Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction.
Conflicting evidence exists on the relationship between bicycle riding and erectile dysfunction (ED). A major limitation to several prior studies is the lack of a validated measure of ED. To assess the relationship between cycling and clinically validated ED based on existing literature. We searched several major databases from database inception through 2018 using a variety of search terms relating to "cycling" and "erectile dysfunction." Studies were included if they were written in English, reported original data, compared ED between cyclists and non-cycling controls, and used a validated measure of ED, such as the International Index of Erectile Function or the subset Sexual Health Inventory for Men (SHIM). Age, SHIM score, and comorbidities were extracted for all groups. Primary outcomes for each group were mean SHIM score and presence of ED (SHIM ≤ 21). A generalized linear mixed-effects model was used to fit the collected data for meta-analysis. Main outcome measures were unadjusted odds ratios of ED for cyclists and non-cyclists, mean SHIM score difference between cyclists and noncyclists, and both of these measures adjusted for age and comorbidities. After a systematic evaluation of 843 studies, 6 studies met our inclusion criteria, encompassing 3,330 cyclists and 1,524 non-cycling controls. When comparing cyclists to non-cyclists in an unadjusted analysis, there were no significant differences in the odds of having ED or mean SHIM score. However, when controlling for age and comorbidities, cyclists had significantly higher odds of having ED (odds ratio: 2.00; 95% confidence interval: 1.57, 2.55). Limited evidence supports a positive correlation between cycling and ED when adjusting for age and several comorbidities. Heterogeneity among studies suggests that further investigation into certain populations of cyclists that may be more vulnerable to ED may be beneficial. Gan ZS, Ehlers ME, Lin FC, et al. Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction. Sex Med 2021;9:304-311.


Return to preinjury activity levels after surgical management of femoroacetabular impingement in athletes.
A systematic review was conducted to identify, assess, and summarize the available evidence pertaining to surgical intervention for femoroacetabular impingement (FAI) in athletes. Summary estimates of treatment effect (proportion with 95% confidence interval [CI]) were calculated specifically for the rate of return to sport. Electronic databases (Medline, Embase, and Cochrane Library) were searched from inception to November 2011. The references of included articles were reviewed for eligible studies. The inclusion criteria were clinical studies, studies involving humans, minimum 6 months' follow-up, exclusive FAI treatment, and focus on athletes. Exclusion criteria were review articles, basic science investigations, radiologic studies, arthroplasty, and nonathlete clinical studies. A quality assessment of the included articles was conducted by 2 reviewers using a quality assessment tool developed by Yang et al. We used a random-effects model (DerSimonian-Laird method) to calculate weighted proportions. Percentages with 95% CIs are reported. Nine articles met the inclusion and exclusion criteria in this review. There was 72% agreement (95% CI, 0% to 94%) between the 2 independent reviewers for inclusion and quality assessment of the studies. A total of 418 athletes were surgically treated for FAI and were available for assessment. The rate of return to sport was 92% (95% CI, 87% to 96%), and the rate of return to the previous level of competition was 88% (95% CI, 80% to 94%). Despite the limitations of our systematic review, the findings suggest that surgical treatment for FAI resulted in a high return to preinjury activity levels of sports. Level IV, systematic review of Level IV studies (case series).


A polymorphism in the cachexia-associated gene INHBA predicts efficacy of regorafenib in patients with refractory metastatic colorectal cancer.
Activin/myostatin signaling has a critical role not only in cachexia but also in tumor angiogenesis. Cachexia is a frequent complication among patients with advanced cancer and heavily pretreated patients. We aimed to evaluate the prognostic significance of cachexia-associated genetic variants in refractory metastatic colorectal cancer (mCRC) patients treated with regorafenib. Associations between twelve single nucleotide polymorphisms in 8 genes (INHBA, MSTN, ALK4, TGFBR1, ALK7, ACVR2B, SMAD2, FOXO3) and clinical outcome were evaluated in mCRC patients of three cohorts: a discovery cohort of 150 patients receiving regorafenib, a validation cohort of 80 patients receiving regorafenib and a control cohort of 128 receiving TAS-102. In the discovery cohort, patients with any G variant in FOXO3 rs12212067 had a significantly lower response rate (P = 0.031) and overall survival (OS) than those with a T/T in univariate analysis (4.5 vs. 7.6 months, hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.09-2.46, P = 0.012). Among female patients, those with any G variant in INHBA rs2237432 had a significantly longer OS than those with an A/A in both univariate (7.6 vs. 4.3 months, HR = 0.57, 95%CI = 0.34-0.95, P = 0.021) and multivariable (HR = 0.53, 95%CI = 0.29-0.94, adjusted P = 0.031) analysis. This association was confirmed in female patients of the validation cohort, though without statistical significance (P = 0.059). Conversely, female patients with any G allele in the control group receiving TAS-102 did not show a longer OS. This was the first study evaluating the associations between polymorphisms in cachexia-associated genes and outcomes in refractory mCRC patients treated with regorafenib. Further studies should be conducted to confirm these associations.


The immunological hazard of Cushing's syndrome.
A 24-year-old woman was found to have cryptococcal meningitis and Cushing's syndrome due to an adrenal adenoma. Her meningitis was successfully arrested with fluorouracil. Treatment with metyrapone decreased her cortisol production and produced clinical remission of Cushing's syndrome. On admission her peripheral T lymphocytes were few and hyporeactive. When the overproduction of cortisol ceased the numbers of T lymphocytes and their reactivity returned to normal and she developed in-vitro lymphocyte responsiveness to the cryptococci.


Panel of Bacillus subtilis reporter strains indicative of various modes of action.
In a recent project, we collected the transcriptional profiles of Bacillus subtilis 168 after treatment with a large set of diverse antibacterial agents. One result of the data analysis was the identification of marker genes that are indicative of certain compounds or compound classes. We cloned these promoter regions in front of a luciferase reporter gene and reintroduced the constructs individually into the B. subtilis chromosome. Strains were analyzed for their responsiveness after treatment with a set of 37 antibacterials. Twelve functional reporter strains were generated that were selectively and significantly upregulated by the compounds. The selectivity of the reporter strains ranged from generic pathways like protein biosynthesis, cell wall biosynthesis, and fatty acid biosynthesis to compound classes (quinolones and glycopeptides) and individual compounds (rifampin, cycloserine, and clindamycin). Five of the strains are amenable for high-throughput applications, e.g., pathway-specific screening. In summary, we successfully generated B. subtilis reporter strains that are indicative of the mechanisms of action of various classes of antibacterials. The set of reporter strains presented herein can be used for mode-of-action analyses and for whole-cell screening of compound libraries in a mode-of-action-specific manner.


[Diseases of the lymphopharyngeal ring in the employees engaged in dust-producing industries].
The objective of the present work was to study changes in the mucous membrane of the upper respiratory tract of the employees subjected to the action of industrial aerosols. The clinically and functionally significant mucosal changes in the nasal cavity and pharynx induced by industrially-derived irritants are described, the classification of nosological forms of the diseases of upper respiratory tract is proposed based on the character and extent of the pathological process, the criteria for occupational chronic rhinopharyngolaryngitis have been developed. The frequency of development of pathological changes in the mucous membrane of the upper respiratory tract (UPT) in the workers undergoing effects of industrial aerosols (IA) is shown to amount to 89%. The highest dust concentrations to which such persons were exposed are known to occur in coal, metal, timber, textile, and cotton industries as well as in certain branches of machine-building and agricultural industries. The industrial environment not infrequently contains dust of the mixed composition, such as mineral, metallic, organic, and synthetic particulate components. The authors propose the classification of pathological changes in the UPT mucosa. It is emphasized that rhinopharyngolaryngites are included in the List of occupational diseases approved by the Russian Ministry of Health on 27 April 2012.


Serum anticholinergic activity and cerebral cholinergic dysfunction: an EEG study in frail elderly with and without delirium.
Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence. 61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained. 15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 +/- 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Delirium-associated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels. In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis.


Knowledge, attitudes and practices on influenza vaccination during pregnancy in Quito, Ecuador.
Vaccination is the most effective way to prevent infection and severe outcomes caused by influenza viruses in pregnant women and their children. In Ecuador, the coverage of seasonal influenza vaccination in pregnant women is low. The aim of this study was to assess the knowledge, attitudes, and practices (KAP) of pregnant women toward influenza vaccination in Quito-Ecuador. A cross-sectional study enrolled 842 women who delivered at three main public gynecological-obstetric units of the Metropolitan District of Quito. A questionnaire regarding demographics, antenatal care, risk conditions and knowledge, attitudes and practices related to influenza vaccination was administered. We examined factors associated with vaccination using log-binomial regression models. A low vaccination rate (36.6%) against influenza was observed among pregnant women. The factors associated with vaccination included the recommendations from health providers (adjusted PR: 15.84; CI 95% 9.62-26.10), belief in the safety of the influenza vaccine (adjusted PR: 1.53; CI 95% 1.03-2.37) and antenatal care (adjusted PR: 1.21; CI 95% 1.01-1.47). The most common reasons for not vaccinating included the lack of recommendation from health care providers (73.9%) and lack of access to vaccine (9.0%). Health educational programs aimed at pregnant women and antenatal care providers have the most potential to increase influenza vaccination rates. Further studies are needed to understand the barriers of health care providers regarding influenza vaccination in Ecuador.


