Practice, practitioner, or placebo? A multifactorial, mixed-methods randomized controlled trial of acupuncture.
The nonspecific effects of acupuncture are well documented; we wished to quantify these factors in osteoarthritic (OA) pain, examining needling, the consultation, and the practitioner. In a prospective randomised, single-blind, placebo-controlled, multifactorial, mixed-methods trial, 221 patients with OA awaiting joint replacement surgery were recruited. Interventions were acupuncture, Streitberger placebo acupuncture, and mock electrical stimulation, each with empathic or nonempathic consultations. Interventions involved eight 30-minute treatments over 4 weeks. The primary outcome was pain (VAS) at 1 week posttreatment. Face-to-face qualitative interviews were conducted (purposive sample, 27 participants). Improvements occurred from baseline for all interventions with no significant differences between real and placebo acupuncture (mean difference -2.7 mm, 95% confidence intervals -9.0 to 3.6; P=.40) or mock stimulation (-3.9, -10.4 to 2.7; P=.25). Empathic consultations did not affect pain (3.0mm, -2.2 to 8.2; P=.26) but practitioner 3 achieved greater analgesia than practitioner 2 (10.9, 3.9 to 18.0; P=.002). Qualitative analysis indicated that patients' beliefs about treatment veracity and confidence in outcomes were reciprocally linked. The supportive nature of the trial attenuated differences between the different consultation styles. Improvements occurred from baseline, but acupuncture has no specific efficacy over either placebo. The individual practitioner and the patient's belief had a significant effect on outcome. The 2 placebos were equally as effective and credible as acupuncture. Needle and nonneedle placebos are equivalent. An unknown characteristic of the treating practitioner predicts outcome, as does the patient's belief (independently). Beliefs about treatment veracity shape how patients self-report outcome, complicating and confounding study interpretation.


Mental health service use in a community head start population.
Evaluating access to and delivery of mental health services for young children was a primary objective of the national research demonstration program Starting Early Starting Smart (SESS). To present preliminary findings on family mental health and use of services in a community Head Start population at time of entry into a longitudinal study as part of the SESS program. Children enrolled for Head Start entry in 1998 and 1999 (N = 290; mean age, 4.3 years). Of these children, 52% were boys. Data on demographic factors, child and parent mental health, and service use were collected from the sample at baseline. Information was gathered from primary caregivers and teachers using standardized questionnaires and structured interviews. There was low concordance between parent and teacher ratings of child behavior. Factors predicting behavior problems in young children varied according to whether the parent or teacher rated the child as having behavior problems. Sex (male) and home environment were associated with teachers rating the child as having a behavior problem. Parent mental health problems and problems in the parent-child relationship were associated with parent ratings. Only home environment was associated with child-focused service utilization (services that help parents manage children's behavior). Demographic risk factors were not associated with child behavior problems or use of mental health services in this group of Head Start children. Findings suggest that children with behavioral problems have unmet mental health service needs. Interventions designed to address both parent mental health needs and sensitivity to the developmental needs of children may increase child-focused mental health service utilization.


Dynamic skinfold thickness measurement in infants fed breast-milk, low- or high-sodium formula.
A stratified sample of normal infants born at term at Johannesburg Hospital, who attended the hospital for a routine 6-week follow-up visit, were selected to include 43 infants who were exclusively breast-fed, 42 fed a low-sodium formula and 39 fed a high-sodium formula (greater than 10 mmol sodium/l). Dynamic skinfold thickness measurements (DSTM), designed to assess the amount of interstitial fluid, were performed on each infant by the application of a skinfold caliper for a 3-second sampling period at two sites. The curves generated by these applications were recorded and analysed by microcomputer. There were no differences between any of the feeding groups for DSTM measurements of blood pressure suggesting that the range of sodium ingested by these groups of infants had no significant effects on extracellular water content. However, using multiple linear regression, both DSTM and blood pressure were best predicted by body weight and not by age or any other anthropometric measurement. Thus the normal postnatal decrease in extracellular fluid volume and increase in blood pressure appears to be most closely related to an increase in body weight.


Cardiac sympathetic nerve activity: changes induced by ouabain and propranolol.
A study of the effects of ouabain and propranolol on the spontaneous activity in the preganglionic sympathetic nerves to the cat heart showed that ouabain can produce both an inhibition and a stimulation of the spontaneous activity in sympathetic nerves. The inhibition appears to be reflex in nature and is not present when the buffer nerves are sectioned. The stimulation is correlated with the development of cardiac arrhythmias and is antagonized by propranolol.


Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the Italian Cohort Naive Antiretrovirals (I.Co.N.A.) study.
This nonrandomized study compared the virologic and immunologic responses to potent regimens containing either efavirenz or nevirapine after considering potential systematic differences between patients receiving these drugs. Virologic failure was defined as the first of 2 consecutive measurements of virus load >500 human immunodeficiency virus RNA copies/mL. Of the 694 patients included in the analysis, 460 (66.3%) started nevirapine and 234 (33.7%) started efavirenz. The adjusted relative hazard of virologic failure for patients who started nevirapine, compared with those who started efavirenz, was 2.08 (95% confidence interval, 1.37-3.15; P=.0006). In addition, patients receiving efavirenz tended to recover 5 CD4 cells/microL more per quarter (P=.05). Although comparisons of drug efficacy in nonrandomized studies should be viewed with caution, no results from randomized controlled comparisons of these drugs are thought to be available. The findings of this study are in agreement with those of other observational studies.


Relationships between persistent organic pollutants and circulating immunoglobulin-Y in black-legged kittiwakes and Atlantic puffins.
Have Although persistent organic pollutants (POPs) may affect the immune system, few field studies actually examined this effect. There are indications that POP exert effects on the immune system; however, in the Arctic ecosystem data are scarce. The aim of this study was to examine immune functions in two medium trophic-positioned seabirds, the black-legged kittiwakes (Rissa tridactyla) and Atlantic puffins (Fratercula arctica). Overall POP concentrations were higher in kittiwakes than puffins and males had significantly higher concentrations than females. Mean concentrations of total polychlorinated biphenyls (ΣPCB9) were 4700 ± 200 and 9600 ± 1400 ng/g lipid weight and 2800 ± 180 and 3900 ± 200 ng/g lipid weight in female and male kittiwake and puffin blood, respectively. Levels of immunoglobulin-Y (IgY) in blood of kittiwakes were not markedly affected by concentrations of POP. Similarly, the primary IgY response to tetanus toxoid was not affected by POP concentrations in a subsample of immunized kittiwakes. In puffins, there were significant correlations between the IgY-response and some of the POPs, but with low explanatory values. These results suggest that POPs concentrations were lower than, or just at the threshold level for effects of the proposed IgY biomarker. It is also conceivable that the IgY levels are not a suitable endpoint for evaluating perturbation of the immune system in free-living seabirds.


Theoretical insight into the photophysical properties of six heteroleptic Ir(iii) phosphorescent complexes bearing ppy-type ligands.
By using density functional theory and time-dependent density functional theory, the geometrical, electronic and photophysical properties of six complexes with two ppy-type ligands and one acetylacetone anion around the Ir center have been explored. The lowest energy absorption wavelengths are located at 414 nm for 1, 434 nm for 2, 434 nm for 3, 421 nm for 4, 436 nm for 5, and 425 nm for 6, respectively. The lowest energy emissions of these complexes are localized at 617, 492, 633, 634, 491 and 491 nm, respectively, for complexes 1-6, simulated in CH2Cl2 medium at the M062X level. The calculated lowest lying absorption wavelength and the lowest energy emission wavelength for complex 3 are very close to the available experimental values. The position and number of the incorporated electron-withdrawing fluorine substituents have some effect on the electronic and photophysical properties of these studied complexes.


Rotavirus isolate WI61 representing a presumptive new human serotype.
A virus (strain WI61) representing a presumptive new human serotype was isolated from an 18-month-old child with gastroenteritis admitted to Children's Hospital of Philadelphia in February 1983. The WI61 virus was clearly distinguished by cross-neutralization tests from human rotaviruses of serotypes 1, 2, 3, and 4, human 69M, and representative bovine (NCDV), porcine (OSU), and chicken (Ch2) rotaviruses. Antisera generated in guinea pigs hyperimmunized to WI61 virus displayed a partial cross-reactivity with rotaviruses of human serotypes 1, 2, 3, and 4. By means of studies with reassortant rotaviruses, it was presumptively determined that the WI61 virus cross-reactive antigenic determinants are localized on the vp3 surface polypeptide coded by gene segment 4. The characteristic RNA genome electropherotype of WI61 virus was observed in 5 of 59 cases of infant gastroenteritis detected in 1983 and 1984 but has not been observed in a subsequently at Children's Hospital. Serotype WI61-specific neutralizing antibodies were observed in a majority of sera of normal adults and infants of less than 4 or greater than 12 months of age collected in the Philadelphia area. Median antibody titers to WI61 equaled or exceeded those to rotaviruses of serotype 1 or 3. Each of seven samples of commercial cow's milk exhibited neutralizing antibodies to WI61 virus at a titer greater than or equal to that to serotype 1 or 3 or bovine (strain NCDV) rotavirus. However, WI61 rotavirus did not induce disease or a specific serum-neutralizing antibody response when fed to a caesarean-derived colostrum-deprived newborn calf. WI61 rotavirus caused diarrhea in newborn mice with a 50% diarrhea-inducing dose of 10(7.0) PFU.


Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis.
To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-kappaB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.


The novel bZIP transcription factor Fpo1 negatively regulates perithecial development by modulating carbon metabolism in the ascomycete fungus Fusarium graminearum.
Fungal sexual reproduction requires complex cellular differentiation processes of hyphal cells. The plant pathogenic fungus Fusarium graminearum produces fruiting bodies called perithecia via sexual reproduction, and perithecia forcibly discharge ascospores into the air for disease initiation and propagation. Lipid metabolism and accumulation are closely related to perithecium formation, yet the molecular mechanisms that regulate these processes are largely unknown. Here, we report that a novel fungal specific bZIP transcription factor, F. graminearum perithecium overproducing 1 (Fpo1), plays a role as a global transcriptional repressor during perithecium production and maturation in F. graminearum. Deletion of FPO1 resulted in reduced vegetative growth, asexual sporulation and virulence and overproduced perithecium, which reached maturity earlier, compared with the wild type. Intriguingly, the hyphae of the fpo1 mutant accumulated excess lipids during perithecium production. Using a combination of molecular biological, transcriptomic and biochemical approaches, we demonstrate that repression of FPO1 after sexual induction leads to reprogramming of carbon metabolism, particularly fatty acid production, which affects sexual reproduction of this fungus. This is the first report of a perithecium-overproducing F. graminearum mutant, and the findings provide comprehensive insight into the role of modulation of carbon metabolism in the sexual reproduction of fungi.


Oxytocin inhibits male sexual behavior in prairie voles.
Intracerebroventricular (ICV) injection of oxytocin (300 ng) produced an immediate cessation in sexual behavior in sexually active male prairie voles (Microtus ochrogaster). Other social behaviors including social contact, aggression, and autogrooming were not significantly affected by oxytocin, but males that received oxytocin ICV, versus injections that missed the ventricles, showed more sleep postures. Sexual behavior remained inhibited for at least 24 hours and was not activated in tests with a novel receptive female. Sexual and social behavior were not significantly altered in animals in which the oxytocin injection missed the ventricles or in saline-treated males. These findings are consistent with the hypothesis that oxytocin plays a role in sexual satiety.


A systematic review of acupuncture and moxibustion treatment for chronic fatigue syndrome in China.
Studies on the treatment of chronic fatigue syndrome (CFS) with acupuncture and moxibustion in China were reviewed. All studies concluded the treatments were effective, with response rates ranging from 78.95% to 100%. However, the qualities of the studies were generally poor, and none of them used a RCT design. The common acupoints/sites used in the treatment of CFS, which may reflect the collective experience of acupuncturists in China based on Traditional Chinese Medicine theories can be used to evaluate the effectiveness of acupuncture for the treatment of CFS in future studies using more scientifically rigorous study designs.


Feasibility of Onchocerciasis Elimination Using a "Test-and-not-treat" Strategy in Loa loa Co-endemic Areas.
Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months. Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.


Channelrhodopsin-1 initiates phototaxis and photophobic responses in chlamydomonas by immediate light-induced depolarization.
Channelrhodopsins (CHR1 and CHR2) are light-gated ion channels acting as sensory photoreceptors in Chlamydomonas reinhardtii. In neuroscience, they are used to trigger action potentials by light in neuronal cells, tissues, or living animals. Here, we demonstrate that Chlamydomonas cells with low CHR2 content exhibit photophobic and phototactic responses that strictly depend on the availability of CHR1. Since CHR1 was described as a H+-channel, the ion specificity of CHR1 was reinvestigated in Xenopus laevis oocytes. Our experiments show that, in addition to H+, CHR1 also conducts Na+, K+, and Ca2+. The kinetic selectivity analysis demonstrates that H+ selectivity is not due to specific translocation but due to selective ion binding. Purified recombinant CHR1 consists of two isoforms with different absorption maxima, CHR1505 and CHR1463, that are in pH-dependent equilibrium. Thus, CHR1 is a photochromic and protochromic sensory photoreceptor that functions as a light-activated cation channel mediating phototactic and photophobic responses via depolarizing currents in a wide range of ionic conditions.


Probucol release from novel multicompartmental microcapsules for the oral targeted delivery in type 2 diabetes.
In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6 ± 0.25% PB content, and zeta potential of -66 ± 1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p < 0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85 ± 5 and 92 ± 2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules.


Intra-individual variation in Galium odoratum is affected by experimental drought and shading.
Climate-change induced warmer spring temperatures advance tree leaf-out and result in earlier shading of the forest floor. Climate change also leads to more frequent droughts. Forest understorey herbs may respond to these environmental changes by varying traits at different hierarchical levels of organization. While trait mean variation at the inter-individual level in response to environmental changes is well-studied, little is known about how variation at the intra-individual level responds. We sampled genets of the forest understorey herb Galium odoratum from 21 populations in three regions in Germany, varying in microclimatic conditions. The genets were transplanted into a common garden, where we applied shading and drought treatments. We measured plant height and leaf length and width, and calculated the coefficient of variation (CV) at different hierarchical levels: intra-population, intra-genet, intra-ramet and intra-shoot. Variance partitioning showed that intra-shoot CV represented most of the total variation, followed by intra-ramet CV. We found significant variation in CV of plant height and leaf width among populations of origin, indicating that CV is at least partly genetically based. The soil temperature at populations' origins correlated negatively with CV in plant height, suggesting adaptation to local conditions. Furthermore, we observed that early shade led to increased intra-ramet CV in leaf length, while drought reduced intra-shoot CV in leaf width. Finally, intra-shoot leaf width mean and CV were independent under control conditions but correlated under drought. Our experimental results reveal correlations of intra-individual variation with soil temperature, indicating that intra-individual variation can evolve and may be adaptive. Intra-individual variation responded plastically to drought and shading, suggesting functional changes to improve light capture and reduce evapotranspiration. In conclusion, intra-individual variation makes up the majority of total trait variation in this species and can play a key role in plant adaptation to climatic change.


Ultrasonography predicts the results of labial salivary gland biopsy in patients with suspected Sjögren's syndrome: a matrix risk model.
Although a positive result of labial salivary gland biopsy (LSGB) is critical for the diagnosis of Sjögren's syndrome, rheumatologists prefer assessing the non-invasive objective items and hope to learn the predicted probability of positive LSGB before referring patients with suspected Sjögren's syndrome to receive biopsy. This study aimed to explore the predictive value of combined B-mode ultrasonography (US) and shear-wave elastography (SWE) examination on LSGB results. A derivation cohort and later a validation cohort of patients with suspected Sjögren's syndrome were recruited. All participants received clinical assessments, B-mode US and SWE examination on bilateral parotid and submandibular glands before LSGB. Positive LSGB was defined by a focus score ⩾1 per 4 mm2 of glandular tissue. In the derivation cohort of 91 participants, either the total US scores or the total SWE values of four glands significantly distinguished patients with positive LSGB from those with negative results (area under the curve (AUC) = 0.956, 0.825, both p < 0.001). The positive predictive value (PPV) was 100% in patients with total US scores ⩾9 or with total SWE values ⩾33 kPa. The negative predictive value (NPV) was 100% in patients with total US scores <5, but 68% in patients with total SWE values <27 kPa. A matrix risk model was derived based on the combination of total US scores and total SWE values. Patients can be stratified into high, moderate, and low risk of positive LSGB. In the validation cohort of 52 participants, the PPV was 94% in the high-risk subpopulation and the NPV was 93% in the low-risk subpopulation. A novel matrix risk model based on the combined B-mode US and SWE examination can help rheumatologists to make a shared decision with suspected Sjögren's syndrome patients on whether the invasive procedure of LSGB should be performed.


Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl (Menispermaceae).
Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70% (v/v) ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 g/ml), anti-delta-dextran (IC50 = 13.9 g/ml) and anti-IgM (IC50 = 24.3 g/ml) but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 g/ml induced a 700% increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice) and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 g/ml induced a 20% inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75%. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.


