Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice.
During their lifetime, people are commonly exposed to several vascular risk factors that may affect brain ageing and cognitive function. In the last few years, increasing evidence suggests that pathological plasma lipid profiles contribute to the pathogenesis of late-onset Alzheimer's disease. Importantly, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol values, that is, increased apolipoprotein B-100 (ApoB-100) levels, represents an independent risk factor. In this study, the effects of ApoB-100 overexpression, either alone or in combination with cerebral expression of human amyloid precursor protein (hAPP), on cognitive functions and brain pathology were assessed. Our results show that ApoB-100 overexpression induces memory decline and increases cerebral lipid peroxidation and amyloid beta levels compared to those in wild-type animals. Although double-transgenic ApoBxAPP animals did not develop more distinct behavioral deficits than single-transgenic hAPP littermates, hApoB-100 expression caused additional pathophysiological features, such as high LDL and low HDL-cholesterol levels, increased lipid peroxidation, and pronounced ApoB-100 accumulation in cerebral vessels. Thus, our results indicate that ApoBxAPP mice might better reflect the situation of elderly humans than hAPPsl overexpression alone.


Diagnosis of Duchenne muscular dystrophy: parents' experiences and satisfaction.
The purpose of the study was to investigate parents' experiences of diagnosis of Duchenne muscular dystrophy. Data were collected retrospectively by postal questionnaire from the parents of 158 boys diagnosed at different times and locations and, for some, after lengthy periods of uncertainty. Most parents knew nothing about Duchenne before being given the diagnosis. There was considerable variation in parents' experiences but the only independent predictors of parents' satisfaction with how the diagnosis was given were obtaining the information that they wanted and feeling that they had understood and remembered it. What distinguishes Duchenne from, say, Down syndrome is that doctors are having to deliver a death sentence on a child. Our data show that this can be done in a way that is satisfactory to parents. What is required is empathy and sensitivity to parents' informational and emotional needs.


Phenomenology of one-dimensional quantum liquids beyond the low-energy limit.
We consider the zero temperature behavior of dynamic response functions of 1D systems near edges of support in the momentum-energy plane (k,omega). The description of the singularities of dynamic response functions near an edge epsilon(k) is given by the effective Hamiltonian of a mobile impurity moving in a Luttinger liquid. For Galilean-invariant systems, we relate the parameters of such an effective Hamiltonian to the properties of the function epsilon(k). This allows us to express the exponents which characterize singular response functions of spinless bosonic or fermionic liquids in terms of epsilon(k) and Luttinger liquid parameters for any k. For an antiferromagnetic Heisenberg spin-1/2 chain in a zero magnetic field, SU(2) invariance fixes the exponents from purely phenomenological considerations.


A further analysis of the relationship between yellow ripe-fruit color and the capsanthin-capsorubin synthase gene in pepper (Capsicum sp.) indicated a new mutant variant in C. annuum and a tandem repeat structure in promoter region.
Mature pepper (Capsicum sp.) fruits come in a variety of colors, including red, orange, yellow, brown, and white. To better understand the genetic and regulatory relationships between the yellow fruit phenotype and the capsanthin-capsorubin synthase gene (Ccs), we examined 156 Capsicum varieties, most of which were collected from Northwest Chinese landraces. A new ccs variant was identified in the yellow fruit cultivar CK7. Cluster analysis revealed that CK7, which belongs to the C. annuum species, has low genetic similarity to other yellow C. annuum varieties. In the coding sequence of this ccs allele, we detected a premature stop codon derived from a C to G change, as well as a downstream frame-shift caused by a 1-bp nucleotide deletion. In addition, the expression of the gene was detected in mature CK7 fruit. Furthermore, the promoter sequences of Ccs from some pepper varieties were examined, and we detected a 176-bp tandem repeat sequence in the promoter region. In all C. annuum varieties examined in this study, the repeat number was three, compared with four in two C. chinense accessions. The sequence similarity ranged from 84.8% to 97.7% among the four types of repeats, and some putative cis-elements were also found in every repeat. This suggests that the transcriptional regulation of Ccs expression is complex. Based on the analysis of the novel C. annuum mutation reported here, along with the studies of three mutation types in yellow C. annuum and C. chinense accessions, we suggest that the mechanism leading to the production of yellow color fruit may be not as complex as that leading to orange fruit production.


The prediction of adverse maternal outcomes in preeclampsia.
(1) To evaluate whether clinical variables reflecting the multiorgan dysfunctions of preeclampsia can predict adverse maternal outcomes of preeclampsia; (2) to determine the usefulness of the mean platelet volume (MPV):platelet ratio as a novel measure of platelet consumption in predicting the severity of preeclampsia. A retrospective chart review was conducted of cases of preeclampsia seen in 3 tertiary level units from January 2001 to December 2001. Candidate predictors of adverse maternal outcome were gestational age (GA) on admission to hospital, blood pressure, proteinuria, urine output, uric acid, creatinine, aspartate transaminase (AST), lactate dehydrogenase, bilirubin, albumin, fraction of inspired oxygen:oxygen saturation (FIO2:SaO2) ratio, platelet count, MPV, MPV:platelet ratio, fibrinogen, and seizures. The combined adverse maternal outcomes included maternal death; 1 or more of hepatic failure, hematoma, or rupture; Glasgow coma scale <13; stroke; 2 or more seizures; cortical blindness; positive inotrope support; myocardial infarction; infusion of any third antihypertensive; dialysis; renal transplantation; > or =50% FIO2 for >1 hour; intubation; or transfusion of > or =10 units of blood products. Descriptive, univariable, and multivariable analyses were performed, with significance set at P < .05. Of a total of 594 women with preeclampsia, 60 (10.1%) developed at least 1 element of the combined adverse outcome; 1 of these 60 women died. The most common outcomes were increased oxygen requirements, the use of a third infused antihypertensive, and transfusion >10 units. In women who developed an adverse outcome, GA and fibrinogen were lower, and total leukocyte count, creatinine, and AST were greater. Multivariable logistic regression revealed that admission GA (odds ratio [OR], 0.91), dipstick protein (OR, 1.31), and MPV:platelet ratio (OR, 391.0) independently predicted the outcome. Several promising markers were identified: admission GA, dipstick proteinuria, and the MPV:platelet ratio. MPV:platelet ratio also showed promise as a marker of platelet consumption. A prospective study is required to develop a clinical prediction model for preeclampsia.


Preventive effect of tannic acid on 2-acetylaminofluorene induced antioxidant level, tumor promotion and hepatotoxicity: a chemopreventive study.
Tannic acid, present in almost every food derived from plants, has been widely investigated as a chemopreventive agent because, apart from its use as a food additive, pharmacological studies have demonstrated its many health-promoting properties. In this study, we show the modulatory effect of tannic acid on 2-acetylaminofluorene (2-AAF)-mediated hepatic oxidative stress and cell proliferation in rats. 2-AAF (50 mg/kg body weight) caused reduction in hepatic glutathione content and the activities of hepatic anti-oxidant enzymes and phase-II metabolizing enzymes with an enhancement of xanthine oxidase activity, lipid peroxidation and hydrogen peroxide content. 2-AAF treatment also induced serum oxaloacetate and pyruvate transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase. Treatment of rats orally with tannic acid (125 and 250 mg/kg body weight) resulted in significant recovery of hepatic glutathione content, antioxidant and phase-II metabolizing enzymes. Also, significant decreases in lipid peroxidation, xanthine oxidase, hydrogen peroxide generation and liver damage marker enzymes were observed. The antiproliferative efficacy of the tannic acid was also evaluated. The promotion parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in the diet with partial hepatectomy (PH) were also significantly suppressed, dose dependently, by tannic acid. Hence, we propose that tannic acid might suppress the promotion stage via inhibition of oxidative stress and polyamine biosynthetic pathway.


A dynamic social norm messaging intervention to reduce meat consumption: A randomized cross-over trial in retail store restaurants.
Perceptions of social norms around eating behavior can influence food choices. Communicating information about how others are changing their eating behavior over time (dynamic descriptive social norms) may motivate individuals to change their own food selection and consumption. Following a four-week baseline period, 22 in-store restaurants of a major retail chain across the UK were randomized to display a dynamic descriptive social norm message intended to motivate a shift from meat-to plant-based meals either during the first two, or last two weeks of the four-week study period. A linear regression model showed there was no evidence of an effect of the intervention (β = -0.022, p = .978, 95% CIs: -1.63, 1.58) on the percentage sales of meat- vs plant-based dishes. Fidelity checks indicated that adherence to the intervention procedure was often low, with inconsistencies in the placement and display of the intervention message. In four stores with high fidelity the estimated impact of the intervention was not materially different. The lack of apparent effectiveness of the intervention may reflect poor efficacy of the intervention or limitations in its implementation in a complex food purchasing environment. The challenges highlighted by this study should be considered in future design and evaluation of field trials in real-world settings.


Induction of fetal hemoglobin by propionic and butyric acid derivatives: correlations between chemical structure and potency of Hb F induction.
Short-chain fatty acids (C2-C9) induce fetal hemoglobin synthesis in primary cell cultures, primates, and patients. We carried out experiments to test whether relationships exist between chemical structure and the Hb F-inducing potential of several short-chain fatty acid derivatives. BFUe cultures were performed in the presence of propionic and butyric congeners, covering the full spectrum of substitutions of these molecules, including polar and non-polar groups, esters, and double bonds. We found that the fetal hemoglobin inducibility is related to the chemical structure of the inducing compound. This structure-activity relation depends on the length of carbon chain, the nature of the substitutions, and the position of more potent substitutions on the carbon chain. It appears that substitutions enhancing the inducibility of these compounds are (with decreasing potency): methyl > phenyl > hydroxy >> amino groups. Placement of these substitutions at a position distal to the carboxyl group enhances gamma-globin inducibility. Presence of the carboxyl group is prerequisite for gamma-globin inducibility.


