A narrative review: current upper limb prosthetic options and design.
Purpose: This review was conducted to provide an overview of current literature as it relates to upper limb difference, available componentry, and prosthetic options and design. Emerging technologies combined with an increased awareness of the limb difference community have contributed to recent advancements in upper extremity prosthetics.Methods: A search of five major clinical databases utilizing keywords relating to upper limb prostheses, componenty and limb difference levels resulted in over 1200 articles. These articles were subjected to inclusion and exclusion criteria in order to identify current peer reviewed research relevant to this topic.Results: Fifty-five applicable articles and sources of standards were reviewed based on the inclusion and exclusion criteria, presenting five general options for prosthetic intervention. This information was assimilated and categorized in this article, which provides an overview of the aforementioned options.Conclusion: While a noteworthy amount of research focuses on technological advancements, the five options for prosthetic intervention are inherently represented in the current literature. For individuals with upper limb difference, as well as their care team, successful rehabilitation hinges on awareness of new components, the functional efficacy of these components, and the evolved techniques used in prosthetic design and fabrication. It is noted that the rapid evolution of upper limb prosthetics consistently outpaces research and publication of information.Implications for rehabilitationTo provide an overview of prosthetic design considerations and options to help create a more informed rehabilitation team, leading to improved outcomes in prescription and management of upper limb prosthetics.To bring awareness of current research in the field of upper limb prosthetics in order to provoke further exploration of the efficacy of prosthetic options and design considerations.


G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells.
Regulator of G protein Signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates both conventional and unconventional G protein signaling pathways. Like other RGS (regulator of G protein signaling) proteins, RGS14 acts as a GTPase accelerating protein to terminate conventional Gα(i/o) signaling. However, unlike other RGS proteins, RGS14 also contains a G protein regulatory/GoLoco motif that specifically binds Gα(i1/3)-GDP in cells and in vitro. The non-receptor guanine nucleotide exchange factor Ric-8A can bind and act on the RGS14·Gα(i1)-GDP complex to play a role in unconventional G protein signaling independent of G protein-coupled receptors (GPCRs). Here we demonstrate that RGS14 forms a Gα(i/o)-dependent complex with a G(i)-linked GPCR and that this complex is regulated by receptor agonist and Ric-8A (resistance to inhibitors of cholinesterase-8A). Using live cell bioluminescence resonance energy transfer, we show that RGS14 functionally associates with the α(2A)-adrenergic receptor (α(2A)-AR) in a Gα(i/o)-dependent manner. This interaction is markedly disrupted after receptor stimulation by the specific agonist UK14304, suggesting complex dissociation or rearrangement. Agonist-mediated dissociation of the RGS14·α(2A)-AR complex occurs in the presence of Gα(i/o) but not Gα(s) or Gα(q). Unexpectedly, RGS14 does not dissociate from Gα(i1) in the presence of stimulated α(2A)-AR, suggesting preservation of RGS14·Gα(i1) complexes after receptor activation. However, Ric-8A facilitates dissociation of both the RGS14·Gα(i1) complex and the Gα(i1)-dependent RGS14·α(2A)-AR complex after receptor activation. Together, these findings indicate that RGS14 can form complexes with GPCRs in cells that are dependent on Gα(i/o) and that these RGS14·Gα(i1)·GPCR complexes may be substrates for other signaling partners such as Ric-8A.


Finding and estimating chemical property data for environmental assessment.
The ability to predict the behavior of a chemical substance in a biological or environmental system largely depends on knowledge of the physicochemical properties and reactivity of that substance. We focus here on properties, with the objective of providing practical guidance for finding measured values and using estimation methods when necessary. Because currently available computer software often makes it more convenient to estimate than to retrieve measured values, we try to discourage irrational exuberance for these tools by including comprehensive lists of Internet and hard-copy data resources. Guidance for assessors is presented in the form of a process to obtain data that includes establishment of chemical identity, identification of data sources, assessment of accuracy and reliability, substructure searching for analogs when experimental data are unavailable, and estimation from chemical structure. Regarding property estimation, we cover estimation from close structural analogs in addition to broadly applicable methods requiring only the chemical structure. For the latter, we list and briefly discuss the most widely used methods. Concluding thoughts are offered concerning appropriate directions for future work on estimation methods, again with an emphasis on practical applications.


Association analysis of Arg16Gly polymorphism of the beta2-adrenergic receptor gene in offspring from hypertensive and normotensive families.
Since beta2-adrenergic receptors (beta2AR) can influence blood pressure not only by vasodilation, but also participate in noradrenaline release from sympathetic nerve endings, we have studied whether Arg16Gly polymorphism of the beta2AR gene is associated with predisposition to essential hypertension and increased plasma noradrenaline concentration in offspring from normotensive (SN) and hypertensive parents (SH). The study population consisted of 105 young SN and 101 SH subjects matched for age and body mass index. Arg16Gly polymorphism of the beta2AR gene was determined by polymerase chain reaction (PCR) technique and subsequent incubation with NcoI restriction enzyme. Resulting fragments were separated using electrophoresis on a 4.2% Metaphor agarose gel. SH already had significantly higher systolic BP, and a tendency to higher diastolic BP than the SN group. The frequency of Arg/Arg homozygotes was significantly increased in SH when compared to SN (25% vs 15%). Results of logistic regression analysis showed the highest relative risk for the Arg/Arg genotype and suggested a recessive action of the Arg16 variant. There was an increased diastolic BP in Arg/Arg homozygotes of the SN group (p = 0.029). This genotype also had a tendency to increased heart rate in both groups (p = 0.049). There was no relationship of this polymorphism with plasma noradrenaline concentration. Our findings suggest that genetic variability of the beta2AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the beta2AR gene is indirect, through multiple intermediate phenotypes and gene interactions.


A two-dimensional MXene-supported metal-organic framework for highly selective ambient electrocatalytic nitrogen reduction.
The conversion of nitrogen into ammonia is crucial for human activities. The electrochemical synthesis of ammonia from nitrogen and water is a green process with great application prospects; to this end, much effort has been made to improve the catalytic activity and selectivity. Here, a Co-based metal-organic framework (MOF), that is, zeolitic imidazolate framework-67 (ZIF-67), supported on a Ti3C2 MXene (defined as ZIF-67@Ti3C2) was prepared via in situ growth. Due to the high porosity and large active surface area of the MOF and the superior conductivity of the Ti3C2 MXene, the composite could efficiently synthesize ammonia electrochemically. In particular, the prepared ZIF-67@Ti3C2 catalyst exhibited an excellent NH3 yield (6.52 μmol h-1 cm-2), significantly higher than those achieved by Ti3C2 and ZIF-67 (2.77 and 1.61 μmol h-1 cm-2, respectively) alone, and good Faraday efficiency (20.2%) at -0.4 V (vs. the reversible hydrogen electrode). This study not only expands the application of the MXene family in the electrochemical nitrogen reduction reaction but also provides ideas for the development of high-performance electrocatalysts for NRR.


Gastric emptying and first-pass metabolism of ethanol in elderly subjects with and without atrophic gastritis.
Oral ethanol intake results in lower blood ethanol concentrations than intravenous administration of the same dose of ethanol. This first-pass metabolism is thought to be due to gastric metabolism of ethanol via alcohol dehydrogenase and also to hepatic first-pass metabolism. Since a loss of gastric mucosa may decrease first-pass metabolism of ethanol, this metabolism was studied in 10 elderly subjects (6 women and 4 men) with atrophic gastritis and bacterial overgrowth and in 17 control subjects with normal gastric secretory function. Atrophic gastritis was verified by means of the serum pepsinogen I to pepsinogen II ratio and the hypochlorhydria occurring after pentagastrin stimulation. Bacterial overgrowth was assessed by bacteria. In addition, gastric emptying rates of ethanol solution with technetium-99m sulfur colloid were calculated from scintigraphic images. Furthermore, gastric biopsy specimens were taken from 12 female patients with atrophic gastritis and from 12 controls for determination of alcohol dehydrogenase activity. Neither gender (female versus male, 28 +/- 5% versus 42 +/- 5%), atrophic gastritis (normal versus atrophic gastritis, 35 +/- 4% versus 32 +/- 6%), nor tetracycline treatment in atrophic gastritis subjects (before versus after, 32 +/- 6% versus 41 +/- 5%) had a statistically significant effect on the first-pass metabolism of ethanol in the elderly. Gastric alcohol dehydrogenase activity was significantly lower in atrophic gastritis subjects than in controls (p < 0.01). A significant correlation was found between the first-pass metabolism of ethanol in healthy controls and gastric half-emptying time (p = 0.032). We conclude from these data that the rate of gastric emptying modulates first-pass metabolism of ethanol in elderly individuals.


Geographical mobility research with panel data.
"The objective of this article is to introduce panel survey data and to demonstrate its value for geographical mobility research [in the United States]. A brief history of panel surveys is provided that emphasizes the blossoming of this form of data collection during the past two decades. The potential utility of the Census Bureau's new Survey of Income and Program Participation is discussed at some greater length."


Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice.
The significance of the peripheral immune system in Alzheimer's disease pathogenesis remains controversial. To study the CNS invasion of hematopoietic cells in the course of cerebral amyloidosis, we used a green fluorescence protein (GFP)-bone marrow chimeric amyloid precursor protein transgenic mouse model (APP23 mice). No difference in the number of GFP-positive invading cells was observed between young APP23 mice and nontransgenic control mice. In contrast, in aged, amyloid-depositing APP23 mice, a significant increase in the number of invading ameboid-like GFP-positive cells was found compared with age-matched nontransgenic control mice. Interestingly, independent of the time after transplantation, only a subpopulation of amyloid deposits was surrounded by invading cells. This suggests that not all amyloid plaques are a target for invading cells or, alternatively, all amyloid plaques attract invading cells but only for a limited time, possibly at an early stage of plaque evolution. Immunological and ultrastructural phenotyping revealed that macrophages and T-cells accounted for a significant portion of these ameboid-like invading cells. Macrophages did not show evidence of amyloid phagocytosis at the electron microscopic level, and no obvious signs for T-cell-mediated inflammation or neurodegeneration were observed. The observation that hematopoietic cells invade the brain in response to cerebral amyloidosis may hold an unrecognized therapeutic potential.


[Drug-induced cholestasis].
Cholestasis is one kind of reaction of the liver to intolerable drugs. It is estimated that 2% of the patients who are treated for icterus in hospital suffer from drug intolerance. A differentiation is made between obligtory and optional liver-damaging substances. The latter are clinically important because they occur far more frequently. In principle nearly every drug may cause cholestasis, which must be taken into consideration especially with newly introduced drugs, e.g. in cholestasis caused by co-enzyme-A-reductase inhibitors in the treatment of hypercholesterinaemia. Cholestasis is most likely to occur after administration of the following group of substances: antiarrhythmics, antibiotics, tuberculostatics, salicylates, immunosuppressives, narcotics, tranquilizers, some antirheumatics, antidepressants, anticonvulsives, and sex hormones. This list does not claim to be complete or to be in any order of frequency.


Transumbilical single-incision laparoscopic cholecystectomy: preliminary experiences.
As safe techniques and adequate equipment are easily accessible, the minimally invasive approach to cholecystectomy has become the gold standard over the last decade. Nowadays, further minimally invasive techniques using only 1 skin incision to gain access to the abdominal cavity have become available. Transvaginal, transcolonic, or transgastric approaches have recently been described. We present a laparoscopic single-incision transumbilical approach to cholecystectomy with commonly used laparoscopic instruments.


FDG PET/CT in Immunoglobulin G4-Related Spinal Hypertrophic Pachymeningitis.
A 49-year-old woman complained of right upper back pain for 1 month. Serum tests showed increased erythrocyte sedimentation rate. Thoracic spinal MRI showed an epidural lesion at the T1-T4 level with inhomogeneous signal intensity on T2-weighted images, slightly higher signal intensity than spinal cord on T1-weighted images, and remarkable enhancement on enhanced T1-weighted images. Epidural malignant tumor was suspected. FDG PET/CT was performed showing increased FDG uptake of the lesion extending to the right T1-T2 and T2-T3 neural foramina. A decompressive posterior thoracic laminectomy with the lesion resection was performed. Immunoglobulin G4-related spinal hypertrophic pachymeningitis was confirmed by pathology.


A bootstrap approach for assessing the uncertainty of outcome probabilities when using a scoring system.
Scoring systems are a very attractive family of clinical predictive models, because the patient score can be calculated without using any data processing system. Their weakness lies in the difficulty of associating a reliable prognostic probability with each score. In this study a bootstrap approach for estimating confidence intervals of outcome probabilities is described and applied to design and optimize the performance of a scoring system for morbidity in intensive care units after heart surgery. The bias-corrected and accelerated bootstrap method was used to estimate the 95% confidence intervals of outcome probabilities associated with a scoring system. These confidence intervals were calculated for each score and each step of the scoring-system design by means of one thousand bootstrapped samples. 1090 consecutive adult patients who underwent coronary artery bypass graft were assigned at random to two groups of equal size, so as to define random training and testing sets with equal percentage morbidities. A collection of 78 preoperative, intraoperative and postoperative variables were considered as likely morbidity predictors. Several competing scoring systems were compared on the basis of discrimination, generalization and uncertainty associated with the prognostic probabilities. The results showed that confidence intervals corresponding to different scores often overlapped, making it convenient to unite and thus reduce the score classes. After uniting two adjacent classes, a model with six score groups not only gave a satisfactory trade-off between discrimination and generalization, but also enabled patients to be allocated to classes, most of which were characterized by well separated confidence intervals of prognostic probabilities. Scoring systems are often designed solely on the basis of discrimination and generalization characteristics, to the detriment of prediction of a trustworthy outcome probability. The present example demonstrates that using a bootstrap method for the estimation of outcome-probability confidence intervals provides useful additional information about score-class statistics, guiding physicians towards the most convenient model for predicting morbidity outcomes in their clinical context.


Fine mapping of Pi57(t) conferring broad spectrum resistance against Magnaporthe oryzae in introgression line IL-E1454 derived from Oryza longistaminata.
Wild species of the genus Oryza are excellent gene pools for improvement of agronomic traits of Asian cultivated rice. The blast resistance gene Pi57(t) in the introgression line IL-E1454 derived from Oryza longistaminata was previously mapped on rice chromosome 12. Inoculation with 322 Magnaporthe oryzae isolates collected from 6 countries indicated that Pi57(t) conferred broad spectrum resistance against M. oryzae. Two mapping populations consisting of 29070 and 10375 F2 plants derived from the crosses of resistant donor IL-E1454 with susceptible parents RD23 and Lijiangxintuanheigu respectively, were used for fine mapping of Pi57(t) locus. Based on genotyping and phenotyping results of recombinants screened from the two crosses, Pi57(t) was finally mapped to a 51.7-kb region flanked by two molecular markers (STS57-320 and STS57-372) on the short arm and close to the centromere of chromosome 12. Six candidate resistance genes were predicted in the target region according to the reference sequence of Nipponbare. These results could facilitate both marker-assisted selection for disease-resistant breeding and gene cloning.


Estimating passive mechanical properties in a myocardial infarction using MRI and finite element simulations.
Myocardial infarction (MI) triggers a series of maladaptive events that lead to structural and functional changes in the left ventricle. It is crucial to better understand the progression of adverse remodeling, in order to develop effective treatment. In addition, being able to assess changes in vivo would be a powerful tool in the clinic. The goal of the current study is to quantify the in vivo material properties of infarcted and remote myocardium 1 week after MI, as well as the orientation of collagen fibers in the infarct. This will be accomplished by using a combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numerical optimization to analyze a porcine model ([Formula: see text]) of posterolateral myocardial infarction. Specifically, properties will be determined by minimizing the difference between in vivo strains and volume calculated from MRI and finite element model predicted strains and volume. The results indicate that the infarct region is stiffer than the remote region and that the infarct collagen fibers become more circumferentially oriented 1 week post-MI. These findings are consistent with previous studies, which employed ex vivo techniques. The proposed methodology will ultimately provide a means of predicting remote and infarct mechanical properties in vivo at any time point post-MI.


Case report: high-grade atrioventricular block in suspected COVID-19 myocarditis.
In the ongoing pandemic of COVID-19, respiratory failure has been reported as the main cause of death in those who develop critical illness. A few cases of concurrent myocarditis have been reported, but the extent of cardiac complications with the SARS-CoV-2 strain of coronavirus is still largely unknown. A 53-year-old man, suspected to have COVID-19 due to a new-onset cough, shortness of breath, and hypoxia, was referred to Cardiology with sudden symptomatic bradycardia. Initial rhythm analysis revealed Type 2 atrioventricular block (Mobitz II). On arrival at the coronary care unit, he was found to be in complete heart block (Type 3). Routine blood tests showed normal electrolytes and renal function, and no elevation in troponin-I levels. Echocardiography showed mild impairment in left ventricular systolic function, with no regional wall motion abnormalities or valvular lesions. He then developed high-degree AV block lasting 6.2 s, prompting the need for an urgent permanent pacemaker implantation. Just over a third of patients with myocarditis reportedly develop a rise in cardiac troponin. Clinically suspected myocarditis can occur in the absence of a troponin rise and rarely can cause high-grade bradyarrhythmias. Myocarditis and non-specific cardiac arrhythmias have been reported in a few cases of COVID-19, but this is the first reported case of a high-grade atrioventricular conduction block with SARS-CoV-2 infection.


Tailoring online information retrieval to user's needs based on a logical semantic approach to natural language processing and UMLS mapping.
Depression can derail teenagers' lives and cause serious chronic health problems. Acquiring pertinent knowledge and skills supports care management, but retrieving appropriate information can be difficult. This poster presents a strategy to tailor online information to user attributes using a logical semantic approach to natural language processing (NLP) and mapping propositions to UMLS terms. This approach capitalizes on existing NLM resources and presents a potentially sustainable plan for meeting consumers and providers information needs.


Maternal Rest/Nrsf Regulates Zebrafish Behavior through snap25a/b.
During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. Adult male fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternal rest in blastula stage embryos. Furthermore, we found that maternal rest is required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in either snap25a or snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest Both maternal rest mutants and snap25a RE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts. Maternal factors deposited in the oocyte have well-established roles during embryonic development. We show that, in zebrafish, maternal rest (RE1-silencing transcription factor) regulates expression of target genes during larval development and has lifelong impacts on behavior. The Rest transcriptional repressor interacts with chromatin-modifying complexes to limit transcription of neural genes. We identify several synaptic genes that are repressed by maternal Rest and demonstrate that snap25a/b are key targets of maternal rest that modulate larval locomotor activity. These results reveal that zygotic rest is unable to compensate for deficits in maternally supplied rest and uncovers novel temporal requirements for Rest activity, which has implications for the broad roles of Rest-mediated repression during neural development and in disease states.