Evaluating changes in workplace culture: Effectiveness of a caregiver-friendly workplace program in a public post-secondary educational institution.
Workplace experience, defined as the evaluation of the work environment and performance, and a characteristic of workplace culture, can influence an employee's work-life balance. Most carer-employees, who combine paid full-time work and informal caregiving responsibilities, struggle to maintain a healthy work-life balance. Caregiver-Friendly Workplace Programs are designed to improve the work experience, and ultimately, the work-life balance of carer-employees. The purpose of this study is to identify changes in workplace culture through the examination of the efficacy of a caregiver-friendly workplace program on workplace experience. First, we identify whether awareness of a caregiver-friendly workplace program directly increases the amount of work support received and, in turn, improves workplace experience. Second, we will examine if significant differences in the amount of work support received translates into an improved workplace experience for carer-employees over time. Two university-wide online surveys were conducted separately; time 1 (T1) during the summer of 2015, and time 2 (T2), in the summer of 2017. In each survey, nearly 7000 employees received the invitation to participate with a response rate ranging 10% (T1) to 12% (T2). Respondents were asked about their sociodemographic characteristics, caregiving responsibilities (if applicable), awareness of caregiver-friendly workplace program, types of work support received, and work experience. Reliability analyses was conducted for three scales: awareness of caregiver-friendly workplace program; work support, and; workplace experience. Proportional T-tests were used to examine the difference amongst the intervention scales over time. Structural equation modeling (SEM), via path analysis, was used to investigate the causal indirect (awareness of caregiver-friendly workplace program to work support to workplace experience) relationship that define the workplace culture. No significant changes in workplace culture were found over time. However, awareness of caregiver-friendly workplace programs is shown to positively impact the amount of support received, which sequentially improves workplace experience, and ultimately workplace culture. This therefore suggests that the implementation of caregiver-friendly workplace programs is potentially effective. Results suggest that amount of support received, and workplace experience would be better reassessed via a longer time period (i.e., 5 yr. window), and improved support for managers and supervisors is needed to supplement relationships with their employees.


The measure and discuss intervention: a procedure for client empowerment and quality control in residential care homes.
This article presents an intervention that is used to empower clients in residential care homes in the Netherlands. The intervention comprises a standardized survey-feedback procedure in which residents' opinions on life and care in their particular home are gauged, discussed, and reported. The procedure is designed to influence individuals and processes in the institution. It results in a report containing residents' collective opinion and recommendations and a plan for action. This provides residents' committees and management with a basis for policy making and quality control.


Can demand-side policies stop the tobacco industry's damage? Lessons from Turkey.
Trade and investment liberalisation in the post-1980 period allowed the penetration of transnational tobacco companies into the Turkish market. State control over the market was gradually removed and tobacco farming, manufacturing, trade and consumption were reshaped in line with the needs of transnational tobacco companies. The resultant increase in product proliferation and aggressive marketing strategies led to a dramatic rise in cigarette consumption in the 1990s, making Turkey a market with one of the sharpest consumption increases in the world. While Turkey implemented demand-side tobacco control policies to reduce consumption after 1996, it continued to stimulate manufacturing and trade in a conflicting way. The Turkish case verifies that the liberalisation process facilitated by the state under the auspices of international institutions conflicts with tobacco control. Liberalisation paves the way for market expansions of transnational tobacco companies that resist tobacco control in their drive for profit. Current global tobacco control policies, with no interest in controlling manufacturing, have limited effect on consumption. The Turkish case indicates the necessity of establishing public control over tobacco manufacturing and trade from a public health perspective.


Assay, purification and properties of mammalian D-2-hydroxy acid dehydrogenase.
1. A new method is described for the measurement of d-2-hydroxy acid dehydrogenase in samples of animal tissues. 2. The distribution of the enzyme in a number of animals was determined. Of the animal tissues tested, the most active source of the enzyme was found to be rabbit kidney cortex. 3. The enzyme was purified from rabbit kidney to a stage at which it appears to be homogeneous in the analytical ultracentrifuge and on polyacrylamide-gel electrophoresis. 4. The molecular weight was estimated by gel filtration to be approx. 102000; combination of gelfiltration data and the sedimentation coefficient gave a value of 95000. 5. The purified enzyme has a spectrum typical of a flavoprotein. The change induced in the spectrum on addition of d-malate or d-lactate suggests the formation of a flavin semiquinone. 6. Flavin can be removed by treatment with acid ammonium sulphate, and activity can be restored to the inactive apoenzyme by addition of FAD, but not of FMN or riboflavin. 7. Studies of acceptor specificity showed that the enzyme has a relatively weak d-2-hydroxy acid oxidase activity.


The Molecular Chaperone Artemin Efficiently Blocks Fibrillization of TAU Protein In Vitro.
Aggregation of the TAU proteins in the form of neurofibrillary tangles (NFTs) in the brain is a common risk factor in tauopathies including Alzheimer's disease (AD). Several strategies have been implemented to target NFTs, among which chaperones, which facilitate the proper folding of proteins, appear to hold great promise in effectively inhibiting TAU polymerization. The aim of this study was to analyze the impact of the chaperone Artemin on TAU aggregation in vitro. In this experimental study, recombinant TAU- or Artemin proteins were expressed in E.coli bacteria, and purified using ion-exchange and affinity chromatography. Sodium dodecyl sulfate-poly acrylamide gel electrophoresis (SDS-PAGE) was used to run the extracted proteins and check their purity. Heparin was used as an aggregation inducer. The interaction kinetics of TAU aggregation and disassembly was performed using thioflavin T (ThT) fluorescence analysis and circular dichroism (CD) spectroscopy. Ion-exchange and affinity chromatography yielded highly pure TAU and Artemin proteins for subsequent analyses. In addition, we found that heparin efficiently induced TAU fibrillization 48 hours post-incubation, as evidenced by ThT assay. Importantly, Artemin was observed to effectively block the aggregation of both physiologic- and supraphysiologic TAU concentrations in a dose-dependent manner, as judged by ThT and CD spectroscopy analyses. Our collective results show, for the first time, that the chaperone Artemin could significantly inhibit aggregation of the TAU proteins in a dose-dependent manner, and support Artemin as a potential potent blocker of TAU aggregation in people with AD.


Diversity of CO2-concentrating mechanisms and responses to CO2 concentration in marine and freshwater diatoms.
The presence of CO2-concentrating mechanisms (CCMs) is believed to be one of the characteristics that allows diatoms to thrive in many environments and to be major contributors to global productivity. Here, the type of CCM and the responses to variable CO2 concentration were studied in marine and freshwater diatoms. At 400 ppm, there was a large diversity in physiological and biochemical mechanisms among the species. While Phaeodactylum tricornutum mainly used HCO3-, Thalassiosira pseudonana mainly used CO2. Carbonic anhydrase was an important component of the CCM in all species and C4 metabolism was absent, even with T. weissflogii. For all species, at 20 000 ppm, the affinity for dissolved inorganic carbon was lower than at 400 ppm CO2 and the reliance on CO2 was higher. Despite the difference in availability of inorganic carbon in marine and fresh waters, there were only small differences in CCMs between species from the two environments, and Navicula pelliculosa behaved similarly when grown in the two environments. The results suggest that species-specific differences are great, and more important than environmental differences in determining the nature and effectiveness of the CCM in diatoms.


Understanding the costs of cancer care before and after diagnosis for the 21 most common cancers in Ontario: a population-based descriptive study.
The first year after cancer diagnosis is a period of intensive treatment and high cost. We sought to estimate costs for the 21 most common cancers in Ontario in the 3-month period before and the first year after diagnosis. We used the Ontario Cancer Registry to select patients who received diagnoses between 1997 and 2007 at 19 years of age or older, with valid International Classification of Diseases for Oncology (ICD-O) and histology codes, who survived 30 days or longer after diagnosis and had no second cancer within 90 days of the initial cancer (n = 402 399). We used linked administrative data to calculate mean costs for each cancer during the pre- and postdiagnosis periods for patients who died within 1 year after diagnosis and patients who survived beyond 1 year after diagnosis. Mean prediagnosis costs were $2060 (95% confidence interval [CI] $2023-$2098) for all patients with cancer. Costs ranged from $890 (95% CI $795-$985) for melanoma to $4128 (95% CI $3591-$4664) for liver cancer among patients who survived beyond 1 year after diagnosis, and ranged from $2188 (95% CI $2040-$2336) for esophageal cancer to $5142 (95% CI $4664-$5620) for multiple myeloma among patients who died within 1 year. The mean postdiagnosis cost for our cohort was $25 914 (95% CI $25 782-$26 046). Mean costs were lowest for melanoma ($8611 [95% CI $8221-$9001]) and highest for esophageal cancer ($50 620 [95% CI $47 677-$53 562] among patients who survived beyond 1 year after diagnosis, and ranged from $27 560 (95% CI $25 747-$29 373) for liver cancer to $81 655 (95% CI $58 361-$104 949) for testicular cancer among patients who died within 1 year. Our research provides cancer-related cost estimates for the pre- and postdiagnosis phases and offers insight into the economic burden incurred by the Ontario health care system. These estimates can help inform policy-makers' decisions regarding resource allocation for cancer prevention and control, and can serve as important input for economic evaluations.


