The transition of a large-scale quality improvement initiative: a bibliometric analysis of the Productive Ward: Releasing Time to Care programme.
To examine the literature related to a large-scale quality improvement initiative, the 'Productive Ward: Releasing Time to Care', providing a bibliometric profile that tracks the level of interest and scale of roll-out and adoption, discussing the implications for sustainability. Productive Ward: Releasing Time to Care (aka Productive Ward) is probably one of the most ambitious quality improvement efforts engaged by the UK-NHS. Politically and financially supported, its main driver was the NHS Institute for Innovation and Improvement. The NHS institute closed in early 2013 leaving a void of resources, knowledge and expertise. UK roll-out of the initiative is well established and has arguably peaked. International interest in the initiative however continues to develop. A comprehensive literature review was undertaken to identify the literature related to the Productive Ward and its implementation (January 2006-June 2013). A bibliometric analysis examined/reviewed the trends and identified/measured interest, spread and uptake. Overall distribution patterns identify a declining trend of interest, with reduced numbers of grey literature and evaluation publications. However, detailed examination of the data shows no reduction in peer-reviewed outputs. There is some evidence that international uptake of the initiative continues to generate publications and create interest. Sustaining this initiative in the UK will require re-energising, a new focus and financing. The transition period created by the closure of its creator may well contribute to further reduced levels of interest and publication outputs in the UK. However, international implementation, evaluation and associated publications could serve to attract professional/academic interest in this well-established, positively reported, quality improvement initiative. This paper provides nurses and ward teams involved in quality improvement programmes with a detailed, current-state, examination and analysis of the Productive Ward literature, highlighting the bibliometric patterns of this large-scale, international, quality improvement programme. It serves to disseminate updated publication information to those in clinical practice who are involved in Productive Ward or a similar quality improvement initiative.


The effect of iloprost and N-acetylcysteine on skeletal muscle injury in an acute aortic ischemia-reperfusion model: an experimental study.
The objective of this study was to examine the effects of iloprost and N-acetylcysteine (NAC) on ischemia-reperfusion (IR) injuries to the gastrocnemius muscle, following the occlusion-reperfusion period in the abdominal aorta of rats. Forty male Sprague-Dawley rats were randomly divided into four equal groups. Group 1: control group. Group 2 (IR): aorta was occluded. The clamp was removed after 1 hour of ischemia. Blood samples and muscle tissue specimens were collected following a 2-hour reperfusion period. Group 3 (IR + iloprost): during a 1-hour ischemia period, iloprost infusion was initiated from the jugular catheter. During a 2-hour reperfusion period, the iloprost infusion continued. Group 4 (IR + NAC): similar to the iloprost group. The mean total oxidant status, CK, and LDH levels were highest in Group 2 and lowest in Group 1. The levels of these parameters in Group 3 and Group 4 were lower compared to Group 2 and higher compared to Group 1 (P < 0.05). The histopathological examination showed that Group 3 and Group 4, compared to Group 2, had preserved appearance with respect to hemorrhage, necrosis, loss of nuclei, infiltration, and similar parameters. Iloprost and NAC are effective against ischemia-reperfusion injury and decrease ischemia-related tissue injury.


Kruppel-like factor4 regulates PRDM1 expression through binding to an autoimmune risk allele.
A SNP identified as rs548234, which is found in PRDM1, the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers. Female rs548234 risk allele carriers, but not nonrisk allele carriers, exhibited decreased levels of BLIMP1 in MO-DCs, showing that the regulatory function of KLF4 is influenced by the risk allele. In addition, KLF4 directly recruits histone deacetylases (HDAC4, HDAC6, and HDAC7), established negative regulators of gene expression. Finally, the knock down of KLF4 expression reversed the inhibitory effects of the risk SNP on promoter activity and BLIMP1 expression. Therefore, the binding of KLF4 and the subsequent recruitment of HDACs represent a mechanism for reduced BLIMP1 expression in MO-DCs bearing the SLE risk allele rs548234.


Long-term follow-up of heel spur surgery. A 10-year retrospective study.
A comparative retrospective study of 48 open heel spur surgeries and 20 endoscopic plantar fasciotomies was conducted involving 59 patients over a 10-year period. There was a significant reduction in heel pain at the time of follow-up (average, 3 years) for both groups. Overall, 85% of procedures were associated with patient satisfaction with the results, and patients said that they would recommend heel spur surgery for relief of severe heel pain in 94% of cases. Factors influencing the postoperative outcome, such as duration of preoperative symptoms, extent of conservative care, and obesity, are discussed.


Radiation exposure with use of the mini-C-arm for routine orthopaedic imaging procedures.
The use of mobile fluoroscopic devices during orthopaedic procedures is associated with substantial concern with regard to the radiation exposure to surgeons and support staff. The perceived increased risks associated with large c-arm devices have been well documented. However, no study to date has documented the relative radiation risk associated with the use of a mini-c-arm device. The purpose of the current study was to determine the amount of radiation received by the surgeon during the use of a mini-c-arm device and to compare this amount with documented measurements associated with the large c-arm device. With use of a radiation dosimeter, measurements were carried out with tissue-equivalent anthropomorphic phantoms to quantitatively determine exposure rates at various locations and distances from the mini-c-arm for two common upper and lower extremity procedures. Regardless of position, distance, or relative duration of exposure, exposure rates resulting from the use of the mini-c-arm device were one to two orders of magnitude lower than those reported in the literature in association with the use of the large c-arm device. The mini-c-arm device should be utilized whenever feasible in order to eliminate many of the concerns associated with use of the large c-arm device, specifically those related to cumulative radiation hazards, positioning considerations, relative distance from the beam, and the need for protective shielding.


The sphingolipid-rich rafts of ALK+ lymphomas downregulate the Lyn-Cbp/PAG signalosome.
Human anaplastic lymphoma kinase (ALK) + lymphomas express the constitutively active ALK as a fusion protein that drives several survival pathways. The catalytic domain of the anaplastic receptor tyrosine kinase is frequently fused with the nuclear localization protein nucleophosmin but may also fuse with other proteins that associate it with other subcellular structures. Similarly to other B human lymphomas, ALK+ lymphomas express the Cbp/PAG adaptor protein and the non-receptor Lyn kinase in the plasma membrane. In the majority of human lymphomas, the Cbp/PAG adaptor and the Lyn kinase constitute an oncogenic signalosome that serves as a membrane anchor for other signaling enzymes and transcription factors. We show that ALK+ lymphoma membranes harbor sphingolipid-rich microdomains (rafts) in which Lyn is poorly active. However, Lyn activity and consequently Cbp/PAG tyrosine phosphorylation can be restored by extracting sphingolipids from ALK+ lymphoma plasma membranes. In the membrane environment of ALK+ lymphoma rafts, where the glycosphingolipid to signaling protein ratio is higher than in B-NHL rafts, the Lyn activity is suboptimal and does not allow the formation of an efficient Lyn-Cbp/PAG signalosome.


Expert Report: Making Decisions about the Risks of Chemicals in Foods with Limited Scientific Information: An IFT Expert Report Funded by the IFT Foundation.
On occasion, food safety managers may detect an undesirable chemical contaminant or unanticipated chemical substance in a food commodity, ingredient, or finished product, thereby warranting an assessment of the health impact of the substance at the level detected. Many times, such an assessment must be made with limited scientific information. In such situations, food safety managers must expeditiously evaluate the available data and other information and make decisions such as whether to implement a food product recall to protect public health and maintain integrity of and confidence in the food supply. Under such circumstances, making decisions about risk can be very complicated by the interactions of a number of issues. Interpretation of scientific and public policy can cause confusion as a result of insufficient data for conducting a risk assessment, conflicting data, uncertainty stemming from toxicological issues or temporal constraints, emerging nature of the state of the science, and regulatory constraints (for example, zero tolerance). A user-friendly conceptual framework would aid food safety managers faced with making decisions about the risks of newly detected, undesired chemical substances in foods-whether naturally occurring toxins, direct or indirect food additives, substances arising through food processing, or other substances. The Institute of Food Technologists (IFT) convened a group of experts to (1) examine the complexities that challenge timely decision-making about such substances when available scientific information is limited and (2) define and develop a workable tool to guide food safety managers in effectively and knowledgeably evaluating available scientific evidence pertinent to assessing the risk from exposure to a chemical substance to make timely decisions. This Expert Report delves into the legal U.S. underpinnings of the risk management of chemical substances in foods, international considerations, risk-benefit evaluation, importance of the food matrix to risks and benefits, risk assessment and management, and the need for a new approach to timely decision-making with limited scientific information. This report includes case studies that demonstrate (1) the various complexities and how sound decision-making with sufficient available pertinent data is reinforced as additional supportive data subsequently become available and (2) the importance of assessing and balancing consideration of risks and benefits from a whole food perspective.


