Measuring effectiveness in community-based palliative care programs: A systematic review.
Community-based palliative care (CBPC) serves seriously ill individuals by integrating care for symptom and stress relief with local health care systems. This review provides the first systematic review of the literature to date on the effectiveness of CBPC programs and includes their measures of success, challenges faced, and characteristics of the populations served. A systematic review on CBPC program effectiveness was conducted across four electronic databases for academic articles published through August 2021. PRISMA reporting guidelines were followed throughout this review, study quality was assessed using the Mixed Methods Appraisal Tool, and results were summarized in a narrative synthesis. The 61 included articles were separated into quantitative and qualitative studies, with eight having mixed methods and belonging to both groups. Overall, the quantitative articles indicate that CBPC programs increase the likelihood that seriously ill patients in their community have their place of death as home, fewer hospitalizations, fewer emergency department visits, decreased hospital length of stays, improved quality of life, and lower health care costs. There was, however, also evidence showing certain programs were unsuccessful in improving the stated outcomes. The qualitative studies reported positive findings and highlighted areas for future program improvement, like training staff and volunteers in communication and other skills. There was a lack of quantitative and qualitative studies investigating CBPC programs in low-income and lower-middle-income countries. In addition, there is a paucity of research examining CBPC program impact on vulnerable and key populations across the globe. Although findings generally support the notion that CBPC programs are a cost-effective way to improve end-of-life quality, further research is needed examining the characteristics of the more successful programs. Findings also suggest the need for collaboration between researchers, health systems, and governments to design and implement effective CBPC programs and to share best practices across communities worldwide.


The gene encoding the hematopoietic stem cell regulator CCN3/NOV is under direct cytokine control through the transcription factors STAT5A/B.
Cytokines control the biology of hematopoietic stem cells (HSCs) and progenitor cells in part through the transcription factors STAT5A/B. To investigate the target genes of STAT5A/B activated by cytokines in HSCs and progenitors, we performed microarray analyses using Lineage(-) Sca-1(+) c-Kit(+) (KSL) cells in the presence and absence of STAT5A/B. Stimulation with a mixture containing IL-3, IL-6, stem cell factor, thrombopoietin, and Flt3 ligand induced Ccn3/Nov mRNA over 100-fold in WT (control) but not Stat5a/b-null KSL cells. CCN3/NOV is a positive regulator of human HSC self-renewal and development of committed blood cells. Without stimulation, the Ccn3/Nov signal level was low in control KSL cells similar to Stat5a/b-null KSL cells. To determine which cytokine activates the Ccn3/Nov gene, we analyzed Lineage(-) c-Kit(+) (KL) and 32D cells using quantitative PCR and ChIP assays. Although stimulation with a mixture lacking IL-3 prevented the induction of Ccn3/Nov in control KL cells, IL-3 alone could induce Ccn3/Nov mRNA in control KL and 32D cells. ChIP assays using 32D cells revealed IL-3-induced binding of STAT5A/B to a γ-interferon-activated sequences site in the Ccn3/Nov gene promoter. This is the first report that Ccn3/Nov is directly induced by cytokines through STAT5A/B.


Towards measurement of homonuclear dipolar couplings in 1H solid-state NMR: recoupling with a rotor-synchronized decoupling scheme.
We describe a magic-angle spinning NMR experiment for (1)H-(1)H homonuclear dipole-dipole coupling estimations in organic solids. The methodology involves reintroducing dipolar interactions with rotor-synchronized homonuclear decoupling pulse sequences. Frequency-selective DANTE pulses are used to isolate a specific spin pair from a natural isotopic abundance sample. The coupling of interest, between the selected spin pair, may be extracted by a non linear least-squares fit of the experimentally observed modulation of the signal intensity to an exact analytical formula. The experiment is demonstrated on natural isotopic abundance glycine and alanine powder samples.


Cost-effectiveness of adolescent pertussis vaccination for the Netherlands: using an individual-based dynamic model.
Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies.


Stabilometric Correlates of Motor and Motor Imagery Expertise.
Motor Imagery (MI) reproduces cognitive operations associated with the actual motor preparation and execution. Postural recordings during MI reflect somatic motor commands targeting peripheral effectors involved in balance control. However, how these relate to the actual motor expertise and may vary along with the MI modality remains debated. In the present experiment, two groups of expert and non-expert gymnasts underwent stabilometric assessments while performing physically and mentally a balance skill. We implemented psychometric measures of MI ability, while stabilometric variables were calculated from the center of pressure (COP) oscillations. Psychometric evaluations revealed greater MI ability in experts, specifically for the visual modality. Experts exhibited reduced surface COP oscillations in the antero-posterior axis compared to non-experts during the balance skill (14.90%, 95% CI 34.48-4.68, p < 0.05). Experts further exhibited reduced length of COP displacement in the antero-posterior axis and as a function of the displacement area during visual and kinesthetic MI compared to the control condition (20.51%, 95% CI 0.99-40.03 and 21.85%, 95% CI 2.33-41.37, respectively, both p < 0.05). Predictive relationships were found between the stabilometric correlates of visual MI and physical practice of the balance skill, as well as between the stabilometric correlates of kinesthetic MI and the training experience in experts. Present results provide original stabilometric insights into the relationships between MI and expertise level. While data support the incomplete inhibition of postural commands during MI, whether postural responses during MI of various modalities mirror the level of motor expertise remains unclear.


Pulmonary gas exchange in anaesthetised horses mechanically ventilated with oxygen or a helium/oxygen mixture.
It is unknown whether administration of gas-mixtures high in inspired fraction of oxygen (FiO2) under general anaesthesia may increase formation of pulmonary atelectasis and impair gas exchange. To evaluate the effects of different FiO2 on pulmonary gas exchange in isoflurane-anaesthetised horses breathing a helium/oxygen (He/O2) mixture. Thirty healthy mature horses were sedated with i.v. acepromazine (0.02 mg/kg bwt), detomidine (0.002 mg/kg bwt) and xylazine (02-0.4 mg/kg bwt). General anaesthesia was induced with i.v. 5% guaifenesin to effect, diazepam (0.1 mg/kg bwt) and ketamine (2 mg/kg bwt), and maintained with isoflurane. Fifteen horses (Group HX) were ventilated mechanically with gas mixtures of successively increasing FiO2 (0.25-030, 0.50-0.55, > 0.90), obtained by blending 02 with Heliox (70% He/30% O2). The other 15 horses (Group O) were ventilated immediately with 100% O2 (FiO2 > 0.90). After 20 min of ventilation at the different FiO2 levels in Group HX and after 60 min in Group O, PaO2 and PaCO2 were measured and the alveolar to arterial PO2 gradient (P(A-a)O2) was calculated. Data analysis included robust categorical regression with clustering on horse (P < 0.05). Inhalation of a He/O2 mixture with FiO2 as low as 0.25-030 ensured adequate arterial oxygenation and was associated with a smaller P(A-a)O2 gradient than inhalation of pure O2 (P < 0.05). In Group HX, PaO2 increased with each rise in FiO2 and so did P(A-a)O2 (P < 0.05). The PaO2 was significantly lower and the P(A-a)O2 higher in Group O compared to Group HX at a FiOz >0.90 (P < 0.05). Administration of a He/O2 gas mixture low in FiO2 can better preserve lung function than ventilation with pure oxygen. A step-wise increase of FiO2 using a He/O2 gas mixture might offer advantages with respect to pulmonary gas exchange over an immediate exposure to 100% 2O2.


Preprocessing with Photoshop Software on Microscopic Images of A549 Cells in Epithelial-Mesenchymal Transition.
To establish a preprocessing method for cell morphometry in microscopic images of A549 cells in epithelial-mesenchymal transition (EMT). Adobe Photoshop CS2 (Adobe Systems, Inc.) was used for preprocessing the images. First, all images were processed for size uniformity and high distinguishability between the cell and background area. Then, a blank image with the same size and grids was established and cross points of the grids were added into a distinct color. The blank image was merged into a processed image. In the merged images, the cells with 1 or more cross points were chosen, and then the cell areas were enclosed and were replaced in a distinct color. Except for chosen cellular areas, all areas were changed into a unique hue. Three observers quantified roundness of cells in images with the image preprocess (IPP) or without the method (Controls), respectively. Furthermore, 1 observer measured the roundness 3 times with the 2 methods, respectively. The results between IPPs and Controls were compared for repeatability and reproducibility. As compared with the Control method, among 3 observers, use of the IPP method resulted in a higher number and a higher percentage of same-chosen cells in an image. The relative average deviation values of roundness, either for 3 observers or 1 observer, were significantly higher in Controls than in IPPs (p < 0.01 or 0.001). The values of intraclass correlation coefficient, both in Single Type or Average, were higher in IPPs than in Controls both for 3 observers and 1 observer. Processed with Adobe Photoshop, a chosen cell from an image was more objective, regular, and accurate, creating an increase of reproducibility and repeatability on morphometry of A549 cells in epithelial to mesenchymal transition.


Soybean (Glycine max) hull valorization through the extraction of polyphenols by green alternative methods.
Soybean is one of the greatest crops in the world, with about 348.7 million tons being produced in 2018. Soybean hull is a by-product produced during the processing of soybean to obtain flour and oil. Though not being actually exploited, it is a source of polyphenols with antioxidant activity. Here, the extraction of polyphenols from soybean hull was performed by means of an alkaline hydrolysis treatment, which was optimized by the response surface methodology. At the optimal region, a total phenolic content of 0.72 g gallic acid equivalents per 100 g of soybean hull was obtained with an antioxidant activity of 2.17 mmoles of Trolox equivalents. Polyphenols responsible for the antioxidant activities were identified by LC-MS, including phenolic acids, anthocyanins, stilbenes, and the two main isoflavones of soybean, daidzein and genistein, in their non-glycosylated form. Other alternative extraction methods based on Aspergillus oryzae fermentation and α-amylase hydrolysis are also proposed.


