How much labor is in a labor epidural? Manpower cost and reimbursement for an obstetric analgesia service in a teaching institution.
Some anesthesiologists avoid provision of obstetric analgesia services (OAS) because of low reimbursement rates for the work involved. This study defines the manpower costs of operating an OAS in a tertiary referral center and examines reimbursement for this cost. The time spent providing OAS in a total of 55 parturients was studied prospectively using a modification of classic time and motion studies. Mean duration of OAS in our population was 412 +/- 313 min. Mean bedside anesthesia staff time was 90 +/- 40 min, and mean number of visits to each patient's bedside was 6.3 +/- 2.0 visits. Assuming staffing on demand for service (intermittent staffing), a minimum of 2.5 full-time equivalent (FTE) attending anesthesiologists was required to meet demand. With intermittent staffing, labor cost was $325 per patient. Actual practice at Duke University Medical Center is around-the-clock (dedicated) staffing, which requires 4.4 FTEs at a cost of $728 per patient. Neither average indemnity reimbursement ($299) nor Medicaid reimbursement ($204) covered the cost per OAS patient. Breaking even is possible under indemnity reimbursement because operating room reimbursement subsidizes OAS costs. Breaking even cannot occur with Medicaid reimbursement under any circumstances. Obstetric analgesia services requires a minimum of 2.5 FTE attending anesthesiologists at Duke University Medical Center. With the current payer mix, positive-margin operating room activities associated with the obstetric service are not sufficient to compensate for the losses incurred by an OAS. Around-the-clock dedicated obstetric staffing (4.4 FTEs) cannot operate profitably under any reasonable circumstances at our institution.


Genotyping of Campylobacter spp. from retail meats by pulsed-field gel electrophoresis and ribotyping.
To determine the genetic relatedness of Campylobacter spp. from retail meat products, and compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and automatic ribotyping. A total of 378 Campylobacter isolates recovered from 159 raw meats (130 chicken, 25 turkey, three pork and one beef) sampled from 50 retail grocery stores of four supermarket chains in the Maryland suburban area from August 1999 to July 2000 were analysed by PFGE with SmaI, 120 isolates of which were also characterized by ribotyping with PstI using RiboPrinter system. A total of 148 unique PFGE patterns were identified, 91 of which were present in multiple Campylobacter isolates and 24 in multiple meat samples. Nineteen Campylobacter clones with identical PFGE patterns recurred frequently (up to nine times) throughout the sampling period. Comparing ribotyping with PFGE, we identified 44 PFGE patterns and 22 RiboGroups among the 120 isolates tested. Multiple PFGE patterns within one RiboGroup were commonly observed, as well as multiple RiboGroups within one PFGE pattern. Although Campylobacter present in retail meats were genetically diverse, certain clones persisted in poultry meats. PFGE had a greater discriminatory power than ribotyping, and the two methods were complementary in genotyping Campylobacter. Genomic DNA fingerprinting of Campylobacter confirmed diverse and recurrent Campylobacter clones in the retail meats, which provides additional data for a better understanding of the epidemiological aspect of Campylobacter infection.


ANIA: ANnotation and Integrated Analysis of the 14-3-3 interactome.
The dimeric 14-3-3 proteins dock onto pairs of phosphorylated Ser and Thr residues on hundreds of proteins, and thereby regulate many events in mammalian cells. To facilitate global analyses of these interactions, we developed a web resource named ANIA: ANnotation and Integrated Analysis of the 14-3-3 interactome, which integrates multiple data sets on 14-3-3-binding phosphoproteins. ANIA also pinpoints candidate 14-3-3-binding phosphosites using predictor algorithms, assisted by our recent discovery that the human 14-3-3-interactome is highly enriched in 2R-ohnologues. 2R-ohnologues are proteins in families of two to four, generated by two rounds of whole genome duplication at the origin of the vertebrate animals. ANIA identifies candidate 'lynchpins', which are 14-3-3-binding phosphosites that are conserved across members of a given 2R-ohnologue protein family. Other features of ANIA include a link to the catalogue of somatic mutations in cancer database to find cancer polymorphisms that map to 14-3-3-binding phosphosites, which would be expected to interfere with 14-3-3 interactions. We used ANIA to map known and candidate 14-3-3-binding enzymes within the 2R-ohnologue complement of the human kinome. Our projections indicate that 14-3-3s dock onto many more human kinases than has been realized. Guided by ANIA, PAK4, 6 and 7 (p21-activated kinases 4, 6 and 7) were experimentally validated as a 2R-ohnologue family of 14-3-3-binding phosphoproteins. PAK4 binding to 14-3-3 is stimulated by phorbol ester, and involves the 'lynchpin' site phosphoSer99 and a major contribution from Ser181. In contrast, PAK6 and PAK7 display strong phorbol ester-independent binding to 14-3-3, with Ser113 critical for the interaction with PAK6. These data point to differential 14-3-3 regulation of PAKs in control of cell morphology. Database URL: https://ania-1433.lifesci.dundee.ac.uk/prediction/webserver/index.py.


Family involvement and patient-experienced improvement and satisfaction with care: a nationwide cross-sectional study in Danish psychiatric hospitals.
Randomised controlled trials suggest that family therapy has a positive effect on the course of depression, schizophrenia and anorexia nervosa. However, it is largely unknown whether a positive link also exists between caregiver involvement and patient outcome in everyday psychiatric hospital care, using information reported directly from patients, i.e. patient-reported experience measures (PREM), and their caregivers. The objective of this study is to examine whether caregiver-reported involvement is associated with PREM regarding patient improvement and overall satisfaction with care. Using data from the National Survey of Psychiatric Patient Experiences 2018, we conducted a nationwide cross-sectional study in Danish psychiatric hospitals including patients and their caregivers who had been in contact with the hospital (n = 940 patients, n = 1008 caregivers). A unique patient identifier on the two distinct questionnaires for the patient and their caregiver enabled unambiguous linkage of data. In relation to PREM, five aspects of caregiver involvement were analysed using logistic regression with adjustment for patient age, sex and diagnosis. We consistently find that high caregiver-reported involvement is statistically significantly associated with high patient-reported improvement and overall satisfaction with care with odds ratios (OR) ranging from 1.69 (95% confidence interval (CI) 0.95-2.99) to 4.09 (95% CI 2.48-6.76). This applies to the following aspects of caregiver-reported involvement: support for the patient-caregiver relationship, caregiver information, consideration for caregiver experiences and the involvement of caregivers in decision making. No statistically significant association is observed regarding whether caregivers talk to the staff about their expectations for the hospital contact. This nationwide study implies that caregiver involvement focusing on the patient-caregiver relationship is positively associated with patient improvement and overall satisfaction with care in everyday psychiatric hospital care.


[Application of copper bactericidal properties in medical practice].
Copper is essential for cell metabolism in animals and plants and thus for life. Along centuries, copper has been identified as a metal containing antimicrobial properties. In recent years, laboratory assays and clinical studies have revealed that surfaces of metallic copper or its alloys, containing at least 70% copper, eliminate in a few hours several pathogenic organisms including bacterial strains associated with nosocomial infections, influenza virus, HIV, and fungi such as Candida albicans. In March 2008, the American Environmental Protection Agency (EPA), supported by scientific evidence gathered to date, registered copper as the first and only metal with antimicrobial properties. We herein review certain mechanisms proposed for the antibacterial, antiviral and antifungal activity of copper. We also discuss in vitro and clinical efficacy studies developed world wide and in Chile, focusing on bactericidal activity of copper surface areas in comparison to materials typically used in hospital environments such as stainless steel and polymers. Scientific evidence gathered to date, consistently shows that the use of copper surface areas in high contact critical points in hospitals, significantly reduces environmental bacterial load. This is associated with a decreased risk of pathogen transmission to patients and represents therefore an interesting complement to infection control programs.


Genetic correlations between pain phenotypes and depression and neuroticism.
Correlations between pain phenotypes and psychiatric traits such as depression and the personality trait of neuroticism are not fully understood. In this study, we estimated the genetic correlations of eight pain phenotypes (defined by the UK Biobank, n = 151,922-226,683) with depressive symptoms, major depressive disorders and neuroticism using the the cross-trait linkage disequilibrium score regression (LDSC) method integrated in the LD Hub. We also used the LDSC software to calculate the genetic correlations among pain phenotypes. All pain phenotypes, except hip pain and knee pain, had significant and positive genetic correlations with depressive symptoms, major depressive disorders and neuroticism. All pain phenotypes were heritable, with pain all over the body showing the highest heritability (h2 = 0.31, standard error = 0.072). Many pain phenotypes had positive and significant genetic correlations with each other indicating shared genetic mechanisms. Our results suggest that pain, neuroticism and depression share partially overlapping genetic risk factors.


