Management of massive acetabular bone defects in revision arthroplasty of the hip using a reconstruction cage and porous metal augment.
It may not be possible to undertake revision total hip arthroplasty (THA) in the presence of massive loss of acetabular bone stock using standard cementless hemispherical acetabular components and metal augments, as satisfactory stability cannot always be achieved. We aimed to study the outcome using a reconstruction cage and a porous metal augment in these patients. A total of 22 acetabular revisions in 19 patients were performed using a combination of a reconstruction cage and porous metal augments. The augments were used in place of structural allografts. The mean age of the patients at the time of surgery was 70 years (27 to 85) and the mean follow-up was 39 months (27 to 58). The mean number of previous THAs was 1.9 (1 to 3). All patients had segmental defects involving more than 50% of the acetabulum and seven hips had an associated pelvic discontinuity. Three failures were observed in two hips, both of which had undergone a previous resection of a tumour affecting the acetabulum. Other complications included a late arterial injury, a sciatic nerve palsy, a dislocation treated with a femoral revision, a deep infection treated with irrigation and debridement and a fracture of the greater trochanter treated conservatively. The mean Oxford Hip Score significantly increased from 13.9 (2 to 23) to 28.7 (13 to 38) (p < 0.00001). The mean vertical distance between the centre of rotation of the hip and its normal location decreased from 30 mm to 10 mm. Acceptable early survivorship can be achieved using this novel technique, but it may be unsuitable for use in patients who have previously undergone the resection of a tumour involving the acetabulum. Cite this article: Bone Joint J 2017;99-B:607-13.


[Variable rates of diseases in health survey and family practitioners' registries].
To compare the data from the health survey of the Central Bureau for Statistics (CBS: about episodes of chronic diseases experienced by those questioned) and from general practice registration projects (regarding episodes of care). Descriptive. Department of General Practice, Academic Medical Centre, Amsterdam, the Netherlands. Frequency figures from the CBS health survey regarding chronic diseases for 1992 were compared with data from three large continuous general practice registration projects: the Amsterdam Transition Project, the Nijmegen Continuous Morbidity Registration and the fourth British National Morbidity Study. From the Transition Project not only one-year data were used but also data referring to a four-year period (1989/'93). Incidence and prevalence figures concerning illness and care were in good agreement regarding cardiovascular diseases, uterine prolapse, diabetes mellitus, thyroid disorders, epilepsy and cancer. The health survey had higher frequencies than the GP registration for respiratory disorders, hypertension (both mostly in the age group 25-44 years) gastrointestinal disorders, articular disorders and migraine. With regard to a number of diseases, the four-year registration was in better agreement with the health survey than the one-year registration (e.g. joint disorders): with other disorders the reverse was true (e.g. stroke). There were similarities as well as differences between the frequencies from the health survey and the general practice registration projects. Regarding a number of these differences interpretation was possible by using not only one-year data from the GP practice but also data concerning a longer period (4 years) and by comparing the information for different age groups.


Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells.
Cancer and normal stem cells (SCs) share proliferative properties of self-renewal and expression of key transcription factors (TFs). Despite similar TF identities, the functional role of specific TFs responsible for retaining SC state has yet to be examined in cancer. Here, we compare the role of Oct4 and Nanog, two-core pluripotent TFs, in transformed (t-hPSCs), and normal human pluripotent stem cells (hPSCs). Unlike normal SCs, self-renewal and survival of t-hPSCs were found to be independent of Oct4. In contrast, t-hPSCs exhibit hypersensitivity to reduction in Nanog and demonstrate complete loss of self-renewal coupled with apoptosis. Dual and sequential knockdown of Oct4 and Nanog revealed that sensitivity of t-hPSCs to Nanog was Oct4 dependent. Our study indicates a bifurcation for the role of two-core SC and cancer related TFs in self-renewal and survival processes. We suggest that the divergent roles of these TFs establish a paradigm to develop novel therapeutics towards selective destruction of aggressive tumors harboring cancer stem cells (CSCs) with similar molecular signatures.


Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone.
This study compared the safety and withdrawal discomfort associated with transitioning pregnant opioid-dependent women from short-acting morphine onto buprenorphine or methadone under well-controlled double-blind conditions. Participants (n=18) were patients in a comprehensive treatment setting and were part of a larger randomized controlled trial comparing the neonatal abstinence syndrome in mothers treated with individualized doses of sublingual buprenorphine or oral methadone. Methadone was first given to all patients within 24h of treatment admission. After written informed consent was signed (3-5 days post-admission), methadone was discontinued and Immediate Release Morphine (IRM) was initiated. The initial total daily dose of IRM was six times the last daily methadone dose. The daily dose of IRM was divided in four daily doses. Induction onto double-blind, double dummy (i.e., two medications were administered with only one being active) methadone or buprenorphine was accomplished over 3 days (i.e., induction). Withdrawal scores during the IRM and induction onto randomized medication were judged mild and not statistically different for both methadone (mean dose 53.5 mg) and buprenorphine (mean dose 10.9 mg). No significant differences between medication groups were observed when individual withdrawal items were examined. No observed differences in safety measures including fetal movement, maternal physiological parameters of body temperature, heart rate and blood pressure were observed between groups. Transitioning opioid-dependent pregnant women from IRM to methadone or buprenorphine during the second trimester of pregnancy can be conducted with similar comfort and safety.


[Identification and antifungal susceptibility of Candida spp isolated from invasive mycoses. Influence of growth inhibition percentage to determine minimal inhibitory concentration].
An increase in the frequency of resistant strains to antifungal drugs has been detected in the last decade. To report the minimal inhibitory concentration (MIC) to amphotericin B, fluconazole, ketoconazole and itraconazole. To compare the MIC obtained with 80% and 50% of growth inhibition to the azoles. Fifty yeast strains isolated between 1998 and 1999, from 17 adults and 33 children with invasive mycosis were studied. Susceptibility was determined by broth microdilution method with RPMI 1640 plus glucose 2% according to the National Committee for Clinical Laboratory Standards (1997). The most frequently isolated strains were C albicans in 27 cases and C parapsilosis in 12. All isolates were susceptible to amphotericin B. According to the MICs obtained with 80% of inhibition, 12 strains had MICs considered as resistant to azoles. Five strains were resistant both to fluconazole and itraconazole. Considering MICs obtained with 50% of inhibition, only five strains were found resistant to azoles (p < 0.05). Using this criterion, only one C glabrata strain was found to be simultaneously resistant to fluconazole and itraconazole. Similar results in the pattern of susceptibility of Candida spp to azoles, to those reported abroad, are obtained when the MIC is calculated using 50% inhibition.


H Long Terminal Repeat-Associating 2 (HHLA2) is a Biomarker of Advanced Stage Hepatocellular Carcinoma and Promotes Tumor Cell Development In Vitro.
BACKGROUND Several risk factors contribute to the inflammation promoting hepatocellular carcinoma (HCC) development, but the underlying mechanisms are unknown. Human endogenous retrovirus H long terminal repeat-associating 2 (HHLA2), a B7 family member, is highly expressed in various malignant tumor tissues and is related to tumor progression and metastasis. MATERIAL AND METHODS Bioinformatics analysis was used to analyze the gene expression chip GSE33006 of HCC tissue in the GEO database, draw a heat map of differentially expressed genes, and analyze the GO pathway of gene function annotation. Then, we compared HCC tissues with para-carcinoma liver tissues from 55 patients for expression patterns and associations with HHLA2. Effects of HHLA2 knockdown were examined in the human HCC cell line HepG2 to explore effects of HHLA2 on HepG2 cells. RESULTS A significantly higher expression of HHLA2 at the mRNA and protein levels was detected in HCC tissues than in para-carcinoma liver tissues, which was similar to HHLA2 expression in the GSE33006 data. A higher expression of HHLA2 protein was associated with advanced cancer stage, tumor differentiation, and invasion of adjacent structures. In vitro knockdown of HHLA2 expression significantly increased HepG2 cell adhesion, promoted cell apoptosis, induced cell cycle arrest in the G1/S phase, and inhibited cell proliferation, migration, and invasion. CONCLUSIONS Our data indicated there was a higher expression of HHLA2 in HCC tissues than in para-carcinoma liver tissues, and HHLA2 plays a major role in the development and progression of HCC. Owing to its higher expression, HHLA2 is a potential prognostic biomarker for HCC.


