Coded statutory data sets for evaluation of public health law.
The evaluation of public health law requires reliable accounts of underlying statutes and regulations. States often enact public health-related statutes with nonuniform provisions, and variation in the structure of state legal codes can foster inaccuracy in evaluating the impact of specific categories of law. The optimal format for empirical analysis is a machine-readable 50-state coded data set. This study provides a comprehensive assessment of these resources and related materials with a focus on statutory data sets. An exhaustive literature search was followed by a "pearling" or "snowball" approach to assure the most complete inventory of this very diverse and diffuse information. We also interviewed three leading investigators to identify barriers to wider use and availability of coded legal data sets. We identified relatively few accessible coded statutory data sets, and others that are not available for use outside the group or individual that compiled them. The Robert Wood Johnson Foundation-funded Public Health Law Research Program has made funding available for the development and dissemination of additional data sets, as well as extensive guidance regarding their use in the evaluation of public health law. Investigators reported serious obstacles to these activities in the past. Compilation of coded statutory data sets requires a focused investment of resources that has only recently become available. Funders should require grantees to make their work accessible to other investigators so as to assure development of public health law research and evaluation.


Optimal packing characteristics of rolled, continuous stationary-phase columns.
Rolled, continuous stationary phases were constructed by tightly rolling and inserting a whole textile fabric into a chromatography column. This work reports the column performance, in terms of plate height, void fraction, and resolution, of 10 cellulose-based fabrics. The relation between fabric structural properties of yarn diameter, fabric count, fabric compressibility, and column performance are quantitated. General requirements, including reproducibility of packing, for choosing fabrics to make a good SEC column are identified. This research showed that the packed columns have an optimal mass of fabric that minimizes plate height and maximizes resolution, in a manner that is consistent with chromatography theory. Mass of material packed is then an important column parameter to consider when optimizing columns for the rapid desalting of proteins. Proteins were completely separated from salt and glucose in less than 8 min at a pressure drop less than 500 psi on the rolled, continuous stationary-phase columns. These results, together with stability and reproducibility, suggest potential industrial applications for cellulose-based rolled, continuous stationary-phase columns where speed is a key parameter in the production process.


Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle.
This study investigated localization and expression of relaxin and its receptor, LGR7, in the human endometrium during the proliferative and secretory phases of the menstrual cycle. H2 relaxin binding was identified in endometrium, but not myometrium, and particularly in the epithelium of the endometrial glands and uterine lumen. Binding sites increased in the early secretory phase of the menstrual cycle and were paralleled by similar increases in LGR7 mRNA measured by Q-PCR. The increase in LGR7 expression and H2 relaxin binding in the secretory phase of the menstrual cycle suggests a specific role for relaxin after ovulation in the human uterus.


Use of transcutaneous oxygen and carbon dioxide tensions for assessing indices of gas exchange during exercise testing.
The slow response characteristics of the combined transcutaneous electrode have been viewed as a major disadvantage when compared with other types of non-invasive assessment of gas exchange during exercise testing. We have previously shown that by using the highest recommended temperature of 45 degrees C to reduce response times, and combining this with an exercise protocol of gradual work load increments, that this allows changes in arterial blood gases to be closely followed by transcutaneous values. In the present study we have validated the use of a transcutaneous electrode for estimation of alveolar-arterial oxygen gradient (AaO2) and dead space to tidal volume ratio (V(D)/V(T)) during exercise, against values calculated from direct arterial blood gas analysis. One hundred measurements were made in 20 patients with various cardiopulmonary disorders who underwent exercise testing. Exercise testing was performed by bicycle ergometry with a specific protocol involving gradual work load increments at 2 min intervals. Transcutaneous gas tensions were measured by a heated combined O2 and CO2 electrode. Arterial blood was sampled at the midpoint of each stage of exercise and transcutaneous tensions noted at the end of each stage. The mean difference of the AaO2 gradient calculated from blood gas tensions obtained by the two methods was 0.14 kPa. The limits of agreement were -0.26 and 0.63 kPa. The same values for V(D)/V(T) calculated from gas tensions measured by the two methods were: mean difference 0001; limits of agreement -0.0242 and 0.0252. For both these parameters there was an even scatter around the mean value on Bland and Altman analysis. The findings of this study suggest that estimation of parameters of gas exchange using transcutaneous values during exercise testing is reliable, provided the electrode is heated to a slightly higher temperature than usual and the work load increments are gradual, allowing for the latency in the response time of the system. This system allows the assessment of the contribution of ventilation/perfusion inequality to breathlessness on exertion in patients, provided an initial arterial or ear lobe capillary sample is obtained for calibration purposes. This technique is particularly valuable in patients undergoing repeat exercise tests as it circumvents the need for arterial cannulation.


Educational Level, Underachievement, and General Mental Health Problems in 10,866 Adolescents.
Previous research suggests that cognitive functioning is associated with the risk of several adult psychiatric disorders. In this study we investigated whether adolescents who perform worse than expected at secondary school are at a higher risk for general mental health problems. In a cross-sectional survey comprising 10,866 Dutch adolescents aged 13 to 16 years, underachievement at secondary school was defined as the discrepancy between predicted school grade and actual grade 1 or 3 years later. Mental health problems were assessed using the Strengths and Difficulties Questionnaire. We investigated the association of underachievement with mental health problems using logistic regression, adjusting for potential confounders. Underachievement was associated with general psychopathology in pupils aged 13 to 14 years (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.47-2.37) and in pupils aged 15 to 16 years (OR, 2.05; 95% CI, 1.67-2.52) in a multivariate analysis including sociodemographic factors. The association between underachievement and mental health problems was attenuated when school factors such as teacher advice and interaction between underachievement and teacher advice were added, but underachievement remained significantly associated with mental health problems in adolescents in the higher educational tracks (pupils aged 13-14 years: OR, 2.22; 95% CI, 1.07-4.60 and OR, 2.41; 95% CI, 1.10-5.30, age 15-16 years: OR, 2.63; 95% CI, 1.38-5.03). In the multivariate analysis including the interaction between underachievement and teacher advice, a significant interaction effect occurs between underachievement and teacher advice in the higher tracks. Values of OR and CI are given for each significant interaction term. In the younger age group (pupils aged 13-14 years) this results in 2 sets of OR and CI. This association was most pronounced for the hyperactivity subscale of the Strengths and Difficulties Questionnaire. Underachievement at secondary school is associated with general mental health problems, especially with hyperactivity symptoms, in pupils who started at high educational tracks.


The World Starts With Me: a multilevel evaluation of a comprehensive sex education programme targeting adolescents in Uganda.
This paper evaluates the effect of the World Starts With Me (WSWM), a comprehensive sex education programme in secondary schools in Uganda. The aim of the present study was to assess the effects of WSWM on socio-cognitive determinants of safe sex behaviour (delay; condom use and non-coercive sex). A survey was conducted both before and immediately after the intervention among students in intervention (N = 853) and comparison (N = 1011) groups. A mixed model repeated measures analysis was performed to assess the effectiveness of the WSWM programme on the main socio-cognitive determinants of safe sex behaviour at post-test. A similar post-hoc comparison was made between schools based on completeness and fidelity of implementation of WSWM. Significant positive effects of WSMW were found on beliefs regarding what could or could not prevent pregnancy, the perceived social norm towards delaying sexual intercourse, and the intention to delay sexual intercourse. Furthermore, significant positive effects of WSWM were found on attitudes, self-efficacy and intention towards condom use and on self-efficacy in dealing with sexual violence (pressure and force for unwanted sex). A reversed effect of intervention was found on knowledge scores relating to non-causes of HIV (petting, fondling and deep kissing). A follow-up comparison between intervention schools based on completeness of the programme implementation revealed that almost all significant positive effects disappeared for those schools that only implemented up to 7 out of 14 lessons. Another follow-up analysis on the basis of implementation fidelity showed that schools with a "partial" fidelity score yielded more significant positive effects than schools with a "full" fidelity of implementation score. The study showed an intervention effect on a number of socio-cognitive determinants. However, the effectiveness of WSWM could be improved by giving more systematic attention to the context in which such a programme is to be implemented. Implications for the systematic development and implementation of school-based safe sex interventions in Uganda will be discussed.


A review and update on cholangiocarcinoma.
Cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium that was first described by Durand-Fardel in 1840. Today, it continues to defy diagnosis and treatment. It is difficult to diagnose in part because of its relative rarity, and because it is clinically silent until it becomes advanced disease with obstructive symptoms. The worldwide incidence of cholangiocarcinoma has risen over the past three decades. There is marked geographic variability in the prevalence of this disease, due in large part to regional environmental risk factors. Surgical resection remains the only curative treatment, and high priorities are improving diagnostic methods, and clinical staging for resection once the disease is suspected. A recent trend towards aggressive surgical management has improved outcomes. Chemotherapy, palliative stenting, and radiation are reserved for patients who are not resectable, those with recurrence after surgery, and those who decline surgical intervention. Recent trials using combination systemic chemotherapy and neoadjuvant chemoradiation are promising, but require further study. Over the past five years, several important studies have yielded new insights into the molecular mechanisms of cholangiocarcinoma tumorigenesis. In this review we discuss epidemiology, etiologic factors, molecular pathogenesis, diagnosis, staging, and treatment of cholangiocarcinoma. Particular focus is on recent studies into the cellular and molecular pathogenesis of the disease, recent chemotherapy trials, and newer methods of staging and screening for this devastating malignancy.