The use of an autogenous Dichelobacter nodosus vaccine to eliminate clinical signs of virulent footrot in a sheep flock in Bhutan.
An outbreak of virulent footrot was investigated in a flock of 605 Merino cross-bred sheep in Bhutan. Conventional control methods in the preceding eight years had reduced its prevalence from 36-79% in different components of the flock to about 15% overall. Only one serogroup (B) of Dichelobacter nodosus was identified among 40 isolates cultured from affected sheep. A vaccine prepared from this strain was used in a pilot trial to compare the response of 14 treated and 14 untreated sheep. All affected, vaccinated animals in this trial healed quickly and were protected against re-infection while additional cases developed among untreated sheep during a period favourable for the spread of footrot. The serogroup B vaccine was administered to the whole flock for two successive years. No other footrot treatment was given during these or subsequent years. The whole flock was examined three times, foot by foot, for two years and twice yearly for another two years. When vaccination began there were 88 affected sheep in the flock, an affected sheep being defined as an animal with a foot-score of 2 or greater in one or more feet. There were neither affected sheep in the flock 30 days after the first dose of vaccine nor were any identified in later inspections. Virulent footrot, originating from the farm under investigation, persisted in neighbouring village flocks during this period. It was concluded that whole flock specific D. nodosus vaccination made a major contribution to the elimination of all clinical signs of footrot from the flock of 605 sheep where the condition had previously persisted for 10 years.


Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions.
The presence of certain underlying medical conditions is known to increase the risk of pneumococcal disease in persons of all ages and across a wide spectrum of conditions, as demonstrated in two recent evaluations. Corresponding estimates of attributable economic costs have not been well characterized. We thus undertook a retrospective evaluation to estimate rates and costs of pneumococcal disease among children and adults with and without underlying medical conditions in the United States. Data were obtained from three independent healthcare claims repositories. The study population included all persons enrolled in participating health plans during 2007-2010, and was stratified into subgroups based on age and risk profile: healthy; at-risk, due to selected comorbid conditions; and high-risk, due to selected immunocompromising conditions. At-risk and high-risk conditions, as well as episodes of invasive pneumococcal disease (IPD) and all-cause pneumonia (PNE), were identified via diagnosis, procedure, and drug codes. Rates and healthcare costs of IPD and PNE (2010US$) among at-risk and high-risk persons were compared with those from age-stratified healthy counterparts using incidence rate ratios (IRR) and cost ratios. Rates of IPD and PNE were consistently higher among at-risk persons (IRR = 4.1 [95 % CI 3.9-4.3] and 4.5 [4.49-4.53]) and high-risk persons (IRR = 10.3 [9.7-11.0] and 8.2 [8.2-8.3]) of all ages versus their healthy counterparts. Rates were notably high for at-risk persons with ≥2 conditions (IRR = 9.0 [8.4-9.7] and 10.3 [10.3-10.4]), as well as those with asthma (IRR = 3.4 [3.0-3.8] and 4.5 [4.47-4.53]) or diabetes (IRR = 4.3 [4.0-4.6] and 4.7 [4.6-4.7]). Healthcare costs totaled $21.7 million per 100,000 at-risk person-years and $58.5 million per 100,000 high-risk person-years, which were 8.7 [8.5-8.8] and 23.4 [22.9-23.8] times higher than corresponding costs for healthy persons. Rates and costs of IPD and PNE are substantially higher among persons with certain chronic and immunocompromising conditions versus those without any such conditions. Rates and costs for persons with asthma and diabetes were especially increased, and rates and costs for individuals with ≥2 at-risk conditions approached those among persons with high-risk conditions.


Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet.
Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thiobarbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.


Impact of Proteinase 3 versus Myeloperoxidase Positivity on Risk of End-Stage Renal Disease in ANCA-Associated Glomerulonephritis Stratified by Histological Classification: A Population-Based Cohort Study.
End-stage renal disease (ESRD) risk in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis (ANCA-GN) according to ANCA serotype and stratified by histological classification has not been previously investigated. Patients from the Norwegian Kidney Biopsy Registry (NKBR) between 1991 and 2012 who had biopsy-verified pauci-immune glomerulonephritis and positive antineutrophil cytoplasmic antibody serology were included. Cases with ESRD during follow-up were identified in the Norwegian Renal Registry. ESRD-free survival with proteinase 3 (PR3) versus myeloperoxidase- (MPO-) ANCA positivity stratified into 4 histological classes was investigated. Three hundred fifty-eight patients, of whom 87 progressed to ESRD during follow-up, were included. Patients with PR3- as compared to MPO-ANCA were younger (58 versus 64 years, p = 0.001), had a higher percentage of males (62 versus 41%, p < 0.001), had a lower percentage with a sclerozing glomerulonephritis pattern (4 versus 16%, p < 0.001), and had a significantly higher cumulative ESRD-free survival (90 versus 80%, p = 0.007) at 1-year follow-up. No significant differences in cumulative ESRD-free survival with PR3- as compared to MPO-ANCA were observed by histological stratification. Advanced glomerular sclerosis is found more frequently in patients with MPO-ANCA, explaining the higher risk of ESRD. ANCA serotypes have no impact on prognosis of patients with similar histological findings.


Access to medical care and health-related quality of life for low-income persons with symptomatic human immunodeficiency virus.
Despite growing interest in the accessibility of medical care and health-related quality of life for persons infected with human immunodeficiency virus, an association between these variables has not been documented. The authors conducted a cross-sectional study of access to care and its association with health-related quality of life among 205 persons of low income infected with the human immunodeficiency virus with constitutional symptoms and/or diarrhea at one public and one Veterans Administration hospital, using a 9-item measure of perceived access and a 55-item health-related quality of life instrument. Problems with access were widespread: 55% traveled for longer than 30 minutes to their usual source of care (compared with 9% to 12% of general populations in national surveys), 49% had problems meeting costs of care, and 48% had problems with clinic hours (compared with 23% in national surveys). In multivariate analyses, uninsured patients reported worse access than patients with Medicaid or Veterans Administration insurance, particularly for meeting the cost of care (P < 0.01). Adjusted health-related quality of life scores in this sample were far lower (by about 1 SD) than those of subjects in a large national acquired immune deficiency syndrome clinical trial. For 8 of 11 health-related quality of life subscales, worse perceived access was significantly (P < 0.05) associated with poorer health-related quality of life, even after controlling for T-4 lymphocyte count, symptoms and other factors. Access and health-related quality of life measures similar to those used in this study may prove useful in future evaluations of medical care systems serving poor, clinically ill populations infected with human immunodeficiency virus.


Gram-negative bacterial sensors for eukaryotic signal molecules.
Ample evidence exists showing that eukaryotic signal molecules synthesized and released by the host can activate the virulence of opportunistic pathogens. The sensitivity of prokaryotes to host signal molecules requires the presence of bacterial sensors. These prokaryotic sensors, or receptors, have a double function: stereospecific recognition in a complex environment and transduction of the message in order to initiate bacterial physiological modifications. As messengers are generally unable to freely cross the bacterial membrane, they require either the presence of sensors anchored in the membrane or transporters allowing direct recognition inside the bacterial cytoplasm. Since the discovery of quorum sensing, it was established that the production of virulence factors by bacteria is tightly growth-phase regulated. It is now obvious that expression of bacterial virulence is also controlled by detection of the eukaryotic messengers released in the micro-environment as endocrine or neuro-endocrine modulators. In the presence of host physiological stress many eukaryotic factors are released and detected by Gram-negative bacteria which in return rapidly adapt their physiology. For instance, Pseudomonas aeruginosa can bind elements of the host immune system such as interferon-γ and dynorphin and then through quorum sensing circuitry enhance its virulence. Escherichia coli sensitivity to the neurohormones of the catecholamines family appears relayed by a recently identified bacterial adrenergic receptor. In the present review, we will describe the mechanisms by which various eukaryotic signal molecules produced by host may activate Gram-negative bacteria virulence. Particular attention will be paid to Pseudomonas, a genus whose representative species, P. aeruginosa, is a common opportunistic pathogen. The discussion will be particularly focused on the pivotal role played by these new types of pathogen sensors from the sensing to the transduction mechanism involved in virulence factors regulation. Finally, we will discuss the consequence of the impact of host signal molecules on commensally or opportunistic pathogens associated with different human tissue.


