Mothers' childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways.
Research suggests the health consequences of economic hardship can be transmitted across generations. Some of these disparities are thought to be passed to offspring during gestation. But this hypothesis has not been tested in contemporary American samples, and the mechanisms of transmission have not been characterized. Accordingly, this study had two goals: first, to determine if women exposed to economic hardship during childhood showed higher rates of adverse birth outcomes; and second, to evaluate the contribution of inflammation, psychosocial, lifestyle, and obstetric characteristics to this phenomenon. This prospective study enrolled 744 women with singleton pregnancies (59.1% White; 16.3% Black; 18.7% Latina; 5.9% Other). Childhood economic hardship was measured by self-report. Birth outcomes included length of gestation and incidence of preterm birth; birth weight percentile and small for gestational age; length of hospital stay and admission to Special Care Nursery. Analyses revealed that mothers' childhood economic hardship was independently associated with multiple adverse birth outcomes, even following adjustment for demographics, maternal education, and obstetrical confounders. Women raised in economically disadvantaged conditions had shorter gestation length and higher preterm delivery rates. Their babies had lower birth weights, were more likely to be small for gestational age, stayed in the hospital longer, and had more Special Care Nursery admissions. Mediation analyses suggested these associations arose through multiple pathways, and highlighted roles for inflammation, education, adiposity, and obstetric complications. Collectively, these findings suggest that childhood economic hardship predisposes women to adverse birth outcomes, and highlights likely behavioral and biological mechanisms.


Sori tumas: the decision not to treat.
I am convinced that one of the most important and difficult aspects of the work on a specialist surgeon in Papua New Guinea, is knowing when not to treat conditions that would be enthusiastically treated in other countries. Most of our patients would rather die at home than in hospital, and they appreciate and can accept an honest assessment of their prognosis.


Impact of SMBG on control of diabetes as measured by HbA1. 3-yr survey of a juvenile IDDM clinic.
Three hundred twelve diabetic children and adolescents were seen in our diabetic clinic and instructed to test their capillary blood glucose (CBG) twice daily and to use an algorithm to adjust their short-acting insulin. Of this group, 219 youngsters had a full 3-yr period of observation. At each clinic visit, blood was obtained for fasting blood glucose and HbA1 and, once a year, cholesterol and triglycerides were also measured. Patient and parent accuracy in measuring CBG was found to be adequate. The changes over time in HbA1 were nondifferential across age and sex, and there was no difference in the level of HbA1 between age and sex groups, the number of tests reported to have been done by the patients, the number of injections of insulin per day, or the serum cholesterol. There was a significant relationship between the HbA1 and the fasting blood glucose (P less than .001) measured by the laboratory as well as with the serum triglyceride (P less than .01). The failure to improve diabetic control, despite measures that would have been expected to do so, was believed to relate more to a lack of compliance than to a flaw in the therapeutic approach. It was interesting to note that the adolescent patients in the study were in no worse control than the younger children in the group. Although better technical skills are available today to manage diabetes, the psychosocial approach to patient motivation requires improvement.


Is problematic internet use an indicator of eating disorders among Turkish university students?
The aim of this study was to investigate the relationship between problematic internet use and eating attitudes in a group of university students. The study sample consisted of 314 students attending programs at the faculties of education, medicine and communications at the Karadeniz Technical University in Turkey. One hundred forty-seven (46.8 %) were male and 167 (53.2 %) female. The Problematic Internet Use Scale was used to measure problematic internet use levels among university students and the Eating Attitudes Test to determine anorexia nervosa symptoms. Additionally, a Personal Data Form was used to determine age, gender, faculty attended and computer ownership. Data were analyzed on SPSS 15.00. Pearson's product moments correlation coefficient, multiple linear regression analysis, the independent t test and one-way ANOVA were used for data analysis. The research findings showed that 46.8 % of students were female and 53.2 % male. Mean age was 20.65 (SD 1.42). Analysis showed a significant positive correlation between problematic internet use and eating attitudes (r = 0.77, p < 0.01). Problematic internet use was found to be a significant predictor of eating attitudes. The results also showed a significant difference in problematic internet use with regard to program variables [F (2,311) = 102.79]. There were no significant differences in problematic internet use in terms of gender or computer ownership. The results of this study indicate that problematic internet use is significantly correlated with eating disorders, that problematic internet use does not vary on the basis of gender or computer ownership and that variations arise in problematic internet use depending on the faculty attended.


Medical evaluation for driver qualification for patients with cardiovascular disorders.
Primary care physicians commonly care for patients whose disabilities caused by cardiovascular diseases result in difficulty driving an automobile. Patients often seek their physician's advice as to whether they can continue to drive safely. A MEDLINE literature search was performed from 1966 to 2000, using the query terms "automobile driving" and "automobile driving and cardiac." Selected articles were reviewed, as well as additional articles found through review of the references. In some cases articles were found by searching the Internet using the above key words and new query terms guided by the results of the original search. The most important factor determining eligibility is whether the patient reports manifestations of cerebral hypoxia. Laboratory procedures are available for patients in whom the decision is difficult. Sometimes a referral to a specialist is needed. Many patients with a known cardiovascular disorder can continue to drive safely. Some conditions require a waiting period before driving can be resumed, while others call for a complete cessation of driving. Several guidelines from the literature are listed that can be helpful to primary care physicians when dealing with questions from their patients on this important topic.


The potassium current activated by 2-nicotinamidoethyl nitrate (nicorandil) in single ventricular cells of guinea pigs.
Membrane currents through potassium channels activated by nicorandil, which has a potent coronary vasodilating action, have been studied in ventricular cells of guinea pigs by using the single pipette whole-cell clamp technique. In the presence of 0.1 mM nicorandil, the duration of the action potential was shortened from 196 to 145 ms. Nicorandil markedly increased outward currents at potentials positive to the resting potential. When the difference in the currents before and after the application of nicorandil were plotted against the membrane potential, the current-voltage relation reversed close to the potassium equilibrium potential. The difference current during depolarizing pulses showed no time-dependent relaxation. These results indicate that the current evoked by nicorandil is carried by K+ ions and has voltage-independent kinetics. Power-density spectra obtained in the presence of nicorandil were fitted well by a single Lorentzian curve with a corner frequency of 4.4 Hz. The amplitude of the single-channel unit current was estimated from the relation between the variance and the mean current, and was 0.27 +/- 0.1 pA (n = 7) at -35 mV. The estimated slope conductance was 4.6 +/- 1.7 pS. Nicorandil did not affect Ca2+ currents. It is concluded that nicorandil activates a small-conductance K+ channel without affecting the Ca2+ channel.


Extrapolation from animals to man: predictions, pitfalls and perspectives.
Comparative drug disposition studies can be useful in extrapolating from animals to man provided that the criteria indicating interspecies similarity in disposition reflect similar exposure to the foreign compound. Interspecies variability, on the other hand, can often be related to physiological or biochemical differences, thereby providing a rationale for the unsuitability or limitations of a species as a model for human metabolism. Retrospective evaluation of the following examples illustrates the relevance of the indicated disposition characteristics to risk and efficacy assessment: (a) oxaprozin (route of excretion, enterohepatic circulation and exposure; plasma concentrations and efficacy prediction); (b) ciramadol (species differences in presystemic elimination and major metabolic pathway); (c) acebutolol (pharmacologically active human metabolite absent in one of the toxicology species); (d) esmolol (duration of pharmacologic effect controlled by species dependent nature of blood esterases). Stereochemical preferences in the disposition of racemic drugs often differ among species. Extrapolations from one species to another cannot be made in this situation. Pharmacokinetic parameters based on measurements of the sum of the isomers are meaningless and potentially misleading. Future improvements can come from: computer assisted predictions of metabolic pathways; increased use of human tissues; and use of animal species physiologically similar to humans, e.g. the miniature swine.


Gender, caponization and exogenous estrogen effects on lipids, bone and blood characteristics in Taiwan country chickens.
This study investigated gender, caponization and exogenous estrogen effects on lipids, bone and blood characteristics in Taiwan country chickens. Thirty male chickens were caponized at 8 weeks (capons); 15 capons were injected with estrogen (5 mg/bird estradiol 3-benzoate) every 2 weeks from 8 to 28 weeks, and 15 sham-operated male (shams) chickens and 15 females were selected for this trial. The results showed that the shams had lower relative abdominal and chest subcutaneous fat than females (P < 0.05). The estrogen-treated capons had greater relative abdominal and chest subcutaneous fat than shams and capons (P < 0.05), which might result from higher blood very low-density lipoproteins and triacylglycerol concentrations (P < 0.05). Caponization could dramatically increase relative abdominal fat (506%; P < 0.05). The shams had higher tibia weight and biomechanical properties, such as maximum bone strength and bending moment values than the capons (P < 0.05). Tibia biomechanical properties were reduced by estrogen treatment (P < 0.05). The females obtained the lowest biomechanical value in all treatments (P < 0.05). Histological examination revealed cavity formation in the cortical bone of estrogen-treated capons and female chickens, which suggested that estrogen reduced bone biomechanical properties by destroying its structural integrity.