Will the PCSK9 Inhibitors Be Employers' "Line in the Sand"?
After the introductions of sofosbuvir (Sovaldi) and ledipasvir plus sofosbuvir (Harvoni) for the treatment of hepatitis C, employers have become very sensitive to new, and especially unforeseen, factors that significantly raise healthcare costs. With the recent launch of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, self-insured and fully insured employers have been seeking information on this drug class and its potential for off-label use, which could amount to up to $23 billion in healthcare expenditures, according to a report from Prime Therapeutics. Based on their approved indications, 0.4% of commercial members may be eligible to use PCSK9 inhibitors, at a cost of $3.29 per member per month. Corporate employers are evaluating their options to manage the new expense associated with the novel PCSK9 inhibitors.


Predictions of spatially averaged cadmium contents in rice grains in the Fuyang Valley, P.R. China.
Soils in the Fuyang valley (Zhejiang province, southeast China) have been contaminated by heavy metals. Since rice (Oryza sativa L.) is the dominant crop in the valley and because of its tendency to accumulate Cd in its grains, assessment of the human health risk resulting from consumption of locally produced rice is needed. In this study, we used a regression model to predict the average Cd content in rice grains for paddy fields. The multiple linear model for log(Cd) content in rice grains with log(HNO(3)-Cd), pH, log(clay), and log(soil organic matter, SOM) as predictors performed much better (R(2)(adj) = 66.1%) than the model with log(CaCl(2)-Cd) as a single predictor (R(2)(adj) = 28.1%). This can be explained by the sensitivity of CaCl(2)-extracted Cd for changes in redox potential and as a result of the drying of the soil samples in the laboratory. Consequently, the multiple linear model was used to predict the average Cd contents in rice grains for paddy fields, and to estimate the probability that the FAO/WHO standard of 0.2 mg kg(-1) will be exceeded. Eleven blocks had a probability smaller than 10% of exceeding this standard (safe blocks). If a lognormal distribution is assumed, 35 blocks had a probability larger than 90% (blocks at risk). Hence, risk reduction measures should be undertaken for the blocks at risk. For 27 blocks the probability was between 10 and 90%. For these blocks the uncertainty should be reduced via improvement of the regression model and/or increasing the number of sample locations within blocks.


Effects of amantadine in children with impaired consciousness caused by acquired brain injury: a pilot study.
To conduct a pilot study of amantadine in children with impaired consciousness caused by acquired brain injury, to establish design feasibility, and to assess the effect on level of arousal and consciousness. Randomized, double-blind, placebo-controlled crossover trial. Seven subjects (mean age, 12.7 yrs) with an acquired brain injury (mean duration, 6 wks) were randomized to receive either 3 wks of placebo or amantadine, followed by a 1-wk washout period and then 3 wks of the other agent. Main outcome measures were the Coma/Near-Coma Scale and Coma Recovery Scale-Revised, each done three times per week. Subjective evaluations of change in arousal and consciousness by the parent and physician were done weekly. Five subjects completed the study. There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies.


Environmental, policy, and cultural factors related to physical activity among Latina immigrants.
According to national surveillance studies, participation in leisure-time physical activity remains low among minority women. Furthermore, the correlates of such activity in this group are not well understood. To better understand the environmental, policy, and sociocultural correlates of physical activity among Latina immigrants, six focus groups were conducted in rural North Carolina. Among the 49 participants, median age was 32 years and median education 11 years. Participants were first generation immigrants from Mexico (n = 43), El Salvador (n = 3), Colombia (n = 1), the Dominican Republic (n = 1), and Honduras (n = 1). Environmental and policy barriers to activity were identified, including transportation, lack of facilities, cost, and safety. Sociocultural correlates of activity included gender roles for activity, importance of support from the family and husband, child care issues tied to having few relatives who lived close by, language, and isolation in the community. The women suggested changes and programs that could promote physical activity through multiple channels, especially involving the family. This information can be used to develop culturally appropriate interventions to increase physical activity among Latinas.


[Process of "aseri" as experienced in the daily life of young adults].
"Aseri" is a Japanese term referring to an emotional state of "being impatient" or "feeling time urgency" that is experienced in everyday life. This study explored how people in early adulthood experienced aseri in their daily lives. Interviews were conducted with twenty young adults who recalled events or situations involving aseri. Grounded theory was referred in collection and analysis of data. The results showed that aseri developed in situations where there were several competing thoughts. Regarding the process in which aseri changed, two patterns were found: (a) when aseri was strongly experienced in the short term, it settled down easily; (b) when aseri was felt mildly in the long term, it gradually became latent. The theme of latent aseri reflected the developmental tasks of early adulthood that were considered significant for the participants including developmental tasks typically achieved in adolescence that were put off until early adulthood. Implications for aseri and directions for further research are discussed.


Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity.
The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin(+) dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin(+) DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically applied antigen to draining lymph nodes and reduced CHS in the absence of all Langerin(+) skin DC. In this study, we demonstrate that mice with a selective depletion of LC exhibit attenuated CHS only upon sensitization with a low hapten dose but not with a high hapten dose. In contrast, when painting a higher concentration of hapten onto the skin, which leads to increased antigen dissemination into the dermis, CHS is still diminished in mice lacking all Langerin(+) skin DC. Taken together, these data suggest that the magnitude of a CHS reaction depends on the number of skin DC, which have access to the hapten, rather than on the presence or absence of a particular skin DC population. LC and (Langerin(+)) dermal DC thus seem to have a redundant function in regulating CHS.


A novel gonadotropin-regulated testicular RNA helicase. A new member of the dead-box family.
A gonadotropin-regulated testicular RNA helicase (GRTH) was identified and characterized. GRTH cloned from rat Leydig cell, mouse testis, and human testis cDNA libraries is a novel member of the DEAD-box protein family. GRTH is transcriptionally up-regulated by chorionic gonadotropin via cyclic AMP-induced androgen formation in the Leydig cell. It has ATPase and RNA helicase activities and increases translation in vitro. This helicase is highly expressed in rat, mouse, and human testes and weakly expressed in the pituitary and hypothalamus. GRTH is produced in both somatic (Leydig cells) and germinal (meiotic spermatocytes and round haploid spermatids) cells and is developmentally regulated. GRTH predominantly localized in the cytoplasm may function as a translational activator. This novel helicase could be relevant to the control of steroidogenesis and the paracrine regulation of androgen-dependent spermatogenesis in the testis.


Platelets and cytokines.
Cytokines that are capable of stimulating megakaryocytopoiesis provide new approaches to ameliorate clinical thrombocytopenia. Administration of non-lineage-specific factors that promote megakaryocytic progenitor cell proliferation has been shown to increase platelet counts following chemotherapy. Preclinical and preliminary clinical studies have shown that cytokines that enhance maturation of megakaryocytes also accelerate platelet recovery. Combinations of factors may prove even more efficacious and novel approaches to enhance platelet recovery using mobilized peripheral blood stem cells have been introduced. Lineage-specific cytokines may appear in the near future. The notion that platelet function might be enhanced with cytokines has been proposed; whether this will translate into clinical utility is not clear. Despite this recent progress in the development of thrombopoietic cytokine therapy, an important but unresolved matter is the establishment of precise clinical indications for such treatment.


Relation of autonomous and interleukin-2-responsive growth of leukemic cells to survival in adult T-cell leukemia.
We examined autonomous and interleukin-2 (IL-2)-responsive growth activities of leukemic cells derived from peripheral blood, as well as several clinical manifestations, including serum lactate dehydrogenase (LDH) level, of 35 patients with adult T-cell leukemia (ATL) to determine whether these properties were related to prognosis. Growth activities were measured by [3H]-thymidine incorporation of the cells after 24 hours' culture with or without exogenous IL-2. Both autonomous and IL-2-responsive growth activities were higher in the patients than in healthy controls and were significantly correlated with each other (P < .0001, r = .956). Both higher growth activities were significantly associated with shorter survival times (P = .0042, r = .472 and P = .0117, r = .421, respectively). An increased serum LDH value was also significantly associated with shorter survival times (P = .0011, r = .530), but corrected calcium level, sex, white blood cell count, or age were not. These results strongly suggest that both growth activities of primary tumor cells, in addition to the serum LDH value, are prognostic determinants in ATL. We propose a new prognostic classification combining LDH values and autonomous growth activity into three groups: (1) high growth activity and high LDH; (2) high growth activity and low LDH, or low growth activity and high LDH; and (3) low growth activity and low LDH, which showed a significant relationship to survival time (P = .0014; the median survival time for each group was 39, 94, and 340 days, respectively).


Cytokine targeting in psoriasis and psoriatic arthritis: beyond TNFalpha.
Targeting TNFalpha provided proof of concept for the role of pro-inflammatory cytokines in promoting cutaneous inflammation, particularly psoriasis. Recent studies have elucidated the presence of numerous cytokine and chemokine activities in psoriatic skin and synovium. There is considerable interest in the potential of such activities as novel therapeutic targets. IL-15 is an innate response cytokine that activates leukocyte subsets via binding to its unique IL-15Ralpha and shared beta and gamma chain receptors. IL-15 promotes T cell memory and sustains local T cell activation, in part via prevention of apoptosis and mediates activation of monocytes, neutrophils and NK cells. IL-15 is up-regulated in psoriatic skin and psoriatic arthritis synovium. IL-15 blockade in a murine model of psoriasis led to marked suppression of typical psoriatic skin features. Clinical intervention in other chronic inflammatory disease states is now ongoing with encouraging early efficacy, raising the possibility for the first time of targeting this novel inflammatory moiety in psoriasis.


Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells.
The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus. This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES). Cells were treated with proinflammatory molecules and mimics of infection [lipopolysaccharide (LPS) and lipoteichoic acid (LTA)]. mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR. HBD1 mRNA was present at very low levels preventing conclusive study of its regulation. However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha. SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha. LPS had little effect on antimicrobial expression. However, there was a trend towards increased expression with LTA treatment for 4-8 h. Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment. These results suggest that in endometrium some natural antibiotics (e.g. SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g. HBD2) are inducible allowing maximal antimicrobial activity during infection. Natural antimicrobials will have an important role in endometrium in protecting against infection.


Native lattice strain induced structural earthquake in sodium layered oxide cathodes.
High-voltage operation is essential for the energy and power densities of battery cathode materials, but its stabilization remains a universal challenge. To date, the degradation origin has been mostly attributed to cycling-initiated structural deformation while the effect of native crystallographic defects induced during the sophisticated synthesis process has been significantly overlooked. Here, using in situ synchrotron X-ray probes and advanced transmission electron microscopy to probe the solid-state synthesis and charge/discharge process of sodium layered oxide cathodes, we reveal that quenching-induced native lattice strain plays an overwhelming role in the catastrophic capacity degradation of sodium layered cathodes, which runs counter to conventional perception-phase transition and cathode interfacial reactions. We observe that the spontaneous relaxation of native lattice strain is responsible for the structural earthquake (e.g., dislocation, stacking faults and fragmentation) of sodium layered cathodes during cycling, which is unexpectedly not regulated by the voltage window but is strongly coupled with charge/discharge temperature and rate. Our findings resolve the controversial understanding on the degradation origin of cathode materials and highlight the importance of eliminating intrinsic crystallographic defects to guarantee superior cycling stability at high voltages.


1,25-dihydroxyvitamin D3 protects against macrophage-induced activation of NFκB and MAPK signalling and chemokine release in human adipocytes.
Increased accumulation of macrophages in adipose tissue in obesity is linked to low-grade chronic inflammation, and associated with features of metabolic syndrome. Vitamin D3 may have immunoregulatory effects and reduce adipose tissue inflammation, although the molecular mechanisms remain to be established. This study investigated the effects of vitamin D3 on macrophage-elicited inflammatory responses in cultured human adipocytes, particularly the signalling pathways involved. Macrophage-conditioned (MC) medium (25% with adipocyte maintenance media) markedly inhibited protein expression of the nuclear factor-κB (NFκB) subunit inhibitor κBα (IκBα) (71%, P<0.001) and increased NFκB p65 (1.5-fold, P = 0.026) compared with controls. Treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) abolished macrophage-induced activation of NFκB signalling by increasing IκBα expression (2.7-fold, P = 0.005) and reducing NFκB p65 phosphorylation (68%; P<0.001). The mitogen-activated protein kinase (MAPK) signalling was activated by MC medium, which was also blunted by 1,25(OH)2D3 with a downregulation of phosphorylated p38 MAPK (32%, P = 0.005) and phosphorylated Erk1/2 (49%, P = 0.001). Furthermore, MC medium (12.5% or 25%) dose-dependently upregulated secretion of key proinflammatory chemokines/cytokines (22-368-fold; all P<0.001) and this was significantly decreased by 1,25(OH)2D3: IL-8 (61% and 31%, P<0.001), MCP-1 (37%, P<0.001 and 36%, P = 0.002), RANTES (78% and 62%, P<0.001) and IL-6 (29%, P<0.001 and 34%, P = 0.019). Monocyte migration-elicited by adipocytes treated with 1,25(OH)2D3 was also reduced (up to 25%, P<0.001). In conclusion, vitamin D3 could be anti-inflammatory in adipose tissue, decreasing macrophage-induced release of chemokines and cytokines by adipocytes and the chemotaxis of monocytes. Our data suggests these effects are mediated by inhibition of the NFκB and MAPK signalling pathways.


The tribology of metal-on-metal total hip replacements.
Total hip surgery is an effective way of alleviating the pain and discomfort caused by diseased or damaged joints. However, in the majority of cases, these joints have a finite life. The main reason for failure is osteolysis (bone resorption). It is well documented that an important cause of osteolysis, and therefore the subsequent loosening and failure of conventional metal- or ceramic-on-ultra-high molecular weight polyethylene joints, is the body's immunological response to the polyethylene wear particles. To avoid this, interest has been renewed in metal-on-metal joints. The intention of this paper is to review the studies that have taken place within different laboratories to determine the tribological performance of new-generation metal-on-metal total hip replacements. These types of joint offer a potential solution to enhance the longevity of prosthetic hip systems; however, problems may arise owing to the effects of metal ion release, which are, as yet, not fully understood.


Sugar-sweetened beverages consumption is associated with worse cognitive functions in older adults: from the national health and nutrition examination survey and food patterns equivalents database.
Objectives: This study aimed to investigate the association between sugar-sweetened beverages (SSB) consumption (including individual SSB) and cognitive function from the National Health and Nutrition Examination Survey (NHANES) and Food Patterns Equivalents Database (FPED) and whether it is age-dependent.Methods: Older adults aged 60 years old and over were included during the NHANES 2011-2014. SSB consumption was defined as the amount of added sugar obtained by connecting the NHANES and FPED. Cognitive function tests included the consortium to establish a registry for Alzheimer's disease test, Animal Fluency Test and Digit Symbol Substitution Test. We calculated z-score using the average of the total standardized scores on three cognitive tests to estimate the level of whole cognition. Multi-variable linear regression models and interaction analysis were conducted in this study.Results: For individual SSB types, increased carbonated soft drinks, sweetened tea, fruit drinks, energy drinks, and sport drinks were all significantly linked to declined cognitive function (P < 0.05), respectively. Nevertheless, interaction effects by age groups were not significant (P for interaction > 0.05).Discussion: SSB consumption (including individual SSB) was negatively associated with cognitive function, which was not age-dependent. Future studies may advance the knowledge in the field considering the association between SSB consumption and cognitive function.


Photoregulation of RNA digestion by RNase H with azobenzene-tethered DNA.
RNA digestion by RNase H, which is responsible for the antisense effect, was efficiently photoregulated by use of the duplex of azobenzene-tethered sense DNA and native antisense DNA. In the dark, RNA digestion was suppressed because antisense DNA was strongly hybridized with azobenzene-tethered sense DNA, and accordingly RNA was isolated. On UV irradiation, antisense DNA was released from the azobenzene-tethered DNA due to the trans-to-cis isomerization and hybridized with RNA, which was digested by RNase H.


[Image guided stereotactic biopsy for brain tumors: experience of 71 cases].
Despite advances in the neuroimaging of the brain, an accurate diagnosis of intrinsic lesion of the brain requires tissue sampling and histological verification. Seventy-one patients with intraparenchymal lesion of the brain underwent CT or MRI-directed stereotactic biopsy at Okayama University Hospital between June, 1987 and March, 1995. There were 32 men and 39 women whose ages ranged between 7 and 78 years (mean 46.1 years). All patients underwent preoperative cerebral angiography, high resolution contrast enhanced CT and MRI. The lesions were located in the hemisphere in 40 cases, the thalamus or basal ganglia in 14, the midline (corpus callosum or ventricle) in 11, the pineal region in 4, the suprasellar in one and multiple sites in one. A Brown-Roberts-Wells (BRW) CT-directed stereotactic system was used for biopsy under CT guidance. For MRI-directed biopsies a prototype modification of the BRW frame was employed. Target localization was performed using either CT or MRI. Usually one or two targets within the lesion were chosen and target coordinates were calculated using the CT or MRI scan soft ware. Positive diagnosis was obtained in 67 cases and the accuracy of the histological diagnosis was 94.4%. There were 53 gliomas, 4 metastasis, 5 germinomas, 3 malignant lymphomas, one pineoblastoma, one infarction and 4 negative biopsies. Bleeding as a complication due to stereotactic intervention occurred in one patient (1.4%). To patients with potentially inoperable lesions or lesions which might be best treated by chemotherapy or irradiation, modern techniques of neurosurgery now offer the option of precise stereotactic biopsy through small twist-drill burr holes as opposed to open biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement Predictors in a Workplace Program Promoting Healthy Lifestyle Habits.
The baseline characteristics of employees to predict improvements in healthy lifestyle habits (LHs) following workplace health promotion programs are underexplored. This study sought to identify predictors of improvements in physical activity (PA), eating habits, sleep habits, and stress management, and health risk factors resulting from healthy LHs. The Activate Your Health program included 3 packages of an increasing number of interventions: light, moderate, and high. Participating employees (n = 506) completed baseline and postintervention questionnaires that collected sociodemographic data, health- and LH-related variables, stress-related variables, and perceptions of general health and life satisfaction. Only those with the potential to improve were included in each improvement outcome analysis. Being in high and intending to reduce alcohol consumption increased the odds of improving PA. Very good/excellent perceived general health, poor sleep habits, high alcohol consumption, and intending to improve stress management increased the odds of improving stress levels at work. Depression and intending to improve sleep habits increased the odds of improving stress management. Reporting feelings of pleasure increased the odds of improving body mass index. Baseline characteristics predicting improvements differed for each LH. A targeted approach may be needed to help employees improve LHs and related outcomes.