Effects of stretching and fatigue on peak torque, muscle imbalance, and stability.
The present study examined the acute effects of hamstrings stretching and fatigue on knee extension and flexion peak torque (PT), hamstrings to quadriceps (H:Q) ratio, and postural stability. Seventeen women (mean±SD age=21.8±2.1 years; body mass=63.0±10.5 kg; height=164.7±6.2 cm) and eighteen men (25.8±4.6 years; 83.6±13.2 kg; 175.3±6.0 cm) took part in three laboratory visits. The first visit was a familiarization session, and the subsequent two visits were randomly assigned as a control or stretching condition. For the testing visits, subjects performed a postural stability assessment, stretched (or sat quietly during the control condition), performed a 50-repetition unilateral isokinetic fatigue protocol, and repeated the postural stability assessment. There were no significant differences between control and stretching conditions for initial quadriceps and hamstrings PT, initial H:Q ratio, quadriceps and hamstrings PT fatigue indexes, H:Q ratio Fatigue Index, rating of perceived exertion (RPE), or postural stability (P>0.05). When analyzing 5 intervals of 10 repetitions, significant declines in quadriceps PT were found in all intervals for both conditions (P<0.05). However, a decline in hamstrings PT was only found until the fourth interval (i.e., repetitions 31 to 40) for the stretching condition (P<0.05). Stretching the hamstrings immediately prior to long-duration activities may eventually cause adverse effects in force-generating capacity of this muscle group to occur earlier when fatiguing tasks are involved. Nevertheless, no changes were found for the H:Q ratios after stretching when compared to no-stretching.


Why are acute ischemic stroke patients not receiving IV tPA? Results from a national registry.
To determine patient and hospital characteristics associated with not providing IV tissue plasminogen activator (tPA) to eligible patients with acute ischemic stroke (AIS) in clinical practice. We performed a retrospective cohort study of patients with AIS arriving within 2 hours of onset to hospitals participating in Get With The Guidelines-Stroke without documented contraindications to IV tPA from April 2003 through December 2011, comparing those who received tPA to those who did not. Multivariable generalized estimating equation logistic regression modeling identified factors associated with not receiving tPA. Of 61,698 eligible patients with AIS presenting within 2 hours of onset (median age 73 years, 51% female, 74% non-Hispanic white, median NIH Stroke Scale score 11, interquartile range 6-18), 15,282 (25%) were not treated with tPA within 3 hours. Failure to give tPA decreased over time from 55% in 2003 to 2005 to 18% in 2010 to 2011 (p < 0.0001). After adjustment for all covariates, including stroke severity, factors associated with failure to treat included older age, female sex, nonwhite race, diabetes mellitus, prior stroke, atrial fibrillation, prosthetic heart valve, NIH Stroke Scale score <5, arrival off-hours and not via emergency medical services, longer onset-to-arrival and door-to-CT times, earlier calendar year, and arrival at rural, nonteaching, non-stroke center hospitals located in the South or Midwest. Overall, about one-quarter of eligible patients with AIS presenting within 2 hours of stroke onset failed to receive tPA treatment. Thrombolysis has improved dramatically over time and is strongly associated with stroke center certification. Additionally, some groups, including older patients, milder strokes, women, and minorities, may be undertreated.


[Determination of the optimal dose of a cultured inactivated vaccine for preventing Japanese encephalitis].
The article presents the summarized results of the controlled field trial of a new inactivated liquid absorbed tissue-culture vaccine developed in the USSR. The optimal immunization dose has been determined: 1.5 ml of the vaccine introduced with a syringe or a jet injector. The intensity and character of postvaccinal immunity have been studied.


Depression in palliative care patients: a survey of assessment and treatment practices of Australian and New Zealand palliative care specialists.
To explore the practices of members of the Australian and New Zealand Society of Palliative Medicine (ANZSPM) in assessing and treating depression in palliative care patients. Semistructured questionnaires were forwarded to ANZSPM members in consecutive mail-outs to survey diagnostic and treatment practices for depression. The response rate was 62.3%. The median prevalence of depression, as perceived by respondents, in the present respondent patient populations was 20% (range 0%-90%); 57.1% of respondents always assessed for depression, whereas 42.9% assessed for depression sometimes. The majority (98.9%) of respondents relied on clinical interviews to assess depression; non-somatic symptoms of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria were more useful than somatic symptoms. The depression screening tools most frequently used were one- and two-item questions. Pharmacological and non-pharmacological methods were used to treat depression, with selective serotonin reuptake inhibitors the most frequently prescribed medications. Psycho-educational and supportive counselling were the most frequently used non-pharmacological interventions. Nominated measures to augment depression management included improving access to psychiatry, psychology and other allied health services, the development of a screening tool specific to palliative care patients and associated guidelines for depression management. This is the first Australasian study to explore the practice of medical practitioners regarding depression in palliative patients. Incorporation of screening tool questions into palliative care assessment interviews may warrant future research. WHAT IS KNOWN ABOUT THE TOPIC? Depression in palliative care patients has a negative impact on quality of life; however, little is known about how Australasian palliative care medical practitioners manage depression in this patient population. WHAT DOES THIS PAPER ADD? To the researchers' knowledge, this is the first Australasian study that explores the practices of local palliative care specialists in the management of depression in palliative patients. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Overall management of depression in palliative care populations by Australasian practitioners is similar to that of their European colleagues. Consensus is that for assessment of depression in palliative patients, non-somatic symptoms of DSM-IV criteria are more useful than somatic symptoms. Practitioners report the need for improved access to psychiatric, psychological and other support services, for a palliative care-specific depression screening tool and for depression management guidelines applicable to palliative care patients.


The Impact of Receiving a Family-Oriented Therapeutic Conversation Intervention Before and During Bereavement Among Family Cancer Caregivers: A Nonrandomized Trial.
Effective communication is the foundation of quality care in palliative nursing. As frontline palliative home care providers, nurses could foster more effective bereavement coping skills through therapeutic conversations. The purpose of this study was to evaluate the impact of a nursing intervention offered to bereaved family cancer caregivers. This was a quasi-experimental design, with a posttest-only comparison of the intervention and control groups receiving usual care. Bereaved caregivers (n = 51) receiving services from a specialized palliative home care unit participated and completed measures of depression, anxiety, stress, and grief reactions 3, 5, and 6 months after their close relative had died.There was a significant decrease in anxiety symptoms in the intervention group compared with the control group across all 3 time points. Anxiety and stress symptoms also decreased over time in the 2 groups combined, but this decrease was not observed for depression. When evaluating grief reactions, the intervention group had a lower mean of controlled grief responses, across the posttest period, than the control group.Results demonstrate that providing bereaved family caregivers the opportunity to participate in a therapeutic conversation intervention might reduce distressing symptoms in early bereavement.


Phenotypes of dnaXE145A Mutant Cells Indicate that the Escherichia coli Clamp Loader Has a Role in the Restart of Stalled Replication Forks.
The Escherichia colidnaXE145A mutation was discovered in connection with a screen for multicopy suppressors of the temperature-sensitive topoisomerase IV mutation parE10 The gene for the clamp loader subunits τ and γ, dnaX, but not the mutant dnaXE145A , was found to suppress parE10(Ts) when overexpressed. Purified mutant protein was found to be functional in vitro, and few phenotypes were found in vivo apart from problems with partitioning of DNA in rich medium. We show here that a large number of the replication forks that initiate at oriC never reach the terminus in dnaXE145A mutant cells. The SOS response was found to be induced, and a combination of the dnaXE145A mutation with recBC and recA mutations led to reduced viability. The mutant cells exhibited extensive chromosome fragmentation and degradation upon inactivation of recBC and recA, respectively. The results indicate that the dnaXE145A mutant cells suffer from broken replication forks and that these need to be repaired by homologous recombination. We suggest that the dnaX-encoded τ and γ subunits of the clamp loader, or the clamp loader complex itself, has a role in the restart of stalled replication forks without extensive homologous recombination.IMPORTANCE The E. coli clamp loader complex has a role in coordinating the activity of the replisome at the replication fork and loading β-clamps for lagging-strand synthesis. Replication forks frequently encounter obstacles, such as template lesions, secondary structures, and tightly bound protein complexes, which will lead to fork stalling. Some pathways of fork restart have been characterized, but much is still unknown about the actors and mechanisms involved. We have in this work characterized the dnaXE145A clamp loader mutant. We find that the naturally occurring obstacles encountered by a replication fork are not tackled in a proper way by the mutant clamp loader and suggest a role for the clamp loader in the restart of stalled replication forks.


Effect of an acute care surgical service on the timeliness of care.
In the spring of 2008, St. Boniface General Hospital in Winnipeg, Man., created an acute care surgical service (ACSS) designed to improve care for emergent, nontrauma surgical patients. We sought to assess the effect of the ACSS on patient care timeliness. We retrospectively examined the time intervals in care for patients admitted with acute appendicitis, acute cholecystitis and small bowel obstruction in 3 study periods: pre-ACSS, newly formed ACSS and established ACSS. There was a 2-fold increase in patient volume after the ACSS was created. Patient characteristics were similar in all 3 groups. Time from triage to surgical consultation was also similar. The ACSS significantly reduced the duration of the surgical consultation (1 h 43 min in period 1 v. 62 min in period 2 and 49 min in period 3, p = 0.029). Time from admission to operation was similar despite a significant increase in patient load after the ACSS was created. Total length of hospital stay was similar except in the subgroup analysis (appendicitis + cholecystitis only), where the length of stay was reduced after creation of the ACSS (2 d 15 h pre- v. 1 d 19 h post-ACSS, p = 0.009). Most operations occurred between 4 pm and midnight. With the implementation of an ACSS, the number of surgical patients assessed and treated doubled. Despite the increased volume, consultations were completed significantly faster, there was no significant difference in time to operation, and on subgroup analysis length of hospital stay was significantly faster.


