Meditation, melatonin and breast/prostate cancer: hypothesis and preliminary data.
The objective of this study was to test the hypothesis that the regular practice of mindfulness meditation is associated with increased physiological levels of melatonin. Melatonin may be related to a variety of biologic functions important in maintaining health and preventing disease, including breast and prostate cancer. Previous studies have shown melatonin production is photosensitive and we suggest here that it also may be psychosensitive. A cross-sectional study of 12-hour (20:00-08:00) urinary 6-sulphatoxymelatonin was conducted from which we analyzed data from 8 women who regularly meditate (RM) and 8 women who do not meditate (NM). All samples were collected in the homes of study participants. Volunteers were recruited to provide 12-hour overnight samples of urine. All subjects collected the samples on one night during the same 1-week period. There was no explicit intervention. However, all RM were either graduates of, or teachers in, the University of Massachusetts Stress Reduction and Relaxation Program. The main outcome measure was the total excretion of urinary 6-sulphatoxymelatonin. Multiple linear regression (Proc GLM in SAS) was performed to test the effect of meditation (RM vs NM) on 6-sulphatoxymelatonin. The results of the study were that after controlling for the non-significant effect of menstrual period interval, we found an effect of meditation group (RM vs NM: b = 1.983; F = 6.78; p = 0.02) and age (for each integer year: b = 0.169; F = 8.41; p = 0.01). The conclusion is that study results are consistent with our hypothesis and indicate that melatonin might be a useful parameter in testing similar psycho-social interventions.(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides.
Ganglioside GM3 inhibits epidermal growth factor (EGF)-dependent cell proliferation in a variety of cell lines. Both in vitro and in vivo, this glycosphingolipid inhibits the kinase activity of the EGF receptor (EGFR). Furthermore, membrane preparations containing EGFR can bind to GM3-coated surfaces. These data suggest that GM3 may interact directly with the EGFR. In this study, the interaction of gangliosides with the extracellular domain (ECD) of the EGFR was investigated. The purified human recombinant ECD from insect cells bound directly to ganglioside GM3. The ganglioside interaction site appears to be distinct from the EGF-binding site. In agreement with previous reports on the effects of specific gangliosides on EGFR kinase activity, the ECD preferentially interacted with GM3. The order of relative binding of other gangliosides investigated was as follows: GM3 GM2, GD3, GM4 > GM1, GD1a, GD1b, GT1b, GD2, GQ1b > lactosylceramide. These data suggest that NeuAc-lactose is essential for binding and that any sugar substitution reduces binding. In agreement with the specificity of soluble ECD binding to gangliosides, GM3 specifically inhibited EGFR autophosphorylation. Identification of a ganglioside interaction site on the ECD of the EGFR is consistent with the hypothesis that endogenous GM3 may function as a direct modulator of EGFR activity.


Elucidation of the O-antigen structure of Escherichia coli O63.
The structure of the O-antigen polysaccharide (PS) from the Shiga-toxin producing Escherichia coli O63 has been elucidated using a combination of bioinformatics, component analyses and NMR spectroscopy. The O-antigen is comprised of tetrasaccharide repeating units with the following structure: →2)-β-d-Quip3N(d-allo-ThrAc)-(1→2)-β-d-Ribf-(1→4)-β-d-Galp-(1→3)-α-d-GlcpNAc-(1→ in which the N-acetylated d-allo-threonine is amide-linked to position 3 of the 3-amino-3-deoxy-d-Quip sugar residue. The presence of a predicted flippase and polymerase encoded in the O63 gene cluster is consistent with the Wzx/Wzy biosynthetic pathway and consequently the biological repeating unit has likely an N-acetyl-d-glucosamine residue at its reducing end. A bioinformatics approach based on predictive glycosyltransferase function present in ECODAB (E. coli O-antigen database) suggested the structural element β-d-Galp-(1→3)-d-GlcpNAc in the O-antigen. Notably, multiple gene sequence alignment of fdtA and qdtA from E. coli to that in E. coli O63 resulted in discrimination between the two, confirmation of the latter in E. coli O63, and consequently, together with qdtB, biosynthesis of dTDP-d-Quip3N. The E. coli O63 O-antigen polysaccharide differs in two aspects from that of E. coli O114 where the latter carries instead an l-serine residue, and the glycosidic linkage positions to and from the Quip3N residue are both changed. The structural characterization of the O63 antigen repeat supports the predicted functional assignment of the O-antigen cluster genes.


Holdaway's analysis of the nose prominence of an adult Nigerian population.
Facial beauty is a function of harmonious balance among all parts of the face, and the nose plays a dominant role in this because of its location exactly in the middle of the face. Therefore, an evaluation of the nasal form and its position relative to other facial structures should play an important part in the assessment of patients before orthognathic surgery, rhinoplasty or orthodontics. The aim was to establish normative values for the nose prominence of an adult Nigerian population using Holdaway's soft tissue cephalometric analysis. Lateral cephalometric radiographs of 100 adults aged 18-25 years, with normal occlusion and a harmonious facial appearance were analyzed. The nose prominence was assessed using Holdaway's analysis. Twenty radiographs randomly selected, were retraced to assess for errors. Data analysis included descriptive statistics, Student's t-tests and analysis of variance using the Statistical Package for Social Sciences. The mean value recorded for the nose prominence of the study population was 3.49 mm (standard deviation [SD], 3.26 mm), with a range of -5.0 mm to 15.0 mm. Mean values obtained for females were 3.73 mm (SD, 2.88 mm) and males 3.19 mm (SD, 3.70 mm). No statistically significant gender difference was observed (P>0.05). In addition, no significant difference was observed between the nose prominence values recorded for different age-groups (P>0.05). Normative values were established for the nose prominence of an adult Nigerian population. The values obtained for Nigerians in this study are comparatively lower than that reported for other populations. These values would aid in treatment planning for orthognathic surgery, rhinoplasty and orthodontics in Nigerians.


Boolean networks using the chi-square test for inferring large-scale gene regulatory networks.
Boolean network (BN) modeling is a commonly used method for constructing gene regulatory networks from time series microarray data. However, its major drawback is that its computation time is very high or often impractical to construct large-scale gene networks. We propose a variable selection method that are not only reduces BN computation times significantly but also obtains optimal network constructions by using chi-square statistics for testing the independence in contingency tables. Both the computation time and accuracy of the network structures estimated by the proposed method are compared with those of the original BN methods on simulated and real yeast cell cycle microarray gene expression data sets. Our results reveal that the proposed chi-square testing (CST)-based BN method significantly improves the computation time, while its ability to identify all the true network mechanisms was effectively the same as that of full-search BN methods. The proposed BN algorithm is approximately 70.8 and 7.6 times faster than the original BN algorithm when the error sizes of the Best-Fit Extension problem are 0 and 1, respectively. Further, the false positive error rate of the proposed CST-based BN algorithm tends to be less than that of the original BN. The CST-based BN method dramatically improves the computation time of the original BN algorithm. Therefore, it can efficiently infer large-scale gene regulatory network mechanisms.


Apoptosis-related protein expression during pre- and post-natal testicular development after administration of glucocorticoid in utero in the sheep.
Pre-natal glucocorticoids are used in women at risk of preterm delivery to induce foetal lung maturation. However, glucocorticoids can produce negative outcomes for other tissues such as the reproductive system. We therefore tested the effects of pre-natal betamethasone on testicular morphology and apoptotic protein immune expression during pre- and post-natal development. Pregnant ewes (n = 42) bearing singleton male foetuses were randomly allocated to receive intramuscular injections of saline or betamethasone (0. 5 mg/kg) at 104, 111 and 118 days of gestation (DG). Testes were collected at 121 and 132 DG, and at 45 and 90 post-natal days (PD) and subjected to morphometric analysis (volume densities of sex cords and interstitial tissues; sex cord diameter). Immunohistochemistry (% stained area) was used to assess active caspase-3, Bax, Bcl-2 and cell-cycle proteins (PCNA). Compared with control values, betamethasone treatment decreased sex cord diameter at 121 DG, 45 and 90 PD, and sex cord volume at 90 PD. Active caspase-3 was decreased by betamethasone at 121 DG and 90 PD, but Bax was increased in all betamethasone groups. Bcl-2 and PCNA decreased in the betamethasone groups at 121 DG and 45 PD, but increased at 132 DG and 90 PD. We conclude that high levels of pre-natally administered glucocorticoid reduce foetal testicular development, perhaps via changes in the balance between pro- and anti-apoptotic proteins and cell-cycle proteins. These outcomes could compromise the future spermatogenic potential of male offspring.