The utility of heart sounds and systolic intervals across the care continuum.
Acoustic cardiography is an exciting, new, easy-to-use, modernized technology that incorporates already proven techniques of phonocardiography. Application of acoustic cardiography to clinical practice can improve diagnosis and management of heart failure patients. Its clinical use should help address some of the need for robust, inexpensive, and widely accessible technology for proactive heart failure diagnosis and management. Acoustic cardiographically recorded measurements have been correlated with both cardiac catheterization and echocardiographically determined hemodynamic parameters. Heart sounds captured by acoustic cardiograms have proven to assist clinicians in assessing dyspneic patients in the emergency department by utilizing the strong specificity of an S3 for detecting acute decompensated heart failure. Acoustic cardiography offers a cost-efficient, easy-to-use method to optimize the devices used in cardiac resyncronization therapy. The rapidly and easily obtainable information gathered by acoustic cardiography should foster its more widespread use in diagnosis and treatment of heart failure, including cardiac resyncronization therapy device optimization.


High-yield sol-gel synthesis of well-dispersed, colorless ZrO(2) nanocrystals.
A 93% high-yield synthesis of well-dispersed, colorless zirconium dioxide (ZrO(2)) nanocrystals is reported. In this synthesis, hydrolysis and condensation reactions of zirconium(IV) tert-butoxide in the presence of oleic acid (100 degrees C) formed ZrO(2) precursors. The ZrO(2) precursors were made of -Zr-O-Zr- networks surrounded by oleic acid molecules. Annealing (280 degrees C) the precursors dispersed in dioctyl ether caused crystallization of the -Zr-O-Zr- networks, thereby generating 4 nm ZrO(2) nanocrystals stabilized with oleic acid. The particles were highly crystalline and tetragonal phase. A dense ZrO(2) nanocrystal dispersion in toluene (280 mg/mL) showed a transmittance of about 90% (3 mm optical path length) in the whole visible region.


The 2:1 complex of maleic acid and 1,4-diazabicyclo[2.2.2]octane: hydrogen-bonded sheets linked by C-H...O hydrogen bonds.
In the title complex, 1,4-diazoniabicyclo[2.2.2]octane bis(hydrogen maleate), C(6)H(14)N(2)(2+).2C(4)H(3)O(4)(-), the C(4)H(3)O(4)(-) and C(6)H(14)N(2)(2+) ions, derived from maleic acid and 1,4-diazabicyclo[2.2.2]octane, respectively, are disordered across a mirror plane in space group Cmc2(1), and they are linked by two nearly linear N-H...O hydrogen bonds, with N...O distances of 2.662 (3) and 2.614 (4) A, and N-H...O angles of 173 degrees. The crystal structure consists of sheets with reticulations of 3.3792 (4) A in stratum and 7.3892 (8) A in width. The sheets are linked by C-H...O hydrogen bonds.


Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by androgen deprivation.
Prostate cancer patients treated with high dose rate brachytherapy and external beam radiation therapy were stratified by risk group for analysis to determine whether androgen deprivation therapy (ADT) affected outcome. From 1991 through 1998, 411 patients were treated with 4 fractions of 5.5 to 6.0 Gy high dose rate brachytherapy and a total of 36.0 to 39.6 Gy external beam radiation therapy (dose escalation over time). The dataset was prospective. Administration of ADT was not randomized, but it was the primary study variable. During this period, ADT was administered across all risk groups for various indications. It did not necessarily reflect advanced disease or large prostate size. There were 200 patients in the "ADT Group" (20% low, 48% intermediate, and 32% high risk) and 211 in the "No ADT Group" (33% low, 44% intermediate, 23% high risk). The median follow-up was 6.4 years. Cases were grouped according to low, intermediate, and high risk groups to reduce the effects of unrecognized selection bias for or against the ADT group. The prostate specific antigen (PSA) nadir plus 2.0 ng/ml (nadir + 2) was used as the biochemical control end point. Local control, PSA progression-free survival, distant metastasis free survival, and cause-specific survival were compared. The 10 year PSA-PFS (nadir + 2) for all 411 patients was 81%. The results stratified by risk group were: low 92%, intermediate 87%, and high 63%. The low and intermediate risk groups were not statistically different from one another but they were both significantly better than the high risk group. ADT versus No ADT 10-year survival showed no significant differences for any outcome variable: PSA-PFS (83% vs. 81% ns), local control (97% vs. 99%), distant metastasis free survival (94% vs. 97%), and cause-specific survival (97% vs. 97%). A subset analysis of PSA-PFS (nadir + 2) stratified by risk group revealed no difference between the ADT and No ADT groups. high dose rate brachytherapy and external beam radiation therapy resulted in high rates of local control, PSA progression-free survival, distant metastasis free survival, and cause-specific survival in all risk groups. Improved outcome from the use of androgen deprivation was not observed.


Influenza activity in Kenya, 2007-2013: timing, association with climatic factors, and implications for vaccination campaigns.
Information on the timing of influenza circulation remains scarce in Tropical regions of Africa. We assessed the relationship between influenza activity and several meteorological factors (temperature, specific humidity, precipitation) and characterized the timing of influenza circulation and its implications to vaccination strategies in Kenya. We analyzed virologically confirmed influenza data for outpatient influenza-like illness (ILI), hospitalized for severe acute respiratory infections (SARI), and cases of severe pneumonia over the period 2007-2013. Using logistic and negative binomial regression methods, we assessed the independent association between climatic variables (lagged up to 4 weeks) and influenza activity. There were multiple influenza epidemics occurring each year and lasting a median duration of 2-4 months. On average, there were two epidemics occurring each year in most of the regions in Kenya, with the first epidemic occurring between the months of February and March and the second one between July and November. Specific humidity was independently and negatively associated with influenza activity. Combinations of low temperature (<18°C) and low specific humidity (<11 g/kg) were significantly associated with increased influenza activity. Our study broadens understanding of the relationships between seasonal influenza activity and meteorological factors in the Kenyan context. While rainfall is frequently thought to be associated with influenza circulation in the tropics, the present findings suggest low humidity is more important in Kenya. If annual vaccination were a component of a vaccination strategy in Kenya, the months of April to June are proposed as optimal for associated campaigns.


Confidentiality, disseminated regulation and ethico-legal liabilities in research with hidden populations of illicit drug users.
An assurance of confidentiality is at the core of trusting relationships in outreach, ethnographic research and patient/client encounters. In the past, centralized State health care services have provided assurances of confidentiality to those engaged in health-related research either through common law or by statute. However, unless specific confidentiality legislation is in place, no assurances of confidentiality can now be made to research subjects involved in either longitudinal, interview-based or ethnographic research. The consequences of this situation become more serious given the recent emergence of the use of peer and community outreach. A significant problem with the outreach model is the failure to provide adequate legal and ethical support for those in outreach roles. Additionally, unless research subjects can be granted assurances of confidentiality, they will not engage in research for fear of later prosecution. At this time when outreach models are the modus operandi, the lack of a fundamental commitment to sustain confidentiality may seriously undermine further research. This paper will draw on the experiences of some Australian qualitative research and will review some of the ethical and legal liabilities for research that arise when an assurance of confidentiality cannot be given to those participating in research.


Frequency, characteristics and management of adolescent inpatient aggression.
Inpatient aggression is a serious challenge in pediatric psychiatry. A chart review study in adolescent psychiatric inpatients consecutively admitted over 24 months was conducted, to describe aggressive events requiring an intervention (AERI) and to characterize their management. AERIs were identified based on specific institutional event forms and/or documentation of as-needed (STAT/PRN) medication administration for aggression, both recorded by nursing staff. Among 408 adolescent inpatients (age: 15.2±1.6 years, 43.9% male), 1349 AERIs were recorded, with ≥1 AERI occurring in 28.4% (n=116; AERI+). However, the frequency of AERIs was highly skewed (median 4, range: 1-258). In a logistical regression model, the primary diagnosis at discharge of disruptive behavior disorders and bipolar disorders, history of previous inpatient treatment, length of hospitalization, and absence of a specific precipitant prior to admission were significantly associated with AERIs (R(2)=0.32; p<0.0001). The first line treatment of patients with AERIs (AERI+) was pharmacological in nature (95.6%). Seclusion or restraint (SRU) was used at least once in 59.4% of the AERI+ subgroup (i.e., in 16.9% of all patients; median within-group SRU frequency: 3). Treatment and discharge characteristics indicated a poorer prognosis in the AERI+ (discharge to residential care AERI+: 22.8%, AERI-: 5.6%, p<0.001) and a greater need for psychotropic polypharmacy (median number of psychotropic medications AERI+: 2; AERI-: 1, p<0.001). Despite high rates of pharmacological interventions, SRU continue to be used in adolescent inpatient care. As both of these approaches lack a clear evidence base, and as adolescents with clinically significant inpatient aggression have increased illness acuity/severity and service needs, structured research into the most appropriate inpatient aggression management is sorely needed.