Acupuncture or acupressure for induction of labour.
This is one of a series of reviews of methods of cervical ripening and labour induction. The use of complementary therapies is increasing. Women may look to complementary therapies during pregnancy and childbirth to be used alongside conventional medical practice. Acupuncture involves the insertion of very fine needles into specific points of the body. Acupressure is using the thumbs or fingers to apply pressure to specific points. The limited observational studies to date suggest acupuncture for induction of labour has no known adverse effects to the fetus, and may be effective. However, the evidence regarding the clinical effectiveness of this technique is limited. To determine, from the best available evidence, the effectiveness and safety of acupuncture and acupressure for third trimester cervical ripening or induction of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016), PubMed (1966 to 25 November 2016), ProQuest Dissertations & Theses (25 November 2016), CINAHL (25 November 2016), Embase (25 November 2016), the WHO International Clinical Trials Registry Portal (ICTRP) (3 October 2016), and bibliographies of relevant papers. Randomised controlled trials comparing acupuncture or acupressure, used for third trimester cervical ripening or labour induction, with placebo/no treatment or other methods on a predefined list of labour induction methods. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. The quality of the evidence was assessed using GRADE. This updated review includes 22 trials, reporting on 3456 women. The trials using manual or electro-acupuncture were compared with usual care (eight trials, 760 women), sweeping of membranes (one trial, 207 women), or sham controls (seven trials, 729 women). Trials using acupressure were compared with usual care (two trials, 151 women) or sham controls (two trials, 239 women). Many studies had a moderate risk of bias.Overall, few trials reported on primary outcomes. No trial reported vaginal delivery not achieved within 24 hours and uterine hyperstimulation with fetal heart rate (FHR) changes. Serious maternal and neonatal death or morbidity were only reported under acupuncture versus sham control. Acupuncture versus sham control There was no clear difference in caesarean sections between groups (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.15, eight trials, 789 women; high-quality evidence). There were no reports of maternal death or perinatal death in the one trial that reported this outcome. There was evidence of a benefit from acupuncture in improving cervical readiness for labour (mean difference (MD) 0.40, 95% CI 0.11 to 0.69, one trial, 125 women), as measured by cervical maturity within 24 hours using Bishop's score. There was no evidence of a difference between groups for oxytocin augmentation, epidural analgesia, instrumental vaginal birth, meconium-stained liquor, Apgar score < 7 at five minutes, neonatal intensive care admission, maternal infection, postpartum bleeding greater than 500 mL, time from the trial to time of birth, use of induction methods, length of labour, and spontaneous vaginal birth. Acupuncture versus usual care There was no clear difference in caesarean sections between groups (average RR 0.77, 95% CI 0.51 to 1.17, eight trials, 760 women; low-quality evidence). There was an increase in cervical maturation for the acupuncture (electro) group compared with control (MD 1.30, 95% CI 0.11 to 2.49, one trial, 67 women) and a shorter length of labour (minutes) in the usual care group compared to electro-acupuncture (MD 124.00, 95% CI 37.39 to 210.61, one trial, 67 women).There appeared be a differential effect according to type of acupuncture based on subgroup analysis. Electro-acupuncture appeared to have more of an effect than manual acupuncture for the outcomes caesarean section (CS), and instrumental vaginal and spontaneous vaginal birth. It decreased the rate of CS (average RR 0.54, 95% CI 0.37 to 0.80, 3 trials, 327 women), increased the rate of instrumental vaginal birth (average RR 2.30, 95%CI 1.15 to 4.60, two trials, 271 women), and increased the rate of spontaneous vaginal birth (average RR 2.06, 95% CI 1.20 to 3.56, one trial, 72 women). However, subgroup analyses are observational in nature and so results should be interpreted with caution.There were no clear differences between groups for other outcomes: oxytocin augmentation, use of epidural analgesia, Apgar score < 7 at 5 minutes, neonatal intensive care admission, maternal infection, perineal tear, fetal infection, maternal satisfaction, use of other induction methods, and postpartum bleeding greater than 500 mL. Acupuncture versus sweeping if fetal membranes One trial of acupuncture versus sweeping of fetal membranes showed no clear differences between groups in caesarean sections (RR 0.64, 95% CI 0.34 to 1.22, one trial, 207 women, moderate-quality evidence), need for augmentation, epidural analgesia, instrumental vaginal birth, Apgar score < 7 at 5 minutes, neonatal intensive care admission, and postpartum bleeding greater than 500 mL. Acupressure versus sham control There was no evidence of benefit from acupressure in reducing caesarean sections compared to control (RR, 0.94, 95% CI 0.68 to 1.30, two trials, 239 women, moderate-quality evidence). There was no evidence of a clear benefit in reduced oxytocin augmentation, instrumental vaginal birth, meconium-stained liquor, time from trial intervention to birth of the baby, and spontaneous vaginal birth. Acupressure versus usual care There was no evidence of benefit from acupressure in reducing caesarean sections compared to usual care (RR 1.02, 95% CI 0.68 to 1.53, two trials, 151 women, moderate-quality evidence). There was no evidence of a clear benefit in reduced epidural analgesia, Apgar score < 7 at 5 minutes, admission to neonatal intensive care, time from trial intervention to birth of the baby, use of other induction methods, and spontaneous vaginal birth. Overall, there was no clear benefit from acupuncture or acupressure in reducing caesarean section rate. The quality of the evidence varied between low to high. Few trials reported on neonatal morbidity or maternal mortality outcomes. Acupuncture showed some benefit in improving cervical maturity, however, more well-designed trials are needed. Future trials could include clinically relevant safety outcomes.


[Peculiarities of the surgical treatment of nasal septum perforations].
The objective of the present study was the retrospective analysis of the results of nasal septum perforation (NSP) surgery. We report our experience with the operations on the perforated nasal septum based on the treatment of a total of 84 patients. Plastic repair of the perforated nasal septum was undertaken in 54 of them. The endonasal approach with the use of local tissue flaps was employed in 47 cases. Additional bucco-gingival flaps were used in another 4 patients and the open rhinoplastic approach in 3 cases. The complete closure of nasal septum perforations was achieved in 34 (63%) patients. The reduction of the size of perforations was documented in 17 (31%) patients whereas in the remaining three the perforation size slightly increased. The surgical technique and peculiarities of the postoperative management of the patients are described; the possible causes of NSP relapses following surgery are discussed.


[Effect of inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid oxidation on the immune response and the activity of the monoxygenase system and lipid peroxidation in the spleen and liver in mice].
In experiments on CBA mice we studied an immune response (IR) to sheep red blood cells, the activity of monooxygenase system and lipid peroxidation (LP) in a spleen and a liver after administration of indomethacin (IND) and nordihydroguaiaretic acid (NDGA) as the inhibitors of cyclooxygenase and lypoxygenase pathways of oxydation of arachidonic acid consequently. We have found that the both inhibitors changed differently the intensity of IR during its development. IND and NDGA activate the accumulation of antibody-forming cells in the mouse spleen in a dose-dependent fashion at both the inductive and fading phases of IR. At the productive phase these changes are less expressed and they are different depending on the dose of NDGA: the smaller dose increases the immune response and the bigger one decreases it a bit. Changes in the activity of the monooxygenase system in spleen and liver, affected with the both inhibitors, independing on the dose, were of different direction: after IND administration the activity increased, but after NDGA administration it decreased at all the terms of investigation, excluding the term of the 5-th day (productive phase of IR). In these conditions changes in the activity of IR were of opposite direction as compared to the changes in the monooxygenase system.


The mechanism of action of insulin on phospholipid metabolism in rat adipose tissue. Requirement for protein synthesis and a carbohydrate source, and relationship to activation of pyruvate dehydrogenase.
We studied certain metabolic requirements for insulin-induced increases in phospholipids, and the relationship of phospholipid changes to the insulin-induced activation of pyruvate dehydrogenase, in rat adipocytes and fat pads in vitro. Increases in the contents of phosphatidylinositol and phosphatidylserine mass were maximal in rat fat pads within 10 min of incubation with insulin, and preceded or accompanied measurable increases in pyruvate dehydrogenase activity. In dose-response studies, the contents of these phospholipids and pyruvate dehydrogenase activity increased in parallel in response to increasing concentrations of insulin. Cycloheximide and puromycin inhibited insulin-induced increases in the mass of both of these phospholipids, as well as (in confirmation of previous reports) pyruvate dehydrogenase activity. Effects of insulin on phospholipid metabolism and pyruvate dehydrogenase were found to require an exogenous carbohydrate source, and fructose was nearly as effective as glucose in this regard. Insulin-induced increases in phosphatidylinositol and phosphatidylserine were demonstrated in the mitochondrial fraction, which is also the subcellular locus of pyruvate dehydrogenase. The present findings suggest that there is a relationship between insulin-induced increases in phospholipids and pyruvate dehydrogenase activity, but the nature of this relationship remains to be defined.


Two new species and updated checklist of Oxyethira Eaton, 1873 (Trichoptera, Hydroptilidae) from Brazil.
Two new species of Oxyethira Eaton, 1873 are described: Oxyethira cascadanta sp. n. and Oxyethira quadrilobata sp. n. Description and illustrations of the new species are provided based on specimens collected in Parque Nacional da Serra da Canastra, Minas Gerais State, Southeast Brazil. Both species are assigned to the subgenus Loxotrichia but differ from other species mainly in morphology of the subgenital plate, subgenital processes and inferior appendages. Additionally, we provide an updated checklist of the Oxyethira species from Brazil.


