-versus-host disease (GVHD), but recently the concept has been challenged. Th17 cells play a critical role in mediating autoimmune diseases, but their role in the pathogenesis of GVHD remains unclear. Herein we compare the ability of in vitro generated Th1 and Th17 cells from C57BL/6 mice to induce GVHD in lethally irradiated BALB/c recipients. Allogeneic Th17 cells had superior expansion and infiltration capabilities in GVHD target organs, which correlated with their increased pathogenicity when compared with naïve or Th1 controls. Th17 cells caused no pathology in the syngeneic recipients, indicating that antigen-activation was required for their pathogenicity. Polarized Th17 cells could not maintain their phenotype in vivo as they produced a significant amount of interferon (IFN)-gamma after being transplanted into allogeneic recipients; however, IFN-gamma was not required for Th17 cell-induced GVHD. Further, we evaluated the pathogenesis of Th17 cells in GVHD by using polyclonal nonprimed CD4T cells in a clinically relevant allogeneic bone marrow transplantation (BMT) setting. We found that disruption of Th17-differentiation alone by targeting RORgammat (Th17-specific transcription factor) had no significant effect on GVHD development. We conclude that Th17 cells are sufficient but not necessary to induce GVHD.


National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants.
Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6-11·2) in men and 9·2% (8·0-10·5) in women in 2008, up from 8·3% (6·5-10·4) and 7·5% (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5%, 11·6-20·1 for men; and 15·9%, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. Bill & Melinda Gates Foundation and WHO.


[A consideration of the relation between psychiatric knowledge and natural science].
Schools of psychiatric thought are as numerous as they are various, each developed from different sources and presuppositions and each claiming faithful adherents. One inherent difficulty in this profusion of choice lies in discerning whether or not a particular school's presuppositions are valid. To accept one theory is to choose one opinion towards philosophical aporiae--often at the expense of all others. In this paper, issues of scientific philosophy are examined in considering the presuppositions and progress of psychiatric schools. Popper convincingly argued that scientific statements should be "falsifiable." However, because propositions of psychoanalysis or phenomenological psychiatry are closely tied to individual clinical experiences, such statements tend to be exclusive and difficult to check or falsify by other reseachers. They are, in this respect and according to Popper's point of view, necessarily less scientific. Phenomena of the human mind, by its very nature, cannot be observed nor measured directly. Interpretation of the phenomena therefore depends almost entirely upon which theoretical school the researcher has adopted. Biological psychiatry, however, insists that any researcher can objectively measure such phenomenon, and that propositions of biological psychiatry can be connected with those of other branches of natural science. Natural science grandly attempts to comprehensively describe the whole world using one language. This means the researcher is supposedly measuring an object positioned in an ideal and definite position, reached only through infinite steps. Phenomenology is very conscious that the observed object consists at least partly of the observing subject, and so this ideal positioning seems untenable. Phenomenology therefore describes this world from another point of view, different from natural science, and the distinction between measurement of certain systems from inside or outside is important for purposes of explanation and clarification. Although natural science attempts to attain the ideal infinite view, on-going science is naturally limited. In psychiatric practice, we can never rely on one definitive theory; but must rather adopt an appropriate theory to solve an appropriate problem.


Inactivated human rotavirus vaccine induces heterotypic antibody response: correction and development of IgG avidity assay.
To improve lower efficacy among infants in low income countries and the safety (e.g., rare but severe intussusception) of live oral rotavirus vaccines, we have developed CDC-9 strain with G1P[8] specificity as a candidate inactivated rotavirus vaccine (IRV). This IRV of 3 doses elicits high titers of IgG, neutralizing activity to homotypic and heterotypic human strains and IgG avidity in guinea pigs, thus is a promising alternative to enhance global immunization against rotavirus in children.


Removal of dissolved 85Kr by vacuum degassing method.
In the irradiation apparatus where unsealed 85Kr gas is used as an internal radiation source for liquid-phase chemical reaction, the 85Kr gas dissolved in a liquid reactant must be removed after irradiation. Experiments on removal of dissolved 85Kr by the vacuum degassing method were carried out to examine the influence of degassing temperature, initial 85Kr concentration and stirring of a solution on the removal. The liquid reactant used was a water of 500 ml in which 85Kr gas was dissolved. The removal effect became greater with increasing temperature. The dissolved 85Kr concentration after removal decreased exponentially with the reciprocal of degassing temperature. Further, the removal effect was intensely affected by stirring of the solution and was independent of the initial 85Kr concentration. The removal factor of dissolved 85Kr at 33 degrees C reached 5 X 10(3) after a 30 minute lapse.