Self-Collected versus Clinician-Collected Sampling for Chlamydia and Gonorrhea Screening: A Systemic Review and Meta-Analysis.
The increases in STI rates since the late 1990s in Canada have occurred despite widespread primary care and targeted public health programs and in the setting of universal health care. More innovative interventions are required that would eliminate barriers to STI testing such as internet-based or mail-in home and community service testing for patients that are hard to reach, who refuse to go for clinician-based testing, or who decline an examination. Jurisdictions such as New Zealand and some American states currently use self-collected sampling, but without the required evidence to determine whether self-collected specimens are as accurate as clinician-collected specimens in terms of chlamydia and gonorrhea diagnostic accuracy. The objective of the review is to compare self-collected vaginal, urine, pharyngeal and rectal samples to our reference standard - clinician-collected cervical, urethral, pharyngeal and rectal sampling techniques to identify a positive specimen using nucleic acid amplification test assays. The hierarchical summary receiver operating characteristic and the fixed effect models were used to assess the accuracy of comparable specimens that were collected by patients compared to clinicians. Sensitivity and specificity estimates with 95% confidence intervals (CI) were reported as our main outcome measures. We included 21 studies based on over 6100 paired samples. Fourteen included studies examined chlamydia only, 6 compared both gonorrhea and chlamydia separately in the same study, and one examined gonorrhea. The six chlamydia studies comparing self-collection by vaginal swab to a clinician-collected cervical swab had the highest sensitivity (92%, 95% CI 87-95) and specificity (98%, 95% CI 97-99), compared to other specimen-types (urine/urethra or urine/cervix). Six studies compared urine self-samples to urethra clinician-collected samples in males and produced a sensitivity of 88% (95% CI 83-93) and a specificity of 99% (95% CI 0.94-0.99). Taking into account that urine samples may be less sensitive than cervical samples, eight chlamydia studies that compared urine self-collected verses clinician-collected cervical samples had a sensitivity of 87% (95% CI 81-91) and high specificity of 99% (95% CI 0.98-1.00). For gonorrhea testing, self-collected urine samples compared to clinician-collected urethra samples in males produced a sensitivity of 92% (95% CI 83-97) and specificity of 99% (95% CI 0.98-1.00). The sensitivity and specificity of vaginal self-collected swabs compared to swabs collected by clinicians supports the use of vaginal swab as the recommended specimen of choice in home-based screening for chlamydia and gonorrhea. Urine samples for gonorrhea collected by men had comparably high sensitivity and specificity, so could be recommended as they can be left at room temperature for several days, allowing for the possibility of mail-in home-based testing. In populations that may not go for testing at all, do not have the option of clinical testing, or who refuse a clinical examination, self-collected screening would be a good alternative. We recommend that guidelines on how to self-collect gonorrhea and chlamydia urine, vaginal, rectal and pharyngeal specimens be published.


Pediatric appendicitis score: A retrospective analysis.
Evaluation of the pediatric appendicitis score (PAS), in all patients who had an appendicectomy over a one-year period. Retrospective study of 56 patients aged 4-15 years, who underwent an emergency appendicectomy. PAS was applied and patients were divided according to the PAS protocol into high probability and low probability groups. These results were then correlated with histology. The PAS had sensitivity 0.87, specificity 0.59, positive predictive value 0.83, and negative predictive value 0.67. The negative appendicectomy rate would have been reduced to 17%, but five patients with appendicitis would have been denied early surgical treatment and may have been discharged. The PAS cannot be recommended as it would lead to an unacceptable risk of wrongly discharging or delaying necessary surgery in 13% of patients with appendicitis.


Screening of intron 1 inversion and three intragenic factor VIII gene polymorphisms in Pakistani hemophilia A families.
Indirect linkage analysis using highly informative polymorphic markers is the method of choice for carrier detection of hemophilia A in developing countries because direct DNA or mRNA sequence analysis is manifold costly and difficult than indirect gene tracking. Worldwide populations have revealed marked variation in the informativeness of polymorphic markers because of which each country has to select its own panel of markers for linkage analysis in hemophilia A families. The present study aimed at determining the informativeness of three factor VIII gene polymorphisms [intron 13(CA)n repeats, HindIII and AlwNI] in the Pakistani population. One hundred and forty-three individuals from 32 hemophilia A families and 68 unrelated anonymous females from the general population were screened for these polymorphisms using PCR and RFLP techniques. An inversion in intron 1 of the factor VIII gene causing 2-5% of severe hemophilia A cases was also screened in 128 Pakistani hemophilia A patients. None of the affected individuals carried the intron 1 inversion at least in peripheral blood leucocytes. The informativeness of intron 13 repeats, HindIII and AlwNI was 59.1% (13/22 hemophilia A families revealing five different alleles), 40.6% (13/32 hemophilia A families) and 6.25% (2/32 hemophilia A families), respectively. The cumulative informativeness of intron 13 repeats and HindIII was 63.6% (14/22 hemophilia A families), revealing strong linkage disequilibrium between these two polymorphic markers. These results suggest that there is a need to determine the informativeness of other polymorphic markers of the factor VIII gene to achieve 100% success rate for carrier detection of hemophilia A in Pakistan.


The burden of disease and the cost of illness attributable to child maltreatment in Japan: long-term health consequences largely matter.
Child maltreatment leads to enormous adverse short- and long-term health outcomes. The aim of this study is to estimate the burden of disease and the cost of illness attributable to child maltreatment in Japan. An incidence-based top-down cost of illness analysis was conducted to estimate medical costs and burden of disease attributable to child maltreatment based on a societal perspective. The assessment included short-term and long-term medical costs and burden of disease measured by Disability-Adjusted Life Years (DALYs) that generates mortality and morbidities, based on several national surveys and systematic review. We considered the main types of child maltreatment as exposure, for which the incidence was obtained from literature review. Based on population attributable fractions (PAFs), burden of disease of physical and mental health consequences attributable to child maltreatment were estimated. Then DALYs were converted into monetary value. The lifetime economic burden was finally estimated by combining with medical costs and subject to sensitivity analysis. The lifetime disease burden expressed in DALYs was estimated at 1,047,580 DALYs (95% CI 788,388 - 1326,80 DALYs) for the cohort victims in 2016. Based on the incidence according to literature review, the overall lifetime economic burden was 50.24 billion USD, equivalent to 1.3 million times of gross domestic product (GDP) per capita. Among the total economic burden, costs of suffering and pain based on DALYs were accounting for 81.3%. These estimates were 7-8 times of conservative estimates which used incidence data from official reported cases. This study found that the national lifetime cost was huge and equivalent to 1.3 million GDP per capita, and its burden of disease was approximately equal to that of colon and rectum cancers or stomach cancer. Our findings particularly in terms of revealed the considerable burden of disease in long term and potential effects of the strengthened maternal and child care as the preventive strategy.


What makes our hospitals different: the nursing role in a specialty hospital.
MedCath, Inc. is the largest provider of cardiovascular services in the United States; therefore, tremendous opportunities present themselves to us in regard to improving and redesigning care for this patient population. With that in mind, we actively address the nursing model of care specifically for a specialty hospital. This article illustrates why we believe our nursing delivery model is different and better than traditional health care models in the country. We believe that our approach to patient-focused care offers the resources and tools that nurses require to adequately care for the complex patients that present to our hospitals. A key part of our strategy is the commitment we have to education, training, adequate staffing ratios, safety, and collaborative care processes. We consider our model to be dynamic in nature, and we rely on the input from nurses, physicians, and other caregivers to continuously improve our model of care. Data and analysis are provided daily through our balanced scorecard initiatives and from our clinical metrics, clinical best practice teams, and throughput efforts. We seek to be a learning organization and recognize that knowledge is enhanced by the collective ideas and actions of our key stakeholders, which include the nursing staff.


Detection of early embryonic development in chicken eggs using visible light transmission.
1. In two separate experiments, the possibility of detecting embryonic development in chicken eggs was assessed using the same spectrophotometric method used to detect blood in Table eggs, using a combination of two wavelengths (577 and 610 nm) of the transmission spectrum. 2. In the first experiment, during the first 10 d of incubation, transmission spectra of 30 Hisex White eggs and 30 Hybro eggs were measured daily. 3. In the second experiment, 292 Hisex White eggs were incubated. Seven groups were randomly assigned. Six received an injection of sodium azide (NaN3) at different times during incubation in order to stop embryonic development, and during the first 12 d of incubation the transmission spectrum was measured daily. The acoustic resonance analysis method was also used on a group of uninjected eggs. 4. In the first experiment, it was possible to detect embryonic development from 120 h of incubation onwards in fertile eggs. In the second experiment changes in light transmission due to embryonic development were detected from 108 h of incubation. Detection of embryonic development using the acoustic resonance analysis method in the second experiment was possible only from 120 h of incubation. 5. It was concluded that the detection of embryonic development using visible light transmission is not directly linked with the formation of blood, but with the formation of sub-embryonic fluid, which takes place from 72 h of incubation onwards. This fluid makes the yolk sac translucent so that absorption of light at 577 nm can be detected.


The NAC transcription factor family in Eucommia ulmoides: Genome-wide identification, characterization, and network analysis in relation to the rubber biosynthetic genes.
The NAC transcription factor family is a large plant gene family, participating in plant growth and development, secondary metabolite synthesis, biotic and abiotic stresses responses, and hormone signaling. Eucommia ulmoides is a widely planted economic tree species in China that can produce trans-polyisoprene: Eucommia rubber (Eu-rubber). However, genome-wide identification of the NAC gene family has not been reported in E. ulmoides. In this study, 71 NAC proteins were identified based on genomic database of E. ulmoides. Phylogenetic analysis showed that the EuNAC proteins were distributed in 17 subgroups based on homology with NAC proteins in Arabidopsis, including the E. ulmoides-specific subgroup Eu_NAC. Gene structure analysis suggested that the number of exons varied from 1 to 7, and multitudinous EuNAC genes contained two or three exons. Chromosomal location analysis revealed that the EuNAC genes were unevenly distributed on 16 chromosomes. Three pairs of genes of tandem duplicates genes and 12 segmental duplications were detected, which indicated that segmental duplications may provide the primary driving force of expansion of EuNAC. Prediction of cis-regulatory elements indicated that the EuNAC genes were involved in development, light response, stress response and hormone response. For the gene expression analysis, the expression levels of EuNAC genes in various tissues were quite different. To explore the effect of EuNAC genes on Eu-rubber biosynthesis, a co-expression regulatory network between Eu-rubber biosynthesis genes and EuNAC genes was constructed, which indicated that six EuNAC genes may play an important role in the regulation of Eu-rubber biosynthesis. In addition, this six EuNAC genes expression profiles in E. ulmoides different tissues were consistent with the trend in Eu-rubber content. Quantitative real-time PCR analysis showed that EuNAC genes were responsive to different hormone treatment. These results will provide a useful reference for further studies addressing the functional characteristics of the NAC genes and its potential role in Eu-rubber biosynthesis.