Aromatherapy with citrus aurantium oil and anxiety during the first stage of labor.
Anxiety is the most common psychological response of women to labor. Aromatherapy, i.e. the use of fragrant essential oils to stimulate the olfactory system, can create a state of calmness and help to alleviate anxiety. The present study tried to determine the efficacy of aromatherapy with Citrus aurantium oil in reducing anxiety during the first stage of labor. This randomized clinical trial was conducted on two groups of pregnant women, referred to Vali-Asr Hospital (Tuyserkan, Iran) between June and September 2013. The sample size was comprised of 63 subjects in each group. Gauzes impregnated with 4 mL of C. aurantium distillate and normal saline were attached to the collar of subjects in the aromatherapy and control groups, respectively. The gauzes were changed every 30 minutes. The levels of anxiety in both groups were measured at baseline and after the intervention at dilations of 3-4 and 6-8 cm. The participants were followed up until delivery and the first- and fifth-minute Apgar scores were recorded. Data were collected using a demographic and obstetric characteristics questionnaire, an examination and observation checklist, and Spielberger state-trait anxiety questionnaire. Data analysis was performed with independent-t, Mann-Whitney, and chi-square tests in SPSS-22. P values less than 0.05 were considered significant. Before the intervention, both groups had same levels of anxiety. However, the levels of anxiety at dilations of 3-4 and 6-8 cm were significantly lower in the aromatherapy group compared with the control group. The results of this study confirmed aromatherapy with C. aurantium blossom oil as a simple, inexpensive, noninvasive, and effective intervention to reduce anxiety during labor.


Novel molecular method for identification of Streptococcus pneumoniae applicable to clinical microbiology and 16S rRNA sequence-based microbiome studies.
The close phylogenetic relationship of the important pathogen Streptococcus pneumoniae and several species of commensal streptococci, particularly Streptococcus mitis and Streptococcus pseudopneumoniae, and the recently demonstrated sharing of genes and phenotypic traits previously considered specific for S. pneumoniae hamper the exact identification of S. pneumoniae. Based on sequence analysis of 16S rRNA genes of a collection of 634 streptococcal strains, identified by multilocus sequence analysis, we detected a cytosine at position 203 present in all 440 strains of S. pneumoniae but replaced by an adenosine residue in all strains representing other species of mitis group streptococci. The S. pneumoniae-specific sequence signature could be demonstrated by sequence analysis or indirectly by restriction endonuclease digestion of a PCR amplicon covering the site. The S. pneumoniae-specific signature offers an inexpensive means for validation of the identity of clinical isolates and should be used as an integrated marker in the annotation procedure employed in 16S rRNA-based molecular studies of complex human microbiotas. This may avoid frequent misidentifications such as those we demonstrate to have occurred in previous reports and in reference sequence databases.


Transcriptional and posttranscriptional silencing of rodent alpha1(I) collagen by a homologous transcriptionally self-silenced transgene.
Transient transfection of rodent fibroblasts with plasmids carrying a full-size pro-alpha1(I) collagen gene (pWTC1) results in rapid reduction of the endogenous transcripts by >90%, while the transgene mRNA is undetectable. Using deletion constructs, two adjacent 5' noncoding regions of the gene are identified as causing transcriptional silencing of the endogene in normal and v-fos-transformed cells but not in nontumorigenic revertants, which show partial relief from v-fos transformation-induced alpha1(I) gene suppression. The 3' end of the transgene carries an additional element(s), causing posttranscriptional silencing of the endogene in all cells including the revertant. Data indicate that the transgenes are transcriptionally self-silenced. Genome-integrated transgenes that are transcriptionally active also allow expression of the endogene, suggesting gene activation by chromosomal factors missing in pWTC1. Silencing is not regulated by antisense RNA. Silencing of the endogenous pro-alpha1(I) collagen gene is not linked to the level of transgene expression.


Sensitization of the Tritonia escape swim.
When repeatedly elicited, the oscillatory escape swim of the marine mollusc Tritonia diomedea undergoes habituation of the number of cycles per swim. Previous work has shown that this habituation is accompanied by sensitization of another feature of the behavior: latency to swim onset. Here we focused on the behavioral features of sensitization itself. Test swims elicited 5 min after a strong sensitizing head stimulus differed in several ways from control swims: sensitized animals had shorter latencies for gill and rhinophore withdrawal, a shorter latency for swim onset, a lower threshold for swim initiation, and an increased number of cycles per swim. Sensitized animals did not, however, swim any faster (no change in cycle period). A separate experiment found that swim onset latency also sensitized when Tritonia came into contact with one of their natural predators, the seastar Pycnopodia helianthoides, demonstrating the ecological relevance of this form of nonassociative learning. These results define the set of behavioral changes to be explained by cellular studies of sensitization in Tritonia.


Is healthy behavior contagious: associations of social norms with physical activity and healthy eating.
Social norms are theoretically hypothesized to influence health-related behaviors such as physical activity and eating behaviors. However, empirical evidence relating social norms to these behaviors, independently of other more commonly-investigated social constructs such as social support, is scarce and findings equivocal, perhaps due to limitations in the ways in which social norms have been conceptualized and assessed. This study investigated associations between clearly-defined social norms and a range of physical activity and eating behaviors amongst women, adjusting for the effects of social support. Self-report survey data about particular physical activity (leisure-time moderate-vigorous activity; volitional walking; cycling for transport) and eating behaviors (fast food, soft drink and fruit and vegetable consumption), and social norms and support for these, were provided by 3,610 women aged 18-46 years living in socioeconomically disadvantaged neighborhoods in Victoria, Australia. Results of regression analyses showed that social norms for physical activity and eating behaviors predicted these respective behaviors relatively consistently; these associations generally remained significant after adjustment for social support. Acknowledging the cross-sectional study design, these data confirm theoretical accounts of the importance of social norms for physical activity and eating behaviors, and suggest that this is independent from social support. Intervention strategies aimed at promoting physical activity and healthy eating could incorporate strategies aimed at modifying social norms relating to these behaviors.


Identifying specific matrix metalloproteinase-2-inhibiting peptides through phage display-based subtractive screening.
Gelatinases A and B, which are members of the matrix metalloproteinase (MMP) family, play essential roles in cancer development and metastasis, as they can break down basal membranes. Therefore, the determination and inhibition of gelatinases is essential for cancer treatment. Peptides that can specifically block each gelatinase may, therefore, be useful for cancer treatment. In this study, subtractive panning was carried out using a 12-mer peptide library to identify peptides that block gelatinase A activity (MMP-2), which is a key pharmacological target. Using this method, 17 unique peptide sequences were determined. MMP-2 inhibition by these peptides was evaluated through zymogram analyses, which revealed that four peptides inhibited MMP-2 activity by at least 65%. These four peptides were synthesized and used for in vitro wound healing using human umbilical vein endothelial cells, and two peptides, AOMP12 and AOMP29, were found to inhibit wound healing by 40%. These peptides are, thus, potential candidates for MMP-2 inhibition for cancer treatment. Furthermore, our findings suggest that our substractive biopanning screening method is a suitable strategy for identifying peptides that selectively inhibit MMP-2.


FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women.
A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by FokI restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican-American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic (n = 164), osteopenic (n = 117), and normal (n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between FokI polymorphism and lumbar BMD (p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD (p = 0.5, ANCOVA). Interestingly, the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause (p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed (p = 0.04, Chi-square test). Finally, ff genotype resulted significantly over-represented in the group of women with a vertebral fracture as compared with controls (p = 0.003, Chi-square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36-4.91). We conclude that in this population, FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.


Catechol estrogen conjugates and DNA adducts in the kidney of male Syrian golden hamsters treated with 4-hydroxyestradiol: potential biomarkers for estrogen-initiated cancer.
Formation of depurinating adducts by reaction of catechol estrogen-3,4-quinones with DNA was proposed to be a tumor initiating event by estrogens [E.L. Cavalieri et al. (1997) Proc. Natl Acad. Sci. USA, 94, 10937-10942]. Under estrogenic imbalance, oxidation of catechol estrogens to quinones may compete with their detoxification by protective enzymes. The quinones formed can be detoxified by reaction with glutathione (GSH) or can covalently bind to DNA. To provide more support for this hypothesis, we developed a method to identify and quantify GSH, cysteine (Cys) and N-acetylCys conjugates of 4-hydroxyestrogens (4-OHE) in the kidneys of male Syrian hamsters treated with 4-hydroxyestradiol (4-OHE2) by intraperitoneal injection. The highest level of conjugates was observed 1 h after treatment, and almost none was detected after 24 h. Dose-response studies indicated conjugate formation after treatment with 0.5 micromol of 4-OHE2/100 g body weight, and formation increased up to a treatment level of 12 micromol/100 g body weight. GSH, Cys and N-acetylCys conjugates of 4-OHE were identified in the picomole range by high-performance liquid chromatography (HPLC) with multichannel electrochemical detection and confirmed by HPLC/tandem mass spectrometry. Treatment of tissue homogenates with beta-glucuronidase/sulfatase at 37 degrees C for 6 h before extraction resulted in a 12- to 20-fold increase in Cys conjugates from picomole to nanomole levels. Similar enhancement was observed by just incubating the tissue at 37 degrees C for 6 h. Evidence for the 4-OHE-1-N7Gua depurinating adducts was obtained by mass spectrometry. We conclude that GSH and Cys conjugates of the 4-OHE and the 4-OHE-N7Gua adducts can be utilized as biomarkers to detect estrogenic imbalance and potential susceptibility to tumor initiation.


MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth Schistosoma mansoni.
Schistosomes are parasitic helminths that cause schistosomiasis, a disease affecting circa 200 million people, primarily in underprivileged regions of the world. Schistosoma mansoni is the most experimentally tractable schistosome species due to its ease of propagation in the laboratory and the high quality of its genome assembly and annotation. Although there is growing interest in microRNAs (miRNAs) in trematodes, little is known about the role these molecules play in the context of developmental processes. We use the completely unaware "miRNA-blind" bioinformatics tool Sylamer to analyse the 3'-UTRs of transcripts differentially expressed between the juvenile and adult stages. We show that the miR-277/4989 family target sequence is the only one significantly enriched in the transition from juvenile to adult worms. Further, we describe a novel miRNA, sma-miR-4989 showing that its proximal genomic location to sma-miR-277 suggests that they form a miRNA cluster, and we propose hairpin folds for both miRNAs compatible with the miRNA pathway. In addition, we found that expression of sma-miR-277/4989 miRNAs are up-regulated in adults while their predicted targets are characterised by significant down-regulation in paired adult worms but remain largely undisturbed in immature "virgin" females. Finally, we show that sma-miR-4989 is expressed in tegumental cells located proximal to the oesophagus gland and also distributed throughout the male worms' body. Our results indicate that sma-miR-277/4989 might play a dominant role in post-transcriptional regulation during development of juvenile worms and suggest an important role in the sexual development of female schistosomes.


Exposure to bullying among students with autism spectrum conditions: a multi-informant analysis of risk and protective factors.
Research has consistently shown that children and young people with autism spectrum conditions are more likely to be bullied than those with other or no special educational needs. The aim of this study was to examine risk and protective factors that could help to explain variation in exposure to bullying within this group. A sample of 722 teachers and 119 parents reported on their child's experience of being bullied. This response variable was regressed onto a range of explanatory variables representing individual and contextual factors. The teacher- and parent-rated regression models were statistically significant, explaining large proportions of variance in exposure to bullying. Behaviour difficulties and increased age were associated with bullying in both models. Positive relationships and attending a special school were associated with a decrease in bullying in the teacher model, with use of public/school transport predicting an increase. In the parent model, special educational needs provision at School Action Plus (as opposed to having a Statement of Special Educational Needs) was a significant risk factor, and higher levels of parental engagement and confidence were associated with reductions in bullying. These findings are discussed in relation to the autism spectrum conditions literature, and opportunities for intervention are considered.


Sexual and in-contact transmission of asinine strain of equine arteritis virus among donkeys.
Two in a group of five naturally seropositive donkey stallions were found to shed equine arteritis virus (EAV) in their semen as demonstrated by virus isolation. Direct intramuscular inoculation of sonicated semen from one virus-shedding stallion (S3) caused clinical disease in two donkeys from which virus was recovered and in which seroconversion was detected. Sexual transmission was confirmed in two mares mated to S3 when after a febrile response during which EAV was isolated from huffy coats and nasal and ocular exudates, both mares were found to have seroconverted. In-contact transmission in a susceptible stallion was demonstrated after its exposure to a sexually infected mare. The 3' end of the asinine virus was amplified directly from donkey semen with EAV-specific primers, and its nucleotide sequence was found to be homologous to that of the prototype Bucyrus virus isolated from horses. These results indicate that EAV and its disease transmission are analogous in donkeys and horses.


Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States.
No US national data are available on the prevalence and correlates of DSM-5-defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5. To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV. In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017. Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders. Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality. Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.


Use of urine polymerase chain reaction to define the prevalence and clinical presentation of Trichomonas vaginalis in men attending an STD clinic.
To determine the prevalence and clinical features of Trichomonas vaginalis (TV) infection in men. Men attending a public STD clinic in Baltimore, Maryland, were evaluated between March and July 2000. Clinicians recorded a standardised history and clinical examination. Urethral swab specimens were collected for Gram stain and Neisseria gonorrhoeae culture. First fraction urine samples were evaluated with TV culture and chlamydia and TV polymerase chain reaction (PCR). True positive TV was defined as a positive TV culture or a positive TV PCR confirmed with a second primer set. 355 men were evaluated in 363 visits. The prevalence of gonorrhoea, TV, and chlamydia were 19%, 13%, and 11%, respectively. In men over 28 years, the prevalence of TV was significantly higher than chlamydia. Age and urethritis by Gram stain were associated with a positive result on TV culture (p=0.03 and p=0.02, respectively) but not associated with TV infection as defined by a positive TV culture or a confirmed TV PCR. Discharge or dysuria was reported in 47% and 22% of men with TV, respectively. TV prevalence in an urban STD clinic setting was high. Older age and urethritis were not significantly associated with TV infection as defined by a positive TV culture or a confirmed TV PCR.


Is arthroscopic surgery beneficial in treating non-traumatic, degenerative medial meniscal tears? A five year follow-up.
The aim of this prospective randomized intervention study was to evaluate the outcome at a 2 and 5 year follow-up whether combined arthroscopic surgery followed by exercise therapy was superior to the same exercise therapy alone when treating non-traumatic, degenerative medial meniscal tears. Ninety-six middle-aged patients with MRI-verified degenerative medial meniscus tear and radiographic osteoarthritis grade ≤1 (Ahlbäck) participated in the study. Radiographic examination was done before randomization and after 5 years. The patients were randomly assigned to either arthroscopic treatment followed by exercise therapy for 2 months or to the same exercise therapy alone. At the start of the study and at the follow-ups at 24 and 60 months the patients answered three questionnaires KOOS, Lysholm Knee Scoring Scale and Tegner Activity Scale and made pain ratings on the Visual Analogue Scale (VAS). Both groups showed highly significant clinical improvements from baseline to the follow-ups at 24 and 60 months on all subscales of KOOS, Lysholm Knee Scoring Scale and VAS (p < 0.0001). No group differences were found at any of the testing occasions. One third of the patients that were treated with exercise therapy alone did not feel better after the treatment but were improved after arthroscopic surgery. According to radiographic findings two patients from each group had a slight progression of their osteoarthritis after 5 years. The findings indicate that arthroscopic surgery followed by exercise therapy was not superior to the same exercise therapy alone for this type of patients. Consequently, exercise therapy can be recommended as initial treatment. However, one third of the patients from the exercise group still had disabling knee symptoms after exercise therapy but improved to the same level as the rest of the patients after arthroscopic surgery with partial meniscectomy. I.


Role of steric repulsions on the precipitation kinetics and the structure of calcium-silicate-hydrate gels.
The microstructure and properties of calcium-silicate-hydrate (C-S-H) gels are largely controlled by the physicochemical environment during their precipitation. However, the role of the steric repulsive environment induced by the pore solution chemistry on the kinetics, structure, and properties of C-S-H gels remains unclear. Here, we develop two potential formalisms, namely sinusoidal and polynomial, to simulate the role of steric repulsions in C-S-H. The results show excellent agreement with experimental observations of precipitation kinetics and elastic properties. We demonstrate that the repulsive interactions result in delayed precipitation and percolation, and an open and branched microstructure. Interestingly, the elastic properties (which are equilibrium properties) are also significantly affected by these second-neighbor interactions. Overall, the present study demonstrates that the kinetics, structure, and equilibrium properties of colloidal gels are controlled by the steric repulsions induced by the chemical environment.


Neuroendocrine tumor in the liver of a patient with isolated polycystic liver disease: A case report and review of the literature.
Neuroendocrine tumors (NETs) frequently metastasize to the liver, but it is rare to find them there as primary tumors. Isolated polycystic liver disease (PCLD) is a rare autosomal dominant disease. There is no known association between polycystic liver disease and neuroendocrine or other tumors. We report a case of a 64-year-old female with a past medical history of isolated PCLD who presented with increasing abdominal pain over a two-week period. Our patient underwent open surgical biopsy one month after presentation. The histological examination and immunohistochemical findings suggested an intermediate grade neuroendocrine tumor. A 24-h delayed whole-body scintigraphy technique was utilized for the identification and localization of neuroendocrine tumors via the administration of In-111-labeled OctreoScan; however, no extrahepatic accumulation was observed. No previous studies in the literature describe a patient with PCLD and a primary or metastatic neuroendocrine tumor of the liver.


Testing for autonomic neuropathy: heart rate changes after orthostatic manoeuvres and static muscle contractions.
1. The initial heart rate (HR) response evoked by standing, 70 degrees head-up tilt, handgrip and contraction of abdominal and leg muscles was analysed in diabetic patients with autonomic neuropathy and in matched controls. 2. In healthy subjects standing induced an immediate, large, HR increase lasting 20s that far exceeded the small HR rise induced by tilt. The HR response with handgrip and to contraction of abdominal and leg muscles was strikingly similar for the first 5 s to the HR increase after standing. 3. In diabetic patients handgrip and standing induced a small HR increase starting after 2-3 s. Contraction of abdominal and leg muscles evoked little or no HR changes. The HR rise after tilt up was delayed by 10 s compared with healthy controls. 4. It is concluded that the circulatory response to active and passive changes of posture differs fundamentally. Standing and handgrip are superior to head-up tilt as a test for vagal HR control. An abrupt and large HR increase after standing excludes cardiac parasympathetic neuropathy. A modified response, however, may be due to afferent as well as to efferent lesions, e.g. in muscle afferents or in vagal afferents from cardiopulmonary receptors.


[The content of selected minerals (Ca, Mg, Zn, Cu, Fe) in daily food rations of adolescents: comparison of analytical and calculated data].
The content of calcium, magnesium, zinc, copper and iron in daily food rations of adolescents served in two residential centres in Copper Basin Legnica region and two high schools in Poznań were studied. The content of minerals was determined by two independent methods: chemical analysis and calculation based upon food composition tables. It was found that the calculated results were markedly higher, suggesting that daily meals covered recommended allowances for minerals established for the adolescents group. However, the analytical results were 10% lower on average, but in the case of zinc and magnesium they did not even reach 50% of norms showing that the daily food did not provide sufficient amounts of minerals for adolescents. Moreover, analysis of regression showed a significant correlation for the magnesium, iron, zinc and copper content obtained by the two methods which allowed to calculate empirical formulae that may help to establish the content of these elements in daily food with the use of the FOOD computer program.