Proton and molecular permeation through the basal plane of monolayer graphene oxide.
Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.


Nutritional care in inflammatory bowel disease--a literature review.
During recent years, an increasing number of young adults have developed inflammatory bowel disease (IBD). The caring perspective on IBD is now changing to adapt to the development of the illness and prescribing new health promotion methods of care, with a focus on nutrition, education and patient supervision. IBD, immunology and nutrition are the main focus in the selected articles, with presentation of possible connections to contribute to broader understanding of the illness. This present article is part of an empirical research project and is providing an overview of the current research knowledge in this field. The article is based on an extensive, systematic survey of literature comprising 28 review and original articles from June 2008 to July 2009. The important topics are emphasized and described. Two areas of knowledge are considered instrumental in inter-disciplinary health-promoting work with IBD patients: a focus on gut immunology and stress, nutritional care and diet. Healing damage to the gut wall by introducing an individually prescribed diet may take time, but will reduce internal stress on the body. Documentation shows that use of probiotics, fatty acids and antioxidants has been effective in a number of clinical scenarios relating to IBD. Individually prescribed nutrition, primarily through the diet, may be decisive in terms of a sustainable improvement in outcomes for patients with IBD. Addressing the educational challenges in caring to cure suffering from IBD is crucial. Emergency medical treatment helps patients during the acute phase of the disease. Once the acute phase is passed, the recommendation is a focus on investigating the environmental factors that could act as triggers for IBD in humans. Diet is the most important environmental factor in terms of the gut. Proper nutrition and micronutrients assist the body by subtly strengthening its capacity for self-healing and regeneration. Education, confirmation, and a reflection into ones illness, create insight and a basis for coping.


Distributed Fibre Optic Sensor-Based Continuous Strain Measurement along Semicircular Paths Using Strain Transformation Approach.
Distributed fibre optic sensors (DFOS) are popular for structural health monitoring applications in large engineering infrastructure because of their ability to provide spatial strain measurements continuously along their lengths. Curved paths, particularly semicircular paths, are quite common for optical fibre placement in large structures in addition to straight paths. Optical fibre sensors embedded in a curved path configuration typically measure a component of strain, which often cannot be validated using traditional approaches. Thus, for most applications, strain measured along curved paths is ignored as there is no proper validation tool to ensure the accuracy of the measured strains. To overcome this, an analytical strain transformation equation has been developed and is presented here. This equation transforms the horizontal and vertical strain components obtained along a curved semicircular path into a strain component, which acts tangentially as it travels along the curved fibre path. This approach is validated numerically and experimentally for a DFOS installed on a steel specimen with straight and curved paths. Under tensile and flexural loading scenarios, the horizontal and vertical strain components were obtained numerically using finite element analysis and experimentally using strain rosettes and then, substituted into the proposed strain transformation equation for deriving the transformed strain values. Subsequently, the derived strain values obtained from the proposed transformation equation were validated by comparing them with the experimentally measured DFOS strains in the curved region. Additionally, this study has also shown that a localised damage to the DFOS coating will not impact the functionality of the sensor at the remaining locations along its length. In summary, this paper presents a valid strain transformation equation, which can be used for transforming the numerical simulation results into the DFOS measurements along a semicircular path. This would allow for a larger scope of spatial strains measurements, which would otherwise be ignored in practice.


[New methods for the diagnosis of acute pulmonary embolism].
Pulmonary embolism is a high mortality cardiovascular disease, which is difficult to diagnose even today. In this study the symptoms and the results of diagnostic methods were analysed in 81 patients with acute pulmonary embolism, admitted during a one-year period to Kaposi Mór County Hospital. The patient records were examined with special emphasis on the diagnostic value of novel methods such as D-dimer assay and chest computed tomography scanning along with the routine techniques used in the management of pulmonary embolism. In all patients ECG, in 88% of the cases chest X-ray, in 57% blood gas analysis and in 53% D-dimer assay results were evaluated. 14.8% of the patients died during hospitalisation. The following diagnostic imaging procedures were undertaken: in 80.2% of the cases lung scan, in 59.3% echocardiography and in 8.7% of the cases spiral computed tomography scan were prepared. In 12.3% of all cases thrombolysis proved necessary. The results were compared with data from International Cooperative Pulmonary Embolism Registry Study, which analyses 2454 patient cases. It is foreseen that the increasing use of echocardiography, lower limb ultrasound and highly informative spiral computed tomography scanning as an additional means in pulmonary embolism diagnostics may in some cases spare the use of pulmonary scintigraphy.


Outcomes of coronary artery bypass grafting with coronary endarterectomy: A systematic review and meta-analysis of recent studies.
Objective: The aim of this systematic review and meta-analysis was to evaluate the short-term and long-term outcomes of coronary artery bypass grafting (CABG) with coronary endarterectomy (CE) versus isolated CABG.Methods: Studies evaluating outcomes of CABG with CE (CE-CABG) were searched from 1 January 2000 to 30 September 2022, on PubMed, Embase, and Cochrane databases. The primary outcome was 30 -days mortality. Secondary outcomes were postoperative myocardial infraction, low output syndrome, cardiac arrhythmia, renal dysfunction, and 5 years survival.Results: A total of 12 observational studies including 114,319 patients assessing CE-CABG (n = 35,174) versus isolated CABG (n = 79,145) were included. Compared to isolated CABG alone, CE-CABG was significantly associated with increased incidences of 30-days mortality (RR, 1.87; 95% CI, 1.73-2.07; p < 0.01), postoperative myocardial infraction (RR, 1.61; 95% CI, 1.26-2.05; p < 0.01), low output syndrome (RR, 1.54; 95% CI, 1.17-2.02; p < 0.01), and renal dysfunction (RR, 1.56; 95% CI, 1.44-1.69; p < 0.01). However, there was no difference in either rate of cardiac arrhythmia (RR, 1.06; 95% CI, 0.97-1.15; p = 0.20) or 5 years survival (RR, 1.05; 95% CI, 0.95-1.16; p = 0.34) between the CE-CABG group and the control group. Subgroup analysis on CE technique showed that CE-CABG was also associated with 30 days mortality in patients undergoing closed CE (RR, 1.49; 95% CI, 1.09-2.03), whereas this association between CE and 30 days mortality was not observed in patients undergoing open CE (RR, 1.76; 95% CI, 0.58-5.32).Conclusions: Despite poor short-term outcomes, CE-CABG appeared to offer satisfactory long-term survival in patients with diffuse coronary artery disease.


University of Iowa Hospital and Clinics: outcomes management.
Delivery of quality patient care and management of patient outcomes is critical to the success of academic medical centers in the ever-changing health care market. The University of Iowa Hospitals and Clinics (UIHC) promotes quality care through the provision of organizational structures and processes that are described in this article. In addition, quality of care and outcomes management are described by members in various roles within the UIHC health care system. It is the authors' belief that understanding quality from these various perspectives helps UIHC work across departments to achieve excellence in patient care.


S-nitrosoglutathione enhances neutrophil DNA fragmentation and cell death.
Enhancing the clearance of neutrophils by enhancing apoptotic cell death and macrophage recognition may be beneficial in acute lung injury. Exogenous nitric oxide gas depresses neutrophil oxidative functions and accelerates cell death (A. H. Daher, J. D. Fortenberry, M. L. Owens, and L. A. Brown. Am. J. Respir. Cell Mol. Biol. 16: 407-412, 1997). We hypothesized that S-nitrosoglutathione (GSNO), a physiologically relevant nitric oxide donor, could also enhance neutrophil DNA fragmentation. Neutrophils were incubated for 2-24 h in the absence and presence of GSNO (dose range 0.1-5 mM) and evaluated for cell death by a fluorescent viability/cytotoxicity assay. Neutrophil DNA fragmentation was assessed by cell death detection ELISA and by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling assay. Neutrophil oxidative function was also determined. Incubation with GSNO increased cell death at 2, 4, and 24 h. GSNO incubation for 24 h significantly increased DNA fragmentation in a dose-dependent fashion at 0.5 (median 126% of control value; P = 0.002) and 5 mM (185% of control value; P = 0.002) by terminal deoxynucleotidyltransferase-mediated fluorescence-labeled dUTP nick end labeling and at 0.5 mM by ELISA (164% of control value; P = 0.03). The apoptosis-to-total cell death ratio increased with increasing GSNO concentration (P < 0.05). Effects were mitigated by coincubation with superoxide dismutase. Five millimolar GSNO decreased overall superoxide generation and O2 consumption but not when adjusted for dead neutrophils. GSNO significantly enhances cell death and neutrophil DNA fragmentation in a dose-dependent fashion.


The global poliomyelitis eradication initiative: progress and challenges.
In 1988, The World Health Assembly committed WHO and its member states to the goal of poliomyelitis eradication by the year 2000. Global progress in implementation of strategies include routine and supplementary immunisation, AFP surveillance strategy and mopping up. Progress made in global polio eradication within 10 years has been dramatic. Challenges consist of tailoring and fine tuning strategies and sustaining adequate levels of findings. Although the intensified effort will increase needed resources in the short term, it will save costs in the long term.