Temporal Healing of Achilles Tendons After Injury in Rodents Depends on Surgical Treatment and Activity.
Achilles tendon ruptures affect 15 of 100,000 women and 55 of 100,000 men each year. Controversy continues to exist regarding optimal treatment and rehabilitation protocols. The objective of this study was to investigate the temporal effects of surgical repair and immobilization or activity on Achilles tendon healing and limb function after complete transection in rodents. Injured tendons were repaired (n = 64) or left nonrepaired (n = 64). The animals in both cohorts were further randomized into groups immobilized in plantar flexion for 1, 3, or 6 weeks that later resumed cage and treadmill activity for 5, 3, or 0 weeks, respectively (n = 36 for each regimen), which were euthanized at 6 weeks after injury, or into groups immobilized for 1 week and then euthanized (n = 20). At 6 weeks after injury, the groups that had 1 week of immobilization and 5 weeks of activity had increased range of motion and decreased ankle joint toe stiffness compared with the groups that had 3 weeks of immobilization and 3 weeks of activity. The groups with 6 weeks of immobilization and no activity period had decreased tendon cross-sectional area but increased tendon echogenicity and collagen alignment. Surgical treatment dramatically decreased fatigue cycles to failure in repaired tendons from groups with 1 week of immobilization and 5 weeks of activity. Normalized comparisons between 1-week and 6-week postinjury data demonstrated that changes in tendon healing properties (area, alignment, and echogenicity) were maximized by 1 week of immobilization and 5 weeks of activity, compared with 6 weeks of immobilization and no activity period. This study builds on an earlier study of Achilles tendon fatigue mechanics and functional outcomes during early healing by examining the temporal effects of different immobilization and/or activity regimens after initial postinjury immobilization. This study demonstrates how the temporal postinjury healing response of rodent Achilles tendons depends on both surgical treatment and the timing of immobilization/activity timing. The different pattern of healing and qualities of repaired and nonrepaired tendons suggest that two very different healing processes may occur, depending on the chosen immobilization/activity regimen.


Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues.
In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally reduced the inhibition of glycosidases. However, this was not the case at pH 5.0, where the gem-difluoromethylenated iminosugar 6 was a stronger inhibitor than comparable iminosugars 1 and 36, suggesting that the influence of this group is mainly through its effect on the amine. It is proposed that the unprotonated iminosugar is the species preferably bound by beta-glucosidase, due to the lower pK(a) value of iminosugar 6 than of 1 or 36, leaving iminosugars 1 and 36 mostly protonated at pH 5.0, while iminosugar 6 is not. Iminosugar 6 also displayed good and selective inhibition of beta-glucosidase at pH 6.8.


Insights into the Luminescence Quantum Yields of Cyclometalated Iridium(III) Complexes: A Density Functional Theory and Machine Learning Approach.
Cyclometalated iridium(III) complexes have been used in various optical materials, including organic light-emitting diodes (OLEDs) and photocatalysts, and a deeper understanding and prediction of their luminescence quantum yields (LQYs) greatly aid in accelerating material design. In this study, we integrated density functional theory (DFT) calculations with machine learning (ML) techniques to extract factors controlling LQY. Although a substantial data set of Ir(III) complexes and their LQYs is indispensable for constructing accurate ML models to predict LQYs, generating this type of data set is challenging due to the complexities associated with ab initio calculations of LQYs. To address this issue, we investigated the nonradiative decay process of nine Ir(III) complexes emitting blue to green, each exhibiting varying experimental LQYs, by using DFT calculations. For all nine complexes, the quenching process was induced by the rotation of the single bond in one of the ligands, which converted the six-coordinate structure to the five-coordinate structure. Since the decay mechanism was common for the nine Ir(III) complexes, parameters correlated with LQYs could be used as objective variables instead of LQYs. Based on this idea, we collected a data set featuring Ir(III) complexes and the energy differences between their six- and five-coordinate triplet structures, which correlated with LQYs. We also constructed ML models using the calculated LQYs as the objective variables with the parameters from the ground-state calculations as explanatory variables. The analyses of the constructed model revealed that the LUMO energy of the ligand made the most significant negative contribution to LQY. This suggests that the potential energy surface of the metal-to-ligand charge transfer (MLCT) excited state, which stabilizes the six-coordinate structure, is reduced by decreasing the energy of the unoccupied orbitals.


Catalytic oxidation of benzene with ozone over Mn/KIT-6.
Benzene is one of the target compounds to be removed from air owing to its carcinogenicity. In this study, benzene oxidation with ozone over a MnOx/KIT-6 catalyst was carried out for the first time. MnOx/KIT-6 was synthesized using two different Mn precursors: Mn acetate and Mn nitrate. The characteristics of the synthesized catalysts were examined by X-ray diffraction, X-ray photoelectron spectroscopy, temperature-programmed reduction, Brunauer-Emmett-Teller (BET) surface area, and N2 adsorption-desorption. The catalytic activity was found to be dependent on the amount of ozone consumed and the dispersion and reducibility of MnOx on the catalyst surface.


Homeobox gene hoxa3 is essential for the formation of the carotid body in the mouse embryos.
Homeobox gene Hoxa3 is strongly expressed in the third pharyngeal arch and pouch. We found that Hoxa3 homozygous null mutant mice had the lack of the carotid body. In all late-term mutant embryos examined (n = 10), no carotid body was present. The carotid body rudiment is formed in the wall of the third branchial artery, which develops into the common carotid artery and the first part of the internal carotid artery. The symmetrical patterns of the third, fourth, and sixth arch arteries were observed in wild-type littermates at embryonic day (E) 10.5-12.5. In Hoxa3 homozygous mutant embryos, however, the third arch artery began to degenerate at E10.5 and almost disappeared at E11.5. Furthermore, the bifurcation of the common carotid artery at the normal position, i.e., at the upper end of the larynx, was never detected in the mutant embryos at E16.5-E18.5. The common carotid artery of the homozygous mutants was separated into the internal and external carotid arteries immediately after its origin. Thus, the present study evidenced that the absence of the carotid body in Hoxa3 homozygous mutants is due to the defect of development of the third arch artery, resulting in malformation of the carotid artery system. During fetal development, the carotid body of mice is in close association with the superior cervical ganglion of the sympathetic trunk. The superior cervical ganglion rather showed hypertrophic features in Hoxa3 homozygous mutants lacking the carotid body.


Chromosomal radiosensitivity of lymphocytes from skin cancer-prone patients.
Frequencies of spontaneous and radiation-induced chromosome aberrations were documented in lymphocytes from patients with basal cell nevus syndrome (BCNS) and from those with epidermodysplasia verruciformis (EV). Cells were irradiated with single or double doses of gamma-rays or UV light. For the double dose irradiation protocol, the two doses were separated from each other by 60 min. After irradiation of cells with 4 or 2 + 2 J/m2 UV light, lymphocytes from seven BCNS patients had a similar number of aberrant cells compared with normal controls, while cells from three EV patients showed a significantly increased number of cells containing aberrations, particularly chromatid-type aberrations, compared to controls (p < 0.03, Student's t-test). Similar results were observed whether the cells were irradiated with single or double doses of UV light. In addition, lymphocytes from EV patients had significantly lower mitotic indices than controls whether the cultures were irradiated with UV light or unirradiated (p < 0.05; Student's t-test). After irradiation with 100, 100 + 100 or 50 + 50 cGy gamma-rays, the mean chromosome aberration frequencies from nine BCNS patients and two EV patients were not significantly different from the controls. The spontaneous chromosome aberration frequencies were similar for the patients and the controls. Our data indicate that BCNS and EV lymphocytes irradiated with gamma-rays have a normal DNA repair response. However, cells from EV patients have an abnormal repair response to UV light induced DNA damage. This abnormality is probably caused by deficiency in DNA repair and it is consistent with the patients' sensitivity to UV light induced cutaneous squamous cell carcinomas.


Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease.
Aging-related, nonresolving inflammation in both the central nervous system (CNS) and periphery predisposes individuals to the development of neurodegenerative disorders (NDDs). Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to inflammation and NDDs. However, few agents have been clinically shown to reduce NDD incidence by targeting inflammasomes. Our study indicated that NLRP3 (NLR family, pyrin domain containing 3) inflammasome is involved in Parkinson disease (PD) progression in patients and various murine models. In addition, the small molecule kaempferol (Ka) protected mice against LPS- and SNCA-induced neurodegeneration by inhibiting NLRP3 inflammasome activation as evidenced by the fact that Ka reduced cleaved CASP1 expression and disrupted NLRP3-PYCARD-CASP1 complex assembly with concomitant decreased IL1B secretion. Mechanically, Ka promoted macroautophagy/autophagy in microglia, leading to reduced NLRP3 protein expression, which in turn deactivated the NLRP3 inflammasome. Intriguingly, ubiquitination was involved in Ka-induced autophagic NLRP3 degradation. These findings were further confirmed in vivo as knockdown of Atg5 expression or autophagy inhibitor treatment significantly inhibited the Ka-mediated NLRP3 inflammasome inhibition and neurodegeneration amelioration. Thus, we demonstrated that Ka promotes neuroinflammatory inhibition via the cooperation of ubiquitination and autophagy, suggesting that Ka is a promising therapeutic strategy for the treatment of NDDs. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1, autophagy related; CASP1: caspase 1; CNS: central nervous system; CQ: chloroquine; DA neurons: dopaminergic neurons; DAMPS: damage-associated molecular patterns; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFAP: glial fibrillary acidic protein; IP: immunoprecipitation; i.p.: intraperitoneally; Ka: kaempferol; KD: knockdown; KO: knockout; LPS: lipopolysaccharide; IL1B: interleukin 1 beta; IL6: interleukin 6; Ly: lysate; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NC: negative control; NDD: neurodegenerative diseases; NLRP3: NLR family, pyrin domain containing 3; OE: overexpression; PD: Parkinson disease; poly-Ub: poly-ubiquitin; PTM: post-translational modification; PYCARD/ASC: PYD and CARD domain containing; Rapa: rapamycin; RFP: red fluorescent protein; SN: supernatant; SNCA: synuclein alpha; SNpc: substantia nigra pars compacta; SQSTM1: sequestosome 1; TH: tyrosine hydroxylase; TNF/TNF-alpha: tumor necrosis factor; Ub: ubiquitin; WT: wild type.