Déjà vu all over again: finding and analyzing protein structure similarities.
Structure comparison is a crucial aspect of structural biology today. The field of structure comparison is developing rapidly, with the development of new algorithms, similarity scores, and statistical scores. The predicted large increase of experimental structures and structural models made possible by high-throughput efforts means that structural comparison and searching of structural databases using automated methods will become increasingly common. This Ways & Means article is meant to guide the structural biologist in the basics of structural alignment, and to provide an overview of the available software tools. The main purpose is to encourage users to gain some understanding of the strengths and limitations of structural alignment, and to take these factors into account when interpreting the results of different programs.


Extrasynaptic localization of GABA in the developing mouse cerebellum.
In the adult brain, gamma-amino butyric acid (GABA) is synaptically released and mediates inhibitory transmission. Recent studies have revealed that GABA is a trophic factor for brain development. To reveal the distribution of GABA and its secretion mechanisms during brain development, we investigated the immunohistochemical localization of two molecules, GABA and vesicular GABA transporter (VGAT), which is a GABAergic vesicle protein, in the developing mouse cerebellum by means of newly developed antibodies. Furthermore, we tested the relationship between developmental changes in distribution of above two molecules in the presynapses and ontogeny of GABAergic synapses. GABAergic synapses were detected by immunohistochemistry for the GABA(A) receptor alpha1 subunit, which is an essential subunit for inhibitory synaptic transmission in the mature cerebellar cortex. Until postnatal day 7 (P7), GABA was localized throughout the GABAergic neurons, and VGAT accumulated at axon varicosities and growth cones, where the alpha1 subunit did not accumulate. After P10, both GABA and VGAT became confined to the terminal sites where the alpha1 subunit was localized. These results suggested that GABA was extrasynaptically released from axon varicosities and growth cones by vesicular secretion 'exocytosis' and from all parts of GABAergic neurons during the cerebellar development by non-vesicular secretion 'diacrine'.


Phomol, a new antiinflammatory metabolite from an endophyte of the medicinal plant Erythrina crista-galli.
Phomol (1), a novel antibiotic, was isolated from fermentations of a Phomopsis species in the course of a screening of endophytic fungi from the medicinal plant Erythrina crista-galli. For this Argentinean leguminosa antiinflammatory and neuroleptic activities have been described. The compound exhibits antifungal, antibacterial and weak cytotoxic acticity. The antiinflammatory activity was tested in different reporter gene assays (TNF-alpha, STAT1/STAT2 and NF-kappaB) and in an ear edema model in mice. In the reporter gene assays 1 exhibited no activity, whereas 1 showed interesting antiinflammatory activity in the mouse ear assay. The compound is a polyketide lactone and its structure was elucidated by spectroscopic methods.


LDL-C plays a causal role on T2DM: a Mendelian randomization analysis.
Diabetic dyslipidemia is a common condition in patients with Type 2 diabetes mellitus (T2DM). However, with the increasing application of statins which mainly decrease low-density lipoprotein cholesterol (LDL-C) levels, clinical trials and meta-analysis showed a clearly increase of the incidence of new-onset DMs, partly due to genetic factors. To determine whether a causal relationship exists between LDL-C and T2DM, we conducted a two-sample Mendelian Randomization (MR) analysis using genetic variations as instrumental variables (IVs). Initially, 29 SNPs significantly related to LDL-C (P≤ 5.0×10-8) were selected as based on results from the study of Henry et al, which processed loci data influencing lipids identified by the Global Lipids Genetics Consortium (GLGC) from 188,577 individuals of European ancestry. While 6 SNPs related to T2DM (P value < 5×10-2) were deleted, with the remaining 23 SNPs without LD eventually being deemed as IVs. The combined effect of all these 23 SNPs on T2DM, as generated with use of the penalized robust inverse-variance weighted (IVW) method (Beta value 0.24, 95%CI 0.087~0.393, P-value=0.002) demonstrated that elevated LDL-C levels significantly increased the risk of T2DM. The relationship between LDL-C and Type 1 diabetes mellitus (T1DM) with this analysis producing negative pooled results (Beta value -0.202, 95%CI -2.888~2.484, P-value=0.883).