On the networked architecture of genotype spaces and its critical effects on molecular evolution.
Evolutionary dynamics is often viewed as a subtle process of change accumulation that causes a divergence among organisms and their genomes. However, this interpretation is an inheritance of a gradualistic view that has been challenged at the macroevolutionary, ecological and molecular level. Actually, when the complex architecture of genotype spaces is taken into account, the evolutionary dynamics of molecular populations becomes intrinsically non-uniform, sharing deep qualitative and quantitative similarities with slowly driven physical systems: nonlinear responses analogous to critical transitions, sudden state changes or hysteresis, among others. Furthermore, the phenotypic plasticity inherent to genotypes transforms classical fitness landscapes into multiscapes where adaptation in response to an environmental change may be very fast. The quantitative nature of adaptive molecular processes is deeply dependent on a network-of-networks multilayered structure of the map from genotype to function that we begin to unveil.


Characterisation of protein stability in rod-insert vaginal rings.
A major goal in vaccine development is elimination of the 'cold chain', the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 °C, but not when stored at 40 °C/75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 °C/75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation compared to the original formulation when stored at 40 °C/75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general.


Treatment of a bone defect consequent to the removal of a periapical cyst with equine bone and equine membranes: clinical and histological outcome.
While deproteinized bovine bone and bovine membranes have been well studied and can yield good results when used to treat bone defects and peri-implant dehiscences, enzymatically deantigenated equine bone and equine membranes have emerged as possible alternative biomaterials. The objective of this study was the clinical and histological assessment of such materials: equine bone granules, an equine collagen membrane and an equine pericardium membrane. Enzymatically deantigenated equine bone and an equine collagen membrane were used to restore a bone defect caused by the removal of a bone cyst in the upper anterior maxilla. After 4.5 months, an implant was placed and a bone core sample was obtained from the grafted site. Implants threads, though, were exposed. This defect was grafted with a mixture of autogenous and equine bone and covered with an equine pericardium membrane. Four months after implant placement the peri-implant bone levels were maintained. A prosthesis was delivered three months later providing functional and esthetic rehabilitation. Also four-year follow-up controls showed implant success. Histological analysis of the bone core revealed that the graft material had undergone remodelling, and a fair amount of newly formed vital bone was present at the time of sample collection. The deantigenated equine bone is biocompatible and undergoes osteoclastic remodelling. Both the equine collagen and pericardium membrane acted as effective barriers for guided bone regeneration.


Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women.
Background: Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D), but there is a lack of objective tools for assessing the relation between diet and T2D. Biomarkers of dietary intake are unconfounded by recall and reporting bias, and using multiple dietary biomarkers could help strengthen the link between a healthy diet and the prevention of T2D.Objective: The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and to future development of T2D irrespective of common T2D and cardiovascular disease risk factors by using multiple dietary biomarkers.Design: Dietary biomarkers were measured in plasma from 64-y-old Swedish women with different GTS [normal glucose tolerance (NGT; n = 190), impaired glucose tolerance (IGT; n = 209), and diabetes (n = 230)]. The same subjects were followed up after 5 y to determine changes in glucose tolerance (n = 167 for NGT, n = 174 for IGT, and n = 159 for diabetes). ANCOVA and logistic regression were used to explore baseline data for associations between dietary biomarkers, GTS, and new T2D cases at follow-up (n = 69).Results: Of the 10 dietary biomarkers analyzed, β-alanine (beef) (P-raw < 0.001), alkylresorcinols C17 and C19 (whole-grain wheat and rye) (P-raw = 0.003 and 0.011), eicosapentaenoic acid (fish) (P-raw = 0.041), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) (P-raw = 0.002), linoleic acid (P-raw < 0.001), oleic acid (P-raw = 0.003), and α-tocopherol (margarine and vegetable oil) (P-raw < 0.001) were associated with GTS, and CMPF (fish) (OR: 0.72; 95% CI: 0.56, 0.93; P-raw = 0.013) and α-tocopherol (OR: 0.71; 95% CI: 0.51, 0.98; P-raw = 0.041) were inversely associated with future T2D development.Conclusions: Several circulating dietary biomarkers were strongly associated with GTS after correction for known T2D risk factors, underlining the role of diet in the development and prevention of T2D. To our knowledge, this study is the first to use multiple dietary biomarkers to investigate the link between diet and disease risk.


Expression of low molecular weight cytokeratin proteins in cervical neoplasia.
CAM 5.2 is a monoclonal antibody which identifies lower molecular weight cytokeratin proteins (50, 43 and 38 kD). It is an antibody which works reliably on formalin-fixed, paraffin-embedded tissues. In this study, using CAM 5.2 in the indirect immunoperoxidase method we have examined ectocervical epithelium ranging from normal, through metaplasia and cervical intraepithelial neoplasia to invasive squamous carcinoma. CAM 5.2 is demonstrated to be a useful indicator of changes associated with malignant transformation in the ectocervix.


Sources of Help for Dating Violence Victims: A Qualitative Inquiry Into the Perceptions of African American Teens.
Although teen dating violence victims' reticence in seeking help from adults is well documented, little is known about youths' comparative perceptions of the types of help offered by and effectiveness of various sources. This qualitative study solicited teens' perceptions of sources of help for victims using in-depth interviews with African American youth (ages 13-18) in two public high schools in New Orleans (N = 38). Participants were recruited purposively by researchers during lunchtime and via referral by school personnel. Interviews were transcribed verbatim and coded independently by two study team members. Thematic content analyses were conducted. Teens reported that victims were most likely to seek help from friends, who were largely expected to provide advice and comfort. Nearly half reported that teens would be likely to seek help from family, who would provide more active responses to dating violence (i.e., reporting to authorities, confronting the abuser). Fewer respondents believed teens would seek help from other adults, such as school personnel, who were also perceived as likely to enlist outside authorities. Fears about lack of confidentiality and over-reaction were the main perceived barriers to accessing help from adults. Furthermore, although respondents believed teens would be less likely to seek help from adults, adults were perceived as more effective at stopping abuse compared with peers. Interventions that train peer helpers, explain confidentiality to teens, increase school personnel's ability to provide confidential counseling, and promote use of health services may improve access to help for teen dating violence victims.


Challenges for biosimilars: focus on rheumatoid arthritis.
Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.


A Descriptive Analysis of an Ambulatory Kidney Palliative Care Program.
Background: Many patients with serious kidney disease have an elevated symptom burden, high mortality, and poor quality of life. Palliative care has the potential to address these problems, yet nephrology patients frequently lack access to this specialty. Objectives: We describe patient demographics and clinical activities of the first 13 months of an ambulatory kidney palliative care (KPC) program that is integrated within a nephrology practice. Design/Measurements: Utilizing chart abstractions, we characterize the clinic population served, clinical service utilization, visit activities, and symptom burden as assessed using the Integrated Palliative Care Outcome Scale-Renal (IPOS-R), and patient satisfaction. Results: Among the 55 patients served, mean patient age was 72.0 years (standard deviation [SD] = 16.7), 95% had chronic kidney disease stage IV or V, and 46% had a Charlson Comorbidity Index >8. The mean IPOS-R score at initial visit was 16 (range = 0-60; SD = 9.1), with a mean of 7.5 (SD = 3.7) individual physical symptoms (range = 0-15) per patient. Eighty-seven percent of initial visits included an advance care planning conversation, 55.4% included a medication change for symptoms, and 35.5% included a dialysis decision-making conversation. Overall, 96% of patients who returned satisfaction surveys were satisfied with the care they received and viewed the KPC program positively. Conclusions: A model of care that integrates palliative care with nephrology care in the ambulatory setting serves high-risk patients with serious kidney disease. This KPC program can potentially meet documented gaps in care while achieving patient satisfaction. Early findings from this program evaluation indicate opportunities for enhanced patient-centered palliative nephrology care.