The validation of a computer-based food record for older adults: the Novel Assessment of Nutrition and Ageing (NANA) method.
Dietary assessment in older adults can be challenging. The Novel Assessment of Nutrition and Ageing (NANA) method is a touch-screen computer-based food record that enables older adults to record their dietary intakes. The objective of the present study was to assess the relative validity of the NANA method for dietary assessment in older adults. For this purpose, three studies were conducted in which a total of ninety-four older adults (aged 65-89 years) used the NANA method of dietary assessment. On a separate occasion, participants completed a 4 d estimated food diary. Blood and 24 h urine samples were also collected from seventy-six of the volunteers for the analysis of biomarkers of nutrient intake. The results from all the three studies were combined, and nutrient intake data collected using the NANA method were compared against the 4 d estimated food diary and biomarkers of nutrient intake. Bland-Altman analysis showed a reasonable agreement between the dietary assessment methods for energy and macronutrient intake; however, there were small, but significant, differences for energy and protein intake, reflecting the tendency for the NANA method to record marginally lower energy intakes. Significant positive correlations were observed between urinary urea and dietary protein intake using both the NANA and the 4 d estimated food diary methods, and between plasma ascorbic acid and dietary vitamin C intake using the NANA method. The results demonstrate the feasibility of computer-based dietary assessment in older adults, and suggest that the NANA method is comparable to the 4 d estimated food diary, and could be used as an alternative to the food diary for the short-term assessment of an individual's dietary intake.


Genetic services survey-experience of people with rare diseases and their families accessing genetic services in the Irish Republic.
Irish Health Service objectives state that patients with rare diseases should have timely access to genomic diagnostics with appropriate pre and post-test counselling. However, waiting times for clinical genetics outpatient appointments, during the study period, were up to two years as staffing levels remain low. A targeted public online survey was conducted in January 2022 to capture the experiences of Rare Disease families trying to access genetic testing and clinical genetic clinics in the Irish Republic. Irish patients experience significant waiting times to access clinical genetic services and self-report anxiety and stress, related to delayed access to diagnosis, clarity around recurrence risk and follow-up management. This negatively impacts personal decisions around family planning, education and employment and has a significant impact on family members seeking clarity on their own risk. Mainstream genetic testing activity is significant. Families report concern over the competency of health care professionals arranging and delivering genetic results and delays in accessing clinical genetics expertise to take them through the clinical implications. Timely access to clinical genetics expertise is important to ensure families with rare diseases have an appropriate understanding of the medical and reproductive implications of a genetic diagnosis and access to relevant care pathways. A national framework to develop competency in genomic literacy for health-care professionals including a national genetic test directory may be beneficial. Clinical genetics teams require ongoing support and investment to ensure the delivery of a safe and effective service for Irish families with rare diseases.


Effects of cellulose degradation products on the mobility of Eu(III) in repositories for low and intermediate level radioactive waste.
The deep repository for low and intermediate level radioactive waste SFR in Sweden will contain large amounts of cellulosic waste materials contaminated with radionuclides. Over time the repository will be filled with water and alkaline conditions will prevail. In the present study degradation of cellulosic materials and the ability of cellulosic degradation products to solubilize and thereby mobilise Eu(III) under repository conditions has been investigated. Further, the possible immobilization of Eu(III) by sorption onto cement in the presence of degradation products has been investigated. The cellulosic material has been degraded under anaerobic and aerobic conditions in alkaline media (pH: 12.5) at ambient temperature. The degradation was followed by measuring the total organic carbon (TOC) content in the aqueous phase as a function of time. After 173days of degradation the TOC content is highest in the anaerobic artificial cement pore water (1547mg/L). The degradation products are capable of solubilising Eu(III) and the total europium concentration in the aqueous phase was 900μmol/L after 498h contact time under anaerobic conditions. Further it is shown that Eu(III) is adsorbed to the hydrated cement to a low extent (<9μmol Eu/g of cement) in the presence of degradation products.


Oncolytic adenovirus expressing interferon alpha in a syngeneic Syrian hamster model for the treatment of pancreatic cancer.
The addition of interferon (IFN) alpha to adjuvant chemoradiotherapy regimens resulted in remarkable improvements in survival for pancreatic cancer patients. However, systemic toxicities and insufficient levels of IFN at the tumor sites have limited its widespread adoption in treatment schemes. We have previously developed an IFN-expressing conditionally replicative oncolytic adenovirus and demonstrated its therapeutic effects both in vitro and in vivo. Here, the same vectors were tested in a syngeneic and immunocompetent Syrian hamster model to better understand the roles of adenoviral replication and of the pleiotropic effects of IFN on pancreatic tumor growth suppression. Oncolytic adenoviruses expressing human or hamster IFN were designed and generated. Viral vectors were tested in vitro to determine qualitative and quantitative cell viability, cyclooxygenase 2 (Cox2) promoter activity, and IFN production. For the in vivo studies, subcutaneous hamster pancreatic cancer tumors were treated with 1 intratumoral dose of virus. Similarly, 1 intraperitoneal dose of virus was used to prolong survival in a carcinomatosis model. All cell lines tested demonstrated Cox2 promoter activity. The oncolytic potential of a replication competent adenovirus expressing the IFN cytokine was clearly demonstrated. These viruses resulted in significant tumor growth suppression and survival increases compared with controls in a hamster model. The profound therapeutic potential of an IFN-expressing oncolytic adenovirus for the treatment of pancreatic cancer was demonstrated in a syngeneic Syrian hamster model. These results strongly suggest the potential application of our viruses as part of combination regimens with other therapeutics.


First-year changes in blood lead and zinc protoporphyrin levels within two groups of occupational lead workers.
Quarterly changes in blood lead (PbB) and zinc protoporphyrin (ZPP) levels experienced by 30 male lead-acid storage battery workers and 24 auto assembly workers during their initial year of occupational lead exposure are described. The greatest absolute and percentage increases above baseline PbB levels occurred during the first 3 months of continuous exposure when battery and assembly workers' average PbB levels increased by 99% and 134%, respectively. Peak average PbB levels were reached during the second quarter of exposure for battery workers (27.3 micrograms/dL) and during the third quarter for assembly workers (34.3 micrograms/dL). Mean ZPP levels increased steadily through the first 3 quarters of exposure for both groups of workers before declining slightly during the final 3 months. Third-quarter average ZPP levels were 46.6 micrograms/dL for battery workers and 59.4 micrograms/dL for assembly workers. In general, for the assembly workers, the slopes of quarterly dose (PbB)-effect (loge ZPP) regressions increased with increasing exposure duration (up to 0.044 by the third quarter of exposure) and were significant (p less than 0.0001). Similar calculations for the battery workers were not statistically significant (p greater than 0.05) and showed no exposure-related trends. Probit-based dose (PbB)-response (ZPP level greater than two standard deviations above the baseline ZPP) analyses of the assembly worker data resulted in a 30.0 micrograms/dL ED50 estimate (PbB concentration at which 50% of a similarly exposed population would be expected to develop an "elevated" ZPP level).(ABSTRACT TRUNCATED AT 250 WORDS)


Colorado family practice graduates' preparation for and practice of emergency medicine.
Family physicians provide care in emergency departments, especially in rural areas; however, no published data describe how they perceive their preparation for emergency practice. We surveyed graduates of Colorado family practice residencies concerning their emergency medicine practice, their comfort working in emergency departments, and their perceived preparation for practicing emergency medicine. Seventy recent graduates of Colorado residencies were surveyed regarding their location, work in emergency departments, contact with emergency medical services (EMS) personnel, and perceptions about their emergency medical training. Forty-five percent of respondents practiced in rural settings, 33% worked in emergency departments (56% rural, 14% urban), 60% reported contact with EMS personnel (91% rural, 32% urban), 54% believed their training adequately prepared them for working in emergency departments (82% rural vs 32% urban), 63% of rural and 22% of urban respondents indicated they wanted more major trauma experience during training, 70% reported discomfort with managing trauma, and 44% were interested in a 6-month emergency medicine fellowship. Most respondents believed their training in emergency medicine was adequate; however, most also reported discomfort with trauma management. Improved training for family physicians who provide emergency care could include expanded trauma care opportunities, increased work with EMS personnel, and postresidency training.


Spotted fever rickettsiosis in Coronel Fabriciano, Minas Gerais State.
We report cases of spotted fever rickettsiosis in Coronel Fabriciano Municipality of Minas Gerais State, Brazil. The cases occurred in May and June of 2000. During this period there were two deaths among children from an area named Pedreira in a periurban area of this municipality. In a boy who died with clinical manifestations of Brazilian spotted fever, a necropsy revealed the presence of a spotted fever group Rickettsia. The serological results confirm the difficulty in the differential diagnosis of patients with symptoms of rickettsial diseases.


CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice.
The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 participate in the retention of normal hematopoietic stem cells within the bone marrow (BM) and their release into the circulation. Homing and engraftment of human stem cells in immunodeficient mice are dependent on cell surface CXCR4 expression and the production of BM SDF-1, which acts also as a survival factor for both human and murine stem cells. However, the role of SDF-1/CXCR4 interactions in the control of human acute myelogenous leukemia (AML) cell trafficking and disease progression is poorly understood. In this study, we report that although some AML cells do not express surface CXCR4, all AML cells tested express internal CXCR4 and SDF-1. Culture of AML cells with SDF-1 promoted their survival, whereas addition of neutralizing CXCR4 antibodies, SDF-1 antibodies, or AMD3100 significantly decreased it. Pretreatment of primary human AML cells with neutralizing CXCR4 antibodies blocked their homing into the BM and spleen of transplanted NOD/SCID/B2m(null) mice. Furthermore, weekly administrations of antihuman CXCR4 to mice previously engrafted with primary AML cells led to a dramatic decrease in the levels of human AML cells in the BM, blood, and spleen in a dose- and time-dependent manner. Interestingly, the same treatment did not affect significantly the levels of normal human progenitors engrafted into NOD/SCID mice. Taken together, our findings demonstrated the importance of the SDF-1/CXCR4 axis in the regulation of in vivo motility and development of human AML stem cells and identified CXCR4 neutralization as a potential treatment for AML.


'Our Care through Our Eyes': a mixed-methods, evaluative study of a service-user, co-produced education programme to improve inpatient care of children and young people admitted following self-harm.
Within Europe, the UK has one of the highest rates of self-harm, with a particularly high prevalence in children and young people (CYP). CYP who are admitted to paediatric hospital wards with self-harm are cared for by registered children's nurses who have been identified to lack specific training in caring for this patient group. This may impede the delivery of high quality care. Therefore, this study aims to co-produce, implement and evaluate an education programme for registered children's nurses to improve their knowledge, attitudes and confidence when caring for CYP admitted with self-harm. This mixed-methods evaluative study will involve a three-stage design. Stage 1: A priority-setting workshop will be conducted with 19 registered children's nurses. A Delphi technique will be used to establish consensus of information needs. Stage 2: An online educational intervention will be co-produced with 25 CYP and 19 registered children's nurses based on the priorities identified in Stage 1. Stage 3: The intervention will be implemented and evaluated with 250 registered children's nurses at a single hospital. Online Likert scale questionnaires will be administered at baseline and postintervention to assess levels of knowledge, attitudes and confidence in caring for CYP who self-harm. Descriptive and inferential statistics will be used to analyse the data. Statistical significance will be assessed at the 5% (two-sided) level. One-to-one qualitative interviews will also be undertaken with approximately 25 participants to explore any perceived impact on clinical practice. An interpretive descriptive approach will guide qualitative data collection and analysis. This study aims to develop, trial and evaluative a service-user, co-produced education programme for acute hospital registered children's nurses to improve the care of CYP admitted due to self-harm. The study has ethical approval from the National Health Services Research Ethics Committee and full governance clearance.


Effect of accelerated aging on the color stability of cemented laminate veneers.
The effect of the aging process on color stability of light-cure, dual-cure, and self-cure resin cements used for luting laminate veneers was investigated in this study. Dyract Cem (self cure), Twinlook (dual cure), and En Force (light cure) cements, 0.30 mm thick, were polymerized on laminate veneers that were 13 mm in diameter and 0.50 mm thick in an A2 shade. Five specimens were made for each material. The specimens were subjected to an accelerated aging process in a Weather-Ometer for 900 hours. Spectrophotometric analyses were made after 300, 600, and 900 hours of accelerated aging time. Overall color difference (delta E*ab) was determined using the CIE-LAB system for measuring small color differences. Chroma changes (delta C*ab) and hue differences (delta H*ab) were also determined. delta E*ab, delta C*ab, and delta H*ab were analyzed by one-way analysis of variance, t test for dependent samples, and Tukey honestly significant difference (HSD) tests. delta E*ab values determined for the materials in this study varied in the acceptable range of 1.9 to 2.7. Different aging times caused no significant differences in delta E*ab, delta C*ab, or delta H*ab values for any of the materials. There were no significant differences in the amount of overall color change among the 3 resin cements at the same aging period. Twinlook material showed the greatest chroma change at each aging time. The greatest hue change was determined for Dyract Cem material. The light-cure resin cement tested can be proposed as a suitable material for luting laminate veneers, but long-term clinical studies are necessary to verify these experimental findings.


Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance.
Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic beta(2)-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K(+) at the nodes of Ranvier and a reduced release of K(+) in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.


PIC cystography in occult vesicoureteral reflux: A systematic review highlighting its utility in children with recurrent urinary tract infections and normal VCUG.
Vesicoureteral reflux (VUR) affects 1-2% of children, predisposing them to pyelonephritis, renal scarring, and reflux nephropathy. Treatment aims to prevent febrile urinary tract infections (f-UTI) and long-term sequelae. While guidelines differ, the current consensus proposes individual risk-stratification and subsequent management strategies. Here, we systematically analyzed the current literature on Positional Instillation of Contrast Cystography (PIC) for individualized diagnostics in patients with recurrent f-UTIs. We present a comprehensive qualitative and quantitative synthesis. Outcomes were: 1. the ability of PIC to predict VUR in patients with negative voiding cystographies (VCUG), 2. the ability of PIC to predict occult contralateral VUR, 3. the correlation of occult VUR in PIC with dimercaptosuccinic acid (DMSA) scan findings, and 4. the incidence of postoperative f-UTI in children treated for occult VUR picked up on PIC. We conducted a systematic review following the PRISMA guidelines, applying the following inclusion criteria: Children with occult VUR in PIC with negative VCUG. We included nine studies with 496 symptomatic patients with a mean age of 6.8 years, published between 2003 and 2021. PIC detected VUR in 73% of patients. Out of them, 81% had low-grade and 19% high-grade VUR. Occult contralateral VUR was present in 41% children. The presence of renal scars on DMSA scan was 1.39 times more likely with occult VUR on PIC. 85% of patients did not experience recurrent f-UTIs after PIC and subsequent treatment. PIC can detect occult VUR in patients with recurrent f-UTIs in whom VCUG is negative. However, we recommend a cautious approach in the use of PIC in clinical practice until further prospective studies confirm the validity of our outcome measures. Identification, risk stratification, and prompt action are central in managing VUR. PIC can be helpful in identifying VUR in patients with recurrent f-UTI.


[Polymerization of myorod, a surface protein of thick filaments of molluscan smooth muscle].
The study is concerned with the polymerization of myorod, a protein from thick filaments of molluscan smooth muscles, which is an alternative product of the gene of myosin heavy chains. The dependences of the properties and polymer structure of myorod on the conditions of its formation were investigated. It was shown that myorod loses the ability to form viscous polymers after proteolytic removal of the unique sequence. It was supposed that the specificity of polymerization of myorod are determined by its unique N-terminal sequence.


Health Care Use Before and After Entering Long-Term Services and Supports.
We examined the health care utilization patterns of Medicare and Medicaid enrollees (MMEs) before and after initiating long-term care in the community or after admission to a nursing facility (NF). We used administrative data to compare hospitalizations, emergency department (ED) visits, and post-acute care use of MMEs receiving long-term care in California in 2006-2007. MMEs admitted to a NF for long-term care had much greater use of hospitalizations, ED visits, and post-acute care before initiating long-term care than those entering long-term care in the community. Post-entry, community service users had less than half the average monthly hospital and ED use compared with the NF cohort. Hospital and ED use prior to and following NF and personal care program entry suggest a need for reassessing the monitoring of these high-risk populations and the communication between health and community care providers.


Chlorpropamide-alcohol flushing, aldehyde dehydrogenase activity, and diabetic complications.
Many diabetics who take chlorpropamide (a sulphonylurea compound) experience facial flushing after drinking even small amounts of alcohol. These flushers have a noticeably lower prevalence of late complications of diabetes (microangiopathy, macroangiopathy, and neuropathy) than non-flushers. This flush reaction is accompanied by increased blood acetaldehyde concentrations, suggesting an inhibition of aldehyde dehydrogenase activity. In the present study the activity of this enzyme in erythrocytes was assessed in the absence of chlorpropamide. Erythrocyte homogenates obtained from flushers and non-flushers were incubated with acetaldehyde and the rate of metabolism studies. Flushers eliminated acetaldehyde more slowly at a low range of concentrations (0--30 mumol/l), suggesting a difference in aldehyde dehydrogenase activity. Further studies are needed to clarify the role of this enzyme in the pathogenesis of diabetic complications.


Spatially Selective, High-Density Placement of Polyfluorene-Sorted Semiconducting Carbon Nanotubes in Organic Solvents.
High-performance logic based on carbon nanotubes (CNTs) requires high-density arrays of selectively placed semiconducting CNTs. Although polymer-wrapping methods can allow CNTs to be sorted to a >99.9% semiconducting purity, patterning these polymer-wrapped CNTs is an outstanding problem. We report the directed self-assembly of polymer-coated semiconducting CNTs using self-assembled monolayers that bind CNTs into arrays of patterned trenches. We demonstrate that CNTs can be placed into 100 nm wide HfO2 trenches with an electrical connection yield as high as 90% and into 50 nm wide trenches with a yield as high as 70%. Our directed self-assembly method is an important step forward in pitch scaling.