Corrective osteotomy in forearm fracture malunion improves functional outcome in adults.
Malunions of forearm fractures in adults can present with limitation of forearm rotation, or as distal radioulnar joint instability with functional impairment. This contrasts with paediatric patients in whom malunions of similar severities are often better tolerated. We did a retrospective review of six adult patients after corrective forearm osteotomy for symptomatic malunited forearm shaft fractures. The corrective operations were done between 7 and 168 months after initial injury, using oblique or wedge osteotomies. Median follow-up was 22.5 months. The patients recovered well, with statistically significant improvement in forearm rotation and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. No significant complications occurred.


Survival after ethylene glycol poisoning in a patient with an arterial pH of 6.58.
This ethylene glycol poisoning case had a blood pH of 6.58 and severe hypothermia (30.9 C). The patient received supportive care with dialysis and ethanol therapy. He survived in his premorbid state after 23 days in the hospital. A similar case survived ethylene glycol poisoning neurologicaly intact with an initial pH of 6.46. Although severe acidosis in the presence of serious illness is usually associated with a poor prognosis, our case emphasized the importance of aggressive supportive care and antidotal therapy for ethylene glycol poisoning even when there is a low pH.


Resin-retained bridges re-visited. Part 2. Clinical considerations.
Resin-retained bridges have been used clinically since the 1970s, and offer a more conservative approach to the restoration of edentulous spaces than conventional bridgework. They are easy to place, cheap to fabricate and have been shown to be cost-effective. Despite this, they are not frequently used in general dental practice and they have an undeserved reputation for failure. Since their initial introduction, they have undergone a number of changes to their method of retention, and the materials used in their construction. This has resulted in a predictable, aesthetic restoration which, barring the use of implants, is often the treatment of choice where teeth adjacent to an edentulous space are minimally or not restored. This article hopes to show the clinical techniques required to produce predictable resin-retained bridgework in general practice.


A Calcium-Selective Site in Photosystem II of Spinach Chloroplasts.
After acid-treatment of spinach (Spinacia oleracea) chloroplasts, various partial electron transport reactions are inactivated from 25 to 75%. Divalent cations in concentrations from 10 to 50 millimolar can partially restore electron transport rates. Two cation-specific sites have been found in photosystem II: one on the 3-(3,4-dichlorophenyl)-1, 1-dimethylurea-insensitive silicomolybdate pathway, which responds better to restoration by Mg(2+) than by Ca(2+) ions, the other on the forward pathway to photosystem I, located on the 2,5-dimethylbenzoquinone pathway. This site is selectively restored by Ca(2+) ions. When protonated chloroplasts are treated with N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aziridine, a carboxyl group modifying reagent, presumed to react with glutamic and aspartic acid residues of proteins, restoration of electron transport at the Ca(2+)-selective site on the 2,5-dimethylbenzoquinone pathway is impaired, while no difference in restoration is seen at the Mg(2+) site on the 3-(3,4-dichlorophenyl)-1,1-dimethylurea-insensitive silicomolybdate pathway.Trypsin treatment of chloroplasts modifies the light-harvesting pigment-protein complex, destroys the dibromothymoquinone-insensitive 2,5-dimethyl-benzoquinone reduction, but does not interfere with the partial restoration of activity of this pathway by Ca(2+) ions, implying that the selective Ca(2+) effect on photosystem II (selective Ca(2+) site) is different from its effects as a divalent cation on the light-harvesting pigment-protein complex involved in the excitation energy distribution between the two photosystems.


Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer.
Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy.


Bilateral Training Improves Agility and Accuracy for Both Preferred and Non-Preferred Legs in Young Soccer Players.
As laterality of the lower limbs is regarded as a relevant influence on soccer performance, we assessed whether a bilateral training program for both the preferred leg (PL) and non-preferred leg (NPL) would improve soccer players' lateral asymmetry, agility, and accuracy. Sixty right-foot-dominant young soccer players were randomly assigned to either an experimental group (EXP) that underwent bilateral training or a control group (CONT) that performed their usual training schedule without bilateral exercise. We assessed the players' lateral asymmetries before and after training on four soccer skill tasks: a zigzag test with and without a ball, a receiving and direct volley-shooting accuracy test, and a passing accuracy test. Results showed post-test versus pre-test performance improvements for the EXP group on the index of technical skills and agility (p < .001). A post-hoc analysis further revealed a pre-test to post-test performance improvement on shooting and passing accuracy with both legs only for the EXP group (p < .001). These results support the role of bilateral practice in improving lateral asymmetries, agility, and accuracy.


Feeding heated soyabean flour increases the density of B and T lymphocytes in the small intestine of calves.
The effect of dietary antigens on the gut morphology and density of immune cells was studied in preruminant calves fed milk substitutes containing skim milk powder (SMP), non-antigenic hydrolysed soya protein isolate (HSPI) or antigenic heated soyabean flour (HSF) as their main protein source for 3 months. The height and perimeter of proximal jejunum villi were highest in the calves fed SMP and lowest in those fed HSF (P < 0.05). In contrast, the crypt depth and perimeter were apparently not influenced by the dietary treatments studied. This morphological alteration was associated with a dramatic infiltration of the lamina propria by B and T lymphocytes in the calves fed HSF (P < 0.01). Increased B cell density was essentially accounted for by IgA-, IgG1- and IgG2-bearing cells. The density of CD2-positive T lymphocytes increased (P < 0.01) in the jejunal lamina propria of HSF calves, involving helper (CD4+) and suppressor-cytotoxic (CD8+) T cell subsets. The density of gamma-delta (WC1+) T cells also increased (P < 0.01). The major change concomitantly observed in the villus epithelium was an increased density of CD8+ cells (P < 0.05) and WC1 + cells (P < 0.01).


[Fine needle aspiration biopsy (FNAG) guided with tomodensitometry of pulmonary and mediastinal masses. Personal experience].
CT-guided fine-needle aspiration biopsy (FNAB) was performed on the patients with pulmonary or mediastinal masses to obtain material for cytologic/histologic diagnosis. Diagnostic accuracy and safety of the technique were evaluated in 75 patients affected with thoracic lesions still undiagnosed after thorough radiological and endoscopic investigations. The cytologic and/or microhistologic samples allowed a correct diagnosis to be made in 61 cases (81%), with no false positives and 7 false negatives (9%). The samples were inadequate for diagnostic purposes in 7 cases (9%). Specificity, sensitivity, and diagnostic accuracy were 68%, 76%, and 81%, respectively. No major complication was recorded and a case of asymptomatic pneumothorax resolved spontaneously within 48 hours. CT-guided FNAB of space-occupying lesions in the lung and mediastinum is therefore a rapid and valuable diagnostic tool and is quite safe when performed by skilled operators.


Anemia during and at discharge from intensive care: the impact of restrictive blood transfusion practice.
To document the prevalence of anemia among patients admitted to intensive care (ICU) and, among survivors, at ICU discharge when restrictive transfusion practice was used. This was an observational cohort study. Ten of the 26 general ICUs in Scotland. One thousand twenty-three sequential ICU admissions over 100 days, representing 44% of all ICU admissions in Scotland during the study period, studied daily from admission to discharge or death in the ICU. None. The median transfusion trigger used, in the absence of bleeding, was 78 g/l (interquartile range 73-84); <2% of transfusion triggers were above the upper limit of the national transfusion trigger guideline (100 g/l). Overall, 25% of admissions had a hemoglobin concentration <90 g/l at ICU admission. Seven hundred sixty-six patients admitted survived to ICU discharge. Among these, the prevalence of anemia (male <130 g/l; female <115 g/l) at ICU discharge was 87.0 (95% CI: 83.6 to 89.9)% for males and 79.6 (74.8 to 83.7)% for females. Of the male survivors 24.1 (20.3 to 28.3)% and of the female 27.9 (23.4 to 33.2)% had a hemoglobin <90 g/l at ICU discharge. The prevalence was similar for patients with and without pre-existing ischemic heart disease. Logistic regression found independent associations between having a hemoglobin concentration <90 g/l at ICU discharge and the first measured hemoglobin in ICU, the presence of acute renal failure and thrombocytopenia during ICU stay. Anemia is highly prevalent in ICUs that use restrictive transfusion triggers. The impact of anemia on functional recovery after intensive care requires investigation.


Emerging diseases of Cannabis sativa and sustainable management.
Cultivation of cannabis plants (Cannabis sativa L., marijuana) has taken place worldwide for centuries. In Canada, legalization of cannabis in October 2018 for the medicinal and recreational markets has spurned interest in large-scale growing. This increased production has seen a rise in the incidence and severity of plant pathogens, causing a range of previously unreported diseases. The objective of this review is to highlight the important diseases currently affecting the cannabis and hemp industries in North America and to discuss various mitigation strategies. Progress in molecular diagnostics for pathogen identification and determining inoculum sources and methods of pathogen spread have provided useful insights. Sustainable disease management approaches include establishing clean planting stock, modifying environmental conditions to reduce pathogen development, implementing sanitation measures, and applying fungal and bacterial biological control agents. Fungicides are not currently registered for use and hence there are no published data on their efficacy. The greatest challenge remains in reducing microbial loads (colony-forming units) on harvested inflorescences (buds). Contaminating microbes may be introduced during the cultivation and postharvest phases, or constitute resident endophytes. Failure to achieve a minimum threshold of microbes deemed to be safe for utilization of cannabis products can arise from conventional and organic cultivation methods, or following applications of beneficial biocontrol agents. The current regulatory process for approval of cannabis products presents a challenge to producers utilizing biological control agents for disease management. © 2021 The Author. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas.
Approximately 66,000 Americans develop non-Hodgkin lymphoma (NHL) each year. Although the use of unlabeled antibodies such as rituximab has significantly improved survival when combined with standard chemotherapy regimens, approximately two-thirds of lymphoma patients eventually develop disease recurrence and die of their disease. Novel treatments are urgently needed to cure these patients. One strategy involves the use of radiolabeled immunoconjugates that specifically localize radiation delivery to sites of lymphoma while minimizing toxicity to normal tissues. A growing number of studies support the contention that radiolabeled antibody therapy can improve overall survival of lymphoma patients and lead to durable remissions, with probable cures, in many patients. Various approaches for enhancing the effectiveness of radioimmunoconjugates have been studied, including: use in newly diagnosed lymphoma patients, combination with chemotherapy or other monoclonal antibodies, use with hematopoietic stem cell transplantation, multistep pretargeting strategies to further minimize toxicity, and simultaneous targeting of multiple B-cell antigens. This article summarizes the current knowledge supporting the use of radioimmunotherapy, an underused but effective treatment modality in NHL patients.