Mind the gap: the mismatch between clinical and imaging metrics in ALS.
Advanced magnetic resonance imaging (MRI) techniques hold the promise to capture upper motor neuron loss and extramotor brain changes in amyotrophic lateral sclerosis (ALS) and as such deliver biomarkers relevant to diagnosis, prognosis and monitoring disease progression. However, a correlation between imaging parameters and clinical metrics has thus far been inconsistent across studies. We discuss the contributing factors to this clinical-imaging correlation gap as well as its implications for future research.


Evaluation of the National Surgical Quality Improvement Program Universal Surgical Risk Calculator for a gynecologic oncology service.
The National Surgical Quality Improvement Program is aimed at preventing perioperative complications. An online calculator was recently published, but the primary studies used limited gynecologic surgery data. The purpose of this study was to evaluate the performance of the National Surgical Quality Improvement Program Universal Surgical Risk Calculator (URC) on the patients of a gynecologic oncology service. We reviewed 628 consecutive surgeries performed by our gynecologic oncology service between July 2012 and June 2013. Demographic data including diagnosis and cancer stage, if applicable, were collected. Charts were reviewed to determine complication rates. Specific complications were as follows: death, pneumonia, cardiac complications, surgical site infection (SSI) or urinary tract infection, renal failure, or venous thromboembolic event. Data were compared with modeled outcomes using Brier scores and receiver operating characteristic curves. Significance was declared based on P < 0.05. The model accurately predicated death and venous thromboembolic event, with Brier scores of 0.004 and 0.003, respectively. Predicted risk was 50% greater than experienced for urinary tract infection; the experienced SSI and pneumonia rates were 43% and 36% greater than predicted. For any complication, the Brier score 0.023 indicates poor performance of the model. In this study of gynecologic surgeries, we could not verify the predictive value of the URC for cardiac complications, SSI, and pneumonia. One disadvantage of applying a URC to multiple subspecialties is that with some categories, complications are not accurately estimated. Our data demonstrate that some predicted risks reported by the calculator need to be interpreted with reservation.


Inactivation of delta 5-3-oxo steroid isomerase with active-site-directed acetylenic steroids.
Several steroid analogues containing conjugated acetylenic ketone groups as part of a seco-ring structure or as substituents on the intact steroid system are irreversible inhibitors of delta 5-3-oxo steroid isomerase (EC 220.127.116.11) from Pseudomonas testosteroni. Thus 10 beta-(1-oxoprop-2-ynyl)oestr-4-ene-3,17-dione (I), 5,10-seco-oestr-4-yne-3,10,17-trione (II), 17 beta-hydroxy-5,10-seco-oestr-4-yne-3,10-dione (III) and 17 beta-(1-oxoprop-2-ynyl)androst-4-en-3-one (IV) irreversibly inactivate isomerase in a time-dependent manner. In all cases saturation kinetics are observed. Protection against inactivation is afforded by the powerful competitive inhibitor 19-nortestosterone. The inhibition constants (Ki) for 19-nortestosterone obtained from such experiments are in good agreement with those determined from conventional competitive-inhibition studies of enzyme activity. These compounds thus appear to be active-site directed. In every case the inactivated enzyme could be dialysed without return of activity, indicating that a stable covalent bond probably had formed between the steroid and enzyme. Compound (I) is a very potent inhibitor of isomerase [Ki = 66.0 microM and k+2 = 12.5 x 10(-3) s-1 (where Ki is the dissociation constant of the reversible enzyme-inhibitor complex and k+2 is the rate constant for the inactivation reaction of the enzyme-inhibitor complex)] giving half-lives of inactivation of 30-45 s at saturation. It is argued that the basic-amino-acid residue that abstracts the intramolecularly transferred 4 beta-proton in the reaction mechanism could form a Michael-addition product with compound (I). In contrast, although compound (IV) has a lower inhibition constant (Ki = 14.5 microM), it is a relatively poor alkylating agent (k+2 = 0.13 x 10(-3) s-1). If the conjugated acetylenic ketone groups are replaced by alpha-hydroxyacetylene groups, the resultant analogues of steroids (I)-(IV) are reversible competitive inhibitors with Ki values in the range 27-350 microM. The enzyme binds steroids in the C19 series with functionalized acetylenic substituents at C-17 in preference to steroids in the C18 series bearing similar groups in the ring structure or as C-10 substituents. In the 5,10-seco-steroid series the presence of hydroxy groups at both C-3 and C-17 is deleterious to binding by the enzyme.


The effect of guided imagery upon first semester nursing students performing their first injections.
This study examined the effect of guided imagery upon the anxiety of baccalaureate nursing students learning to perform their first injections. The quasi-experimental post test design used a treatment (imagery) group and a control group of subjects who were first semester undergraduate students. Anxiety was measured by State-Trait Anxiety Inventory (STAI), Biodot stress dots, performance time, and performance score. Analyses of covariance were performed on the post treatment STAI scores, performance times, and performance scores. A Kruskal-Wallis was performed on post treatment Biodot stress dot reading. Results indicated statistically significant lower anxiety levels by self-report (STAI), p = .008, in the experimental group. No statistically significant differences were found in the Biodot stress dot readings, p = .6777, performance times, p = .130, or performance scores, p = .774. The significance of the findings is that if guided imagery reduces self-reported anxiety levels in nursing students, introduction of this teaching strategy early in the curriculum may be beneficial to students.


Women's role in sanitation decision making in rural coastal Odisha, India.
While women and girls face special risks from lack of access to sanitation facilities, their ability to participate and influence household-level sanitation is not well understood. This paper examines the association between women's decision-making autonomy and latrine construction in rural areas of Odisha, India. We conducted a mixed-method study among rural households in Puri district. This included a cross sectional survey among 475 randomly selected households. These were classified as either having a functional latrine, a non-functional latrine or no latrine at all. We also conducted 17 in-depth interviews and 9 focus group discussions among household members of these three categories of households. Decisions on the construction of household level sanitation facilities were made exclusively by the male head in 80% of households; in 11% the decision was made by men who consulted or otherwise involved women. In only 9% of households the decision was made by women. Households where women were more involved in general decision making processes were no more likely to build a latrine, compared to households where they were excluded from decisions. Qualitative research revealed that women's non-involvement in sanitation decision making is attributed to their low socio-economic status and inability to influence the household's financial decisions. Female heads lacked confidence to take decisions independently, and were dependent on their spouse or other male family members for most decisions. The study revealed the existence of power hierarchies and dynamics within households, which constrained female's participation in decision-making processes regarding sanitation. Though governments and implementers emphasize women's involvement in sanitation programmes, socio-cultural factors and community and household level dynamics often prevent women from participating in sanitation-related decisions. Measures are needed for strengthening sanitation policies and effective implementation of programmes to address gender power relations and familial relationships that influence latrine adoption and use.


Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.
Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.


Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP.
Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.


Design and simulations of a dynamic polarization-mode dispersion compensator for long-haul optical networks.
A new technique and apparatus design for compensation of first-, second-, and higher-order polarization-mode dispersion (PMD) is proposed. Rigorous simulations show that the effects of the high-PMD long-haul fiber are dynamically mitigated or minimized and that the data are recovered from the distorted signals. The technique uses a real-time signal-monitoring and feedback method in the design of the PMD compensator that consists of a combination of polarization-based optical components. The resulting apparatus will enhance the transmission quality, extend the reach of current high-bit-rate (OC-192) optical signal transport, and enable the next-generation ultrahigh-bit-rate optical signals (OC-768 and beyond). The module and method provide a dynamically reconfigurable functional control to mitigate the influence of high-PMD fiber on high-bit-rate optical data. It can be packaged into a box or board/card or with other functional blocks (MUX/DEMUX, optical amplifiers, and the like) at the optical network nodes.


van der Waals force layered multiferroic hybrid perovskite (CH3NH3)2CuCl4 single crystals.
In inorganic-organic perovskites, the three-dimensional arrangement of the organic group results in more subtle balance of charge, spin and space, thereby providing an attractive route toward new multiferroics. Here we report the existing of multiple ferroic orderings in inorganic-organic layered perovskites with relative strong hydrogen bond ordering of the organic chains intra plane. In addition, the inter plane in perovskite is stacking via van der Waals force. However, such magnetoelectric coupling properties for this compound have not been reported since it is difficult to characterize the properties in single crystals since most of the hybrid perovskites are usually deliquescent and unstable when exposed to air. To deal with these problems, we synthesized a (CH3NH3)2CuCl4 single crystal by using a simple evaporation technique, and demonstrated ferroelectric, magnetic and magneto-electric properties of (CH3NH3)2CuCl4. The internal hydrogen bonding of easily tunable organic unit combined with 3d transition-metal layers in such hybrid perovskites make (CH3NH3)2CuCl4 a multiferroic crystal with magnetoelectrical coupling and offer an new way to engineer multifunctional multiferroic.