Deletion mutagenesis in Synechocystis sp. PCC6803 indicates that the Mn-stabilizing protein of photosystem II is not essential for O2 evolution.
The photosystem II (PSII) reaction center complex coordinates a cluster of Mn atoms that are involved in the accumulation of oxidizing equivalents generated by light-induced charge separations within the intrinsic portion of the PSII complex. A 33-kDa extrinsic protein, termed the Mn-stabilizing protein (MSP), has been implicated in the stabilization of two of the four Mn atoms of the cluster, yet the precise role of this protein in O2 evolution remains to be elucidated. Here we describe the construction of a mutant of the cyanobacterium Synechocystis sp. PCC6803 in which the entire gene encoding MSP has been deleted. Northern and immunoblot analyses indicate that other PSII proteins are expressed and accumulated, despite the absence of MSP. Fluorescence emission spectra at 77 K indicate PSII assembles in the mutant, but that the binding of MSP is required for the normal fluorescence characteristics of the PSII complex, and suggest a specific interaction between MSP and CP47. Fluorescence induction measurements indicate a reduced rate of forward electron transport to the primary electron donor, P680, in the mutant. It is concluded that in contrast to previous reports, MSP is not required for the assembly of active PSII complexes nor is it essential for H2O-splitting activity in vivo.


Survey data of a traditional communal water irrigation system in Northern Thailand.
This data article contains a description of a dataset collected by a survey on a traditional communal water irrigation system. This is the Muang fai, a 700-years old communal irrigation system in Northern Thailand. The Muang fai is managed through a series of regulations that are close to Ostrom's principles of effective common property resources (Ostrom, 1990). The survival of this long-standing practice, including its knowledge of the water-flow characteristics of the watershed, is under threat as new technologies, such as groundwater pumping, become increasingly accessible. The target population of the survey was the group of Longan farmers who are located within the 12 villages that are engaged in Muang fai Sop Rong in Chiang Mai Province, Northern Thailand. Information was specifically collected about irrigation practices, farmland characteristics and socio-economic variables from 570 longan (their main crop) farmer households. Roughly half of these sampled farmers practise Muang fai, the other half practise underground pumping irrigation. The irrigation information collected includes type of irrigation (surface or underground), the quantity of water used, pumping methods (if pumps are used). Farming characteristics collected include volume and value of the harvests, land size, and distance to irrigation canal. Socioeconomic characteristics included among others: farmers' income, expenditure, education, off-farm employment and Muang-fai membership. This dataset can be a source of baseline information for future research as well as help preserve the knowledge of this tradition.


Costs and benefits of preemployment drug screening.
This study provides a cost-benefit analysis of preemployment drug screening and evaluates the sensitivity of this analysis to variation in its underlying assumptions. Cost-benefit analysis, based on a cohort analytic study previously reported. Employees of the US Postal Service in Boston, Mass. Estimates of costs and benefit are based on a cohort of 2533 postal workers in Boston and on average costs for the Postal Service in Boston and nationwide. Drug screening would have saved the Postal Service $162 per applicant hired. However, these results were sensitive to the assumptions in the model. If the prevalence of drug use in the population screened were 1% rather than 12%, the program would lose money. Similarly, if the cost per urine sample screened were $95 rather than the $49 assumed, then the program would lose money, even if the prevalence of drug positives was as high as 9%. Because of the sensitivity of this analysis to changes in its underlying assumptions, any company considering preemployment drug screening should carefully weigh the costs and benefits in its own industry.


High expression of dedicator of cytokinesis 1 (DOCK1) confers poor prognosis in acute myeloid leukemia.
DOCK family genes encode evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase involving multiple biological functions. Yet the patterns and prognostic significance of their expression in acute myeloid leukemia (AML) remain unexplored. Here we analyzed the expression patterns of 11 DOCK family genes in AML cells based on the array data of 347 patients from our cohort and several other published datasets. We further focused on the implications of the expression of DOCK1 since it was the only one in DOCK family to be associated with survival. Physiological functions and biological pathways associated with DOCK1 were identified using bioinformatics approaches. With a median follow up of 57 months, higher DOCK1 expression was associated with shorter disease free and overall survival. The finding could be validated by two independent cohorts. Multivariate analysis showed higher DOCK1 expression as a strong independent unfavorable prognostic factor. Higher DOCK1 expression was closely associated with older age, higher platelet and peripheral blast counts, intermediate-risk cytogenetics, FLT3-ITD, MLL-PTD and mutations in PTPN11, NPM1, RUNX1, ASXL1 and DNMT3A. Functional enrichment analysis suggested the association of DOCK1 overexpression with several key physiological pathways including cell proliferation, motility, and chemotaxis. Therefore, we suggested that AML with higher DOCK1 expression showed characteristic clinical and biological features. DOCK1 expression is an important prognostic marker and a potential therapeutic target for the treatment of AML. Studies in large prospective cohorts are necessary to confirm our findings. Further mechanistic studies to delineate the role of DOCK1 in the leukemogenesis are warranted.


Bacterial Spectrum and Infective Foci in Patients Operated for Infective Endocarditis: Time to Rethink Strategies?
The rising incidence of infective endocarditis (IE) accompanied by the de-escalation of antibiotic prophylaxis and the complexity of surgical treatment makes IE a daunting foe. We reviewed all patients who underwent cardiac surgery for IE at our institution with a focus on causative organisms and infective foci. A review of 3,952 consecutive patients who underwent cardiac surgery at our institution between January 2013 and December 2017 revealed 160 patients (4%) who were operated for IE. The predominantly affected valves were the aortic (30%) and mitral valve (26.9%) as well as a combination of both (8.8%). A total of 28.8% of patients suffered from prosthetic valve endocarditis (PVE). The most frequently identified causative organisms were Staphylococcus (45.7%), Streptococcus (27.5%), and Enterococcus species (16.7%), which was predominantly associated with PVE (p = 0.050). In 13.1% of patients, a causative organism has not been detected. The most frequent infective foci were dental (15%), soft-tissue infections (15%), spondylodiscitis (10%), and infected intravascular implants (8.8%). Relevant predisposing factors were immunosuppression (9.4%) and intravenous drug abuse (4.4%). Septic cerebral infarctions were diagnosed in 28.8% of patients. Postoperative mortality was 22.5%. As the bacterial spectrum and the infective foci are still the "old acquaintances," and with regard to the increasing incidence of IE, current risk-benefit evaluations concerning antibiotic prophylaxis may need to be revisited.


Evidence for the in vitro metabolism of allylisopropylacetamide to reactive intermediates. Mechanistic studies with oxygen-18.
Metabolism of allylisopropylacetamide (AIA) (1) in microsomal preparations from phenobarbital-pretreated rats is shown to proceed by way of three cytochrome P-450-dependent pathways: (i) aliphatic (C-3') hydroxylation, (ii) allylic (C-3) hydroxylation and (iii) olefin oxidation. The latter represents the major route of biotransformation and leads ultimately to the formation of the gamma-butyrolactone 2. In order to elucidate the mechanism by which AIA is converted to this gamma-lactone, and to gain information on the nature of chemically reactive intermediates in the process, the metabolism of AIA to 2 was investigated in 18O2 or H218O and the pattern of label incorporated into the product was determined by gas chromatography/mass spectrometry (GC/MS). The results support the formation of AIA epoxide as an initial product of olefin oxidation and indicate that this species undergoes rapid intramolecular rearrangement to a protonated iminolactone which, in turn, is hydrolysed to the stable gamma-lactone. On the other hand, the 'dihydrodiol' metabolite of AIA, which would be expected to result from direct hydrolysis of AIA epoxide, was not detected in incubation products and, furthermore, the 18O labeling data specifically exclude the possibility that it served as a precursor of 2. It may be concluded, therefore, that AIA epoxide and the protonated iminolactone to which it gives rise represent reactive intermediates in the oxidation of AIA which may play a key role in the alkylation of certain cellular constituents which accompanies metabolism of AIA by liver enzymes.


Brain involvement in extracranial internal carotid artery aneurysms.
No prospective study of extracranial internal carotid artery aneurysms (EICAA) has been reported to date. The aim of this study was to evaluate central nervous system complications associated with surgical intervention for EICAA. A total of seven patients, representing all cases observed at our institution from December 1997 to December 1998, were entered in this prospective study. Three patients had bilateral involvement. The aneurysms were both atherosclerotic and dysplastic. All patients were males, with mean age of 70 years (range 65 to 74). Internal or common carotid artery to EICAAs diameter ratios were calculated on the angiograms. The transverse diameter as well as the craniocaudal extension of the lesions were accurately measured intraoperatively. Follow-up evaluations were performed at three, six and twelve months postoperatively, and consisted of a clinical evaluation by both a neurologist and a vascular surgeon who were not part of the primary surgical team. Six patients presented with neurological symptoms ranging from non-hemispheric TIAs to hemispheric stroke. One patient was asymptomatic. The severity of symptoms was correlated with the size of the aneurysm. Preoperative symptoms were more severe in EICAAs of > or = 3 cm in transverse diameter. One case had a postoperative stroke, no perioperative deaths occurred. All the internal carotid arteries operated on were patent during follow-up evaluations. No new neurologic event was observed during follow-up. The severity of central neurologic symptoms seems to depend on the size of the aneurysmatic lesion. Prompt surgical management of small EICAAs may reduce the occurrence of severe CNS complications, both preoperatively and postoperatively, due to the lower risk of embolization associated with small aneurysms compared to larger lesions.