Flaws and pitfalls in the chemical analysis of feathers: bad news-good news for avian chemoecology and toxicology.
Ecologists have frequently used biochemical assays as proxies for processes or phenomena too difficult to explore by traditional means of investigation. Feathers have been subjected to a number of chemical analyses to study such things as their elemental composition, contaminants, and hormones. The reliance on standard methodology of using concentrations to express quantities of chemical substances is seriously problematic because it creates artifacts by ignoring the physiology of feathers. Some elements and compounds are incorporated into the feather as part of the very building blocks of the keratin. However, others that are less functionally important to feathers (but not necessarily to the bird) enter the developing cells in proportion to their abundance in the bloodstream; in other words, feathers are merely receptacles, and deposition of chemicals is time dependent. In the latter case, one that applies to much of the work done on feather chemistry, data expressed as concentrations are meaningless because the varying mass across the feather alters concentrations in a way that has no biological significance. I discuss this problem and various pitfalls in the chemical analysis of feathers, and offer solutions that ultimately will offer a better understanding of the mechanisms influencing feather composition and, thus, the ecological patterns and processes they were meant to study.


[Clinicopathological features of basal cell type dysplasia of esophagus].
Objective: To investigate the clinicpathological features of basal cell type dysplasia of the esophagus. Methods: The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People's Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed. Results: The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma. Conclusions: Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.


Two-Channel SPR Sensor Combined Application of Polymer- and Vitreous-Clad Optic Fibers.
By combining a polymer-clad optic fiber and a vitreous-clad optic fiber, we proposed and fabricated a novel optic fiber surface plasmon resonance (SPR) sensor to conduct two-channel sensing at the same detection area. The traditional optic fiber SPR sensor has many disadvantages; for example, removing the cladding requires corrosion, operating it is dangerous, adjusting the dynamic response range is hard, and producing different resonance wavelengths in the sensing area to realize a multi-channel measurement is difficult. Therefore, in this paper, we skillfully used bare fiber grinding technology and reverse symmetry welding technology to remove the cladding in a multi-mode fiber and expose the evanescent field. On the basis of investigating the effect of the grinding angle on the dynamic range change of the SPR resonance valley wavelength and sensitivity, we combined polymer-clad fiber and vitreous-clad fiber by a smart design structure to realize at a single point a two-channel measurement fiber SPR sensor. In this paper, we obtained a beautiful spectral curve from a multi-mode fiber two-channel SPR sensor. In the detection range of the refractive rate between 1.333 RIU and 1.385 RIU, the resonance valley wavelength of channel Ⅰ shifted from 622 nm to 724 nm with a mean average sensitivity of 1961 nm/RIU and the resonance valley wavelength of channel Ⅱ shifted from 741 nm to 976 nm with a mean average sensitivity of 4519 nm/RIU.


Hydrogen sulfide promotes lipopolysaccharide-induced apoptosis of osteoblasts by inhibiting the AKT/NF-κB signaling pathway.
Apoptosis of osteoblasts plays a crucial role in osteomyelitis. Hydrogen sulfide (H2S) levels are increased in the pathophysiological processes of osteomyelitis. However, the effect of H2S on the apoptosis of osteoblasts remains unclear. To investigate the specific role of H2S in osteoblast apoptosis, MC3T3-E1 and hFOB cells were treated with NaHS or Na2S, a donor of H2S, and lipopolysaccharide (LPS), during osteomyelitis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analysis, western blotting, immunofluorescence, polymerase chain reaction, and Alizarin red staining were performed to examine the effects of H2S on osteoblast cell apoptosis, cell osteogenic differentiation, and AKT kinase (AKT)/nuclear factor kappa B (NF-κB) signaling. Hydrogen sulfide increased cell apoptosis, and inhibited the proliferation and osteogenic differentiation of osteoblast cells impaired by LPS. H2S increased apoptosis through upregulation of the FAS ligand (FASL) signaling pathway. H2S-induced apoptosis was alleviated using a FAS/FASL signaling pathway inhibitor. Treatment with NaHS also increased cell apoptosis by downregulating AKT/NF-κB signaling. In addition, treatment with an AKT signaling pathway activator decreased apoptosis and reversed the inhibitory effects of H2S on osteogenic differentiation. Hydrogen sulfide promotes LPS-induced apoptosis of osteoblast cells by inhibiting AKT/NF-κB signaling.