Discovery and evaluation of inhibitory activity and mechanism of arylcoumarin derivatives on Theileria annulata enolase by in vitro and molecular docking studies.
In this study, the inhibition potential of 3- and 4-arylcoumarin derivatives on Theileria annulata enolase (TaENO) was assessed for the first time in the literature. Firstly, protein stabilization analyses of TaENO were performed and it was found that the enzyme remains stable with the addition of 6 M ethylene glycol at + 4 °C. Inhibitor screening analyses were carried out using 25 coumarin derivatives on highly purified TaENO (> 95%), and four coumarin derivatives [4-(3,4-dimethoxyphenyl)-6,7-dihydroxy-2H-chromen-2-one (C8); 4-(3,4-dihydroxyphenyl)-7,8 dihydroxy-2H-chromen-2-one (C9); 4-(3,4-dihydroxyphenyl)-6,7-dihydroxy-2H-chromen-2 one (C21); and 3-(3,4-dihydroxyphenyl)-7,8-dihydroxy-2H-chromen-2-one (C23)] showed the highest inhibitory effects with the IC50 values of 10.450, 13.170, 8.871 and 10.863 µM, respectively. The kinetic results indicated that these compounds inhibited the enzyme by uncompetitive inhibition. In addition, the successful binding of the most potent inhibitor (C21) into TaENO was confirmed by using MALDI-TOF mass spectrophotometry. Molecular docking analyses have predicted that C8 and C21 coumarin derivatives which showed high inhibitory effects on TaENO were interacted with high affinity to the potential regions out of the active site. Taken together, these coumarin derivatives (C8, C9, C21 and C23) are first known potent, nonsubstrate, uncompetitive inhibitors of TaENO and these results will facilitate further in vitro and in vivo analysis toward structure-based drug design studies.


Transition state and ground state properties of the helix-coil transition in peptides deduced from high-pressure studies.
Volume changes associated with protein folding reactions contain valuable information about the folding mechanism and the nature of the transition state. However, meaningful interpretation of such data requires that overall volume changes be deconvoluted into individual contributions from different structural components. Here we focus on one type of structural element, the α-helix, and measure triplet-triplet energy transfer at high pressure to determine volume changes associated with the helix-coil transition. Our results reveal that the volume of a 21-amino-acid alanine-based peptide shrinks upon helix formation. Thus, helices, in contrast with native proteins, become more stable with increasing pressure, explaining the frequently observed helical structures in pressure-unfolded proteins. Both helix folding and unfolding become slower with increasing pressure. The volume changes associated with the addition of a single helical residue to a preexisting helix were obtained by comparing the experimental results with Monte Carlo simulations based on a kinetic linear Ising model. The reaction volume for adding a single residue to a helix is small and negative (-0.23 cm(3) per mol = -0.38 Å(3) per molecule) implying that intrahelical hydrogen bonds have a smaller volume than peptide-water hydrogen bonds. In contrast, the transition state has a larger volume than either the helical or the coil state, with activation volumes of 2.2 cm(3)/mol (3.7 Å(3) per molecule) for adding and 2.4 cm(3)/mol (4.0 Å(3) per molecule) for removing one residue. Thus, addition or removal of a helical residue proceeds through a transitory high-energy state with a large volume, possibly due to the presence of unsatisfied hydrogen bonds, although steric effects may also contribute.


Heterogeneity of the calcitonin receptor: functional aspects in osteoclasts and other sites.
The recent cloning of the calcitonin receptor reveals it as a member of a new family of 7-transmembrane, G protein-linked receptors. Data from rat, mouse and human receptor cloning reveal that in each of these species the receptor exists in more than one form, most likely the result of alternate, splicing. In the rat, the two forms are C1a and C1b, the latter differing from C1a in that it contains a 37-amino acid insert in the second extracellular domain. The two receptor isoforms differ in their distribution in vivo, with the C1b predominantly in the central nervous system and C1a in other tissues. Both forms have been shown to be present in mature and developing osteoclasts, with the C1a isoform predominating. The two isoforms differ in their kinetics and pharmacological properties, with C1b being virtually unable to bind the human and rat calcitonins but readily binding salmon calcitonin. It will be important to elucidate the physiological significance of the structural heterogeneity of the calcitonin receptor.


Phenotypic diversity of Methylobacterium associated with rice landraces in North-East India.
The ecology and distribution of many bacteria is strongly associated with specific eukaryotic hosts. However, the impact of such host association on bacterial ecology and evolution is not well understood. Bacteria from the genus Methylobacterium consume plant-derived methanol, and are some of the most abundant and widespread plant-associated bacteria. In addition, many of these species impact plant fitness. To determine the ecology and distribution of Methylobacterium in nature, we sampled bacteria from 36 distinct rice landraces, traditionally grown in geographically isolated locations in North-East (NE) India. These landraces have been selected for diverse phenotypic traits by local communities, and we expected that the divergent selection on hosts may have also generated divergence in associated Methylobacterium strains. We determined the ability of 91 distinct rice-associated Methylobacterium isolates to use a panel of carbon sources, finding substantial variability in carbon use profiles. Consistent with our expectation, across spatial scales this phenotypic variation was largely explained by host landrace identity rather than geographical factors or bacterial taxonomy. However, variation in carbon utilisation was not correlated with sugar exudates on leaf surfaces, suggesting that bacterial carbon use profiles do not directly determine bacterial colonization across landraces. Finally, experiments showed that at least some rice landraces gain an early growth advantage from their specific phyllosphere-colonizing Methylobacterium strains. Together, our results suggest that landrace-specific host-microbial relationships may contribute to spatial structure in rice-associated Methylobacterium in a natural ecosystem. In turn, association with specific bacteria may provide new ways to preserve and understand diversity in one of the most important food crops of the world.


FlbA-Regulated Gene rpnR Is Involved in Stress Resistance and Impacts Protein Secretion when Aspergillus niger Is Grown on Xylose.
Proteins are secreted throughout the mycelium of Aspergillus niger except for the sporulating zone. A link between sporulation and repression of protein secretion was underlined by the finding that inactivation of the sporulation gene flbA results in mycelial colonies that secrete proteins throughout the colony. However, ΔflbA strain hyphae also lyse and have thinner cell walls. This pleiotropic phenotype is associated with differential expression of 36 predicted transcription factor genes, one of which, rpnR, was inactivated in this study. Sporulation, biomass, and secretome complexity were not affected in the ΔrpnR deletion strain of the fungus. In contrast, ribosomal subunit expression and protein secretion into the medium were reduced when A. niger was grown on xylose. Moreover, the ΔrpnR strain showed decreased resistance to H2O2 and the proteotoxic stress-inducing agent dithiothreitol. Taking the data together, RpnR is involved in proteotoxic stress resistance and impacts protein secretion when A. niger is grown on xylose.IMPORTANCEAspergillus niger secretes a large amount and diversity of industrially relevant enzymes into the culture medium. This makes the fungus a widely used industrial cell factory. For instance, carbohydrate-active enzymes of A. niger are used in biofuel production from lignocellulosic feedstock. These enzymes represent a major cost factor in this process. Higher production yields could substantially reduce these costs and therefore contribute to a more sustainable economy and less dependence on fossil fuels. Enzyme secretion is inhibited in A. niger by asexual reproduction. The sporulation protein FlbA is involved in this process by impacting the expression of 36 predicted transcription factor genes. Here, we show that one of these predicted transcriptional regulators, RpnR, regulates protein secretion and proteotoxic stress resistance. The gene is thus an interesting target to improve enzyme production in A. niger.