Direct Observation on Reaction Intermediates and the Role of Bicarbonate Anions in CO2 Electrochemical Reduction Reaction on Cu Surfaces.
Cu is the only monometallic catalyst that produces a large amount of hydrocarbon fuels during the CO2 electrochemical reduction reaction (CO2RR). However, the CO2RR mechanism and the impact of electrolyte are unclear. In this communication, two important issues regarding the CO2RR on Cu surfaces are studied: (1) the direct observation on reaction intermediates and (2) the role of the electrolyte (KHCO3) in the reaction. Surface-enhanced infrared absorption spectroscopy allows direct observation of several reaction intermediates that have never been detected before, except for the commonly detected CO. Another important finding is that CO2 molecules are mediated to the Cu surface via their equilibrium with bicarbonate anions instead of direct adsorption from the solution. These results shed light on the full understanding of the CO2RR on Cu surfaces and developing more advanced catalysts.


Impact of an Electronic Monitoring Intervention to Improve Adherence to Inhaled Medication in Patients with Asthma and Chronic Obstructive Pulmonary Disease: Study Protocol for a Randomized Controlled Trial.
Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among patients with asthma and chronic obstructive pulmonary disease (COPD) is high and patients are frequently hospitalized due to exacerbations. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. This causes substantial mortality, morbidity, and costs to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase and maintain treatment adherence in chronic diseases is of major clinical importance. The primary objective of this study is to investigate the impact of using specific, validated electronic devices on adherence to inhaled medication in patients with chronic obstructive lung diseases such as asthma and COPD. Furthermore, it aims to assess the impact of a reminder and close supervision of the course of disease and quality of life. In this ongoing prospective, single-blind, randomized controlled study, adherence to inhaled medication is analyzed over a 6-month period in at least 154 in- and outpatients with asthma or COPD who have experienced at least 1 exacerbation during the last year. Adherence is measured using electronic data capture devices, which save the date and time of each inhalative device actuation and transfer these data daily via a wireless connection to a Web-based database. Patients are randomly assigned to either the intervention or the control group. The clinical intervention consists of an automated and personal reminder. The intervention group receives an audio reminder and support calls in case medication has not been taken as prescribed or if rescue medication is used more frequently than pre-specified in the study protocol. During the study, participants are assessed every 2 months in the form of clinical visits. Recruitment started in January 2014. To date, a total of 169 patients have been recruited. Follow-up assessments are still ongoing. The study will be concluded in the first quarter of 2017. Data analysis will take place during 2017. Few studies have investigated medication adherence in patients with chronic obstructive lung diseases. With this prospective study design and the use of state-of-the-art devices for measuring adherence, we expect scientifically relevant and clinically meaningful results that will have a substantial and positive impact on the provision of healthcare in chronically ill patients suffering from asthma or COPD. ClinicalTrials.gov: NCT02386722; https://clinicaltrials.gov/ct2/show/NCT02386722 (Archived by WebCite at http://www.webcitation.org/6oJq1fel0).


Modulation of dendritic differentiation by corticotropin-releasing factor in the developing hippocampus.
The interplay of environmental and genetic factors in the developmental organization of the hippocampus has not been fully elucidated. The neuropeptide corticotropin-releasing factor (CRF) is released from hippocampal interneurons by environmental signals, including stress, to increase synaptic efficacy. In the early postnatal hippocampus, we have previously characterized a transient population of CRF-expressing Cajal-Retzius-like cells. Here we queried whether this stress-activated neuromodulator influences connectivity in the developing hippocampal network. Using mice deficient in the principal hippocampal CRF receptor [CRF(1)(-/-)] and organotypic cultures grown in the presence of synthetic CRF, or CRF receptor antagonists, we found robust effects of CRF on dendritic differentiation in hippocampal neurons. In CRF(1)(-/-) mice, the dendritic trees of hippocampal principal cells were exuberant, an effect that was induced in normal hippocampi in vitro by the presence of CRF(1) antagonists. In both cases, total dendritic length and dendritic branching were significantly increased. In contrast, exogenous synthetic CRF blunted the dendritic growth in hippocampal organotypic cultures. Taken together, these findings suggest that endogenous CRF, if released excessively by previous early postnatal stress, might influence neuronal connectivity and thus function of the immature hippocampus.


Does overcorrecting minus lens therapy for intermittent exotropia cause myopia?
Overcorrecting minus lens therapy has been used as a treatment for intermittent exotropia. It is based on the principle that an exotropic deviation will be decreased by stimulating accommodative convergence with additional minus power in spectacles. Because excessive accommodation has been implicated as a cause of myopia, there is theoretical concern that overcorrecting minus lens therapy for exotropia may cause myopia. To investigate the effect of overcorrecting minus lens therapy for exotropia on the progression of myopia. A retrospective chart review. Seventy-four patients with intermittent exotropia were treated with overcorrecting minus lens therapy for at least 6 months (6-month treatment group), and a 34-patient subset of them received overcorrecting minus lens therapy for 5 years (5-year treatment group). The mean change in refractive error (spherical equivalent of the fixing eye) of these 2 groups 5 years after initial examination was compared with the mean change in refractive error of a control group of 45 patients with intermittent exotropia who did not receive overcorrecting minus lens therapy. At the time of initial examination, the mean (+/-SD) refractive error was 0.00 +/- 1.40 diopters (D) in the control group, 0.00 +/- 1.50 D in the study group, and -0.10 +/- 1.50 D in the 5-year study group, all of which were essentially identical. Five years after initial examination, the mean change in refractive error was -1.40 +/- 2.80 D in the control group, -1.52 +/- 1.80 D in the 6-month treatment group, and -1.54 +/- 1.80 D in the 5-year treatment group. These differences in the change in refractive error (myopic shift) were not statistically significant (t test), and the differences are clinically unimportant. Overcorrecting minus lens therapy for intermittent exotropia does not appear to cause myopia.


Dielectric continuum model examination of real-space electrostatic treatments.
Electrostatic interaction is long ranged; thus, the accurate calculation is not an easy task in molecular dynamics or Monte Carlo simulations. Though the rigorous Ewald method based on the reciprocal space has been established, real-space treatments have recently become an attractive alternative because of the efficient calculation. However, the construction is not yet completed and is now a challenging subject. In an earlier theoretical study, Neumann and Steinhauser employed the Onsager dielectric continuum model to explain how simple real-space cutoff produces artificial dipolar orientation. In the present study, we employ this continuum model to explore the fundamental properties of the recently developed real-space treatments of three shifting schemes. The result of the distance-dependent Kirkwood function GK(R) showed that the simple bare cutoff produces a well-known hole-shaped artifact, whereas the shift treatments do not. Two-dimensional mapping of electric field well explained how these shift treatments remove the hole-shaped artifact. Still, the shift treatments are not sufficient because they do not produce a flat GK(R) profile unlike ideal no-cutoff treatment. To test the continuum model results, we also performed Monte Carlo simulations of dipolar particles. The results found that the continuum model could predict the qualitative tendency as to whether each electrostatic treatment produces the hole-shaped artifact of GK(R) or not. We expect that the present study using the continuum model offers a stringent criterion to judge whether the primitive electrostatic behavior is correctly described or not, which will be useful for future construction of electrostatic treatments.


Diffusion tensor imaging (DTI) in the detection of white matter lesions in patients with mild cognitive impairment (MCI).
Mild cognitive impairment (MCI) is recognized as a precursor to dementia. The amnestic MCI progresses usually to Alzheimer disease. Amnestic MCI multiple domain (md-MCI) seems to progress more rapidly than amnestic MCI single domain (a-MCI). In an attempt to identify patients at risk, we examined white matter changes in MCI subtypes using diffusion tensor imaging (DTI). We also tried to correlate DTI findings to neuropsychological tests. Forty-four amnestic single domain (a-MCI) patients, 19 amnestic multi domain (md-MCI), and 25 cognitively normal (NC) controls were included in the present study. All participants were assessed clinically using a battery of cognitive tests. DTI was performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Areas studied were corpus callosum, posterior cingulum (PC), anterior cingulum (AC), and superior longitudinal fasciculus (SLF). ADC and FA of the above areas were related to the scores of certain neuropsychological tests that evaluate visual and verbal memory. No difference in DTI measurements was found between the two MCI subtypes. ADC in MCI cases was increased in comparison with NC in the genu, PC, right SLF, and left AC. FA was spared. Verbal memory was related to ADC of the genu, PC, right AC and right SLF, and to FA of the left SLF. Visual memory was related to ADC of the genu, PC, right AC, and SLF. The strongest correlation found was between the visual memory and the ADC of the right PC (Spearman ρ = 0.45, p < 0.001). DTI revealed that ADC was increased in certain brain areas in MCI patients. No difference in DTI measurements was found between the two MCI subtypes. DTI indices correlate with cognitive performance.


Photoreversible DNA condensation using light-responsive surfactants.
A means to control DNA compaction with light illumination has been developed using the interaction of DNA with a photoresponsive cationic surfactant. The surfactant undergoes a reversible photoisomerization upon exposure to visible (trans isomer, more hydrophobic) or UV (cis isomer, more hydrophilic) light. As a result, surfactant binding to DNA and the resulting DNA condensation can be tuned with light. Dynamic light scattering (DLS) measurements were used to follow lambda-DNA compaction from the elongated-coil to the compact globular form as a function of surfactant addition and light illumination. The results reveal that compaction occurs at a surfactant-to-DNA base pair ratio of approximately 7 under visible light, while no compaction is observed up to a ratio of 31 under UV light. Upon compaction, the measured diffusion coefficient increases from a value of 0.6 x 10(-8) cm2/s (elongated coil with an end-to-end distance of 1.27 microm) to a value of 1.7 x 10(-8) cm2/s (compact globule with a hydrodynamic radius of 120 nm). Moreover, the light-scattering results demonstrate that the compaction process is completely photoreversible. Fluorescence microscopy with T4-DNA was used to further confirm the light-scattering results, allowing single-molecule detection of the light-controlled coil-to-globule transition. These structural studies were combined with absorbance and fluorescence spectroscopy of crystal violet in order to elucidate the binding mechanism of the photosurfactant to DNA. The results indicate that both electrostatic and hydrophobic forces are important in the compaction process. Finally, a DNA-photosurfactant-water phase diagram was constructed to examine the effects of both DNA and surfactant concentration on DNA compaction. The results reveal that precipitation, which occurs during the latter stages of condensation, can also be reversibly controlled with light illumination. The combined results clearly show the ability to control the interaction between DNA and the complexing agent and, therefore, DNA condensation with light.