Derivation and reliability of kinematic measures of sperm motion.
Studies of sperm movement are relevant in the diagnosis of sperm function and in investigations of cellular biology. Such studies have been traditionally performed by analysing the kinematics of the flagellum or the head. Analysis of the flagellum can provide insights into the cell biological mechanisms responsible for the control of movement. However, the mathematical correspondence between head kinematics and flagellum kinematics is not unique. Therefore, it is not possible to use head kinematics to obtain detailed insights into cell mechanisms or physiology. The accuracy and precision of kinematic measurements are limited by a number of technical and biological factors. Therefore, the interpretation of kinematic data is dependent on a thorough understanding of the assumptions and conditions underlying the analysis. Evaluation of the reliability of kinematic measurements has suffered because no absolute standard for measurement has existed. The development and application of a new standard based on images which were simulated using the equations of motion is described. Because the kinematics of these images are known prior to empirical measurement, the performance of different methods can be determined absolutely. Some kinematic measures are unreliable because they are inappropriate analogues for engineering concepts. The development and use of appropriate engineering measures for the frequency and amplitude of sperm motion is also described. Some types of sperm motion cannot be analysed using kinematic measures (e.g. hyperactivated movement). The concept of the fractal dimension as a more accurate measurement for such motions is introduced. It is concluded that kinematic measurements of sperm motion can provide valuable information about cell biological mechanisms (in the case of the flagellum) and about general membrane and axoneme function (in the case of the head) when the measurements are made under the appropriate conditions, when standard techniques are followed, and when the assumptions underlying the analysis are well understood.


[Importance of vitamin A deficiency in pathology and immunology of viral infections].
Vitamin deficiencies and infections caused by viruses and other pathogens often coexist and exhibit complex interactions. Malnutrition, vitamin A deficiency and infections among populations of the developing countries, these are the leading cause of death, particularly in children. Several micronutrients were in study, vitamin A deficiency is strongly involved in measles and diarrhea. There are also some scientific data against this thesis. These vitamins, virus infection and immune function interactions are briefly reviewed in this article.


Design of second generation phosphodiesterase 5 inhibitors.
The clinical significance of phosphodiesterase 5 (PDE5) inhibition is increasingly understood following the pioneering work with sildenafil, and the continuing development programmes for both sildenafil and other marketed inhibitors. Since the initial launch of sildenafil for male erectile dysfunction (MED), approval has now been granted for treatment of pulmonary hypertension, whilst ongoing studies have indicated the potential of PDE5 inhibition for the treatment of a range of additional indications including cardioprotection, memory retention and diabetes. Many of these additional indications are best suited to chronic oral dosing and emphasise the need for highly selective inhibitors with extended duration of action. This article will focus on a research programme aimed at the discovery of improved second-generation PDE5 inhibitors. Essential features of these new PDE5 inhibitors would be enhanced selectivity across the whole PDE family and pharmacokinetics compatible with once daily dosing. Key elements used in this programme are high throughput screening (HTS), exploitation of co-crystal structural information for bound inhibitor in the PDE5 active site, and employment of parallel chemistry to speed progress. Under the guidance of co-crystal structural information, a non-selective HTS hit with poor physicochemistry was initially modified using parallel chemistry to give a lead compound (3) that established a new PDE5 inhibitor series. Notably, (3) displayed physicochemistry compatible with a long plasma half-life, and wide chemical scope. Subsequent optimisation of (3) using crystal structure information to guide design, led rapidly to highly potent and selective PDE5 inhibitors (47, 50). Continued focus on physical properties through ligand efficiency evaluation and lipophilicity (cLogP), maintained the inherently desirable physicochemistry of the initial lead.


Lingual cortical mandibular bone depression: frequency and clinical-radiological features in a Brazilian population.
The aim of this study was to report the frequency and clinical-radiological features of cases of lingual cortical mandibular bone depressions (LCMBD) diagnosed in consecutive panoramic radiographs and cone-beam computed tomography (CBCT) scans from a Brazilian population. The methods included a retrospective analysis of consecutive panoramic radiographs, charts from the Oral Medicine clinic and consecutive CBCT scans. All cases diagnosed as LCMBD were selected and clinical-radiological data were retrieved from the clinical charts and by the analysis of the image exams. Twenty LCMBD cases diagnosed in 18 patients were found, including 2 from 3,000 consecutive panoramic radiographs (0.07%), 6 from 2,421 Oral Medicine patients (0.25%) and 10 from 1,684 CBCT scans (0.59%). The 18 patients had a mean age of 51.5 years and 13 were males. Two patients presented bilateral lesions. Fourteen images (70%) were classified as well-defined. Eighteen affected the posterior area of the mandible and two affected the anterior mandible. Size of the lesions was larger in younger patients. In conclusion, there seemed to be a considerable radiological heterogeneity when comparing the LCMBD cases and it seemed that the images decreased in size with the increase of patient's age.


Risk of nasopharyngeal carcinoma in patients with chronic rhinosinusitis: A nationwide propensity score matched study in Taiwan.
Chronic inflammation is linked to cancer. This study aims to evaluate the association between chronic rhinosinusitis (CRS) and nasopharyngeal carcinoma (NPC) through a Taiwanese nationwide database. We used the National Health Insurance Research Database between January 1, 2003, and December 31, 2012. The starting date is either the date of the first clinical visit or the diagnosis of CRS. Patients were followed up until the first occurrence of target disease or the last date of medical record. Propensity score 1 to 2 matching was used to match pairs of patients with/without CRS. A total of 951 380 eligible patients were included in our study, with 36 210 patients diagnosed with CRS. After 1 to 2 propensity score matching, non-CRS cohort consisted of 69 258 patients and CRS cohort consisted of 34 629 patients. CRS was associated with the risk of developing NPC (adjusted OR = 2.23; 95% CI, 1.61-3.09). However, no significant association among CRS and NPC was observed in patients followed up for more than 1 year (adjusted OR = 1.16; 95% CI, 0.76-1.78). Patients with CRS diagnosis have relationship with developing NPC within 1 year of follow-up, but not for longer intervals. The short-term association may be due to reversed causation or biased diagnosis. Accordingly, the study suggests CRS a weak role for NPC.


Attrition bias in rheumatoid arthritis databanks: a case study of 6346 patients in 11 databanks and 65,649 administrations of the Health Assessment Questionnaire.
Patient dropout (attrition) can bias and threaten validity of databank-based studies. Although there are several databanks of rheumatoid arthritis (RA) in operation, this phenomenon has not been well studied. We studied the attrition patterns of patients with RA in 11 long-running databanks where patients were followed using semiannual Health Assessment Questionnaires. Attrition rates were calculated as the proportion of living patients who were in active followup at the cutoff date. Mantel-Haenszel methods and Weibull regression were used to model the relationship between attrition and age, sex, race, education, disease duration, functional disability, and other characteristics. Overall, 6346 patients with RA were recruited into the study cohorts and followed for 32,823 person-years with 65,649 observations. The crude attrition rate was 3.8% per cycle. Rates were lowest in community-based databanks. Smaller size of the centers, inner-city location, and university clinic settings were associated with worse attrition. In multivariable analyses, younger age, lower levels of education, and non-Caucasian race predicted attrition. Level of disability and disease duration were not associated with attrition. Conclusion. In terms of person-years of followup and observation-points, this may be the largest study on attrition to date. While it is possible to have very high overall retention rates, certain types of databanks (smaller, inner-city-based, and university-based) are more likely to be biased due to selective retention of older, more educated Caucasian patients.