Ophthalmic magnetic resonance imaging at 7 T using a 6-channel transceiver radiofrequency coil array in healthy subjects and patients with intraocular masses.
This study was designed to examine the feasibility of ophthalmic magnetic resonance imaging (MRI) at 7 T using a local 6-channel transmit/receive radiofrequency (RF) coil array in healthy volunteers and patients with intraocular masses. A novel 6-element transceiver RF coil array that makes uses of loop elements and that is customized for eye imaging at 7 T is proposed. Considerations influencing the RF coil design and the characteristics of the proposed RF coil array are presented. Numerical electromagnetic field simulations were conducted to enhance the RF coil characteristics. Specific absorption rate simulations and a thorough assessment of RF power deposition were performed to meet the safety requirements. Phantom experiments were carried out to validate the electromagnetic field simulations and to assess the real performance of the proposed transceiver array. Certified approval for clinical studies was provided by a local notified body before the in vivo studies. The suitability of the RF coil to image the human eye, optical nerve, and orbit was examined in an in vivo feasibility study including (a) 3-dimensional (3D) gradient echo (GRE) imaging, (b) inversion recovery 3D GRE imaging, and (c) 2D T2-weighted fast spin-echo imaging. For this purpose, healthy adult volunteers (n = 17; mean age, 34 ± 11 years) and patients with intraocular masses (uveal melanoma, n = 5; mean age, 57 ± 6 years) were investigated. All subjects tolerated all examinations well with no relevant adverse events. The 6-channel coil array supports high-resolution 3D GRE imaging with a spatial resolution as good as 0.2 × 0.2 × 1.0 mm, which facilitates the depiction of anatomical details of the eye. Rather, uniform signal intensity across the eye was found. A mean signal-to-noise ratio of approximately 35 was found for the lens, whereas the vitreous humor showed a signal-to-noise ratio of approximately 30. The lens-vitreous humor contrast-to-noise ratio was 8, which allows good differentiation between the lens and the vitreous compartment. Inversion recovery prepared 3D GRE imaging using a spatial resolution of 0.4 × 0.4 × 1.0 mm was found to be feasible. T2-weighted 2D fast spin-echo imaging with the proposed RF coil afforded a spatial resolution of 0.25 × 0.25 × 0.7 mm. This work provides valuable information on the feasibility of ophthalmic MRI at 7 T using a dedicated 6-channel transceiver coil array that supports the acquisition of high-contrast, high-spatial resolution images in healthy volunteers and patients with intraocular masses. The results underscore the challenges of ocular imaging at 7 T and demonstrate that these issues can be offset by using tailored RF coil hardware. The benefits of such improvements would be in positive alignment with explorations that are designed to examine the potential of MRI for the assessment of spatial arrangements of the eye segments and their masses with the ultimate goal to provide imaging means for guiding treatment decisions in ophthalmological diseases.


Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer.
Radix Rehmanniae (RR) has a very long history of usage in traditional Chinese medicine and is usually one of the principal herb found in many herbal formulae used in diabetic foot ulcer. RR aqueous extract was investigated for its wound healing effects in a diabetic foot ulcer rat model and its detailed mechanism of actions. A previously established diabetic foot ulcer rat model was used to assess the effect of RR extract on wound area reduction, tissue regeneration and angiogenesis. Carrageenan-induced inflammation rat model was used for inflammation study; and diabetic control was evaluated using a neonatal streptozotocin-induced diabetic rat model. In the RR treated group, a trend of reduction of the wound area was observed from days 8 to 18 and a significant difference (as compared with control group) was found on day 8. The ulcer healing effect of RR extract was further supported by better developed scars and epithelialization as well as good formation of capillaries with enhanced VEGF expression. Carrageenan-induced inflammation was also significantly alleviated with RR extract. Our results demonstrated for the first time that Radix Rehmanniae was effective in promoting diabetic foot ulcer healing in rats through the processes of tissue regeneration, angiogenesis and inflammation control, but not glycemia control. The present study provided scientific basis to support the traditional use of Radix Rehmanniae in diabetic foot ulcer.


Effects of self-efficacy, affectivity and collective efficacy on nursing performance of hospital nurses.
This paper is a report of a study conducted to examine the influence of self-efficacy and affectivity (individual-level variables) and collective efficacy (group-level variable) on nursing performance among hospital nurses. Previous studies of nursing performance, which have focused on individual factor outcomes, have shown limitations. Due to the heavy focus on the analysis of single-level performances, the influence of organizational contextual factors on nursing performance has rarely been studied. Hence, for a better understanding of nurses' professional development and effective functioning in hospitals, there is a need to study the effects of organizational characteristics as well as individual characteristics on nursing performance. A descriptive-correlational design was used with a convenience sample of 1996 nurses selected from 182 nursing units in 28 hospitals in six metropolitan cities and seven provinces in Korea. Data were collected in 2006 using self-administered questionnaires, which were analysed with using descriptive statistics, Pearson correlation coefficients and multilevel analysis. Individual-level variables, including job position, years of experience, employment status, self-efficacy and positive affectivity were positively related to nursing performance. Collective efficacy and the number of in-service meetings within units were statistically significant group-level variables. Group-level variables reduced the error variances in nursing performance. Understanding the effects of group-level variables on nursing performance improves performance management approaches in hospitals.


Optimal management of gastric cancer: results from an international RAND/UCLA expert panel.
Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.


Origins and recombination of the bacterial-sized multichromosomal mitochondrial genome of cucumber.
Members of the flowering plant family Cucurbitaceae harbor the largest known mitochondrial genomes. Here, we report the 1685-kb mitochondrial genome of cucumber (Cucumis sativus). We help solve a 30-year mystery about the origins of its large size by showing that it mainly reflects the proliferation of dispersed repeats, expansions of existing introns, and the acquisition of sequences from diverse sources, including the cucumber nuclear and chloroplast genomes, viruses, and bacteria. The cucumber genome has a novel structure for plant mitochondria, mapping as three entirely or largely autonomous circular chromosomes (lengths 1556, 84, and 45 kb) that vary in relative abundance over a twofold range. These properties suggest that the three chromosomes replicate independently of one another. The two smaller chromosomes are devoid of known functional genes but nonetheless contain diagnostic mitochondrial features. Paired-end sequencing conflicts reveal differences in recombination dynamics among chromosomes, for which an explanatory model is developed, as well as a large pool of low-frequency genome conformations, many of which may result from asymmetric recombination across intermediate-sized and sometimes highly divergent repeats. These findings highlight the promise of genome sequencing for elucidating the recombinational dynamics of plant mitochondrial genomes.


Low response rate schools in surveys of adolescent risk taking behaviours: possible biases, possible solutions.
To examine the potential biases introduced when students in low response rate schools are dropped from classroom based surveys of adolescent risk taking behaviour. Self administered confidential surveys were conducted in classrooms, with follow up visits to each school to survey students absent during the initial survey administration. Data on students in schools that achieved a 70% response rate are compared with data on students in schools that did not achieve this level of response. New York City, United States. 1854 10th graders in 13 public (state supported) high schools. Students in schools with low response rates resulting from high rates of absenteeism have different demographic characteristics and engage in more risk behaviours than students in schools with low absenteeism and high response rates. Excluding schools with low rates of response can have an effect on estimates of risk behaviour, even after data are weighted for individual absences. The potential for bias is greatest when, in sampling schools, the proportion of schools with low response rates is large, and when such schools represent a large share of the students in the area under study. Excluding schools with poor response rates from survey samples using a classroom based approach does not improve, and may, under some circumstances, underestimate risky behaviour among adolescent populations.


Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis.
For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA.


Identification of a cell-surface antigen (LEA.135) associated with favorable prognosis in human breast cancer.
The present study was undertaken with a rationale that loss of certain "normal tissue" antigens might have prognostic significance, reflecting inactivation of the corresponding genes during neoplastic progression. An attempt was made to identify such antigens by means of generating monoclonal antibodies using a tolerization/immunization procedure. A monoclonal antibody generated by immunization of BALB/c mice with normal breast tissue extract, following prior tolerization with mammary carcinoma cells, recognized a cell-surface glycoprotein, luminal epithelial antigen, with an apparent molecular weight of 135,000 (LEA.135). The pattern of expression on LEA.135 was determined by immunohistochemical-staining techniques on frozen and formalin-fixed and paraffin-embedded tissue sections. LEA.135 was demonstrable on the apical plasma membrane of normal and nonneoplastic epithelial cells in breast and other tissues. Studies have shown that LEA.135 is distinct from receptors for epidermal growth factor and from known antigens associated with epithelial cells, including the family of keratins. In a retrospective study, with a follow-up ranging from 5 to 15 years, patients whose breast tumor cells expressed LEA.135 had a superior overall survival rate (78 0.139% at > 5 years; P = 0.025). Furthermore, in patients with histologically poorly differentiated tumors, LEA.135-positive cases had a better prognosis (80 0.179% at > 5 years; P = 0.013) compared with LEA.135-negative cases. In addition, in patients with aneuploid tumors, LEA.135-positive cases again showed an improved survival (90 0.001% at > 5 years; P = 0.039) compared with those that were with LEA.135 negative. The results suggest that the expression of LEA.135 provides a useful indication of clinical outcome in patients with breast carcinomas.