In vivo quantitative measurement of arthritis activity based on hydrophobically modified glycol chitosan in inflammatory arthritis: more active than passive accumulation.
We demonstrated that arthritis could be visualized noninvasively using hydrophobically modified glycol chitosan nanoparticles labeled with Cy5.5 (HGC-Cy5.5) and an optical imaging system. Activated macrophages expressing Mac-1 molecules effectively phagocytosed HGC-Cy5.5, which formed spherical nanoparticles under physiologic conditions. We estimated the applicability of HGC-Cy5.5 to quantitative analysis of arthritis development and progression. Near-infrared fluorescence images, captured after HGC-Cy5.5 injection in mice with collagen-induced arthritis, showed stronger fluorescence intensity in the active arthritis group than in the nonarthritis group. According to the progression of arthritis in both collagen-induced arthritis and collagen antibody-induced arthritis models, total photon counts (TPCs) increased in parallel with the clinical arthritis index. Quantitative analysis of fluorescence after treatment with methotrexate showed a significant decrease in TPC in a dose-dependent manner. Histologic evaluation confirmed that the mechanism underlying selective accumulation of HGC-Cy5.5 within synovitis tissues included enhanced phagocytosis of the probe by Mac-1-expressing macrophages as well as enhanced permeability through leaky vessels. These results suggest that optical imaging of arthritis using HGC-Cy5.5 can provide an objective measurement of disease activity and, at the same time, therapeutic responses in rheumatoid arthritis.


The process audit.
Few executives question the idea that by redesigning business processes--work that runs from end to end across an enterprise--they can achieve extraordinary improvements in cost, quality, speed, profitability, and other key areas Yet in spite of their intentions and investments, many executives flounder, unsure about what exactly needs to be changed, by how much, and when. As a result, many organizations make little progress--if any at all--in their attempts to transform business processes. Michael Hammer has spent the past five years working with a group of leading companies to develop the Process and Enterprise Maturity Model (PEMM), a new framework that helps executives comprehend, formulate, and assess process-based transformation efforts. He has identified two distinct groups of characteristics that are needed for business processes to perform exceptionally well over a long period of time. Process enablers, which affect individual processes, determine how well a process is able to function. They are mutually interdependent--if any are missing, the others will be ineffective. However, enablers are not enough to develop high-performance processes; they only provide the potential to deliver high performance. A company must also possess or establish organizational capabilities that allow the business to offer a supportive environment. Together, the enablers and the capabilities provide an effective way for companies to plan and evaluate process-based transformations. PEMM is different from other frameworks, such as Capability Maturity Model Integration (CMMI), because it applies to all industries and all processes. The author describes how several companies--including Michelin, CSAA, Tetra Pak, Shell, Clorox, and Schneider National--have successfully used PEMM in various ways and at different stages to evaluate the progress of their process-based transformation efforts.


Prevalence of Type 2 Diabetes Mellitus among Urban Sikh Population of Amritsar.
Type 2 Diabetes Mellitus (T2DM) refers to a group of common metabolic disorders that share the phenotype of Hyperglycemia. More than 60% of the world's population with diabetes comes from Asia. To study the prevalence of Type 2 Diabetes Mellitus among Sikh individuals living in the urban localities of Amritsar. The study was designed in the Faculty of Sports Medicine & Physiotherapy, Guru Nanak Dev University, Amritsar, Punjab, India. The data collection was carried out in various urban localities of Amritsar. Blood samples were analyzed in the Biochemistry laboratory, whereas data analysis and article preparation was carried out in the Faculty of Sports Medicine and Physiotherapy. Multi-stage random sampling was done with a sample size of 1089 patients. The data was analyzed in Stata 11.2 software. Various tests used in the study are Mean ± SD, Pearson Chi Square Test, Students' t test and multiple logistic regression test. Our study showed that the prevalence rate of Type 2 Diabetes Mellitus is 23.2% with the confidence interval of 20.7-25.7. Proportionately more patients with T2DM had hypertension (46.6%). Likewise proportionately more patients, 67.5% had hypertrigylerdemia, 67.6% had low HDL levels, 59.2 % had hypercholesterolemia and 73.1% suffered from metabolic syndrome. Our study clearly indicates that the young Sikh adults below 40 years of age have similar high BMI, WC and WHR to that of the older adults above 40 years of age. It is necessary to adopt appropriate preventive strategies and interventions in high-risk individuals to curb the growing epidemic of diabetes. Innovative community outreach programs need to be designed and implemented to create awareness and early screening and treatment of diabetes, especially in the urban population.


Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes.
Virus or tumor Ag-derived peptides that are displayed by MHC class I molecules are attractive starting points for vaccine development because they induce strong protective and therapeutic cytotoxic T cell responses. In thus study, we show that the MHC binding and consequent T cell reactivity against several HLA-A*02 restricted epitopes can be further improved through the incorporation of nonproteogenic amino acids at primary and secondary anchor positions. We screened more than 90 nonproteogenic, synthetic amino acids through a range of epitopes and tested more than 3000 chemically enhanced altered peptide ligands (CPLs) for binding affinity to HLA-A*0201. With this approach, we designed CPLs of viral epitopes, of melanoma-associated Ags, and of the minor histocompatibility Ag UTA2-1, which is currently being evaluated for its antileukemic activity in clinical dendritic cell vaccination trials. The crystal structure of one of the CPLs in complex with HLA-A*0201 revealed the molecular interactions likely responsible for improved binding. The best CPLs displayed enhanced affinity for MHC, increasing MHC stability and prolonging recognition by Ag-specific T cells and, most importantly, they induced accelerated expansion of antitumor T cell frequencies in vitro and in vivo as compared with the native epitope. Eventually, we were able to construct a toolbox of preferred nonproteogenic residues with which practically any given HLA-A*02 restricted epitope can be readily optimized. These CPLs could improve the therapeutic outcome of vaccination strategies or can be used for ex vivo enrichment and faster expansion of Ag-specific T cells for transfer into patients.


Novel detection of formylated phloroglucinol compounds (FPCs) in the wound wood of Eucalyptus globulus and E. nitens.
This study characterized the chemical responses of Eucalyptus globulus and Eucalyptus nitens to artificial inoculation with a basidiomycete decay fungus. Nine-year-old trees responded to mechanical wounding or inoculation with the decay fungus by producing new wound wood characterized by the presence of dark extractives 17 months after wounding. Analysis of crude wound wood extracts by HPLC coupled to negative ion electrospray mass spectrometry revealed the presence of a complex mixture of many unidentified formylated phlorglucinol compounds (FPCs), in addition to a diverse range of other polyphenolic compounds (hydrolyzable tannins, proanthocyanidins, flavanone glycoside, stilbene glycosides). Prior to this study, FPCs have only been reported from leaves and buds of Eucalyptus spp. Unequivocal evidence for the presence of macrocarpal A and B, and sideroxylonal A and B in the crude extracts was obtained, as well as evidence for a wide range of as yet unreported FPCs. Subsequent preliminary in vitro fungal and bacterial bioassays did not support an antimicrobial role for FPCs in host-pathogen interactions in eucalypts.


Acupressure for nausea: results of a pilot study.
To compare differences in nausea experience and intensity in women undergoing chemotherapy for breast cancer between those receiving usual care plus acupressure training and treatment and those receiving only usual care. Single-cycle, randomized clinical trial. Outpatient oncology clinic in a major teaching medical center and a private outpatient oncology practice. Seventeen women participated in the study. The typical participant was 49.5 years old (SD = 6.0), Caucasian (59%), not married/partnered (76%), on disability (53%), born a U.S. citizen (76%), and heterosexual (88%); lived alone (59%); had at least graduated from high school (100%); and had an annual personal income of $50,000 or greater (65%). The intervention included finger acupressure bilaterally at P6 and ST36, acupressure points located on the forearm and by the knee. Baseline and poststudy questionnaires plus a daily log were used to collect data. Nausea experience measured by the Rhodes inventory of Nausea, Vomiting, and Retching and nausea intensity. Significant differences existed between the two groups in regard to nausea experience (p < 0.01) and nausea intensity (p < 0.04) during the first 10 days of the chemotherapy cycle, with the acupressure group reporting less intensity and experience of nausea. Finger acupressure may decrease nausea among women undergoing chemotherapy for breast cancer. This study must be replicated prior to advising patients about the efficacy of acupressure for the treatment of nausea.


Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts.
Phaleria macrocarpa, commonly known as Mahkota dewa is a medicinal plant that is indigenous to Indonesia and Malaysia. Extracts of P. macrocarpa have been used since years in traditional medicine that are evaluated scientifically as well. The extracts are reported for a number of valuable medicinal properties such as anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant and vasorelaxant effect. The constituents isolated from different parts of P. macrocarpa include Phalerin, gallic acid, Icaricide C, magniferin, mahkoside A, dodecanoic acid, palmitic acid, des-acetylflavicordin-A, flavicordin-A, flavicordin-D, flavicordin-A glucoside, ethyl stearate, lignans, alkaloids andsaponins. The present review is an up-to-date summary of occurrence, botanical description, ethnopharmacology, bioactivity and toxicological studies related to P. macrocarpa.


Assessing Program Coverage of Two Approaches to Distributing a Complementary Feeding Supplement to Infants and Young Children in Ghana.
The work reported here assesses the coverage achieved by two sales-based approaches to distributing a complementary food supplement (KOKO Plus™) to infants and young children in Ghana. Delivery Model 1 was conducted in the Northern Region of Ghana and used a mixture of health extension workers (delivering behavior change communications and demand creation activities at primary healthcare centers and in the community) and petty traders recruited from among beneficiaries of a local microfinance initiative (responsible for the sale of the complementary food supplement at market stalls and house to house). Delivery Model 2 was conducted in the Eastern Region of Ghana and used a market-based approach, with the product being sold through micro-retail routes (i.e., small shops and roadside stalls) in three districts supported by behavior change communications and demand creation activities led by a local social marketing company. Both delivery models were implemented sub-nationally as 1-year pilot programs, with the aim of informing the design of a scaled-up program. A series of cross-sectional coverage surveys was implemented in each program area. Results from these surveys show that Delivery Model 1 was successful in achieving and sustaining high (i.e., 86%) effective coverage (i.e., the child had been given the product at least once in the previous 7 days) during implementation. Effective coverage fell to 62% within 3 months of the behavior change communications and demand creation activities stopping. Delivery Model 2 was successful in raising awareness of the product (i.e., 90% message coverage), but effective coverage was low (i.e., 9.4%). Future programming efforts should use the health extension / microfinance / petty trader approach in rural settings and consider adapting this approach for use in urban and peri-urban settings. Ongoing behavior change communications and demand creation activities is likely to be essential to the continued success of such programming.


Tissue-specific targeting of DNA nanodevices in a multicellular living organism.
Nucleic acid nanodevices present great potential as agents for logic-based therapeutic intervention as well as in basic biology. Often, however, the disease targets that need corrective action are localized in specific organs, and thus realizing the full potential of DNA nanodevices also requires ways to target them to specific cell types in vivo. Here, we show that by exploiting either endogenous or synthetic receptor-ligand interactions and leveraging the biological barriers presented by the organism, we can target extraneously introduced DNA nanodevices to specific cell types in Caenorhabditis elegans, with subcellular precision. The amenability of DNA nanostructures to tissue-specific targeting in vivo significantly expands their utility in biomedical applications and discovery biology.


Radiometric calibration by rank minimization.
We present a robust radiometric calibration framework that capitalizes on the transform invariant low-rank structure in the various types of observations, such as sensor irradiances recorded from a static scene with different exposure times, or linear structure of irradiance color mixtures around edges. We show that various radiometric calibration problems can be treated in a principled framework that uses a rank minimization approach. This framework provides a principled way of solving radiometric calibration problems in various settings. The proposed approach is evaluated using both simulation and real-world datasets and shows superior performance to previous approaches.


Mechanistic insights for the development of Li-O2 battery materials: addressing Li2O2 conductivity limitations and electrolyte and cathode instabilities.
The Li-air battery has received significant attention over the past decade given its high theoretical specific energy compared to competing energy storage technologies. Yet, numerous scientific challenges remain unsolved in the pursuit of attaining a battery with modest Coulombic efficiency and high capacity. In this Feature Article, we provide our current perspective on challenges facing the development of nonaqueous Li-O2 battery cathodes. We initially present a review on our understanding of electrochemical processes occurring at the nonaqueous Li-O2 cathode. Electrolyte and cathode instabilities and Li2O2 conductivity limitations are then discussed, and suggestions for future materials research development to alleviate these issues are provided.


Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?
The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation. We compared 300 newly diagnosed (never antiretroviraltreated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group. Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants.


Evaluation of treatment satisfaction, efficacy and safety of dipeptidyl peptidase-4 inhibitors in geriatric patients with type 2 diabetes mellitus: A cross-sectionalcomparative study.
Dipeptidyl peptidase 4 (DPP4) inhibitors are attractive agents to be used in the elderly patients with Type 2 diabetes mellitus (T2DM) because of their beneficial effects. In this cross-sectional, observational study, we evaluated and compared the treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire (DTSQ) in two groups (i.e., regimens containing DPP4 inhibitors vs. other regimens). Efficacy was evaluated by assessing and comparing the glycosylated hemoglobin (HbA1c) values and the percentage of patients who achieved the glycemic control (HbA1c <7%). The adverse drug reactions (ADRs) were also recorded and compared among two groups. A total of 115 patients participated in the study (42 in Group 1 and 73 in Group 2). Significantly better DTSQ scores were observed among Group 1 patients in terms of DTSQ score total (P = 0.01) and DTSQ score for perception of hyperglycemia (P = 0.008) as compared to Group 2 patients. Significant difference was observed in HbA1c values among two groups (P = 0.02, 95% confidence interval [CI], 0.06-1.14). Also, significantly higher proportion of patients had achieved glycemic control, i.e., HbA1c <7% in Group 1 as compared to Group 2 (P = 0.002, 95% CI, 11.8%-48.1%). Significantly higher number of ADRs were observed among Group 1 patients as compared to Group 2 (P = 0.003). DPP4 inhibitors seem to offer better treatment satisfaction and efficacy in geriatric T2DM patients but at the expense of increased frequency of ADRs; however, further research is warranted.


Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly.
Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP-STIL interaction constitutes a conserved key step in centriole biogenesis. DOI:http://dx.doi.org/10.7554/eLife.01071.001.


Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart.
For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart. Using label-free quantitative proteomics and molecular approaches, we report that primary infection with pandemic influenza A virus leads to increased Streptococcus pneumoniae translocation to the myocardium, leading to general biological alterations. We also observed that each infection alone led to proteomic changes in the heart, and these were exacerbated in the secondary bacterial infection (SBI) model. Gene ontology analysis of significantly upregulated proteins showed increased innate immune activity, oxidative processes, and changes to ion homeostasis during SBI. Immunoblots confirmed increased complement and antioxidant activity in addition to increased expression of angiotensin-converting enzyme 2. Using an in vitro model of sequential infection in human cardiomyocytes, we observed that influenza enhances S. pneumoniae cytotoxicity by promoting oxidative stress enhancing bacterial toxin-induced necrotic cell death. Influenza infection was found to increase receptors that promote bacterial adhesion, such as polymeric immunoglobulin receptor and fibronectin leucine-rich transmembrane protein 1 in cardiomyocytes. Finally, mice deficient in programmed necrosis (i.e., necroptosis) showed enhanced innate immune responses, decreased virus-associated pathways, and promotion of mitochondrial function upon SBI. The presented results provide the first in vivo evidence that influenza infection promotes S. pneumoniae infiltration, necrotic damage, and proteomic remodeling of the heart. IMPORTANCE Adverse cardiac events are a common complication of viral and bacterial pneumonia. For over a century, it has been recognized that influenza infection promotes severe forms of pulmonary disease mainly caused by the bacterium Streptococcus pneumoniae. The extrapulmonary effects of secondary bacterial infections to influenza virus are not known. In the present study, we used a combination of quantitative proteomics and molecular approaches to assess the underlying mechanisms of how influenza infection promotes bacteria-driven cardiac damage and proteome remodeling. We further observed that programmed necrosis (i.e., necroptosis) inhibition leads to reduced damage and proteome changes associated with health.