Central antiserotonin action of fluperlapine.
The effect of fluperlapine--a new nonclassical neuroleptic--on the central serotoninergic system was studied. Fluperlapine antagonizes the head-twitch response induced by 5-hydroxytryptophan in mice and rats (the ED50 values are 0.3 mg/kg ip and 0.89 mg/kg ip respectively), counteracts forepaw clonic convulsions and tremor induced by tryptamine in rats (ED50 = 9.0 mg/kg ip and 7.5 mg/kg ip respectively), and abolishes hyperthermia induced by fenfluramine. In the flexor reflex preparation in spinal rats fluperlapine depresses the reflex only when given in higher doses. The drug given in low doses abolishes the stimulation of the flexor reflex evoked by quipazine and LSD (serotonin agonists) but not by clonidine (noradrenaline agonist). Higher doses of fluperlapine antagonise also the stimulatory effect of clonidine. Our findings demonstrate that fluperlapine shows potent central antiserotonin activity.


Interaction among Worm-like Micelles in Polyoxometalate-Based Supramolecular Hydrogel.
The co-assembly of zwitterionic amphiphile and polyoxometalate is a new and promising technique to construct a hierarchical and multifunctional supramolecular hydrogel. To comprehensively investigate the assemble mechanism, zwitterionic amphiphiles with different cations, namely, 3-(1-hexadecyl-3-imidazolio) propanesulfonate (C16IPS) and 3-(1-hexadecyl-2-methyl-3-imidazolio) propanesulfonate (C16bIPS), were designed to complex with silicotungstic acid (HSiW). Hydrogen bonding between the oxygen atoms of HSiW and the protons on C-2 of the imidazolium rings and the steric effect significantly influence the morphology and rheological property of the hydrogel. Interestingly, cross-linked worm-like micelles in parallel, vertical, and tilted distribution were observed using cryogenic transmission electron microscopy. In addition, these aggregates were further stacked into hexagonal phases on a large scale. Hence, deep insights into the relationship among the structure of zwitterionic amphiphile, self-assembled architecture, and the mechanical property of a polyoxometalate-based hydrogel were disclosed.


Free-ranging rural dogs are highly infected with helminths, contaminating environment nine times more than urban dogs.
Regardless of the highly efficient anthelmintics available and the control measures taken by dog owners and veterinarians, gastrointestinal parasites, especially zoonotic helminths, are still abundant in dogs and pose a health risk to humans. Free-ranging dogs in rural areas can be an important source of helminth infection. The aims of the present work were to collect scats of rural dogs, determine the environmental contamination caused by helminth infections among rural dogs of Western Estonia, analyse how diet affects helminth infection rate and compare the findings to a previous study focusing on dog helminths in urban areas of Estonia. To differentiate the scats of dogs from other sympatric canids, a genetic method was applied. Of 328 samples, genetic analysis identified 84 scats belonging to dogs, of which 87.0% were infected with helminths. A high proportion of rural dog scats harboured eggs of Taeniidae (65.5%), followed by Trichuris spp./Eucoleus spp. (15.5%), Uncinaria stenocephala (14.7%) and Toxocara canis (4.3%). Coinfections occurred in 34.5% of the samples, being the most common between Taeniidae and U. stenocephala (41.4%). The intensity model indicated higher helminth infection rate in rural dogs preying on rodents and game. In comparison to urban dogs, rural dogs were nine times more likely to be infected with intestinal parasites. These results emphasize the need to implement measures to reduce helminth infections in dogs living in rural areas of Western Estonia. Among a complex of measures to be taken, we suggest that it is also important to diagnose which gastrointestinal parasite species infect dogs to determine specific anthelmintic treatment against these parasites.


[Diagnosis of acute appendicitis over two decades - effects of increasing number of imaging procedures on costs, preoperative reliability and patient outcome].
An increasing number of modern imaging procedures are being applied for the diagnosis of appendicitis. We compared one hundred consecutive appendectomies of the years 1988, 1998 and 2008 concerning reliability of preoperative diagnosis and resulting costs. We analysed the first one hundred consecutive patients undergoing appendectomy during the years 1988, 1998 and 2008, 59 % were female and 41 % male. The average age was 26 years, the average BMI 21.09. The costs and results of radiological investigations (US, CT, MRI, X-ray) have been compared in all patients. The sensitivity of ultrasound and CT scan in preoperative diagnosis has been analysed. The number of preoperative imaging procedures for the diagnosis of appendicitis has increased over the last two decades. Simultaneously increased the costs (total costs and costs per partient) for imaging procedures. 2008 the costs were 10 times higher than 1988. CT had a higher sensitivity (77 %) in the diagnosis of appendicitis than ultrasound (33 %). The number of operations because of subacute and chronic appendicitis was lower in 2008 (34 of 100) compared with 1988 (80 of 100) and 1998 (60 of 100). In 2008 (14) we found a higher number of gangrenous and perforated appendicitis compared to 1988 (2) and 1998 (5). The majority (50 of 100) of patients in the group with acute and phlegmonous appendicitis was found in 2008. There has been an increase in the use of preoperative imaging procedures in the diagnosis of appendicitis during the last 20 years. This causes more costs in the public health system. Ultrasound as the standard imaging method for diagnosing appendicitis showed poor sensitivity. CT scans had good results concerning sensitivity, but are expensive and involve exposure to radiation for the patient.


The 17-gene Genomic Prostate Score assay as a predictor of biochemical recurrence in men with intermediate and high-risk prostate cancer.
The validated 17-gene Oncotype DX Genomic Prostate Score® (GPS™) assay risk-stratifies prostate-cancer patients with localized disease. The assay has primarily been utilized in lower risk patients deciding between active surveillance versus definitive therapy. In this retrospective cohort study, we analyze the association of the GPS result with time to biochemical recurrence post-prostatectomy in patients with National Comprehensive Cancer Network® (NCCN) intermediate and higher risk prostate cancer. The 141 patients included in the study were from the NorthShore University HealthSystem diagnosed 2014-2019 with NCCN intermediate (n = 109) or higher risk (n = 32) prostate cancer, treated with radical prostatectomy 2015-2019. The association of GPS result with time to biochemical recurrence was evaluated using univariable and multivariable Cox proportional hazards models in 120 patients with unfavorable intermediate or higher risk. Median (interquartile range) follow-up time was 28 (20 to 38) months. The GPS result was significantly associated with time to biochemical recurrence as both a continuous and dichotomous variable in univariable (hazard ratio [HR] per 20 GPS units 2.36, 95% CI 1.45-3.80, p < 0.001; HR for GPS result 41-100 vs 0-40 3.28, 95% CI 1.61-7.19, p < 0.001) and in multivariable models accounting for NCCN risk group (HR per 20 GPS units 2.14, 95% CI 1.31-3.46, p = 0.003; HR for GPS result 41-100 vs 0-40 3.00, 95% CI 1.43-6.72, p = 0.003) or biopsy Gleason Score and diagnostic PSA or PSA density. These results indicate that the GPS assay was a strong predictor of biochemical recurrence after radical prostatectomy in this unfavorable intermediate and higher risk prostate cancer patient population.


Cortical laminar necrosis and central pontine myelinolysis in a patient with Sheehan syndrome and severe hyponatremia.
Hypoxic encephalopathy and osmotic demyelination are independent clinical entities. We describe a rare case with these two complications as demonstrated by magnetic resonance imaging (MRI). A 58-year-old woman had adrenal crises twice a decade due to Sheehan syndrome. At the second crisis, hyponatremia was remarkable with consciousness disturbance which was rapidly corrected by intravenous administration of glucocorticoid and hypertonic saline. The maneuver improved consciousness disturbance, but resulted in hypokalemic ventricular fibrillation with circulatory failure. After the normalization of the circulation, however, her consciousness level deteriorated again. Repeated brain MRI revealed acute and chronic phases of cortical laminar necrosis and central pontine myelinolysis.


A systematic review of rehabilitation and exercise recommendations in oncology guidelines.
Guidelines promote high quality cancer care. Rehabilitation recommendations in oncology guidelines have not been characterized and may provide insight to improve integration of rehabilitation into oncology care. This report was developed as a part of the World Health Organization (WHO) Rehabilitation 2030 initiative to identify rehabilitation-specific recommendations in guidelines for oncology care. A systematic review of guidelines was conducted. Only guidelines published in English, for adults with cancer, providing recommendations for rehabilitation referral and assessment or interventions between 2009 and 2019 were included. 13840 articles were identified. After duplicates and applied filters, 4897 articles were screened. 69 guidelines were identified with rehabilitation-specific recommendations. Thirty-seven of the 69 guidelines endorsed referral to rehabilitation services but provided no specific recommendations regarding assessment or interventions. Thirty-two of the 69 guidelines met the full inclusion criteria and were assessed using the AGREE II tool. Twenty-one of these guidelines achieved an AGREE II quality score of ≥ 45 and were fully extracted. Guidelines exclusive to pharmacologic interventions and complementary and alternative interventions were excluded. Findings identify guidelines that recommend rehabilitation services across many cancer types and for various consequences of cancer treatment signifying that rehabilitation is a recognized component of oncology care. However, these findings are at odds with clinical reports of low rehabilitation utilization rates suggesting that guideline recommendations may be overlooked. Considering that functional morbidity negatively affects a majority of cancer survivors, improving guideline concordant rehabilitative care could have substantial impact on function and quality of life among cancer survivors.


Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses.
Influenza A H3N2 variant [A(H3N2)v] viruses, which have caused human infections in the United States in recent years, originated from human seasonal H3N2 viruses that were introduced into North American swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating H3N2 strains. A reference A(H3N2)v virus, A/Minnesota/11/2010 (MN/10), and a seasonal H3N2 strain, A/Beijing/32/1992 (BJ/92), were chosen to determine the molecular basis for the antigenic difference between A(H3N2)v and the ancestral viruses. Viruses containing wild-type and mutant MN/10 or BJ/92 hemagglutinins (HAs) were constructed and probed for reactivity with ferret antisera against MN/10 and BJ/92 in hemagglutination inhibition assays. Among the amino acids that differ between the MN/10 and BJ/92 HAs, those in antigenic site A had little impact on the antigenic phenotype. Within antigenic site B, mutations at residues 156, 158, 189, and 193 of MN/10 HA to those in BJ/92 switched the MN/10 antigenic phenotype to that of BJ/92. Mutations at residues 156, 157, 158, 189, and 193 of BJ/92 HA to amino acids present in MN/10 were necessary for BJ/92 to become antigenically similar to MN/10. The HA amino acid substitutions responsible for switching the antigenic phenotype also impacted HA binding to sialyl receptors that are usually present in the human respiratory tract. Our study demonstrates that antigenic site B residues play a critical role in determining both the unique antigenic phenotype and receptor specificity of A(H3N2)v viruses, a finding that may facilitate future surveillance and risk assessment of novel influenza viruses. Influenza A H3N2 variant [A(H3N2)v] viruses have caused hundreds of human infections in multiple states in the United States since 2009. Most cases have been children who had contact with swine in agricultural fairs. These viruses originated from human seasonal H3N2 viruses that were introduced into the U.S. swine population in the mid-1990s, but they are different from both these ancestral viruses and current circulating human seasonal H3N2 strains in terms of their antigenic characteristics as measured by hemagglutination inhibition (HI) assay. In this study, we identified amino acids in antigenic site B of the surface glycoprotein hemagglutinin (HA) that explain the antigenic difference between A(H3N2)v and the ancestral H3N2 strains. These amino acid mutations also alter binding to minor human-type glycans, suggesting that host adaptation may contribute to the selection of antigenically distinct H3N2 variants which pose a threat to public health.


Functional Organization of the Chlorophyll-Containing Complexes of Chlamydomonas reinhardi: A Study of Their Formation and Interconnection with Reaction Centers in the Greening Process of the y-1 Mutant.
The stepwise synthesis and assembly of photosynthetic membrane components in the y-1 mutant of Chlamydomonas reinhardi have been previously demonstrated (Ohad 1975 In Membrane Biogenesis, Mitochondria, Chloroplasts and Bacteria, Plenum, pp 279-350). This experimental system was used here in order to investigate the process of formation and interconnection of the energy collecting chlorophylls with the reaction centers of both photosystems I and II. The following measurements were carried out: photosynthetic electron flow at various light intensities, including parts or the entire electron transfer chain; analysis of the kinetics of fluorescence emission at room temperature and fluorescence emission spectra at 77 K, and electrophoretic separation of membrane polypeptides and chlorophyll protein complexes. Based on the data obtained it is concluded that: (a) each photosystem (PSI and PSII) contains, in addition to the reaction center, an interconnecting antenna and a main or light harvesting antenna complex; (b) the formation of the light harvesting complex, interconnecting antenna, and reaction centers for each photosystem can occur independently. (c) the interconnecting antennae link the light harvesting complexes with the respective reaction centers. In their absence, energy transfer between the light harvesting chlorophylls and the reaction centers is inefficient. The formation of the interconnecting antennae and efficient assembly of photosystem components occur simultaneously with the de novo synthesis of chlorophyll and at least three polypeptides, one translated in the cytoplasm and two translated in the chloroplast. The synthesis of these polypeptides was found to be light dependent.


African urbanization: dependent linkages in a global economy.
"The colonial experience drastically altered the indigenous urban system in Africa, replacing it with a European-driven urban system designed to facilitate the extraction of resources. The urban system and the nature of ties with the colonial power allowed African integration into the world economy only in a dependent fashion. These dependent ties were deepened as the world economy became more globalized in the post-colonial period. The continent rapidly urbanized, with much of the population concentrating in primate cities. This urbanization was not accompanied by economic growth; as a result Africa will soon become a continent of large cities--with urban population they cannot physically and economically support."


Delivery of mobile dental services to dependent elderly people: results from a pilot study in rural Switzerland.
The objective of this pilot study was to provide data on the oral health status and oral health behaviour of care-dependent elderly people in the canton of Uri. The study aimed at assessing whether age and duration of living in a nursing home is associated with dental attendance, whether there is a relationship between age and the DMF-T index, and how high the risk was for participants to develop oral health problems. The study offered mobile dental services to people residing in nursing homes (NHG) and to community dwellers (CDG). Data was collected on demographics, medical history, presence of pain, ability to eat and oral health behaviour by means of a questionnaire. A clinical examination was performed and data on the oral status was collected. Statistical methods were: median tests, linear regressions and descriptive statistics. Uptake of the programme was low. 56 participants were examined. 47 participants (24 females, 23 males, average age 86.3 ± 7.36 years) resided in nursing home, nine participants (seven females, two males, average age 76 ± 12.8 years) were community dwellers. No significant differences were found between frequency of dental attendance and age (p = 0.35) or duration of stay in a nursing home (p = 0.55). The number of decayed teeth (p=0.005), missing teeth (p=0.01), and the DMF-T index (average in NHG = 26.5, CDG = 20.2, p < 0.001) increased, the number of filled teeth (p=0.02) decreased as age increased. Upon calculation of the 'Teamwerk-index', which takes into account oral health behaviour, dental caries, periodontal status, the majority of participants had a medium risk of developing oral health problems. Our pilot study in rural Switzerland provides first results of the oral health status in dependent elderly people. As people age, oral health deteriorates. More attention should be given in order to achieve better oral hygiene maintenance and more regular dental visits, to ensure a better oral health status in dependent elderly people.


Slow-cooling protocols for crystallographic refinement by simulated annealing.
An improved protocol for crystallographic refinement by simulated annealing is presented. It consists of slow cooling starting at high temperatures. Tests of refinements of aspartate aminotransferase and procin pepsin show that the slow-cooling protocol produces lower R factors and better geometry than other protocols previously published. The influence of the temperature-control method, weighting, cooling rate and duration of the heating stage on the success of the slow-cooling protocol is studied. Analysis of the time course of the potential-energy fluctuations indicates no global changes in the state of order of the system. Fluctuations of the potential energy are interpreted as localized conformational changes during the course of the refinement.


Variation in OPRM1 and risk of suicidal behavior in drug-dependent individuals.
Completed suicide and nonfatal suicide-related outcomes (SROs), such as suicidal ideation and attempts, are heritable. A recent genetic association study in a sample of suicide victims reported a protective effect of the G allele of Asn40Asp (rs1799971) on risk for completed suicide. We examined the association of three OPRM1 single nucleotide polymorphisms (SNPs) (rs1799971, rs609148, and rs648893) with SRO in 426 European Americans, using GEE logistic regression analysis to examine the association of a lifetime history of SRO. There was no allelic association with the SRO phenotypes. A larger sample may be needed to identify risk variants that convey SRO risk. OPRM1 may not be important in the risk of SRO.


Estimating radiation doses to the skin from interventional radiology procedures for a patient population with cancer.
To estimate the peak radiation skin doses for interventional radiology cases performed at a cancer center, identify procedure types likely to result in skin doses exceeding the American College of Radiology's 3 Gy follow-up level, and determine a kerma area product (P(KA)) for use in monitoring. A single-center retrospective study was performed to estimate doses from consecutive procedures performed during 2006. Of 6,598 procedures, 3,925 (60%) had P(KA) recorded and were included. Forty-three procedure types are represented. The median estimated peak skin dose was 39 mGy (third quartile, 205 mGy). In 2.6% of the cases, the estimated skin dose exceeded 3 Gy. No procedures resulted in skin doses greater than 15 Gy, and 94% of the cases resulted in skin doses less than 1 Gy. Procedure types with instances of skin doses greater than 1 Gy included hepatic, portal, and other arterial embolizations; diagnostic arteriography; biliary drainages; stent placements and catheter exchanges; nephrostomy/nephroureterostomy; urinary catheter exchanges; inferior vena cava filters; foreign body retrieval; abscess drainage; catheter exchange; and fistulography. Hepatic embolizations, nonhepatic arterial embolizations, and biliary drain/stent procedures were most likely to result in skin doses greater than 1 Gy. Significant variations in skin dose were noted within the same procedure type. No patients were noted to have developed any sequelae from radiation. It is unlikely that typical cases in an oncologic interventional radiology practice would exceed the Joint Commission's "reviewable sentinel event" skin dose level of 15 Gy. A P(KA) trigger of 300 Gy cm(2) could be used in the authors' clinic to identify follow-up requirements.


[Children as a burden, children as a joy: theses on family formation and number of children].
"This article surveys significant changes in fertility and nuptiality in Central and Western Europe since the middle of the 19th century. In this context the secular decline in birth rates is understood as a consequence of changes in the social structure as well as of diffusion of social norms." It is noted that for the period after 1920, and especially after 1950, no "determinants" exist that can completely explain fluctuations in marriages and births. "Hence, the central thesis of this article is the following: There is no stable pattern of family formation in a modern industrial society and the number of children is not directly linked to mortality conditions or economic constraints. Subsequently, the article develops several hypotheses concerning the significance of marriage and parenting in the late 20th century, and points out that ups and downs in marriages, divorces, and births may be seen in analogy to other fashion-like processes (such as consumer behavior or social behavior)." (summary in ENG)


Fibronectin peptide DRVPHSRNSIT and fibronectin receptor peptide DLYYLMDL arrest gastrulation of Rana pipiens.
Gastrulation is characterized by dramatic cell migration which is thought to require the interaction of cell adhesion molecules with extracellular molecules. We have tested two novel peptides, a fibronectin peptide and a fibronectin receptor peptide, for their effects on gastrulation of the leopard frog Rana pipiens. The fibronectin peptide DRVPHSRNSIT corresponds to residues 1373-1383 of the cell-binding domain of fibronectin; the receptor peptide DLYYLMDL corresponds to residues 124-131 of beta 1 subunit of a variety of integrins including alpha 5 beta 1. Either of these peptides significantly inhibited gastrulation after being microinjected into mid-blastulae. These results indicate that these sequences may correspond to the ligand/receptor interaction sites of fibronectin and its receptor(s).