Ultrastructure of the human dermal microcirculation. II. The capillary loops of the dermal papillae.
Electron microscopy was used to define the ultrastructure of the capillary loops in the dermal papillae of normal, eczematous, and psoriatic skin. Capillary loops were reconstructed from 1-mum plastic-embedded sections. Ultrathin sections were taken at 4- to 6-mum intervals for correlation with the thick sections. The capillary loops of normal forearm and elbow skin could be divided into two segments: an intrapapillary and extrapapillary portion. The intrapapillary portion had the ultrastructural characteristics of an arterial capillary--homogeneous-appearing basement membrane without bridged fenestrations. The ascending limb in the extrapapillary portion was also an arterial capillary and the descending limb in the same portion had venous characteristics--multilayered basement membrane. The intrapapillary arterial loop developed venous characteristics abruptly after the vessel left the dermal papilla proper. The capillary loops in acute nummular eczema were identical in ultrastructure to those of normal skin. Bridged fenestrations were found in one capillary loop in eczema but not in normal skin. By contrast, the intrapapillary capillary loops in psoriasis were venous capillaries which were characterized by bridge fenestrations and multilayered basement membrane. The ultrastructural features of the capillary loops and those of the microcirculatory segments in the horizontal dermal plexus should provide sufficient criteria for one to evaluate the nature of vascular abnormalities that occur in the upper dermis.


Population genetic structure of Anopheles gambiae and Anopheles arabiensis in Niger.
The increasing usage of long-lasting insecticide-treated nets allows protection of millions of people from malaria infection. Monitoring studies should be planned during any wide-scale malaria control program integrating insecticide-treated materials, to evaluate their effects and effectiveness on epidemiologically relevant parameters. Such operational control interventions may be challenged by insecticide resistance spread within vector populations, as a result of wide insecticide pressure. A nationwide distribution of long-lasting insecticidal nets was implemented throughout Niger in 2005. We studied the population genetic structure of major malaria vectors across Nigerien Sahel, and investigated potential effects of this large malaria control intervention. Wild-caught Anopheles gambiae sensu lato females from seven villages and two wet seasons were genotyped at 12 microsatellite loci. The genetic diversity within both species appeared homogenous between villages and years. The estimated genetic differentiation among samples was very low within both species, indicating high gene flow across the area. An absence of differentiation was also found between 2005 and 2006 wet seasons, for all samples but one, showing that the net distribution did not impact significantly the genetic diversity and structure of vector populations in a single year. We provide valuable results participating to document effects of large malaria control programs, to maximize the efficiency of available tools in future interventions.


Randomized comparative study of indocyanine green and India ink for colonic tattooing: an animal survival study.
Indocyanine green has been reported previously as a useful agent for colonic tattooing, but its durability, ease of use, cost, and safety have not been compared with India ink. Eight pigs were randomized to colonic tattooing using sterile indocyanine green or India ink injected through tandem filters. The animals were recovered and killed after 2 weeks and were examined. All animals survived the study period with no complications. We identified 17 of 29 (59%) indocyanine green tattoos and 48 of 52 (92%) India ink tattoos at autopsy (p = 0.0003). Histologic reactions were mild and were distributed similarly in each group and the intensity of the tattoos diminished similarly in both groups. Although indocyanine green was slightly more expensive, it was easier to handle compared with India ink. Both indocyanine green and India ink tattoos cause only mild histologic reaction in the swine colon when examined 2 weeks after injection. India ink is superior to indocyanine green, when used for colonic tattooing.


A longitudinal study of the moderating role of extraversion: leader-member exchange, performance, and turnover during new executive development.
Identifying factors that help or hinder new executives in "getting up to speed" quickly and remaining with an organization is vital to maximizing the effectiveness of executive development. The current study extends past research by examining extraversion as a moderator of relationships between leader-member exchange (LMX) and performance, turnover intentions, and actual turnover for an executive sample. The sample consisted of 116 new executives who were surveyed prior to starting their employment and at 3 months postentry. A total of 67 senior executives rated these new executives in terms of overall performance at 6 months postentry. Turnover data were gathered from company records 3 1/2 years later. Hierarchical regression results showed that LMX was not related to performance or turnover intentions for those high in extraversion; but for individuals low in extraversion, there was a relation between LMX, performance, and turnover intentions. Furthermore, survival analyses showed that LMX was only related to turnover-hazard rate for individuals low in extraversion.


[Ala6]gastrin-releasing peptide-10: an analogue with dissociated biological activities.
COOH-terminal decapeptide of gastrin-releasing peptide (GRP-10) is a bombesin-like peptide, which has bioactivities to stimulate gastrin, insulin, and glucagon secretion. We have synthesized an analogue of GRP-10 that inhibits GRP-10's stimulation of insulin secretion both in vivo and in vitro and glucagon secretion in vivo, while potentiating the stimulation of gastrin secretion. The amino acid sequence of this peptide is H-Gly-Asn-Trp-Ala-Ala-Gly-His-Leu-Met-NH2 ([Ala6]GRP-10). Because the stimulation of insulin and gastrin secretion by GRP-10 has been ascribed to a direct effect on B- and G-cells, these findings suggest that there are two subtypes of receptors for bombesin-like peptides in mammalian tissues.


Does the liner material influence pulpal vitality in deep carious cavities submitted to selective caries removal? A network meta-analysis review.
To evaluate whether the restorative material in direct contact with the dentin influences pulp vitality in primary and permanent teeth with deep carious lesions restored after selective caries removal (SCR). Systematic searches of databases MEDLINE via PubMed, Scopus and ISI Web of Science were performed for primary and permanent teeth. Inclusion criteria were applied for title and abstract reading of databases search results. After full texts review of included studies, those that did not meet exclusion criteria were excluded from meta-analysis. For meta-analysis, 2 studies were included for permanent teeth and 6 for primary teeth. The failure events reported were meta-analyzed using two statistical methods: standard pairwise meta-analysis (SPMA) and network meta-analysis (NMA). The SPMA identified similar failure occurrence of restorations performed with calcium hydroxide (CH) and other liner materials (RR 0.84, 95% CI 0.41, 1.74; p = 0.64), no significant difference between the use of alternative liners or CH regardless deciduous or permanent teeth (RR 0.79, 95% CI 0.36, 1.71; p = 0.55) and similar risk of failing at different follow-ups for all liner materials tested (RR 0.77, 95% CI 0.35, 1.70; p = 0.52). Probabilistic analysis indicated GIC as liner material with the highest probability of clinical success (SUCRA = 72.76%), and CH ranked as the worst liner material (SUCRA = 21.81%). Pulpal vitality was not affected by material used as liner after selective caries removal in deep carious cavities. Current clinical evidence supports the weak recommendation to not use calcium hydroxide as liner after SCR.


Visual discrimination of target displacement remains after damage to the striate cortex in humans.
Damage to the striate cortex usually causes blindness in those regions of the visual field which map to the area of neural damage. Nonetheless, there are reports that some patients with such damage can localize and perform certain visual discriminations between light stimuli presented within the 'blind' area of the visual field. Experiments on animals with different brain areas ablated suggest that visual function is served by two principal projection pathways from the retina. That to the striate cortex is primarily responsible for fine discrimination between stimulus parameters such as colour and spatial pattern, whereas that to the superior colliculus in the midbrain is responsible for visual localization of stimuli. The residual visual functions in patients with cortical damage are usually attributed to the non-striate retinal projection to the superior colliculus. We now present measurements of spatial discrimination in two observers with large visual field defects (scotomata) caused by damage to the striate cortical region. Both exhibit a near normal ability to discriminate displacements of targets when two lights are flashed sequentially in their defective visual field, but they are unable to discriminate spatial pattern or size. We argue that these results are consistent with the 'two visual systems' interpretation of ablation studies on non-human species.


The epidemic that never was: yellow fever in Hawaii.
The Kingdom of Hawaii suffered a disastrous series of epidemics starting from the first contact with Captain Cook's crew and continuing to the present. Despite the huge volume of shipping to and through Hawaii, one plague failed to appear. Yellow Jack (yellow fever) engendered more fear in sailors of the 19th century than any other disease. By 1910 the details of transmission were well-known and Hawaii met all the requirements for an epidemic. On October 30, 1910, the first case of shipboard yellow fever arrived at Honolulu but quarantine averted the threat. On October 28, 1911, a Hawaiian man, employed as a quarantine guard, was reported to have yellow fever and efforts were initiated to control a possible epidemic. This was the only occurrence of yellow fever in Hawaii.


Feeding segregation of two sympatric eubranchiid nudibranchs (Aeolidacea).
Two closely related species of aeolid nudibranchs, Eubranchus misakiensis and E. horii, were found abundantly on the same leaves of seaweeds, Ecklonia kurome. Three thecata hydroid species also grew in large numbers on the surface of the weeds. E. misakiensis occurred always only on colonies of Obelia geniculata, with E. horii always only on colonies of Plumularia filicaulis japonica. Neither aeolid was found on Orthopyxis platicarpa. These field observations and results of choice experiments demonstrate considerable feeding segregation in the two aeolids.