Characterization of extracellular vesicles by IR spectroscopy: Fast and simple classification based on amide and CH stretching vibrations.
Extracellular vesicles isolated by differential centrifugation from Jurkat T-cell line were investigated by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). Amide and CH stretching band intensity ratios calculated from IR bands, characteristic of protein and lipid components, proved to be distinctive for the different extracellular vesicle subpopulations. This proposed 'spectroscopic protein-to-lipid ratio', combined with the outlined spectrum-analysis protocol is valid also for low sample concentrations (0.15-0.05mg/ml total protein content) and can carry information about the presence of other non-vesicular formations such as aggregated proteins, lipoproteins and immune complexes. Detailed analysis of IR data reveals compositional changes of extracellular vesicles subpopulations: second derivative spectra suggest changes in protein composition from parent cell towards exosomes favoring proteins with β-turns and unordered motifs at the expense of intermolecular β-sheet structures. The IR-based protein-to-lipid assessment protocol was tested also for red blood cell derived microvesicles for which similar values were obtained. The potential applicability of this technique for fast and efficient characterization of vesicular components is high as the investigated samples require no further preparations and all the different molecular species can be determined in the same sample. The results indicate that ATR-FTIR measurements provide a simple and reproducible method for the screening of extracellular vesicle preparations. It is hoped that this sophisticated technique will have further impact in extracellular vesicle research.


The effect of trabeculectomy surgery on the central visual field in patients with glaucoma using microperimetry and optical coherence tomography.
To determine the functional and structural effects of trabeculectomy surgery on patients with advanced glaucoma and central visual field defects in the early post-operative period. Thirty consecutive adult subjects with advanced glaucoma requiring trabeculectomy surgery and an established visual field defect within 10° of fixation underwent microperimetry (MAIA MP-1, CenterVue, Padova, Italy) and optic disc optical coherence tomography (OCT) imaging (Spectralis, Heidelberg Engineering, Germany) pre-operatively, and 1 month and 3 months following trabeculectomy surgery. Main outcome measures were post-trabeculectomy change in mean threshold on microperimetry and nerve fibre layer thickness on OCT. Fellow eyes were used as controls. The mean change in MP average threshold values from pre-operative to post-operative was 0.6 ± 1.9 dB for treated eyes and 0.1 ± 1.3 dB for control eyes (p = 0.14) at 1 month and 0.2 ± 2.3 and -0.3 ± 1.6 dB at 3 months (p = 0.22). Mean change in global nerve fibre layer thickness was -0.6 and -0.5 µm for operated and control eyes, respectively (p = 0.83), at 1 month and 0.8 and -0.4 µm at 3 months (p = 0.88). The kappa agreement for structure-function correlation between OCT and MP was 0.735 (confidence interval 0.59-0.88) (p < 0.005). Central visual function and retinal nerve fibre layer thickness appear to be preserved in glaucoma patients with central visual field defects undergoing trabeculectomy surgery in the early post-operative period. These data may inform glaucoma surgeons considering trabeculectomy surgery in this patient group.


Cytokine signature in convalescent SARS-CoV-2 patients with inflammatory bowel disease receiving vedolizumab.
While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses.


Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2. Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and analyzed. An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0 years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground-glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001). Detailed clinical investigation of 140 hospitalized COVID-19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.


Serum carotenoid concentrations predict lung function evolution in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study.
A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results. We examined the longitudinal association between serum carotenoids (β-cryptoxanthin, α-carotene, β-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function. We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20. Year 0 sum of provitamin A carotenoids and β-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P ≤ 0.01) and forced expiratory volume in 1 s (FEV(1)) (P ≤ 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, β-carotene, and β-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV(1) (P ≤ 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P ≤ 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV(1) (P ≤ 0.04). These findings support an association between serum carotenoid concentrations and a decline in lung function.


A monoclonal antibody to intestinal alkaline phosphatase made against D98/AH-2 (HeLa) cells.
A monoclonal antibody (AAP1) to human intestinal alkaline phosphatase (ALP) was produced by immunizing a mouse with D98/AH-2 (HeLa) cells, which produce the enzyme ectopically. The antibody, which did not inhibit enzyme activity using p-nitrophenyl phosphate as the substrate, was of the IgG2A class and did not show complement-dependent cytotoxicity. In trace binding assays AAP1 bound only to cells that expressed an intestinal-like form of human ALP, including some human intraspecific (D98/AG-2 x human lymphocyte or fibroblast) hybrids. Immunoprecipitation of immune complexes from cell-free extracts of D98/AG-2 cells, using protein A containing S. aureus and AAP1 antibody, resulted in precipitation of all the ALP activity. The precipitated material had a subunit molecular weight of 80,000 daltons, as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. In non-denaturing conditions, AAP1 antibody prevented the migration of ALP activity into the gel when cell-free extracts were made from human adult or fetal intestine, or D98/AH-2 cells. Similarly, AAP1 could be used to precipitate ALP activity from these extracts but not from extracts of human liver, kidney or placenta.


Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media.
The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25 °C and 37 °C) were investigated in this work. Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions. All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25 °C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37 °C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures. Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25 °C may not predict the supersaturation behavior at physiologically relevant temperatures.


Early head specification in Xenopus laevis.
The head represents the most dorsal and anterior extent of the body axis. In Xenopus, the progressive determination of the head is an extremely complex process involving the activation and localized antagonism of a number of interdependent intracellular signaling pathways including the Wingless/Int-1 (Wnt), bone morphogenetic protein (BMP), and nodal-related pathways. The sequence of events that specify the head are: dorsal-ventral polarization and head organizer specification in the blastula; gastrulation; neural induction; and patterning of the anterior-posterior and dorsal-ventral neuraxes. Wnt signaling is required for the specification of the dorsal side initially but is then inhibited within the organizer once it has formed. Similarly, Wnt signaling is required along the length of the neural tube, but must be suppressed at its rostral end for normal brain development. Nodal signaling is also necessary for induction of the mesendoderm, but is subsequently suppressed in its dorsal-anterior extreme to specify head organizer. BMP signaling is required for ventral mesoderm and non-neural ectoderm, and must also be suppressed in the head organizer region and for the differentiation of the ventral midline of the neural tube. Thus, development of the head, and indeed the body plan in general, requires precisely timed and spatially restricted activation and repression of these signaling pathways.


Plant extracts in the medical management of benign prostatic hyperplasia: fact or fiction?
The objective of this study was to critically review the published literature on the role of phytotherapeutic agents and phytosterols (also referred to as plant extracts) in the medical management of benign prostatic hyerplasia. Data sources included a bibliographic database that was searched to retrieve articles on benign prostatic hyperplasia with a time constraint of 1985-1993. Indexing terms used included plant extracts, phytosterols, cernilton, paraprost and medical management. Studies selected were randomized trials incorporating plant extracts. English abstracts were reviewed for articles published in other languages and these reviews are noted. English articles were critically reviewed based on study design, patient selection, length of follow up, postulated mechanisms of action and benign prostatic hyperplasia subjective and objective outcome measures. A number of plant extracts are being used in the management of benign prostatic hyperplasia, predominantly in Europe. These plant extracts, which are biochemically heterogenous, have been found to act through a variety of mechanisms: an anti-inflammatory effect, a decrease in globulin, a direct cytotoxic effect, anti-prolactin activity and bladder compliance modification. More importantly, these plant extracts have not been associated with the side effects of chemical castration. Their alleged efficacy may be based upon a mechanism which is currently not understood and a combination of these extracts with accepted medications may have the potential of improving the overall efficacy of medical therapy in the treatment of benign prostatic hyperplasia. Despite the shortcomings of the published trials, there is enough evidence to warrant additional study in the form of randomized control trials using scientific validated outcome measures. Using validated scores with patients of mild to moderate symptomatology would help to further elucidate the relative efficacy of cernilton, curbicin and permixon.


Research collaboration in the discovery, development, and delivery networks of a statewide cancer coalition.
This study examines and evaluates collaborative network involvement among 18 organizations within the Arizona Cancer Coalition. All were involved in one or more of three types of research activity: discovery, development, and delivery, consistent with the 3D continuum developed by the National Cancer Institute. Data were collected in 2007 using surveys of key informants in each organization. Using network analysis methods, we examined the structure of each type of network as well as the relationship between network position and the importance of cancer research to each organization's mission. Findings indicated that while both the discovery and delivery networks were comparably densely connected, their centrality structures were quite different. In contrast, the structures of both these networks were similar to the development network. Centrality in the discovery and development networks was positively related to the importance of cancer research to the organization, but not in the delivery network. Implications of the findings for future research, policy, and planning are discussed.