Pressure controlled inverse ratio ventilation in acute respiratory distress syndrome patients.
Appropriate ventilatory intervention is life saving in acute respiratory distress syndrome (ARDS). Pressure controlled inverse ratio ventilation (PC-IRV) is the likely mode of ventilation benefiting in extreme conditions of ARDS. However, guidelines when to start PC-IRV is not yet well defined. The ventilation-related dilemma, which we faced in two illustrative cases of ARDS are presented. The first patient presenting clinically with ARDS but with high peak airway pressure (PIP) and low dynamic lung compliance, PC-IRV helped in reducing PIP, improved haemodynamics and the oxygenation of blood. In second patient with similar clinical presentation of ARDS, where although PIP was high but the dynamic compliance was better, the PC-IRV caused deterioration in PaO2. Here, patient rather did better with high PEEP (15 cm H2O) and usual I: E ratio (1:2). It is probable that the dynamic lung compliance (< 20ml/cmH2O), PIP (> 50 cm H2O) at conventional I: E ratio (1:2) ventilation (10 ml/kg) with hypotension might form the basis to develop a scoring system for guidance to switch over to PC-IRV ventilation. Further randomised prospective controlled clinical trials will then be required to establish indication to start PC-IRV in ARDS.


To the bone: Prevalence and correlates of depression and anxiety among orthopedic residents in Mexico.
The present study examined among orthopedic residents the relationship between the presence of depressive or anxious symptoms and the degree of perfectionism, perceived work-related distress, and involvement in the care of patient(s) who died. A cross-sectional online survey based on self-reported measures was used to collect the data from October 2019 to April 2021. The sample consisted of 642 orthopedic residents (50.6% response rate; 70.9% male; average age 29.8 years old). A total of 12.5 and 18.4% reported depressive or anxious symptoms, respectively. On a scale of 0-100, the mean score of perceived work-related distress was 51.9. A third (33.6%) reported being involved in the care of patient(s) who had died. Higher levels of perceived work-related distress and higher scores on the indecision of action/perfectionism dimension were associated with depressive and anxious symptoms. Being involved in the care of patient(s) who had died was associated with having anxious symptoms (OR = 1.79; 95%CI = 1.18-2.72). These results highlight the need for the systematic monitoring of the mental health status of orthopedic residents in Mexico, particularly those who report a high level of work-related distress or perfectionism or who have recently experienced the death of a patient.


Molecular targets and early response biomarkers for the prediction of developmental toxicity in vitro.
There is an urgent need for new in vitro methods to predict the potential developmental toxicity of candidate drugs in the early lead identification and optimisation process. This would lead to a reduction in the total number of animals required in full-scale developmental toxicology studies, and would improve the efficiency of drug development. However, suitable in vitro systems permitting robust high-throughput screening for this purpose, for the most part, remain to be designed. An understanding of the mechanisms involved in developmental toxicity may be essential for the validation of in vitro tests. Early response biomarkers - even a single one - could contribute to reducing assay time and facilitating automation. The use of toxicogenomics approaches to study in vitro and in vivo models in parallel may be a powerful tool in defining such mechanisms of action and the molecular targets of toxicity, and also for use in finding possible biomarkers of early response. Using valproic acid as a model substance, the use of DNA microarrays to identify teratogen-responsive genes in cell models is discussed. It is concluded that gene expression in P19 mouse embryocarcinoma cells represents a potentially suitable assay system, which could be readily used in a tiered testing system for developmental toxicity testing.


[Factors associated with voice disorders among women teachers].
This study aimed to identify risk factors for voice disorders (hoarseness in the previous six months as an initial manifestation, and vocal cord nodules as a more severe manifestation of overt disease) among teachers. The cross-sectional study included 747 women teachers from elementary and middle schools in the public school system in Vitória da Conquista, Bahia State, Brazil. Data were collected using a self-applied, standardized questionnaire. Hoarseness in the previous six months was reported by 59.2% of teachers and vocal cord nodules by 12.9%. Logistic regression techniques showed that hoarseness was statistically associated with > 24 classroom hours per week, work in more than one school, and having to make an effort to speak. Vocal cord nodules were associated with working > 5 years as a teacher, work in more than one school, working at another job besides teaching, and having to make an effort to speak. In conclusion, voice disorders are frequent among schoolteachers and are associated with multiple occupational risk factors, besides purely biological ones.


New efficient synthesis of resorcinylic macrolides via ynolides: establishment of cycloproparadicicol as synthetically feasible preclinical anticancer agent based on Hsp90 as the target.
A program currently ongoing in our laboratory envisions natural macrolide radicicol-based inhibitors targeting the molecular chaperone Hsp90. Such inhibitors can be potential anticancer agents due to their ability to induce the breakdown of a variety of oncogenic proteins. In this account, we first concern ourselves with a vastly important total synthesis of such an inhibitor. We accomplished this via a new approach, which we term the "ynolide method", directed to the synthesis of resorcinylic macrolides, including cycloproparadicicol and aigialomycin D. The key features of the syntheses involve cobalt-complexation-promoted ring-closing metathesis (RCM) to generate ynolides, followed by Diels-Alder reaction with dimedone-derived bis-siloxy dienes to elaborate the benzo system. A number of interesting analogues were synthesized using this protocol. They were evaluated for their inhibitory activity against the growth of breast cancer cell line, MCF-7. The potency of their cytotoxicity was found to be consistent with their ability to degrade the oncogenic protein, Her2. From these assays, cycloproparadicicol was identified as a most promising candidate for further development.


Plasmon mediated SERS and photocatalysis enhancement in Au nanoparticle decorated 2D-TiSe2.
The combination of 2D materials and noble metallic nanostructure is becoming an attractive research domain for label-free, highly sensitive surface-enhanced Raman spectroscopy (SERS) applications. This study demonstrated photocatalysis degradation and SERS enhancements of organic fluorophore (Rhodamine 6G) on two-dimensional (2D) TiSe2using Raman spectroscopy. The Au nanoparticles (NPs) were decorated on TiSe2thin films by thermal annealing at variable temperatures. The selective deposition of Au NPs on the hexagonal TiSe2nanocrystals increases surface roughness, creating a larger surface area for molecule adsorption. It has been observed that the Au decoration at 250oC on TiSe2exhibits efficient detection capabilities for R6G with the Raman intensity enhancement factors of the order of ∽ 105along with the significantly improved visible light-induced photodegradation efficiency. The optimized Au NP size creates large electromagnetic hot spots produced by strong plasmon coupling that assists in the charge transfer mechanism among TiSe2, Au NPs, and R6G for enhanced SERS and photocatalysis activities. It has been observed that the intensity of Raman scattering decreases as the Au NP size increases on the TiSe2material. A possible charge transfer mechanism is proposed with an energy band diagram. The simultaneous measurement of SERS and photocatalytic dye degradation in Au decorated TiSe2can be used as a sensitive technique for water pollution treatment and biodegradable organic contaminants for the environmental ecosystem.


Uterine and fetal hemodynamics and fetal cardiac function after atenolol and pindolol infusion. A randomized study.
To evaluate the short-term effects of intravenously given atenolol and pindolol on utero- and umbilicoplacental vascular impedance, fetal hemodynamics and cardiac function in patients suffering from pregnancy-induced hypertension. A total of 24 women were randomized to receive atenolol or pindolol infusion. By using pulsed color Doppler techniques, uterine, placental arcuate, umbilical fetal middle cerebral and renal arteries were examined before, at the end and 30 min after the end of infusion. Pulsatility indices (PI) were calculated to assess vascular impedance. Fetal myocardial function was evaluated by using pulsed Doppler and M-mode echocardiography. Peak systolic velocities from the ascending aorta and pulmonary trunk, and also inner diameters and fractional shortenings of both ventricles were measured. Both drugs significantly decreased maternal blood pressure. Immediately after the infusion, maternal heart rate was significantly decreased in both groups; but the decrease was clearer and lasted longer in the atenolol group. Pindolol caused no changes in utero- or umbilicoplacental vascular impedance, while atenolol increased it in the nonplacental uterine artery. After atenolol infusion, PI in the umbilical artery was higher than after pindolol. Pindolol had no effects on fetal hemodynamics, while atenolol decreased PI value in the fetal renal artery. Peak systolic velocity in the pulmonary trunk was decreased after atenolol. Pindolol did not affect the fetal cardiac function. In subgroups with originally increased utero- or umbilicoplacental vascular impedance, the responses in uterine and umbilical vascular impedance and in fetal hemodynamics and cardiac function after atenolol and pindolol were different compared to whole groups. Differently acting antihypertensive agents seem to affect differently uteroplacental vascular impedance. Atenolol may have some direct effects on fetal hemodynamics and cardiac function. According to our results, pindolol seems to be more preferable in the treatment of pregnancy-induced hypertension than atenolol.