Dys-regulation of effector CD4+ T cell function by the V3 domain of the HIV-1 gp120 during antigen presentation.
It was recently demonstrated that the semiconserved domain of the V3 region of the HIV-1 surface glycoprotein gp120 can induce an activation-apoptosis phenomenon to memory CD4+ cells from healthy individuals. Studying the effects of V3 on the interaction of antigen presentation between monocyte-derived macrophages and resting memory CD4+ T cells, we observed that V3 affects both cell populations. Macrophages exposed to composite liposomes containing V3 on the surface and tetanus toxoid (TT) as the recall antigen entrapped in the aqueous phase (lipoV3/TT liposomes) were able to activate CD4+ T cells during primary stimulation, but not after restimulation nine days later. Unstimulated macrophages or macrophages exposed to soluble TT responded to second stimuli, lipoV3/TT liposomes, and soluble TT in activating CD4+ T cells. Soluble TT-activated CD4+ T cells could be restimulated by soluble TT but not by lipoV3/TT liposomes, whereas lipoV3/TT liposome-activated CD4+ T cells became unresponsive to a second stimulus. These results show that resting memory CD4+ cells activated by macrophages presenting the recall antigen together with V3 become unresponsive to restimulation.


P-selectin inhibition enhances thrombus resolution and decreases vein wall fibrosis in a rat model.
The purpose of this study was to compare the efficacy of P-selectin inhibition with standard anticoagulant and thrombolytic therapy in a rodent model of established deep vein thrombosis (DVT). Rats underwent temporary inferior vena cava (IVC) ligation for 2 days to create a stasis-induced thrombosis. On day 2, the animals had the IVC ligature removed and received either recombinant P-selectin glycoprotein ligand-Ig (rPSGL-Ig; 4 mg/kg) intravenously, low-molecular weight heparin (LMWH; 450 IU/kg) subcutaneously, tissue plasminogen activator (tPA; 0.5 mg/kg) intravenously, combination rPSGL-Ig plus tPA, or saline vehicle. IVC segments were harvested from rats at 4 (n = 8) and 7 (n = 3) days after treatment. All treatments were given as a single dose except for daily LMWH. Evaluation included contrast venography with computer image analysis, thrombus weight/length (mass), vein wall leukocyte counts, cytokine and tissue factor analysis with enzyme-linked immunosorbent assay, and (ED1) monocyte immunohistochemical staining. Collagen was estimated with a quantitative assay. Contrast venography revealed that rats with both rPSGL-Ig and tPA treatment had significantly smaller thrombi as compared with controls at day 7 (0.34 +/- 0.07 cm(2) and 0.34 +/- 0.05 cm(2) versus 0.68 +/- 0.13 cm(2); P <.05). LMWH and tPA groups had significantly decreased thrombus mass at harvest compared with controls on day 4 (0.06 +/- 0.009 g/cm and 0.08 +/- 0.01 g/cm versus 0.1 +/- 0.005 g/cm; P <.05), and rPSGL-Ig showed a similar trend (P =.072). Vein wall, but not thrombus, monocytes were more numerous in those rats receiving rPSGL-Ig versus controls at day 4 (30 +/- 4 cells/5 high power fields [HPFs] versus 19 +/- 2 cells/5 HPFs; P <.05) and at day 7 (32 +/- 2 cells/5 HPFs versus 20 +/- 3 cells/5 HPFs; P <.05). rPSGL-Ig treatment was associated with significantly reduced vein wall collagen at day 7 versus controls (1.3 +/- 0.6 pg/mg versus 3.7 +/- 0.5 pg/mg; P <.05) and a trend toward lower tissue factor levels. rPSGL-Ig, LMWH, and tPA showed equal DVT resolution efficacy over 7 days. However, only rPSGL-Ig was associated with a decrease in vein wall fibrosis, suggesting that purely accelerating DVT resolution may not decrease long-term vein scarring.