Importance of subtype in the immune response to the pre-S(2) region of the hepatitis B surface antigen. I. T cell fine specificity.
Previous studies of murine T cell recognition of the pre-S(2) region of the hepatitis B surface Ag (HBsAg) identified high (H-2b,d,q), intermediate (H-2s,k), and low to nonresponder (H-2f) haplotypes. However, these studies utilized the y subtype of HBsAg. The purpose of this study was to examine the influence of viral subtype on T cell recognition of the pre-S(2) region and to identify specific T cell recognition sites in a panel of H-2 congenic strains. Immunization with pre-S(2) containing HBsAg particles of the d and y subtypes indicated that T cell recognition of the pre-S(2) region is predominantly subtype-specific in murine strains of eight different H-2 haplotypes. Furthermore, the B10.M strain (H-2f) classified as a T cell nonresponder to the y subtype of the pre-S(2) region responds efficiently to the d subtype, indicating that pre-S(2) responder status can be subtype-dependent as well as subtype-specific. Studies using a truncated pre-S(2) polypeptide and synthetic peptides illustrated that the C-terminal sequence (p148-174) of the pre-S(2) region is the dominant focus of T cell recognition in multiple murine strains. Specifically, 17 distinct T cell recognition sites were defined within the C-terminal half of the pre-S(2) region. The fine specificity of T cell recognition of the pre-S(2) region was dependent on the H-2 haplotype of the responding strain. T cell recognition of all 17 sites was subtype specific, which is consistent with the fact that the C-terminal sequence is highly polymorphic between the d and y subtypes of the pre-S(2) region. Lastly, it was shown that the ability of synthetic peptides to elicit T cells cross-reactive with the native pre-S(2) region was variable and depended on the nature of the immunizing peptide. The pre-S(2)-containing HBsAg vaccines currently in clinical trials are composed of ra single subtype, either d or y. The results of this study suggest that both subtypes should be incorporated to increase the frequency of T cell responders to the pre-S(2) region, and to insure Th cell memory relevant to infection with hepatitis B virus of either the d or y subtypes.


CM-physician alignment cuts length of stay.
When Sentara Healthcare enacted a pilot project in which a care coordinator was assigned to a hospitalist group and followed patients throughout the hospital stay, the average length of stay for patients in the program dropped by one day. One care coordinator was assigned to two to three hospitalists and had a caseload of 20 to 23 patients with pneumonia, sepsis, or heart failure and other patients determined to be at high risk. Care coordinators meet with hospitalists each morning to review patients likely to be discharged that day, meet again during multidisciplinary rounds, and communicate constantly during the day. Other initiatives include providing box lunches for patients discharged around noon and establishing a team of discharge facilitators in a central location to send referrals to post-acute providers and set up transportation.


TGF-β enhances the cytotoxic activity of Vδ2 T cells.
TGF-β is a pleiotropic cytokine with multiple roles in immunity. Apart from its suppressive activity, TGF-β is a driving cytokine in the differentiation of induced regulatory T cells (iTreg) but also in the polarization of interleukin-9 (IL-9) producing T helper 9 (Th9) T cells. Human Vδ2 expressing γδ T cells exert potent cytotoxicity towards a variety of solid tumor and leukemia/lymphoma target cells and thus are in the focus of current strategies to develop cell-based immunotherapies. Here we report that TGF-β unexpectedly augments the cytotoxic effector activity of short-term expanded Vδ2 T cells when purified γδ T cells are activated with specific pyrophosphate antigens and IL-2 or IL-15 in the presence of TGF-β. TGF-β up-regulates the expression of CD54, CD103, interferon-γ, IL-9 and granzyme B in γδ T cells while CD56 and CD11a/CD18 are down-regulated. Moreover, we show that CD103 (αE/β7 integrin) is recruited to the immunological synapse in γδ T cells. Increased cytotoxic activity of TGF-β-exposed γδ T cells is reduced by anti-CD103 and further diminished upon additional anti-CD11a antibody treatment, pointing to a role of cellular adhesion in the enhanced cytolytic activity. Furthermore, magnetically sorted CD103-positive Vδ2 T cells exhibit superior cytolytic activity. In view of the importance of CD103 for tissue homing of lymphocytes, our results suggest that adoptive transfer of CD103-expressing Vδ2 T cells might favor their homing to solid tumors.


[Study of extracellular antigens by immunodiffusion methods in differentiation of pathogenic burkholderiae].
Isolation and composition comparison of extracellular antigens (ECA) of pathogenic burkholderiae in SDS-PAGE electrophoresis and their use for differentiation of these microorganisms by immunodiffusion methods. 60 Burkholderia pseudomallei strains, 14 B. mallei strains, 5 B. thailandensis strains, 4 B. cepacia strains were studied. ECA was obtained by Liu technique on F-agar covered with cellophane. SDS-PAGE electrophoresis was performed in 10% gel by Laemmli, immunodiffusion reaction (IDR) in 1% agarose gel, IDR with live cultures, immunoelectrophoresis (IEPH) was performed by the standard techniques. Sera was obtained by immunizing rabbits with a mixture of ECA and incomplete Freund adjuvant. ECA spectra of typical strains of the studied burkholderiae strains after the electrophoresis in SDS-PAGE stained by silver have 8 - 9 major fractions. ECA electrophoregrams of B. pseudomallei and B. thailandensis had a high similarity. ECA analysis by IDR with antisera against ECA revealed maximum number of cross-reactive ECA (3) between B. pseudomallei B. thailandensis. These strains had only a single crossreactive ECA to B. mallei strain. IDR with live culture and antisera to B. thailandensis ECA revealed ECA in all the B. pseudomallei, B. thailandensis strains and did not reveal those in B. mallei strains. Analysis of electrophoregram obtained with IEPH method of pathogenic burkholderiae ECA with antisera to ECA revealed differences of the composition sufficient for their differentiation. The differences of ECA composition revealed by immunodiffusion methods allowed to develop additional approaches of differentiation ofglanders and melioidosis pathogenic agents.


Amino acid composition of some calcified proteins.
Amino-acid analysis shows that the proteins from two calcified tissues, enamel and snail shell, are related to collagen in that they also contain hydroxylysine . The presence of hydroxyproline is suggested but not confirmed. This evidence, together with other recent findings, suggests that hydroxylysine may have an important role in the calcification of each of these otherwise diverse proteins.


Cardiac growth and angiogenesis coordinated by intertissue interactions.
Cardiac hypertrophy and angiogenesis are coordinately regulated during physiological or adaptive cardiac growth, and disruption of the balanced growth and angiogenesis leads to contractile dysfunction and heart failure. Coordination of growth and angiogenesis is in part mediated by the secretion of angiogenic growth factors from myocytes in response to hypertrophic stimuli, which enables the vasculature to "catch up" to the growth of the myocardium. In this issue of the JCI, two studies provide novel insights into the regulatory mechanisms of cardiac growth and coronary angiogenesis. Heineke et al. demonstrate that GATA4 acts as a stress-responsive transcription factor in murine cardiac myocytes that induces the expression of angiogenic growth factors (see the related article beginning on page 3198). Tirziu et al. show that enhanced coronary angiogenesis per se leads to hypertrophic growth of myocytes through a nitric oxide-dependent mechanism (see the related article beginning on page 3188). These studies, together with previous reports, suggest the existence of reciprocal signals between the myocardium and the vasculature that promote the growth of each other in a paracrine fashion.


Methylene blue and vasoplegia: who, when, and how?
Systemic inflammatory response can be associated with clinically significant and, at times, refractory hypotension. Despite the lack of uniform definitions, this condition is frequently called vasoplegia or vasoplegic syndrome (VS), and is thought to be due to dysregulation of endothelial homeostasis and subsequent endothelial dysfunction secondary to direct and indirect effects of multiple inflammatory mediators. Vasoplegia has been observed in all age groups and in various clinical settings, such as anaphylaxis (including protamine reaction), sepsis, hemorrhagic shock, hemodialysis, and cardiac surgery. Among mechanisms thought to be contributory to VS, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role. In search of effective treatment for vasoplegia, methylene blue (MB), an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC), has been found to improve the refractory hypotension associated with endothelial dysfunction of VS. There is evidence that MB may indeed be effective in improving systemic hemodynamics in the setting of vasoplegia, with reportedly few side effects. This review describes the current state of clinical and experimental knowledge relating to MB use in the setting of VS, highlighting the potential risks and benefits of therapeutic MB administration in refractory hypotensive states.


Density-dependent signaling: An alternative hypothesis on the function of chemical signaling in a non-territorial solitary carnivore.
Brown bears are known to use rubbing behavior as a means of chemical communication, but the function of this signaling is unclear. One hypothesis that has gained support is that male bears rub to communicate dominance to other males. We tested the communication of dominance hypothesis in a low-density brown bear population in southeast British Columbia. We contrasted rubbing rates for male and female bears during and after the breeding season using ten years of DNA-mark-recapture data for 643 individuals. Here we demonstrate that male brown bears rub 60% more during the breeding than the non-breeding season, while female rubbing had no seasonal trends. Per capita rub rates by males were, on average, 2.7 times higher than females. Our results suggest that the function of rubbing in the Rocky Mountains may not only be to communicate dominance, but also to self-advertise for mate attraction. We propose that the role of chemical communication in this species may be density-dependent, where the need to self-advertise for mating is inversely related to population density and communicating for dominance increases with population density. We suggest that future endeavors to elucidate the function of rubbing should sample the behavior across a range of population densities using camera trap and genotypic data.