Strength around the hip and flexibility of soft tissues in individuals with and without patellofemoral pain syndrome.
Case control design. To investigate whether differences exist in lower extremity muscle strength and soft tissue length between patients with patellofemoral pain syndrome (PFPS) and age- and gender-matched control subjects. Based on our clinical experience and emerging data, impairments such as muscular weakness surrounding the hip and limited flexibility of key lower extremity muscles may be important impairments to consider in the conservative management of PFPS. Thirty patients with PFPS and 30 age- and gender-matched controls without PFPS (17 females and 13 males in each group) participated in the study. Data were collected during 1 testing session by an examiner not blinded to group assignment. Demographic, health history, physical activity levels, and pain and function were assessed using patient-completed measures. Physical examination measures included assessment of hip external rotation strength, hip abduction strength, length of the iliotibial band/tensor fascia lata complex, gastrocnemius length, soleus length, and quadriceps and hamstrings muscles length. Patients with PFPS demonstrated significantly less flexibility of the gastrocnemius, soleus, quadriceps, and hamstrings compared to healthy control subjects. No differences existed in flexibility of the iliotibial band/tensor fascia lata complex and strength of the hip external rotators and abductors. Multivariate stepwise discriminant analysis identified gastrocnemius length, hip abduction strength, and soleus length as being able to distinguish between patients with PFPS and healthy individuals without PFPS. This study suggests that further research is warranted regarding the association of these impairments of muscle strength and soft tissue length in patients with PFPS.


Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.
Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.


Measuring diffusion with polarization-modulation dual-focus fluorescence correlation spectroscopy.
We present a new technique, polarization-modulation dual-focus fluorescence correlation spectroscopy (pmFCS), based on the recently intro-duced dual-focus fluorescence correlation spectroscopy (2fFCS) to measure the absolute value of diffusion coefficients of fluorescent molecules at pico- to nanomolar concentrations. Analogous to 2fFCS, the new technique is robust against optical saturation in yielding correct values of the diffusion coefficient. This is in stark contrast to conventional FCS where optical saturation leads to an apparent decrease in the determined diffusion coefficient with increasing excitation power. However, compared to 2fFCS, the new technique is simpler to implement into a conventional confocal microscope setup and is compatible with cw-excitation, only needing as add-ons an electro-optical modulator and a differential interference contrast prism. With pmFCS, the measured diffusion coefficient (D) for Atto655 maleimide in water at 25?C is determined to be equal to (4.09 +/- 0.07) x 10(-6)cm(2)/s, in good agreement with the value of 4.04 x 10-6cm2/s as measured by 2fFCS.


Gene regulation during late embryogenesis: the RY motif of maturation-specific gene promoters is a direct target of the FUS3 gene product.
The Arabidopsis mutants fus3 and abi3 show pleiotropic effects during embryogenesis including reduced levels of transcripts encoding embryo-specific seed proteins. To investigate the interaction between the B3-domain-containing transcription factors FUS3 and ABI3 with the RY cis-motif, conserved in many seed-specific promoters, a promoter analysis as well as band-shift experiments were performed. The analysis of promoter mutants revealed the structural requirements for the function of the RY cis-element. It is shown that both the nucleotide sequence and the alternation of purin and pyrimidin nucleotides (RY character) are essential for the activity of the motif. Further, it was shown that FUS3 and ABI3 can act independently of each other in controlling promoter activity and that the RY cis-motif is a target for both transcription factors. For FUS3, which is so far the smallest known member of the B3-domain family, a physical interaction with the RY motif was established. The functional and biochemical data demonstrate that the regulators FUS3 and ABI3 are essential components of a regulatory network acting in concert through the RY-promoter element to control gene expression during late embryogenesis and seed development.


Effects of resistive load on performance and surface EMG activity during repeated cycling sprints on a non-isokinetic cycle ergometer.
To determine the effects of resistive load on performance and surface electromyogram (SEMG) activity during repeated cycling sprints (RCS) on a non-isokinetic cycle ergometer. Participants performed two RCS tests (ten 10-second cycling sprints) interspersed with both 30- and 360-second recovery periods under light (RCS(L)) and heavy load conditions (RCS(H)) in a random counterbalanced order. Recovery periods of 360 seconds were set before the fifth and ninth sprints. In the 9th and 10th sprints, the values of peak power output divided by body mass were significantly higher in RCS(H) than in RCS(L). Changes in blood lactate concentration were not different between the two conditions. In RCS(L), the root mean square calculated from the SEMG was significantly lower in the ninth sprint than in the first sprint, but there were no differences between the root mean square in the first sprint and that in the ninth sprint in RCS(H). During RCS on a non-isokinetic cycle ergometer, performance and SEMG activity are influenced by resistive load. It is thought that regulation of skeletal muscle recruitment by the central nervous system is associated with fatigue during RCS with a light resistive load.


Proliferative and morphological changes in the pulmonary epithelium of the Syrian golden hamster during carcinogenesis initiated by 210Po alpha alpha-radiation.
The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups.


Contribution of systemic inflammation to permanence of KATP-induced neonatal diabetes in mice.
Gain-of-function (GOF) mutations in the ATP-sensitive potassium (KATP) channels cause neonatal diabetes. Despite the well-established genetic root of the disease, pathways modulating disease severity and treatment effectiveness remain poorly understood. Patient phenotypes can vary from severe diabetes to remission, even in individuals with the same mutation and within the same family, suggesting that subtle modifiers can influence disease outcome. We have tested the underlying mechanism of transient vs. permanent neonatal diabetes in KATP-GOF mice treated for 14 days with glibenclamide. Some KATP-GOF mice show remission of diabetes and enhanced insulin sensitivity long after diabetes treatment has ended, while others maintain severe insulin-resistance. However, insulin sensitivity is not different between the two groups before or during diabetes induction, suggesting that improved sensitivity is a consequence, rather than the cause of, remission, implicating other factors modulating glucose early in diabetes progression. Leptin, glucagon, insulin, and glucagon-like peptide-1 are not different between remitters and nonremitters. However, liver glucose production is significantly reduced before transgene induction in remitter, relative to nonremitter and nontreated, mice. Surprisingly, while subsequent remitter animals exhibited normal serum cytokines, nonremitter mice showed increased cytokines, which paralleled the divergence in blood glucose. Together, these results suggest that systemic inflammation may play a role in the remitting versus non-remitting outcome. Supporting this conclusion, treatment with the anti-inflammatory meloxicam significantly increased the fraction of remitting animals. Beyond neonatal diabetes, the potential for inflammation and glucose production to exacerbate other forms of diabetes from a compensated state to a glucotoxic state should be considered.


Maturational timing and overweight prevalence in US adolescent girls.
This study examined the relation of age at menarche to overweight in US adolescent girls. Effects of age at menarche and race/ethnicity on overweight were estimated via logistic regression, after adjustment for sociodemographic characteristics, in a sample of 6507 Hispanic, Black, White, and Asian American girls who participated in wave 2 of the National Longitudinal Study of Adolescent Health. Overweight prevalence rates were significantly higher in early maturing adolescents of all racial/ethnic groups but highest (57.5%) among early maturing Black girls. Early maturation nearly doubled the odds of being overweight (body mass index at or above the 85th percentile). Greater public health attention should be focused on the high prevalence of overweight, particularly among minority female adolescents.


Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis.
To investigate the biologic significance of Smad3 in the progression of osteoarthritis (OA), the crosstalk between Smad3 and activating transcription factor 2 (ATF-2) in the transforming growth factor beta (TGFbeta) signaling pathway, and the effects of ATF-2 overexpression and p38 activation in chondrocyte differentiation. Joint disease in Smad3-knockout (Smad3(-/-)) mice was examined by microfocal computed tomography and histologic analysis. Numerous in vitro methods including immunostaining, real-time polymerase chain reaction, Western blotting, an ATF-2 DNA-binding assay, and a p38 kinase activity assay were used to study the various signaling responses and protein interactions underlying the altered chondrocyte phenotype in Smad3(-/-) mice. In Smad3(-/-) mice, an end-stage OA phenotype gradually developed. TGFbeta-activated kinase 1 (TAK1)/ATF-2 signaling was disrupted in Smad3(-/-) mouse chondrocytes at the level of p38 MAP kinase (MAPK) activation, resulting in reduced ATF-2 phosphorylation and transcriptional activity. Reintroduction of Smad3 into Smad3(-/-) cells restored the normal p38 response to TGFbeta. Phosphorylated p38 formed a complex with Smad3 by binding to a portion of Smad3 containing both the MAD homology 1 and linker domains. Additionally, Smad3 inhibited the dephosphorylation of p38 by MAPK phosphatase 1 (MKP-1). Both ATF-2 overexpression and p38 activation repressed type X collagen expression in wild-type and Smad3(-/-) chondrocytes. P38 was detected in articular cartilage and perichondrium; articular and sternal chondrocytes expressed p38 isoforms alpha, beta, and gamma, but not delta. Smad3 is involved in both the onset and progression of OA. Loss of Smad3 abrogates TAK1/ATF-2 signaling, most likely by disrupting the Smad3-phosphorylated p38 complex, thereby promoting p38 dephosphorylation and inactivation by MKP-1. ATF-2 and p38 activation inhibit chondrocyte hypertrophy. Modulation of p38 isoform activity may provide a new therapeutic approach for OA.