Do Plantago lanceolata Skin Prick Test-Positive Patients Display IgE to Genuine Plantain Pollen Allergens? Investigation of Pollen Allergic Patients from the North-East of France.
English plantain (Plantago lanceolata) is an important weed pollen allergen source triggering allergic symptoms during summer. To elucidate genuine versus cross-reactive sensitization, we investigated IgE reactivity patterns and inhibition capacities of plantain-sensitized patients. Sera of 35 rhinoconjunctivitis patients from the north-east of France with positive skin prick tests (SPT) to Plantago lanceolata pollen were tested with clinically relevant allergen sources using ELISA, ImmunoCAP, and immunoblot inhibition. The patients were multisensitized with additional reactivity to grass (94.3%), ash (74.3%), birch (71.4%), and mugwort (55.2%) pollen in SPT. Sensitization prevalence to allergen molecules was 34.3% (Pla l 1), 94.3% (Phl p 1/5), 60.0% (Ole e 1), 65.7% (Bet v 1), 37.1% (profilin), and 40.0% (CCD). In immunoblot, IgE reactivity to plantain pollen was inhibited with relevant pollen extracts and purified rPla l 1. Two sera did not reveal any IgE cross-reactivity, while reactivity to plantain was efficiently inhibited by grass pollen in the sera of 10 patients. The sera from 17 different patients could be inhibited by grass, birch, or ash pollen to varying degrees. Thus, only 37.1% of our patients demonstrated true plantain pollen sensitization, while 62.9% were solely positive due to IgE cross-reactive molecules from other clinically relevant pollen. Plantain pollen-sensitized patients are multi-reactors demonstrating varying and complex IgE-reactivity profiles. In vivo and in vitro tests using extracts are typically blurred due to the presence of homologous allergens or CCD in grass, birch, or ash pollen. So far, Pla l 1 represents the only indicative marker allergen for the diagnosis of genuine plantain pollen sensitization.


Disability Outcome Measures in Phase III Clinical Trials in Multiple Sclerosis.
Accumulating neurological disability has a substantial impact on the lives of patients with multiple sclerosis (MS). As well as the established Expanded Disability Status Scale (EDSS), several other outcome measures are now available for assessing disability progression in MS. This review extends the findings of a previous analysis of relapsing-remitting MS (RRMS) trials published up to 2012, to determine whether there has been a shift in outcome measures used to assess disability in phase III clinical trials in RRMS and progressive MS. Forty relevant trials were identified (RRMS, n = 16; progressive MS, n = 18; other/mixed phenotypes, n = 6). Sustained EDSS worsening, particularly over 3 months, was included as an endpoint in almost all identified trials. Other disability-related endpoints included the Multiple Sclerosis Functional Composite z-score and scores for the physical component summary of the Multiple Sclerosis Impact Scale and Medical Outcomes Study Short-Form (36-item) Health Survey. Tests assessing manual dexterity, ambulation, vision and cognition were also employed, and in some trials, composite endpoints were used. However, there was no obvious trend in choice of disability outcome measures over time. Sustained EDSS worsening over short time periods continues to be the most widely used measure of disability progression in pivotal MS trials, despite its well-recognised limitations. A new tool set is needed for use in MS clinical trials that detects the benefit of potential treatments that slow (or reverse) progressive disability.


Aromatase: the enzyme and its inhibition.
The genetic control, mechanism of action and inhibition of aromatase for potential therapeutic benefits in the arena of hormone dependent illness continues to be of considerable interest. The work presented here concentrates on recent advances in the mechanistic aspects of the aromatase enzyme and the nature of the chemical entities that lead to its inhibition.


c-Fos immunoreactivity in the neurons of the lateral geniculate nucleus in albino rats by light exposure after dark rearing.
To investigate the effect of dark rearing immediately after birth on the maturation of the visual relay neurons in the lateral geniculate nucleus. Fifty neonatal rats were used. Neonates of the control groups were raised under a normal light/dark cycle. Neonates of the experiment groups were dark reared and isolated from light during the entire experimental period, then exposed to the sun light for 1 hour before sacrifice. In the control groups, the neurons in the dorsal lateral geniculate nucleus developed normally at each age tested. In the experiment groups, the cytoplasm of the large neurons in the dorsal lateral geniculate nucleus of 2-week-old rats contained small vesicles, and the cytoplasm of the large neurons of 4-week-old rats was converted into a vacuole-like space. Moreover, c-Fos immunoreactivity of the large neurons in the dorsal lateral geniculate nucleus in the experiment groups was significantly increased compared to that of the control groups. We suppose that the maturation of the neurons in the lateral geniculate nucleus might be influenced by light stimulation during the critical period. Furthermore, c-Fos could be a marker of the functional activity of the visual relay neurons of the lateral geniculate nucleus in albino rats.