Active versus expectant management for women in the third stage of labour.
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. To compare the effectiveness of active versus expectant management of the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (May 2010). Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We included five studies (6486 women), all undertaken in hospitals in high-income countries. Four compared active versus expectant management, and one compared active versus a mixture of managements. Analysis used random-effects because of clinical heterogeneity. Active management reduced the average risk of maternal primary haemorrhage (more than 1000 ml) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, three studies, 4636 women) and of maternal haemoglobin less than 9 g/dl following birth (RR 0.50, 95% CI 0.30 to 0.83, two studies, 1572 women) for women irrespective of their risk of bleeding. We identified no difference in Apgar scores less than seven at five minutes. Active management showed significant increases in maternal diastolic blood pressure, after-pains, use of analgesia and more women returning to hospital with bleeding. There was also a decrease in the baby's birthweight with active management, reflecting the lower blood volume from interference with placental transfusion. There were similar findings for women at low risk of bleeding except there was no significant difference identified for severe haemorrhage. Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, e.g. omitting ergot and deferring cord clamping, but we have no direct evidence of this here. Active management of third stage reduced the risk of haemorrhage greater than 1000 ml in an unselected population, but adverse effects are identified. Women should be given information on the benefits and harms to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third stage management. Data are also required from low-income countries.


Unicompartmental arthroplasty of the knee: a review of three-five year follow-up.
Unicompartmental arthroplasty for the treatment of osteoarthritis, that primarily involves a single femorotibial compartment of the knee, has been a controversial procedure. The purpose of this study was to retrospectively review the results of 59 cases in 55 patients, an average of four years after operation. Forty-five of the knees were rated excellent or good and there were eight failures. The thin 6 mm tibial component seemed to be associated with an increased occurrence of loosening and failure of the procedure. There were no failures when thick tibial components were used. The results of this study are encouraging for the use of unicompartmental arthroplasty in the treatment of osteoarthritis of the knee.


Laboratory studies with a selective Enterococcus medium.
Lancefield group D streptococci are involved with appreciable frequency in a variety of infectious processes. The presumptive recognition of these bacteria on initial culturing of clinical specimens is an objective not attained readily by selective media available in the clinical laboratory. Selective Enterococcus agar was evaluated with emphasis on its ability to sequester enterococci from specimens with many microbial components. In addition, the sensitivity of this new agar was compared with Trypticase Soy agar containing sheep blood and Mitis Salivarius agar. All enterococci isolated from clinical material were classified in accordance with accepted biochemical and immunochemical criteria. The enterococci grew on the new medium as distinctive colonies surrounded by a black zone. Only Listeria monocytogenes presented similar colonial morphology after 48 hr. Most other bacteria did not grow at all or appeared markedly different. The sensitivity of the new agar was of the same order of magnitude as on blood or Mitis-Salivarius agars, but its selectivity was superior.


A pilot survey of attitudes and knowledge about opioid substitution therapy for HIV-infected prisoners.
A majority of inmates in the state of Connecticut Department of Corrections use opioids or are opioid dependent before incarceration. None of the state's prisons offer opioid substitution therapy other than for detoxification or maintenance therapy for women during pregnancy. On release to the community, most prisoners relapse to drug use and this has been associated with higher recidivism rates, and less adherence to antiretroviral medications for HIV-infected persons. Nationally and internationally, methadone (METH) and buprenorphine (BUP) have been found to decrease relapse to drug use, decrease recidivism rates, improve adherence to antiretroviral medications, decrease HIV-risk taking behaviors, and improve mortality. However, the general knowledge about opioid substitution therapy among correctionalfacility staff has been reported as substandard. This pilot study compiled results of answers to anonymous surveys from 27 individuals who work directly with inmates in a patient-care capacity for the Connecticut Department of Corrections (CT DOC) and CT DOC case-management referral program (Project TLC) in the year 2006. The surveys included questions regarding current attitudes and knowledge about opioid substitution therapy for prisoners. A minority of respondents refer released prisoners with a history of opioid dependency to METH or BUP treatment. The majority of correctional workers and case-management referral workers did not have knowledge about BUP or METH's ability to improve health and decrease HIV risk taking behaviors. This study found that more education of individuals treating and caring for HIV-infected opioid dependent prisoners is needed.


Appropriate maximum holding times for analysis of total suspended solids concentration in water samples taken from open-channel waterways.
Many scientific laboratories follow, as standard practice, a relatively short maximum holding time (within 7 days) for the analysis of total suspended solids (TSS) in environmental water samples. In this study we have subsampled from bulk water samples stored at ∼4 °C in the dark, then analysed for TSS at time intervals up to 105 days after collection. The nonsignificant differences in TSS results observed over time demonstrates that storage at ∼4 °C in the dark is an effective method of preserving samples for TSS analysis, far past the 7-day standard practice. Extending the maximum holding time will ease the pressure on sample collectors and laboratory staff who until now have had to determine TSS within an impractically short period.


The effects of tendon load and posture on carpal tunnel pressure.
Two pressure measurement techniques (catheter and bulb) were used to decompose the effects of tendon loads on carpal tunnel pressure (CTP). The catheter technique measures true hydrostatic pressure, whereas the bulb technique is a estimate of contact force or pressure on the median nerve. Eight cadaveric wrists were moved through a range of flexion-extension (0 degrees, 10 degrees, 20 degrees, 30 degrees, and 45 degrees of each) and radioulnar deviation (10 degrees and 20 degrees radial and 0 degrees, 10 degrees, 20 degrees, and 30 degrees ulnar) while CTPs were measured under 4 muscle loading conditions with the thumb, index, and long finger in a pinch-grip posture. The first of these was zero load. Then a 1-kg mass was applied in turn to both flexors of the index and long fingers, the palmaris longus (PL); and the flexor pollicis longus. The hydrostatic pressure was found to be affected by both wrist posture and tendon load. With no load, highest pressures were seen in wrist extension. Muscular loading elevated CPT, particularly the loading of palmaris longus with the wrist in extension and the digital flexors with the wrist flexed. Bulb pressure measurements, related to local contact forces by the digital flexors, indicated the highest loads on the median nerve with the wrist flexed. Palmaris longus loading created the highest pressures in extension and only moderate pressure in flexion, indicating that it may alter the geometry of the transverse carpal ligament. In view of the data from this study, it is necessary to incorporate measures of hydrostatic pressure and local contact forces to describe possible trauma to the median nerve in the carpal tunnel, as neither appears sufficient when used independently.


Dopamine agonists in Parkinson's disease.
Levodopa (LD), the immediate precursor of dopamine, is the most effective agent in the treatment of Parkinson's disease (PD). While quite successful in treating the primary motor deficits of PD, most patients eventually develop LD-related motor fluctuation, dyskinesias and other adverse effects associated with chronic LD therapy. There is also concern that LD is neurotoxic, although this has not been demonstrated in any in vivo studies. Dopamine agonists (DAs) have been shown to be about as effective as LD in symptomatic treatment of mild-to-moderate PD. In addition, there is a lower tendency to develop motor fluctuations and dyskinesias with DA treatment than after initiation of therapy with LD. Furthermore, there is preclinical and clinical data to suggest a slowing of neurodegeneration with DAs. The adverse effects of DAs are similar to those experienced with LD, except that the ergot agents are associated with a small risk of tissue fibrosis not noted with the non-ergot DAs.