Strengthening the research to policy and practice interface: exploring strategies used by research organisations working on sexual and reproductive health and HIV/AIDS.
This commentary introduces the HARPS supplement on getting research into policy and practice in sexual and reproductive health (SRH). The papers in this supplement have been produced by the Sexual Health and HIV Evidence into Practice (SHHEP) collaboration of international research, practitioner and advocacy organizations based in research programmes funded by the UK Department for International Development.The commentary describes the increasing interest from research and communication practitioners, policy makers and funders in expanding the impact of research on policy and practice. It notes the need for contextually embedded understanding of ways to engage multiple stakeholders in the politicized, sensitive and often contested arenas of sexual and reproductive health. The commentary then introduces the papers under their respective themes: (1) The theory and practice of research engagement (two global papers); (2) Applying policy analysis to explore the role of research evidence in SRH and HIV/AIDS policy (two papers with examples from Ghana, Malawi, Uganda and Zambia); (3) Strategies and methodologies for engagement (five papers on Kenya, South Africa, Ghana, Tanzania and Swaziland respectively); (4) Advocacy and engagement to influence attitudes on controversial elements of sexual health (two papers, Bangladesh and global); and (5) Institutional approaches to inter-sectoral engagement for action and strengthening research communications (two papers, Ghana and global).The papers illustrate the many forms research impact can take in the field of sexual and reproductive health. This includes discursive changes through carving out legitimate spaces for public debate; content changes such as contributing to changing laws and practices, procedural changes such as influencing how data on SRH are collected, and behavioural changes through partnerships with civil society actors such as advocacy groups and journalists.The contributions to this supplement provide a body of critical analysis of communication and engagement strategies across the spectrum of SRH and HIV/AIDS research through the testing of different models for the research-to-policy interface. They provide new insights on how researchers and communication specialists can respond to changing policy climates to create windows of opportunity for influence.


Effect of drying and storage on the degradation of total carotenoids in orange-fleshed sweetpotato cultivars.
Orange-fleshed sweetpotato (OFSP) can be used to tackle vitamin A deficiency, a major public health problem in most developing countries. In East Africa, common ways of using sweetpotato include drying and subsequent storage. The aim of the study was to investigate the impact of drying and storage on the total carotenoid retention (as an estimate of provitamin A retention) from OFSP. Losses of total carotenoid during drying were generally low (15% or less). Total carotenoid retention in OFSP was not dependent on the type of dryer (solar or sun). Sweetpotato cultivar (Ejumula, Kakamega, SPK004/1, SPK004/1/1, SPK004/6 or SPK004/6/6) had a significant effect on retention in drying (P < 0.05). High percentage losses of total carotenoids were, however, correlated with high moisture content and high carotenoid content in fresh sweetpotato roots. After 4 months' storage at room temperature in Uganda, losses of total carotenoid in dried sweetpotato chips were high (about 70%) and this was not dependent on the use of opaque or transparent packaging. Losses of carotenoids during storage were considered to be more of a nutritional constraint to the utilisation of dried sweetpotato than losses occurring during drying. The relationship between characteristics of the cultivars and losses of carotenoids during drying should be taken into account in selection of cultivars for processing.


Using Point-of-Choice Prompts to Reduce Sedentary Behavior in Sit-Stand Workstation Users.
Introduction: Desk-based office workers are at occupational risk for poor health outcomes from excessive time spent sitting. Sit-stand workstations are used to mitigate sitting, but lack of workstation usage has been observed. Point-of-choice (PoC) prompts offer a complementary strategy for office workers to break up their sitting time. Study purpose: The purpose of this study was to examine the preliminary efficacy, preference, and acceptability of a theory-driven (i.e., 40 unique prompts encompassing social cognitive theory; TD-PoC) and an atheoretical basic reminder PoC prompt intervention (R-PoC) on reducing sedentary behavior in office workers with self-reported low sit-stand workstation usage (≤4 h per day). Methods: In a cross-over design, participants (N = 19, 78.9% female, 39.4 ± 10.7 years of age) completed a 5-days no-prompt control condition followed by a random and counterbalanced assignment to one of the TD-PoC and R-PoC active conditions with a 1-week washout period between. Preliminary efficacy was assessed during work hours with the activPAL micro accelerometer. Preference was assessed prior to each active condition and acceptability was assessed following each active condition via questionnaire. Results: The R-PoC prompt condition significantly decreased sitting time (b[se] = -49.0 [20.8], p = 0.03) and increased standing time (b[se] = 49.8 [19.7], p = 0.02) and displayed a significant increase in sit-stand transitions (b[se] = 2.3 [1.1], p = 0.04), relative to no-prompt control. Both the R-PoC and TD-PoC prompt conditions significantly decreased time spent in prolonged sitting bouts at b[se] = -68.1 [27.8], (p = 0.02), (b[se] = -76.7 [27.1], p = 0.008) relative to no-prompt control. Overall, the TD-PoC prompt condition displayed higher preference and acceptability ratings; however, these differences were not significant (p's > 0.05). Conclusion: While the R-PoC prompt condition was slightly more efficacious than the TD-PoC prompt condition, the TD-PoC prompt condition was rated with higher preference and acceptability scores. Large variations between participants in preference, acceptability, and intervention feedback may indicate need for tailored messaging which may facilitate sustained use in the long-term.


Dopaminergic axons in different divisions of the adult rat striatal complex do not express vesicular glutamate transporters.
Midbrain dopamine neurons signal rapid information about rewards and reward-related events. It has been suggested that this fast signal may, in fact, be conveyed by co-released glutamate. Evidence that dopamine neurons co-release glutamate comes largely from studies involving cultured neurons or tissue from young animals. Recently, however, it has been shown that this dual glutamatergic/dopaminergic phenotype declines with age, and can be induced by injury, suggesting that it is not a key feature of adult dopamine neurons. Here, we provide further support for this view by showing that dopaminergic axons and terminals in subregions of the adult striatum do not express vesicular glutamate transporters (VGluT1, VGluT2 or VGluT3). Striatal tissue from the adult rat was immunolabelled to reveal tyrosine hydroxylase (TH; biosynthetic enzyme of dopamine) and one of the three known VGluTs. Importantly, we compared the immunogold labelling for each of the VGluTs associated with TH-positive structures with background labelling at the electron microscopic level. In addition, we carried out a subregional analysis of the core and shell of the nucleus accumbens. We found that dopaminergic axons and terminals in the dorsolateral striatum and ventral striatum (nucleus accumbens core and shell) do not express VGluT1, VGluT2 or VGluT3. We conclude, therefore, that in the normal, adult rat striatum, dopaminergic axons do not co-release glutamate.


Avoidance of biliary injury during laparoscopic cholecystectomy.
Biliary injury during laparoscopic cholecystectomy is still a serious problem. Injury occurs as a result of technical errors or misidentification of ducts. Inexperience, inflammation, and aberrant anatomy are key risk factors. The most serious technical problem is cautery-induced injury. This problem may be avoided by use of cautery under very low power settings in the triangle of Calot. Misidentification injuries occur when the surgeon mistakes the common bile duct or an aberrant right hepatic duct for the cystic duct. This error usually occurs when the surgeon uses the "infundibular" technique to identify the cystic duct. This technique, which depends on seeing the cystic duct flare as it becomes the infundibulum, is especially prone to be misleading in the face of acute inflammation. This technique is unreliable and should not be used alone for anatomic identification of the ducts. It is preferable to use the critical view technique or to perform a cholangiogram.


Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats.
The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes.


Randomised clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome.
To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS). The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose. There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance. The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.


Alcohol misuse and psychological resilience among U.S. Iraq and Afghanistan era veterans.
The present study sought to investigate the longitudinal effects of psychological resilience against alcohol misuse adjusting for socio-demographic factors, trauma-related variables, and self-reported history of alcohol abuse. Data were from the National Post-Deployment Adjustment Study (NPDAS) participants who completed both a baseline and one-year follow-up survey (N=1090). Survey questionnaires measured combat exposure, probable posttraumatic stress disorder (PTSD), psychological resilience, and alcohol misuse, all of which were measured at two discrete time periods (baseline and one-year follow-up). Baseline resilience and change in resilience (increased or decreased) were utilized as independent variables in separate models evaluating alcohol misuse at the one-year follow-up. Multiple linear regression analyses controlled for age, gender, level of educational attainment, combat exposure, PTSD symptom severity, and self-reported alcohol abuse. Accounting for these covariates, findings revealed that lower baseline resilience, younger age, male gender, and self-reported alcohol abuse were related to alcohol misuse at the one-year follow-up. A separate regression analysis, adjusting for the same covariates, revealed a relationship between change in resilience (from baseline to the one-year follow-up) and alcohol misuse at the one-year follow-up. The regression model evaluating these variables in a subset of the sample in which all the participants had been deployed to Iraq and/or Afghanistan was consistent with findings involving the overall era sample. Finally, logistic regression analyses of the one-year follow-up data yielded similar results to the baseline and resilience change models. These findings suggest that increased psychological resilience is inversely related to alcohol misuse and is protective against alcohol misuse over time. Additionally, it supports the conceptualization of resilience as a process which evolves over time. Moreover, our results underscore the importance of assessing resilience as part of alcohol use screening for preventing alcohol misuse in Iraq and Afghanistan era military veterans.