A biomechanical study of the Birmingham mid head resection arthroplasty: effect of stem size on femoral neck fracture.
The Birmingham mid head resection (BMHR) arthroplasty can be used as an alternative to conventional stemmed total hip arthroplasty in young patients unsuitable for hip resurfacing. This study investigated the effect of stem size on femoral neck fracture in the BMHR. Sawbones composite femurs were randomly allocated to one of the following groups: (1) unprepared femur with no prosthesis, (2) femur prepared with a Birmingham hip resurfacing (BHR) prosthesis, (3) femur prepared with a BMHR stem size 1 (BMHR-1) and (4) femur prepared with a BMHR stem size 3 (BMHR-3). Each femur was subjected to a compressive force using a materials testing machine until fracture of the femoral neck occurred. The highest force at fracture was in the unprepared femurs with a mean (±standard deviation) force at failure of 5.9 ± 0.2 kN. The mean force at failure for the femurs fitted with a prosthesis was 2.6 ± 0.4, 3.0 ± 0.4 and 3.5 ± 0.5 kN for the BHR, BMHR-1 and BMHR-3, respectively. Statistical analysis showed that the failure force for the unprepared femur was significantly (p<0.05) greater than that of the BHR, BMHR-1 and BMHR-3. There was a significant difference (p<0.05) between the force at failure for the BMHR-1 and BMHR-3, indicating that these two stem sizes have an effect on fracture force.


Redefining consumer roles: changing culture & practice in mental health care settings.
The creation of positions for CSPs is a phenomenon with a promising future for the delivery of mental health services. People who have direct experiences are the ones who best know the possibility of recovery from mental illness. They are the only ones who can serve as role models for others, providing them with hope and inspiration. With courage and determination, CSPs will make good partners with non-consumer providers, each needing to listen and learn from the other to work together effectively and to keep the wishes of those they serve as their highest priority.


[Development of child mental health services in Lithuania: achievements and obstacles].
In 1990, political, economic and social changes in Lithuania introduced the possibility to develop for the first time in nations's history an effective and modern system of child mental health services. During the period between 1990 and 1995 a new model of services was developed in the Department of Social pediatrics and child psychiatry of Vilnius University. The model included development of child and adolescent psychiatric services, as well as early intervention services for infants and preschool children with developmental disabilities. The emphasis, following recommendations of WHO and existing international standards, was made on deinstitutionalization and development of family-oriented and community-based services, which have been ignored by previous system. In the first half of 90's of 20th century, new training programs for professionals were introduced, more than 50 methods of assessment, treatment and rehabilitation, new for Lithuanian clinical practice, were implemented, and a new model of services, including primary, secondary and tertiary level of prevention, was introduced in demonstration sites. However, during next phase of development, in 1997-2001, serious obstacles for replicating new approaches across the country, have been identified, which threatened successful implementation of the new model of services into everyday clinical practice. Analysis of obstacles, which are blocking development of new approaches in the field of child mental health, is presented in the article. The main obstacles, identified during analysis of socioeconomic context, planning and utilization of resources, running of the system of services and evaluation of outcomes, are as follows: lack of intersectorial cooperation between health, education and social welfare systems; strong tradition of discrimination of psychosocial interventions in funding schemes of health services; societal attitudes, which tend to discriminate and stigmatize marginal groups, including disabled children and dysfunctional families; lack of evidence-based decision making in the process of health care reform and reform of social infrastructure.


Inequality as a basis for the U.S. emergence from the great stagnation.
A significant body of evidence suggests that capitalism entered an economic crisis phase in the late 1960s due to a fall in the rate of profit. With falling profits, corporations are compelled to find means of reducing costs by lowering wages and taxes and/or raising productivity. Attacks on the welfare state (in the form of the war on deficits and debts), unions, and government in general resulted in falling wages, longer hours of work, and increased poverty. Only in 1997, despite years of exaggeration about its macroeconomic recovery, did the United States finally have a true boom year, like something from the Golden Age of the 1950s or early 1960s: GDP, investment, productivity, employment, and even wages grew by reasonable historical standards. This article is an account of how this tentative recovery was accomplished--in part, by the state and corporate sectors' ability to generate inequality over the past quarter century--and how these changes in the macroeconomy changed the context for health and the health sector.


A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.
The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.


Broadening the scope of worksite stress programs: a guiding framework.
Abstract Worksite stress programs have proliferated in recent years. A large proportion of these programs focus on helping individual employees learn about stress and develop better coping skills. Few programs attempt to reduce the stressful aspects of the job or the organizational context. In order to facilitate the development of a broader array of stress reduction programs, the authors provide: 1) a conceptual framework upon which worksite stress programs should be based, 2) a guide to the variety of decision points in the program development process, 3) an exploration of the reasons why a broader range of stress programs have not heretofore been developed, and 4) suggestions for creating a context amenable to innovative worksite stress programs.


Determining the relationship between health anxiety and healthy lifestyle behaviors, and the factors that affect them: A cross-sectional study in Turkey.
This study was conducted to determine the relationship between health anxiety (HA) and healthy lifestyle behaviors (HLBs), and the factors that affect them. This descriptive, cross-sectional, and relational study was conducted with 1007 voluntary participants between June 1 and September 30, 2020. The participants' mean age was 33.46 ± 15.42 years. A positive-significant relationship was found between the participants' total HA and HLBs scores (r = 0.06, p = 0.03). The simple linear regression analysis performed by the researchers indicated that the explanatory power of HA as a determinant of HLBs was statistically significant (R2 = 0.05). This study determined that health anxiety increased the tendency towards HLBs.


Athlete Leadership Development Within Teams: Current Understanding and Future Directions.
Leadership has been shown to be a fundamental factor influencing the performance of sport teams. Within these teams, leadership can be provided by coaches, formal athlete leaders, such as team captains, and other 'informal' athlete leaders. The role of the athlete leader in a team, either formal or informal, has been consistently reported over the last 10 years to have a significant impact upon a teams' functioning and effectiveness, as well as teammates' general health and mental wellbeing. As such, cultivating the provision of this leadership within a team has emerged as an important focus for managers, coaches, sport psychologists and scholars alike. While the recognition of the importance of athlete leadership is well established, there has been a lag in the development of systematic approaches to enhance and develop the leadership skills and capabilities of the athletes within sport teams. As a result, this paper seeks to review contemporary examples and current understanding of approaches to athlete leadership development. The paper will also highlight future areas for research and applied practice development.


Auditory affective norms for German: testing the influence of depression and anxiety on valence and arousal ratings.
The study of emotional speech perception and emotional prosody necessitates stimuli with reliable affective norms. However, ratings may be affected by the participants' current emotional state as increased anxiety and depression have been shown to yield altered neural responding to emotional stimuli. Therefore, the present study had two aims, first to provide a database of emotional speech stimuli and second to probe the influence of depression and anxiety on the affective ratings. We selected 120 words from the Leipzig Affective Norms for German database (LANG), which includes visual ratings of positive, negative, and neutral word stimuli. These words were spoken by a male and a female native speaker of German with the respective emotional prosody, creating a total set of 240 auditory emotional stimuli. The recordings were rated again by an independent sample of subjects for valence and arousal, yielding groups of highly arousing negative or positive stimuli and neutral stimuli low in arousal. These ratings were correlated with participants' emotional state measured with the Depression Anxiety Stress Scales (DASS). Higher depression scores were related to more negative valence of negative and positive, but not neutral words. Anxiety scores correlated with increased arousal and more negative valence of negative words. These results underscore the importance of representatively distributed depression and anxiety scores in participants of affective rating studies. The LANG-audition database, which provides well-controlled, short-duration auditory word stimuli for the experimental investigation of emotional speech is available in Supporting Information S1.


Crossed polydactyly type I in a mother and son: an autosomal dominant trait?
In a Japanese family, a propositus and his mother had crossed polydactyly type I. A maternal grandaunt also had preaxial polydactyly of the feet. The findings that both of the mother and son had the identical type of polydactyly are consistent with an autosomal dominant inheritance with variable expressivity. Other explanations include X-linked recessive inheritance, polygenic inheritance, and a chance occurrence of the 2 different kinds of polydactyly.


The repair patch of E. coli (A)BC excinuclease.
The size of repair patch made by E. coli DNA polymerase I (Poll) following the removal of a thymine-psoralen monoadduct by E. coli (A)BC excinuclease was determined by using an M13mp19 DNA with a single psoralen monoadduct at the polylinker region. Incubation of this substrate with (A)BC excinuclease, Poll and a combination of 3 dnTP plus 1 dNTP(alpha S) for each nucleotide, and DNA ligase resulted in a repair patch with phosphorothioate linkages. The preferential hydrolysis of phosphorothioate bonds by heating in iodoethanol revealed a patch size--with minimal nick translation--equal in length to the 12 nucleotide gap generated by this excision nuclease.