Assaying the circulating factor VIII activity in hemophilia A patients treated with recombinant factor VIII products.
Large discrepancies between factor VIII assay methods have been reported from pharmacokinetic studies of recombinant factor VIII concentrates. In the assay of postinfusion patient plasma samples, traditional activated partial thromboplastin time (aPTT)-based one-stage clotting methods usually give results that are 20 to 50% lower than those obtained by chromogenic substrate assays. Investigations into the cause of these discrepancies have shown that the choice of phospholipid in the one-stage assay is crucial. The use of platelets or liposomes resembling platelet factor 3 instead of traditional aPTT reagents results in an increase in the apparent one-stage activity and a fairly good correlation with the chromogenic results. These and other functional test results, antigen measurements as well as clinical data, support the view that the chromogenic assay most accurately reflects the therapeutic effect. In addition to the differences among assay methods, there is also a discrepancy between the World Health Organization (WHO) standards for concentrates and plasma. The use of product-specific standards, prepared by diluting the factor VIII concentrate into hemophilic plasma, when assaying postinfusion plasma samples seems to be a feasible approach to overcome the problems encountered in pharmacokinetic studies.


Exposure to ZnO/TiO2 Nanoparticles Affects Health Outcomes in Cosmetics Salesclerks.
Concerns about the effects of nanoparticles (NPs) on human health are being raised by researchers because the risks of nanocosmetics like sunscreen are unknown. We explored the association between urinary oxidative stress markers and exposure of cosmetics salesclerks to 20 cosmetics that might contain titanium dioxide (TiO2)/zinc oxide (ZnO) NPs. We then recruited 40 cosmetics salesclerks and 24 clothing salesclerks and categorized them based on their exposure to ZnO and TiO2 NPs. Nineteen and 15 samples met the EU definition for TiO2 and ZnO nanomaterials, respectively. Participants with a higher co-exposure index of ZnO and TiO2 NPs had a significantly higher base level of urinary 8-hydroxy-2'-deoxyguanosin (8-OHdG) concentrations than the lower co-exposure group (5.82 vs. 2.85 ng/mL, p < 0.001). After potential confounding factors had been adjusted for, the TiO2 and ZnO NP co-exposure index was significantly positively associated with the urinary 8-OHdG base concentration (β = 0.308, 95% CI = 0.106 to 0.510) and the creatinine-adjusted concentration (β = 0.486, 95% CI = 0.017 to 0.954). Current evidence suggests that the likelihood of harm from using sunscreens containing nanoparticles might result in higher urinary 8-OHdG. However, our limited number and types of sample cosmetics might underestimate the risk.


Oral appliance to assist non-invasive ventilation in a patient with amyotrophic lateral sclerosis.
From the moment the respiratory muscle groups are affected in amyotrophic lateral sclerosis (ALS), respiratory complications will be the major cause of morbidity and mortality. Untreated respiratory muscle impairment leads to respiratory insufficiency and additionally to difficulties in airway secretion clearance. Non-invasive ventilation (NIV) is the first choice in treating respiratory insufficiency in ALS as it improves sleep-related symptoms, quality of life and life expectancy. Nevertheless, NIV is not always effective, probably due to bulbar dysfunction or anatomical abnormalities. As a result, tracheostomy ventilation (TV) may become necessary. In this case report, we present a 60-year-old female with ALS, for whom it was not possible to provide a sufficient tidal volume with NIV. A chin lift was performed while the patient was awake to see if a more anterior jaw position would lead to an increased tidal volume. As this was the case, a mandibular advancement device (MAD) was fabricated. With a combination of a MAD and NIV, the upper airway obstructions were overcome and a good ventilation and adherence to therapy were seen. When there is the presumption of airway obstructions in combination with an ineffective NIV, we advise to perform a chin lift to assess whether the obstructions can be overcome by a more anterior jaw position. If that is the case, NIV may be combined with MAD to establish effective ventilation and avoid the use of TV.


Cutaneous necrosis and pulse oximetry.
We report on two patients who developed cutaneous necrosis from the use of pulse oximetry monitoring. One developed digital skin necrosis from a finger sensor, while the other had a lesion of the pinna from an ear probe. Pulse oximetry monitoring is often used in the management of anesthetized and critically ill patients. Recognition of cutaneous necrosis with pulse oximetry may prevent unnecessary evaluation and prompt initiation of simple measures to protect against its occurrence.


Non-invasive imaging of a transgenic mouse model using a prostate-specific two-step transcriptional amplification strategy.
Non-invasive assessment of transgenic animals using bioluminescence imaging offers a rapid means of evaluating disease progression in animal models of disease. One of the challenges in the field is to develop models with robust expression to image repetitively live intact animals through solid tissues. The prostate-specific antigen (PSA) promoter is an attractive model for studying gene regulation due to its hormonal response and tissue-specificity permitting us to measure signaling events that occur within the native tissues. The use of the GAL4-VP16 activator offers a powerful means to augment gene expression levels driven by a weak promoter. We have used a two-step transcriptional amplification (TSTA) system to develop a transgenic mouse model to investigate the tissue-specificity and developmental regulation of firefly luciferase (fl) gene expression in living mice using bioluminescence imaging. We employed an enhanced prostate-specific promoter to drive the yeast transcriptional activator, GAL4-VP16 (effector). The reporter construct carries five Gal4 binding sites upstream of the fl gene. We generated a transgenic mouse model using a single vector carrying the effector and reporter constructs. The transgenic mice show prostate-specific expression as early as three weeks of age. The bioluminescence signal in the prostate is significantly higher than in other organs. We also demonstrate that blocking androgen availability can downregulate the fl expression in the prostate. The transgenic mice display normal physical characteristics and developmental behavior, indicating that the high level of GAL4 driven expression is well tolerated. These findings suggest that the GAL4-VP16 transactivator can be used to amplify reporter gene expression from a relatively weak promoter in a transgenic mouse model. The transgenic TSTA model in conjunction with other transgenic cancer models should also help to detect and track malignancies. The strategies developed will be useful for transgenic research in general by allowing for amplified tissue specific gene expression.


Access to intra-arterial therapies for acute ischemic stroke: an analysis of the US population.
Intra-arterial therapies for ischemic stroke offer promise as a means to extend the time window for acute treatment. The purpose of this study was to identify the percentage of the US population with potential access to interventional neuroradiologic expertise within 6 hours of the onset of stroke symptoms. Hospital locations of interventional neuroradiologists were identified from the 2002 roster of the American Society of Interventional and Therapeutic Neuroradiology. Data for populations in surrounding regions were extracted from US Census 2001 data by zip code. Standard transport speeds for emergency medical services were used in our estimates of the population living within a 5-hour transport time, which was a 6-hour treatment window less a 1-hour door-to-needle time, resulting in a 200-mile radius. A 2-hour transport time, or 3-hour treatment window, reflected a 65-mile radius. A total of 385 interventional neuroradiologists were identified, practicing in 45 states. With a 200-mile radius, 99% of the total US population had access to neurointerventional treatment within 6 hours of symptom onset. With a 65-mile radius, 82% of the population had access within 3 hours of symptom onset. Alaska and the Mid-Northwest region covering Idaho, Wyoming, North Dakota, and South Dakota had limited coverage. Most of the US population has access to interventional neuroradiologic expertise for acute stroke therapy. These data suggest that interventional therapies that extend the time window for treating acute ischemic stroke could have a major effect on public health and merit further research development and investment.


Kinetics of the structure of neurites in mollusk brain after its dissociation.
Using phase microscopy the behaviour of living neurons directly after their enzymatic isolation from ganglia of Clione limacina and Lymnaea stagnalis was studied. Apart from single-processed unipolar neurons, numerous dipolar and unipolar ones were found in mollusc which does not conform to neuron classification generally adopted. Disrupted neurons were seen to shorten gradually in Ringer solution and -1640 medium at the rate of 0.84-0.27 mm min. Serial photomicrography revealed that the process has two stages. Neurite retraction is interrupted by the expansion stage (extrusion and urgent regeneration). Duration of retraction and extrusion stages made 22.7-3.3 and 6.6-9.1 min respectively. Retraction speed was 24-0.5 mm/min while that of extrusion was 2.8-0.4 mm/min. different processes of the same neuron contract asynchronously. Process invagination leads to its rounding. Thus the cell acquires most thermodynamically stable from which is arranged to prompt its survival. Spherical neurons lacking processes migrate and demonstrate capacity of regeneration. As the conditions somehow resembling the experimental ones (high proteolytic activity of the medium and process loss in part of neurons) arise in cerebral trauma nidus of it is suggested that viable neuron behaviour is alike in this situation.