Photodissociation dynamics of ethanethiol in clusters: complementary information from velocity map imaging, mass spectrometry and calculations.
We investigate the solvent effects on photodissociation dynamics of the S-H bond in ethanethiol CH3CH2SH (EtSH). The H fragment images are recorded by velocity map imaging (VMI) at 243 nm in various expansion regimes ranging from isolated molecules to clusters of different sizes and compositions. The VMI experiment is accompanied by electron ionization mass spectrometry using a reflectron time-of-flight mass spectrometer (RTOFMS). The experimental data are interpreted using ab initio calculations. The direct S-H bond fission results in a peak of fast fragments at Ekin(H) ≈ 1.25 eV with a partly resolved structure corresponding to vibrational levels of the CH3CH2S cofragment. Clusters of different nature ranging from dimers to large (EtSH)N, N ≥ 10, clusters and to ethanethiol clusters embedded in larger argon "snowballs" are investigated. In the clusters a sharp peak of near-zero kinetic energy fragments occurs due to the caging. The dynamics of the fragment caging is pictured theoretically, using multi-reference ab initio theory for the ethanethiol dimer. The larger cluster character is revealed by the simultaneous analysis of the VMI and RTOFMS experiments; none of these tools alone can provide the complete picture.


Ankle flexors produce peak torque at longer muscle lengths after whole-body vibration.
Whole-body vibration (WBV) has become a popular training method in recent years. This study investigated the effect of WBV on the length-tension relationship of the ankle dorsi- and plantarflexors as measured by a Biodex dynamometer (Biodex Medical Systems Inc, Shirley, NY). Twenty healthy young adult males participated in this study and were exposed to two treatments. The first treatment (nonvibration) involved passive stretching of the plantarflexors at end range of motion (ROM) for five 1-min bouts. The second treatment involved the same passive stretch with superimposed WBV (frequency = 26 Hz) for five 1-min bouts on a rotary vibration plate (Galileo 900; Novotec, Pforzheim, Germany). Voluntary ROM, peak torque, and corresponding joint angle of the plantar- and dorsiflexors were recorded pre- and posttreatment. Within-treatment (before and after) and between-treatment (WBV and nonvibration) outcomes were assessed by repeated-measures MANOVA. No significant changes in the measures of ankle dorsiflexion were found within or between treatments. No significant changes in the measures of ankle plantarflexion were found after the nonvibration treatment. After WBV, however, there was a significant 7.1 degree shift in the angle (P = 0.001) of peak plantarflexor torque production corresponding to a longer muscle length. This study shows that stretched human ankle plantarflexors respond to WBV by generating peak voluntary torque at longer muscle lengths. This has possible benefits for the rehabilitation of patients with neuromuscular disorders (e.g., stroke) who experience short ankle flexor resting lengths.


Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q.
Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Statistical analysis was performed using multipoint parametric and nonparametric linkage. Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1). The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.


Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population.
To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis. Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02-2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.


Association Between Implementation of the Athlete Biological Passport and Female Elite Runners' Performance.
The purpose of this research was to evaluate the performances of female middle- and long-distance runners before and after the implementation of a new antidoping strategy (the Athlete Biological Passport [ABP]) in a country accused of systematic doping. A retrospective analysis of the results of Russian National Championships from 2008 to 2017 was performed. The 8 best female performances for the 800-m, 1500-m, 3000-m steeplechase, 5000-m, and 10,000-m events from the semifinals and finals were analyzed. The yearly number of athletes fulfilling standard qualifications for international competitions was also evaluated. Overall, numbers of athletes banned for doping in 2008-2017 were calculated. As a result, 4 events (800, 1500, 5000 [all P < .001], and 10,000 m [P < .01]) out of 5 showed statistically significant deterioration in the performances when comparing before and after the introduction of the ABP. The 3000-m steeplechase was the only event that did not show statistically significant change. The highest relative decrease in the number of runners who met standard qualification for international competition was for the 5000-m event (46%), followed by 1500-m (42%), 800-m (38%), 10,000-m (17%), and 3000-m steeplechase (1%). In conclusion, implementation of the ABP was followed by a significant reduction in the performance of female runners in a country accused of systematic doping. It can be reasonably speculated that more stringent antidoping testing, more specifically the introduction of the ABP, is a key reason for this reduction.


Predictors of recurrent febrile seizures: a metaanalytic review.
The 1980 National Institutes of Health Consensus Development Conference on Febrile Seizures identified five circumstances in which it might be appropriate to consider anticonvulsant prophylaxis after a first febrile seizure: (1) a focal or prolonged seizure, (2) neurologic abnormalities, (3) afebrile seizures in a first-degree relative, (4) age less than 1 year, and (5) multiple seizures occurring within 24 hours. We performed a metaanalysis of 14 published reports to evaluate the strength of association between each of these indications and recurrent febrile seizures. Young age at onset (less than or equal to 1 year) and a family history of febrile seizures (not listed in the recommendations) each distinguished between groups with approximately a 30% versus a 50% risk of recurrence. Family history of afebrile seizures was not consistently associated with an increased risk. Focal, prolonged, and multiple seizures were associated with only a small increment in risk of recurrence. The data were not adequate to assess the risk associated with neurologic abnormalities. By considering children with combinations of risk factors, some studies were able to distinguish between groups with very low and very high recurrence risks. Only age at onset was consistently predictive of having more than one recurrence. These results suggest that the great majority of children who have a febrile seizure do not need anticonvulsant treatment even if one of the factors listed in the Consensus Statement is present, and that the rationale and indications for treating febrile seizures need to be reconsidered.


A gamma-melanocyte stimulating hormone-like peptide causes reflex natriuresis after acute unilateral nephrectomy.
Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-beta-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that gamma-melanocyte stimulating hormone (gamma-MSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive gamma-MSH-like material was 40 +/- 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive gamma-MSH was 81 +/- 36 fmol/ml (p less than 0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive gamma-MSH (r = 0.75, p less than 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against gamma-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic gamma-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-gamma-MSH antiserum blocked this effect of peptide infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene.
Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.


Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations.
Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of 1 in 700 live births. The paired box (PAX) genes have been suggested as candidate genes for CL/P based largely on mouse models; however, few human studies have focused on this gene family. This study tests for association between markers in four PAX genes and CL/P using a case-parent trio design considering parent-of-origin effects. Trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 34 single nucleotide polymorphisms (SNPs) in the PAX3, PAX6, PAX7, and PAX9 genes. We performed the transmission disequilibrium test (TDT) on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test (TAT) and the parent-of-origin likelihood ratio test (PO-LRT). TDT analysis showed one SNP (rs766325) in PAX7 yielding evidence of linkage and association when parent-of-origin was not considered, with an OR(transmission)=1.62 (P=0.003), and five SNPs in PAX6 (including two pairs in near perfect linkage disequilibrium). TAT analysis of all trios revealed two SNPs in PAX7 and four SNPs in PAX3 showing significant excess maternal transmission. For these six SNPs, the maternal OR(transmission) ranged between 1.74 and 2.40, and PO-LRT was also significant (P-values=0.035-0.012). When this analysis was limited to trios with male cases, SNPs in PAX7 showed higher maternal OR(transmission) and greater significance. PAX genes may influence the risk of CL/P through maternal effects, possibly imprinting, which seems to be stronger among male cases.