Pitfalls of ophthalmic radiographic imaging.
Ophthalmologists are dependent on computed tomography (CT) and MRI to aid in the diagnosis and management of patients with orbital and visual conditions. Pitfalls in the imaging process can lead to inefficient care or patient harm. This review summarizes these problems and provides methods to reduce imaging errors. There has been exponential growth in the number of radiographic scans performed, resulting in increased awareness of the risks from medical radiation. Strategies to minimize radiation exposure include reducing the need for sequential scans, using appropriate technology, and substituting MRI for CT. Contrast administration can be associated with systemic reactions, renal disease, and thyroid dysfunction. Scan interpretation errors are reduced by the ophthalmologist reviewing the study and communication with the radiologist. Medical radiation exposure can be reduced by initially ordering the appropriate scan and substituting MRI for CT when possible. MRI is contraindicated in patients with certain implants and metallic foreign bodies. Noncontrast studies are adequate to evaluate many conditions and some patients should not receive contrast. Imaging errors can be reduced by the ophthalmologist personally reviewing the orbital scans and correlating the results with the clinical findings.


Surface ultrastructure of metacercaria and adult of Gymnophalloides seoi (Digenea: Gymnophallidae).
The surface ultrastructure of metacercariae and adults of Gymnophalloides seoi, the only known gymnophallid infecting humans, was observed by scanning electron microscopy. Metacercariae were ovoid or pyriform in shape and slightly concave ventrally. The oral sucker had two sizes of type I papillae, small and large, encircling its lip. Type I papillae were arranged in a row on both side of the body. The ventral pit had several type I papillae on its inner surface. The ventral sucker was covered with cobble-stone like cytoplasmic processes and had 6 type I papillae on its lip. The surface of the body was covered with the tegumental spines except for the ventromedian area between the two suckers. The spines at anterior body were digitated into 3-5 points, and their size decreased at posterior one third of the body. Adult worms were rhomboid or ellipsoid in shape and covered with tegumental spines except for the ventromedian area. The shape and distribution of the tegumental spines and sensory papillae were similar to those of metacercariae. However, sensory papillae arranged in a row on the ventral surface of metacercariae were not observed in adults. The ventral pit became larger and more prominent as the fluke grew. It is suggested that the ventral pit function as an additional adhesive organ to the host tissue.


Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster.
After screening the Berkeley Drosophila Genome Project database with sequences from a recently characterized Leu-rich repeats-containing G protein-coupled receptor (LGR) from Drosophila (DLGR-1), we identified a second gene for a different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino acid residues long and shows a striking structural homology with members of the glycoprotein hormone [thyroid-stimulating hormone (TSH); follicle-stimulating hormone (FSH); luteinizing hormone/choriogonadotropin (LH/CG)] receptor family from mammals and with two additional, recently identified mammalian orphan LGRs (LGR-4 and LGR-5). This homology includes the seven transmembrane region (e.g., 49% amino acid identity with the human TSH receptor) and the very large extracellular amino terminus. This amino terminus contains 18 Leu-rich repeats-in contrast with the 3 mammalian glycoprotein hormone receptors and DLGR-1 that contain 9 Leu-rich repeats, but resembling the mammalian LGR-4 and LGR-5 that each have 17 Leu-rich repeats in their amino termini. The DLGR-2 gene is >18.6 kb pairs long and contains 15 exons and 14 introns. Four intron positions coincide with the intron positions of the three mammalian glycoprotein hormone receptors and have the same intron phasing, showing that DLGR-2 is evolutionarily related to these mammalian receptors. The DLGR-2 gene is located at position 34E-F on the left arm of the second chromosome and is expressed in embryos and pupae but not in larvae and adult flies. Homozygous knock-out mutants, where the DLGR-2 gene is interrupted by a P element insertion, die around the time of hatching. This finding, together with the expression data, strongly suggests that DLGR-2 is exclusively involved in development.


Promoting appropriate utilisation of laboratory tests for inflammation at an academic medical centre.
Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) are commonly ordered in clinical practice to evaluate for inflammation. CRP is a more sensitive and specific test for detecting acute phase inflammation, and the American Society for Clinical Pathology recommends ordering CRP rather than ESR to detect acute phase inflammation in patients with undiagnosed conditions. We sought to understand CRP and ESR ordering practices and reduce unnecessary use of ESR testing at our academic medical centre. We surveyed physician leaders in clinical areas with high utilisation of ESR testing to understand the drivers of potential overutilisation of these tests. Based on survey responses, we designed an intervention focused on education, clinical decision support within the electronic medical record and quarterly audit and feedback. We evaluated appropriateness of ESR ordering before and after the intervention via structured chart audit. Comparison of monthly rates of ESR tests during the preintervention and postintervention periods was conducted using interrupted time series analysis. Clinical habit and ease of test ordering were identified as key drivers of ESR overuse. Compared with the preintervention period, we observed a 33% reduction in the number of ESR tests per month and a 25% reduction in combined CRP and ESR tests per month during the postintervention period. This reduction corresponded to an annual avoidance of 2633 ESR tests with a corresponding estimated direct cost avoidance of $23 701 annually. Although the rate of ESR testing decreased, there was no significant improvement in the clinical appropriateness of residual ESR test ordering following the intervention. A multifaceted intervention was associated with significant decreases in unnecessary ESR tests and concurrent ESR and CRP tests at our academic medical centre. Despite these reductions, there are continued opportunities to reduce inappropriate ESR testing.


Selection process for surgeons in the Asymptomatic Carotid Atherosclerosis Study.
The Asymptomatic Carotid Atherosclerosis Study is a prospective, multicenter, randomized clinical trial of carotid endarterectomy for the treatment of asymptomatic hemodynamically significant stenosis. This report describes the selection process for participating surgeons in the trial. The Surgical Management Committee established guidelines for minimal annual experience and maximum neurological morbidity and mortality for surgeons to qualify to participate in the study. For approval, a surgeon must perform at least 12 carotid endarterectomies per year. Based on a review of the surgeon's last 50 consecutive endarterectomies, the combined neurological morbidity and mortality rate must be no greater than 5% for all indications and no greater than 3% for endarterectomies performed on asymptomatic patients. One hundred sixty-four surgeons from 48 centers applied for approval: 117 were approved, 17 were rejected, and 30 were not reviewed. The 117 approved surgeons submitted a total of 5,641 endarterectomies with a combined mortality and neurological morbidity rate of 2.3% for the variety of indications for operation. This overall experience with carotid endarterectomy is one of the largest series reported to date. The data from approved surgeons are well within the range of acceptable neurological morbidity and mortality rates recommended by the Stroke Council of the American Heart Association, which attests to the overall quality of the surgeons participating in the study.


MorphoCluster: Efficient Annotation of Plankton Images by Clustering.
In this work, we present MorphoCluster, a software tool for data-driven, fast, and accurate annotation of large image data sets. While already having surpassed the annotation rate of human experts, volume and complexity of marine data will continue to increase in the coming years. Still, this data requires interpretation. MorphoCluster augments the human ability to discover patterns and perform object classification in large amounts of data by embedding unsupervised clustering in an interactive process. By aggregating similar images into clusters, our novel approach to image annotation increases consistency, multiplies the throughput of an annotator, and allows experts to adapt the granularity of their sorting scheme to the structure in the data. By sorting a set of 1.2 M objects into 280 data-driven classes in 71 h (16 k objects per hour), with 90% of these classes having a precision of 0.889 or higher. This shows that MorphoCluster is at the same time fast, accurate, and consistent; provides a fine-grained and data-driven classification; and enables novelty detection.


Immunohistochemical evaluation of novel and traditional markers associated with urothelial differentiation in a spectrum of variants of urothelial carcinoma of the urinary bladder.
Data on immunohistochemical expression of novel and traditional urothelial markers in the wide range of urothelial carcinoma variants have so far been very limited. In this study, whole tissue sections from 130 bladder urothelial carcinoma and variants were stained with a panel of novel and traditional immunomarkers supportive of urothelial lineage. The positivity rates were as follows: (a) urothelial carcinomas with or without divergent differentiation: GATA3 (50%), S-100P (86%), uroplakin III (20%), thrombomodulin (40%), cytokeratin 7 (CK7) (80%), CK20 (55%), p63 (87%), and high molecular weight cytokeratin (HMCK) (89%); (b) urothelial carcinoma variants (micropapillary, plasmacytoid, nested, clear cell, and microcystic): GATA3 (88%), S-100P (96%), uroplakin III (33%), thrombomodulin (49%), CK7 (95%), CK20 (61%), p63 (69%), and HMCK (96%); and (c) undifferentiated carcinomas (lymphoepithelioma-like carcinoma, small cell carcinoma, sarcomatoid carcinoma and carcinoma with rhabdoid and giant cells): GATA3 (28%), S-100P (31%), uroplakin III (0%), thrombomodulin (22%), CK7 (50%), CK20 (3%), p63 (50%), and HMCK (49%). In urothelial carcinoma with squamous differentiation, GATA3 expression was lower (20%) in contrast to p63 and S-100P. In urothelial carcinoma with glandular differentiation, GATA3 (50%) and p63 (60%) expression was lower than S-100P (100%). p63 expression was relatively lower in micropapillary (54%) and plasmacytoid (50%) variants compared with the other urothelial carcinoma variants. This study provides comprehensive data for novel and traditionally used markers to support urothelial lineage in urothelial carcinoma variants. Our findings show that GATA3, S-100P, CK7, CK20, HMCK, and p63, in the appropriate differential diagnostic setting, are useful to support urothelial lineage of variant morphologies.


Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides.
Dendritic cells (DC) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness in vitro. The expression of costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with their capacity to induce or suppress immune responses. Expression of these molecules is associated with NF-kB-dependent transcription of their genes. DC tolerogenicity has been associated with impaired NF-kB-dependent transcription of costimulatory genes as well as NF-kB translocation to the nucleus. In this report, we demonstrate that double-stranded oligodeoxyribonucleotides containing binding sites for NF-kB (NF-kB ODN) are efficiently incorporated by bone marrow-derived DC and specifically inhibit NF-kB-dependent transcription of a reporter gene. Moreover, exposure of DC to the oligonucleotide decoys inhibited lipopolysaccharide (LPS)-induced nitric oxide production, a marker of DC maturation. Treatment of bone marrow-derived DC progenitors with NF-kB ODN selectively suppressed the cell-surface expression of costimulatory molecules without interfering with MHC class I or class II expression. Furthermore, NF-kB ODN DC induced allogeneic donor-specific hyporesponsiveness in mixed leukocyte cultures, and this was associated with inhibition of Th1-type cytokine production. Finally, infusion of NF-kB ODN-modified bone marrow-derived DC into allogeneic recipients prior to heart transplantation resulted in significant prolongation of allograft survival in the absence of immunosuppression. Specific interference with NF-kB and other transcriptional pathways involved in immune stimulation in DC using ODN decoy approaches could be one means to promote tolerance induction in organ transplantation.


Case Report: Toripalimab: a novel immune checkpoint inhibitor in advanced nasopharyngeal carcinoma and severe immune-related colitis.
Toripalimab, a specific immune checkpoint inhibitor targeting the programmed death 1 (PD-1) receptor, represents a novel immunotherapeutic approach for advanced nasopharyngeal carcinoma, showing promising curative potential. However, it is not without drawbacks, as some patients experience immune-related adverse events (irAEs) associated with this treatment, and there remains a limited body of related research. Here, we present a case of advanced nasopharyngeal carcinoma in a patient who developed colitis as an irAE attributed to Toripalimab. Subsequent to Toripalimab treatment, the patient achieved complete remission. Notably, the development of colitis was accompanied by inflammatory manifestations evident in colonoscopy and pathology results. Further investigation revealed cytomegalovirus (CMV) infection, detected through immunohistochemistry in 11 colon biopsies. Subsequent treatment with ganciclovir and steroids resulted in symptom relief, and colonoscopy indicated mucosal healing. Our case highlights the association between irColitis induced by Toripalimab and CMV infection. Toripalimab demonstrates remarkable efficacy in treating advanced nasopharyngeal carcinoma, albeit with a notable risk of irAEs, particularly in the form of colitis. The link between symptoms and endoscopic pathology findings in irColitis is noteworthy. Standardized biopsy procedures can effectively confirm the diagnosis of CMV infection. Our findings may provide valuable guidance for managing acute CMV infection and irAEs associated with Toripalimab in the treatment of nasopharyngeal carcinoma in the future.


Family history-based colorectal cancer screening in Australia: A modelling study of the costs, benefits, and harms of different participation scenarios.
The Australian National Bowel Cancer Screening Programme (NBCSP) was introduced in 2006. When fully implemented, the programme will invite people aged 50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2 years. To investigate colorectal cancer (CRC) screening occurring outside of the NBCSP, we classified participants (n = 2,480) in the Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories (average, moderately increased, and potentially high) based on CRC family history and assessed their screening practices according to national guidelines. We developed a microsimulation to compare hypothetical screening scenarios (70% and 100% uptake) to current participation levels (baseline) and evaluated clinical outcomes and cost for each risk category. The 2 main limitations of this study are as follows: first, the fact that our cost-effectiveness analysis was performed from a third-party payer perspective, which does not include indirect costs and results in overestimated cost-effectiveness ratios, and second, that our natural history model of CRC does not include polyp sojourn time, which determines the rate of cancerous transformation. Screening uptake was low across all family history risk categories (64%-56% reported no screening). For participants at average risk, 18% reported overscreening, while 37% of those in the highest risk categories screened according to guidelines. Higher screening levels would substantially reduce CRC mortality across all risk categories (95 to 305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For those at average risk, a fully implemented NBCSP represented the most cost-effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted life year [QALY]). For those at moderately increased risk, higher adherence to recommended screening was also highly cost-effective (AUS$19,000-24,000 per QALY). Investing in public health strategies to increase adherence to appropriate CRC screening will save lives and deliver high value for money.


Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.
We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p<or =0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistently H pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed between H pylori eradicated and persistently H pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26). H pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.


Assessment of airway neutrophils by sputum colour: correlation with airways inflammation.
Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases. To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum. The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001). These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.


The sparse matrix transform for covariance estimation and analysis of high dimensional signals.
Covariance estimation for high dimensional signals is a classically difficult problem in statistical signal analysis and machine learning. In this paper, we propose a maximum likelihood (ML) approach to covariance estimation, which employs a novel non-linear sparsity constraint. More specifically, the covariance is constrained to have an eigen decomposition which can be represented as a sparse matrix transform (SMT). The SMT is formed by a product of pairwise coordinate rotations known as Givens rotations. Using this framework, the covariance can be efficiently estimated using greedy optimization of the log-likelihood function, and the number of Givens rotations can be efficiently computed using a cross-validation procedure. The resulting estimator is generally positive definite and well-conditioned, even when the sample size is limited. Experiments on a combination of simulated data, standard hyperspectral data, and face image sets show that the SMT-based covariance estimates are consistently more accurate than both traditional shrinkage estimates and recently proposed graphical lasso estimates for a variety of different classes and sample sizes. An important property of the new covariance estimate is that it naturally yields a fast implementation of the estimated eigen-transformation using the SMT representation. In fact, the SMT can be viewed as a generalization of the classical fast Fourier transform (FFT) in that it uses "butterflies" to represent an orthonormal transform. However, unlike the FFT, the SMT can be used for fast eigen-signal analysis of general non-stationary signals.


Effects of puerarin on synaptic structural modification in hippocampus of ovariectomized mice.
There is growing interest in whether phytoestrogens, especially isoflavones, affect cognitive function and have beneficial effects on neurodegenerative diseases. Previous work from our laboratory showed that puerarin (Pur), a major component of the Pueraria lobata isoflavones, displayed protective effects on learning and memory in ovariectomized (Ovx) female mice. In the present study, we investigated the effects of Pur on the synaptic structural modifications of the hippocampus in Ovx female mice. One week after ovariectomy or sham operation, female mice were given a 4-week treatment of Pur (50 or 100 mg/kg, I. G.) or estradiol benzoate (EB, 120 microg/kg, S. C.). The results from synaptic structural measurement and analysis did not show any differences in the hippocampal volumes, the synaptic numeric density, and the curvature of synaptic interface among Sham, Ovx, and Ovx plus EB or Pur replacement female mice. However, Pur replacement effectively normalized some structural changes induced by Ovx, reducing the width of the synaptic cleft, enlarging the thickness of postsynaptic density (PSD), and lengthening the synaptic active zone of the pre-existing synapses in the hippocampus CA1 area (P < 0.05 or P < 0.01). Furthermore, through Western blotting, we found that the immunocontent of the NMDA receptor subunit NR2 was not altered by Pur (108 % and 114 % of Ovx); however, the content of postsynaptic protein PSD-95 (145 % and 176 % of Ovx) and phosphorylation of NMDA receptor subunit NR2B (141 % and 172 % of Ovx) strongly increased in Ovx mice following treatment with Pur (50 or 100 mg/kg) for 4 weeks. These results suggest that Pur possesses phytoestrogen activity with 1,000 -fold lower activity than EB, and the beneficial effects of Pur on improving memory behavior of Ovx female mice are associated with the changes of synaptic structural modifications in the hippocampus.


Adverse events in humans associated with accidental exposure to the livestock brucellosis vaccine RB51.
Brucella abortus strain RB51 vaccine, is an attenuated live bacterial vaccine that was licensed conditionally by the Center for Veterinary Biologics, Veterinary Services, Animal and Plant Health Inspection Service, USDA, on 23 February 1996, for vaccination of cattle in the United States. Accidental human inoculations can occur during vaccination of cattle, and previous live Brucella vaccines designed for cattle have been known to cause brucellosis in humans. The Centers for Disease Control and Prevention (CDC) established passive surveillance for accidental inoculation with the RB51 vaccine in the United States to determine if this veterinary vaccine is associated with human disease, to describe the circumstances of accidental inoculation, to evaluate the potential efficacy of post-exposure chemoprophylaxis, and to develop recommendations for post-exposure management following exposure to RB51. Reports were received from 26 individuals. Accidental exposure to RB51 occurred by needle stick injury in 21 people (81%), conjunctival spray exposure in four (15%), and spray exposure of an open wound in one (4%) individual. At least one systemic symptom was reported in 19 (73%) people, including three (12%) who reported persistent local reactions with systemic involvement. One case required surgery, and B. abortus strain RB51 was isolated from the wound of that individual. Seven cases reported no adverse event associated with accidental exposure. Nine cases reported previous exposure to Brucella vaccines, including one case who also reported a previous diagnosis of brucellosis following exposure to S19 vaccine. Accidental needle stick injuries and conjunctival or open wound exposures of humans with the RB51 vaccine are associated with both local and systemic adverse events in the United States that are consistent with brucellosis; however, it remains undetermined if strain RB51 vaccine can cause systemic brucellosis in humans. Early culture attempts on those exposed and developing disease in the future and serologic diagnostic assays for anti-RB-51 antibodies are needed to define if these adverse events are due to RB51 and to define appropriate prophylaxis regimens.