Assessment of a Clinical Pharmacy Activity in a Pediatric Inpatient Department in Cote D'ivoire.
Clinical pharmacy activities in a pediatric inpatient department help to improve the management of patients clinically and economically. To assess the relevance of pharmaceutical interventions (PIs) in a pediatric inpatient department in Abidjan (Cote d'Ivoire). We carried out a cross-sectional, descriptive study from February to September 2014. The information collected was classified according to the classification of drug-related problems (DRPs) and PIs of the French Society of Clinical Pharmacy. The score assigned to each PI varied from PI0 (without direct clinical impact) to PI3 (vital clinical impact) as the importance of the potential clinical impact of the DRP was correlated to the severity of clinical consequences avoided by the PI. The relevance of PIs was assessed by their rate of acceptance by physicians and by the analysis of their clinical impact. A total of 116 PIs were performed with 31% performed during medical rounds, 68.1% during patients' records analysis, and 0.1% on patient's admission. The main DRPs were related to noncompliance with recommendations (24.1%), overdose (21.1%), and underdosing (13.8%). The most important PIs were dose adjustment (31.8%), accuracy of drugs administration modalities (29.3%), and proposals of therapeutic choice (27.6%). The acceptance rate of PIs was highly significant (94.8%). The majority of PIs (67.3%) was assessed as having a significant clinical impact (PI1) and 16.4% of PIs as very significant clinical impact (PI2). A single PI (0.9%) was found with vital clinical impact. PIs performed were relevant and contributed to the therapeutic optimization and the prevention of iatrogenic events in pediatric inpatients.


The occurrence of macrophages in the retina and periretinal tissues in ocular diseases.
Specimens obtained from eyes with various ocular diseases were examined immunohistochemically using a panel of monoclonal antibodies (Ki-M1P, K1-M4, CD68, anti-lysozyme, and anti-cytokeratins) to establish the occurrence of macrophages in the retina and periretinal tissues and to determine whether they can be distinguished from migrated cells of the retinal pigment epithelium (RPE). Eyes with proliferative diseases and intraocular melanomas were found to contain more macrophages in the retina than those with uveitis and glaucoma. The epiretinal membranes and subretinal space in eyes of the former group often exhibited additional clustered macrophages and migrated RPE cells. In all specimens studied, RPE cells reacted with antibodies KL-1, CK7, CK18, or CK19 but not with the CD68, Ki-M1P, or lysozyme antibodies. Control eyes without any known disease also contained rare macrophages in the retina. In conclusion, macrophages are regular and normal constituents of the retina that can be clearly distinguished immunohistochemically from migrated RPE cells. Their frequency varies depending on the type of ocular disease involved.


The burden of polyparasitism among primary schoolchildren in rural and farming areas in Zimbabwe.
A cross-sectional study was conducted in Zimbabwe among 1303 primary schoolchildren from a rural (53.3%) and a commercial farming area (46.7%) to determine the prevalence of co-infection by helminths and Plasmodium falciparum. Urine was examined on three successive days using the filtration method. Two stool specimens were processed using the Kato-Katz method and a third specimen was processed using the sedimentation method. Plasmodium falciparum was diagnosed from thick blood films. The prevalence of Schistosoma haematobium in the rural and farming areas was 66.8% and 52.3%, respectively, and for S. mansoni the prevalence was 12.4% and 22.7%, respectively. Plasmodium falciparum, hookworms, Ascaris lumbricoides and Trichuris trichiura occurred only in the farming area, with a prevalence of 27.9%, 23.7%, 2.1%, 2.3%, respectively. Co-infection and triple infection with schistosomes, P. falciparum and soil-transmitted helminths occurred in the commercial farming area only. Hookworm and S. mansoni infections were associated with P. falciparum malaria (P<0.001, OR=2.48, 95% CI 1.56-3.93 and P=0.005, OR=1.85, 95% CI 1.20-2.87, respectively). Overlap of helminths with malaria is a concern among primary schoolchildren and incorporating helminth control in programmes aiming to control malaria will improve funding and increase the efficiency of control for neglected tropical diseases in identified co-endemic settings.


Light distribution photometry in Japan.
Of the representative distribution photometers constructed in Japan, a large-size photometer without mirrors, a compensation method for the variation in light output of a lamp, and an automatic recording of a sinusoidal isocandela diagram are illustrated. Next, a new idea for integrating the luminous flux of a lamp proposed by Ishii and Muroi and a photometer based on it are explained. The error due to two kinds of light distribution from light sources in the sphere photometer using a light distribution photometer are discussed. Finally, a theory is introduced on the photometric error due to the error in positioning the light source in the light distribution photometer. Application of the theory shows that the error in luminous flux is negligible if reasonable care is taken in positioning the lamp.


A Critical Assessment of Child Custody Evaluations: Limited Science and a Flawed System.
-Most parents who live apart negotiate custody arrangements on their own or with the help of lawyers, mediators, or other professionals. However, psychologists and other mental health professionals increasingly have become involved in evaluating children and families in custody disputes, because of the large number of separated, divorced, and never-married parents and the substantial conflict that often accompanies the breakup of a family. Theoretically, the law guides and controls child custody evaluations, but the prevailing custody standard (the "best interests of the child" test) is a vague rule that directs judges to make decisions unique to individual cases according to what will be in children's future (and undefined) best interests. Furthermore, state statutes typically offer only vague guidelines as to how judges (and evaluators) are to assess parents and the merits of their cases, and how they should ultimately decide what custody arrangements will be in a child's best interests. In this vacuum, custody evaluators typically administer to parents and children an array of tests and assess them through less formal means including interviews and observation. Sadly, we find that (a) tests specifically developed to assess questions relevant to custody are completely inadequate on scientific grounds; (b) the claims of some anointed experts about their favorite constructs (e.g., "parent alienation syndrome") are equally hollow when subjected to scientific scrutiny; (c) evaluators should question the use even of well-established psychological measures (e.g., measures of intelligence, personality, psychopathology, and academic achievement) because of their often limited relevance to the questions before the court; and (d) little empirical data exist regarding other important and controversial issues (e.g., whether evaluators should solicit children's wishes about custody; whether infants and toddlers are harmed or helped by overnight visits), suggesting a need for further scientific investigation. We see the system for resolving custody disputes as deeply flawed, for reasons that go beyond the problem of limited science. The coupling of the vague "best interests of the child" test with the American adversary system of justice puts judges in the position of trying to perform an impossible task, and it exacerbates parental conflict and problems in parenting and coparenting, which psychological science clearly shows to be key factors predicting children's psychological difficulties in response to their parents' separation and divorce. Our analysis of the flawed system, together with our desire to sharply limit custody disputes and custody evaluations, leads us to propose three reforms. First, we urge continued efforts to encourage parents to reach custody agreements on their own-in divorce mediation, through collaborative law, in good-faith attorney negotiations, in therapy, and in other forums. Some such efforts have been demonstrated to improve parent-parent and parent-child relationships long after divorce, and they embrace the philosophical position that, in the absence of abuse or neglect, parents themselves should determine their children's best interests after separation, just as they do in marriage. Second, we urge state legislatures to move toward adopting more clear and determinative custody rules, a step that would greatly clarify the terms of the marriage contract, limit the need for custody evaluations, and sharply narrow the scope of the evaluation process. We find particular merit in the proposed "approximation rule" (recently embraced by the American Law Institute), in which postdivorce parenting arrangements would approximate parenting involvement in marriage. Third and finally, we recommend that custody evaluators follow the law and only offer opinions for which there is an adequate scientific basis. Related to this, we urge professional bodies to enact more specific standards of practice on this and related issues.


Radiotherapy of CD19 expressing Daudi tumors in nude mice with Yttrium-90-labeled anti-CD19 antibody.
Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies.


Evaluation of Parent- and Speech-Language Pathologist-Delivered Multiple Oppositions Intervention for Children With Phonological Impairment: A Multiple-Baseline Design Study.
Purpose Evidence for the multiple oppositions intervention approach indicates it should be delivered 3 times weekly; however, this high dose frequency is not provided by many speech-language pathologists worldwide. This study investigated whether parents could be involved in delivering phonological intervention to fulfill this intensity shortfall. Method Five children with moderate-to-severe phonological impairment aged 3;3-5;11 (years;months) and 1 of their parents participated in this study using a multiple-baseline across participants design. Participants attended one 60-min clinic-based session per week for 8 weeks, and parents completed home practice 2 times per week over this period after receiving training. Parents also attended a 60-min training session prior to commencing intervention. Results All children showed a treatment effect to treated words. Three of the 5 children demonstrated a large effect size for generalization to nontreatment words, with 1 child demonstrating a moderate effect and 1 child demonstrating no effect. However, all children showed qualitative changes to their speech system. Three of the 5 children experienced significant changes to communicative participation. Measures of treatment fidelity indicated that parents were able to competently deliver the intervention both within the clinic and at home. Conclusions Combined parent- and speech-language pathologist-delivered multiple oppositions intervention is effective for some children with moderate-to-severe phonological impairment. The findings indicate that parents can be trained to competently and confidently deliver phonological intervention. Further evidence is needed to identify optimal child and parent characteristics most suited to this modified service delivery approach. Supplemental Material https://doi.org/10.23641/asha.10565885.