Gene therapy for colorectal cancer.
Colorectal cancer is an important public health problem worldwide. Gene therapy has therapeutic potential for patients with advanced or recurrent colorectal cancer, incurable by conventional treatments. To date, many strategies of gene therapy have been explored, including mutant gene correction, prodrug activation, immune stimulation and genetically-modified oncolytic viruses. Although the preclinical results of gene therapy for colorectal cancer have shown promise, gene therapy is still at an early stage of clinical development and has not yet shown a significant therapeutic benefit for patients. The main obstacles for introduction of gene therapy to patients are poor targeting selectivity of the vectors and inefficient gene transfer. As the science supporting tumour-selective vectors evolves, gene therapy may expand rapidly in the clinical practice of colorectal cancer treatment.


Young people with intellectual disability--the role of self-advocacy in a transformed Swedish welfare system.
A growing number of young people in Sweden with intellectual disability have organized themselves during the last 15 years in self-advocacy groups for socializing, empowerment, and expressing opposition to the norms and attitudes in a society that labels them as disabled. At the same time, the Swedish welfare system has transformed dramatically with processes of far-reaching individualization, closure of the major institutions, decentralization of responsibility from the state to local governments, and an emerging welfare market where service users are turned into customers. The aim of this article is to analyse and discuss the significance of self-advocacy in the new welfare context. Data were collected over a period of more than 10 years using repeated interviews with members of two self-advocacy groups and participation observations. Findings suggest that participation in self-advocacy groups opens up members for increasing health and well-being through new roles and identities, and it strengthens their control over everyday life. Support is still needed, however, but in new ways; otherwise, the restrictions of the institutions will simply be reconstructed in the new welfare system.


Theoretical and practical results of the optimisation of Hamburg's WWTPs with dynamic simulation.
To assess the influence of the connection of a further 250,000 PE in addition to the 1.86 m PE already served by the combined WWTPs Köhlbrandhöft/Dradenau, a dynamic simulation study was started in 1996. A previous study developing the extension of the WWTP proposed several solutions with costs between 25 million euros and 100 million euros. Those concepts were examined by a dynamic simulation study for comparison and further optimisation. The simulation results indicated that with an increased volume for the storage of sludge liquor it would be likely to fulfil the effluent requirements in spite of the increased load. The construction of the additional storage tank was finished at the end of 1999 together with the connection of the additional load to the WWTP. The cost of this concept was less than 1 million euros, which is significantly less than if the plants had been extended in a traditional manner. The first two years of operation showed that the chosen solution is able to fulfil the requirements. The effluent values can be kept within the required limits. A very good correspondence between the measured and the simulated values could be observed.


A biopsychosocial approach to primary hypothyroidism: treatment and harms data from a randomized controlled trial.
Hypothyroidism is a common endocrine condition. There is evidence to suggest that, for a proportion of sufferers, the standard medical treatment does not completely reverse the constitutional and neuropsychiatric symptoms brought about by this condition. The management of hypothyroidism follows a biomedical model with little consideration given to alternative management approaches. There exists anecdotal evidence and case reports supporting the use of a biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for this population. The aim of this study was to explore the potential short-medium term clinical efficacy and safety of NET for individuals with primary hypothyroidism.DesignPlacebo-controlled, blinded, parallel groups, randomized trial. Ninety adults with a diagnosis of primary hypothyroidism were recruited from Sydney, Australia. Blinded participants were randomized to either the NET or placebo group and received ten intervention sessions over a six week period. The primary outcome involved the measurement of states of depression using the DASS-42 questionnaire. Secondary outcomes included thyroid function, thyroid autoimmunity testing, SF-36v2 questionnaire, resting heart rate and temperature measurement. Outcomes were obtained at baseline, seven weeks and six months. Questionnaires were completed at the private clinics, and serum measures were obtained and analysed at commercial pathology company locations. Heart rate and temperature were also measured daily by participants. Linear mixed-effects models were used to analyse the continuous outcomes. Unadjusted odds ratios with 95% confidence intervals were calculated for the binary outcomes. Participants were randomly allocated to the NET (n=44) and placebo (n=46) groups. A proportion of the sample displayed neuropsychiatric disturbances and alterations in quality of life measures at baseline. There were no statistically significant or clinically relevant changes in the primary or secondary outcomes between the NET and placebo groups at time seven weeks or six months. There were a few short-lived minor adverse events reported in both the NET and placebo groups that coincided with the application of the intervention. The application of the NET intervention appears to be safe, but did not confer any clinical benefit to the participants in this study and is unlikely to be of therapeutic use in a hypothyroid population. Australian and New Zealand Clinical Trials Registry Number: 12607000040460.


Blip-summed quantum-classical path integral with cumulative quantum memory.
The quantum-classical path integral (QCPI) offers a rigorous methodology for simulating quantum mechanical processes in condensed-phase environments treated in full atomistic detail. This paper describes the implementation of QCPI on system-bath models, which are frequently employed in studying the dynamics of reactive processes. The QCPI methodology incorporates all effects associated with stimulated phonon absorption and emission as its crudest limit, thus can (in some regimes) converge faster than influence functional-based path integral methods specifically designed for system-bath Hamiltonians. It is shown that the QCPI phase arising from a harmonic bath can be summed analytically with respect to the discrete bath degrees of freedom and expressed in terms of precomputed influence functional coefficients, avoiding the explicit enumeration of forced oscillator trajectories, whose number grows exponentially with the length of quantum memory. Further, adoption of the blip decomposition (which classifies the system paths based on the time length over which their forward and backward components are not identical) and a cumulative treatment of the QCPI phase between blips allows elimination of the majority of system paths, leading to a dramatic increase in efficiency. The generalization of these acceleration techniques to anharmonic environments is discussed.


How has COVID-19 impacted disability employment?
While the COVID-19 public health emergency has had disastrous health impacts for people with disabilities, it remains unclear what impact the associated economic recession and subsequent recovery have had on disability employment. We evaluated employment trends for people with and without disabilities over the course of the COVID-19 recession and subsequent economic recovery, both overall and by occupational category (essential, non-essential, teleworkable, non-teleworkable, frontline, non-frontline). We made use of data from the nationally representative Current Population Survey. Linear probability models were used to estimate percent changes in employment-to-population ratios and identify differences between disabled and non-disabled employment in each quarter broadly and within specific occupational categories. As the COVID-19 recession began in Q2 2020, people with disabilities experienced employment losses that were proportionately similar to those experienced by people without disabilities. However, during the subsequent economic recovery, the employment rate of people with disabilities grew more quickly in Q4 2021 through Q2 2022, driven by increased labor force participation. These employment gains have been concentrated in teleworkable, essential, and non-frontline occupations. Our findings suggest that people with disabilities are disproportionately benefiting from the rapid recovery from the initial economic contraction at the start of the pandemic.


Stereoisomer-Specific Trophodynamics of the Chiral Brominated Flame Retardants HBCD and TBECH in a Marine Food Web, with Implications for Human Exposure.
Stereoisomers of 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) were determined in sediments and 30 marine species in a marine food web to investigate their trophic transfer. Lipid content was found to affect the bioaccumulation of ΣHBCD and ΣTBECH in these species. Elevated biomagnification of each diastereomer from prey species to marine mammals was observed. For HBCD, biota samples showed a shift from γ- to α-HBCD when compared with sediments and technical mixtures; trophic magnification potential of (-)-α- and (+)-α-HBCD were observed in the food web, with trophic magnification factors (TMFs) of 11.8 and 8.7, respectively. For TBECH, the relative abundance of γ- and δ-TBECH exhibited an increasing trend from abiotic matrices to biota samples; trophic magnification was observed for each diastereomer, with TMFs ranging from 1.9 to 3.5. The enantioselective bioaccumulation of the first eluting enantiomer of δ-TBECH in organisms at higher TLs was consistently observed across samples. This is the first report on the trophic transfer of TBECH in the food web. The estimated daily intake of HBCD for Hong Kong residents was approximately 16-times higher than that for the general population in China, and the health risk to local children was high, based on the relevant available reference dose.