Nurse home visitors' perceptions of mandatory reporting of intimate partner violence to law enforcement agencies.
In the United States, there is an ongoing debate about requiring health care professionals to report intimate partner violence (IPV) to law enforcement agencies. A comprehensive examination of the perspectives of those required to report abuse is critical, as their roles as mandated reporters often pose legal, practical, moral, and ethical questions. Even so, the perspective of health care professionals who are required to report is often overlooked and research is scarce on mandated reporters who work outside of clinical settings, such as nurses who engage in home visitation with clients. The purpose of this study was to examine nurse home visitors' perspectives regarding the mandatory reporting of IPV, specifically focusing on their attitudes toward reporting, perceived awareness of reporting requirements, and intended reporting behaviors. A web-based survey was administered to nurses in the Nurse-Family Partnership home visitation program across the United States. A total of 532 completed surveys were returned (response rate = 49%). In terms of support for reporting IPV, 40% of nurses indicated that they should "always" be required to report. Almost half of the sample indicated that they would report a case of IPV, yet less than one-third of participants were aware of a legal mandate. Attitudes and support toward reporting as well as the perception of a reporting requirement significantly predicted intention to report. Furthermore, 29% of participants did not know if they were required to report IPV perpetrated against their clients. Comprehensive information about mandatory reporting duties is needed for health care professionals in home visitation settings. The findings of the current study highlight the need to reduce variation among practitioners and establish consistent program practices that are grounded in the program's principals, supported by existing research, and compliant with existing state policies.


Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis.
This study tests the hypothesis that circulating mononuclear cells expressing osteocalcin (OCN) and bone alkaline phosphatase (BAP) are associated with distinct plaque tissue components in patients with early coronary atherosclerosis. Plaque characteristics implying vulnerability develop at the earliest stage of coronary atherosclerosis. Increasing evidence indicates that cells from the myeloid lineage might serve as important mediators of destabilization. Plaque burden and its components were assessed regarding their relationship to monocytes carrying both pro-inflammatory (CD14) and osteogenic surface markers OCN and BAP. Twenty-three patients with angiographically non-obstructive coronary artery disease underwent coronary endothelial function assessment and virtual histology-intravascular ultrasound of the left coronary artery. Plaque composition was characterized in the total segment (TS) and in the target lesion (TL) containing the highest amount of plaque burden. Blood samples were collected simultaneously from the aorta and the coronary sinus. Circulating cell counts were then identified from each sample and a gradient across the coronary circulation was determined. Circulating CD14+/BAP+/OCN+ monocytes correlate with the extent of necrotic core and calcification (r=0.53, p=0.010; r=0.55, p=0.006, respectively). Importantly, coronary retention of CD14+/OCN+ cells also correlates with the amount of necrotic core and calcification (r=0.61, p=0.003; r=0.61, p=0.003) respectively. Our study links CD14+/BAP+/OCN+ monocytes to the pathologic remodeling of the coronary circulation and therefore associates these cells with plaque destabilization in patients with early coronary atherosclerosis.


[Can HBsAg levels guide to differentiate inactive HBsAg carriers from HBeAg negative chronic B hepatitis?].
It is valuable to differentiate the inactive HBsAg carrier state from HBeAg negative chronic B hepatitis (CBH) which develops due to precore or core promoter region mutations in hepatitis B virus (HBV). The aim of this study was to investigate the role of HBsAg S/N (sample rate/index calibrator mean rate) levels in the differentiation of inactive HBsAg carriers from HBeAg negative CBH cases. A total of 134 HBsAg positive patients followed-up in Kocaeli University Medical Faculty hospital between June 2004-September 2005, were included to the study. The patients were classified into four groups according to their serological patterns (Group 1: HBeAg and HBV-DNA negative 34 cases with normal ALT levels; Group 2: HBeAg negative, anti-HBe positive, HBV-DNA >10(5) copies/ml, 36 cases with increased ALT levels; Group 3: HBeAg negative, anti-HBe positive, HBV-DNA 102-10(5) copies/ml, 32 cases with normal ALT levels; Group 4: HBeAg positive, HBV-DNA >10(5) copies/ml, 32 cases with increased ALT levels). The age and gender distributions of the groups were similar. HBV markers have been detected by microparticle enzyme immunoassay (AxSYM System, v3.0, Abbott Laboratories, USA), and viral load were investigated by real-time polymerase chain reaction (iCycler IQ, v3.0a, Bio Rad Laboratories, USA). As a result, the mean HBsAg S/N level in group 2 who were HBeAg negative with a viral load of >10(5) copies/ml, was found significantly higher than group 1 who were inactive HBsAg carriers (285.9+/-78.8 and 214.4+/-108.6, respectively; p<0.05). In contrast there was no statistically significant difference between group 1 (HBV-DNA negative) and group 3 (HBV-DNA <10(5) copies/mL) by means of mean HBsAg S/N levels (214.4+/-108.6 and 216.3+/-57.2, respectively; p>0.05). Although HBsAg levels seem to guide the differentiation of inactive HBsAg carriers from HBeAg negative CBH cases with high viral loads (>10(5) copies/ml), advanced studies are needed to clarify this relationship with the use of quantitative HBsAg measurements (IU/ml) in large patient groups and by performing mutation analysis.


Effects of the Intervention "Reflective STRENGTH-Giving Dialogues" for Older Adults Living with Long-Term Pain: A Pilot Study.
Long-term musculoskeletal pain is a major, often undertreated, disabling health problem among an increasing number of older adults. Reflective STRENGTH-giving dialogues (STRENGTH) may be a tool to support older adults living with long-term pain. The main aim of this pilot study was to investigate the immediate and longitudinal effect of the intervention STRENGTH on levels of pain, wellbeing, occurrence of depression symptoms, and sense of coherence (SOC) among community-dwelling older adults suffering from musculoskeletal pain compared to a control group. The study was semiexperimental with an intervention group and a control group. The effect of a single STRENGTH intervention was reported on the Numeric Rating Scale (NRS) regarding pain and wellbeing. To evaluate the longitudinal effect of STRENGTH, using the Brief Pain Inventory-Short Form (BPI-SF), the Geriatric Depression Scale-20 (GDS-20), SOC-13 at baseline (T1), and six months after the intervention/no intervention (T2), a total of 30 older adults, aged 72 to 97 years (Mdn 86 years), were included consecutively and fulfilled the intervention series (n = 18) or untreated controls (n = 12). The intervention with STRENGTH decreases pain (NRS 6 Mdn versus NRS 4 Mdn, p < 0.001) and increases wellbeing (NRS 7 Mdn versus NRS 8 Mdn, p < 0.001). After a six-month study period with STRENGTH, no longitudinal effect difference was found compared to baseline. Compared to the control group, there was an increasing trend between decreased pain level and increased SOC level for STRENGTH intervention. This pilot study supports STRENGTH's effect as a pain-alleviating model that provides a decrease in pain levels and an increase of wellbeing in older adults with long-term pain. STRENGTH dialogues could be a useful intervention to provide individually holistic care in older adults living with long-term pain.


Vectorial optical field generator for the creation of arbitrarily complex fields.
Generation of vectorial optical fields with complex spatial distribution in the cross section is of great interest in areas where exotic optical fields are desired, including particle manipulation, optical nanofabrication, beam shaping and optical imaging. In this work, a vectorial optical field generator capable of creating arbitrarily complex beam cross section is designed, built and tested. Based on two reflective phase-only liquid crystal spatial light modulators, this generator is capable of controlling all the parameters of the spatial distributions of an optical field, including the phase, amplitude and polarization (ellipticity and orientation) on a pixel-by-pixel basis. Various optical fields containing phase, amplitude and/or polarization modulations are successfully generated and tested using Stokes parameter measurement to demonstrate the capability and versatility of this optical field generator.


Cleavage and serum reactivity of the severe acute respiratory syndrome coronavirus spike protein.
Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. S protein could be cleaved by exogenous trypsin but not by coexpressed furin, suggesting that the protein is not normally processed during infection. Reactivity was evident by both flow cytometry and Western blot assays, but the pattern of reactivity varied according to assay and sequence of the antigen. The antibody response to SCoV S protein involves antibodies to both linear and conformational epitopes, with linear epitopes associated with the carboxyl domain and conformational epitopes associated with the amino terminal domain. Recombinant SCoV S protein appears to be a suitable antigen for the development of an efficient and sensitive diagnostic test for SARS, but our data suggest that assay format and choice of S antigen are important considerations.


Spurious claims for health-care products: an experimental approach to evaluating current UK legislation and its implementation.
The lay media, and especially the Internet, contain many misleading claims for health products which have previously been inadequately regulated by consumer law. This was an experimental interventional survey within a consumer health-care setting. Three health products were chosen on the basis of being widely available on the UK market and having no available evidence of effectiveness. Twelve volunteers submitted 39 complaints to Consumer Direct (UK portal for the regulator Trading Standards) regarding false health claims, and 36 complaints were followed up for a maximum of 4.8 months. The mean time from submission of complaints to Consumer Direct to acknowledgement by the relevant Trading Standards office was 13 days. There were no responses from Trading Standards for 22% of complaints. At the end of the study one supplier had amended their website following Trading Standards advice, but did not stop all health claims. Another stopped advertising their product on the Internet and the third continued the health claims unchanged. EU directive 2005/29/EC is largely ineffective in preventing misleading health claims for consumer products in the UK.