Eye movement desensitisation and reprocessing therapy for posttraumatic stress disorder in a child and an adolescent with mild to borderline intellectual disability: A multiple baseline across subjects study.
This study explored the effectiveness of eye movement desensitisation and reprocessing (EMDR) therapy for post-traumatic stress disorder (PTSD) in persons with mild to borderline intellectual disability (MBID) using a multiple baseline across subjects design. One child and one adolescent with MBID, who met diagnostic criteria for PTSD according to a PTSD clinical interview (i.e., ADIS-C PTSD section), adapted and validated for this target group, were offered four sessions of EMDR. PTSD symptoms were measured before, during and after EMDR, and at six weeks follow-up. For both participants, number of PTSD symptoms decreased in response to treatment and both no longer met PTSD criteria at post-treatment. This result was maintained at 6-week follow-up. The results of this study add further support to the notion that EMDR can be an effective treatment for PTSD in children and adolescents with MBID. Replication of this study in larger samples and using a randomized controlled design is warranted.


Molecular characterization of Cronobacter lipopolysaccharide O-antigen gene clusters and development of serotype-specific PCR assays.
Cronobacter (formerly Enterobacter sakazakii) is a recently defined genus consisting of six species, C. sakazakii, C. malonaticus, C. dublinensis, C. muytjensii, C. turicensis, and Cronobacter genomospecies 1. In this study, MboII restriction fragment length polymorphism (RFLP) patterns of O-antigen gene clusters, located between galF and gnd, were used to identify serotypes in Cronobacter spp. Seven O-antigen RFLP clusters were generated, including three C. sakazakii clusters, previously identified as serotypes O1, O2, and O3. The O-antigen regions of six strains with unique RFLP patterns, including two C. sakazakii strains, two C. malonaticus strains, one C. turicensis strain, and one C. muytjensii strain, revealed three O-antigen gene clusters shared among Cronobacter species. PCR assays were developed, targeting the wzx O-antigen polymerase gene, and used to screen 231 Cronobacter strains to determine the frequency of these newly identified serotypes.


Effects of recombinant apolipoprotein A-I(Milano) on aortic atherosclerosis in apolipoprotein E-deficient mice.
We previously reported marked inhibitory effects of recombinant apolipoprotein (apo) A-I(Milano)/phospholipid complex (A-I[Milano]/PC) on neointimal lesions in balloon-injured iliofemoral arteries of hypercholesterolemic rabbits. In this study, we tested the hypothesis that apo A-I(Milano)/PC would inhibit aortic atherosclerosis in apo E-deficient mice. Thirty-five apo E-deficient mice fed a high-cholesterol diet were included in the study. Control mice were killed at 20 (n=8) or 25 (n=7) weeks. Treated mice received 18 injections of either 40 mg/kg apo A-I(Milano)/PC (n=15) or PC only (n=5) intravenously every other day from 20 weeks until death at 25 weeks. Aortic atherosclerosis was identified with Sudan IV staining. Lipid and macrophage contents of the aortic sinus plaques were measured after oil-red O and Mac-1 antibody staining, respectively, and quantified with computed morphometry. In control mice, from 20 to 25 weeks, aortic atherosclerosis increased by 59% (11 +/- 1% versus 17 +/- 5% of the aortic surface, P=.002), and lipid content increased by 45% (22 +/- 8% versus 32 +/- 6% of plaque area, P=.02) without a significant change in macrophage content (10.8 +/- 2% versus 13.2 +/- 6%). Compared with 20-week-old untreated control mice, PC only-treated mice at 25 weeks demonstrated a 32% increase in aortic atherosclerosis (11 +/- 1% versus 15 +/- 4%, P=.01) and an increase in lipid content (22 +/- 8% versus 47 +/- 3%, P<.0001) without a change in macrophage content (10.8 +/- 2% versus 11 +/- 2%). In comparison with 20-week-old untreated control mice, 25-week-old apo A-I(Milano)/PC-treated mice demonstrated no increase in aortic atherosclerosis (11 +/- 1% versus 10 +/- 4%, P=NS), a 40% reduction in lipid content (22 +/- 8% versus 13 +/- 8%, P=.01), and a 46% reduction in macrophage content (10.8 +/- 2% versus 5.8 +/- 2.9%; P=.03). Serum cholesterol levels were markedly elevated in all groups and did not change significantly with apo A-I(Milano)/PC or PC only. In vitro, apo A-I(Milano)/PC stimulated cholesterol efflux from cholesterol-loaded FU5AH hepatoma cell lines in a dose-dependent manner, whereas PC only or PC-free apo A-I(Miano) had no effect. Recombinant A-I(Milano)/PC prevented progression of aortic atherosclerosis and reduced lipid and macrophage content of plaques in apo E-deficient mice despite severe hypercholesterolemia. Thus, A-I(Milano)/PC may have a role in inhibiting progression and promoting stabilization of atherosclerosis.


Mechanism of binding of a benzomorphan opiate to the acetylcholine receptor from Torpedo electroplaque.
The mechanism of binding of the benzomorphan opiate, (-)-N-allylnormetazocine [(-)-ANMC], to Torpedo acetylcholine receptor (AcChR)-rich membranes was investigated. Using a centrifugation assay, two equilibrium binding affinities were observed with KD values of 0.4 and 2 microM. The KD and the apparent Bmax of the higher affinity component were decreased by cholinergic agonists and antagonists but not by alpha-bungarotoxin alone. The high affinity binding site (KD = 0.4 microM) was found to be distinct from the binding site for tetracaine, a noncompetitive blocker. The apparent association rate constant was essentially independent of receptor concentration both in the presence and absence of the cholinergic agonist, carbamoylcholine. When carbamoylcholine was equilibrated with the AcChR prior to (-)-[3H]ANMC addition, the association rate constant was 2- to 3-fold greater than in the absence of cholinergic effectors. When carbamoylcholine and (-)-[3H]ANMC were added simultaneously to AcChR-rich membranes, association was too rapid to resolve manually and binding measured at 5 sec was greater than the equilibrium level both in the presence and absence of carbamoylcholine. Binding decreased as a function of time, reaching its equilibrium level with a time constant of approximately 1 min. This effect appeared to be agonist specific since it was not observed when the antagonist, d-tubocurarine, replaced carbamoylcholine. In the absence of cholinergic ligands, dissociation of (-)-ANMC was biphasic (t1/2 values of less than 5 sec and approximately 2.5 min) and, in the presence of cholinergic ligands, was monophasic (t1/2 of 40 sec). The simultaneous addition of carbamoylcholine and (-)-[3H]ANMC to the membranes initially results in a biphasic dissociation (t1/2 of 5 and 30 sec) which becomes monophasic with increasing times of incubation. A mechanism is proposed involving an isomerization of the receptor-ligand complex which agrees quantitatively and qualitatively with the data.


Kindling as a model of drug-resistant partial epilepsy: selection of phenytoin-resistant and nonresistant rats.
Complex partial seizures comprise the major uncontrolled seizure type in adult patients with epilepsy. Any improvement of our understanding of the mechanisms through which these seizures are often refractory to antiepileptic drugs is therefore of considerable importance. By examining the effects of the anti-epileptic drug phenytoin in a large group of kindled rats, a widely used model of complex partial seizures, animals with different sensitivity to this drug were selected. Using determination of the focal seizure threshold for evaluation of phenytoin's anticonvulsant effect, most animals (about 60%) showed variable effects in response to phenytoin. However, about 20% of the animals ("phenytoin nonresponders") showed no increase in their focal seizure threshold at repeated test trials with phenytoin, and 20% ("phenytoin responders") exhibited reproducible increases in focal seizure threshold after injection of phenytoin. Phenytoin responders and nonresponders thus selected were used for subsequent experiments. The different response of focal seizures to phenytoin was not related to differences in pharmacokinetics or location of the stimulating electrode. Although phenytoin reproducibly increased the threshold for induction of afterdischarges in responders, it did not alter severity or duration of the elicited seizure response. In contrast to phenytoin, carbamazepine induced increases in focal seizure threshold in all kindled rats. Duration of seizures and afterdischarges were significantly reduced by carbamazepine in phenytoin responders, but not in nonresponders, although plasma levels of carbamazepine were the same in both groups. The difference in response of kindled rats to phenytoin was restricted to kindled seizures, because phenytoin induced the same anticonvulsant effect on the threshold for generalized tonic electroconvulsions (determined via transauricular electrodes) in both groups of kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinico-morphologic parallels in acute forms of Hirschsprung disease in newborns and infants].
39 newborns with an acute form of Hirschsprung's disease were under observation: rectal form 18%, recto-sigmoid 28.2%, subtotal 25.6%, total 28.2%. Clinical manifestations appeared soon after the birth and were characterized by the impediment of the meconium discharge, vomiting or eructations, abdominal swelling. The evaluation of the validity of histochemical and histological diagnostic methods in infants and morphologic description of the tissue acetylcholinesterase activity are presented. Hypoganglionic form of the disease was found in 4 cases. Clinical and morphologic picture of the hypogangliosis in newborns is described.