Modifying Hata-Davidson Propagation Model for Remote Sensing in Complex Environments Using a Multifactional Drone.
The coupling of drones and IoT is a major topics in academia and industry since it significantly contributes towards making human life safer and smarter. Using drones is seen as a robust approach for mobile remote sensing operations, such as search-and-rescue missions, due to their speed and efficiency, which could seriously affect victims' chances of survival. This paper aims to modify the Hata-Davidson empirical propagation model based on RF drone measurement to conduct searches for missing persons in complex environments with rugged areas after manmade or natural disasters. A drone was coupled with a thermal FLIR lepton camera, a microcontroller, GPS, and weather station sensors. The proposed modified model utilized the least squares tuning algorithm to fit the data measured from the drone communication system. This enhanced the RF connectivity between the drone and the local authority, as well as leading to increased coverage footprint and, thus, the performance of wider search-and-rescue operations in a timely fashion using strip search patterns. The development of the proposed model considered both software simulation and hardware implementations. Since empirical propagation models are the most adjustable models, this study concludes with a comparison between the modified Hata-Davidson algorithm against other well-known modified empirical models for validation using root mean square error (RMSE). The experimental results show that the modified Hata-Davidson model outperforms the other empirical models, which in turn helps to identify missing persons and their locations using thermal imaging and a GPS sensor.


Association study of human MTH1 gene polymorphisms with type 1 diabetes mellitus.
Reactive oxygen species are considered to play a role in the development of diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined whether Val83Met polymorphism of human MTH1 gene is associated with type 1 diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97 females). The polymorphism was analyzed by restriction fragment length polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare in both control and patient groups. Val/Met genotype tended to be more frequent in the whole type 1 diabetic patients than in controls. When subjects were divided into subgroups according to gender, there were no differences in the genotype and allele frequencies between patients and controls in males. On the other hand, in female type 1 diabetic patients, the Val/Met genotype was more frequent than in female controls (corrected P = 0.102). The Met allele was significantly more frequent in female type 1 diabetic patients than in female controls (corrected P = 0.022). Our results suggested that the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population.


Reliability of environmental DNA surveys to detect pond occupancy by newts at a national scale.
The distribution assessment and monitoring of species is key to reliable environmental impact assessments and conservation interventions. Considerable effort is directed towards survey and monitoring of great crested newts (Triturus cristatus) in England. Surveys are increasingly undertaken using indirect methodologies, such as environmental DNA (eDNA). We used a large data set to estimate national pond occupancy rate, as well as false negative and false positive error rates, for commercial eDNA protocols. Additionally, we explored a range of habitat, landscape and climatic variables as predictors of pond occupancy. In England, 20% of ponds were estimated to be occupied by great crested newts. Pond sample collection error rates were estimated as 5.2% false negative and 1.5% false positive. Laboratory error indicated a negligible false negative rate when 12 qPCR replicates were used. Laboratory false positive error was estimated at 2% per qPCR replicate and is therefore exaggerated by high levels of laboratory replication. Including simple habitat suitability variables into the model revealed the importance of fish, plants and shading as predictors of newt presence. However, variables traditionally considered as important for newt presence may need more precise and consistent measurement if they are to be employed as reliable predictors in modelling exercises.


3D printing technology and internet of things prototyping in family practice: building pulse oximeters during COVID-19 pandemic.
Family doctors can have an active role in identifying significant population needs and solutions. During the COVID-19 epidemic, patient home monitoring with pulse oximetry has been a key aspect of care of patients. However, pandemics bring shortage of medical equipment such as pulse oximeters. Through the local maker community, in a matter of days four "smart" pulse oximeters were built. Following Internet of Things principles, the prototypes were programmed to transmit real-time data through Wi-Fi directly to the doctors. Each pulse oximeter served a family doctor during the pandemic. In this article we describe the process that led to the production of the technology and provide detailed instructions, which have also been shared in maker-oriented websites. Dissemination can potentially lead to additional small-scale productions, limiting future shortages.


Affective valence of neurons in the vicinity of the rat amygdala: Single unit activity in response to a conditioned behavior and vocal sound playback.
We recorded single unit activity within and around the rat amygdala while rats were engaged in an operant task (which included both reward and aversive trials) and during playback of ultrasonic vocalizations (USVs) to determine if there existed neurons which responded to two different types of either positive contexts (i.e., water reward and positively associated 50kHz vocalizations) or negative contexts (i.e., white noise and negatively associated 22kHz vocalizations). Ultimately, we wanted to determine if these two contexts (operant condition task and vocal sounds) could be represented as either positive or negative in a single neuron. Neural activity in 90% of cells was modulated in response to one or more of those events. A small number of those cells showed neural responses to both the aversive operant trials and 22kHz USVs, but did not show responses to reward operant trials or 50kHz USVs, suggesting the activity of these neurons encodes for similar negative emotion in response to these two contexts. Some cells showed responses to either the reward trials or 50kHz USVs, but no cells showed responses to both, suggesting that these cells do not show a common response to events associated with positive emotion. This might mean that 50kHz vocal sounds and the operant rewards were segregated into two different categories within the neural representation at the level of the amygdala, even though it appeared that both events were associated with positive emotions in rats.


Genetic manipulation of blood group carbohydrates alters development and pathfinding of primary sensory axons of the olfactory systems.
Primary sensory neurons in the vertebrate olfactory systems are characterised by the differential expression of distinct cell surface carbohydrates. We show here that the histo-blood group H carbohydrate is expressed by primary sensory neurons in both the main and accessory olfactory systems while the blood group A carbohydrate is expressed by a subset of vomeronasal neurons in the developing accessory olfactory system. We have used both loss-of-function and gain-of-function approaches to manipulate expression of these carbohydrates in the olfactory system. In null mutant mice lacking the alpha(1,2)fucosyltransferase FUT1, the absence of blood group H carbohydrate resulted in the delayed maturation of the glomerular layer of the main olfactory bulb. In addition, ubiquitous expression of blood group A on olfactory axons in gain-of-function transgenic mice caused mis-routing of axons in the glomerular layer of the main olfactory bulb and led to exuberant growth of vomeronasal axons in the accessory olfactory bulb. These results provide in vivo evidence for a role of specific cell surface carbohydrates during development of the olfactory nerve pathways.


Seasonal variations in circadian rhythms persist in gonadectomized golden-mantled ground squirrels.
Circadian wheel-running activity was monitored in intact and gonadectomized female and male golden-mantled ground squirrels maintained in a 14L:10D photoperiod at 21 degrees C. Marked advances in phase angle of activity onset and increases in the duration of the daily active phase occurred each year in intact animals coincident with the phase of reproductive activity. Surprisingly, long-term gonadectomized squirrels of both sexes manifested similar seasonal changes in the circadian system. Seasonal circadian variations in locomotor activity are generated by a circannual clock independent from and not influenced by concurrent changes in secretion of gonadal hormones.


Physical and psychosocial working conditions as explanations for occupational class inequalities in self-rated health.
Socio-economic health inequalities are well documented, but efforts to explain health inequalities are less. However, previous studies suggest that working conditions provide potential explanations for inequalities in health. Cross-sectional questionnaire survey data, collected from municipal employees of the City of Helsinki, aged 40-60 years (n = 8960, response rate 67%) in 2000-02, were examined using binomial regression analysis. Socio-economic position was measured by six occupational social classes ranging from top managers to manual workers, and the outcome was self-rated health (SRH). Key physical and psychosocial working conditions and work arrangements were included as explanatory factors for inequalities in health. Occupational class inequalities in SRH were clear among women [prevalence ratio (PR) 1.89, 95% confidence interval (CI) 1.54-2.32] and men (PR 1.78, 95% CI 1.40-2.25). Heavy physical workload explained a half of the health inequalities among women and almost one-third among men. Physical and chemical exposures at work explained one-fifth of the health inequalities among women and a half among men. Job control explained 24% of the men's and 40% of women's inequalities, whereas job demands widened the inequalities by 13-14%. The effects of shift work and working hours were negligible. In the fully adjusted model, 60% of the women's and 32% of the men's inequalities in SRH were explained. Physical working conditions explained a large part and job control, a somewhat smaller part of socio-economic inequalities in SRH. Improving physical working conditions and increasing job control provide potential routes to reduced inequalities in health among employees.


Genetic mapping of EST-derived microsatellites from the diploid Gossypium arboreum in allotetraploid cotton.
To increase the numbers of microsatellites available for use in constructing a genetic map, and facilitate the use of functional genomics to elucidate fiber development and breeding in cotton, we sampled microsatellite sequences from expressed sequence tags (ESTs) transcribed during fiber elongation in the A-genome species Gossypium arboreum to evaluate their frequency of occurrence, level of polymorphism and distribution in the At and Dt subgenomes of tetraploid cotton. From among ESTs derived from G. arboreum fibers at 7-10 days post anthesis (dpa), 931 ESTs were found to contain simple sequence repeats (SSRs); 544 (58.4%) EST-SSR primer pairs were developed, and 468 (86%) amplified PCR products from allotetraploid cotton (G. hirsutumcv. TM-1 and G. barbadense cv. Hai7124). However, only 99 (18.2%) of these were found to be polymorphic and segregating in our interspecific BC1 mapping population [(TM-1xHai7124)xTM-1]. In these amplified and informative EST-SSRs, hexa- and tri-nucleotide repeat motifs were the most frequent, representing 40.1 and 30%, respectively, of the total. A total of 111 loci detected with these 99 EST-SSRs were integrated into our backbone map including 511 SSR loci. The distribution of the EST-SSRs appeared to be non-random, since 72 loci were anchored to the At and 37 to the Dt subgenome of allotetraploid cotton based on linkage tests. Interestingly, out of the 10 pairs of duplicate loci amplified, seven were mapped to the corresponding homologous linkage groups and/or chromosomes. BLASTX analysis revealed that 69 of the 99 ESTs showed significant similarities to known genes. Some genes important for fiber development, such as sucrose synthase, were mapped to corresponding chromosomes. These EST-SSRs provide structural and functional genomic information that will be useful for understanding cotton fiber development.