"Recovery" vena cava filter: experience in 96 patients.
The purpose of the study was to assess the clinical safety and efficacy of the "Recovery(TM)" (Bard) inferior vena cava (IVC) filter. We retrospectively evaluated the clinical and imaging data of patients who had a "Recovery(TM)" IVC filter placed between January 2003 and December 2004 in our institution. The clinical presentation, indications, and procedure-related complications during placement and retrieval were evaluated. Follow-up computed tomography (CT) examinations of the abdomen and chest were evaluated for filter-related complications and pulmonary embolism (PE), respectively. "Recovery" filters were placed in 96 patients (72 males and 24 females; age range: 16-87 years; mean: 46 years). Twenty-four patients presented with PE, 13 with deep vein thrombosis (DVT) and 2 with both PE and DVT. The remaining 57 patients had no symptoms of thromboembolism. Indications for filter placement included contraindication to anticoagulation (n = 27), complication of anticoagulation (n = 3), failure of anticoagulation (n = 5), and prophylaxis (n = 61). The device was successfully deployed in the infrarenal (n = 95) or suprarenal (n = 1) IVC through a femoral vein approach. Retrieval was attempted in 11 patients after a mean period of 117 days (range: 24-426). The filter was successfully removed in nine patients (82%). Failure of retrieval was due to technical difficulty (n = 1) and the presence of thrombus in the filter (n = 1). One of the nine patients who had the filter removed developed IVC thrombus after retrieval and another had an intimal tear of the IVC. Follow-up abdominal CT (n = 40) at a mean of 80 days (range: 1-513) showed penetration of the IVC by the filter arms in 11, of which 3 had fracture of filter components. In one patient, a broken arm migrated into the pancreas. Asymmetric deployment of the filter legs was seen in 12 patients and thrombus within the filter in 2 patients. No filter migration or caval occlusion was encountered. Follow-up chest CT (n = 27) at a mean of 63 days (range: 1-386) showed PE in one patient (3%). During clinical follow-up, 12 of 96 patients developed symptoms of PE and only 1 of the 12 had PE on CT. There was no fatal pulmonary embolism in our group of patients following "Recovery" filter placement. However, the current version of the filter is associated with structure weakness, a high incidence of IVC wall penetration, and asymmetric deployment of the filter legs.


Complete hydatidiform mole coexisting with a live fetus.
Hydatidiform mole co-existing with a normal fetus is very rare. We report a case of a 36 year old woman Para 4+0 who presented with amenorrhoea of twenty four weeks duration, vaginal bleeding, abdominal pain and pre-eclampsia. Ultrasound examination revealed a hydatidiform mole coexisting with a normal living fetus. The patient underwent a caesarean section at twenty eight weeks for maternal distress due to unbearable abdominal pain. The baby died after seven days. Post operatively she had an eclamptic fit and developed oliguria and persistent trophoblastic disease which were all successfully treated.


Comparing adaptive algorithms to measure temporal gait parameters using lower body mounted inertial sensors.
The purpose of this research was to compare different adaptive algorithms in terms of their ability to determine temporal gait parameters based on data acquired from inertial measurement units (IMUs). Eight subjects performed 25 walking trials over a force plate under five different conditions; normal, fast, slow, simulated stiff ankle and simulated stiff knee walking. Data from IMUs worn on the shanks and on the feet were used to identify temporal gait features using three different adaptive algorithms (Green, Selles & Sabatini). Each method's ability to estimate temporal events was compared to the gold standard force plate method for stance time (Greene, r= .990, Selles, r= 0.865, Sabatini, r= 0.980) and double support time (Greene, r= .837, Selles, r= .583, Sabatini, r= .745). The Greene method of estimating gait events from inertial sensor data resulted in the most accurate stance and double support times.


Bladder tissue characterization using probe-based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction.
Existing approaches for early-stage bladder tumor diagnosis largely depend on invasive and time-consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real-time tumor diagnosis can enable immediate laser-based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real-time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe-based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low- and high-grade tumor.


Active surveillance for low-risk prostate cancer compared with immediate treatment: a Canadian cost comparison.
Clinical consequences of active surveillance compared with immediate treatment have been evaluated in patients with low-risk prostate cancer; yet, its financial benefits have not been adequately studied in Canada or elsewhere. Our study objective was to evaluate the direct costs associated with active surveillance and immediate treatment in the Canadian context. We developed a Markov model with Monte Carlo microsimulations to estimate the Canadian cost of prostate cancer associated with immediate treatment and active surveillance strategies. The patients receiving active surveillance were assumed to receive delayed treatment at a rate of 8.35%, 4.17% and 2.1% per year for the first 2 years, years 3 to 5, and years 6 to 10 of follow-up, respectively. All costs were assigned in Canadian dollars and reflect Quebec's health system. With active surveillance, the mean cost of prostate cancer management over the first year and 5 years of follow-up was estimated at $6200 (95% confidence interval [CI] $6083-$6317) per patient. The mean cost corresponding to immediate treatment was estimated at $13 735 (95% CI $13 615-$13 855) per patient. We estimated that patients receiving active surveillance who received delayed treatment incurred higher costs of $16 257 per patient. Active surveillance could offer important economic benefits to the Canadian health system, estimated at $96.1 million for each annual cohort of incident prostate cancer. These results add to the economic rationale advocating active surveillance for eligible men with low-risk prostate cancer.


[Psychosocial Risk Factors in Patients With Most Common Cardiovascular Diseases Such as Hypertension and Coronary Artery Disease (Based on Results From the Russian Multicenter COMET Study)].
Psychosocial risk factors (RFs) play a major role in the development and progression of cardiovascular diseases (CVDs). The COMET study aimed to obtain current data on psychosocial RFs in outpatients with arterial hypertension (AH) and/or coronary heart disease (CHD) seen in primary care facilities in 30 cities of Russia. In 2016-2017, a multicenter cross-sectional study was carried out involving 325 physicians from community primary care facilities who enrolled 2,775 patients with AH and/or CHD ≥ 55 years of age. However, only 73 CHD patients (2.6%) were not hypertensive, therefore, these patients were excluded from the analyses. As a result, current paper is based on the comparison of AH patients (n=1687) vs. participants with both CHD and AH (AH+CHD; n=1015). We collected patients' socio-demographic data, clinical features, traditional and psychosocial RFs, such as anxiety and depression, stress level, type D personality, and treatment adherence. The study population (women, 72%; mean age ± SD, 66.7 ± 7.9 years) had a significant prevalence of psychosocial RF. 43.8% of AH patients and 45.5 % of participants with AH+CHD rated their income as low or very low, a low educational level was reported in 21.6% and 26.0%, respectively (both p=n/s). Social isolation was uncommon, but it occurred more frequently in AH+CHD patients (8.3% vs. 5.2%, p<0.01). Nevertheless, 40.2% of AH patients and 39.4% of AH+CHD were not married, and 26.0% and 24.6% were living alone, respectively. Elevated stress level was prevalent in more than 60% of patients (67.9% in AH patients vs. 67.7% in AH+CHD patents, p=n/s), and 63.3% and 64.8% of patients, respectively, reported stressful life events in the preceding year (p=n/s). Type D personality was more common in AH+CHD patients (41.2% vs. 35.8%; p<0.01). Clinically significant anxiety symptoms were prevalent in 24.7% ofAH patients and in 27.4% ofAH+CHD patients (p=n/s), and clinically significant depressive symptoms were identified in 13.9% and 20.9%, respectively (p<0.001). We obtained current data on psychosocial RFs prevalence in outpatients with the most common CVDs in primary care setting. At the moment, their prevalence remains significant.


Factors associated with poor response in cognitive-behavioral therapy for pediatric obsessive-compulsive disorder.
Cognitive-behavioral therapy (CBT) with exposure and response prevention has proved to be an effective intervention for youth with obsessive-compulsive disorder (OCD). Given advantages over psychiatric medications (i.e., serotonin reuptake inhibitors) based on superior safety, maintenance of response, and efficacy, CBT is considered the first-line treatment for youth with OCD. Nevertheless, a number of clinical factors can complicate CBT for OCD course and outcome. The authors review factors associated with poor treatment response, highlighting variables that pertain to the child, the family environment, and the treatment process. Specific topics include diminished insight, family accommodation, comorbidity, symptom presentation, and cognitive deficits. Remarkably, CBT for OCD is robust to these encumbrances in the majority of cases, despite the need for protocol modifications to tailor treatment to the individual child.