[Normalized difference ratio pigment index for estimating chlorophyll and cartenoid contents of in leaves of rice].
The objective of the present study was (1) to construct new pigment indices based on making full use of all the spectral bands in the 350-2,500 nm region and (2) to compare the performance of these new pigment indices with that of the published normalized difference ratio pigment indices in estimating pigment content of rice. The 252 leaves of rice were sampled at different development stages, representing a wide range of pigment contents. The hyperspectral reflectance of leaves of rice and the corresponding chlorophyll contents and carotenoid contents were measured. A rigorous method using all the wavebands in the range of 350-2,500 nm was applied to generate all possible two-band normalized difference pigment indices, and then the linear models between these indices and chlorophyll and carotenoid contents were constructed. Finally, the index with the highest determination coefficients was selected as the optimal index for corresponding pigment. The model was tested and these selected indices were compared with the published indices. The result indicated that the indices [(R1729-R707)/(R1729+R707), (R1554-R572)/(R1554+R572), (R1729-R706)/(R1729+R706)), (R1536-R707)/(R1536+R707)] can relatively accurately estimate chlorophyll and cartenoid contents. The reference bands of the these new indices are mainly located in short wave infrared spectral region, which indicate that the spectral bands in the short wave infrared region are significant to construct normalized ratio pigment index, while the index bands of these indices are mostly in the region near 700 nm, and the longer bands of green region in the next place. Compared to the published indices, in general, the new indices give more accurate estimation of chlorophyll and carotenoid contents, or they behave the same as the best published index.


Being right on Q: shaping eukaryotic evolution.
Reactive oxygen species (ROS) formation by mitochondria is an incompletely understood eukaryotic process. I proposed a kinetic model [BioEssays (2011) 33: , 88-94] in which the ratio between electrons entering the respiratory chain via FADH2 or NADH (the F/N ratio) is a crucial determinant of ROS formation. During glucose breakdown, the ratio is low, while during fatty acid breakdown, the ratio is high (the longer the fatty acid, the higher is the ratio), leading to higher ROS levels. Thus, breakdown of (very-long-chain) fatty acids should occur without generating extra FADH2 in mitochondria. This explains peroxisome evolution. A potential ROS increase could also explain the absence of fatty acid oxidation in long-lived cells (neurons) as well as other eukaryotic adaptations, such as dynamic supercomplex formation. Effective combinations of metabolic pathways from the host and the endosymbiont (mitochondrion) allowed larger varieties of substrates (with different F/N ratios) to be oxidized, but high F/N ratios increase ROS formation. This might have led to carnitine shuttles, uncoupling proteins, and multiple antioxidant mechanisms, especially linked to fatty acid oxidation [BioEssays (2014) 36: , 634-643]. Recent data regarding peroxisome evolution and their relationships with mitochondria, ROS formation by Complex I during ischaemia/reperfusion injury, and supercomplex formation adjustment to F/N ratios strongly support the model. I will further discuss the model in the light of experimental findings regarding mitochondrial ROS formation.


Linkage Mapping Reveals Strong Chiasma Interference in Sockeye Salmon: Implications for Interpreting Genomic Data.
Meiotic recombination is fundamental for generating new genetic variation and for securing proper disjunction. Further, recombination plays an essential role during the rediploidization process of polyploid-origin genomes because crossovers between pairs of homeologous chromosomes retain duplicated regions. A better understanding of how recombination affects genome evolution is crucial for interpreting genomic data; unfortunately, current knowledge mainly originates from a few model species. Salmonid fishes provide a valuable system for studying the effects of recombination in nonmodel species. Salmonid females generally produce thousands of embryos, providing large families for conducting inheritance studies. Further, salmonid genomes are currently rediploidizing after a whole genome duplication and can serve as models for studying the role of homeologous crossovers on genome evolution. Here, we present a detailed interrogation of recombination patterns in sockeye salmon (Oncorhynchus nerka). First, we use RAD sequencing of haploid and diploid gynogenetic families to construct a dense linkage map that includes paralogous loci and location of centromeres. We find a nonrandom distribution of paralogs that mainly cluster in extended regions distally located on 11 different chromosomes, consistent with ongoing homeologous recombination in these regions. We also estimate the strength of interference across each chromosome; results reveal strong interference and crossovers are mostly limited to one per arm. Interference was further shown to continue across centromeres, but metacentric chromosomes generally had at least one crossover on each arm. We discuss the relevance of these findings for both mapping and population genomic studies.


Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions.
Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.


Investigation of relationship between vitamin D status and reproductive fitness in Scottish hill sheep.
There is a growing interest in the influence of vitamin D on ovine non-skeletal health. The aim of this study was to explore the relationship between pre-mating vitamin D status, as assessed by serum concentrations of 25-Hydroxyvitamin D [25(OH)D; comprising D2 and D3] and subsequent reproductive performance of genetically unimproved Scottish Blackface (UBF), genetically improved Scottish Blackface (IBF) and Lleyn ewes kept under Scottish hill conditions. 25-Hydroxyvitamin D2 (25(OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were determined in serum samples harvested in November from ewes grazed outdoors. There were no significant differences in 25(OH)D2concentrations amongst the 3 genotypes. Lleyn ewes had significantly higher 25(OH)D3 and 25(OH)D concentrations than both Scottish Blackface ewe genotypes, whereas these vitamin D parameters did not differ significantly between the UBF and IBF ewes. Concentrations of 25(OH)D3 and 25(OH)D were positively associated with subsequent birth weights of singleton and of twin lamb litters. No significant associations between vitamin D status and number of lambs born or weaned per ewe were found. This study demonstrates that concentrations of cutaneously-derived 25(OH)D3, but not of orally consumed 25(OH)D2, differed between breeds. The positive association between ewe vitamin D status and offspring birth weight highlights the need for further investigations.


Effects of modulated and continuous microwave irradiation on the morphology and cell surface negative charge of 3T3 fibroblasts.
Mouse embryo 3T3 cells were irradiated with 2450 MHz continuous and low frequency (16 Hz) square modulated waves of absorbed energy ranging from 0.0024 to 2.4 mW/g. The low frequency modulated microwave irradiation yielded more morphological cell changes than did the continuous microwave fields of the same intensity. The amount of free negative charges (cationized ferritin binding) on cell surfaces decreased following irradiation by modulated waves but remained unchanged under the effect of a continuous field of the same dose. Modulated waves of 0.024 mW/g dose increased the ruffling activity of the cells, and caused ultrastructural alteration in the cytoplasm. Similar effects were experienced by continuous waves at higher (0.24 and 2.4 mW/g) doses.


A time for learning and a time for sleep: the effect of sleep deprivation on contextual fear conditioning at different times of the day.
Sleep deprivation negatively affects memory consolidation, especially in the case of hippocampus-dependent memories. Studies in rodents have shown that 5 hours of sleep deprivation immediately following footshock exposure selectively impairs the formation of a contextual fear memory. In these studies, both acquisition and subsequent sleep deprivation were performed in the animals' main resting phase. However, in everyday life, subjects most often learn during their active phase. Here we examined the effects of sleep deprivation on memory consolidation for contextual fear in rats when the task was performed at different times of the day, particularly, at the beginning of the resting phase or right before the onset of the active phase. Results show that sleep deprivation immediately following training affects consolidation of contextual fear, independent of time of training. However, in the resting phase memory consolidation was impaired by 6 hours of posttraining sleep deprivation, whereas, in the active phase, the impairment was only seen after 12 hours of sleep deprivation. Since rats sleep at least twice as much during the resting phase compared with the active phase, these data suggest that the effect of sleep deprivation depends on the amount of sleep that was lost. Also, control experiments show that effects of sleep deprivation were not related to the amount of stimulation the animals received and were therefore not likely an indirect effect of the sleep-deprivation method. These results support the notion that sleep immediately following acquisition, independent of time of day, promotes memory consolidation and that sleep deprivation may disrupt this process depending on the amount of sleep that is lost.


Sutherland's legacy in the new millennium: the osteopathic cranial model and modern osteopathy.
The concept of cranial osteopathy was introduced by W. G. Sutherland, DO, and became the foundation for setting the rules for use of skull palpation and many other techniques in the many types of dysfunctional patterns that craniosacral therapy treats. Sutherland's theories enabled modern osteopathy to develop and improve. The mechanism of primary respiration as well as the motion of neurocranial and viscerocranial sutures are phenomena intrinsic to the field and can be found in every living organism, independent of thoracic breathing and cardiac impulse. The sphenobasilar synchondrosis (ie, the joint between the base of the occiput and the body of the sphenoid bone) is the pillar supporting the concepts of craniosacral therapy. This article compares the cranial model devised by Sutherland with the present, relevant scientific research, aiming at clarifying the possibility of applying the craniosacral model in the new millennium.