Fetal and neonatal iron deficiency causes volume loss and alters the neurochemical profile of the adult rat hippocampus.
Perinatal iron deficiency results in persistent hippocampus-based cognitive deficits in adulthood despite iron supplementation. The objective of the present study was to determine the long-term effects of perinatal iron deficiency and its treatment on hippocampal anatomy and neurochemistry in formerly iron-deficient young adult rats. Perinatal iron deficiency was induced using a low-iron diet during gestation and the first postnatal week in male rats. Hippocampal size was determined using volumetric magnetic resonance imaging at 8 weeks of age. Hippocampal neurochemical profile, consisting of 17 metabolites indexing neuronal and glial integrity, energy reserves, amino acids, and myelination, was quantified using high-field in vivo (1)H NMR spectroscopy at 9.4T (N = 11) and compared with iron-sufficient control group (N = 10). The brain iron concentration was 56% lower than the control group at 7 days of age in the iron-deficient group, but had recovered completely at 8 weeks. The cross-sectional area of the hippocampus was decreased by 12% in the formerly iron-deficient group (P = 0.0002). The hippocampal neurochemical profile was altered: relative to the control group, creatine, lactate, N-acetylaspartylglutamate, and taurine concentrations were 6-29% lower, and glutamine concentration 18% higher in the formerly iron-deficient hippocampus (P < 0.05). Perinatal iron deficiency was associated with reduced hippocampal size and altered neurochemistry in adulthood, despite correction of brain iron deficiency. The neurochemical changes suggest suppressed energy metabolism, neuronal activity, and plasticity in the formerly iron-deficient hippocampus. These anatomic and neurochemical changes are consistent with previous structural and behavioral studies demonstrating long-term hippocampal dysfunction following perinatal iron deficiency.


Formation and stability of synaptic receptor domains.
Neurotransmitter receptor molecules, concentrated in postsynaptic domains along with scaffold and a number of other molecules, are key regulators of signal transmission across synapses. Combining experiment and theory, we develop a quantitative description of synaptic receptor domains in terms of a reaction-diffusion model. We show that interactions between only receptors and scaffolds, together with the rapid diffusion of receptors on the cell membrane, are sufficient for the formation and stable characteristic size of synaptic receptor domains. Our work reconciles long-term stability of synaptic receptor domains with rapid turnover and diffusion of individual receptors, and suggests novel mechanisms for a form of short-term, postsynaptic plasticity.


The Feedback Tango: An Integrative Review and Analysis of the Content of the Teacher-Learner Feedback Exchange.
To conduct an integrative review and analysis of the literature on the content of feedback to learners in medical education. Following completion of a scoping review in 2016, the authors analyzed a subset of articles published through 2015 describing the analysis of feedback exchange content in various contexts: audiotapes, clinical examination, feedback cards, multisource feedback, videotapes, and written feedback. Two reviewers extracted data from these articles and identified common themes. Of the 51 included articles, about half (49%) were published since 2011. Most involved medical students (43%) or residents (43%). A leniency bias was noted in many (37%), as there was frequently reluctance to provide constructive feedback. More than one-quarter (29%) indicated the feedback was low in quality (e.g., too general, limited amount, no action plans). Some (16%) indicated faculty dominated conversations, did not use feedback forms appropriately, or provided inadequate feedback, even after training. Multiple feedback tools were used, with some articles (14%) describing varying degrees of use, completion, or legibility. Some articles (14%) noted the impact of the gender of the feedback provider or learner. The findings reveal that the exchange of feedback is troubled by low-quality feedback, leniency bias, faculty deficient in feedback competencies, challenges with multiple feedback tools, and gender impacts. Using the tango dance form as a metaphor for this dynamic partnership, the authors recommend ways to improve feedback for teachers and learners willing to partner with each other and engage in the complexities of the feedback exchange.


Elevated germline mutation rate in teenage fathers.
Men age and die, while cells in their germline are programmed to be immortal. To elucidate how germ cells maintain viable DNA despite increasing parental age, we analysed DNA from 24 097 parents and their children, from Europe, the Middle East and Africa. We chose repetitive microsatellite DNA that mutates (unlike point mutations) only as a result of cellular replication, providing us with a natural 'cell-cycle counter'. We observe, as expected, that the overall mutation rate for fathers is seven times higher than for mothers. Also as expected, mothers have a low and lifelong constant DNA mutation rate. Surprisingly, however, we discover that (i) teenage fathers already set out from a much higher mutation rate than teenage mothers (potentially equivalent to 77-196 male germline cell divisions by puberty); and (ii) ageing men maintain sperm DNA quality similar to that of teenagers, presumably by using fresh batches of stem cells known as 'A-dark spermatogonia'.


Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis.
Percutaneous closure of patent foramen ovale (PFO) has been shown to be superior to medical treatment alone for prevention of recurrent stroke after cryptogenic transient ischaemic attack or non-disabling stroke in patients aged 60 years or younger. The justification for trials in older patients with transient ischaemic attack or stroke depends on whether PFO is shown to be associated with cryptogenic events at older ages, for which existing evidence is conflicting, and on the population burden of PFO-associated events. Therefore, we did a population-based screening study using contrast-enhanced transcranial Doppler (bubble-TCD) to detect probable PFO as indicated by a right-to-left shunt (RLS); we also did a systematic review and meta-analysis to compare our results with previous studies. In this population-based study, nested in the Oxford Vascular Study (OXVASC), we established the prevalence of any RLS, and of large RLS (>20 microbubbles), in consecutive patients attending a rapid-access transient ischaemic attack and stroke clinic, or at 1-month follow-up after stroke unit admission, with transient ischaemic attack or non-disabling ischaemic stroke, comparing cryptogenic events with those of known cause (according to Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria). We stratified participants by age, and extrapolated data to the UK population. We also did a systematic review of published studies of PFO prevalence (using transthoracic or transoesophageal echocardiography or bubble-TCD) according to stroke subtype, which included older patients and reported age-specific results, and determined by meta-analysis (including the OXVASC data) the pooled odds ratio (95% CI) of finding PFO of any size in cryptogenic events compared with events of known cause, stratified by screening modality (transthoracic or transoesophageal echocardiography or bubble-TCD). The study protocol is registered with PROSPERO, number CRD42018087074. Among 572 consecutive patients with transient ischaemic attack or non-disabling stroke between Sept 1, 2014, and Oct 9, 2017 (439 [77%] patients aged >60 years, mean age 70·0 years [SD 13·7]), bubble-TCD was feasible in 523 patients (91%) of whom 397 were aged older than 60 years. Compared with those with transient ischaemic attack or stroke of known cause, patients with cryptogenic events had a higher prevalence of RLS overall (odds ratio [OR] 1·93, 95% CI 1·32-2·82; p=0·001), and in those aged older than 60 years (2·06, 1·32-3·23; p=0·001). When we pooled the OXVASC data with that from two previous smaller studies of bubble-TCD in patients aged 50 years or older, we found an association between RLS and cryptogenic events (OR 2·35, 95% CI 1·42-3·90; p=0·0009; pheterogeneity=0·15), which was consistent with the equivalent estimate from transoesophageal echocardiography studies (2·20, 1·15-4·22; p=0·02; pheterogeneity=0·02). No data on large RLS in patients with TOAST-defined cryptogenic events compared with other events were available from previous studies, but we found no evidence that the association was diminished in such cases. Of 41 patients with large RLS and cryptogenic transient ischaemic attack or non-disabling stroke in our study, 25 (61%) were aged older than 60 years, which extrapolates to 5951 patients per year in the UK (data from mid-2016). Bubble-TCD was feasible in most older patients with transient ischaemic attack or non-disabling stroke, the association of RLS with cryptogenic events remained at older ages, and the population burden of PFO-associated events is substantial. Randomised trials of PFO closure at older ages are required and should be feasible. National Institute for Health Research, Oxford Biomedical Research Centre, Wellcome Trust, and Wolfson Foundation.


The transcriptome of Nrf2-/- mice provides evidence for impaired cell cycle progression in the development of cigarette smoke-induced emphysematous changes.
Cigarette smoke (CS) imposes a strong oxidative burden on exposed tissues resulting in a severely disturbed oxidant/antioxidant balance, which in the context of chronic exposure is assumed to be a key contributor to CS-related diseases. Because of its emerging central role in orchestrating the general cellular antioxidant response, the pathway leading to the activation of the transcription factor Nrf2 has received mounting attention over the past decade in investigations aimed at elucidating CS-induced pathophysiological mechanisms. To comprehensively characterize the impact of Nrf2 in acute and subchronic smoking scenarios, Nrf2(-/-) mice and their wild-type (wt) ICR littermates were exposed to either ambient air (sham exposure) or one of three doses of CS for up to 5 months, with two postexposure endpoints of 1 and 13 days. The lungs of the mice were monitored for transcriptomic changes on a genome-wide level, which confirmed an impaired expression of antioxidant and phase 2-related genes in CS-exposed Nrf2(-/-) mice. Importantly, in comparison to wt mice, an attenuated cell cycle/mitotic response and intensified stress gene expression pattern were observed in exposed Nrf2(-/-) mice, which was paralleled by clear dose-dependent effects on alveolar destruction and impaired lung function. In contrast, the inflammation-related transcriptional response and scores for various bronchioalveolar inflammation parameters were qualitatively and quantitatively similar in CS-exposed mice of both genotypes. Taken together, these results confirm the protective nature of Nrf2 in oxidative stress scenarios and suggest that the enhanced emphysematous phenotype exhibited by CS-exposed Nrf2(-/-) mice is more likely caused by an imbalance in cell loss and regeneration than by increased inflammation.