Lymphographic findings in multiple myeloma.
The lymphographic appearances of the retroperitoneal lymph nodes in 10 patients with multiple myeloma have been analyzed. None of the patients had any signs of extramedullary involvement of myelomatosis before lymphography. In 3 cases irregular filling defects suggestive of myelomatous involvement were found. In one case they were close to a myelomatous bone lesion, whereas in the others the lymphographic abnormality was totally unexpected. In all 3 patients other nodes showed reactive hyperplasia. Such nonspecific hyperplasia was also encountered in 3 other cases. In 2 cases the myelomatous involvement of lymph node was detected before the diagnosis was recognized which is contrary to the belief that multiple myeloma involve nodes late in the disease. In addition to diagnostic aid the lymphographic demonstration of the myelomatous spread into lymph nodes may influence on the selection of the therapeutic approach to the disease.


Mapping the global geographic potential of Zika virus spread.
The Americas are presently experiencing the most serious known outbreak of Zika virus (ZIKV). Here, we present a novel set of analyses using environmental characteristics, vector mosquito distributions, and socioeconomic risk factors to develop the first map to detail global ZIKV transmission risk in multiple dimensions based on ecological niche models. Our model predictions were tested against independent evaluation data sets, and all models had predictive ability significantly better than random expectations. The study addresses urgent knowledge gaps regarding (1) the potential geographic scope of the current ZIKV epidemic, (2) the global potential for spread of ZIKV, and (3) drivers of ZIKV transmission. Our analysis of potential drivers of ZIKV distributions globally identified areas vulnerable in terms of some drivers, but not for others. The results of these analyses can guide regional education and preparedness efforts, such that medical personnel will be better prepared for diagnosis of potential ZIKV cases as they appear.


Preparing for renal replacement therapy in patients with the Ebola virus disease.
The Ebola virus disease (EVD) is a serious illness characterized by fever, severe vomiting and diarrhea, and, in severe cases, multi-organ failure requiring mechanical ventilation and renal replacement therapy. The current outbreak has centered in West Africa and affected over 15,000 individuals. EVD is transmitted by direct contact with blood or other infectious bodily fluid, and as such, numerous heath care workers caring for patients with EVD have become infected. During the current outbreak, a number of patients have received advanced supportive care for EVD in Europe and North America and therefore survived. Now, many hospitals in Europe and North America are planning to accept care for patients with EVD. In this review, we discussed the key issues related to the planning and delivery of advanced supportive care in patients with EVD with a focus on the factors necessary to provide renal replacement therapy (RRT). Since success in the treatment of patients with EVD rests on both patient outcome and prevention of transmission of disease to health care workers, we extensively discussed the modes of Ebola virus transmission and recommended protocols to protect health care workers. Experience now indicates that with appropriate planning and protocols, it is possible to successfully treat EVD patients with advanced supportive care (mechanical ventilation and RRT) while avoiding transmission to health care providers. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=371530.


Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1).
Polymorphisms within the ICAM1 structural gene have been shown to influence circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) but their relation to atherosclerosis has not been clearly established. We sought to determine whether ICAM1 SNPs are associated with circulating sICAM-1 concentration, coronary artery calcium (CAC), and common and internal carotid intima medial thickness (IMT). 3550 black and white Coronary Artery Risk Development in Young Adults (CARDIA) Study subjects who participated in the year 15 and/or 20 examinations and were part of the Young Adult Longitudinal Study of Antioxidants (YALTA) ancillary study were included in this analysis. In whites, rs5498 was significantly associated with sICAM-1 (p<0.001) and each G-allele of rs5498 was associated with 5% higher sICAM-1 concentration. In blacks, each C-allele of rs5490 was associated with 6% higher sICAM-1 level; this SNP was in strong linkage disequilibrium with rs5491, a functional variant. Subclinical measurements of atherosclerosis in either year 15 or year 20 were not significantly related to ICAM1 SNPs. In CARDIA, ICAM1 DNA segment variants were associated with sICAM-1 protein level including the novel finding that levels differ by the functional variant rs5491. However, ICAM1 SNPs were not strongly related to either IMT or CAC. Our findings in CARDIA suggest that ICAM1 variants are not major early contributors to subclinical atherosclerosis.


Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.
Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms.


Twenty-year remission of rheumatoid arthritis in 2 patients after allogeneic bone marrow transplant.
We describe 21 and 19 year followup of 2 patients with severe rheumatoid arthritis (RA) who in 1984 and 1986 underwent allogeneic bone marrow transplantation (BMT) after full myeloablative conditioning, for therapy-induced aplastic anemia. Regarding the arthritis, both patients are well, taking no medications, and free of signs or symptoms of active RA. One patient is in excellent health overall, while the other has coronary artery disease and chronic obstructive pulmonary disease attributable to smoking. We suggest that allogeneic BMT may be a curative treatment for severe RA.


Dual-Signal Microbial Biosensor for the Detection of Dopamine without Inference from Other Catecholamine Neurotransmitters.
Dopamine, one of catecholamine neurotransmitters, plays an important role in many brain functions and behavioral responses. In this study, we developed a novel dual-signal whole-cell biosensor for the detection of dopamine through the generation of red fluorescent proteins and 6-decarboxylated betaxanthin pigments. The proposed system responses specifically to dopamine with a detection limit of 1.43 μM. Furthermore, a combination of dual output signals makes it possible to reduce the interference from other catecholamine neurotransmitters, including L-DOPA, epinephrine, and norepinephrine.


Predictor factors for recurrence in atypical meningiomas.
Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS). Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors. The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm³ had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion. AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume ≥26.4 cm³, Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.


Stacked Bt maize and arthropod predators: exposure to insecticidal Cry proteins and potential hazards.
Genetically engineered (GE) crops with stacked insecticidal traits expose arthropods to multiple Cry proteins from Bacillus thuringiensis (Bt). One concern is that the different Cry proteins may interact and lead to unexpected adverse effects on non-target species. Bi- and tri-trophic experiments with SmartStax maize, herbivorous spider mites (Tetranychus urticae), aphids (Rhopalosiphum padi), predatory spiders (Phylloneta impressa), ladybeetles (Harmonia axyridis) and lacewings (Chrysoperla carnea) were conducted. Cry1A.105, Cry1F, Cry3Bb1 and Cry34Ab1 moved in a similar pattern through the arthropod food chain. By contrast, Cry2Ab2 had highest concentrations in maize leaves, but lowest in pollen, and lowest acquisition rates by herbivores and predators. While spider mites contained Cry protein concentrations exceeding the values in leaves (except Cry2Ab2), aphids contained only traces of some Cry protein. Predators contained lower concentrations than their food. Among the different predators, ladybeetle larvae showed higher concentrations than lacewing larvae and juvenile spiders. Acute effects of SmartStax maize on predator survival, development and weight were not observed. The study thus provides evidence that the different Cry proteins do not interact in a way that poses a risk to the investigated non-target species under controlled laboratory conditions.


Theorists and clinicians have long noted the need for idiographic (i.e., individual-level) designs within clinical psychology. Results from idiographic work may provide a possible resolution of the therapist's dilemma-the problem of treating an individual using information gathered via group-level research. Due to advances in data collection and time series methodology, there has been increasing interest in using idiographic designs to answer clinical questions. Although time series methods have been well-studied outside the field of clinical psychology, there is limited direction on how clinicians can use such models to inform their clinical practice. In this primer, we collate decades of published and word-of-mouth information on idiographic designs, measurement, and modeling. We aim to provide an initial guide on the theoretical and practical considerations that we urge interested clinicians to consider before conducting idiographic work of their own.


Oral testosterone administration detected by testosterone glucuronidation measured in blood spots dried on filter paper.
Blood sampling is not a common practice for sports drug testing. Our aim was to investigate whether dried blood spots on filter paper could be an alternative to plasma samples for monitoring steroid profiles in dope testing. We collected dried blood spots and plasma from six healthy Caucasian subjects after an oral 120-mg dose of testosterone undecanoate (TU). Nonconjugated testosterone, testosterone glucuronide (TG), androsterone glucuronide (AG), and etiocholanolone glucuronide (EtG) were measured by gas chromatography-mass spectrometry in both matrices. 17alpha-Hydroxyprogesterone (17alphaOHP) and luteinizing hormone (LH) also were measured in the plasma samples. For comparison, similar measurements were done on samples obtained from the same subjects given 25 mg of testosterone propionate (TP) plus 110 mg of testosterone enanthate (TE) intramuscularly after a wash-out period. After oral TU intake, TG, AG, and EtG increased sharply, whereas nonconjugated testosterone did not change significantly. Results on dried blood spots correlated well with those on plasma. The TG/testosterone ratio in blood or plasma was verified to be a sensitive and specific marker (significantly increased for up to 8 h after intake; P <0.05) for oral TU intake but not for intramuscular administration of TP plus TE. Little suppression of plasma LH and 17alphaOHP was observed after a single oral dose of TU. One subject did not show a significant increase of blood TG after oral TU intake. The measurement of glucuronide conjugates in blood and plasma samples is relevant for sports drug testing when analyzing the steroid profile. Dried blood spots collected on filter paper are a suitable alternative to plasma for detecting testosterone abuse.