Restriction of neural precursor ability to respond to Nurr1 by early regional specification.
During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS) regionalization, generation of neural precursors (NPs) and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB) has been assigned to the transcription factor Nurr1. Nurr1 controls the expression of key genes involved in dopamine (DA) neurotransmission, e.g. tyrosine hydroxylase (TH) and the DA transporter (DAT), and promotes the dopaminergic phenotype in embryonic stem cells. We investigated whether cells derived from different areas of the mouse CNS could be directed to differentiate into dopaminergic neurons in vitro by forced expression of the transcription factor Nurr1. We show that Nurr1 overexpression can promote dopaminergic cell fate specification only in NPs obtained from E13.5 ganglionic eminence (GE) and MB, but not in NPs isolated from E13.5 cortex (CTX) and spinal cord (SC) or from the adult subventricular zone (SVZ). Confirming previous studies, we also show that Nurr1 overexpression can increase the generation of TH-positive neurons in mouse embryonic stem cells. These data show that Nurr1 ability to induce a dopaminergic phenotype becomes restricted during CNS development and is critically dependent on the region of NPs derivation. Our results suggest that the plasticity of NPs and their ability to activate a dopaminergic differentiation program in response to Nurr1 is regulated during early stages of neurogenesis, possibly through mechanisms controlling CNS regionalization.


Early ambulation: an ugly phrase for a beautiful idea.
The present study was undertaken to assess the effect of scheduled ambulation of selected post-operative outcomes between control and experimental groups in two hospitals of Bangalore; scores of post-operative outcomes of the two groups were also associated with demographic variables. The sample of 60 major abdominal surgery patients admitted in two hospitals was subjected to a rating scale of 14 demographic items and 35 items on parameters of post-operative outcomes like pain, fatigue, urine retention etc. The results showed that scheduled ambulation was effective in reducing the severity of selected post-operative outcomes.


Monoclonal antibodies to the ORF5 product of porcine reproductive and respiratory syndrome virus define linear neutralizing determinants.
Complementary DNA encoding the ORF5 gene of a Quebec reference isolate (IAF-Klop) of porcine reproductive and respiratory syndrome virus (PRRSV) was cloned into the prokaryotic expression vectors pGEX-4T and pET21a to produce ORF5-glutathione S-transferase and ORF5-polyhistidine fusion proteins. Five hybridoma cell lines producing monoclonal antibodies (MAbs) to the 25 kDa viral envelope glycoprotein (GP5) were obtained from BALB/c mice immunized with the affinity chromatography-purified GST-ORF5 fusion protein. The polypeptide specificity of these anti-PRRSV MAbs, belonging to the IgG1 isotype, was confirmed by Western immunoblotting assays with recombinant and native viral proteins, and by radioimmunoprecipitation using [35S]methionine-labelled concentrated extracellular virus. All these MAbs showed virus-neutralizing (VN) activity, with VN titres ranging from 1:32 to 1:128. Two MAbs (IAF-1B8 and IAF-8A8) reacted with similar titres with the modified live attenuated vaccine strain ATCC VR-2332, but all five failed to react to the prototype European strain, the Lelystad virus, in VN and indirect immunofluorescence tests. The results obtained suggest that these five anti-PRRSV MAbs are directed to serotype-specific linear neutralizing epitopes which are not affected by the absence of carbohydrate residues.


Physicochemical Characterization of Five Different Bone Graft Substitutes Used in Periodontal Regeneration: An In Vitro Study.
Periodontal regeneration involves using a variety of bone graft substitutes (BGS) of varying origin and manufacturing processes. These include a wide range of biomaterials that are mainly of two types: the xenografts and alloplasts. The efficacy of these BGS depends upon the physical characteristics such as particle size, porous nature, surface morphology, as well as the chemical characteristics like composition, crystallinity and resorption properties. The present study is a descriptive study that focuses on describing the physicochemical characteristics of five selected commercially available BGS that are frequently used in periodontal regeneration procedures. The BGS studied here included two xenografts (colocast and osseograft) and three alloplasts (B-OstIN, biograft HABG active and biograft HT). The physical properties of the BGS, including particle size, morphology, and surface topography, were analyzed using SEM. The mineral phases and crystallinity of the BGS were analyzed using XRD. The results showed that the xenografts (colocast and osseograft) had minimal mineral composition and crystalline structure. The physical properties such as surface roughness and porosity were less compared to alloplastic materials. The alloplasts (B-OstIN, biograft HABG and biograft HT) that had different chemical compositions showed varying physical and crystalline properties. Biograft HT showed a superior porous scaffold architecture among all BGS studied. It is important for a clinician to have a thorough understanding about the physicochemical characteristics of BGS they use in periodontal regeneration. The xenografts evaluated here had minimal physical and crystalline properties. Among the alloplasts studied, biograft HT showed superior physicochemical properties, while the presence of bioactive glass in biograft HABG enhanced regeneration.


Emerging Metabolic Therapies in Pulmonary Arterial Hypertension.
Pulmonary hypertension (PH) is an enigmatic vascular disorder characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance, ultimately resulting in pressure overload, dysfunction, and failure of the right ventricle. Current medications for PH do not reverse or prevent disease progression, and current diagnostic strategies are suboptimal for detecting early-stage disease. Thus, there is a substantial need to develop new diagnostics and therapies that target the molecular origins of PH. Emerging investigations have defined metabolic aberrations as fundamental and early components of disease manifestation in both pulmonary vasculature and the right ventricle. As such, the elucidation of metabolic dysregulation in pulmonary hypertension allows for greater therapeutic insight into preventing, halting, or even reversing disease progression. This review will aim to discuss (1) the reprogramming and dysregulation of metabolic pathways in pulmonary hypertension; (2) the emerging therapeutic interventions targeting these metabolic pathways; and (3) further innovation needed to overcome barriers in the treatment of this devastating disease.


Ionic Liquid-Enabled Topical Delivery of Immunomodulators.
Skin is one of the most immunologically active organs of the body due to the presence of diverse immune cells and its active involvement in the innate and adaptive immunity. Because of its unique location and immunological role, skin offers an excellent site for the introduction of immunomodulators to synergize with the active immune microenviroment for the desired outcome. However, delivery of immunomodulators to the skin remains a significant challenge due to the skin's barrier properties. Here, we report an ionic liquid (IL)-based strategy to formulate and deliver immunomodulators to the skin. Using imiquimod (IMQ) and triamcinolone acetonide (TCA) as the respective model immunoactive and immunosuppressive drugs, we demonstrated that ILs significantly enhanced the solubility of immunomodulators. In addition, ILs enabled the formulation of the immunomodulators into stable, topically applicable forms. Our ex vivo skin penetration studies revealed that the IL formulations outperformed respective commercial topical comparators and delivered significantly more immunomodulators to deep skin layers. The lead IMQ formulation exhibited >10-fold better efficacy in delivering IMQ to the deep skin layers as compared to the commercial 5% IMQ cream. Lead TCA formulations achieved a dose level in deep skin layers that is comparable to that by clinically used intralesional injections. Our data collectively suggest that the IL-based strategy can be a simple and effective platform for delivery of immunomodulators to the skin.


Epizootic vesicular stomatitis in Colorado, 1982: epidemiologic and entomologic studies.
An epizootic of vesicular stomatitis (VS) caused by the New Jersey serotype of VS virus affected livestock and humans in 14 western states in 1982-1983. Epidemiological observations were made on at least 10% of the cattle in 4 dairy herds that were located in the vicinity of Grand Junction, Colorado. High rates of neutralizing antibody to the New Jersey serotype were seen in all cattle regardless of whether livestock in the dairy had clinical VS or a decrease in mild production. Antibody titers remained high in these cattle for as long as 2 years after the epizootic. No virus isolations were made from 32 humans with clinical signs compatible with viral disease. Entomological information was obtained during the epizootic from 23 premises in northwestern Colorado. Insect collections yielded 4 isolates from Culicoides spp. midges, 2 from C. variipennis, and 1 each from C. stellifer and C. (Selfia) spp. This is the first report of VS virus isolations from field-collected Culicoides.


Percutaneous catheterization of the radial artery in the critically ill neonate.
Percutaneous catheterization of the radial artery appears to be a simple and safe alternative to catheterization of the umbilical artery for monitoring critically ill neonates. This avoids the serious and potentially fatal complications associated with use of the umbilical arterial catheter, and it is also applicable to monitoring of neonates in whom the umbilical artery is no longer patent. We observed no serious sequelae in cannulation of the radial artery and think that the technique should be used more widely.


Exercise thallium-201 myocardial scintigraphy in the follow-up of aortocoronary bypass graft surgery.
The predictive accuracy of exercise thallium-201 (201Tl) myocardial scintigraphy in the evaluation of aortocoronary bypass graft surgery was assessed in 48 patients undergoing angiographic investigation 15 months (mean time) after myocardial revascularisation. 201Tl scintigrams detected 61 out of 77 (79%) patent grafts but only 21 out of 42 (50%) occluded grafts, though, for grafts supplying non-infarcted myocardium, the predictive accuracy of graft patency and graft occlusion was 85 per cent and 81 per cent, respectively. Stress electrocardiography failed to detect 15 out of 21 patients with scintigraphic evidence of regional myocardial ischaemia. Residual ischaemia in the proximal left anterior descending coronary distribution was commonly detected in 201Tl scintigrams despite a patent, well-functioning left anterior descending graft to the distal coronary segment. Additional residual ischaemia attributable to ungrafted coronary disease was detected by scintigraphy in 32 (67%) patients and most commonly occurred in the distribution of the diagonal branch of the left anterior descending especially in the presence of a patent distal left anterior descending graft. Thus, independent grafts to the diagonal branch of the left anterior descending are recommended at the time of aortocoronary bypass graft surgery.