Chromosomal Mapping and QTL Analysis of Resistance to Downy Mildew in Cucumis sativus.
Downy mildew of cucumber (Cucumis sativus), caused by Pseudoperonospora cubensis, is a major foliar disease worldwide. The cucumber inbred lines K8 (resistant to downy mildew) and K18 (susceptible) were used to study the inheritance of resistance to downy mildew. Chromosomal mapping of the resistance genes was completed to provide a theoretical basis for the resistance mechanisms and for marker assisted selection (MAS). Inoculation was used to test the level of resistance to P. cubensis in the F2 and F2:3 families derived from the cross K8 × K18. Simple sequence repeat (SSR) analysis, combined with bulked segregation analysis (BSA), was done with the DNA of F2 plants using 2,360 pairs of SSR primers. JoinMap Version 3.0 and MapInspect were used to construct SSR linkages and to verify the relationships between these SSR linkages and cucumber chromosomes. Quantitative trait locus (QTL) analysis of downy mildew resistance was done using MapQTL Version 4.0. Inheritance of resistance to downy mildew in K8 was quantitative. Five QTLs for resistance to downy mildew were detected: dm1.1, dm5.1, dm5.2, dm5.3, and dm6.1. The loci of dm1.1 and dm6.1 were on chromosomes 1 and 6, respectively. The loci of dm5.1, dm5.2, and dm5.3 were on chromosome 5, and were linked. Six linked SSR markers for these five QTLs were identified: SSR31116, SSR20705, SSR00772, SSR11012, SSR16882, and SSR16110. Six and four nucleotide binding site (NBS)-type resistance gene analogs (RGAs) were predicted in the region of dm5.2 and dm5.3, respectively. These results will be of benefit for fine-mapping the major QTLs for downy mildew resistance, and for MAS in cucumber.


Ancient microRNA profiles of a 14,300-year-old canid samples confirm taxonomic origin and give glimpses into tissue-specific gene regulation from the Pleistocene.
DNA sequencing is the current key technology for historic or ancient biological samples and has led to many exciting discoveries in the field of paleogenomics. However, functional insights into tissue identity, cellular composition or gene regulation cannot be gained from DNA. Recent analyses have shown that, under favorable conditions, RNA can also be sequenced from ancient samples, enabling studies at the transcriptomic and regulatory level. Analyzing ancient RNA data from a Pleistocene canid, we find hundreds of intact microRNAs that are taxonomically informative, show tissue-specificity and have functionally predictive characteristics. With an extraordinary age of 14,300 years, these microRNA sequences are by far the oldest ever reported. The authenticity of the sequences is further supported by a) the presence of canid / Caniformia-specific sequences that never evolved outside of this clade, b) tissue-specific expression patterns (cartilage, liver and muscle) that resemble those of modern dogs and c) RNA damage patterns that are clearly distinct from those of fresh samples. By performing computational microRNA-target enrichment analyses on the ancient sequences, we predict microRNA functions consistent with their tissue pattern of expression. For instance, we find a liver-specific microRNA that regulates carbohydrate metabolism and starvation responses in canids. In summary, we show that straightforward paleotranscriptomic microRNA analyses can give functional glimpses into tissue identity, cellular composition and gene regulatory activity of ancient samples and biological processes that took place in the Pleistocene, thus holding great promise for deeper insights into gene regulation in extinct animals based on ancient RNA sequencing. .


Quality indicators for treatment of respiratory tract infections? An assessment by Danish general practitioners.
In 2008, a set of 41 quality indicators for antibiotic treatment of respiratory tract infections (RTIs) in general practice were developed in an international setting as part of the European project HAPPY AUDIT. To investigate Danish general practitioners' (GPs') assessment of a set of internationally developed quality indicators and to explore if there is an association between the GPs' assessment of the indicators and their practice characteristics as well as their antibiotic prescription pattern. A total of 102 Danish GPs were invited to assess the 41 quality indicators. The GPs were categorized into two groups according to their assessment of indicators. Data concerning practice characteristics and antibiotic treatment were obtained during a three-week registration of patients with RTIs and were linked to the GPs' assessments of the indicators. A total of 62 (61%) responded. Quality indicators focusing on the frequency of prescribing of narrow-spectrum penicillin were rated as suitable by more than 80% of the Danish GPs, while quality indicators concerning cephalosporins or quinolones were rated suitable by less than half of the GPs. The antibiotic prescribing pattern differed significantly and the GPs who disagreed on most indicators prescribed more macrolides and less narrow-spectrum penicillin than the GPs who agreed on most indicators. Even though an international expert panel agreed on a set of quality indicators for antibiotic treatment of RTIs, only a few of them were rated suitable by the GPs, who are supposed to use them.


Graphene-supported 2D cobalt oxides for catalytic applications.
2D materials are attracting increasing attention in many strategic applications. In particular, ultra-thin non-layered oxides have been shown to outperform their 3D counter-parts in several health and energy applications, such as the removal of toxic carbon monoxide by low temperature oxidation and the development of high performance supercapacitors. The general reason for that is the increased surface-to-volume ratio, which maximizes exposure of active species and enhances exchange between the (limited) bulk and the surface. The challenge is to synthesize such 2D configurations of 3D oxides, which generally requires quite harsh multi-step, multi-reagent chemical processes. Here we show that natural graphite can be used as a templating matrix to grow non-stoichiometric 2D transition metal oxides. We focus on highly porous, highly reduced cobalt oxides grown from cobalt nitrate and sodium borohydride under sonication. Extensive characterization, including nitrogen physisorption, thermogravimetric analysis (TGA), scanning and transmission electron microscopy (SEM/TEM), X-ray diffraction (XRD), temperature programmed oxidation and reduction (TPO/TPR), Fourier transformed infrared (FTIR) and Raman spectroscopies, highlights the specific features of the 2D morphologies (nanosheets and nanofilms) obtained. For comparison, 3D morphologies of Co3O4 spinel nanocrystallites are grown from stacked 2D cobalt phthalocyanine-graphene precursors upon controlled thermal oxidation. Finally, low temperature CO oxidation catalysis evidences the superior performance of the graphene-supported CoO-like cobalt oxide 2D nanosheets.


Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system.
We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.


Strategic improvement of the long-term stability of perovskite materials and perovskite solar cells.
Perovskite solar cells (PSCs) have gained tremendous research interest in recent several years. To date the power conversion efficiency (PCE) of PSCs has been increased from 3.8% to over 22.1%, showing that they have a promising future as a renewable energy resource to compete with conventional silicon solar cells. However, a crucial challenge of PSCs currently is that perovskite materials and PSCs have limitations of easy degradation and inferior long-term stabilities, thus hampering their future commercial applications. In this review, the degradation mechanisms for instable perovskite materials and their corresponding solar cells are discussed. The stability study of perovskite materials and PSCs from the aspect of experimental tests and theoretical calculations is reviewed. The strategies for enhancing the stability of perovskite materials and PSCs are summarized from the viewpoints of perovskite material engineering, substituted organic and inorganic materials for hole transportation, alternative electrodes comprising mainly carbon and its relevant composites, interfacial modification, novel device structure construction and encapsulation, etc. Various approaches and outlooks on the future direction of perovskite materials and PSCs are highlighted. This review is expected to provide helpful insights for further enhancing the stability of perovskite materials and PSCs in this exciting field.


Antihypertensive effect of vasopressin withdrawal in young and adult spontaneously hypertensive rats.
The extent to which age influences the effect of prolonged intravenous infusion and withdrawal of arginine vasopressin (AVP) on blood pressure was investigated in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) of 6-, 10-, 14-, 18-, and 22-week age groups. The pressor response to AVP (20 ng/kg/min for 3 hours) was relatively well maintained in WKY but showed an age-dependent tachyphylaxis in SHR. After cessation of the infusion, arterial pressure of SHR fell in all age groups. In contrast, withdrawal of AVP in WKY resulted in little or no hypotensive response. Thus, a withdrawal-induced antihypertensive phenomenon (WAP) to AVP was specific to SHR. The magnitude of the WAP was significantly correlated with the level of initial blood pressure in SHR (r = -0.81, p less than 0.001). The magnitude of the tachyphylaxis during the AVP infusion was also correlated with the level of initial blood pressure in SHR (r = -0.66, p less than 0.001). Accordingly, a significant correlation was found between the magnitude of the WAP and the degree of tachyphylaxis to the pressor activity of AVP in SHR (r = 0.69, p less than 0.001). The significance of this is unknown, but it might mean that a common underlying mechanism existed in the expression of the tachyphylactic phenomenon and the WAP in SHR. Finally, an apparent enhancement in the baroreceptor reflex sensitivity was observed in both SHR and WKY during the infusion of AVP, but the magnitude of this enhancement appeared to be greater in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)


Gender role attitudes across the transition to adolescent motherhood in Mexican-origin families.
Using longitudinal data collected at four time points from 191 dyads of Mexican-origin adolescent first-time mothers and their mother figures, we examined changes in and socialization of traditional gender role attitudes across the transition to parenthood using latent growth curve modeling and actor-partner interdependence modeling. Longitudinal growth models indicated that, regardless of nativity status, adolescent mothers' and their foreign-born mother figures' gender role attitudes became more egalitarian across adolescents' transition to parenthood, spanning from the 3rd trimester of pregnancy to 36 months postpartum. Furthermore, actor-partner interdependence modeling suggested that adolescents' and their mother figures' gender role attitudes during adolescents' third trimester of pregnancy equally contributed to subsequent increases in one another's gender role attitudes at 10 months postpartum. Importantly, this reciprocal socialization process was not moderated by adolescent mothers' nor by their mother figures' nativity status. Findings suggest that it is important to understand the cultural and intergenerational family processes that contribute to the development of gender role attitudes during the transition to parenthood for adolescent mothers and their mother figures in Mexican-origin families.