Hypothalamic-pituitary-adrenocortical axis function in patients with polymyalgia rheumatica and giant cell arteritis.
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are 2 closely related syndromes affecting elderly people. One of the most striking features of these conditions is the development of the disease in an almost exclusive manner in people older than 50 years. Despite this close association with age, the pathogenic mechanisms that could explain this age-related predisposition are unknown. Aging is accompanied by a number of quantitative and qualitative changes in the endocrine system that may predispose to several pathologic conditions that occur in the elderly. To explore the hypothalamic-pituitary-adrenal axis in PMR and GCA. Basal levels of adrenal hormones as well as the response to low-dose adrenocorticotropin hormone (ACTH) were investigated in 20 patients with active untreated disease and compared with levels in 16 healthy age-matched controls. Male patients with active disease had low basal levels of androstenedione compared to the controls. After low-dose ACTH challenge, cortisol and dehydroepiandrosterone reached higher levels in patients than in healthy subjects, indicating that the adrenal gland function was not suppressed. Furthermore, the authors did not find a clear relationship between the levels of acute phase reactants and adrenal hormones in the patient population. The authors' findings are probably more compatible with the hypothesis that the abnormalities found in the patient group are the consequences of chronic illness rather than a crucial factor contributing to the pathogenesis of the disease.


Mucosal delivery of bacterial antigens and CpG oligonucleotides formulated in biphasic lipid vesicles in pigs.
The ineffectiveness of simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies of strategies for appropriate delivery systems and adjuvants. Biphasic lipid vesicles are formulations suitable for the delivery of proteins, peptides, and oligo/polynucleotides. The purpose of these studies was to investigate the ability of biphasic lipid vesicles (as vaccine-targeting adjuvants) containing a bacterial antigen and unmethylated oligonucleotides containing CGdinucleotides - CpG motifs (CpG ODNs) to induce systemic and mucosal immune responses in pigs. Results showed that while the protein, either alone or with CpG ODNs, did not induce mucosal immune responses, administration of antigen and CpG ODNs in biphasic lipid vesicles resulted in induction of both systemic and local antibody responses after immunization using a combined mucosal/systemic approach.


Neuromagnetic instrumentation.
In considering what type of MEG system is needed, there are four main considerations: 1. Ambient magnetic noise at the intend site(s). The need to reject external noise will determine the need for a shielded room. Here, manufacturer's claims can be compared in terms of magnetic field sensitivities (BN/square root Hz) at the measurement site. There are several tradeoffs to consider. A relatively quiet environment may allow use of a less expensive eddy-current-shielded room combined with second-derivative gradiometer coils. A more harsh environment might need an MSR, but a gain in sensitivity may be afforded by using first-derivative gradient coils. A truly hostile environment could require multiple eddy-current shields combined with an MSR using three or more layers of mu-metal. 2. Head coverage and spatial resolution. The number of channels will roughly determine the number of times the Dewar(s) must be moved to cover the entire region of interest. Until MEG systems are available that can cover the entire head, coverage will be an important factor. Spatial resolutions (related to the diameter of the pickup coils and their spacing) should be adequate for all intended measurements. 3. Required sensitivity. Since the objects to be studied are current dipoles, magnetic field sensitivities (in fT/square root Hz) are not appropriate. This should be in terms of sensitivity to a current dipole measured in ampere-meters (Eq. 10) as a function of depth below the bottom of the Dewar tail. 4. Data acquisition systems and system software. Major considerations include the following: At what rate is data to be gathered? What is the total amount of data to be gathered in a single session? Must the data be processed real-time? How is the data to be interpreted? How is the data to be displayed? By examining these factors, it should be possible to compare available systems for neuromagnetic measurements and determine which system is appropriate for your needs.