Characteristics and Stability of Ozone Nanobubbles in Freshwater Conditions.
The characteristics and stability of ozone nanobubbles (NBs) were investigated for the first time under different preparation conditions and freshwater conditions (i.e., pH, natural organic matter [NOM], carbonate, calcium, and temperature) for an extended period. Two oxygen gas flow rates (4 and 1 L/min) used in ozone NB generation affected the characteristics and stability of ozone NBs. The ozone NBs generated at a high initial dissolved ozone (12.5 mg/L) concentration showed a much higher brightness during measurements than the ozone NBs generated at a low initial dissolved ozone concentration (1 mg/L). The former also exhibited a higher negative surface charge and higher stability in comparison to the latter. The stability and half-lives of ozone NBs followed the order of 3 mM Ca2+ < pH 3 < NOM with high specific ultraviolet absorbance at 254 nm (SUVA254 = 4.1 L/mg·m) < pH 7 < pH 9, while the effects of carbonate and temperature were insignificant. Ozone NBs were relatively stable in waters for a long period (e.g., ≥ 60 days) except for high hardness or low pH conditions. Higher levels of hydroxyl radicals were produced from ozone NB solutions as compared to conventional ozonation.


Utilisation of parametric methods to improve percentile-based estimates for the carcinogenic potency of nitrosamines.
N-Nitrosamines have recently been the subject of intense regulatory scrutiny, including the setting of low exposure limits (18 ng/day) (European Medicines Agency (EMA), 2020). This paper evaluates different methodologies to determine statistically robust bounds on the carcinogenic potency of chemical classes, using historic TD50 data (Peto et al., 1984; Thresher et al., 2019) and exemplified for N-nitrosamines. Initially, the distribution of TD50 values (TD50s) for N-nitrosamines of known potency was characterised. From this, it is possible to compare parametric and non-parametric methods to obtain percentiles of interest from the distribution of TD50s, which are shown to be robust to uncertainty in the initial TD50 estimates. These methods may then be applied to different chemical subclasses. The values obtained may be of use in refining acceptable intakes for N-nitrosamines and their subclasses.


Assessment of pharmacists' perception of patient care competence and need for training in rural and urban areas in North Dakota.
Few studies have examined pharmacists' level of patient care competence and need for continuous professional development in rural areas. To assess North Dakota pharmacists' practice setting, perceived level of patient care competencies, and the need for professional development in urban and rural areas. A survey was mailed to all 686 North Dakota pharmacists and included items regarding practice setting, competency areas, and the need for certificate programs. Overall, 401 of 686 (58.5%) surveys were returned and 364 responses were usable. Three practice settings (independent community pharmacies [47.3%], chain stores [13.2%], and hospital pharmacies [22.8%]) comprised 83.3% of the sample. More independent community pharmacists were located in rural areas than urban areas (P < .01). More respondents had a Doctor of Pharmacy (PharmD) degree in urban areas (40.8%) compared to those in rural areas (15.1%) (P < .01). Pharmacists in urban areas rated 18 of 33 competencies higher than did pharmacists in rural areas (P < .01). Pharmacists with a Bachelor of Science degree reported a lower level of preparation than did PharmD trained pharmacists. Although not statistically significant, 28.2% of pharmacists perceived a patient care certificate as a need and a greater percentage were from rural than urban areas. The findings should be interpreted to be primarily due to differences in practice setting and degree earned that were most prevalent in urban and rural areas. Training mode needed most is through the certificate program, particularly by rural pharmacists who reported a lower level of preparation on perceived patient care-related items than did urban pharmacists.


Hypobaric 0.15% bupivacaine versus hypobaric 0.6% lidocaine for posterior spinal anesthesia in outpatient anorectal surgery.
Low doses of bupivacaine and lidocaine have been used for spinal anesthesia in outpatient surgery. The objective of this study was to compare hypobaric solutions of bupivacaine and lidocaine in outpatient anorectal surgery. One hundred and fifty patients, divided in two groups, physical status ASA I-II, scheduled for anorectal surgery in the jackknife position received 3 mL (4.5 mg) of hypobaric 0.15% bupivacaine or 3 mL (18 mg) of hypobaric 0.6% lidocaine. The selectivity of the blockade, quality of surgical anesthesia, intensity of the motor blockade, and time for patient recovery were compared. After patients were discharged, daily phone contact was maintained for three days and on the 30th postoperative day. Adequate surgical blockade was achieved in all patients. The mean level of cephalad dispersion was L(1), ranging from T(10)-L(3), with bupivacaine, and L(1), ranging from T(11)-L(2), with lidocaine. Motor blockade was not observed in 135 patients (65 in the bupivacaine group x 70 in the lidocaine group). None of the patients developed hypotension and bradycardia. The sensorial blockade had a mean duration of 99.1 (11.0) minutes, with bupivacaine, and 64.1 (7.6) minutes, with lidocaine (p < 0.0005). Post-lumbar puncture headache was not observed in any patient. Hypobaric solution of bupivacaine or lidocaine promotes, predominantly, sensorial blockade after subarachnoid injection in patients in the jackknife position. Hypobaric lidocaine provides analgesia with the same dispersion of that of bupivacaine, but with shorter duration. Hemodynamic stability and the absence of motor blockade represent the major advantages.


ADP-ribosylation factor 6 regulates actin cytoskeleton remodeling in coordination with Rac1 and RhoA.
In this study, we have documented an essential role for ADP-ribosylation factor 6 (ARF6) in cell surface remodeling in response to physiological stimulus and in the down regulation of stress fiber formation. We demonstrate that the G-protein-coupled receptor agonist bombesin triggers the redistribution of ARF6- and Rac1-containing endosomal vesicles to the cell surface. This membrane redistribution was accompanied by cortical actin rearrangements and was inhibited by dominant negative ARF6, implying that bombesin is a physiological trigger of ARF6 activation. Furthermore, these studies provide a new model for bombesin-induced Rac1 activation that involves ARF6-regulated endosomal recycling. The bombesin-elicited translocation of vesicular ARF6 was mimicked by activated Galphaq and was partially inhibited by expression of RGS2, which down regulates Gq function. This suggests that Gq functions as an upstream regulator of ARF6 activation. The ARF6-induced peripheral cytoskeletal rearrangements were accompanied by a depletion of stress fibers. Moreover, cells expressing activated ARF6 resisted the formation of stress fibers induced by lysophosphatidic acid. We show that the ARF6-dependent inhibition of stress fiber formation was due to an inhibition of RhoA activation and was overcome by expression of a constitutively active RhoA mutant. The latter observations demonstrate that activation of ARF6 down regulates Rho signaling. Our findings underscore the potential roles of ARF6, Rac1, and RhoA in the coordinated regulation of cytoskeletal remodeling.


Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.
"Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.


Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.
Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.


Little Cigars, Filtered Cigars, and their Carbonyl Delivery Relative to Cigarettes.
Little cigars and filtered cigars are currently growing in popularity due to their low cost and wide variety of flavors while retaining an appearance similar to cigarettes. Given the health consequences associated with cigarette use, it is important to understand the potential harm associated with these similar products. This includes the potential harm associated with carbonyls (eg, acetaldehyde, acrolein, formaldehyde, etc.), an important class of toxicants and carcinogens in tobacco smoke. Our objective was to determine the carbonyl levels in mainstream smoke from little and filtered cigars compared to cigarettes. We examined two brands each of little cigars and filtered cigars, as well as two research cigarettes for carbonyl delivery using the International Organization of Standards (ISO) and the Health Canada Intense (HCI) machine-smoking protocols. On a per puff basis, the levels of five of the seven carbonyls were higher from little cigars than filtered cigars and cigarettes (ISO: 56-116%; HCI: 39-85%; p < .05). On a per unit basis, most carbonyl levels were higher from both cigar types than cigarettes using the ISO method (ISO: 51-313%; p < .05) whereas only filtered cigars were higher using the HCI method (HCI: 53-99%; p < .05). These findings suggest that cigar smokers can be exposed to higher levels of carbonyls per cigar than cigarette smokers per cigarette. These data will increase our understanding of the relative harm from carbonyl exposure from little and filtered cigars both for cigar-only smokers and the cumulative harm among the growing population of cigarette-cigar multi-product smokers.


[Mirizzi syndrome: apropos of 13 cases].
The authors present 13 new cases of Mirizzi's syndrome seen over a 10-year period. An analysis is made of the scant frequency of this syndrome as a cause of extrahepatic obstructive jaundice, the diagnostic difficulties, and the results of surgical treatment.


Improved measurement linearity and precision for AMCW time-of-flight range imaging cameras.
Time-of-flight range imaging systems utilizing the amplitude modulated continuous wave (AMCW) technique often suffer from measurement nonlinearity due to the presence of aliased harmonics within the amplitude modulation signals. Typically a calibration is performed to correct these errors. We demonstrate an alternative phase encoding approach that attenuates the harmonics during the sampling process, thereby improving measurement linearity in the raw measurements. This mitigates the need to measure the system's response or calibrate for environmental changes. In conjunction with improved linearity, we demonstrate that measurement precision can also be increased by reducing the duty cycle of the amplitude modulated illumination source (while maintaining overall illumination power).