Niacin mitigates rumen epithelial damage in vivo by inhibiting rumen epithelial cell apoptosis on a high concentrate diet.
To investigate the effects of niacin on rumen fermentation, rumen epithelial antioxidant activity, and rumen epithelial cell apoptosis on high concentrate (HC) diets, nine male Hu sheep were randomly fed one of three diets: low concentrate diet (LC; concentrate: forage (C:F) = 20:80, high concentrate diet (HC; C:F = 80:20), and HCN diet (HC diet + niacin at 800 mg/kg diet air-dry matter). Compared with the LC group, the HC group had a lower rumen pH, higher volatile fatty acids and lactic acid in the rumen, reduced activity of antioxidant enzymes and total antioxidant capacity, and increased malondialdehyde content in the rumen epithelium (P < 0.05). Rumen epithelial papilla morphology was decreased, and apoptosis-related indicators and serum inflammatory cytokines were increased in the HC group over the LC group (P < 0.05). Compared with the HC diet, the HCN diet increased rumen pH, rumen epithelium antioxidant capacity, and rumen epithelial papilla morphology, decreased rumen lactate content, serum inflammatory cytokines, and apoptosis-related indicators (P < 0.05). Therefore, adding 800 mg/kg niacin helped protect against rumen epithelial damage by avoiding drastic changes in the rumen environment and improved rumen epithelial antioxidant capacity to inhibit rumen epithelial cell apoptosis in sheep on a HC diet.


Effects of Modified Wenjing Decoction Combined with Online Publicity and Education on the Treatment of Primary Dysmenorrhea of Cold Coagulation and Blood Stasis.
To explore the effects of modified Wenjing decoction combined with online publicity and education on the treatment of primary dysmenorrhea of cold coagulation and blood stasis. The materials of 111 patients with primary dysmenorrhea of cold coagulation and blood stasis in the outpatient department (January 2019-June 2021) were collected to conduct the retrospective study. The 111 patients were randomized into treatment group (n = 59) and control group (n = 52). The control group received online publicity and education and conventional treatment, and the treatment group received online publicity and education and modified Wenjing decoction. The patients in the two groups were continuously treated for three menstrual cycles. The treatment effects, the dosage of analgesics, the scores of associated symptoms before and after treatment, and other indexes were compared between the two groups. The differences in the efficacy on abdominal pain were statistically significant between the two groups (P < 0.05). Compared with the control group, the treatment group had lower scores of associated symptoms after treatment (p < 0.5). After the treatment of three menstrual cycles, 54 patients in the treatment group stopped taking ibuprofen, and the average ibuprofen dosage of the other 5 patients was (0.24 ± 0.16)g. The 52 patients in the control group still needed to take ibuprofen, and the mean dosage was (0.51 ± 0.05)g. The differences in the ibuprofen dosage between the two groups had remarkable difference (P < 0.001). Modified Wenjing decoction combined with online publicity and education can obviously improve the clinical symptoms of the patients with primary dysmenorrhea of cold coagulation and blood stasis and reduce the dosage of analgesics. It is worth promoting and applying in practice.


THE ENVIRONMENTAL AND SAFETY PERFORMANCE OF GAS UTILITIES IN THE UNITED STATES.
The performance of energy service providers has important environmental and safety consequences in local communities. This paper uses a novel dataset compiled from operator reports and infrastructure monitoring data obtained from three different US federal agencies to assess the performance of retail gas utilities nationwide in terms of addressing gas leaks and minimizing leak volumes. Our panel data set includes yearly observations for 727 retail gas utilities from 2009 to 2017. We show that safety hazards and environmental costs of gas leaks are widespread across providers that vary in terms of ownership, size, and region. We then use series of Bayesian hierarchical models to regress four outcome variables--hazardous leaks, end-year unfixed leaks, total gas volume leaked, and significant incidents--on infrastructure conditions, regional service context, and socio-economic service population characteristics. Unlike what is observed in other critical infrastructure cases such as drinking water, socioeconomic conditions are not strongly predictive of service outcomes. Public utilities exhibit better environmental performance on average, and no difference in maintenance backlogs. Because the environmental costs of poor performance--primarily in terms of methane greenhouse gas emissions--are predominantly social, policy tools such as consolidation and privatization are unlikely to improve environmental outcomes.


Different effects on the expression of CYP7 and CYP27 in rabbit liver by cholic acid and cholestyramine.
It was recently reported that both cholesterol 7 alpha-hydroxylase CYP7 and sterol 27-hydroxylase CYP27 are subject to negative feedback control by bile acids in isolated rat hepatocytes and rat liver (Twisk et al., (1995) Biochem. J. 305, 505-511; Vlahcevic et al. XIII International Bile Acid Meeting, September 30-October 2, 1994, Abstract 17). In the present work a series of experiments was performed to study whether there is a coordinate regulation of CYP7 and CYP27 also in rabbit liver. Treatments of rabbits with cholic acid or cholestyramine resulted in marked suppression and induction, respectively, of CYP7 mRNA. In contrast, there were no significant effects on the CYP27 mRNA expression, amount of CYP27 protein or mitochondrial 27-hydroxylase activity. Thus, there is an apparent difference between rat and rabbit with respect to regulation of CYP27 by bile acids. It is concluded that, in rabbit, there is little or no coordinate regulation of CYP7 and CYP27 at a transcriptional level, and that CYP27 is not subject to a negative feedback control by bile acids neither at a transcriptional nor at a posttranscriptional level.


Use of ozonation technology to combat viruses and bacteria in aquatic environments: problems and application perspectives for SARS-CoV-2.
COVID-19 is a global health threat with a large number of confirmed cases and deaths worldwide. Person-to-person transmission through respiratory droplets and contact with aerosol-infected surfaces are the main ways in which the virus spreads. However, according to the updated literature, the new coronavirus (SARS-CoV-2) has also been detected in aqueous matrices, with the main route of transmission being feces and masks from patients diagnosed with the disease. Given the emergence of public health and environmental protection from the presence of lethal viruses and bacteria, this review article aims to report the major challenges associated with the application of ozonation in water contaminated with viruses and bacteria, in order to clarify whether these communities can survive or infect after the disinfection process and if it is efficient. Available data suggest that ozonation is able to increase the inactivation effect of microorganisms by about 50% in the logarithmic range, reducing infectivity. In addition, the evidence-based knowledge reported in this article is useful to support water and sanitation safety planning and to protect human health from exposure to cited contaminants through water.


Does everyone with inflammatory bowel disease need to be treated with combination therapy?
This article describes the evolution of combination therapy in inflammatory bowel disease and how to determine when combination may not be necessary. The combination of an immunosuppressive agent with an antibody to tumor necrosis factor has proven to be more effective than monotherapy with either an immunosuppressive agent or an antibody to tumor necrosis factor alone. The emergence of therapeutic drug monitoring has identified the importance of maintaining adequate circulating drug levels and suppressing antibody formation to the biological agent. The concomitant use of an immunosuppressive agent can help effect this. Although this may be optimal therapy in moderately ill patients. I review why there still remains a role for using monotherapy with immunosuppressive agents, as well as consideration of therapy withdrawal. Although combination therapy is the treatment of choice in persons with moderate to severe disease or who have lost response to biological monotherapy, there remains a role for monotherapy with immunosuppressive agents. Though the newer biological therapies are mostly not used in combination, this may be a future approach considering their response rates are also correlated with higher drug levels. Many persons with inflammatory bowel disease can remain well on an immunosuppressive agent alone and some can even maintain a longstanding remission off all therapy.


Effect of Moisture Distribution Changes Induced by Different Cooking Temperature on Cooking Quality and Texture Properties of Noodles Made from Whole Tartary Buckwheat.
While precooking and processing have improved the quality of gluten-free noodles, the effects of different cooking temperatures on their quality-neither gluten-free noodles nor whole Tartary buckwheat noodles-have rarely been clarified. This study investigated the key role of moisture distribution induced by different cooking temperatures in improving the noodle quality of whole Tartary buckwheat. The results showed that cooking temperatures higher than 70 °C led to a sharp increase in cooking loss, flavonoid loss and the rate of broken noodles, as well as a sharp decrease in water absorption. Moreover, the noodles cooked at 70 °C showed the lowest rate of hardness and chewiness and the highest tensile strength of all cooking temperatures from 20 °C to 110 °C. The main positive attribute of noodles cooked at 70 °C might be their high uniform moisture distribution during cooking. Cooking at 70 °C for 12 min was determined as the best condition for the quality improvement of whole Tartary buckwheat noodles. This is the first study to illustrate the importance of cooking temperatures on the quality of Tartary buckwheat noodles. More consideration must also be given to the optimal cooking conditions for different gluten-free noodles made from minor coarse cereals.


Stimulatory effect of a specific substance P antagonist (RPR 100893) of the human NK1 receptor on the estradiol-induced LH and FSH surges in the ovariectomized cynomolgus monkey.
Utilizing a human NK1 receptor antagonist (RPR 100893), the present in vivo study was designed to test the hypothesis that endogenous substance P (SP) modulates the action of 17beta-estradiol in inducing luteinizing hormone (LH) and follicle stimulating hormone (FSH) surges in ovariectomized cynomolgus monkey. Plasma concentrations of LH and FSH as well as NK1 receptor antagonist and SP were measured during the development of the negative and positive feedback phases which follow a single administration of estradiol benzoate (50 microg/kg) to long-term ovariectomized monkeys. Daily administration by gastric intubation of 1 mg/kg or 10 mg/kg of the NK1 receptor antagonist (RPR 100893) leads to detectable levels of the antagonist in the blood of treated animals for at least 6 hr after its administration. These levels are in agreement with the experimentally determined IC50 value of the antagonist. The most striking finding of this study is that LH and FSH releases are enhanced during the descending arm of the estradiol benzoate-induced LH and FSH surges, which suggests that endogenous SP normally has an inhibitory role during this time. The enhancement of LH release is approximately 50%, regardless of the amount of the NK1 antagonist used. However, the enhanced FSH release is more important. Furthermore, blockade of the NK1 receptor with the smaller dose of the antagonist leads to a small, but significant, increase in plasma levels of SP, indicating that blockade of SP receptors leads to an increased release of SP. Collectively, these results further substantiate the link which exists between the ovarian steroid 17beta-estradiol and SP systems. Also, for the first time, these results demonstrate an inhibitory involvement of the human NK1 receptor in the 17beta-estradiol-induced pseudo-ovulatory gonadotropin surges in the ovariectomized monkey.