A Latent Disease Model to Reduce Detection Bias in Cancer Risk Prediction Studies.
In studies of cancer risk, detection bias arises when risk factors are associated with screening patterns, affecting the likelihood and timing of diagnosis. To eliminate detection bias in a screened cohort, we propose modeling the latent onset of cancer and estimating the association between risk factors and onset rather than diagnosis. We apply this framework to estimate the increase in prostate cancer risk associated with black race and family history using data from the SELECT prostate cancer prevention trial, in which men were screened and biopsied according to community practices. A positive family history was associated with a hazard ratio (HR) of prostate cancer onset of 1.8, lower than the corresponding HR of prostate cancer diagnosis (HR = 2.2). This result comports with a finding that men in SELECT with a family history were more likely to be biopsied following a positive PSA test than men with no family history. For black race, the HRs for onset and diagnosis were similar, consistent with similar patterns of screening and biopsy by race. If individual screening and diagnosis histories are available, latent disease modeling can be used to decouple risk of disease from risk of disease diagnosis and reduce detection bias.


[Morphofunctional study of the organization of the peripheral parenchyma of Acoela Oxyposthia praedator].
The ultrastructure of undifferentiated cells in the peripheral parenchyma of Oxyposthia praedator was studied, along with the ways of their differentiation. The type I cells (3.5-4.0 microns in diameter) undergo mitotic division, while the type II cells (9 microns in diameter) produce specialized cells of the parenchyma. At the beginning of secretory cell differentiation one cistern of the rough endoplasmic reticulum (RER) is formed by the outer membrane of the nuclear envelope, the formation of other cisternae follows. The Golgi complex is formed simultaneously. The differentiated secretory cells are characterized by the abundance of RER cisternae and Golgi complexes. In the course of differentiation of other cell types RER cisternae are formed by several portions of the nuclear envelope. The Golgi complex appears in cells 12-14 microns long. The differentiation of digestive cells is characterized by autophagy. Autophagosomes are formed by RER cisternae. The consecutive stages of autophagosome formation are described. Using a cytochemical reaction revealing acid phosphatase the process of digestion of the autophagosome content was followed.


Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study.
Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging. To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals. CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study. Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores. This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered.


Tyrphostin 4-nitrobenzylidene malononitrile reduces chemotherapy toxicity without impairing efficacy.
In mice, 4-nitrobenzylidene malononitrile (AG1714), which belongs to the tyrphostin family, reduced toxicity induced by doxorubicin and cisplatin without impairing their antitumor efficacy. AG1714 reduced mortality induced by doxorubicin and cisplatin. It prevented, in a dose-dependent manner, cisplatin-induced nephrotoxicity as assessed by measurement of serum creatinine and blood urea nitrogen levels. The protective effect of AG1714 was most pronounced on its administration 2 h before cisplatin. AG1714 also prevented doxorubicin-induced myelosuppression as assessed by the scoring of bone marrow nucleated cells and colony-forming units. Cisplatin-induced small intestinal injury was also protected by AG1714 as assessed by histopathological analysis. In vitro, AG1714 reduced cisplatin-induced apoptosis in a murine fibroblastic cell line (A9) and did not affect doxorubicin-induced apoptosis of B-16 melanoma cells. In contrast to its protective effect against mortality and injury of normal tissues induced by chemotherapy, AG1714 did not impair its antitumor activity and in some tumor models enhanced it. This was evident by using the murine tumors B-16 melanoma, Lewis lung carcinoma, and methylcholanthrene-induced fibrosarcoma and the human tumors SK-28 melanoma and human ovary carcinoma xenografts in nude mice. Experiments in which low and high doses of cisplatin and doxorubicin were administered to tumor-bearing mice demonstrated that AG1714 reduced mortality of high-dose chemotherapy and increased its therapeutic index. AG1714 could provide a novel, useful tool to improve chemotherapy by allowing dose intensification.


Acute posterior multifocal placoid pigment epitheliopathy. A recurrence.
Acute posterior multifocal placoid pigment epitheliopathy recurred in a 23-year-old white woman. Forty-two days after the onset of symptoms and following the complete resolution of the initial bilateral lesions, a second crop of ophthalmoscopically and biomicroscopically similar lesions were seen in each eye. The cause of the disorder is unknown, and corticosteroid therapy is of doubtful benefit.


Particulate Matter and Associated Metals: A Link with Neurotoxicity and Mental Health.
Particulate air pollution (PM) is a mixture of heterogenous components from natural and anthropogenic sources and contributes to a variety of serious illnesses, including neurological and behavioral effects, as well as millions of premature deaths. Ultrafine (PM0.1) and fine-size ambient particles (PM2.5) can enter the circulatory system and cross the blood-brain barrier or enter through the optic nerve, and then upregulate inflammatory markers and increase reactive oxygen species (ROS) in the brain. Toxic and neurotoxic metals such as manganese (Mn), zinc (Zn), lead (Pb), copper (Cu), nickel (Ni), and barium (Ba) can adsorb to the PM surface and potentially contribute to the neurotoxic effects associated with PM exposure. Epidemiological studies have shown a negative relationship between exposure to PM-associated Mn and neurodevelopment amongst children, as well as impaired dexterity in the elderly. Inhaled PM-associated Cu has also been shown to impair motor performance and alter basal ganglia in schoolchildren. This paper provides a brief review of the epidemiological and toxicological studies published over the last five years concerning inhaled PM, PM-relevant metals, neurobiology, and mental health outcomes. Given the growing interest in mental health and the fact that 91% of the world's population is considered to be exposed to unhealthy air, more research on PM and PM-associated metals and neurological health is needed for future policy decisions and strategic interventions to prevent public harm.


Reducing under-five mortality through Hôpital Albert Schweitzer's integrated system in Haiti.
The degree to which local health systems contribute to reductions in under-five mortality in severely impoverished settings has not been well documented. The current study compares the under-five mortality in the Hôpital Albert Schweitzer (HAS) Primary Health Care Service Area with that for Haiti in general. HAS provides an integrated system of community-based primary health care services, hospital care and community development. A sample of 10% of the women of reproductive age in the HAS service area was interviewed, and 2390 live births and 149 child deaths were documented for the period 1995-99. Under-five mortality rates were computed and compared with rates for Haiti. In addition, available data regarding inputs, processes and outputs for the HAS service area and for Haiti were assembled and compared. Under-five mortality was 58% less in the HAS service area, and mortality for children 12-59 months of age was 76% less. These results were achieved with an input of fewer physicians and hospital beds per capita than is available for Haiti nationwide, but with twice as many graduate nurses and auxiliary nurses per capita than are available nationwide, and with three cadres of health workers that do not exist nationwide: Physician Extenders, Health Agents and Community Health Volunteers. The population coverage of targeted child survival services was generally 1.5-2 times higher in the HAS service area than in rural Haiti. These findings support the conclusion that a well-developed system of primary health care, with outreach services to the household level, integrated with hospital referral care and community development programmes, can make a strong contribution to reducing infant and child mortality in severely impoverished settings.


Outcome evaluation results of school-based cybersafety promotion and cyberbullying prevention intervention for middle school students.
Guided largely by the Extended Parallel Process Model, the Arizona Attorney General's Social Networking Safety Promotion and Cyberbullying Prevention presentation attempts to shape, change, and reinforce middle school students' perceptions, attitudes, and intentions related to these important social issues. This study evaluated the short-term effects of this presentation in a field experiment using a posttest-only control-group design with random assignment to conditions. A total of 425 sixth, seventh, and eighth graders at a public middle school in a large Southwestern city participated in this study. Results reveal several interesting trends across grade levels regarding cyberbullying perpetration and victimization, and concerning access to various communication technologies. The intervention had the hypothesized main effect on eight of the dependent variables under investigation. Examination of condition by grade interaction effects offered further support for an additional four hypotheses (i.e., the intervention positively affected or reversed a negative trend on four dependent variables in at least one grade). Ideas and implications for future social networking safety promotion and cyberbullying prevention interventions are discussed.


Regeneration of dental pulp tissue in immature teeth with apical periodontitis using platelet-rich plasma and dental pulp cells.
To investigate the new tissues growing into the pulp space of immature dog teeth that were infected, disinfected and filled with blood clot (BC), dental pulp cells (DPCs), platelet-rich plasma (PRP) or a combination of DPCs and PRP in immature dog teeth with apical periodontitis. Fifty-six immature roots from mandibular premolars of four beagles were divided into four experimental groups (n = 40) and two control groups. After the induction of apical periodontitis, the root canals of experimental groups were disinfected with NaOCl irrigation and a tri-antibiotic paste medication. The canals were then filled with different materials according to the experimental group: BC group, DPCs group, PRP group or DPCs + PRP group. Access cavities were sealed with MTA and composite. Radiographs were taken after 90 days, and the jaws including the teeth were processed for histologic analysis. The data were statistically analysed using chi-square evaluation and Student's t-test. Radiographic analyses demonstrated no significant difference between experimental groups in periradicular bone healing (P > 0.05), whilst those groups that used DPCs produced a significantly greater root thickening (P < 0.01). The histologic evaluation showed that the groups with PRP formed more tissues in the canals (P = 0.01). The groups with DPCs had substantially more mineralized tissue formation in the canal than those without DPCs, especially in the apical third. In DPCs + PRP group, bone-like tissue grew into the canal space from the periapical tissue. A combination of DPCs + PRP increased vital tissue regeneration within the root canals of immature teeth associated with apical periodontitis.