Herpes simplex virus type 1 exhibits a tropism for basal entry in polarized epithelial cells.
Herpes simplex virus type 1 (HSV-1) enters its host via epithelia and spreads to neuronal cells where latency is established. Hence, the in vivo route of infection relies on penetration and subsequent passage of HSV-1 through highly polarized cells. Infection studies were performed in both polarized MDCKII cells and primary human keratinocytes to gain insight into the pathway of virus entry into individual epithelial cells. Early viral gene expression was barely detectable in confluent MDCKII cells, even at high m.o.i. However, after wounding the cell layer, infected cells were observed next to the wound, where basolateral membranes were accessible. In subconfluent monolayers, MDCKII cells are organized in islets. After infection, viral capsids and early viral gene expression were detectable in peripheral cells of islets, supporting virus penetration via basolateral membranes. Further infection studies were performed in human keratinocytes, which represent the primary target cells for HSV-1 infection in vivo. In primary keratinocytes grown as monolayer cultures and wounded prior to infection, HSV-1 infection led to early viral gene expression predominantly in cells next to the wound. When stratifying cultures of primary human keratinocytes were infected, early viral gene expression was localized to peripheral cells of basal keratinocytes. Finally, infection of epithelial tissue such as human foreskin epithelia demonstrated HSV-1 entry exclusively via basal cell layers. Staining of the potential coreceptor nectin-1/HveC revealed no correlation of receptor localization and virus entry sites in keratinocytes. These results provide first evidence for a virus entry mechanism that relies on the accessibility to basal surfaces of epithelial tissue and to basolateral membranes, both in MDCKII and primary keratinocytes.


Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects.
The first results of the PREDIMED (PREvencion con Dieta MEDiterranea) randomized trial, after 3-month intervention, showed that the Mediterranean Diet (MD), supplemented with either virgin olive oil (VOO) or nuts, reduced systolic blood pressure, serum cholesterol and triacylglycerol (TG) concentrations and increased high-density lipoprotein (HDL)-cholesterol when compared to a control (low-fat diet) group. Serum TG levels are an independent risk factor for coronary heart disease and are strongly determined by very low-density lipoprotein (VLDL) composition, which can be specifically modified by dietary lipid source. Within the context of the PREDIMED study, we assessed the VLDL composition in 50 participants after 3 months of intake of two MD, supplemented with VOO or nuts, compared with a low-fat diet. Total and low-density lipoprotein cholesterol concentrations were reduced in subjects on the MD+nuts, whereas HDL-cholesterol increased after consumption of the MD+VOO. Serum TG concentrations were significantly lowered in both intervention groups (either the MD+nuts or MD+VOO). However, only the MD+VOO reduced the VLDL-cholesterol and VLDL-TG content and the TG/apolipoprotein B ratio in VLDL, which was used to estimate particle size. Although VLDL-TG fatty acids were very slightly modified, VLDL-TG molecular species in VLDL after consumption of the MD+nuts were characterized by a higher presence of linoleic acid (18:2, n-6), whereas after the intake of MD+VOO, they were rich in oleic acid (18:1, n-9). Therefore, we conclude that the reduction in systemic TG concentrations observed after consumption of the MD may be explained by reduction of the lipid core of VLDL and a selective modification of the molecular species composition in the particle.


ASD restricted and repetitive behaviors associated at 17q21.33: genes prioritized by expression in fetal brains.
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP). Of the 12 RRBs measured by the Autism Diagnostic Interview-Revised, seven were found to be significantly familial and substantially variable, and hence, were tested for genome-wide association in 3104 ASD-affected children from 2045 families. Using a stringent significance threshold (P<7.1 × 10-9), GWAS in the AGP revealed an association between 'the degree of the repetitive use of objects or interest in parts of objects' and rs2898883 (P<6.8 × 10-9), which resides within the sixth intron of PHB. To identify the candidate target genes of the associated single-nucleotide polymorphisms at that locus, we applied chromosome conformation studies in developing human brains and implicated three additional genes: SLC35B1, CALCOCO2 and DLX3. Gene expression, brain imaging and fetal brain expression quantitative trait locus studies prioritize SLC35B1 and PHB. These analyses indicate that GWAS of single heritable features of genetically complex disorders followed by chromosome conformation studies in relevant tissues can be successful in revealing novel risk genes for single core features of ASD.


Balance in the healthy elderly: posturography and clinical assessment.
To measure balance changes in the healthy elderly using quantitative dynamic posturography. To relate these changes to clinical measures of balance and gait. Elderly subjects screened for health criteria in a longitudinal study were examined using standardized cognitive, neurological, and performance-based tests. Quantitative posturography (Equitest, Neurocom International, Clackamas, Ore) was performed to determine the subject's response to sensory (Sensory Organization Test) and motor perturbations (Motor Coordination Test). Thirty-three healthy, old old subjects (> or =80 years; mean+/-SD age, 88+/-5 years) were compared with 15 subjects younger than 80 years (mean+/-SD age, 72+/-3 years). All were free of centrally active medications. The old old had worse quantitative equilibrium scores compared with subjects younger that 80 years when proprioceptive input was inaccurate and visual input was either preserved or completely absent. Old old subjects showed diminished adaptation to repeated platform rotations and fell more frequently during posturography. Quantitative balance measures correlated with age and functional measures of balance (Tinetti Balance Scale score, timed 1 leg standing). Progressive, functionally evident, age-related quantitative balance changes occur independent of typical geriatric pathological changes. These data should facilitate clinical decisions by allowing the distinction to be made between age-related and pathological changes.


Theory of force-extension curves for modular proteins and DNA hairpins.
We study a model describing the force-extension curves of modular proteins, nucleic acids, and other biomolecules made out of several single units or modules. At a mesoscopic level of description, the configuration of the system is given by the elongations of each of the units. The system free energy includes a double-well potential for each unit and an elastic nearest-neighbor interaction between them. Minimizing the free energy yields the system equilibrium properties whereas its dynamics is given by (overdamped) Langevin equations for the elongations, in which friction and noise amplitude are related by the fluctuation-dissipation theorem. Our results, both for the equilibrium and the dynamical situations, include analytical and numerical descriptions of the system force-extension curves under force or length control and agree very well with actual experiments in biomolecules. Our conclusions also apply to other physical systems comprising a number of metastable units, such as storage systems or semiconductor superlattices.


Regulation of CIRP by genetic factors of SP1 related to cold sensitivity.
Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 me diate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p<1×10-5, false discovery rate < 0.05). Among these variants, rs1117050 and rs11170510 had a strong linkage disequilibrium (r2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.


Mantle Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A European Mantle Cell Lymphoma Network Study.
While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6-182), 5-year progression-free survival (PFS) was 45% (95% CI: 35-54) and 5-year overall survival (OS) was 71% (95% CI: 62-79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p = 0.001) and median OS of 9.8 years vs 6.9 years (p = 0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment.


Elastic power but not driving power is the key promoter of ventilator-induced lung injury in experimental acute respiratory distress syndrome.
We dissected total power into its primary components to resolve its relative contributions to tissue damage (VILI). We hypothesized that driving power or elastic (dynamic) power offers more precise VILI risk indicators than raw total power. The relative correlations of these three measures of power with VILI-induced histologic changes and injury biomarkers were determined using a rodent model of acute respiratory distress syndrome (ARDS). Herein, we have significantly extended the scope of our previous research. Data analyses were performed in male Wistar rats that received endotoxin intratracheally to induce ARDS. After 24 h, they were randomized to 1 h of volume-controlled ventilation with low VT = 6 ml/kg and different PEEP levels (3, 5.5, 7.5, 9.5, and 11 cmH2O). Applied levels of driving power, dynamic power inclusive of PEEP, and total power were correlated with VILI indicators [lung histology and biological markers associated with inflammation (interleukin-6), alveolar stretch (amphiregulin), and epithelial (club cell protein (CC)-16) and endothelial (intercellular adhesion molecule-1) cell damage in lung tissue]. Driving power was higher at PEEP-11 than other PEEP levels. Dynamic power and total power increased progressively from PEEP-5.5 and PEEP-7.5, respectively, to PEEP-11. Driving power, dynamic power, and total power each correlated with the majority of VILI indicators. However, when correlations were performed from PEEP-3 to PEEP-9.5, no relationships were observed between driving power and VILI indicators, whereas dynamic power and total power remained well correlated with CC-16 expression, alveolar collapse, and lung hyperinflation. In this mild-moderate ARDS model, dynamic power, not driving power alone, emerged as the key promoter of VILI. Moreover, hazards from driving power were conditioned by the requirement to pass a tidal stress threshold. When estimating VILI hazard from repeated mechanical strains, PEEP must not be disregarded as a major target for modification.


[Seasonal anthropometric variations in adults of 2 different West African populations].
Results of nutritional surveys carried out during the wet and dry seasons in the South of Mali and the North of Senegal (Ferlo) reveal that adults in both areas experience seasonal weight variations of about 4%. These variations are related to the regular occurrence of food shortages during the rainy season. The circumstances in which these food shortages occur are not the same in the two communities: while the nomadic herders of Ferlo can significantly reduce energy outlay by resting during the rainy period, the Malian farmers, on the contrary, must work harder because their agricultural tasks are most demanding in this season. In conclusion, we stress the need to take this phenomenon into account in agricultural development projects and to overcome shortages provoked by the shift in peasants' habits from subsistence agriculture to cash crops.