Ultra-low oxygen, liquid sample cell for in situ synchrotron-based small-wide angle scattering (SAXS-WAXS).
Here, we report the design and successful implementation of an ultra-low oxygen sample cell for use on the SAXS-WAXS (small-wide angle x-ray scattering) beamline I22 at DIAMOND. The rigorous exclusion of oxygen is found to require double jacketing with purge gas throughout the entire system, pipework, pumps, and the sample cell itself. This particularly includes a "double-window" arrangement at the sample location to accommodate the very tight geometrical restrictions of the sample position. The in situ cell design also requires the additional complexity of heating the sample/solution and real-time electrochemical measurements. We demonstrate the successful implementation of this arrangement with real-time in situ characterization of an iron foil corrosion evolving under the "sweet-scale environment," very anoxic conditions common, in particular, commercial situations. The formation of iron carbonate, siderite, rather than iron oxide, indicates that our system is oxygen free down very low levels (<35 ppb at 80 °C).


Nitric oxide-synthesizing perivascular nerves in the rat middle cerebral artery.
Although perivascular nerves containing nitric oxide synthase (NOS) have been anatomically described for rat cerebral arteries, a dilator function for these nerves has eluded investigators when using isolated vessels. Rat middle cerebral arteries (MCAs) were isolated, pressurized, and electrically stimulated. The resting diameter of the MCAs after pressurization was 233 +/- 4 microns (n = 17) in one study. The MCAs showed a frequency-dependent dilation when stimulated. Maximum dilation (25-30% increase in diameter) occurred at a frequency of 8-16 Hz. Removal of endothelium or glibenclamide (10(-5) M), a blocker of ATP-sensitive potassium channels, had no effect on the dilations. The dilations were completely blocked with NG-nitro-L-arginine methyl ester (L-NAME) (10(-5) M), a general NOS inhibitor, and cold storage (24 h). The inhibition by L-NAME could be reversed by the addition of 10(-8) M L-arginine, the active precursor of NOS. Furthermore, 7-nitroindazole (10(-4) M), an inhibitor specific for the neuronal isoform of NOS, reduced the dilations by 43% (P < 0.05). Transections of nerve bundles originating from the sphenopalatine ganglia at the ethmoidal foramen blocked the dilations produced by electrical stimulations. We conclude that rat cerebral arteries have functionally intact perivascular nerves that dilate by releasing nitric oxide.


Differences in the proliferation trend of 'Microsporidium' sp. PL03 in Culex pipiens and C. torrentium larvae.
Our study aimed to examine whether there are differences in the proliferation trend of microsporidia in mosquito larvae of the same genus (Culex spp.). DNA-barcoding and quantitative analyses were used to determine microsporidian rDNA copies in 'early' (L1 + L2) and 'late' (L3 + L4) Culex larvae in a natural population. In the study area, C. pipiens and C. torrentium larvae were infected by 'Microsporidium' sp. PL03 at similar levels. Infection by this microsporidian species probably elicits a notable immune response in C. pipiens, whereas in C. torrentium, it may evade or suppress the host immune response.


Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane.
The intracellular location at which the G protein of vesicular stomatitis virus accumulated when transport was blocked at 20 degrees C has been studied by biochemical, cytochemical, and immunocytochemical methods. Our results indicated that the viral G protein was blocked in that cisterna of the Golgi stack which stained for acid phosphatase. At 20 degrees C this trans cisterna became structurally altered by the accumulation of G protein. This alteration was characterized by extensive areas of membrane buds which were covered by a cytoplasmic coat. These coated structures were of two kinds--those that labeled with anti-clathrin antibodies and those that did not. The clathrin-coated pits consistently did not label with anti-G antibodies. Upon warming infected cells to 32 degrees C, G protein appeared on the surface within minutes. Concomitantly, the trans cisterna lost its characteristic structural organization. Double-labeling experiments were performed in which G protein localization was combined with staining for horseradish peroxidase, which had been taken up from the extracellular medium by endocytosis. The results suggest that the trans cisterna was distinct from the endosome compartment and that the latter was not an obligatory station in the route taken by G protein to the cell surface.


Advantage of the Mark-III FEL for biophysical research and biomedical applications.
Although 6.45 micro m is not the strongest absorption band of biological tissues in the mid-infrared, a Mark-III free-electron laser (FEL) tuned to this wavelength can efficiently ablate tissue while minimizing collateral damage. A model has previously been presented that explains this wavelength dependence as a competition between two dynamic processes--explosive vaporization of saline and denaturation of structural proteins. Here it is shown that this model predicts a 'sweet-spot' for each wavelength, i.e. a region of parameter space (incident intensity and pulse width) in which explosive vaporization is preceded by substantial protein denaturation. This sweet-spot is much larger for wavelengths where protein is the dominant chromophore. At other wavelengths, collateral damage may be minimized within the sweet-spot, but the maximum intensities and pulse widths in these regions are insufficient to remove tissue at surgically relevant rates.


Selective expression of insulin-like growth factor II in the songbird brain.
Neuronal replacement occurs in the forebrain of juvenile and adult songbirds. To address the molecular processes that govern this replacement, we cloned the zebra finch insulin-like growth factor II (IGF-II) cDNA, a factor known to regulate neuronal development and survival in other systems, and examined its expression pattern by in situ hybridization and immunocytochemistry in juvenile and adult songbird brains. The highest levels of IGF-II mRNA expression occurred in three nuclei of the song system: in the high vocal center (HVC), in the medial magnocellular nucleus of the neostriatum (mMAN), which projects to HVC, and to a lesser extent in the robust nucleus of the archistriatum (RA), which receives projections from HVC. IGF-II mRNA expression was developmentally regulated in zebra finches. In canary HVC, monthly changes in IGF-II mRNA expression covaried with previously reported monthly differences in neuron incorporation. Combining retrograde tracers with in situ hybridization and immunocytochemistry, we determined that the HVC neurons that project to area X synthesize the IGF-II mRNA, whereas the adjacent RA-projecting neurons accumulate the IGF-II peptide. Our findings raise the possibility that within HVC IGF-II acts as a paracrine signal between nonreplaceable area X-projecting neurons and replaceable RA-projecting neurons, a mode of action that is compatible with the involvement of IGF-II with the replacement of neurons. Additional roles for IGF-II expression in songbird brain are likely, because expression also occurs in some brain areas outside the song system, among them the cerebellar Purkinje cells in which neurogenesis is not known to occur.


Place, health and dis/advantage: A sociomaterial analysis.
The substantial literature on interactions between places/spaces and well-being/health often differentiate between physical and social aspects of geographical location. This paper sidesteps this dualism, instead considering places as sociomaterial assemblages of human and non-human materialities. It uses this posthuman and 'new materialist' perspective to explore how place-assemblages affect human capacities, in terms of both health and social dis/advantage. Based on secondary analysis of interview data on human/place interactions, it analyses the physical, sociocultural, psychological and emotional effects of place-assemblages, assessing how these produce opportunities for, and constraints upon human bodies. It than assesses how these emergent capacities affect both social dis/advantage and well-being. This analysis of how place-assemblages contribute positively or negatively to health and dis/advantage offers possibilities for further research and for social and public health policy.


Motivational priming as a strategy for maximising exercise outcomes: effects on exercise goals and engagement.
Using a scrambled sentence priming protocol, the first aim of this study was to investigate whether differences in novel exercise-related goals existed between participants primed with motivational or non-motivational material (i.e. autonomous, controlled or neutral primes). The second aim was to explore whether an indirect effect was present between priming condition and the goal-related exercise sessions that individuals performed over the week following administration of the prime. No effects were observed across priming conditions with respect to subjective vitality, goal concordance and the frequency with which participants planned to exercise. However, autonomy-primed individuals set goals for their exercise sessions that were significantly longer in intended duration (M = 57.72 min, SD = 37.42) than those set by their counterparts in both the controlled-prime condition (M = 44.12 min, SD = 27.78) and the neutral-prime condition (M = 37.10 min, SD = 20.47). Bootstrapped analyses also revealed a significant indirect relationship between prime and exercise behaviour, with the autonomy prime predicting longer goal-based exercise sessions, via the effect on the duration of participants' intended exercise sessions. These findings highlight the potential influence that priming autonomous motivation may have on individuals' exercise aspirations, as well as the way in which primes may indirectly shape exercise engagement.