Pregnant and imprisoned in the United States.
This article is excerpted from a report by Amnesty International, entitled "Not Part of My Sentence": Violations of the Human Rights of Women in Custody, March 1999. The article describes violations of the human rights of pregnant women and mothers who are incarcerated in prisons and jails in the United States. Many of the practices employed are not in compliance with international standards and are also prohibited by federal and state laws in the United States. In 1997-1998, more than 2200 pregnant women were imprisoned and more than 1300 babies were born in prisons. In at least 40 states, babies are taken from their imprisoned mothers almost immediately after birth or at discharge from the hospital. International standards restrict the use of restraints to limited situations. Restraints are used as a matter of course in the United States, including on women in labor or immediately after birth, who may be taken to a hospital in handcuffs and chained by a leg to the bed. Amnesty International calls for governments and authorities to take urgent action that will ensure that the laws, regulations, policies, and practices for which they are responsible rigorously conform to international standards and respect the human rights of women deprived of their liberty.


Preferences for life-sustaining treatments in advance care planning and surrogate decision making.
Surrogates and clinicians often make treatment decisions for decisionally incapacitated patients with limited knowledge of their preferences. This study examined patients' life-sustaining treatment preferences to facilitate advance care planning discussions and surrogate decision making. We interviewed 342 participants from 7 groups: younger and older well adults; persons with chronic illness, terminal cancer, and acquired immunodeficiency syndrome (AIDS); stroke survivors; and nursing home residents. Preferences for antibiotics, short- and long-term mechanical ventilation, hemodialysis, tube feeding, and cardiopulmonary resuscitation (CPR) were elicited for each participant's current health state and three hypothetical health states representing severe dementia, coma, and severe stroke. Participants chose to forego more invasive or long-term treatments at a higher rate than less invasive, short-term treatments in all health states. Participants were much more willing to forego treatments in coma than in their current health state, with stroke and dementia somewhere in between. Participants who were older, female, had worse functional status, had more depressive symptoms, or lived in a nursing home were more inclined to forego treatment in their current health state. In contrast, treatment preferences in hypothetical health states showed either no associations or much weaker associations with these factors. Participants who were willing to accept more invasive treatments were highly likely to accept less invasive treatments and participants who preferred to forego a less invasive treatment were highly likely to forego more invasive treatments. Participants who preferred to receive a treatment in a health state with severe impairments were highly likely to want the same treatment in a less impaired health state. Similarly, participants who preferred to forego a treatment in a less impaired health state were highly likely to forego the same treatment in a more impaired state. In advance care planning discussions, clinicians might explore with patients their preferences about short- and long-term treatments with variability in their invasiveness (including CPR) in both their current health state and hypothetical situations representing different levels of functional impairment. When surrogates have no knowledge about the wishes of formerly competent patients, clinicians may help them with medical decisions by discussing what other people commonly want in similar circumstances.


Low-intensity shock wave therapy and its application to erectile dysfunction.
Although phosphodiesterase type 5 inhibitors (PDE5Is) are a revolution in the treatment of erectile dysfunction (ED) and have been marketed since 1998, they cannot restore pathological changes in the penis. Low-energy shock wave therapy (LESWT) has been developed for treating ED, and clinical studies have shown that LESWT has the potential to affect PDE5I non-responders with ED with few adverse effects. Animal studies have shown that LESWT significantly improves penile hemodynamics and restores pathological changes in the penis of diabetic ED animal models. Although the mechanisms remain to be investigated, recent studies have reported that LESWT could partially restore corpus cavernosum fibromuscular pathological changes, endothelial dysfunction, and peripheral neuropathy. LESWT could be a novel modality for treating ED, and particularly PDE5I non-responders with organic ED, in the near future. However, further extensive evidence-based basic and clinical studies are needed. This review intends to summarize the scientific background underlying the effect of LESWT on ED.


Effects of leukotriene D4 on the mechanical and electrical properties of guinea-pig isolated trachealis.
1. The effects of leukotriene D4 (LTD4) on mechanical and electrical activity were examined in guinea-pig isolated trachealis muscle and compared with two other bronchoconstrictors, methacholine and potassium chloride (KCl). 2. LTD4 elicited concentration-dependent increases in tension in trachealis muscle which were slower in time course than responses induced by either methacholine or KCl. The maximum response to LTD4 was approximately 85% of the methacholine maximum. 3. At a concentration close to the EC50 for tension changes, LTD4 had no significant effect on either transmembrane potential or slow wave activity recorded in single trachealis cells. 4. At a concentration close to the EC90 for tension changes, LTD4 caused significant membrane depolarization, transiently reduced the amplitude and increased the frequency of slow wave discharge and ultimately abolished slow wave discharge. LTD4-induced depolarization was less marked, and developed more slowly, than that evoked by either methacholine or KCl. 5. These results show that LTD4 can elicit substantial increases in tension without altering transmembrane potential and are consistent with the view that LTD4 initiates contraction mainly through potential-independent mechanisms. However, at high concentrations the depolarization evoked by LTD4 allows the possibility that potential-dependent mechanisms may contribute to the spasm.


Asymmetric redirection of flow through the heart.
Through cardiac looping during embryonic development, paths of flow through the mature heart have direction changes and asymmetries whose topology and functional significance remain relatively unexplored. Here we show, using magnetic resonance velocity mapping, the asymmetric redirection of streaming blood in atrial and ventricular cavities of the adult human heart, with sinuous, chirally asymmetric paths of flow through the whole. On the basis of mapped flow fields and drawings that illustrate spatial relations between flow paths, we propose that asymmetries and curvatures of the looped heart have potential fluidic and dynamic advantages. Patterns of atrial filling seem to be asymmetric in a manner that allows the momentum of inflowing streams to be redirected towards atrio-ventricular valves, and the change in direction at ventricular level is such that recoil away from ejected blood is in a direction that can enhance rather than inhibit ventriculo-atrial coupling. Chiral asymmetry might help to minimize dissipative interaction between entering, recirculating and outflowing streams. These factors might combine to allow a reciprocating, sling-like, 'morphodynamic' mode of action to come into effect when heart rate and output increase during exercise.


Diagnosing cervicogenic headache.
The notion that disorders of the cervical spine can cause headache is more than a century old, yet there is still a great deal of debate about cervicogenic headache (CEH) in terms of its underlying mechanisms, its signs and symptoms, and the most appropriate treatments for it. CEH is typically a unilateral headache that can be provoked by neck movement, awkward head positions or pressure on tender points in the neck. The headaches can last hours or days, and the pain is usually described as either dull or piercing. Convergence of the upper cervical roots on the nucleus caudalis of the trigeminal tract is the most commonly accepted neurophysiological explanation for CEH. In most cases, CEH is caused by pathology in the upper aspect of the cervical spine, but the type and exact location of the pathology varies substantially among individual cases. Anaesthetic blocks may be necessary to confirm the diagnosis of CEH, showing that the source of pain is in the neck. Differential diagnosis is sometimes a challenge because CEH can be mistaken for other forms of unilateral headache, especially unilateral migraine without aura. Neuroimaging and kinematic analysis of neck motion may aid in diagnosing difficult CEH.


Working during pregnancy: effects on the fetus.
In order to determine whether pregnancy outcome was altered when women were employed outside their homes, 7,722 pregnancies were analyzed. Gestations were not shortened but newborns of women who worked in the third trimester weighed 150 to 400 gm less than newborns of mothers who remained at home. The growth retardation was greatest when women were underweight pregravid and had a low pregnancy weight gain, when they were hypertensive, or when the work required standing. The growth retardation remained after the data were stratified by race, socioeconomic status, and other maternal factors that commonly influence fetal growth. The frequency of large placental infarcts progressively increased when women continued stand-up work into late gestation. Such infarcts reached a peak of 250/1,000 births after the 37th week of gestation in stand-up workers. Low uteroplacental blood flow is a likely explanation for both the fetal growth retardation and the large placental infarcts.


Toxic equine parkinsonism: an immunohistochemical study of 10 horses with nigropallidal encephalomalacia.
Chronic ingestion of yellow star thistle (Centaurea solstitialis) or Russian knapweed (Acroptilon repens) causes nigropallidal encephalomalacia (NPE) in horses with an abrupt onset of neurologic signs characterized by dystonia of lips and tongue, inability to prehend food, depression, and locomotor deficits. The objectives of this study were to reexamine the pathologic alterations of NPE and to conduct an immunohistochemistry study using antibodies to tyrosine hydroxylase and α-synuclein, to determine whether NPE brains show histopathologic features resembling those in human Parkinson disease. Results confirm that the NPE lesions are located within the substantia nigra pars reticulata, sparing the cell bodies of the dopaminergic neurons in the substantia nigra pars compacta, and in the rostral portion of the globus pallidus, with partial disruption of dopaminergic (tyrosine hydroxylase-positive) fibers passing through the globus pallidus. No abnormal cytoplasmic inclusions like the Lewy bodies of human Parkinson disease were seen in these NPE brains. These findings indicate that equine NPE may serve as a large animal model of environmentally acquired toxic parkinsonism, with clinical phenotype directly attributable to lesions in globus pallidus and substantia nigra pars reticulata rather than to the destruction of dopaminergic neurons.