Long-term outcomes of sphincter pharyngoplasty in patients with cleft palate.
The purpose of this study was to evaluate long-term outcomes of sphincter pharyngoplasties, including speech outcomes, revision surgeries, and postoperative incidence of obstructive sleep apnea (OSA). Retrospective matched-cohort study SETTING: Two craniofacial centers in Los Angeles, CA PATIENTS: Patients (n = 166) with cleft lip and palate (CLP) or isolated cleft palate (iCP) who underwent sphincter pharyngoplasty from 1992 to 2022 were identified. An age- and diagnosis-matched control group of 67 patients with CLP/iCP without velopharyngeal insufficiency (VPI) was also identified. The pharyngoplasty group underwent sphincter pharyngoplasty, whereas the non-VPI group had no history of VPI surgery or sphincter pharyngoplasty. Postoperative speech outcomes, revision surgeries, and incidence of OSA were evaluated. Multivariable regression was used to evaluate independent predictors of OSA. Among the patients in the pharyngoplasty cohort, 63.9% demonstrated improved and sustained speech outcomes after a single pharyngoplasty, with a median postoperative follow-up of 8.8 years (interquartile range [IQR], 3.6-12.0 years). One-third of the patients who underwent pharyngoplasty required a revision surgery, with a median time to primary revision of 3.9 years (IQR, 1.9-7.0 years). OSA rates increased significantly among the pharyngoplasty cohort, from 3% before surgery to 14.5% after surgery (p < 0.001). The average time from sphincter pharyngoplasty to OSA diagnosis was 4.4 ± 2.4 years. Multivariable analysis results indicated that sphincter pharyngoplasty surgery was independently associated with a fourfold increase in OSA (p = 0.03). Although sphincter pharyngoplasty remains successful in improving long-term speech outcomes, persistent OSA is a sequela that should be monitored beyond the immediate postoperative period.


A flow cytometry method to quantitate internalized immunotoxins shows that taxol synergistically increases cellular immunotoxins uptake.
Tumor microenvironments present significant barriers to penetration by antibodies, immunoconjugates, and other immunotoxins. In this report, we illustrate a novel strategy to increase tumor cell uptake of immunotoxin by combination with Taxol. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing phase II testing in mesothelioma. Using novel flow cytometry and gel filtration methods, we quantified SS1P uptake in individual tumor cells along with levels of shed mesothelin (sMSLN), a barrier of SS1P therapy. The validity of our flow cytometric method was confirmed by the ability to similarly quantitate tumor cell uptake of Herceptin and an immunotoxin targeting HER2/neu. SS1P uptake peaked several hours after SS1P was cleared from the blood, reflecting an intratumor distribution process of SS1P that is independent of blood supply. Using the methods developed, we demonstrated that Taxol could improve SS1P penetration into tumors in parallel with an associated reduction of sMSLN in tumor extracellular fluid. Our findings offer a mechanistic rationale to combine SS1P with Taxol or another cytotoxic drug as a strategy to increase immunotoxin uptake by tumor cells. Further, we suggest one basis to understand why chemotherapy and antibody-based therapies cooperate when combined in cancer treatment.


Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II.
Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD). Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry. Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD. Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.


Bioactive Compounds in Edible Oils and Their Role in Oxidative Stress and Inflammation.
Diet and inflammatory response are recognized as strictly related, and interest in exploring the potential of edible fats and oils for health and chronic diseases is emerging worldwide. Polyunsaturated fatty acids (PUFAs) present in fish oil (FO), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be partly converted into oxygenated bioactive lipids with anti-inflammatory and/or pro-resolving activities. Moreover, the co-presence of phenolic compounds and vitamins in edible oils may prevent the development of chronic diseases by their anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory activities. Finally, a high content in mono-unsaturated fatty acids may improve the serum lipid profile and decrease the alterations caused by the oxidized low-density lipoproteins and free radicals. The present review aims to highlight the role of lipids and other bioactive compounds contained in edible oils on oxidative stress and inflammation, focusing on critical and controversial issues that recently emerged, and pointing to the opposing role often played by edible oils components and their oxidized metabolites.


Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain.
Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20-21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype.


Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia.
Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The α7 nicotinic acetylcholine receptor (α7nAChR) has already been identified as an important mediator of the anti-inflammatory pathway after stroke. However, whether the α2, α5 and α9/10 nAChR expressed in the lung also play a role in suppression of pulmonary innate immunity after stroke is unknown. In the present study, we investigate the impact of various nAChRs on aspiration-induced pneumonia after stroke. Therefore, α2, α5, α7 and α9/10 nAChR knockout (KO) mice and wild type (WT) littermates were infected with Streptococcus pneumoniae (S. pneumoniae) three days after middle cerebral artery occlusion (MCAo). One day after infection pathogen clearance, cellularity in lung and spleen, cytokine secretion in bronchoalveolar lavage (BAL) and alveolar-capillary barrier were investigated. Here, we found that deficiency of various nAChRs does not contribute to an enhanced clearance of a Gram-positive pathogen causing post-stroke pneumonia in mice. In conclusion, these findings suggest that a single nAChR is not sufficient to mediate the impaired pulmonary defense against S. pneumoniae after experimental stroke.


Prevalence trends for myocardial infarction and conventional risk factors among Greek adults (2002-06).
To examine trends in the prevalence of myocardial infarction (MI) and conventional risk factors in Greek adults between 2002 and 2006. Repeated cross-sectional study. Self-reported data from surveys given in Salamis during two election days in 2002 and 2006 were analysed. The same sampling method and procedures were used on both surveys. The study sample included 2805 and 3478 subjects (> or =20 years) in 2002 and 2006, respectively, with similar age and sex distribution to the target population. The prevalence of MI increased from 4.1% (men, 6.3%; women, 1.9%) in 2002 to 4.8% (men, 7.3%; women, 2.2%) in 2006 (P = 0.18). At the same time, prevalence rates of major risk factors were as follows: diabetes increased from 8.7% to 10.3% (P = 0.037), hypertension from 20.1% to 25.7% (P < 0.001) and hypercholesterolemia (cholesterol >240 mg/dl or the use of cholesterol-lowering medication) increased from 17.5% to 22.3% (P < 0.001). Prevalence of current smokers in 2002 (defined as persons who smoked > or =5 cigarettes/day) was 37.0% and in 2006 (defined as those who smoked > or =1 cigarettes/day) was 40.1%. Logistic regression analysis showed that the aforementioned risk factors were significantly associated with MI in both surveys; the factor that showed the greatest magnitude of association with MI was hypercholesterolemia, followed by diabetes, hypertension and smoking. These findings show that, in the Greek population, prevalence of MI continues to rise (at approximately 4% per year). This trend seems to be driven by a persistently high prevalence of smoking and the rapidly increasing burden of diabetes, hypertension and hypercholesterolemia.


Interaction between PNPLA3 I148M variant and age at infection in determining fibrosis progression in chronic hepatitis C.
The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M) on the fibrosis progression rate (FPR) and the interaction with age at infection in chronic hepatitis C (CHC). FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. Older age at infection was the strongest determinant of FPR (p<0.0001). PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; -0.64±0.2, n = 8 vs. -0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05), but not in those infected at younger age (p = ns). The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2-3 steatosis, genotype 3, and overweight; p<0.05). At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022), independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025). The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032). We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients.