Managing polycystic ovary syndrome in primary care.
Polycystic ovary syndrome (PCOS) presents with a spectrum of conditions resulting from androgen excess, anovulation and metabolic syndrome. Patients with PCOS may see their primary care physicians for various presentations, including hirsutism, acne, menstrual irregularities, infertility, obesity, and psychiatric disorders such as anxiety and depression. Management of these patients should include screening for Type 2 diabetes mellitus, dyslipidaemia and hypertension. Treatment should be targeted to each patient's phenotype and personal expectations such as desire for pregnancy. Psychological well-being due to the effects on physical appearance is also an important consideration. Diet and exercise are major components in the management of patients with PCOS and obesity. The first-line therapy for fertility and metabolic syndrome in PCOS is lifestyle modification with diet and exercise, followed by pharmacological therapy.


Investigation of a screening battery for immunotoxicity of pharmaceuticals within a 28-day oral toxicity study using azathioprine and cyclosporin A as model compounds.
The authors have investigated a panel of parameters for immunotoxicity that may be incorporated in routine screening for toxicity of pharmaceuticals. This panel comprises serum immunoglobulin concentrations, cellularity of bone marrow, weights and histopathology of thymus, spleen, and lymph nodes, histopathology of Peyers' patches, and FACScan analysis of lymphocyte subpopulations in the spleen, in addition to parameters of toxicity to other systems. To study the value of these assays for pharmaceuticals, the authors used the immunosuppressants azathioprine (AZP) and cyclosporin A (CsA) as model compounds with known immunotoxic activity. In two separate experiments, rats were treated by daily gastric intubation with 0, 5, 12.5, and 25 mg AZP/kg body wt or 0, 1.25, 5, and 20 mg CsA/kg body wt. In the AZP study, the histopathology of the thymus and the spleen were valuable parameters of immunotoxicity, since these organs showed microscopic alterations at relatively low dose levels. In the CsA experiment, both the histopathology of the thymus and the data provided by FACScan analysis were sensitive indicators of immunotoxicity detecting effects at the lowest dose level employed. The data indicate that the lymphoid system is the most sensitive target of toxicity after AZP or CsA administration. The authors conclude that their test battery yielded immunotoxicity profiles of AZP and CsA in rats that were consistent with published findings in the literature, indicating the usefulness of the test battery employed.


Blockade of Fgfr1 with PD166866 Protects Cartilage from the Catabolic Effects Induced by Interleukin-1β: A Genome-Wide Expression Profiles Analysis.
Previously we showed that genetic deletion of Fgfr1 in chondrocytes protected mice from progression of osteoarthritis (OA). The aim of this study is to evaluate the effect of PD166866, a potent selective inhibitor of Fgfr1, on cartilage degeneration induced by interleukin-1β (IL-1β) and to clarify underlying global gene expression pattern. Cartilage explants and primary rat chondrocytes were stimulated with IL-1β to establish an inflammatory OA in vitro model. The effects of PD166866 were determined by measuring the release of glycosaminoglycans (GAG) in cartilage explants and primary rat chondrocytes, and the underlying molecular mechanism was analyzed by microarray and RT-PCR analysis in primary chondrocytes. In cartilage explants, PD166866 significantly counteracts IL-β stimulated GAG release. In addition, PD166866 impede IL-1β-stimulated nuclear translocation of p65 in rat chondrocytes. Based on microarray analysis, a total of 67 and 132 genes with more than 1.5-fold changes were identified in IL-1β-treated versus control and PD166866 cotreatment versus IL-1β treatment alone, respectively. Only 19 thereof were coregulated by IL-1β and PD166866 simultaneously. GO and KEGG pathway analysis showed that some pathways, including "cytokine-cytokine receptor interaction," "chemokine signaling pathway," and "complement and coagulation cascades," as well as some key genes like chemokines, complement, and matrix metalloproteinases may relevant for therapeutic application of Fgfr1 blockade in IL-1β-stimulated chondrocytes. Our results clearly demonstrated that blockade of Fgfr1 with PD166866 could effectively suppress the catabolic effects induced by IL-1β, and elucidated whole genomic targets of Fgfr1 inhibition responsible for the therapeutic effects of Fgfr1 blockade against inflammatory OA.


Early atheroma-derived agonists of peroxisome proliferator-activated receptor-γ trigger intramedial angiogenesis in a smooth muscle cell-dependent manner.
Neovascularization favors intraplaque hemorrhage and plaque rupture. Development of therapeutic strategies against atheromatous angiogenesis requires elucidation of its initiating factors. We investigated the contribution of smooth muscle cells (SMCs) and atheroma-derived lipids to the initiation of atheroma-associated neoangiogenesis. Forty human aortic segments, each harvested from a different donor, were classified as healthy or as bearing early atheromatous lesions, including fatty streaks and fibrolipidic atheroma, according to their histological features. Immunostaining for blood vessels and vascular endothelial growth factor-A (VEGF-A), as well as measurement of VEGF-A protein and mRNA levels by ELISA and real-time PCR, revealed that angiogenesis and VEGF-A production were enhanced in the medial layer of atheromatous aortas. The intramedial vessel density and invasiveness and the production of VEGF-A by medial SMCs were indeed increased in atheromatous aortas compared with healthy aortas. Furthermore, intimal layers of atheromatous aortas were enriched in soluble lipid mediators capable of inducing a sustained increase in VEGF-A production by medial SMCs, turning these cells into potent inducers of angiogenesis when incorporated into mouse Matrigel implants. Both effects were inhibited by the peroxisome proliferator-activated receptor-γ inhibitor GW9662 and mimicked by its agonist, rosiglitazone. We show that VEGF-A production is upregulated in medial SMCs of human atheromatous aortas and that peroxisome proliferator-activated receptor-γ agonists derived from early intimal lesions are likely to contribute to this phenotypic change. Our findings suggest that medial SMCs are central organizers of an angiogenic response initiated by the subendothelial accumulation of atherogenic lipids.


Effect of correction of acidosis on nutritional status in dialysis patients.
Malnutrition is a well-recognised feature of end-stage renal failure and contributes to the continuing high morbidity and mortality in this group of patients. One of the aetiological factors is metabolic acidosis which has been shown to increase protein degradation in both experimental models of chronic renal failure and in humans with uraemia. Many patients currently receiving haemodialysis have subnormal values of plasma bicarbonate. However, the values can be normalised by using a dialysate bicarbonate concentration of 35-40 mmol/l and in continuous ambulatory peritoneal dialysis (CAPD), a similar increment in plasma bicarbonate can be achieved using a dialysate lactate content of 35-40 mmol/l. In short-term studies in haemodialysis patients there is evidence of an increase in body weight and other anthroprometric parameters when the plasma bicarbonate has been normalised by increasing the dialysate bicarbonate content. A long-term study in CAPD patients has demonstrated increased body weight, tricep skinfold thickness and midarm muscle circumference in those patients with a plasma bicarbonate of 27.2 +/- 0.3 mmol/l, compared to those with a value of 23.0 +/- 0.3 mmol/l. These studies strongly suggest that correction of acidosis by increased dialysate buffering capacity will improve nutritional status for patients with end-stage renal failure.


Neurodegeneration and contralateral α-synuclein induction after intracerebral α-synuclein injections in the anterior olfactory nucleus of a Parkinson's disease A53T mouse model.
Parkinson's disease is characterized by a proteinopathy that includes aggregates of α-synuclein. A recent hypothesis proposes a prion-like spreading mechanism for this α-synucleinopathy. Early neuropathological deposits occur, among others, in the anterior olfactory nucleus (AON). This study investigates the anterograde and/or retrograde transmissibility of exogenous α-synuclein inoculated in the right AON of the A53T model of Parkinson's disease and wild-type mice as well as neuronal and glial involvement. Seven experimental groups were established: wild-type injected with tracers; A53T mice injected with either α-synuclein or saline 2 months beforehand; wild-type injected with either α-synuclein or saline 2 months beforehand; and wild-type injected with either α-synuclein or saline 4 months beforehand. Weight and behavioral changes were analyzed. Immunohistochemistry against α-synuclein, NeuN, Iba-1 and GFAP was performed. Volume and marker distributions in the olfactory bulb (OB), AON and piriform cortex were analyzed using unbiased stereology. The behavioral analyses reveal higher levels of hyperactivity in transgenic as compared to wild-type mice. Tract-tracing experiments show that the main contralateral afferent projections to the dorsal AON come from the AON and secondarily from the OB. In saline-injected transgenic animals, α-synuclein expression in the OB and the AON is higher in the left hemisphere than in the right hemisphere, which could be due to basal interhemispheric differences. α-synuclein injection could provoke a significant increase in the left hemisphere of the transgenic mice's OB, compared to saline-injected animals. Neuronal loss was observed in saline-injected transgenic mice relative to the saline-injected wild-type group. There were no overall differences in neuron number following injection of α-synuclein into either wild-type or transgenic mice, however some neuron loss was apparent in specific regions of α-synuclein injected wild-types. Microglia labeling appeared to be correlated with surgery-induced inflammation. Astroglial labeling was higher in transgenic animals, which could be due to endogenous α-synucleinopathy. This study suggests α-synucleinopathy induction, via retrograde and contralateral projections, within the olfactory system of transgenic animals.