The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice.
The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α₂-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α₁-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT₃ receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT1, 2 receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α₂-adrenergic receptor, and both α₂-adrenergic and 5-HT₃ receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.


Thrombin and albumin adsorption to PVA and heparin-PVA hydrogels. 2: Competition and displacement.
Thrombin adsorption to polyvinyl alcohol (PVA) was different from its adsorption to polyethylene (PE)--not so much in amount, but in its affinity. Thrombin was more easily displaced from polyethylene and its adsorption was more readily prevented by prior or simultaneous exposure to albumin. From PVA (or heparin-PVA), only approximately 30% of the adsorbed protein could be removed by a series of eluents, including even harsh ones such as 2.5M NaOH and 6M guanidine; > 85% could be removed from PE. Thrombin adsorption to PVA was not affected by the presence of BSA in solution or at the surface, but was virtually prevented on PE by preexposure to or adsorption with BSA. Heparin-PVA was not much different than PVA in most of these experiments, but did exhibit a "Vroman effect". In the absence of fibrinogen or antithrombin III, there was a maximum in thrombin adsorption from plasma at a plasma concentration of 1%. The behavior on this surface was dependent on both exposure time and protein concentration. These studies highlight the complexity of the interaction between plasma proteins and polymer surfaces (particularly hydrogel surfaces) and the difficulty of obtaining a clear picture of what happens when a single protein interacts with a polymer in the presence of other proteins.


Development of the settlement system in the Lithuanian SSR: results, problems, and prospects.
"The authors analyze the factors, results, problems, and prospects of the development of a system of settlement in the Lithuanian SSR, a laboratory of sorts for settlement policy in the Soviet Union. Particular attention is devoted to the formation of an inter-rayon settlement system integrating urban and rural settlements. Several methodological and conceptual approaches to the study of settlement systems are examined in this context."


Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity.
Heparin and heparinoids have long been proposed for stroke treatment. This study investigates the effect of enoxaparin (Lovenox, Clexane), a low-molecular-weight heparin, on functional outcome (neuroscore) and lesion size in stroke models with reversible and irreversible cerebral ischemia using middle cerebral artery occlusion (MCAO) in the rat. Ischemia was induced in rats by transient occlusion for 2 hours or by permanent electrocoagulation of the left MCA. Forty-eight hours after ischemia, neurological deficit was evaluated by scoring sensorimotor functions and ischemic damage was quantified by histological evaluation of lesion volumes. After transient MCAO, enoxaparin at 2x1.5 mg/kg IV (2 and 24 hours after insult) significantly reduced lesion size by 30% (P<0.05) and improved neuroscore (P<0.01). This significant effect on lesion size and neuroscore was still evident when treatment was started 5 hours after insult. Administered under the same protocol with a 5 hours delay post permanent MCAO, enoxaparin reduced lesion size by 49% (P<0.05) and improved neuroscore (P<0.01). This study indicates that standard nonhemorrhagic doses of enoxaparin reduce ischemic damage with a wide therapeutic window. In addition to its anticoagulant properties, other properties of enoxaparin could act in synergy to explain its neuroprotective profile in ischemia. Thus clinical application of enoxaparin treatment in stroke warrants serious consideration.


[Cancer of unknown primary site origin--advances in diagnosis and therapy].
Cancer of unknown primary site (CUP) is defined as a metastatic disease, identified on biopsy, with it's origin remaining unknown despite extensive clinical, laboratory and imaging studies. As much as 3% to 10% of all cancers can be defined as CUP. The primary workup includes history taking, a full physical examination, basic laboratory studies, imaging studies and immunohistochemical staining or genetic analysis of biopsy material. The diagnostic yield of such studies is about 20% to 30% of cases. New advanced techniques can be used to define the genetic profile of the tumor cells. Comparing such profiles to those originating from known tumors may markedly improve our ability to detect the origin of CUP in up to 90% of cases. The treatment of CUP is based on the regimen given for cancer of the presumed origin, and in many cases is completely empiric. The prognosis for patients with CUP is dismal partially due to the late stages in which the disease is diagnosed and the aggressiveness of the tumor. The median survival is 10-12 months and the 2 year survival is 20%-25%. This is a case report demonstrating the dilemmas in managing such patients, followed by a review of the recent medical literature covering the topic.


Review of the prescription of domiciliary long term oxygen therapy in Scotland.
Since 1989 long term oxygen therapy (LTOT) in Scotland has been prescribable only by respiratory physicians, whereas in England and Wales general practitioners can also prescribe this treatment. The effect of this policy has been audited. Six hundred and thirty patients were prescribed LTOT in Scotland between 1 October 1989 and 30 September 1991, of which 519 case notes were reviewed. In 79% of patients the diagnosis was chronic obstructive pulmonary disease (COPD), with a near equal male to female ratio. The mean (SD) age was 65 (13) years (range 0.2-90). Sixty percent of patients died during the study period. Compliance with treatment was 14.9 (6.0) hours daily (range 1-24) and in 44% was less than 15 hours daily. Sixty one percent were clinically unstable when assessed and 14% were still smoking. Only 14% of those with COPD fulfilled all of the relative criteria for the prescription of LTOT. Only 56% had a repeated arterial blood gas measurement within 12 months of prescription and 51% of these were taken during a period of clinical instability. Expenditure on oxygen cylinders was six times greater than on oxygen concentrators over this period. Compliance with LTOT in Scotland, where prescription is the responsibility of respiratory physicians, is similar to other studies and ranges widely. The greatest problem concerning adherence to the guidelines is assessment during clinical instability. The number of deaths suggest that prescription occurs late in the course of the disease. This study highlights the areas where the prescription of LTOT needs to be improved.


Diode-side-pumped, intracavity Nd:YLF/KGW/LBO Raman laser at 573 nm for retinal photocoagulation.
Wavelengths in the yellow-orange range are of significant interest for retinal photocoagulation and are especially important in the case of diabetic retinopathy, which can cause blindness and affects 3.3% of all working-age adults. This work presents a highly-efficient, compact, and cost-efficient side-pumped, intracavity Raman configuration to achieve this objective. A side-pumped Nd:YLF/KGW/LBO frequency-doubled Raman laser producing 11.7 W of output power at 1147 nm with 21% of slope efficiency and 6 W of output power at 573.5 nm with 12% slope efficiency is demonstrated.


Developmental changes in expression of genes involved in regulation of apoptosis in the bovine preimplantation embryo.
The early bovine preimplantation embryo is resistant to proapoptotic signals until around the 8- to 16-cell stage. We hypothesized that 2-cell embryos have higher amounts of antiapoptotic proteins and lower amounts of proapoptotic proteins when compared to embryos ≥16 cells. Steady-state concentrations of mRNA for the antiapoptotic genes BCL2 and HSPA1A were higher for MII oocytes, 2-cell embryos, and 2-cell embryos treated with alpha-amanitin as compared to ≥16-cell embryos. Steady-state concentrations of mRNA for the proapoptotic gene BAD increased in embryos ≥16 cells. There was no significant effect of stage of development on steady-state mRNA concentrations of BCL2L1, DFFA, or BAX. Using immunohistochemistry, it was found that BCL2 was present in greater relative concentrations for 2-cell embryos than for embryos ≥16 cells. These results were confirmed by Western blotting. Relative amounts of immunoreactive BAX detected by immunofluorescence were lower for 2-cell embryos than for embryos ≥16 cells. Using Western blotting, a high molecular weight (46 kDa) form of BAX was highest in ≥16-cell embryos, intermediate in 2-cell embryos, and lowest in MII oocytes. There were no effects of stage of development on relative amounts of immunoreactive BCL2L1, HSPA1A, or BAD, as determined by immunofluorescence. Treatment of embryos with alpha-amanitin from Day 0 to Day 5 or Day 4 to Day 5 after insemination reduced activation of group II caspases and terminal deoxynucleotidyl transferase dUTP nick end labeling after treatment with the proapoptotic signal C(2) ceramide at Day 5 after fertilization. Thus, transcription of BAX or other proteins is required for acquisition of the capacity for apoptosis. Results support the idea that changes in amounts of BCL2 family members are important for the inhibition of apoptosis in the 2-cell embryo and in the establishment of the capacity for apoptosis later in development.


Cytotoxic effect of IFN-gamma plus TNF-alpha on human islet cells.
We have previously reported that the combination of IFN-gamma plus TNF-alpha is able to induce the de novo expression of HLA class II on human beta cells. In the present study, we have investigated the effect of these cytokines, alone or in combination, on the function and viability of human islet cells in vitro. Three hour insulin release was markedly reduced in human islet monolayer cultures after 4 days' exposure to 1000 U/ml of the combination TNF-alpha plus IFN-gamma (36.7 +/- 7.7, % of the control +/- SEM) or to TNF-alpha alone (49.5 +/- 7% of the control) while IFN-gamma had little effect. On direct inspection cell damage was clearly detected only in the cultures treated with TNF-alpha plus IFN-gamma in which staining by indirect immunofluorescence (IFL) for insulin revealed that the number of beta cells was also significantly reduced, thus suggesting a real cytotoxic effect of this cytokine combination. This effect was not beta cell specific since glucagon release and the number of alpha cells were also reduced in the cultures exposed to IFN-gamma plus TNF-alpha. 51Cr release experiments supported the cytoxicity of these cytokines to normal islet cells. There was a time course relationship between class II induction (2 days) and the cytotoxic effect of IFN-gamma plus TNF-alpha (4 days) on the same islet cells. In conclusion, these results indicate that the combination of IFN-gamma and TNF-alpha exerts a cytotoxic effect on human islet cells in vitro.