There is no highly conserved embryonic stage in the vertebrates: implications for current theories of evolution and development.
Embryos of different species of vertebrate share a common organisation and often look similar. Adult differences among species become more apparent through divergence at later stages. Some authors have suggested that members of most or all vertebrate clades pass through a virtually identical, conserved stage. This idea was promoted by Haeckel, and has recently been revived in the context of claims regarding the universality of developmental mechanisms. Thus embryonic resemblance at the tailbud stage has been linked with a conserved pattern of developmental gene expression - the zootype. Haeckel's drawings of the external morphology of various vertebrates remain the most comprehensive comparative data purporting to show a conserved stage. However, their accuracy has been questioned and only a narrow range of species was illustrated. In view of the current widespread interest in evolutionary developmental biology, and especially in the conservation of developmental mechanisms, re-examination of the extent of variation in vertebrate embryos is long overdue. We present here the first review of the external morphology of tailbud embryos, illustrated with original specimens from a wide range of vertebrate groups. We find that embryos at the tailbud stage - thought to correspond to a conserved stage - show variations in form due to allometry, heterochrony, and differences in body plan and somite number. These variations foreshadow important differences in adult body form. Contrary to recent claims that all vertebrate embryos pass through a stage when they are the same size, we find a greater than 10-fold variation in greatest length at the tailbud stage. Our survey seriously undermines the credibility of Haeckel's drawings, which depict not a conserved stage for vertebrates, but a stylised amniote embryo. In fact, the taxonomic level of greatest resemblance among vertebrate embryos is below the subphylum. The wide variation in morphology among vertebrate embryos is difficult to reconcile with the idea of a phyogenetically-conserved tailbud stage, and suggests that at least some developmental mechanisms are not highly constrained by the zootype. Our study also highlights the dangers of drawing general conclusions about vertebrate development from studies of gene expression in a small number of laboratory species.


Hyaluronidase (Hyalase): a useful addition in haematoma block?
To investigate whether hyaluronidase (Hyalase) is a useful and justified addition to haematoma block for pain relief. The study was a randomised double blind trial of 33 consecutive patients attending the accident and emergency department for manipulation of distal radius fracture under haematoma block. Control patients received 1% lignocaine; the treatment group received 1% lignocaine plus 1500 IU hyaluronidase. Manipulation occurred 10 minutes after instituting the block. 16 patients received hyaluronidase, 17 received lignocaine only. One patient with unsuccessful manipulation was excluded. There was no significant difference between the two groups for any of three methods of pain assessment (P > 0.05, Mann Whitney). The addition of hyaluronidase does not increase the efficacy of the haematoma block when 10 minutes are allowed to elapse before manipulation, and the increased cost of adding (and risk of allergy) is not justified by any theoretical increased speed of analgesia.


Short Term Survival after Admission for Heart Failure in Sweden: Applying Multilevel Analyses of Discriminatory Accuracy to Evaluate Institutional Performance.
Hospital performance is frequently evaluated by analyzing differences between hospital averages in some quality indicators. The results are often expressed as quality charts of hospital variance (e.g., league tables, funnel plots). However, those analyses seldom consider patients heterogeneity around averages, which is of fundamental relevance for a correct evaluation. Therefore, we apply an innovative methodology based on measures of components of variance and discriminatory accuracy to analyze 30-day mortality after hospital discharge with a diagnosis of Heart Failure (HF) in Sweden. We analyzed 36,943 patients aged 45-80 treated in 565 wards at 71 hospitals during 2007-2009. We applied single and multilevel logistic regression analyses to calculate the odds ratios and the area under the receiver-operating characteristic (AUC). We evaluated general hospital and ward effects by quantifying the intra-class correlation coefficient (ICC) and the increment in the AUC obtained by adding random effects in a multilevel regression analysis (MLRA). Finally, the Odds Ratios (ORs) for specific ward and hospital characteristics were interpreted jointly with the proportional change in variance (PCV) and the proportion of ORs in the opposite direction (POOR). Overall, the average 30-day mortality was 9%. Using only patient information on age and previous hospitalizations for different diseases we obtained an AUC = 0.727. This value was almost unchanged when adding sex, country of birth as well as hospitals and wards levels. Average mortality was higher in small wards and municipal hospitals but the POOR values were 15% and 16% respectively. Swedish wards and hospitals in general performed homogeneously well, resulting in a low 30-day mortality rate after HF. In our study, knowledge on a patient's previous hospitalizations was the best predictor of 30-day mortality, and this information did not improve by knowing the sex and country of birth of the patient or where the patient was treated.


Impact of preoperative echocardiography on surgical delays and outcomes among adults with hip fracture.
Echocardiography is commonly used in hip fracture patients to evaluate perioperative cardiac risk. However, echocardiography that delays surgical repair may be harmful. The objective of this study was to compare surgical wait times, mortality, length of stay (LOS), and healthcare costs for similar hip fracture patients evaluated with and without preoperative echocardiograms. A population-based, matched cohort study of all hip fracture patients (aged over 45 years) in Ontario, Canada between 2009 and 2014 was conducted. The primary exposure was preoperative echocardiography (occurring between hospital admission and surgery). Mortality rates, surgical wait times, postoperative LOS, and medical costs (expressed as 2013$ CAN) up to one year postoperatively were assessed after propensity-score matching. A total of 2,354 of 42,230 (5.6%) eligible hip fracture patients received a preoperative echocardiogram during the study period. Echocardiography ordering practices varied among hospitals, ranging from 0% to 23.0% of hip fracture patients at different hospital sites. After successfully matching 2,298 (97.6%) patients, echocardiography was associated with significantly increased risks of mortality at 90 days (20.1% vs 16.8%; p = 0.004) and one year (32.9% vs 27.8%; p < 0.001), but not at 30 days (11.4% vs 9.8%; p = 0.084). Patients with echocardiography also had a mean increased delay from presentation to surgery (68.80 hours (SD 44.23) vs 39.69 hours (SD 27.09); p < 0.001), total LOS (19.49 days (SD 25.39) vs 15.94 days (SD 22.48); p < 0.001), and total healthcare costs at one year ($51,714.69 (SD 54,675.28) vs $41,861.47 (SD 50,854.12); p < 0.001). Preoperative echocardiography for hip fracture patients is associated with increased postoperative mortality at 90 days and one year but not at 30 days. Preoperative echocardiography is also associated with increased surgical delay, postoperative LOS, and total healthcare costs at one year. Echocardiography should be considered an urgent test when ordered to prevent additional surgical delay. Cite this article: Bone Joint J 2021;103-B(2):271-278.


Cluster analysis and clinical asthma phenotypes.
Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model. To explore the application of a multivariate mathematical technique, k-means cluster analysis, for identifying distinct phenotypic groups. We performed k-means cluster analysis in three independent asthma populations. Clusters of a population managed in primary care (n = 184) with predominantly mild to moderate disease, were compared with a refractory asthma population managed in secondary care (n = 187). We then compared differences in asthma outcomes (exacerbation frequency and change in corticosteroid dose at 12 mo) between clusters in a third population of 68 subjects with predominantly refractory asthma, clustered at entry into a randomized trial comparing a strategy of minimizing eosinophilic inflammation (inflammation-guided strategy) with standard care. Two clusters (early-onset atopic and obese, noneosinophilic) were common to both asthma populations. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation (early-onset symptom predominant and late-onset inflammation predominant) were specific to refractory asthma. Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster (3.53 [SD, 1.18] vs. 0.38 [SD, 0.13] exacerbation/patient/yr, P = 0.002) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster (mean difference, 1,829 mug beclomethasone equivalent/d [95% confidence interval, 307-3,349 mug]; P = 0.02). Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms.


Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
The MCM2-7 helicase complex is loaded on DNA replication origins during the G1 phase of the cell cycle to license the origins for replication in S phase. How the initiator primase-polymerase complex, DNA polymerase alpha (pol alpha), is brought to the origins is still unclear. We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates with MCM2-7, and with the p180 subunit of DNA pol alpha. And-1 is essential for DNA synthesis and the stability of p180 in mammalian cells. In Xenopus egg extracts And-1 is loaded on the chromatin after Mcm10, concurrently with DNA pol alpha, and is required for efficient DNA synthesis. Mcm10 is required for chromatin loading of And-1 and an antibody that disrupts the Mcm10-And-1 interaction interferes with the loading of And-1 and of pol alpha, inhibiting DNA synthesis. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery. The discovery also adds to the connection between replication initiation and sister chromatid cohesion.