Patients with asthma have reduced functional capacity and sedentary behavior.
The modified shuttle test is a field test that avoids the ceiling effect, and there are no reports of a multidimensional assessment concerning physical activity in asthmatic patients. Thus, the aim was to evaluate functional capacity by MST, additionally to perform a multidimensional assessment as physical activity in daily life, muscle strength, and cytokine levels in children and adolescents with asthma, and to correlate these variables. This cross-sectional study included volunteers aged between 6 and 18 years who were divided into two groups: asthma group (n=43) that received regular treatment and control group (n=24). Functional capacity was evaluated by distance walked during the MST; physical activity in daily life was evaluated using an accelerometer by the number of steps. Quadriceps femoris strength was evaluated by load cell. Distance walked was lower for the asthma group (790m [222m]) when compared with the control group (950m [240m]; p=0.007); however, the number of steps was similar between the two groups (asthma group: 7743 [3075]; control group: 7181 [3040]; p=0.41), and both groups were classified as sedentary behavior. There was no difference in muscle strength. Tumor necrosis factor-α differed, but interleukin levels were similar between groups. Quadriceps strength was correlated to distance walked (r=0.62; p<0.001) and tumor necrosis factor-α to the number of steps taken (r=-0.54, p=0.005). Children and adolescents undergoing regular asthma treatment showed reduced functional capacity and sedentary behavior. The lower the quadriceps strength, the shorter the distance walked; the higher the tumor necrosis factor-α levels, the lower their daily physical activity levels.


Selegiline in the treatment of narcolepsy.
We treated 17 narcolepsy patients in a placebo-controlled, double-blind, crossover trial with 10-, 20-, 30-, and 40-mg daily doses of selegiline, a monoamine oxidase inhibitor widely used in Parkinson's disease. There was a dose-dependent as well as a statistically and clinically significant improvement in narcoleptic symptoms and polygraphic measures. At 40 mg, there was a 36% reduction in the number of daytime sleep episodes and a 34% reduction in their duration (compared with placebo, mean values). The number of excessive sleepiness episodes decreased by 43%, and the duration decreased by 47%. The number of cataplectic attacks was reduced by 89%. On the multiple sleep latency test, the REM sleep latency increased from 5.0 to 13.3 minutes, and the number of sleep-onset REM periods decreased from 3.1 to 0.6. Sleep (S1) latency was not changed. No intolerable adverse events occurred. The effective dose range was 20 to 40 mg, requiring a low-tyramine diet, which was easy to maintain. In conclusion, selegiline alleviates both main symptoms of narcolepsy--the abnormal sleep tendency and cataplexy. Thus, treatment with selegiline makes it possible to avoid polypharmacy and to use a potent stimulant without known addiction risk.


Nationwide Molecular Epidemiology of Measles Virus in Japan Between 2008 and 2017.
Genotyping evidence that supports the interruption of endemic measles virus (MV) transmission is one of the essential criteria to be verified in achieving measles elimination. In Japan since 2014, MV genotype analyses have been performed for most of the measles cases in prefectural public health institutes nationwide. With this strong molecular epidemiological data, Japan was verified to have eliminated measles in March, 2015. However, even in the postelimination era, sporadic cases and small outbreaks of measles have been detected repeatedly in Japan. This study investigated the nationwide molecular epidemiology of MV between 2008 and 2017. The 891 strains in the total period between 2008 and 2017 belonged to seven genotypes (D5, D4, D9, H1, G3, B3, and D8) and 124 different MV sequence variants, based on the 450-nucleotide sequence region of the N gene (N450). The 311 MV strains in the postelimination era between 2015 and 2017 were classified into 1, 7, 8, and 32 different N450 sequence variants in D9, H1, B3, and D8 genotypes, respectively. Analysis of the detection period of the individual N450 sequence variants showed that the majority of MV strains were detected only for a short period. However, MV strains, MVs/Osaka.JPN/29.15/ [D8] and MVi/Hulu Langat.MYS/26.11/ [D8], which are named strains designated by World Health Organization (WHO), have been detected in many cases over 2 or 3 years between 2015 and 2017. The WHO-named strains have circulated worldwide, causing outbreaks in many countries. Epidemiological investigation revealed repeated importation of these WHO-named strains into Japan. To demonstrate the elimination status (interruption of endemic transmission) in situations with repeated importation of the same strains is challenging. Nevertheless, the detailed sequence analysis of individual MV strains and chronological analysis of these strains provided sufficient evidence to show that Japan has still maintained its measles elimination status in 2017.