Discriminatory power of three DNA-based typing techniques for Pseudomonas aeruginosa.
We assessed the capacity of three DNA typing techniques to discriminate between 81 geographically, temporally, and epidemiologically unrelated strains of Pseudomonas aeruginosa. The methods, representing powerful tools for hospital molecular epidemiology, included hybridization of restricted chromosomal DNA with toxA and genes coding for rRNA (rDNA) used as probes and macrorestriction analysis of SpeI-digested DNA by pulsed-field gel electrophoresis. The probe typing techniques were able to classify all strains into a limited number of types, and the discriminatory powers were 97.7 and 95.6% for toxA and rDNA typing, respectively. Strains that were indistinguishable on the basis of both toxA and rDNA types defined 12 probe type homology groups. Of these, one contained five strains, three contained three strains each, and eight groups were represented by two strains each. Strains in 10 of the homology groups had the same O serotype. SpeI macrorestriction patterns discriminated between all strains with at least four band differences, which corresponded to a similarity level of 85%. Fifteen pairs of strains were similar at a level of > 75% and differed by only four to seven bands. Of these pairs, 11 belonged to the same probe type homology group, indicating their clonal relatedness. We conclude that macrorestriction analysis of P. aeruginosa with SpeI provides the best means of discrimination between epidemiologically unrelated strains. However, DNA probe typing with either toxA or rDNA reveals information on the strain population structure and evolutionary relationships.


Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae.
Gross chromosome rearrangements (GCRs), such as translocations, deletion of a chromosome arm, interstitial deletions and inversions, are often observed in cancer cells. Spontaneous GCRs are rare in Saccharomyces cerevisiae; however, the existence of mutator mutants with increased genome instability suggests that GCRs are actively suppressed. Here we show by genetic analysis that these genome rearrangements probably result from DNA replication errors and are suppressed by at least three interacting pathways or groups of proteins: S-phase checkpoint functions, recombination proteins and proteins that prevent de novo addition of telomeres at double-strand breaks (DSBs). Mutations that inactivate these pathways cause high rates of GCRs and show synergistic interactions, indicating that the pathways that suppress GCRs all compete for the same DNA substrates.


Preferences for outcomes in economic evaluation: an economic approach to addressing economic problems.
In this paper we critically appraise the appropriateness and validity from an economic perspective of alternative preference-based approaches to measuring outcomes in economic evaluations of health care interventions. We describe the properties of an outcome measure for economic evaluation to make it compatible with the principles of economics when applied to the problem of resource allocation. We also describe the difference and similarities between the psychometric and the economic approaches for the measurement of outcome. Using these properties we critically appraise the use of QALY and HYE methods of measuring individual and social preferences for health outcome. We argue that the most advanced measure currently available that meets these required properties is the HYE. Because the HYE, unlike the QALY, has its foundations in utility theory under uncertainty, it neither assumes particular formulations of the individual utility function, nor is it incompatible with the principles of economics. As such it represents a further stage in the continuing development of methods for economic evaluation of health care programmes.


p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.
Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.


A Finite Element Model Approach to Determine the Influence of Electrode Design and Muscle Architecture on Myoelectric Signal Properties.
Surface electromyography (sEMG) is the measurement of the electrical activity of the skeletal muscle tissue detected at the skin's surface. Typically, a bipolar electrode configuration is used. Most muscles have pennate and/or curved fibres, meaning it is not always feasible to align the bipolar electrodes along the fibres direction. Hence, there is a need to explore how different electrode designs can affect sEMG measurements. A three layer finite element (skin, fat, muscle) muscle model was used to explore different electrode designs. The implemented model used as source signal an experimentally recorded intramuscular EMG taken from the biceps brachii muscle of one healthy male. A wavelet based intensity analysis of the simulated sEMG signal was performed to analyze the power of the signal in the time and frequency domain. The model showed muscle tissue causing a bandwidth reduction (to 20-92- Hz). The inter-electrode distance (IED) and the electrode orientation relative to the fibres affected the total power but not the frequency filtering response. The effect of significant misalignment between the electrodes and the fibres (60°-90°) could be reduced by increasing the IED (25-30 mm), which attenuates signal cancellation. When modelling pennated fibres, the muscle tissue started to act as a low pass filter. The effect of different IED seems to be enhanced in the pennated model, while the filtering response is changed considerably only when the electrodes are close to the signal termination within the model. For pennation angle greater than 20°, more than 50% of the source signal was attenuated, which can be compensated by increasing the IED to 25 mm. Differences in tissue filtering properties, shown in our model, indicates that different electrode designs should be considered for muscle with different geometric properties (i.e. pennated muscles).


Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial.
Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM. M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m2) on days 1-5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve. There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%. Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).


Shear bond strength of orthodontic resins after caries infiltrant preconditioning.
To investigate the influence of caries infiltrant preconditioning on the shear bond strength of orthodontic resin cements on sound and demineralized enamel. Stainless-steel brackets were bonded to sound or artificially demineralized (14 d, acidic buffer, pH 5.0) bovine enamel specimens using a resin cement or a combination of caries infiltrant preconditioning (Icon, DMG) and the respective resin cement (light-curing composite: Heliosit Orthodontic, Transbond XT, using either Transbond XT Primer or Transbond Plus Self Etching Primer; light-curing resin-modified glass ionomer cement: Fuji Ortho; or self-curing composite: Concise Orthodontic Bonding System). Each group consisted of 15 specimens. Shear bond strength was evaluated after thermo-cycling (10,000×, 5°C to 55°C) at a crosshead speed of 1 mm/min, and data were statistically analyzed by analysis of variance, Mann-Whitney test, and Weibull statistics. Adhesive Remnant Index (ARI) scores and enamel fractures were determined at 25× magnification and were statistically analyzed by regression analyses (P < .05). The caries infiltrant system significantly increased the shear bond strength of Transbond XT Primer, Transbond Plus Self Etching Primer, and Fuji Ortho in sound specimens, and of all resin cements except for the Concise Orthodontic Bonding System in demineralized enamel. Overall, caries infiltrant preconditioning decreased significantly the number of enamel fractures, but it did not affect ARI scores. Preconditioning of sound and demineralized enamel with the caries infiltrant system did not impair but rather increased the shear bond strength of most orthodontic resin cements while decreasing the risk of enamel fracture at debonding.


Resonance Raman characterization of the different forms of ground-state 8-substituted 7-hydroxyquinoline caged acetate compounds in aqueous solutions.
To investigate the substituent effect on the distribution of the forms of the ground-state species of 8-substituted 7-hydroxyquinolines, ultraviolet-absorption and resonance Raman experiments were performed for 8-chloro-7-hydroxyquinoline (CHQ-OAc) and 8-cyano-7-hydroxyquinoline (CyHQ-OAc) in acetonitrile (MeCN), in NaOH-H(2)O/MeCN (60:40, v/v, pH 11-12), and in H(2)O/MeCN (60:40, v/v, pH 6-7) solutions, and these results were compared to those previously reported for the 8-bromo-7-hydroxyquinoline (BHQ-OAc) compound. Swapping a bromine atom in BHQ-OAc for a chlorine atom in CHQ-OAc causes the amount of the tautomeric species to become larger, although the neutral species is still the predominant species for both systems in water-rich solutions. The absorption spectra and the resonance Raman spectra of CyHQ-OAc suggest that, because of the strong electron-withdrawing nature of the cyano substituent, a measurable amount of the anionic species is present and the tautomeric species cannot be easily detected in water-rich solutions. The results reported here reveal large substituent effects on the distribution of the different forms of the XHQ-OAc compounds in largely aqueous solutions. The steric effect of the 8-substituted group and competitive hydrogen bonding between the 8-substituted group and water molecules hinders the formation of a cyclic BHQ-OAc-water complex, and the electron-withdrawing property of the 8-substituted group enhances the deprotonation of the phenol group while disfavoring the formation of the positively charged quinoline nitrogen. We briefly discuss the implications of the substituent effects for using these compounds as phototriggers.