Impact of infectious disease epidemics on xenophobia: A systematic review.
Background Globally, xenophobia towards out-groups is frequently increased in times of economic and political instability, such as in infectious disease outbreaks. This systematic review aims to: (1) assess the xenophobic attitudes and behaviors towards migrants during disease outbreaks; and (2) identify adverse health outcomes linked to xenophobia. Methods We searched nine scientific databases to identify studies measuring xenophobic tendencies towards international migrants during disease outbreaks and evaluated the resulting adverse health effects. Results Eighteen articles were included in the review. The findings were grouped into: (1) xenophobia-related outcomes, including social exclusion, out-group avoidance, support for exclusionary health policies, othering, and germ aversion; and (2) mental health problems, such as anxiety and fear. Depending on the disease outbreak, different migrant populations were negatively affected, particularly Asians, Africans, and Latino people. Factors such as perceived vulnerability to disease, disgust sensitivity, medical mistrust individualism, collectivism, disease salience, social representation of disease and beliefs in different origins of disease were associated with xenophobia. Conclusions Overall, migrants can be a vulnerable population frequently blamed for spreading disease, promoting irrational fear, worry and stigma in various forms, thus leading to health inequities worldwide. It is urgent that societies adopt effective support strategies to combat xenophobia and structural forms of discrimination against migrants.


Transport of sugars, including sucrose, by the msm transport system of Streptococcus mutans.
The range of substrates transported by the sugar-binding protein-dependent msm (multiple sugar metabolism) system of S. mutans was investigated. By determining the ability of unlabeled sugar to compete with radiolabeled melibiose transport, we have demonstrated that the transported sugars included a number of carbohydrates structurally related to raffinose. A model accommodating these results has been devised which accounts for the sugars transported by the msm transport system. Competition with radiolabeled melibiose transport indicated sucrose to be an msm substrate. This was confirmed by examination of uptake of radiolabeled sucrose in scrAB mutants lacking the sucrose-specific phosphotransferase system.


Degradation of BM SDF-1 by MMP-9: the role in G-CSF-induced hematopoietic stem/progenitor cell mobilization.
The major involvement of chemokines and proteolytic enzymes has recently been discovered in the mobilization process. Here, we report that the degradation of BM stromal cell-derived factor (SDF-1) by matrix metalloproteinase (MMP)-9 is important in G-CSF-mediated hematopoietic stem/progenitor cells (HSPCs) mobilization. In this study, the SDF-1 concentration in healthy donors BM plasma decreased significantly after 5 days of G-CSF administration, with no obvious change of SDF-1 in the peripheral blood. We also observed a similar result by immunohistochemical staining on the BM biopsy slides. In vitro, mobilized BM plasma exhibited decreased chemotactic effect on CD34(+) cells, compared with steady-state BM plasma. MMP-9 protein and mRNA increased dramatically in the BM plasma in accordance with SDF-1 decrease. MMP-9 enriched supernatant from HT1080 cell-conditioned medium upregulated CXCR4 expression and the migration of BM CD34(+) cells toward SDF-1. SDF-1 was a substrate for MMP-9, furthermore, SDF-1 also stimulated MMP-9 proteolytic enzyme activity of BM CD34(+) cells, which facilitate HSPCs migration. In BALB/c mice, HSPCs mobilization was significantly inhibited by anti-SDF-1 antibodies or MMP inhibitor, o-phenanthroline. In conclusion, the degradation of BM SDF-1 by MMP-9 is a vital step in mobilization.


Light adaptation/acclimation of photosynthesis and the regulation of ribulose-1,5-bisphosphate carboxylase activity in sun and shade plants.
The consequences of light adaptation and acclimation of photosynthesis on photosynthetic nitrogen use efficiency (NUE), particularly as it relates to the efficiency of ribulose-1,5-bisphosphate carboxylase (Rubisco) use in photosynthetic CO(2) assimilation, was studied in the sun species Glycine max and the shade species Alocasia macrorrhiza. Both G. max and A. macrorrhiza were found to possess the capacity for light acclimation of CO(2) assimilation, but over distinctly different ranges of photon flux density (PFD). For each species, light acclimation of photosynthesis had little effect on the rate of photosynthesis per unit Rubisco protein or the light response of Rubisco carbamylation and CA 1P metabolism. In contrast, photosynthesis per unit Rubisco protein was significantly higher in G. max than in A. macrorrhiza, due in part to a lower total (fully carbamylated) molar activity (activity per unit enzyme) of A. macrorrhiza Rubisco than that of G. max. Comparison of the light response of Rubisco regulatory mechanisms between G. max and A. macrorrhiza indicated some degree of adaptation, such that carbamylation was higher and CA 1P levels lower at lower PFDs in the shade species than the sun species. However, this adjustment was not sufficient for Rubisco in low light grown A. macrorrhiza to be fully active at the growth PFD. Photosynthesis in A. macrorrhiza appeared to become RuBP regeneration-limited at lower PFDs than G. max, and this was probably the determinant of the light saturated rate of photosynthesis in the shade species. The low efficiency of Rubisco use in A. macrorrhiza was a major contributing factor to its five- to sixfold lower photosynthetic NUE than G. max. Shade species such as A. macrorrhiza appear to make far from maximal use of Rubisco protein N.


What is the significance of soluble and endogenous secretory receptor for advanced glycation end products in liver steatosis in obese prepubertal children?
The endogenous secretory receptor for advanced glycation end products (esRAGE) and soluble RAGE (sRAGE) have been shown in human plasma and have emerged as reliable biomarkers of several pathological conditions, including insulin resistance and liver injury. We examined esRAGE and sRAGE levels in obese prepubertal children with and without liver steatosis. esRAGE and sRAGE levels were significantly lower in obese prepubertal children affected by liver steatosis and were independently related to liver steatosis. These findings suggest that AGE-RAGE pathway plays an independent role in the development of liver injury already present in this age group.


Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.
Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2. Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray. Moreover, reverse phase protein array was applied to quantify protein expression of MAPKs in six breast cancer cell lines with different phenotypes including HER2-transfected cells. MAPKs expression was associated with clinicopathological variables characteristic of good prognosis. These associations were most significant in the whole series and in the ER+ subgroup compared to other BC classes. Most of MAPKs showed a positive association with ER, BCL2 and better outcome and were negatively associated with the proliferation marker Ki67 and p53. Association of MAPK with HER2 was mainly seen in the ER- subgroup. Reverse phase protein array confirmed immunohistochemistry results and revealed differential expression of MAPK proteins in ER+ and ER- cell lines. MAPKs are associated with good prognosis and their expression is mainly related to ER. Studying a large panel rather than individual biomarkers may provide improved understanding of the pathway.


Exercise and negative energy balance in males who perform mental work.
Although energy expenditure during mental work is not higher than energy expenditure at rest, a stressful mental task is related to an increase in energy intake. It is suggested that mental work produces physiological changes, thereby influencing food intake. Because physical activity can influence hunger, the aim of the study was to determine if the introduction of an active pause could counteract the negative effects of mental work on energy intake and energy balance. Twelve male students, of normal weight, between 15 and 20 years old were evaluated. All subjects participated in three different sessions realized in a randomized order: (i) without pause = relaxation/mental work/meal; (ii) relaxation pause = mental work/relaxation/meal; and (iii) exercise pause = mental work/exercise/meal. Energy expenditure was measured with indirect calorimetry, energy intake was measured with a cold buffet-type meal of 40 items, and appetite-related sensations were measured with visual analogue scales. The effect of introducing an active pause in energy intake and energy balance was studied. The introduction of an active pause did not influence energy intake; although, higher appetite-related sensations were observed (16-26 mm on a 150-mm scale; P < 0.05). After accounting for the energy expenditure related to physical activity, a lower energy balance was measured for the exercise pause visit compared with the visit without a pause (-1137 kJ; P < 0.05). This study indicates that being active between mental work and a meal could represent a strategy to create a negative energy balance following mental work via an increased energy expenditure and a maintenance of energy intake. Globally, these results could help individuals attain and/or maintain a healthy body weight in a context where mental work is omnipresent.


Stimulatory effect of follicle-stimulating hormone on basal and luteinizing hormone-stimulated testosterone secretions by the fetal rat testis in vitro.
The in vitro effect of FSH on testosterone secretion by the fetal rat testis was studied. Testes were cultured in the presence or absence of either commercial human (h) FSH (Metrodine; 200 mIU/ml) or recombinant hFSH (200 mIU/ml) for 3 days and with 100 ng/ml ovine LH during the last 4 h of culture. To avoid a stimulatory effect by the 0.4% LH that contaminates Metrodine, the cultures were performed in the presence of a monoclonal anti-hLH beta antibody and with a concentration of Metrodine that had no short term stimulatory effect on testosterone production by the fetal testes in vitro. Metrodine treatment had a positive long term effect on both basal and LH-stimulated testosterone secretion by fetal testes explanted on days 18.5, 20.5, and 22.5 postconception, which was abolished by the addition of a monoclonal anti-hFSH beta antibody. LH-free recombinant FSH also augmented basal and LH-stimulated testosterone secretion of testes explanted on days 13.5, 14.5, and 18.5 postconception. The positive effect of recombinant hFSH appeared during the second day of treatment with day 14.5 and 18.5 testes and on the third day of treatment with day 13.5 testes. As it is widely accepted that FSH receptors are exclusively localized on Sertoli cells, these results suggest that on or before day 15.5 of fetal life, 1) Sertoli cells are able to respond to FSH, 2) Sertoli cells can produce factors that are able to act on Leydig cell function, and 3) Leydig cells are sensitive to FSH-induced Sertoli cell factors. In conclusion, this study points out a potential paracrine control of fetal Leydig cell function and/or differentiation by fetal Sertoli cells as soon as fetal Leydig cells differentiate.