A methodology to maximize resident input in improving a pediatric rotation.
To develop a structured process to gain resident input into the improvement of their educational experience by (1) taking a small amount of resident time and effort, (2) fostering the generation of new ideas, (3) allowing the prioritization of ideas, (4) generating implementation plans for the ideas, and (5) offering the participants relative anonymity. Cross-sectional survey and group sessions. Urban, university-based children's hospital. Members of the pediatric residency program in the 1993-1994 academic year. The process was piloted for an emergency department rotation and borrows aspects of the Delphi Technique, Nominal Group Technique, and focus group methods. A survey regarding an emergency department rotation was distributed to all pediatric residents, and the 10 most commonly noted problems were compiled. These problems were brought to group sessions held for each level of training. Problems not listed were added if they were mentioned during the session; however, no problem was removed from the list. The sessions, designed to offer relative anonymity to the residents, included an initial clarification period, a round-robin prioritization of ideas, and an open discussion designed to generate solutions. Resident-generated solutions resulting from the group sessions were reviewed by the attending staff, and changes were implemented during the next year. The technique that we developed is a practical and time-efficient method of incorporating resident perspectives into the improvement of a rotation.


Life history evolution and cellular mechanisms associated with increased size in high-altitude Drosophila.
Understanding the physiological and genetic basis of growth and body size variation has wide-ranging implications, from cancer and metabolic disease to the genetics of complex traits. We examined the evolution of body and wing size in high-altitude Drosophila melanogaster from Ethiopia, flies with larger size than any previously known population. Specifically, we sought to identify life history characteristics and cellular mechanisms that may have facilitated size evolution. We found that the large-bodied Ethiopian flies laid significantly fewer but larger eggs relative to lowland, smaller-bodied Zambian flies. The highland flies were found to achieve larger size in a similar developmental period, potentially aided by a reproductive strategy favoring greater provisioning of fewer offspring. At the cellular level, cell proliferation was a strong contributor to wing size evolution, but both thorax and wing size increases involved important changes in cell size. Nuclear size measurements were consistent with elevated somatic ploidy as an important mechanism of body size evolution. We discuss the significance of these results for the genetic basis of evolutionary changes in body and wing size in Ethiopian D. melanogaster.


Intraobserver reliability of the modified Tardieu scale in the upper limb of children with hemiplegia.
This study investigated the reliability of the modified Tardieu scale in the assessment of biceps spasticity in the upper limbs of children with hemiplegic cerebral palsy (CP). Ten children, with hemiplegic CP participated in the study: six males (mean age 9 years, SD 4 years) and four females (mean age 12 years, SD 3 years). Blinded, duplicate measures of dynamic elbow extension were performed on the hemiplegic arm at time 0 and 7 days later, using the three angular velocities described in the Tardieu scale (V1, slow; V2, speed of gravity; V3, as fast as possible). The resulting elbow joint angles were defined as R1, the angle of catch following a fast velocity stretch at either V2 or V3; and R2, the passive range of movement achieved following a slow velocity stretch at V1. Both elbow joint angle and movement angular velocity were measured by three-dimensional kinematics. Median error in measured elbow joint angle within one session ranged from 3 to 5 degrees. Between sessions median absolute differences in measured elbow joint angle ranged from 4 to 13 degrees, with measurement errors of up to 25 to 30 degrees in some participants at the fastest velocity (V3). The therapist was able to apply three significantly different angular velocities as required for the Tardieu scale (p<0.001). However, the ranges of the three angular velocities overlapped, with fast velocities for some participants being equivalent to slow velocities for other participants. Three out of 10 participants had an intersessional difference in their R2-R1 score of more than 20 degrees. From this study, we concluded that the R2-R1 value determined from the modified Tardieu scale may be of limited value in assessing biceps spasticity the upper limbs in children with hemiplegic CP.


Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).
This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).


Combination Antifungal Therapy for Invasive Mold Infections Among Pediatric Patients with Hematological Malignancies: Data from A Real-Life Case-Series.
Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients' characteristics. Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.


Can the addition of Interleukin-13 affect the cryosurvival of bovine embryos?
In this study, we investigated the impact of incorporating Interleukin-13 (IL-13) into the embryonic culture medium and its influence on cryotolerance and cellular viability of vitrified bovine embryos. Two distinct time points for IL-13 supplementation were explored: during the final hours of culture prior to cryopreservation and during the period of recultivation following cryopreservation and warming. Cryosurvival rates, total cell count, and cell viability were assessed using the TUNEL technique to determine the apoptotic percentage. Re-expansion and hatching rates did not show differences among all groups (P > 0.05), and the total cell number was comparable between the treated and control groups (P > 0.05). However, the group that received IL-13 before vitrification exhibited a higher apoptotic percentage (P < 0.05). This suggests that the anti-inflammatory effect of IL-13 may have impacted the embryo's defense capacity against the stress induced by cryopreservation, leading to an increased percentage of apoptosis, although it did not influence the developmental resumption capability.


Evaluation of ELISA and electron microscopy for the detection of coronavirus and rotavirus in bovine faeces.
Enzyme-linked immunosorbent assay (ELISA) was compared with electron microscopy in the examination of faeces from experimental calves and showed 100 per cent agreement in the detection of 19 bovine coronavirus and 15 bovine rotavirus electron microscope positive samples. In a limited field survey of calf diarrhoea 75 selected faeces were examined independently by ELISA and electron microscopy and the agreement between the two tests was 95 per cent for coronavirus and 84 per cent for rotavirus. A further comparison was made with 74 samples submitted for routine diagnosis and this yielded agreements of 82 per cent (coronavirus) and 89 per cent (rotavirus). Factors contributing to discrepant results were examined and the relative advantages and disadvantages of the two tests for routine detection of these enteric viruses are discussed.


Prediction of pulmonary hypertension related to systemic sclerosis by an index based on simple clinical observations.
To develop a score to estimate the risk of developing pulmonary hypertension (PH) in patients with systemic sclerosis (SSc). We first examined the prevalence and characteristics of precapillary PH confirmed by right-heart catheterization in a cross-sectional (derivation) sample of 1,165 SSc patients, and we developed a risk prediction score (RPS) based on simple clinical observations associated with PH. We next prospectively tested the 3-year predictive power of the "Cochin RPS" in a separate (validation) sample of 443 patients presenting with PH-free SSc at baseline. In the derivation sample, age, forced vital capacity, and diffusing capacity for carbon monoxide/alveolar volume were independently associated with the presence of PH and were used to create the Cochin RPS. PH developed during followup in 20 patients in the validation sample. The area under the receiver operating characteristic curve of the Cochin RPS was 0.87 (95% confidence interval 0.79-0.95). With a cutoff value of 2.73, patients at risk of PH during followup could be identified with 89.5% sensitivity and 74.1% specificity. PH occurred in 0.6% of patients in the lowest 2 quintiles of the Cochin RPS, in 1.7% of patients in the third and fourth quintiles, and in 17.1% of patients in the highest quintile (P<0.0001 by log rank test). Patients in the highest quintile incurred a >35-fold higher risk of developing PH compared with patients in the 2 lowest quintiles (P=0.001). Using routine clinical observations, we developed a simple score that accurately predicted the risk of PH in SSc.


The not so innocent bystander: an unusual cause of progressive breathlessness.
This case report discusses a 76-year-old man who presented with symptomatic diffuse alveolar-septal and tracheobronchial amyloidosis with a low-grade monoclonal gammopathy. This patient had a combination of both symptomatic diffuse alveolar-septal interstitial disease and tracheobronchial amyloidosis, features that contradict the widely accepted presentations seen in this disease. First, tracheobronchial amyloidosis has been documented as localised disease without systemic involvement. Second, diffuse alveolar-septal interstitial disease is rarely identified with clinical symptoms unless there is significant cardiac involvement. This case highlights a number learning points in the diagnosis and management of systemic amyloid light chain amyloidosis;(1) There is a need for a high index of suspicion for diagnosis due to the potential subtlety of a plasma cell clone underlying AL amyloidosis, requiring serum-free light chain assays to increase sensitivity; (2) Haematological response and recovery of organ dysfunction are not a linear relationship due to the slower reversal of amyloid deposition; therefore, ongoing monitoring is required to identify those in need of repeated therapy. However, haematological response is a marker of overall survival and (3) Multisystem assessment and multidisciplinary collaboration are critical in optimising the care of patients with systemic AL amyloidosis.