Improvement in lipid profiles over 6 years of follow-up in adults with AIDS and immune reconstitution.
The aim of the study was to evaluate long-term changes in lipids and to assess other coronary heart disease (CHD) risk factors in highly experienced AIDS patients with immune reconstitution, and to examine their association with antiretroviral therapy (ART). We evaluated 433 AIDS patients with prior severe immunosuppression and ART-based immune reconstitution, followed in a multicentre prospective observational study between 2000 and 2006. We estimated the prevalence at entry of hypercholesterolaemia and metabolic syndrome, and 10-year CHD risks. Trends in total cholesterol (TC), triglycerides (TG) and high-density lipoprotein (HDL) cholesterol were evaluated over time, and use of specific ART drugs at each study visit was assessed using mixed effect models, adjusting for CHD risk factors and use of lipid-lowering agents. At entry to observational follow-up, 28% of the 433 subjects had hypercholesterolaemia and 15% had a predicted 10-year CHD risk above 20%. Average TC and fasting TG levels declined over the follow-up period (median=5.8 years), and these declines were associated with increased use of physician-prescribed lipid-lowering agents and changes in ART regimens. After adjustment for CHD risk factors, TC and TG levels were significantly higher for those on ritonavir-boosted protease inhibitors and those on nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly efavirenz, than for other patients. Abnormalities in serum lipids were common at baseline but became less so over time, and this improvement was associated with increased use of lipid-lowering agents and selection of ART agents with less deleterious effects on lipids.


Effects of alfalfa hay inclusion rate on productivity of lactating dairy cattle fed wet corn gluten feed-based diets.
An experiment was conducted to evaluate the effects of varying the alfalfa inclusion rate in diets containing 31% (dry matter basis) wet corn gluten feed (Sweet Bran, Cargill Inc.). Eighty primiparous and multiparous Holstein cows averaging 178 +/- 90 d in milk (mean +/- SD) were randomly assigned to 1 of 4 sequences in a 4 x 4 Latin square design with 28-d periods. Treatments were diets containing 0, 7, 14, or 21% alfalfa on a dry matter basis, with corn silage, corn grain, soybean meal, expeller soybean meal, and mineral supplements varying across diets to maintain uniform nutrient densities. Diets were formulated for similar crude protein, neutral detergent fiber, and nonfiber carbohydrate concentrations. Feed intake, milk production, body weight, and body condition score were monitored, and linear and quadratic effects of increasing the alfalfa inclusion rate were assessed using mixed model analysis. As the alfalfa inclusion rate increased, dry matter intake tended to increase linearly (26.7, 27.3, 27.4, and 27.5 kg/d for 0, 7, 14, and 21% alfalfa, respectively), and solids-corrected milk (29.9, 30.2, 30.8, and 30.5 kg/d) and energy-corrected milk production (32.9, 33.3, 33.8, and 33.6 kg/d) tended to increase linearly. Body weight gain decreased linearly (22.9, 18.0, 11.2, and 9.5 kg/28 d) with increasing alfalfa inclusion rate. Although increasing the inclusion rate of alfalfa increased the proportion of large particles in the diets, treatments had no effect on milk fat yield or concentration. Feeding more alfalfa (up to 21% of dry matter) tended to increase milk yield while decreasing body weight gain, suggesting that metabolizable energy utilization shifted from body weight gain to milk production in these treatments. However, adding alfalfa to the diet had only minor effects on productivity.


Osteoporosis diagnosis in men: the T-score controversy revisited.
Osteoporosis becomes common with aging in both sexes, but is often ignored in men. The 2013 International Society for Clinical Densitometry consensus conference endorsed a Caucasian female referent database for T-score calculation in men. This recommendation has generated controversy and concern. Accumulating data indicate that at the same DXA-measured body mineral density (BMD) (g/cm(2)), men and women are at approximately the same fracture risk. With this point in mind, using the same database to derive the T-score in men and women is reasonable. As a result, a greater proportion of men who sustain a fragility fracture will have T-scores that are higher than they would if a male database were used; in fact, many men will fracture at T-scores that are "normal." This highlights the importance of diagnosing osteoporosis not just by T-score, but also by the presence of fragility fracture and/or by estimations of fracture risk as generated by tools such as the FRAX calculator. The practical consequences of this change in densitometric definition of osteoporosis in men should be monitored, including the proportion of men at risk identified and treated as well as defining the response to treatment in those assessed by this more comprehensive approach.


Current HDAC Inhibitors in Clinical Trials.
Epigenetic modifications in eukaryotic biological pathways can lead to the up- or downregulation of regulatory proteins contributing to disease onset and progression. In the last three decades, histone deacetylases (HDACs) are among the most studied epigenetic targets. In fact, aberrant HDAC expression is associated with numerous types of cancer and neurodegenerative disorders, making HDACs promising molecular targets for the design of new drugs. Many HDAC inhibitors (HDACi) are currently in clinical evaluation for various types of cancer, and some of them reached the market after approval by the Food and Drug Administration (FDA). The present review summarizes the various HDAC classes and relative isoforms. Then we discuss different class or isoform-selective HDACi with a strong emphasis on late-stage preclinical candidates and drugs in clinical studies. Last but not least, we shed light on the pharmacokinetic challenges and future directions in HDACi design.


Pneumonia in the elderly: empiric antimicrobial therapy.
Pneumonia, the leading cause of death due to infectious disease in the elderly, can be difficult to diagnose in this age group because clinical signs and symptoms are often muted. Without a definitive isolate, the physician must institute empiric therapy with broad-spectrum antibiotics according to the patient's condition and the setting in which the pneumonia developed. The cephalosporins, because of their safety profiles, are often used alone or in combination with other drugs to achieve broad antimicrobial coverage in elderly patients with pneumonia. In general, elderly patients with pneumonia should be hospitalized, although nursing home residents may be managed in the nursing home if adequate staff and resources are available.


Plasticity of galaninergic fibers following neurotoxic damage within the rat basal forebrain: initial observations.
Galanin immunoreactive fibers hypertrophy and hyperinnervate remaining cholinergic basal forebrain neurons within the septum-diagonal band complex in Alzheimer's disease. The present investigation determined whether a similar hyperinnervation of galanin immunoreactive fibers occurs following intraparenchymal injections of ibotenic acid within the cholinergic medial septum or diagonal band nucleus in young adult rats. Sections through the medial septum and the diagonal band were either concurrently immunostained for galanin and the low-affinity p75 neurotrophin receptor (an excellent marker of cholinergic basal forebrain neurons) or single stained for choline acetyltransferase. Following chemical lesion, an increase in the density of galanin immunoreactivity was seen within the medial septum on the lesion, as opposed to the contralateral control side. In contrast, within diagonal band-lesioned animals, the increase in galanin immunoreactivity was low to moderate. In either lesion paradigm we did not observe hyperinnervation of remaining cholinergic basal forebrain neurons. In fact, there was no correlation between the galanin hypertrophy and the amount of cholinergic cell loss. We hypothesize that galanin hyperinnervation within the cholinergic basal forebrain may provide a protective effect by down-regulating acetylcholine release following brain insult.


[Preventive home visits to the elderly: systematic review of available evidence].
The aim of preventive home visits to elderly persons is to reduce mortality, to avoid admissions to nursing homes and hospitals and to improve the functional status and general wellbeing of the elderly. Preventive home visits are rarely a standard service in national health care systems. For over 20 years, controlled randomized studies have been carried out to test their effectiveness. This systematic review evaluates the evidence available on preventive home visits for elderly persons in the context of considerations relating to the incorporation of such a service into the German health care system. Three current systematic reviews (two of them meta-analyses) were identified in a systematic literature survey. They consider a total of 26 studies, most of them RCTs. A further three original controlled studies were identified and evaluated. The original studies were very heterogeneous with respect to goals, target groups, intensity and duration of the home visit programme and with respect to the individuals performing the study (number, profession, qualifications and cooperation). This makes it more difficult to perform a pooled overall evaluation. It was possible to consider mortality, admissions to nursing homes, functional status and psychosocial status as relevant target parameters. The systematic reviews arrive at different assessments of effectiveness. A quantitative, across-studies evaluation demonstrated that preventive home visits to elderly persons were effective both in studies with selected and with unselected inclusion of participants. The second meta-analysis did not confirm this result. Effectiveness here was only demonstrated using stratified analyses which investigated a large number of home visits, the performance of a multidimensional assessment with follow-up visits and the average age and morbidity of participants as relevant influencing factors. However no factor exerted an influence over more than one of the investigated target parameters. The findings thus constitute very unspecific evidence of effectiveness with largely unclear determinants of success. Preventive home visit programmes have been tested in various health systems. Results from controlled (randomised) German studies have not been published to date. The results of studies from other countries have only limited applicability to the conditions in the German health care system because the opportunities for, and extent of, economical and effective improvement in the preventive care of the elderly depend on the standard of care existing in the individual country. The additional value of screening depends on the empirical level of care and not on a given standard. At present the introduction of home visits in Germany cannot be recommended beyond studies. However there appear to be sufficient reasons for controlled studies in Germany which should be carried out in a coordinated way with mutual agreement on concepts.


Long-term region-wide declines in Caribbean corals.
We report a massive region-wide decline of corals across the entire Caribbean basin, with the average hard coral cover on reefs being reduced by 80%, from about 50% to 10% cover, in three decades. Our meta-analysis shows that patterns of change in coral cover are variable across time periods but largely consistent across subregions, suggesting that local causes have operated with some degree of synchrony on a region-wide scale. Although the rate of coral loss has slowed in the past decade compared to the 1980s, significant declines are persisting. The ability of Caribbean coral reefs to cope with future local and global environmental change may be irretrievably compromised.