The more, the better? Curvilinear effects of job autonomy on well-being from vitamin model and PE-fit theory perspectives.
In organizational psychology research, autonomy is generally seen as a job resource with a monotone positive relationship with desired occupational outcomes such as well-being. However, both Warr's vitamin model and person-environment (PE) fit theory suggest that negative outcomes may result from excesses of some job resources, including autonomy. Thus, the current studies used survey methodology to explore cross-sectional relationships between environmental autonomy, person-environment autonomy (mis)fit, and well-being. We found that autonomy and autonomy (mis)fit explained between 6% and 22% of variance in well-being, depending on type of autonomy (scheduling, method, or decision-making) and type of (mis)fit operationalization (atomistic operationalization through the separate assessment of actual and ideal autonomy levels vs. molecular operationalization through the direct assessment of perceived autonomy (mis)fit). Autonomy (mis)fit (PE-fit perspective) explained more unique variance in well-being than environmental autonomy itself (vitamin model perspective). Detrimental effects of autonomy excess on well-being were most evident for method autonomy and least consistent for decision-making autonomy. We argue that too-much-of-a-good-thing effects of job autonomy on well-being exist, but suggest that these may be dependent upon sample characteristics (range of autonomy levels), type of operationalization (molecular vs. atomistic fit), autonomy facet (method, scheduling, or decision-making), as well as individual and organizational moderators. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Cultural and semantic equivalence of the activity measure post-acute care (AM-PAC) after its translation into Mandarin Chinese.
Purpose: The purpose of this study was to investigate the cultural and semantic equivalence of the Activity Measure Post-Acute Care (AM-PAC) outpatient short forms after they were translated from American English to Mandarin Chinese. Method: This study was conducted with a composite sample of a group of 483 American adults (mean age 63.1 years, 42.4% males) and 553 Taiwanese adults (mean age 60.6 years, 47.2% males) who were undergoing home care or outpatient rehabilitation services. A confirmatory factor analysis tested the cultural equivalence of the AM-PAC dimensions between the US and Taiwanese samples. Semantic equivalence was tested through an item response theory-based differential item functioning (DFI) analysis. Results: Results of the confirmatory factor analysis demonstrated good model-data fit of the AM-PAC in both the US and Taiwanese samples. Significant DFI was found for six Basic Mobility items, two Daily Activity items, and four Applied Cognition items. A DFI adjusted conversion table was generated to transform the raw scores of the measure for comparisons between the two countries. Conclusions: This study provides evidence to support the conceptual equivalence of the AM-PAC when used in rehabilitation patients between American and Taiwanese cultural contexts. Some DFI items between the two groups were found, suggesting that some differences in semantic understanding of these items between cultures require cross-cultural adjustments. Implications for Rehabilitation Cultural equivalence needs to be tested before applying a clinical measure to another context. The findings of this study supported the three activity domains that the Activity Measure Post-Acute Care measures: Basic Mobility, Daily Activity, and Applied Cognition, which are all important rehabilitation outcomes that need to be assessed and monitored across rehabilitation settings. Differential item functioning was observed between the English and Chinese versions of the Activity Measure Post-Acute Care, indicating that linguistic and cultural differences across countries need to be adjusted for before using the translated measure in clinical practice.


Function of dislocated hips in children with lower level spina bifida.
We reviewed 52 children, born between 1974 and 1985 with spina bifida affecting L3 and L4, who had dislocated hips. Their motor function was stable and they were able to walk at the time of dislocation. They were interviewed and examined physically and radiologically. Physical function was measured by the Rand Health Insurance Study questionnaire (HIS), the Childhood Health Assessment questionnaire (CHAQ), and by determining the functional level of ambulation according to Hoffer et al (1973). In a subgroup of 12 patients with L4 level of involvement from both treatment groups we measured the metabolic energy consumption while walking. Thirty patient (49 hips) had been treated by operative relocation and 22 conservatively. Ten of the hips treated by operation subluxated or redislocated. The function in the two groups (conservative nu operated) was similar (HIS score 7.8 v 8.0, p = 0.45; CHAQ 14 v 13, p = 0.2; level of mobility 0.61 v 0.63, p = 0.5). Patients in whom operation had failed had worse function than did those with successful surgery (HIS score 8.8 v 6.1, p = 0.025) and those with successful surgery had better function than patients treated conservatively (HIS score 8.8 v 8.0, p = 0.15). Function in patients with failed operations, however, was worse than in those who did not have surgical treatment (HIS score 6.6 v 7.8, p = 0.07). In the 12 so examined the operated group had a 30% more energy-efficient gait (0.271 v 0.361 ml O2 kg/m, p = 0.05). Patients with failed operations had worse function than those who were not operated on. The benefit of surgical relocation of the dislocated hips was marginal.


Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene.
The expansion of sleeping sickness caused by Trypanosoma brucei rhodesiense beyond its traditional focus in southeast Uganda has been linked with large-scale livestock restocking. To assess the risk presented to the human population by domestic livestock, human-infective T b rhodesiense must be distinguished from non-human-infective T brucei brucei, since both parasites can be present in cattle. We investigated the use of a simple genetic marker to characterise parasites collected from cattle in villages within the new sleeping sickness focus in Soroti District, Uganda. 70 T brucei sl samples of known human infectivity status collected from human beings and cattle in Tororo District, Uganda, from 1989 to 1991 were screened for the presence of the human-serum-resistance-associated (SRA) gene by conventional PCR. In 2000-01, blood samples from 200 randomly selected cattle in six villages and two markets in Soroti District were screened for T brucei sl parasites by PCR; positive samples were screened for the presence of the SRA gene. The SRA gene was present in all 29 samples from patients with sleeping sickness in Tororo District. Of the 41 samples collected from cattle at the same time, the SRA gene was present in the eight samples that tested resistant to human serum in vitro, whereas it was absent from all 33 isolates that were sensitive to human serum in vitro. Of the 200 cattle sampled in Soroti District, we estimated that up to 18% (95% CI 12-23) were infected with T b rhodesiense. Detection of the SRA gene could provide the basis for a simple diagnostic test to enable targeted control of T b rhodesiense in the domestic livestock reservoir, thereby reducing the public-health burden of sleeping sickness in east Africa.


Evolutionary anatomies of positions and types of disease-associated and neutral amino acid mutations in the human genome.
Amino acid mutations in a large number of human proteins are known to be associated with heritable genetic disease. These disease-associated mutations (DAMs) are known to occur predominantly in positions essential to the structure and function of the proteins. Here, we examine how the relative perpetuation and conservation of amino acid positions modulate the genome-wide patterns of 8,627 human disease-associated mutations (DAMs) reported in 541 genes. We compare these patterns with 5,308 non-synonymous Single Nucleotide Polymorphisms (nSNPs) in 2,592 genes from primary SNP resources. The abundance of DAMs shows a negative relationship with the evolutionary rate of the amino acid positions harboring them. An opposite trend describes the distribution of nSNPs. DAMs are also preferentially found in the amino acid positions that are retained (or present) in multiple vertebrate species, whereas the nSNPs are over-abundant in the positions that have been lost (or absent) in the non-human vertebrates. These observations are consistent with the effect of purifying selection on natural variation, which also explains the existence of lower minor nSNP allele frequencies at highly-conserved amino acid positions. The biochemical severity of the inter-specific amino acid changes is also modulated by natural selection, with the fast-evolving positions containing more radical amino acid differences among species. Similarly, DAMs associated with early-onset diseases are more radical than those associated with the late-onset diseases. A small fraction of DAMs (10%) overlap with the amino acid differences between species within the same position, but are biochemically the most conservative group of amino acid differences in our datasets. Overlapping DAMs are found disproportionately in fast-evolving amino acid positions, which, along with the conservative nature of the amino acid changes, may have allowed some of them to escape natural selection until compensatory changes occur. The consistency and predictability of genome-wide patterns of disease- associated and neutral amino acid variants reported here underscores the importance of the consideration of evolutionary rates of amino acid positions in clinical and population genetic analyses aimed at understanding the nature and fate of disease-associated and neutral population variation. Establishing such general patterns is an early step in efforts to diagnose the pathogenic potentials of novel amino acid mutations.