Oral health education in Finnish schools.
The public system of oral health care in Finland, as in the other Nordic countries, is responsible for arranging oral health education for school classes. In this study the coverage and the personnel implementing these lessons in Finnish schools were assessed. A questionnaire was sent to all health centers (n = 214). The response rate was 87%. A total of over 23,000 oral health lessons were arranged in schools during the year studied. Coverage was high in primary schools, lower in secondary schools and lower still in high schools. The main implementers of the lessons were dental assistants. The conclusions of the study were: 1) coverage of teenagers should be increased, 2) the role of dental hygienists and dentists in implementing the program should be greater, and 3) oral health personnel and teachers should cooperate more actively.


Oxidative stress in colon tissue induced by vitamin E depletion.
Inflammatory disorders of the bowel and colon cancer are associated with elevated indices of oxidative stress. Analogous elevations in markers of oxidative stress and loss of cell-membrane integrity are also observed in the colons of rats deficient in vitamin E (D-alpha-tocopherol), the major lipid-soluble antioxidant in biological systems. The causal relationship between colon pathologies associated with oxidative stress and dietary deficiency in antioxidant vitamins such as vitamin E is still uncertain. Investigation of potential mechanisms by which lack of dietary vitamin E may lead to clinically relevant pathological changes in colon tissue was conducted using gene expression profiling strategies on vitamin E-sufficient and -deficient rats. Morphological changes and increased indices of lipid peroxidation were linked to vitamin E deficiency. These changes in colon tissue are potentially important in disease pathogenesis of the colon linked with oxidative stress or other direct consequences of inadequate levels of vitamin E.


Identification of key pathways and genes with aberrant methylation in prostate cancer using bioinformatics analysis.
Prostate cancer (PCa), a multifocal clinically heterogeneous disease, is the most commonly diagnosed non-cutaneous neoplasm in men worldwide. The epigenome of PCa is a typical representation of catastrophic model of epigenetic alterations during tumorigenesis and its progression. Alterations in methylation patterns in tumor suppressors, cell cycle, oncogenes and metabolism-related genes are the most commonly observed epigenetic alterations in PCa. In this study, we have developed a computational strategy to identify methylated biomarker signature panels as potential targets of PCa by screening >160 genes reported to be epigenetically dysregulated, and shortlisted 26 differentially methylated genes (DMGs) that significantly contribute to oncogenesis. The gene ontology and functional enrichment analysis were performed, which showed that identified DMGs contribute to cellular and metabolic processes such as cell communication, cell cycle, response to drugs, apoptosis and p53 signaling. The top hub genes AR, CDH13, CDKN2A, DAPK1, GSTP1, CD44 and RASSF1 identified from protein-protein interaction network construction using Search Tool for the Retrieval of Interacting Genes contributed to hormonal response, inflammatory response, cell cycle, reactive oxygen species activity and receptor kinase activity, which are related to hallmarks of cancer as revealed by their functional enrichment analysis by Cytoscape. These genes were further scrutinized for CpG islands, transcription start sites and positions of methylated cytosines to study their methylation profiles. Our analysis revealed high negative correlation values between methylation frequencies and gene expressions of the hub genes, namely, AR, CDH13, CDKN2A, DAPK1, CD44, GSTP1 and RASSF1, which can be used as potential diagnostic biomarkers for PCa.


Relationships between spider constructs in phobics.
An index of tight construing was derived from a Kelly grid in which the elements were spiders. This index, the coefficient of concordance, corresponds to the average correlation between constructs. Concordance was significantly higher in spider phobics than controls, in line with the hypothesis that emotional disorders are associated with higher correlations between symptom-related constructs (i.e. 'tight' construing). Desensitization, though it reduced phobic anxiety, had no effect on concordance.


Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review.
Abnormalities of corpus callosum are one of the most common brain anomalies. Fetuses with isolated corpus callosum agenesis (CCA) have a better prognosis than those with additional anomalies. However, unpredictable neurodevelopmental outcomes of truly isolated CCA make prenatal counseling a challenge. The aim of this review is to evaluate neurodevelopmental outcomes in children with prenatal diagnosis of isolated CCA. Controlled clinical trials published between May 23, 2009, and May 23, 2019, using the MeSH term "agenesis of corpus callosum" were reviewed. A total of 942 articles were identified, and 8 studies were included in the systematic review depending on the inclusion criteria. These studies included 217 fetuses with isolated CCA and no other anomalies at prenatal assessment. Neurodevelopmental outcome was reported to be normal in 83 children with a prenatal diagnosis of isolated CCA confirmed at birth within 128 completed assessments. About 45 children presented borderline, moderate, or severe neurodevelopmental outcome. In this review, neurodevelopment was favorable in two-thirds of the cases, but mild disabilities emerged in older children. Despite this, disabilities can occur later beyond school age and a low risk of severe cognitive impairment exists. Our study highlights the essential early diagnosis and proper supportive therapy.


[Recanalisation of chronic total coronary occlusions - what is the evidence and which patients will benefit?]
Recanalisation of chronic total coronary occlusions - what is the evidence and which patients will benefit? Abstract. Continuous improvement of recanalisation techniques and newer device technologies significantly improved the success of revascularisation in percutaneous coronary intervention (PCI) of chronic total occluded coronary arteries (CTO) in the past few years. The best documented clinical benefit of CTO-PCI is symptom control, based on a reduction of myocardial ischemia. In contrast, there is still an ongoing controversial debate regarding the prognostic benefit of successful CTO-PCI shown in several observational studies. Therefore, the indication for CTO-PCI is primarily based on patients' symptoms and the extent of myocardial ischemia. The risk / benefit ratio for the individual patient has to be estimated from technical complexity of the CTO lesion, the extent of the coronary artery disease and the ventricular function. Recanalisation strategy should be escalating, as most of the CTOs can be successfully recanalised with standard antegrade recanalisation techniques. With the implementation of retrograde CTO techniques, the likelihood for recanalisation success is very high (> 90 %) even in complex anatomies, combined with low complication rates in specialised centers. According to the operator's expertise a complete catheter-based revascularisation can be achieved nowadays even in patients with CTO and coronary multi-vessel disease.


[Outcome of infants operated on for aortic coarctation before 3 months of age].
Between January 1966 and June 1982, 177 infants less than 3 months of age underwent surgical cure of coarctation of the aorta. Seventy-one percent had associated cardiac lesions not including a patent ductus arteriosus. With the cure of the coarctation either by resection anastomosis or angioplasty, 45% underwent associated surgical procedure, mainly pulmonary artery banding. Early mortality was 26% for the last 4 years of the study. Early deaths, significantly correlated with the severity of the preoperative heart failure and the importance of pulmonary hypertension, were not correlated with an associated heart disease. Of the 95 survivors operated on before December 31, 1981 and with a long follow-up, 18 died later on. Late deaths are related with associated cardiac malformations. Thirty-nine (41%) of the survivors had recurrent coarctation. This was correlated with the year of surgery and not with the surgical technique. In cases with coarctation of the aorta surgical cure should not be withheld before age 3 months, when there is heart failure, with or without associated cardiac malformations. The mortality, even in isolated coarctation (6%), the occurrence of sudden deaths after good surgical repair, the frequency of recoarctations lead to suggest that in infants under 3 months of age, careful supervision and conservative medical treatment should be considered, if the coarctation is isolated and well tolerated.


Inhibition of the beta-catenin signaling pathway in blastocyst and uterus during the window of implantation in mice.
Beta-catenin, the mammalian homolog of Drosophila armadillo protein, was first identified as a cadherin-associated protein at cell-cell junctions. Another function of beta-catenin is the transduction of cytosolic signals to the nucleus in a variety of cellular contexts, which usually are elicited by the active form of beta-catenin. The aim of the present study was to examine the potential role of active beta-catenin in the mouse embryo and uterus during embryo implantation. Active beta-catenin was detected differentially in mouse embryos and uteri during the peri-implantation period. Aberrant activation of beta-catenin by LiCl, a well-known glycogen synthase kinase-3 inhibitor, significantly inhibited blastocyst hatching and subsequent adhesion and outgrowth on fibronectin. Results obtained from pseudopregnant and implantation-delayed mice imply an important role for implanting blastocysts in the temporal and spatial changes of active beta-catenin in the uterus during the window of implantation. Collectively, these results suggest that the beta-catenin signaling pathway is inhibited in both blastocyst and uterus during the window of implantation, which may represent a new mechanism to synchronize the development of preimplantation embryos and differentiation of the uterus during this process.


Virus threshold determines disease in SIVsmmPBj14-infected macaques.
Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10(-1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly.


Drying Behavior and Curcuminoids Changes in Turmeric Slices during Drying under Simulated Solar Radiation as Influenced by Different Transparent Cover Materials.
Dried turmeric is used as a spice and traditional medicine. The common drying methods for turmeric (Curcuma longa L.) are sun drying and solar drying. In this study, turmeric slices with a thickness of 2 mm were dried at 40, 50, 60, and 70 °C in a laboratory hot-air dryer with a simulated solar radiation applied through transparent polycarbonate cover (UV impermeable) and PMMA cover (UV permeable). Air velocity and relative humidity of drying air were fixed at 1.0 M·s-1 and 25 g H2O kg-1 dry air, respectively. Light significantly increased the sample temperature under both covers. Page was the best model to predict the drying characteristics of turmeric slices. Drying rate correlated with the effective moisture diffusivity, which increased at higher temperature. The hue angle (h°) of turmeric was distinctly lower at 70 °C under both covers. The dried products were of intensive orange color. Curcumin, demethoxycurcumin, and total curcuminoids were affected by the cumulated thermal load (CTL). The lowest curcumin content was found at 40 °C under PMMA (highest CTL). The optimum drying condition was 70 °C under polycarbonate cover due to shorter drying time and better preservation of color and curcuminoids in the dried product.