Environmental emission of multiresistant Escherichia coli carrying the colistin resistance gene mcr-1 from German swine farms.
Pigs have been the focus of the worldwide spread of colistin resistance. However, there is little information on the transmission of mcr-1 -containing bacteria into the environment of pig farms. We therefore rescreened environmental Escherichia coli isolates from the surrounding farm areas of three previously mcr-1 -positive swine herds in Germany. Thirty-five mixed bacterial cultures obtained from boot swabs, flies, dog faeces and manure from three pig farms in Germany in 2011-12 were non-selectively recultivated and the presence of the mcr-1 gene was checked by real-time PCR. After separation, single E. coli colonies were subsequently isolated and the presence of mcr-1 was confirmed by PCR and sequencing. In addition, phenotypic antimicrobial resistance screening and WGS followed by phylogenetic analysis and resistance genotyping as well as plasmid typing were performed. Seven mcr-1 -positive E. coli strains originating from environmental boot swabs, dog faeces, stable flies and manure were found. The isolates belonged to five different STs (ST10, ST1011, ST1140, ST5281 and ST342) and harboured extensive additional resistance genes. Comparative plasmid analysis predominantly located mcr-1 on IncX4 plasmids, which are strongly related to a recently described plasmid of human clinical origin (pICBEC72Hmcr). WGS-based analysis of the environmental E. coli isolates of farm surroundings showed clear links to mcr-1 -harbouring E. coli recovered from pig production in Europe as well as from human clinical isolates worldwide, presenting another piece of the puzzle, which further complicates the rapidly evolving epidemiology of plasmid-mediated colistin-resistant E. coli strains.


ST segment monitoring for coronary artery reocclusion following thrombolytic therapy and coronary angioplasty: identification of optimal bedside monitoring leads.
Bedside ST segment monitors analyze only one precordial lead and one, two or three limb leads. The precordial lead V1 (or V6 if V1 is not feasible) has been recommended for bedside monitoring because of its value in diagnosing cardiac rhythms with a wide QRS complex. Thus, the remaining lead choices for ST monitoring are limited to the six limb leads. To determine which of the limb leads in conjunction with V1 or V6 provides the greatest sensitivity for myocardial ischemia, a study was undertaken. A total of 30 vessel-unique ischemic episodes were analyzed prospectively using continuous 12-lead electrocardiographic recordings in patients with acute myocardial infarction (n = 2) and patients undergoing coronary angioplasty (n = 25). Ischemic changes were evident in all cases using the full 12-lead electrocardiogram. Right coronary artery-related ischemia was detected in all cases using a single-lead III or aVF. In the group as a whole, the best combinations were: V1 + aVF, V1 + III, V6 + III, and V6 + aVF. Two patients developed sudden coronary artery reocclusion in the cardiac care unit after successful angioplasty. In both, leads identified in the cardiac catheterization laboratory as sensitive for recording ischemia were excellent choices for detection of reocclusion in the cardiac care unit. 12-lead electrocardiogram recordings during coronary angioplasty balloon inflation provide excellent guidance for postprocedure lead selection decisions. The most valuable limb leads for detecting ischemia due to abrupt artery closure are leads III and aVF, either of which is more sensitive than the routinely monitored lead II. The precordial leads valuable for arrhythmia monitoring, V1 and V6, are seldom sensitive in detecting ischemia in these patients.


Cation-Driven Increases of CO2 Utilization in a Bipolar Membrane Electrode Assembly for CO2 Electrolysis.
Advancing reaction rates for electrochemical CO2 reduction in membrane electrode assemblies (MEAs) have boosted the promise of the technology while exposing new shortcomings. Among these is the maximum utilization of CO2, which is capped at 50% (CO as targeted product) due to unwanted homogeneous reactions. Using bipolar membranes in an MEA (BPMEA) has the capability of preventing parasitic CO2 losses, but their promise is dampened by poor CO2 activity and selectivity. In this work, we enable a 3-fold increase in the CO2 reduction selectivity of a BPMEA system by promoting alkali cation (K+) concentrations on the catalyst's surface, achieving a CO Faradaic efficiency of 68%. When compared to an anion exchange membrane, the cation-infused bipolar membrane (BPM) system shows a 5-fold reduction in CO2 loss at similar current densities, while breaking the 50% CO2 utilization mark. The work provides a combined cation and BPM strategy for overcoming CO2 utilization issues in CO2 electrolyzers.


Clustering of C-terminal stromal domains of Tha4 homo-oligomers during translocation by the Tat protein transport system.
The chloroplast Twin arginine translocation (Tat) pathway uses three membrane proteins and the proton gradient to transport folded proteins across sealed membranes. Precursor proteins bind to the cpTatC-Hcf106 receptor complex, triggering Tha4 assembly and protein translocation. Tha4 is required only for the translocation step and is thought to be the protein-conducting component. The organization of Tha4 oligomers was examined by substituting pairs of cysteine residues into Tha4 and inducing disulfide cross-links under varying stages of protein translocation. Tha4 formed tetramers via its transmembrane domain in unstimulated membranes and octamers in membranes stimulated by precursor and the proton gradient. Tha4 formed larger oligomers of at least 16 protomers via its carboxy tail, but such C-tail clustering only occurred in stimulated membranes. Mutational studies showed that transmembrane domain directed octamers as well as C-tail clusters require Tha4's transmembrane glutamate residue and its amphipathic helix, both of which are necessary for Tha4 function. A novel double cross-linking strategy demonstrated that both transmembrane domain directed- and C-tail directed oligomerization occur in the translocase. These results support a model in which Tha4 oligomers dock with a precursor-receptor complex and undergo a conformational switch that results in activation for protein transport. This possibly involves accretion of additional Tha4 into a larger transport-active homo-oligomer.


[Pathophysiology of dyspnea].
The sensation of dyspnea is related to pathologically increased breathing work as a result of hyperventilation and/or increased airway resistance. Low cardiac output resulting in tissue hypoxia provokes hyperventilation. In diffuse interstitial lung diseases, hyperventilation is combined with severely reduced lung compliance. In severe airway obstruction, hypoventilation is the result of excessively enhanced breathing work. Habituation and acute changes of situation have an important bearing on the subjective sensation of dyspnea.


Effect of Psychological Intervention on Fear of Cancer Recurrence: A Systematic Review and Meta-Analysis.
Fear of cancer recurrence (FCR) is a significantly distressing problem that affects a substantial number of patients with and survivors of cancer; however, the overall efficacy of available psychological interventions on FCR remains unknown. We therefore evaluated this in the present systematic review and meta-analysis. We searched key electronic databases to identify trials that evaluated the effect of psychological interventions on FCR among patients with and survivors of cancer. Controlled trials were subjected to meta-analysis, and the moderating influence of study characteristics on the effect were examined. Overall quality of evidence was evaluated using the GRADE system. Open trials were narratively reviewed to explore ongoing developments in the field (PROSPERO registration no.: CRD42017076514). A total of 23 controlled trials (21 randomized controlled trials) and nine open trials were included. Small effects (Hedges's g) were found both at postintervention (g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-up (g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those of traditional CBTs (g = 0.24; β = .22; 95% CI, .04 to .41; P = .018). At follow-up, larger effects were associated with shorter time to follow-up (β = -.01; 95% CI, -.01 to -.00; P = .027) and group-based formats (β = .18; 95% CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate strength for effects of psychological intervention for FCR. Psychological interventions for FCR revealed a small but robust effect at postintervention, which was largely maintained at follow-up. Larger postintervention effects were found for contemporary CBTs that were focused on processes of cognition-for example, worry, rumination, and attentional bias-rather than the content, and aimed to change the way in which the individual relates to his or her inner experiences. Future trials could investigate how to further optimize and tailor interventions to individual patients' FCR presentation.


Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype.
Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.454C>T, leading to change of arginine 152 to cysteine (p.R152C), and a novel heterozygous gene deletion c.1318_1320delAAC, leading to the loss of an asparagine residue at codon 440 (p.N440del). Clinical identification of low serum TNAP activity, dental abnormalities, and pedigree data strongly suggests a genotype-phenotype correlation between p.N440del and odonto-HPP in this family. Computational analysis of the p.N440del protein structure revealed an alteration in the tertiary structure affecting the collagen-binding site (loop 422-452), which could potentially impair the mineralization process. Nevertheless, the probands (compound heterozygous: p.[N440del];[R152C]) feature early-onset and severe odonto-HPP phenotype, whereas the father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose to a more severe dental phenotype in combination with the deletion. These results assist in defining the genotype-phenotype associations for odonto-HPP, and further identify the collagen-binding site as a region of potential structural importance for TNAP function in the biomineralization.


The evolving role of health care aides in the long-term care and home and community care sectors in Canada.
Health Care Aides (HCAs) provide up to 80% of the direct care to older Canadians living in long-term care facilities, or in their homes. They are an understudied workforce, and calls for health human resources strategies relating to these workers are, we feel, precipitous. First, we need a better understanding of the nature and scope of their work, and of the factors that shape it. Here, we discuss the evolving role of HCAs and the factors that impact how and where they work. The work of HCAs includes role-required behaviors, an increasing array of delegated acts, and extra-role behaviors like emotional support. Role boundaries, particularly instances where some workers over-invest in care beyond expected levels, are identified as one of the biggest concerns among employers of HCAs in the current cost-containment environment. A number of factors significantly impact what these workers do and where they work, including market-level differences, job mobility, and work structure. In Canada, entry into this 'profession' is increasingly constrained to the Home and Community Care sector, while market-level and work structure differences constrain job mobility to transitions of only the most experienced workers, to the long-term care sector. We note that this is in direct opposition to recent policy initiatives designed to encourage aging at home. Work structure influences what these workers do, and how they work; many HCAs work for three or four different agencies in order to sustain themselves and their families. Expectations with regard to HCA preparation have changed over the past decade in Canada, and training is emerging as a high priority health human resource issue. An increasing emphasis on improving quality of care and measuring performance, and on integrated team-based care delivery, has considerable implications for worker training. New models of care delivery foreshadow a need for management and leadership expertise--these workers have not historically been prepared for leadership roles. We conclude with a brief discussion of the next steps necessary to generating evidence necessary to informing a health human resource strategy relating to the provision of care to older Canadians.