Knowledge about Disease, Medication Therapy, and Related Medication Adherence Levels among Patients with Hypertension.
Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow the doctor's recommendations and regularly do not control their blood pressure, owing to many factors. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. We investigated their therapy, knowledge about the disease and its control, and demographic differences to assess the adherence of patients with hypertension. Materials and Methods: This was a cross-sectional observational study. Data were collected through a survey of 12 pharmacies in Latvia. The study involved 187 participants with hypertension. Results: The prevalence of non-adherence was 46.20% in Latvia. The oldest patients were the most adherent (p = 0.001, β = 0.27). The higher the self-rated extent from 0 to 10, to which the patient takes their antihypertensives exactly as instructed by their physician, the higher the level of adherence (p < 0.0001, β = 0.38), where at "0", the patient does not follow physician instructions at all, and at "10", the patient completely follows the physician's instructions. Non-adherent patients tend to assess their medication-taking behavior more critically than adherent patients. The longer the patient is known to suffer from hypertension, the more adherent he or she is (p = 0.014, β = 0.19). Conclusions: Medication non-adherence among patients with hypertension is high in Latvia. Further investigations are needed to better understand the reasons for this and to establish interventions for improving patient outcomes.


Effect of inhaled steroids on bone mineral density: a meta-analysis.
Inhaled corticosteroids are currently considered first-line agents for the treatment of asthma. Medium- to long-term administration of inhaled steroids may be associated with bone loss. Various studies have evaluated their effect on bone mineral density (BMD); some have shown loss of BMD with steroid treatment, but others have failed to do so. The present meta-analysis was undertaken to determine the possible effect of inhaled steroids on bone density. Literature was collected using computerized (MEDLINE) and manual searches using index medicus and checking cross-references of the published articles. The studies identified were screened for inclusion/exclusion criteria. Grouped means (XT/XC) and pooled standard deviations (SDT/SDC) for the treatment group (XT[95% CI] = 1.144 [1.019-1.269]; SDT = 0.163, g/cm2) and control group (XC [95% CI] = 1.193 [1.073-1.313]; SDC = 0.157, g/cm2) were worked out respectively for the selected studies. Finally, a comparison between grouped means of steroid-treated and control groups was done by two-sample t-test at the 5% level of significance. The results of the meta-analysis showed that although the mean BMD of the steroid-treated group was reduced by 4.1% as compared to the control group, this failed to achieve statistical significance (p = 0.8; 95% CI for the mean difference between two groups = 0.028-0.070 g/cm2). It is concluded that inhaled steroids for the treatment of asthma can be considered safe with respect to their effect on bone loss.


Dynamin inhibitor impairs Toxoplasma gondii invasion.
The protozoan parasite Toxoplasma gondii infects its host cells through an active mechanism. In this work, we obtained evidence that host cells also play a fundamental role during the infection process. We found that previous incubation of the host cells, but not the parasites, with Dynasore, a small molecule that inhibits dynamin GTPase activity, markedly reduced the penetration of T. gondii tachyzoites into LLC-MK2 cells. In contrast, parasite adhesion to the host cell surface increased, as observed both by light and electron microscopy. Intriguingly, the few parasites internalized by Dynasore-treated cells remained in vacuoles located at the periphery of the cell, in contrast to the perinuclear localization seen in the control.


The epidermal growth factor receptor and the product of the neu protooncogene are members of a receptor tyrosine phosphorylation cascade.
The protein product of the neu protooncogene, p185, is a tyrosine kinase with a high degree of sequence homology to the epidermal growth factor (EGF) receptor. Although p185 does not bind EGF, EGF stimulates tyrosine phosphorylation of p185. To determine the mechanism of this interaction we have used a vaccinia virus/bacteriophage T7-based transient gene expression system to induce production of normal and kinase-deficient forms of p185 in the absence and presence of EGF receptors. Tyrosine phosphorylation of kinase-deficient p185 was observed, but only in the presence of the EGF receptor. These findings strongly support the hypothesis that p185 is a substrate for the EGF receptor tyrosine kinase in a tyrosine kinase cascade.