Higher plant cortical microtubule array analyzed in vitro in the presence of the cell wall.
Plant morphogenesis depends on an array of microtubules in the cell cortex, the cortical array. Although the cortical array is known to be essential for morphogenesis, it is not known how the array becomes organized or how it functions mechanistically. Here, we report the development of an in vitro model that provides good access to the cortical array while preserving the array's organization and, importantly, its association with the cell wall. Primary roots of maize (Zea mays) are sectioned, without fixation, in a drop of buffer and then incubated as desired before eventual fixation. Sectioning removes cytoplasm except for a residuum comprising cortical microtubules, vesicles, and fragments of plasma membrane underlying the microtubules. The majority of the cortical microtubules remain in the cut-open cells for more than 1 h, fully accessible to the incubation solution. The growth zone or more mature tissue can be sectioned, providing access to cortical arrays that are oriented either transversely or obliquely to the long axis of the root. Using this assay, we report, first, that cortical microtubule stability is regulated by protein phosphorylation; second, that cortical microtubule stability is a function of orientation, with divergent microtubules within the array depolymerizing within minutes of sectioning; and third, that the polarity of microtubules in the cortical array is not uniform. These results suggest that the organization of the cortical array involves random nucleation followed by selective stabilization of microtubules formed at the appropriate orientation, and that the signal specifying alignment must treat orientations of +/- 180 degrees as equivalent.


Alcohol consumption in relation to breast cancer risk in a cohort of United States women 25-42 years of age.
We evaluated current and past alcohol consumption prospectively in relation to breast cancer risk among 116,671 women ages 25-42 years old at enrollment in 1989. During 6 years of follow-up, 445 cases of invasive breast cancer were identified. For alcohol consumption in the previous year, the multivariate relative risk associated with more than 20 g/day (approximately 10 drinks/week) was 1.23 (95% confidence interval, 0.68-2.21); the P for trend was 0.85. For average lifetime alcohol consumption, the multivariate relative risk associated with consumption of 10 or more drinks/week was 1.20 (95% confidence interval, 0.69-2.11); the P for trend was 0.18. We examined drinking in several time periods of life; only drinking at ages 23-30 was significantly positively associated with risk. Although this may represent a chance finding, it merits further study. Because drinking levels in this population were low, we had limited information on heavier drinking. Our results suggest that there is unlikely to be a large effect of moderate alcohol consumption on breast cancer risk among young women, although a modest effect cannot be excluded. The association between alcohol consumption and breast cancer is unlikely to be substantially stronger among premenopausal women than among postmenopausal women.


The Pregnancy and EARly Life study (PEARL) - a longitudinal study to understand how gut microbes contribute to maintaining health during pregnancy and early life.
The early life period represents the first step in establishing a beneficial microbial ecosystem, which in turn affects both short and longer-term health. Changes during pregnancy influence the neonatal microbiome; through transmission of maternal microbes during childbirth, and beyond, through nutritional programming. However, in-depth exploration of longitudinal maternal-infant cohorts, with sampling of multiple body sites, complemented by clinical and nutritional metadata, and use of cutting-edge experimental systems are limited. The PEARL study will increase our knowledge of; how microbes (including viruses/phages, bacteria, fungi and archaea) change in composition and functional capacity during pregnancy; transmission pathways from mother to infant; the impact of various factors on microbial communities across pregnancy and early life (e.g. diet), and how these microbes interact with other microbes and modulate host processes, including links to disease onset. PEARL is a longitudinal observational prospective study of 250 pregnant women and their newborns, with stool and blood samples, questionnaires and routine clinical data collected during pregnancy, labour, birth and up to 24 months post birth. Metagenomic sequencing of samples will be used to define microbiome profiles, and allow for genus, species and strain-level taxonomic identification and corresponding functional analysis. A subset of samples will be analysed for host (immune/metabolite) molecules to identify factors that alter the host gut environment. Culturing will be used to identify new strains of health-promoting bacteria, and potential pathogens. Various in vitro and in vivo experiments will probe underlying mechanisms governing microbe-microbe and microbe-host interactions. Longitudinal studies, like PEARL, are critical if we are to define biomarkers, determine mechanisms underlying microbiome profiles in health and disease, and develop new diet- and microbe-based therapies to be tested in future studies and clinical trials. This study is registered in the ClinicalTrials.gov Database with ID: NCT03916874 .


Platelet Reactivity Unit in Predicting Risk of Bleeding in Patients Undergoing Coronary Artery Bypass Graft Surgery.
Bleeding is a common complication of cardiac surgery, accounting for a significant proportion of the total transfusions performed in the United States and Europe. The relationship between platelet reactivity, bleeding, and other adverse events after coronary artery bypass graft surgery (CABGS) has been incompletely characterized. This study investigated the relationship between platelet reactivity and bleeding as a clinical outcome after successful CABGS. A total of 238 patients who underwent CABGS were retrospectively followed for postoperative bleeding. Platelet reactivity unit (PRU) values for all patients were obtained preoperatively to assess the platelet reactivity. The data showed that a range of 180-200 PRU suggests the likelihood of bleeding after CABGS (P = 0.004), with a statistically significant association only for dual antiplatelet therapy with aspirin and clopidogrel. In conclusion, by using PRU values as a method to assess platelet reactivity and antiplatelet responsiveness, our findings suggest that it may be possible to stratify patients undergoing CABGS for the risk of postoperative bleeding particularly patients on dual antiplatelet therapy.


[Chemoreceptor function and metabolism of the carotid body in the rat].
Using fluorimetric and polarographic determination of cell respiration, metabolic reactions of the carotid body of rats to adequate stimulation have been revealed. Functional relationships of the dose--effect type, which were found for these reactions, may be approximated by equations which are similar to those describing the unconditioned reflexes from the carotid chemoreceptors. However, reactions of the metabolics systems of the carotid body account for the perception of not all chemical stimuli, but only of acids and some alkaloids. These data reveal the heteregeneity of the carotid chemosensory system not only in the amphibians (which was known earlier), but in mammals as well.


A Novel Surgical Technique for Patellar Fracture: Application of Extra-articular Arthroscopy With Hanger-Lifting Procedure.
We describe a novel operative technique for patellar fracture. The patient is placed in the supine position for setup of both an image intensifier and arthroscopy. After routine intra-articular inspection with an arthroscope, an extra-articular space including the prepatellar bursa is developed. The space is created with a lifting hanger applied from a portal wherein an arthroscope can then afford both intra- and extra-articular observation of the articular and bony surface of the patella. By use of an image intensifier, the fracture can be treated and fixed in percutaneous fashion with the aid of an arthroscope. This new technique offers surgeons a magnified view of the patella, both intra- and extra-articularly, through a minimally invasive procedure. Although it includes inherent risks and limitations, this new application of arthroscopy would certainly help surgeons to treat patellar fracture.


A facile synthesis of perforated reduced graphene oxide for high performance electrochemical sensors.
Highly active perforated reduced graphene oxide (P-rGO) was synthesized by a facile methodology based on co-deposition of graphene oxide with sacrificial Prussian blue. Electrode surface properties were characterized by SEM and EDS. The GC/P-rGO electrode exhibited a larger specific surface area than that of GCE. These findings highlighted that the signal was enhanced for both dopamine detection and selenium detection by using P-rGO as a relevant supporting substrate. The result indicated that the large number of perforated structures formed numerous electrically conductive channels in the structure, improving the electrocatalytic properties.