Has the time come for cost-effectiveness analysis in US health care?
Cost-effectiveness analysis (CEA) is a powerful analytic tool for assessing the value of health care interventions but it is a method used sparingly in the US. Despite its growing acceptance internationally and its endorsement in the academic literature, most policy analysts have assumed that US decision makers will resist using CEA to inform coverage decisions. This study sought to clarify the extent to which CEA is understood and accepted by US decision makers, including regulators, private and public insurers, and purchasers, and to identify their points of difficulty with its use. We conducted half-day workshops with a sample of six California-based health care organizations that spanned a range of public and private perspectives regarding coverage of health care services. Each workshop included an overview of CEA methods, a priority-setting exercise that asked participants (acting as 'social decision makers') to rank condition treatment pairs prior to and following provision of cost-effectiveness information; and a facilitated discussion of obstacles and opportunities for using CEA in their own organizations. Pre and post-questionnaires inquired as to obstacles toward implementing CEA, attitudes toward rationing, and views on the use of CEA in Medicare and in private insurance coverage decision-making. In post-workshop surveys major obstacles identified included: fears of litigation, concerns about the quality and accuracy of studies that were commercially sponsored, and failure of CEAs to address shorter horizon cost implications. Over 90% of participants felt that CEA should be used as an input to Medicare coverage decisions and 75% supported its use in such decisions by private insurance plans. Despite the wide acceptance of CEA, at the conclusion of the workshop, 40% of the sample remained uncomfortable with support of 'rationing' per se. We suggest that how cost-effectiveness analysis is framed will have important implications for its acceptability to US decision makers.


Multiple chromosomal and phenotypic changes in spontaneous mutants of Candida albicans.
Previous studies have revealed the occurrence of multiple chromosomal alterations among spontaneous colony form mutants and clinical isolates of Candida albicans. In this report we show that such karyotype alterations are also seen in spontaneous and induced non-germinative mutants of the fungus. To determine if phenotypic changes other than colony form and microscopic morphology accompanied the rearrangements of the electrophoretic karyotype, we studied the following characteristics of the non-germinative and some of the colony form mutants: formation of pseudohyphae, chlamydospore production, germ tube formation, colony morphology, auxotrophy, growth at various temperatures, and colony morphology and pigment formation on selected media (bismuth sulphite and Phloxine B). We established that phenotypic and karyotypic variability among spontaneous, non-germinative mutants was no different than such variability among spontaneous colony form mutants. Thus, non-germination may represent another phenotypic consequence of genomic instability in C. albicans. The variability in different phenotypic attributes that occurred amongst the mutants was not associated with any given karyotype. Moreover, neither the low nor the high phenotypic variabilities observed were explained by the relatively high number of alterations in a limited number of chromosomes.


Accuracy evaluation of five blood glucose monitoring systems obtained from the pharmacy: a European multicenter study with 453 subjects.
This multicenter study was conducted to evaluate the performance of five recently introduced blood glucose (BG) monitoring (BGM) devices under daily routine conditions in comparison with the YSI (Yellow Springs, OH) 2300 Stat Plus glucose analyzer. Five hundred one diabetes patients with experience in self-monitoring of BG were randomized to use three of five different BGM devices (FreeStyle Lite® [Abbott Diabetes Care Inc., Alameda, CA], FreeStyle Freedom Lite [Abbott Diabetes Care], OneTouch® UltraEasy® [LifeScan Inc., Milpitas, CA], Accu-Chek® Aviva [Roche Diagnostics, Mannheim, Germany], and Contour® [Bayer Vital GmbH, Leverkusen, Germany]) in a daily routine setting. All devices and strips were purchased from local regular distribution sources (pharmacies, four strip lots per device). The patients performed the finger prick and the glucose measurement on their own. In parallel, a healthcare professional performed the glucose assessment with the reference method (YSI 2300 Stat Plus). The primary objective was the comparison of the mean absolute relative differences (MARD). Secondary objectives were compliance with the International Organization for Standardization (ISO) accuracy criteria under these routine conditions and Clarke and Parkes Error Grid analyses. MARD ranged from 4.9% (FreeStyle Lite) to 9.7% (OneTouch UltraEasy). The ISO 15197:2003 requirements were fulfilled by the FreeStyle Lite (98.8%), FreeStyle Freedom Lite (97.5%), and Accu-Chek Aviva (97.0%), but not by the Contour (92.4%) and OneTouch UltraEasy (91.1%). The number of values in Zone A of the Clarke Error Grid analysis was highest for the FreeStyle Lite (98.8%) and lowest for the OneTouch Ultra Easy (90.4%). FreeStyle Lite, FreeStyle Freedom Lite, and Accu-Chek Aviva performed very well in this study with devices and strips purchased through regular distribution channels, with the FreeStyle Lite achieving the lowest MARD in this investigation.


Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.
The differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology. To identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early stages, the gene expression profiles with temporal series were downloaded to reveal the distinct fates when BMSCs adopt a committed lineage. For both OS and AD lineages, the profiles of days 2-4 were compared with day 0 to screen the differentially expressed genes (DEGs), respectively. Next, the functional enrichment analysis was utilized to find out the biological function, and protein-protein interaction network to predict the central genes. Finally, experiments were performed to verify our finding. FoxO signaling pathway with central genes like FoxO3, IL6, and CAT is the crucial mechanism of OS, while Rap1 signaling pathway of VEGFA and FGF2 enrichment is more significant for AD. Besides, PI3K-Akt signaling pathway might serve as the latent mechanism about the initiation of differentiation of BMSCs into multiple lineages. Above hub genes and early-responder signaling pathways control osteogenic and adipogenic fates of BMSCs, which maybe mechanistic models clarifying the changes of bone metabolism in the clinical progress of osteoporosis. The findings provide a crucial reference for the prevention and therapy of osteoporosis.


Predictive factors for prolonged sick leave in breast cancer patients treated with adjuvant therapies: a retrospective registry study.
Being able to work during and after breast cancer treatments is important for patients to have a sense of normalcy, financial security, and improved quality of life, and for society due to the economic burden of sick leave. Factors influencing the length of sick leave can be sociodemographic factors, workplace adaptations, recurrences, symptoms, and type of treatment. The aim of this study is to analyse factors associated with prolonged sick leave after adjuvant breast cancer treatments. The population of this registry study consists of 1333 early breast cancer patients diagnosed and treated in Helsinki University Hospital between 2016 and 2018. Data on patient demographics, disease characteristics, treatment, and healthcare resource utilization were obtained from Helsinki University Hospital and data on income level and sick leave were obtained from Kela sickness benefits registry. Prolonged sick leave was determined as the patient accumulating 30 or more reimbursed sick leave days during a 60-day follow-up period after the end of active oncological treatment. Univariate analysis and multivariate analysis were conducted. A total of 26% of the patients in this study were on sick leave for 30 or more days after the active treatments ended. Study findings show that chemotherapy, triple-negative breast cancer, reconstructive surgery, amount of outpatient visits, and income are associated with prolonged sick leave. Independent predictors of prolonged sick leave were treatment line, number of outpatient contacts, reconstruction, and triple-negative breast cancer. Our study shows that prolonged sick leave affects a substantial number of working-age women with early breast cancer. Independent predictors for prolonged sick leave were all treatment-related. Targeted support for treatment-related side-effects already during the treatment period could lead to better recovery and earlier return to work.


Aetiological examination of recurrent urinary stone formers in general practice.
As a part of a project performed in general practice 93 recurrent urinary stone formers were examined by means of a programme comprising a thorough medical history, clinical examination, serum determinations, a chemical stone analysis, two consecutive 24h urine collections and i.v.-pyelography. The diagnostic information obtained from the different examinations is presented. In 64 (69%) of the patients the probable aetiology of the stone formation was revealed. Twenty seven (29%) of all patients had combined aetiology. Hyperuricosuria and hypercalciuria were groups of equal size, comprising all together 45 patients, and emphasizing the necessity of 24h urine collections. Hyperparathyroidism (surgically verified) was diagnosed in four patients, based on serum calcium. Seven patients had infectious stone. It is stated that an aetiological examination of the recurrent stone former may be adequately carried out in general practice and lead to important therapeutical consequences.


Imaging magma transport during the 1997 seismic swarm off the izu peninsula, japan
The spatio-temporal evolution of a propagating magma-filled crack was estimated from inversion of Global Positioning System (GPS) data, tiltmeters, and leveling. The dike opened at a maximum rate of 50 millimeters per day and had a peak magma flux of 2 x 10(6) cubic meters per day. Although the spatial resolution was limited, slow upward propagation was resolved during the 9-day-long intrusion. In contrast, the earthquakes migrated rapidly upward during the first 12 hours of the swarm, and nearly all of the seismic energy was released in the first 2 days. Comparison of inversion results with accurate hypocenter locations will lead to improved understanding of magma transport through the brittle crust and of the causes of volcanic seismicity.