Doubled prevalence rates of ANCA-associated vasculitides and giant cell arteritis between 1994 and 2006 in northern Germany.
The aim of this study was to investigate the period prevalences of ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (EGPA)/Churg-Strauss and GCA, in an urban and rural population in northern Germany in 2006 and to compare the data with our previous study performed in 1994. We identified of all patients with AAV or GCA via questionnaires to all hospital departments, physicians, health insurance providers, pension funds, reference laboratories for autoimmune diseases and death registries in Luebeck (city) and the rural region of Segeberg (population 468 962) between January and December 2006. The type of vasculitis, gender, year of birth, postal code and death were documented and re-evaluated. One-hundred and fifty patients were identified, indicating a prevalence of 320 per million inhabitants for the complete catchment area (95% CI 285, 355). GCA was more prevalent than AAV: 171 (146, 197) vs 149 (126, 174). GCA and AAV have almost doubled since 1994. GCA increased from 240 (164, 315) to 440 (399, 481) per million in the population ≥ 50 years of age and AAV increased from 74 to 149 cases per million. GCA and AAV were more prevalent in the urban compared with the rural region. The prevalence rates of AAV and GCA almost doubled from 1994 to 2006 for this region with a stable population and using an identical study design. Increased awareness has led to an earlier diagnosis of systemic vasculitis and improved activity-adapted treatment mostly based on randomized controlled trials has led to longer survival. Aspects such as environmental factors and exposure to certain substances need further research.


Perception of long-term oxygen therapy for chronic lung diseases may affect poor adherence in Korea.
Long-term oxygen therapy (LTOT) improves the survival of patients with hypoxemia due to chronic respiratory diseases. The clinical outcomes of LTOT are strongly associated with patient adherence. To improve the adherence of patients, physicians have focused on the efficacy of LTOT. However, poor adherence may stem from patients' perceptions of LTOT. Herein we evaluated patients' perceptions of LTOT affecting adherence. LWe conducted a cross-sectional survey study using descriptive, open, and closed-ended questionnaire. Patients using oxygen therapy (OT) or requiring it but avoiding OT responded to the questionnaires at three university hospitals. Seventy-nine patients responded to the questionnaires. The number of patients using home and portable OT was 69 (93%) and 37 (46.3%), respectively. Patients with good adherence were 22 (30.1%). Among patients with good adherence, 90.9% used oxygen according to physicians' prescriptions whereas only 37.3% of those with poor adherence followed physicians' prescriptions(p<0.01). The reasons for avoiding using home OT were fear of permanent use (50%), unwanted attention (40%), and lack of symptoms (40%). They avoided portable OT because of unwanted attention (39%), heaviness (n=31.7%), and lack of symptoms (21.6%). Patients on LTOT had the perception of the misunderstanding the effects of oxygen therapy and of psychosocial barriers to initiate or use LTOT. Considering these findings, health professionals need to provide effective education on the purpose of LTOT to improve patient adherence to OT and provide sufficient support for the management of psychosocial barriers in patients using LTOT.


Development of probiotic tablets using microparticles: viability studies and stability studies.
Alternative vectors to deliver viable cells of probiotics, to those conferring limited resistance to gastrointestinal conditions, still need to be sought. Therefore the main goal of the study was to develop tablets able to protect entrapped probiotic bacteria from gastric acidity, thus providing an easily manufacturing scale-up dosage form to deliver probiotics to the vicinity of the human colon. Whey protein concentrate microparticles with Lactobacillus paracasei L26 were produced by spray-drying and incorporated in tablets with cellulose acetate phthalate and sodium croscarmellose. The viability of L. paracasei L.26 throughout tableting as well as its gastric resistance and release from the tablets were evaluated. Storage stability of L. paracasei L26 tablets was also performed by evaluation of viable cells throughout 60 days at 23°C and 33% relative humidity. A decrease of approximately one logarithmic cycle was observed after the acid stage and the release of L. paracasei L26 from the tablets occurred only after 4 h in the conditions tested. Microencapsulated L. paracasei L26 in tablets revealed some susceptibility to the storage conditions tested since the number of viable cells decreased 2 log cycles after 60 days of storage. However, the viability of L. paracasei L26 after 45 days of storage did not reveal significant susceptibility upon exposure to simulated gastrointestinal conditions. The developed probiotic tablets revealed to be potential vectors for delivering viable cells of L. paracasei L26 and probably other probiotics to persons/patients who might benefit from probiotic therapy.


Physics of loose abrasive microgrinding.
This study examined the physics of loose abrasive microgrinding (grinding with micron and submicron sized abrasives). More specifically, it focused on the transition from brittle to ductile mode grinding which occurs in this region of abrasive sizes. Process dependency on slurry chemistry was the primary area of emphasis and was studied for diamond abrasives varying in size from 3.0 to 0.75 microm on both ULE and Zerodur, with emphasis on ULE. Ductile mode grinding was achieved with smaller abrasives, as expected, however two significant discoveries were made. The first observation was that by simply changing slurry chemistry, it was possible to induce the transition from brittle fracture to ductile mode grinding in ULE. This transition point could be intentionally moved about for diamonds 3.0-0.75 microm in diameter. For any given abrasive size within these limits, either brittle fracture or ductile removal may be achieved, depending on the slurry used to suspend the diamonds. Several slurries were studied, including water, a series of homologous n-alcohols, and other solvents chosen for properties varying from molecular size to dielectric constant and zeta potential. The study revealed that this slurry dependency is primarily a Rebinder effect. The second finding was that a tremendous amount of surface stress is introduced in loose abrasive ductile mode grinding. This stress was observed when the Twyman Effect in ULE plates increased by a factor of 4 in the transition from the brittle to the ductile mode. An assessment of the cause of this stress is discussed.


Structural basis for PHDVC5HCHNSD1-C2HRNizp1 interaction: implications for Sotos syndrome.
Sotos syndrome is an overgrowth syndrome caused by mutations within the functional domains ofNSD1 gene coding for NSD1, a multidomain protein regulating chromatin structure and gene expression. In particular, PHDVC5HCHNSD1 tandem domain, composed by a classical (PHDV) and an atypical (C5HCH) plant homeo-domain (PHD) finger, is target of several pathological missense-mutations. PHDVC5HCHNSD1 is also crucial for NSD1-dependent transcriptional regulation and interacts with the C2HR domain of transcriptional repressor Nizp1 (C2HRNizp1)in vitro To get molecular insights into the mechanisms dictating the patho-physiological relevance of the PHD finger tandem domain, we solved its solution structure and provided a structural rationale for the effects of seven Sotos syndrome point-mutations. To investigate PHDVC5HCHNSD1 role as structural platform for multiple interactions, we characterized its binding to histone H3 peptides and to C2HRNizp1 by ITC and NMR. We observed only very weak electrostatic interactions with histone H3 N-terminal tails, conversely we proved specific binding to C2HRNizp1 We solved C2HRNizp1 solution structure and generated a 3D model of the complex, corroborated by site-directed mutagenesis. We suggest a mechanistic scenario where NSD1 interactions with cofactors such as Nizp1 are impaired by PHDVC5HCHNSD1 pathological mutations, thus impacting on the repression of growth-promoting genes, leading to overgrowth conditions.


Do stimulants improve self-esteem in children with ADHD and peer problems?
The self-esteem of children with Attention Deficit Hyperactivity Disorder (ADHD) has been shown to be low. The effects of stimulant medication upon their self-esteem have not been systematically studied. The present study employed a reliable self-report instrument to measure the self-esteem of children with ADHD medicated with stimulants vs. those who were unmedicated. Results showed that stimulants were associated with significantly higher self-esteem. Children with ADHD prescribed stimulants reported feeling more intelligent and more popular than unmedicated children with ADHD. Children with ADHD and Oppositional Defiant Disorder (ODD) prescribed stimulants reported feeling better behaved. Significant correlations indicated that higher doses were associated with higher self-esteem. The present results suggest a need for a well-controlled study to determine if stimulants were responsible for the observed differences in self-esteem.


Authority without identity: defending advance directives via posthumous rights over one's body.
This paper takes a novel approach to the active bioethical debate over whether advance medical directives have moral authority in dementia cases. Many have assumed that advance directives would lack moral authority if dementia truly produced a complete discontinuity in personal identity, such that the predementia individual is a separate individual from the postdementia individual. I argue that even if dementia were to undermine personal identity, the continuity of the body and the predementia individual's rights over that body can support the moral authority of advance directives. I propose that the predementia individual retains posthumous rights over her body that she acquired through historical embodiment in that body, and further argue that claims grounded in historical embodiment can sometimes override or exclude moral claims grounded in current embodiment. I close by considering how advance directives grounded in historical embodiment might be employed in practice and what they would and would not justify.


Improving the cost, quality, and access to healthcare in community hospitals through the use of reorganized integrated delivery systems and implementation of sophisticated clinical information systems: an organizational experience.
It is well recognized that health care is undergoing fundamental and necessary change. These changes rival, if not exceed, changes that have occurred in other industries. The factors underlying the changes are varied, but fundamentally, the economics of health care have altered. A new economic model is evolving that is disciplined by the marketplace and/or regulatory determination of "price" on a per capita basis. Success in this new model will require integrated delivery systems (IDS) serving local communities linked to purchasers through affiliations that span broader geographic areas. The demands of this model are placing unparalleled requirements for change on health care providers including the need to develop new forms of delivery systems and implement sophisticated new information systems that allow collection and detailed analysis of important clinical and financial data in an effort to achieve better value in health care. A case study of the Health and Hospital Services, Inc. (HHS) integrated delivery system and information system strategy will be discussed.