Incidence and progression of astigmatism in Singaporean children.
This study investigated the incidence and progression, as well as factors associated with changes in astigmatism in school children. This was a prospective cohort study. Children 7 to 9 years of age, of Chinese, Malay, and Asian Indian ethnicity, were examined annually over a 4-year period. Cycloplegic autorefraction was performed. A questionnaire was used to evaluate risk factors for incidence and progression of astigmatism. The cumulative 3-year incidence rate of astigmatism was 33.6% (cylinder power of 0.5 D or worse) or 11.5% (cylinder power of 1.0 D or worse). Myopic children had a higher incidence rate of astigmatism than nonmyopes (P <0.001). The mean J0 change per year was 0.012 D (95% CI: 0.007-0.018), whereas J45 did not show a significant change each year (mean, 0.001 D per year). Chinese children had greater worsening of J0 per year (P <0.001). Girls also had significantly greater progression of J0 than did boys (P <0.001). Similarly, myopia at baseline (P <0.001) and the hours of computer use (P=0.049) were associated with a greater progression rate of J0. J0 tended to improve in children with compound hyperopic astigmatism, worsen in children with compound myopic astigmatism, and remain stable in mixed astigmatics. Although there was minimal progression of astigmatism in school age children (0.44-0.53 D) over this period of follow-up, incident cases of astigmatism (>1.0 D) were not uncommon. The progression rate of astigmatism was affected by the ethnicity, presence of myopia, axis, and subtype of astigmatism.


Bronchiectasis: CT evaluation.
CT is the imaging method of choice after standard chest radiography for examining patients with suspected bronchiectasis. In most institutions throughout the world, CT has largely eliminated the need for bronchography in the diagnosis of bronchiectasis. Nonetheless, controversy persists concerning the overall accuracy of CT. In an effort to improve overall diagnostic accuracy, we review the wide range of CT appearances of this protean disorder, and emphasize potential problems and technical pitfalls that may arise in routine clinical imaging.


Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidylglycerols.
Surfactant Protein A (SP-A) is an abundant, multifunctional lectin that resides within the bronchoalveolar compartment of the lung and plays an important role in the innate immunity of the organ. Mycoplasma pneumoniae is a human pathogen that resides in the same compartment as SP-A, and we examined the interaction between the two. Preparations of human and rat SP-A recognized the mycoplasma with high affinity in the presence of Ca(2+), exhibiting apparent K(')(d) values in the nanomolar range. Membranes prepared from the microbe also bound human and rat SP-A with similar characteristics and affinity to the intact cells. The ligand for SP-A was insensitive to proteolysis. Lipid extracts prepared from the mycoplasma, bound SP-A with high affinity when examined by ligand blot analysis. These lipid extracts were also potent competitive inhibitors (IC(50) = 0.2 nM) of human SP-A binding to mycoplasma membranes. The major lipid ligands for the protein identified by mass spectrometry are a group of disaturated phosphatidylglycerols. The addition of SP-A to cultures of M. pneumoniae markedly attenuated the growth of the organism assessed by colony formation, metabolic activity, and DNA replication. The bacteriostatic effects of SP-A were reversed by dipalmitoylphosphatidylglycerol. These findings demonstrate that human SP-A can play a direct role in antibody-independent immunity to M. pneumoniae by interacting with lipid ligands expressed on the surface of the organism and implicate SP-A in the immediate host response to the bacteria.


[Simultaneous determination of exogenous phosphocreatine and its metabolite creatine in rabbit plasma using ion-pair reversed-phase high performance liquid chromatography].
A method for simultaneous determination of exogenous phosphocreatine (PCr) and its metabolite creatine (Cr) in rabbit plasma was developed by using an ion-pair reversed-phase high performance liquid chromatography (IP-RP-HPLC). The pharmacokinetics (PK) of PCr was also investigated. In the IP-RP-HPLC method, a Kromasil C,8 column was used with methanol and phosphate buffer containing tetrabutylammonium hydrogen sulfate (TBA, ion-pair reagent) as the mobile phases in a gradient elution mode, while changing detection wavelength and flow rate. The internal standard method was used to quantify PCr and Cr, and the baseline subtraction method was applied. The calibration curves showed good linearity ranged from 10 to 7 500 mg/L for PCr and from 10 to 1 500 mg/L for Cr, and the correlation coefficients (r) were greater than 0. 999. The methodology validation showed high specificity, precision and recovery with the intra-day and inter-day relative standard deviations (RSDs) of not more than 6. 2%, accuracies of 96. 5% - 102. 4%, and extraction recoveries of more than 92%. After intravenous injection of PCr, the concentration-time profile can be best described by two-compartment model with elimination half time of (20.4 +/- 2.7) min, apparent volume of distribution of (0.179 +/- 0.037) L/kg and clearance rate of (0.019 +/- 0. 002) L/(kg x min). The Cr appeared rapidly with time to maximal concentration of 30 min, elimination half time of (43.7 +/- 4. 5) min. The results of practical application showed that this bio-analytical method can completely meet the requirements for PK study of PCr in rabbit plasma.


Evolution of the class IV HD-zip gene family in streptophytes.
Class IV homeodomain leucine zipper (C4HDZ) genes are plant-specific transcription factors that, based on phenotypes in Arabidopsis thaliana, play an important role in epidermal development. In this study, we sampled all major extant lineages and their closest algal relatives for C4HDZ homologs and phylogenetic analyses result in a gene tree that mirrors land plant evolution with evidence for gene duplications in many lineages, but minimal evidence for gene losses. Our analysis suggests an ancestral C4HDZ gene originated in an algal ancestor of land plants and a single ancestral gene was present in the last common ancestor of land plants. Independent gene duplications are evident within several lineages including mosses, lycophytes, euphyllophytes, seed plants, and, most notably, angiosperms. In recently evolved angiosperm paralogs, we find evidence of pseudogenization via mutations in both coding and regulatory sequences. The increasing complexity of the C4HDZ gene family through the diversification of land plants correlates to increasing complexity in epidermal characters.


Environmental contamination during influenza A virus (H5N1) outbreaks, Cambodia, 2006.
To determine potential risk for bird-to-human transmission during influenza A virus (H5N1) outbreaks among backyard poultry in rural Cambodia, we collected environmental specimens. Viral RNA was detected in 27 (35%) of 77 specimens of mud, pond water, water plants, and soil swabs. Our results underscore the need for regular disinfection of poultry areas.


Concentrations of Indole-3-acetic Acid and Its Esters in Avena and Zea.
An isotope-dilution method has been developed for the assay of free indole-3-acetic acid and ester indole-3-acetic acid as measured by indole-3-acetic acid liberated by mild alkaline hydrolysis. Application of this method to seedlings of Avena sativa and Zea mays indicates the upper limit of free indole-3-acetic acid in Avena to be about 16 mug per kg and in Zea, about 24 mug. The amount of 1 n alkali-labile indole-3-acetic acid in Zea is about 330 mug per kg and there is very little 1 n alkali-labile IAA in Avena. A chemical characterization of the indole-3-acetic acid of Avena and a confirmation of the chemical characterization of the indole-3-acetic acid of Zea is presented.


Efficient phase-cycling strategy for high-resolution 3D gradient-echo quantitative parameter mapping.
Magnetization-prepared (MP) gradient-echo (GRE) sequences suffer from signal contaminations from T1 recovery during the readout train, which can be eliminated by paired RF phase cycling (PC) at the cost of doubling the scan time. The objective of this study was to develop and validate a novel unpaired PC strategy to eliminate the time penalty for high-resolution quantitative parameter mapping in 3D MP-GRE sequences. Based on the observation that the contaminating T1 recovery signal along the GRE readout train is independent of magnetization preparation, its impact can be eliminated using a novel curve-fitting approach with complex-valued data without needing paired PC acquisitions. Four new unpaired PC schemes were compared with two traditional paired PC schemes in both phantom and in vivo human knee studies at 3 T using a MP angle-modulated partitioned k-space spoiled gradient-echo snapshots (MAPSS) T1ρ mapping sequence. In the phantom study, all methods resulted in consistent T1ρ measurements (∆T1ρ < 0.5%) at the center slice when B0 /B1 values were uniform. Results were not consistent when off-center slices with nonideal B0 /B1 were included. Two unpaired PC schemes had comparable or significantly improved quantitative accuracy and scan-rescan reproducibility compared with the paired PC schemes. There was no significant T1ρ quantitative variability increase or spatial fidelity loss using the new unpaired PC schemes. Unpaired PC schemes also had different T1ρ spectral responses at different B0 frequency offsets, which can potentially be exploited to reduce sensitivity to B0 field inhomogeneities. The human knee study results were consistent with the phantom study findings. In conclusion, an unpaired PC strategy potentially allows more accurate quantitative parameter mapping with halved scan time compared with the paired PC approach to eliminate signal contaminations from T1 recovery. It therefore offers additional flexibility in SNR optimization, spatial resolution improvement, and choice of imaging sampling points to obtain more accurate quantitative parameter mapping.


Risk behavior and HIV seroprevalence among injecting drug users in Rio de Janeiro, Brazil.
To characterize HIV seroprevalence and risk behavior among injecting drug users (IDUs) in Rio de Janeiro, Brazil, between 1990 and 1996. We report data from three separate cross-sectional samples of IDUs in Rio de Janeiro: the World Health Organization (WHO) sample (n = 479), the Proviva sample (n = 138) and the Brasil sample (n = 110). These data provide the most comprehensive view available, to date, of this understudied population in Rio. Demographic characteristics, HIV/AIDS risk behavior and HIV seroprevalence were compared across the three samples and combined analyses were performed to determine the factors associated with injecting risk behavior, sexual risk behavior and HIV seropositivity. The overall HIV seroprevalence among IDUs was 25%. Two encouraging findings of the present analysis were the lower levels of needle-sharing among participants recruited in the latest years (1995-1996) and the lower HIV seroprevalence in the Proviva sample composed mainly of less educated, poorer IDUs living in deprived neighborhoods. No trends toward safer behavior were found for sexual risk, younger age being the principal factor associated with high risk. Levels of needle-sharing and sexual risk among IDUs in Rio remain high, demonstrating the urgent need to increase the limited preventive measures undertaken so far. Seroprevalence levels for HIV remain significantly lower in the most deprived sample, arguing for the fundamental importance of prompt and effective prevention strategies to keep infection rates from rising among the poorest and largest strata of Rio's IDUs.