Differential Gaze Patterns on Eyes and Mouth During Audiovisual Speech Segmentation.
Speech is inextricably multisensory: both auditory and visual components provide critical information for all aspects of speech processing, including speech segmentation, the visual components of which have been the target of a growing number of studies. In particular, a recent study (Mitchel and Weiss, 2014) established that adults can utilize facial cues (i.e., visual prosody) to identify word boundaries in fluent speech. The current study expanded upon these results, using an eye tracker to identify highly attended facial features of the audiovisual display used in Mitchel and Weiss (2014). Subjects spent the most time watching the eyes and mouth. A significant trend in gaze durations was found with the longest gaze duration on the mouth, followed by the eyes and then the nose. In addition, eye-gaze patterns changed across familiarization as subjects learned the word boundaries, showing decreased attention to the mouth in later blocks while attention on other facial features remained consistent. These findings highlight the importance of the visual component of speech processing and suggest that the mouth may play a critical role in visual speech segmentation.


Design & rationale of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is a randomized, double-blind, placebo-controlled primary prevention trial. It is designed to test the hypothesis that in addition to a lipid-lowering diet, treatment with lovastatin is more effective than placebo in reducing acute major coronary events (i.e., sudden cardiac death, fatal and nonfatal myocardial infarction, and unstable angina) in a cohort with normal to mildly elevated total (180 to 264 mg/dl) and low-density lipoprotein (LDL) cholesterol (130 to 190 mg/dl) and low high-density lipoprotein (HDL) cholesterol (< or =45 mg/dl for men and < or =47 mg/dl for women). Two sites in Texas, Lackland Air Force Base in San Antonio and the University of North Texas Health Science Center in Fort Worth, will conduct the study. After at least 12 weeks of an American Heart Association Step 1 diet and 2 weeks placebo run-in, 6,605 men and women, ages 45 to 73 and 55 to 73 years, respectively, without clinical evidence of coronary heart disease, are randomized in equal numbers to either lovastatin (20 mg/day) or placebo. Study procedures maintain the blind, allowing titration of lovastatin from 20 to 40 mg/day to achieve an LDL cholesterol goal of < or = 110 mg/dl. All participants are followed until study completion, when 320 participants have had a primary end point or a minimum of 5 years after the last participant is randomized, whichever occurs last. All end points are adjudicated by an independent committee using prespecified criteria. Unique features of this trial are (1) the inclusion of unstable angina in the primary end point to reflect the increasing trend to treat coronary heart disease aggressively before a myocardial infarction has occurred, (2) aggressive pharmacologic intervention, with titration, to attain an LDL cholesterol goal less than the current National Cholesterol Education Panel guidelines for primary prevention, and (3) a cohort that includes women, the elderly, and those with mild to moderate hyperlipidemia and low HDL cholesterol. Compared with earlier studies, results will be applicable to a broader population and may help clarify the role of aggressive LDL cholesterol reduction measures in primary prevention. Treatment of this population is likely to realize the greatest cumulative long-term benefit in the prevention of acute major coronary events.


Phase-locked loop based on machine surface topography measurement using lensed fibers.
We present the phase-locked loop (PLL)-based metrology concept using lensed fibers for on-machine surface topography measurement. The shape of a single-mode fiber at the endface was designed using an ABCD matrix method, and two designed lensed fibers-the ball type and the tapered type-were fabricated, and the performance was evaluated, respectively. As a result, the interferometric fringe was not found in the case of the ball lensed fiber, but the machined surface could be measured by utilization of autofocusing and intensity methods. On the other hand, a very clear Fizeau interferometric fringe was observed in the case of the tapered lensed fiber. Its performance was compared with the results of the capacitance sensor and a commercially available white-light interferometer. We confirmed that PLL-based surface profile measurement using the tapered and ball lensed fibers can be applied for on-machine surface topography measurement applications.


New steady-state microbial community compositions and process performances in biogas reactors induced by temperature disturbances.
The microbial community in a biogas reactor greatly influences the process performance. However, only the effects of deterministic factors (such as temperature and hydraulic retention time (HRT)) on the microbial community and performance have been investigated in biogas reactors. Little is known about the manner in which stochastic factors (for example, stochastic birth, death, colonization, and extinction) and disturbance affect the stable-state microbial community and reactor performances. In the present study, three replicate biogas reactors treating cattle manure were run to examine the role of stochastic factors and disturbance in shaping microbial communities. In the triplicate biogas reactors with the same inoculum and operational conditions, similar process performances and microbial community profiles were observed under steady-state conditions. This indicated that stochastic factors had a minor role in shaping the profile of the microbial community composition and activity in biogas reactors. On the contrary, temperature disturbance was found to play an important role in the microbial community composition as well as process performance for biogas reactors. Although three different temperature disturbances were applied to each biogas reactor, the increased methane yields (around 10% higher) and decreased volatile fatty acids (VFAs) concentrations at steady state were found in all three reactors after the temperature disturbances. After the temperature disturbance, the biogas reactors were brought back to the original operational conditions; however, new steady-state microbial community profiles were observed in all the biogas reactors. The present study demonstrated that temperature disturbance, but not stochastic factors, played an important role in shaping the profile of the microbial community composition and activity in biogas reactors. New steady-state microbial community profiles and reactor performances were observed in all the biogas reactors after the temperature disturbance.


Evaluation of three years of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness and Environmental improvement) for trachoma control in five districts of Ethiopia hyperendemic for trachoma.
Trachoma surveys were conducted at baseline in five districts of Amhara National Regional State, Ethiopia (7478 participants in 1096 households) and at 3-year evaluation (5762 participants in 1117 households). Uptake of SAFE was assessed with programme monitoring data and interviews, and children (1-6 years) were swabbed for detection of ocular Chlamydia. At evaluation, 23,933 people had received trichiasis surgery; 93% of participants reported taking azithromycin at least once; 67% of household respondents (range 46-93) reported participation in trachoma health education; and household latrine coverage increased from 2% to 34%. In children aged 1-9 years percentage decline, by district, for outcomes was: 32% (95% CI 19-48) to 88% (95% CI 83-91) for trachomatous inflammation-follicular (TF); 87% (95% CI 83-91) to 99% (95% CI 97-100) for trachomatous inflammation-intense (TI); and 31% increase (95% CI -42 to -19) to 89% decrease (95% CI 85-93) for unclean face; and in adults percentage decline in trichiasis was 45% (95% CI -13 to 78) to 92% (95% CI 78-96). Overall prevalence of swabs positive for ocular Chlamydia was 3.1%. Although there were substantial reductions in outcomes in children and adults, the presence of ocular Chlamydia and TF in children suggests ongoing transmission. Continued implementation of SAFE is warranted.


Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.
Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity.


Diallyl sulfide alleviates cyclophosphamide-induced nephropathic encephalopathy in rats.
Diallyl sulfide (DAS) is a garlic-derived organosulfur compound. The current study was planned to evaluate the protecting effects of DAS against cyclophosphamide (CP)-induced nephropathic encephalopathy. DAS (100 mg/kg) was orally administered for 4 days, 60 min after the last dose, rats were injected with CP (150 mg/kg). DAS treatment before CP significantly decreased serum urea, creatinine, sodium, potassium, calcium, blood urea nitrogen (BUN), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1β (IL-1ß) and tumor necrosis factor-alpha (TNF-α) compared with CP-treated rats. DAS treatment decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH) levels in the renal tissues and significantly attenuated the elevated neurotransmitters N-methyl-D-aspartate/adenosine triphosphate (NMDA), γ-aminobutyric acid (GABA) levels and remarkably restored neuronal nitric oxide (NO) level and nitric oxide synthase (nNOS) activity in the brain compared to CP-treated rats. DAS for 4 consecutive days before CP showed moderate positive immunohistochemically expression of the glial fibrillary acidic protein (GFAP) in the brain and kidney tissues comparable to CP-treated rats. DAS afforded renal and neuroprotection against CP-induced nephropathic encephalopathy due to its capacity to ameliorates the afore-mentioned biochemical parameters which were supported by histopathological and immunohistochemically examination.


Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation.
Platelet-activating factor is a mediator of lung injury during cardiac operation. Platelet-activating factor antagonists reduce lung injury in animal models of cardiopulmonary bypass but there is no confirmatory evidence in clinical practice. The effect of a low or high dose of a platelet-activating factor antagonist (Lexipafant) was assessed in a single center, double-blind, placebo-controlled, parallel group study. One hundred fifty patients undergoing coronary artery bypass grafting were randomized by minimization into three groups to receive placebo infusion, 10 or 100 mg of lexipafant for over 24 hours. Serial arterial oxygen and carbon dioxide tension, alveolar arterial oxygen gradient, and percent saturation were measured before operation and at 1, 6, 24, 48 hours, and 5 days after operation. Patient groups were similar with respect to age, sex, body surface area, and urgency of operation. Likewise, the groups were similar with respect to duration of cardiopulmonary bypass and the number and type of grafts. Maximum lung injury occurred at 48 hours when the arterial oxygen tension and percent saturation reached a nadir (both p < 0.001) accompanied by the maximum increase in the alveolar arterial gradient (p < 0.001). All measurements demonstrated partial recovery by 5 days but remained significantly (p < 0.001) impaired in comparison to baseline values. Duration of ventilation was similar in all groups. Lexipafant, at low or high dose, did not moderate lung injury after cardiopulmonary bypass and did not influence the duration of postoperative ventilation. Despite experimental and clinical evidence implicating platelet-activating factor in the pathophysiology of lung injury after cardiopulmonary bypass, no beneficial effect of a platelet-activating factor antagonist on lung function or ventilation could be demonstrated in this clinical trial.


APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development.
Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesting that Wnt affects hepatic progenitor cells. To elucidate the role of APC loss and enhanced Wnt activity in liver development, we examined APC mutant and wnt inducible transgenic zebrafish. APC(+/-) embryos developed enlarged livers through biased induction of hepatic gene programs and increased proliferation. Conversely, APC(-/-) embryos formed no livers. Blastula transplantations determined that the effects of APC loss were cell autonomous. Induction of wnt modulators confirmed biphasic consequences of wnt activation: endodermal pattern formation and gene expression required suppression of wnt signaling in early somitogenesis; later, increased wnt activity altered endodermal fate by enhancing liver growth at the expense of pancreas formation; these effects persisted into the larval stage. In adult APC(+/-) zebrafish, increased wnt activity significantly accelerated liver regeneration after partial hepatectomy. Similarly, liver regeneration was significantly enhanced in APC(Min/+) mice, indicating the conserved effect of Wnt pathway activation in liver regeneration across vertebrate species. These studies reveal an important and time-dependent role for wnt signaling during liver development and regeneration.


Postreplicative mismatch repair.
The mismatch repair (MMR) system detects non-Watson-Crick base pairs and strand misalignments arising during DNA replication and mediates their removal by catalyzing excision of the mispair-containing tract of nascent DNA and its error-free resynthesis. In this way, MMR improves the fidelity of replication by several orders of magnitude. It also addresses mispairs and strand misalignments arising during recombination and prevents synapses between nonidentical DNA sequences. Unsurprisingly, MMR malfunction brings about genomic instability that leads to cancer in mammals. But MMR proteins have recently been implicated also in other processes of DNA metabolism, such as DNA damage signaling, antibody diversification, and repair of interstrand cross-links and oxidative DNA damage, in which their functions remain to be elucidated. This article reviews the progress in our understanding of the mechanism of replication error repair made during the past decade.


A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members.
The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further.


Assessment of daily activity patterns and biomarkers of pain, inflammation, and stress in lactating dairy cows diagnosed with clinical metritis.
The objectives of the present case-control study were to assess (1) daily activity patterns (lying time, number of steps, number of lying bouts, and lying bout duration), and (2) circulating concentrations of biomarkers of pain (substance P), inflammation (haptoglobin), and stress (cortisol) in lactating dairy cows diagnosed with clinical metritis. Lactating dairy cows (n = 200) from 2 commercial dairy herds were enrolled in the present study. Cows diagnosed with clinical metritis (n = 100) at 7 ± 3 d in milk were matched according to lactation and days in milk to cows without clinical metritis (NO-CM; n = 100). On study d 1, clinical metritis was diagnosed (using a Metricheck device, Simcro Tech Ltd., Hamilton, New Zealand) by the presence of watery, reddish, or brownish foul-smelling vaginal discharge, and blood samples were collected for assessment of circulating concentration of substance P, haptoglobin, cortisol, total calcium, β-hydroxybutyrate, and blood cells. In addition, on study d 1 body condition of cows was visually assessed, and activity monitors were placed on the hind leg of a subset of cows (CM, n = 56; CON, n = 56) and were kept until study d 7. Cows showing any other signs of other diseases were not included in the study. Cows with clinical metritis tended to spend more time lying (CM = 628.92 min/d; NO-CM = 591.23 min/d) compared with NO-CM cows. Activity analysis by parity revealed that primiparous cows with clinical metritis spent more time lying compared with primiparous cows without clinical metritis. However, no differences in daily lying time were observed between multiparous cows with and without clinical metritis. Furthermore, cows in the CM group had a higher circulating concentration of substance P (CM = 47.15 pg/mL; NO-CM = 37.73 pg/mL) and haptoglobin (CM = 233.00 µg/mL; NO-CM = 99.98 µg/mL) when compared with NO-CM cows. Cows with clinical metritis had lower body condition score, and a greater proportion of cows in this group had hypocalcemia when compared with cows without clinical metritis. The circulating concentration of leukocytes and erythrocytes were decreased in cows with clinical metritis compared with cows without clinical metritis. Results from this study showed that concentrations of markers of inflammation, stress, pain, and activity were affected in cows diagnosed with clinical metritis; thus, strategies aimed to minimize the negative effects associated with clinical metritis may be required to improve the welfare of dairy cows.


Restoring the regenerative balance in neuromuscular disorders: satellite cell activation as therapeutic target in Pompe disease.
Skeletal muscle is capable of efficiently regenerating after damage in a process mediated by tissue-resident stem cells called satellite cells. This regenerative potential is often compromised under muscle-degenerative conditions. Consequently, the damage produced during degeneration is not efficiently repaired and the balance between repair and damage is lost. Here we review recent progress on the role of satellite cell-mediated repair in neuromuscular disorders with a focus on Pompe disease, an inherited metabolic myopathy caused by deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Studies performed in patient biopsies as well as in Pompe disease mouse models demonstrate that muscle regeneration activity is compromised despite progressing muscle damage. We describe disease-specific mechanisms of satellite cell dysfunction to highlight the differences between Pompe disease and muscle dystrophies. The mechanisms involved provide possible targets for therapy, such as modulation of autophagy, muscle exercise, and pharmacological modulation of satellite cell activation. Most of these approaches are still experimental, although promising in animal models, still warrant caution with respect to their safety and efficiency profile.


Understanding of the Mechanism for Laser Ablation-Assisted Patterning of Graphene/ITO Double Layers: Role of Effective Thermal Energy Transfer.
Demand for the fabrication of high-performance, transparent electronic devices with improved electronic and mechanical properties is significantly increasing for various applications. In this context, it is essential to develop highly transparent and conductive electrodes for the realization of such devices. To this end, in this work, a chemical vapor deposition (CVD)-grown graphene was transferred to both glass and polyethylene terephthalate (PET) substrates that had been pre-coated with an indium tin oxide (ITO) layer and then subsequently patterned by using a laser-ablation method for a low-cost, simple, and high-throughput process. A comparison of the results of the laser ablation of such a graphene/ITO double layer with those of the ITO single-layered films reveals that a larger amount of effective thermal energy of the laser used is transferred in the lateral direction along the graphene upper layer in the graphene/ITO double-layered structure, attributable to the high thermal conductivity of graphene. The transferred thermal energy is expected to melt and evaporate the lower ITO layer at a relatively lower threshold energy of laser ablation. The transient analysis of the temperature profiles indicates that the graphene layers can act as both an effective thermal diffuser and converter for the planar heat transfer. Raman spectroscopy was used to investigate the graphite peak on the ITO layer where the graphene upper layer was selectively removed because of the incomplete heating and removal process for the ITO layer by the laterally transferred effective thermal energy of the laser beam. Our approach could have broad implications for designing highly transparent and conductive electrodes as well as a new way of nanoscale patterning for other optoelectronic-device applications using laser-ablation methods.


Myxedema Heart and Pseudotamponade.
Thyroid hormone plays a critical role in cardiovascular function. Severe hypothyroidism can be associated with "myxedema heart" characterized by relative bradycardia and pericardial effusion. Effusions associated with severe hypothyroidism can be large. Despite the large volume of effusions, tamponade is not a common consequence. However, with the incorporation of echocardiography into routine practice for evaluation of effusion, echocardiographic findings suggestive of clinical tamponade occur frequently. We report a series of 3 patients with large pericardial effusions secondary to severe hypothyroidism. These cases serve to demonstrate the discordance between echocardiographic signs consistent with tamponade with a patient's stable clinical hemodynamics. We also report the development of bronchial obstruction, a rare complication of a large effusion due to severe hypothyroidism. While pericardial effusion associated with severe hypothyroidism has been described for decades, the echocardiographic findings may be less well known and may lead to unnecessary downstream testing or invasive management. We use our case series to facilitate a summary of what is known about the epidemiology, mechanism and physiology, and expected outcomes of myxedema associated pericardial effusion. Finally, in the setting of current paucity of clinical guidelines, we aim to familiarize clinicians with the phenomenon of pseudotamponade and suggest management strategies for myxedema associated pericardial effusion to guide clinicians to use conservative medical management in majority of cases.


The role of electronic health record and "add-on" clinical decision support systems to enhance antimicrobial stewardship programs.
Increasingly, demands are placed on healthcare systems to meet antimicrobial stewardship standards and reporting requirements. This trend, combined with reduced financial and personnel resources, has created a need to adopt information technology (IT) to help ease these burdens and facilitate action. The incorporation of IT into an antimicrobial stewardship program can help improve stewardship intervention efficiencies and facilitate the tracking and reporting of key metrics, including outcomes. This paper provides a review of the stewardship-related functionality within these IT systems, describes how these platforms can be used to improve antimicrobial use, and identifies how they can support current and potential future antimicrobial stewardship regulatory and accreditation standards. Finally, recommendations to help close the gaps in existing systems are provided and suggestions for future areas of development within these programs are delineated.