Pyridinophane platform for stable lanthanide(III) complexation.
A detailed investigation of the solid state and solution structures of lanthanide(III) complexes with the macrocyclic ligand 2,11,20-triaza[3.3.3](2,6)pyridinophane (TPP) is reported. The solid state structures of 14 different Ln(3+) complexes have been determined using X-ray crystallography. The ligand is coordinating to the Ln(3+) ion by using its six nitrogen atoms, while nitrate or triflate anions and water molecules complete the metal coordination environments. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by DFT calculations (TPSSh model) performed in aqueous solution. The structures obtained from these calculations for the complexes with the lightest Ln(3+) ions (La-Sm) are in very good agreement with those determined by the analysis of the Ln(3+)-induced paramagnetic shifts. A structural change occurs across the lanthanide series at Sm(3+); the complexes of the large Ln(3+) ions (La-Nd) are chiral due to the nonplanar conformation of the macrocycle, and present effective C3v symmetries in solution as a consequence of a fast interconversion of two enantiomeric forms with C3 symmetry. The activation free energy for this enantiomerization process, as estimated by using DFT calculations, amounts to 33.0 kJ·mol(-1). The TPP ligand in the complexes of the heaviest Ln(3+) ions (Eu-Lu) presents a half-chair conformation, which results in C(s) symmetries in solution.


Predicting outcomes in patients with urologic cancers.
To review the available predictive and prognostic models addressing oncological outcomes in patients with bladder, kidney and prostate cancer. A systematic review of the English literature on the discussed topics was performed. All manuscripts were retrieved from PubMed, and restricted to entries with an abstract. Keywords were 'diagnosis', 'stage', 'prognosis' and 'nomograms' for bladder, kidney and prostate cancer, respectively. Of these, 70 were selected for inclusion, based on content, clinical relevance, quality, level of evidence, and year of publication. We identified six models for prediction of the natural history of treated bladder cancer. We report on 15 models for patients with kidney cancer. Of these, two preoperative prognostic models predict recurrence-free survival, three postoperative models address disease recurrence, five postoperative models predict disease-specific survival, and, finally, five models predict overall survival in patients with metastatic kidney cancer. For prostate cancer, we found eight models predicting biopsy outcome, 17 models for pretreatment prediction of pathologic stage of clinically localized disease, eight models for prediction of biochemical recurrence, and, finally, six models predicting cancer control outcomes in relapsed or hormone-refractory metastatic prostate cancer. In patients with urologic malignancies, cancer control outcomes can be predicted in a highly accurate and evidence-based fashion.


Photobase-Driven Excited-State Intramolecular Proton Transfer (ESIPT) in a Strapped π-Electron System.
We report a new design strategy for an excited-state intramolecular proton transfer (ESIPT) fluorophore that can be used in acidic media. A photobasic pyridine-centered donor-acceptor-donor-type fluorophore is combined with a basic trialkylamine "strap". In the presence of an acid, protonation occurs predominantly at the amine moiety in the ground state. A single-crystal X-ray diffraction analysis confirmed the formation of a pre-organized intramolecular hydrogen-bonded structure between the resulting ammonium moiety and the pyridine ring. Upon excitation, the intramolecular charge-transfer transition increases the basicity of the pyridine moiety in the excited state, resulting in proton transfer from the amine to the pyridine moiety. Consequently, the fluorophore takes on a polymethine-dye character in the ESIPT state, which gives rise to significantly red-shifted emission with an increased fluorescence quantum yield.


Aging of the immune system: Focus on inflammation and vaccination.
Major advances in preventing, delaying, or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching eight to nine decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T-cell or B-cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly.


Cerebral cysticercosis in children in South Africa.
Sixty-one children with cerebral cysticercosis are presented. The commonest clinical manifestation was epilepsy with or without focal signs in 43% of children, followed by the syndrome of raised intracranial pressure in 34% and meningoencephalitis in 13%. The CT scan was positive in 93% of cases and the HAI test in 86% of children so examined. Both were positive in 80%. Skull X-ray revealed evidence of calcification and/or raised intracranial pressure in 60%. Two children died, one each with subacute sclerosing panencephalitis and tuberculous meningitis. Of those who improved on discharge, 43% had epilepsy and 32% neurological deficit of an obvious nature. The parasitology, pathogenesis, pathology and diagnosis of cerebral cysticercosis are briefly reviewed. Present therapy and the suggested use of a specific anti-cysticeral drug are discussed. Case histories are presented to draw attention to the variability of the clinical picture and the particular importance of recognising the acute parenchymatous form of the disease in children which may present with critically elevated intracranial pressure.


An audit of the provision of environmental control systems in Northern Ireland, 1992-1997.
To evaluate the provision of environmental control systems (ECS) in Northern Ireland with regard to assessment and prescription, installation and review and propose guidelines for future service delivery. Structured interview, physical examination, Barthel ADL Index, demonstration and assessment of suitability of ECS for patient. Prescriptions for ECS from April 1992 to 1997 were identified from centrally held records. Current users were assessed in their own homes. Forty-six out of 49 current users identified were assessed. All were severely disabled (Barthel 0-9); 24% were living alone; 7 (15%) were not utilizing the system; 96% were satisfied with their initial assessment. Prior to prescription 52% had information about ECS and 20% had a practical demonstration; 78% felt that this would have been useful; 52% of users were not under routine clinical review; 41% of ECS had been altered since installation. Repairs had taken longer than 7 days in 11% of cases. In 45 cases the ECS was essential and in 43 it was appropriate to the users' needs and abilities. ECS are a valuable tool for severely disabled persons and are appropriately prescribed in Northern Ireland. A multidisciplinary team should perform assessment and prescription. All patients should have a practical trial of the equipment to assist in prescriptions. Regular review by the team should be performed to identify changes in need and alter systems appropriately. Users who live alone should represent a priority for repairs.


Two new species of trypanosomatid parasites isolated from Heteroptera in Costa Rica.
Two new trypanosomatid species (Euglenozoa, Kinetoplastea) isolated from the intestinal tract of heteropteran insect hosts were described based on molecular phylogenetic analyses of Spliced Leader (SL) RNA gene repeats, glycosomal glyceraldehyde phosphate dehydrogenase, and small subunit ribosomal RNA genes, as well as by morphology. Leptomonas barvae n. sp., from a mirid host Collaria oleosa, was found to represent one of the closest monoxenous (one host) relatives of the dixenous (two hosts) parasitic genus Leishmania. This finding further supports the origin of these dixenous parasites from monoxenous progenitors in the Neotropics. Blastocrithidia largi n. sp., from a largid host Largus cinctus, is among a few members of this genus available in culture. The species is a close relative of Blastocrithidia triatomae and is a member of a new monophyletic phylogenetic group characterized by formation of straphanger cysts.


Effect of omega-3 fatty acids on growth of a rat mammary tumor.
The effect of administering marine oil that was rich in omega-3 fatty acids on tumor growth was studied in female inbred F344 rats that received transplants of R3230AC mammary adenocarcinoma. Four groups of rats were maintained on a normal rat chow diet containing 5% fat, and marine oil supplementation was started 1 week prior to transplantation of the tumors. The marine oil provided 17, 33, and 67 mg of 5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) and 16, 32, and 64 mg 4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA) a day. A significant reduction in weight (g) and volume (cm3) of the rat R3230AC mammary tumor was observed after 4 weeks of treatment. EPA (20:5 omega-3) and DHA (22:6 omega-3) were found in choline phospholipid fractions of mammary tumors from rats given marine oil. Both tumor content and synthesis in vitro of prostaglandins of two series were inhibited in the marine oil-treated groups. These data indicated that the mechanism underlying inhibition of mammary tumorigenesis may be linked, in part, to the inhibitory effect of both EPA and DHA on arachidonic acid metabolism.


Potential pharmacokinetic effect of rifampicin on enrofloxacin in broilers: Roles of P-glycoprotein and BCRP induction by rifampicin.
P-glycoprotein ( P-GP: , encoding gene Abcb1) and Breast Cancer Resistance Protein ( BCRP: , encoding gene Abcg2) are transport proteins that play a major role in modulating the bioavailability of oral drugs in humans and rodents. It has been shown that rifampicin is the typical inducer of P-gp in rodents by activating the nuclear receptor. However, its effect on Abcb1, Abcg2, CYP3A, and chicken xenobiotic-sensing orphan nuclear receptor ( CXR: ) mRNA expression in broilers is poorly understood. This study explored the effect of rifampicin on mRNA expression of Abcb1, Abcg2, CYP3A37, CXR as well as its effect on the pharmacokinetics of enrofloxacin in broilers. The mRNA levels of Abcb1, Abcg2, CYP3A37, and CXR were significantly increased in the liver (except Abcg2), kidney, jejunum, and ileum (P < 0.05) but not significantly changed in the duodenum (P > 0.05) after treated with rifampicin. Further analysis revealed that the variation tendencies of Abcb1, Abcg2, and CYP3A37 expression levels were significantly correlated with CXR mRNA expression levels in liver, kidney, jejunum, and ileum. Coadministration of rifampicin significantly changed the pharmacokinetic behavior of enrofloxacin orally administered by showing clearly lower AUC0-∞, AUC0-t, and Cmax as well as longer Tmax. The bioavailability of orally administered enrofloxacin was decreased from 72.5% to 24.8% by rifampicin. However, rifampicin did not significantly change the pharmacokinetics of enrofloxacin following intravenous administration. Our study shows that rifampicin up-regulated the small intestinal level of P-gp and BCRP and suggests that P-gp and BCRP are key factors that affected pharmacokinetic behavior of orally administered enrofloxacin by limiting its absorption from the intestine in broilers.