A conserved surface on the ligand binding domain of nuclear receptors for allosteric control.
Nuclear receptors (NRs) form a large superfamily of transcription factors that participate in virtually every key biological process. They control development, fertility, gametogenesis and are misregulated in many cancers. Their enormous functional plasticity as transcription factors relates in part to NR-mediated interactions with hundreds of coregulatory proteins upon ligand (e.g., hormone) binding to their ligand binding domains (LBD), or following covalent modification. Some coregulator association relates to the distinct residues that shape a coactivator binding pocket termed AF-2, a surface groove that primarily determines the preference and specificity of protein-protein interactions. However, the highly conserved AF-2 pocket in the NR superfamily appears to be insufficient to account for NR subtype specificity leading to fine transcriptional modulation in certain settings. Additional protein-protein interaction surfaces, most notably on their LBD, may contribute to modulating NR function. NR coregulators and chaperones, normally much larger than the NR itself, may also bind to such interfaces. In the case of the androgen receptor (AR) LBD surface, structural and functional data highlighted the presence of another site named BF-3, which lies at a distinct but topographically adjacent surface to AF-2. AR BF-3 is a hot spot for mutations involved in prostate cancer and androgen insensitivity syndromes, and some FDA-approved drugs bind at this site. Structural studies suggested an allosteric relationship between AF-2 and BF-3, as occupancy of the latter affected coactivator recruitment to AF-2. Physiological relevant partners of AR BF-3 have not been described as yet. The newly discovered site is highly conserved among the steroid receptors subclass, but is also present in other NRs. Several missense mutations in the BF-3 regions of these human NRs are implicated in pathology and affect their function in vitro. The fact that AR BF-3 pocket is a druggable site evidences its pharmacological potential. Compounds that may affect allosterically NR function by binding to BF-3 open promising avenues to develop type-specific NR modulators.


Early Permian (Cisuralian) ostracods from Japan: characteristic ostracod assemblage from a seamount of the Panthalassic Ocean.
Silicified ostracods were recovered from Cisuralian micritic limestones of the Ryozensan Limestone Formation from the southwestern part of Ryozensan Mountain, Taga City located in Shiga Prefecture, Central Japan. Twenty-seven species belonging to 19 genera were obtained, of which six species are new and are described here: Bairdia tagaensis Tanaka sp. nov., Bairdiacypris ikeyanoriyukii Tanaka sp. nov., Kellettina noriyukii Tanaka sp. nov., Microcheilinella shigensis Tanaka sp. nov., Oliganisus ryozensannensis Tanaka sp. nov., and Pustulobairdia ohmiensis Tanaka sp. nov. Some Palaeozoic limestone localities in Japan cap greenstones and are surrounded by younger cherts (such as Mino Terrane of this study). They represent a characteristic reef and reef-slope environment around a seamount surrounded by deep sea ocean floor. This result is concordant with the ostracod assemblage. After this report, a Panthalassan ostracod fauna could be defined for the Cisuralian.


Immunocytochemical localization of nitrite reductase in green algae.
The distribution of nitrite reductase (EC 220.127.116.11) in the green algae Chlamydomonas reinhardtii, Monoraphidium braunii, Chlorella fusca, and Scenedesmus obliquus was studied by immunoelectron microscopy. The labeling of ultrathin cryosections was performed with anti-nitrite reductase antibodies followed by gold-labeled goat anti-rabbit antibodies. In C. reinhardtii sections, gold label was mainly associated with the pyrenoid, tonoplast, and plasmalemma. Significant labeling was also detected in the thylakoid region. In all other organisms, label density was lower but distributed in the same locations, except that the plasmalemma of S. obliquus was not significantly labeled. From estimates of the relative volume of different cell regions, we found that approximately 80% of the total enzyme is located in the chloroplastic region (thylakoids plus pyrenoid) of C. reinhardtii, M. braunii, and C. fusca, and 97% in the case of S. obliquus.


[To improve the quality of requisitions for radiologic examinations].
This article presents the different steps implemented in order to improve the quality of requisitions for radiologic examinations in a hospital. and methods. The radiology requests sent from clinical units are periodically analyzed using criteria about tracking, prescription and security required for a good examination. Results are discussed with the clinical units in order to achieve improvements. The periodical analysis of nonconformities shows a gradual improvement of practices. This action contributes to the realization of a single document for every request of examination or analysis in the hospital. The described action is in the context of French regulations, first about the practice of radiology, second about the obligation of quality improvement that health care facilities now have to implement for their accreditation.


Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells.
Panax ginseng is known to have anti-diabetic activity, but the active ingredients are not yet fully identified. In this study, we found the inhibitory effect of Rg(1) on hepatic glucose production through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Rg(1) significantly inhibited hepatic glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. In addition, Rg(1) markedly induced the phosphorylations of liver kinase B1 (LKB1), AMPK and forkhead box class O1 (FoxO1), a key transcription factor for gluconeogenic enzymes, in time- and concentration-dependent manners. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were inhibited by 24% and 21%, respectively, when the cells were exposed to 40 microM of Rg(1), resulting from phosphorylation of FoxO1 and inhibition of gluconeogenic gene expression. Taken together, our results demonstrated the suppressive effect of Rg(1) on hepatic glucose production via LKB1-AMPK-FoxO1 pathway in HepG2 human hepatoma cells.


[Echostructural polymorphism of prostatic carcinoma. Anatomo-pathologic correlations in various developmental stages].
The sonographic appearance of prostatic carcinoma was correlated with the corresponding histopathologic studies in 57 patients after transperineal biopsy. In 21 cases the lesions observed were less than or equal to 2 cm (circumscribed) and in 36 were greater than 2 cm (diffuse). Within the first group there was a prevalence of hypoechoic forms (61,9%). While isoechoic and hyperechoic foci were observed in 14.3% and 23.8%. In diffuse prostatic carcinoma, mixed echogenicity was observed in 50% of patients, hypoechoic in 27.8% and isoechoic in 22.2%. The variations in the appearance of prostatic cancer indicate that sonographic texture is related to the size and histopathologic features of the neoplastic growth.


Association between toll-like receptors/CD14 gene polymorphisms and inflammatory bowel disease in Korean population.
The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohn's disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.


Overwinter Changes in the Lipid Profile of Young-of-the-Year Striped Bass (Morone saxatilis) in Freshwater Ponds.
Young-of-the-year (YOY) striped bass (Morone saxatilis) suffer significant mortality during their first winter. While causes of this mortality are unclear, lipids may play role in adapting to winter stresses, including thermal change and food scarcity. To address this, YOY striped bass were placed in mesh cages in freshwater ponds in the fall (November) and were held until the end of winter, in March. Liver and white muscle tissue were sampled at the beginning and end of the study to compare concentrations of specific lipid classes and fatty acid composition. Muscle-tissue total lipid and triacylglycerol (TAG) was higher in March (late winter) samples. Additionally, concentrations of phosphatidylethanolamine (PE) were higher in the white muscle of striped bass sampled in March; this was accompanied by a decrease in proportions of 18:0 and 22:6n-3 in PE (from ~11 to 7% and 36 to 28%, respectively) and 18:1n-9 and 22:6n-3 in phosphatidylcholine (from ~15 to 10% and 24 to 18%, respectively). This suggests that these fish were not utilizing energy reserves in previously described ways and appear to rely more on other lipid classes or body tissues for overwinter survival than those analyzed in this study.


[Influence of ASODN to the human tenon's fibroblasts in expressing CTGF induced by transforming growth factor beta2].
To investigate the effect of connective tissue growth factor's antisense oligonucleotides (ASODN) on the growth of human tenon' s capsule fibroblasts (HTF) induced by transforming growth factor beta2 (TGF-beta2) in vitro. It was a experimental study. HTF was collected from glaucoma patients and cultured. The 5-6 passage was used for experiments. The HTF induced by TGF-beta2 was divided into the following groups: N group: normal HTF; T group: HTF induced by TGF-beta2; A group: CTGF ASODN antisense:5'-TACTGGCGGCGGTCAT-3' encapsulated with liposome; S group: sense 5'-ATGACCGCCGCCAGTA-3' encapsulated with liposome; D group: HTF encapsulated with liposome only. The activity of HTF treated by different concentrations of liposome was detected using methylthianolyldiphenyl tetrazolium bromide (MT) colorimetry. The expression of CTGF was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assays. The expression of fibronectin (Fn) was examined by Western blot and immunocytochemistry assays. Liposome-ASODN (A group) significantly (F=15.25, 204.88, 19.73, 90.00; P <0.05) inhibit the expression of CTGF and Fn in HTF induced by TGF-beta2 compared with S and D group. However, Liposome alone (T group) has no significant impact in HTF growth compared with T group (t = 0.90, 2.32, 0.75, 2.11; P > 0.05). CTGF-ASODN inhibits the CTGF and Fn expression of HTF induced by TGF-beta2, which may delay the formation of scar in glaucoma filtering surgery.


Domain structure of the glucocorticoid receptor protein.
The purified rat liver glucocorticoid receptor protein was analyzed by limited proteolysis and amino acid sequence determination. The NH2 terminus appears to be blocked. The steroid-binding domain, defined by a unique tryptic cleavage site, corresponds to the COOH-terminal part of the protein with the domain border in the region of residue 518. The DNA-binding domain, defined by a region with chymotryptic cleavage sites, is immediately adjacent to the steroid-binding domain and reflects another domain border in the region of residues 410-414. The results described at the protein level in this report confirm functional data previously obtained by mutations at the genetic level.