The Association of Preoperative Opioid Usage With Patient-Reported Outcomes, Adverse Events, and Return to Work After Lumbar Fusion: Analysis From the Michigan Spine Surgery Improvement Collaborative (MSSIC).
It is important to delineate the relationship between opioid use and spine surgery outcomes. To determine the association between preoperative opioid usage and postoperative adverse events, patient satisfaction, return to work, and improvement in Oswestry Disability Index (ODI) in patients undergoing lumbar fusion procedures by using 2-yr data from a prospective spine registry. Preoperative opioid chronicity from 8693 lumbar fusion patients was defined as opioid-naïve (no usage), new users (<6 wk), short-term users (6 wk-3 mo), intermediate-term users (3-6 mo), and chronic users (>6 mo). Multivariate generalized estimating equation models were constructed. All comparisons were to opioid-naïve patients. Chronic opioid users showed less satisfaction with their procedure at 90 d (Relative Risk (RR) 0.95, P = .001), 1 yr (RR 0.89, P = .001), and 2 yr (RR 0.89, P = .005). New opioid users were more likely to show improvement in ODI at 90 d (RR 1.25, P < .001), 1 yr (RR 1.17, P < .001), and 2 yr (RR 1.19, P = .002). Short-term opioid users were more likely to show ODI improvement at 90 d (RR 1.25, P < .001). Chronic opioid users were less likely to show ODI improvement at 90 d (RR 0.90, P = .004), 1 yr (RR 0.85, P < .001), and 2 yr (RR 0.80, P = .003). Chronic opioid users were less likely to return to work at 90 d (RR 0.80, P < .001). In lumbar fusion patients and when compared to opioid-naïve patients, new opioid users were more likely and chronic opioid users less likely to have improved ODI scores 2 yr after surgery. Chronic opioid users are less likely to be satisfied with their procedure 2 yr after surgery and less likely to return to work at 90 d. Preoperative opioid counseling is advised.


Features of Chaotic Transients in Excitable Media Governed by Spiral and Scroll Waves.
In excitable media, chaotic dynamics governed by spiral or scroll waves is often not persistent but transient. Using extensive simulations employing different mathematical models we identify a specific type-II supertransient by an exponential increase of transient lifetimes with the system size in 2D and an investigation of the dynamics (number and lifetime of spiral waves, Kaplan-Yorke dimension). In 3D, simulations exhibit an increase of transient lifetimes and filament lengths only above a critical thickness. Finally, potential implications for understanding cardiac arrhythmias are discussed.


Expression of the alpha 5 beta 1 fibronectin receptor on T lymphocytes of patients with HIV-1 infection.
To evaluate the expression of the alpha 5 beta 1 integrin fibronectin receptor (FNR), which mediates several processes, including phagocytosis, cell motility and the immune response, on T lymphocytes of patients with HIV-1 infection. T lymphocytes were incubated with monoclonal antibody directed against FNR and then with monoclonal antibodies, conjugated with phycoerythrin, directed against CD3, CD4 and CD8 positive cells. Expression of FNR on CD3, CD4 and CD8 positive cells was analysed using flow cytometry. Normal expression of FNR was observed on CD3 positive cells from asymptomatic HIV positive patients and those with AIDS. Increased expression of FNR was observed on CD8 positive cells from asymptomatic HIV positive patients and on CD4 positive cells from patients with AIDS. Increased FNR expression was observed on CD4 positive cells from patients with AIDS, particularly those with opportunistic infections caused by Pneumocystis carinii, Mycobacterium sp, Toxoplasma gondii, and Cryptococcus neoformans. Increased expression of FNR on CD8 and CD4 positive cells in asymptomatic HIV positive patients and those with AIDS, respectively, may be an epiphenomenon correlated with lymphocyte activation by HIV-1 or opportunistic infection, Further study is required to determine whether upregulation of FNR expression has a direct role in the pathogenesis of AIDS.


[Instrument for patient classification: users' opinions and analisys of healthcare indicators].
This descriptive study was aimed at: 1.) investigating the users' opinions about an instrument for patient classification; 2.) analyzing the healthcare indicators that most contribute to classify patients in the healthcare categories. A questionnaire was used to collect the opinions of 24 users. The classification instrument was applied on 796 patients in a medical school hospital in the state of São Paulo, from September 2006 to May, 2007. Principal Components Analysis (PCA) and Discriminant Analysis were used for statistical analysis. Overall, the investigated users were satisfied with the instrument; however, they pointed out a certain tendency of the instrument to underestimate the nursing care category to which the patients belonged. The results revealed some healthcare indicators such as Therapy, Personal Hygiene, Skin Integrity and Health Education as the greatest discriminating care categories. The effective classification varied from 89.8% (semi-intensive care) to 95.6% (intensive care).


Behavioural responses of free-ranging Asian elephants (Elephas maximus) towards dying and dead conspecifics.
Reactions to dying and dead conspecifics have been observed in many non-human animals. Elephants, particularly African elephants, are thought to have an awareness of the death of their conspecifics, as they show compassionate behaviour towards others in distress. However, there is a paucity of scientific documentation on thanatological responses displayed by Asian elephants. Here, we report three detailed, directly observed cases of free-ranging Asian elephants (Elephas maximus) responding to dying and dead conspecifics. Behavioural responses were recorded opportunistically and described as pre-, peri- and post-mortem phases based on the status of the individual before, near or after its death. In all three observations, elephants showed approach and exploratory (sniffing and inspecting) behaviours, and epimeletic or helping (physically supporting dying calves) in pre- and peri-mortem phases. We also recorded high-frequency vocalizations (trumpets) by an adult female in the presence of a dying calf. Our observations indicate that, like their African counterparts, Asian elephants might experience distress in response to the death of conspecifics, and may have some awareness of death. This information furthers our understanding of the emotional and cognitive complexities of highly social elephants, and contributes to the growing field of elephant thanatology.


Fragmentation dynamics of the ethyl bromide and ethyl iodide cations: a velocity-map imaging study.
The photodissociation dynamics of ethyl bromide and ethyl iodide cations (C2H5Br(+) and C2H5I(+)) have been studied. Ethyl halide cations were formed through vacuum ultraviolet (VUV) photoionization of the respective neutral parent molecules at 118.2 nm, and were photolysed at a number of ultraviolet (UV) photolysis wavelengths, including 355 nm and wavelengths in the range from 236 to 266 nm. Time-of-flight mass spectra and velocity-map images have been acquired for all fragment ions and for ground (Br) and spin-orbit excited (Br*) bromine atom products, allowing multiple fragmentation pathways to be investigated. The experimental studies are complemented by spin-orbit resolved ab initio calculations of cuts through the potential energy surfaces (along the RC-Br/I stretch coordinate) for the ground and first few excited states of the respective cations. Analysis of the velocity-map images indicates that photoexcited C2H5Br(+) cations undergo prompt C-Br bond fission to form predominantly C2H5(+) + Br* products with a near-limiting 'parallel' recoil velocity distribution. The observed C2H3(+) + H2 + Br product channel is thought to arise via unimolecular decay of highly internally excited C2H5(+) products formed following radiationless transfer from the initial excited state populated by photon absorption. Broadly similar behaviour is observed in the case of C2H5I(+), along with an additional energetically accessible C-I bond fission channel to form C2H5 + I(+) products. HX (X = Br, I) elimination from the highly internally excited C2H5X(+) cation is deemed the most probable route to forming the C2H4(+) fragment ions observed from both cations. Finally, both ethyl halide cations also show evidence of a minor C-C bond fission process to form CH2X(+) + CH3 products.


Microglial and astroglial cells in the rat paraclaustral reservoir during postnatal development: an immunohistochemical study.
A immunohistochemical study of postnatal development of the paraclaustral reservoir of migrating cells in the rat brain was performed using anti-GFAP (for astroglia), ED1 and OX-42 (for microglia) antibodies. From birth to the 4th day of postnatal life most GFAP-positive cells in the paraclaustral reservoir are similar to transitional astroglia. From the end of the first postnatal week they have the morphology of mature astrocytes, although during the next week, their density was a slightly higher than in neighboring structures. On the 21st day, the morphology and density of astroglial cells in the ventral part of the external capsule did not differ from the surrounding regions. ED1/OX-42- positive microglial cells present in the paraclaustral reservoir during the first postnatal week represented ameboid microglia; their density was clearly higher than in the neighboring structures. During the second week they began to transform into ramified microglia and from the 21st day on, only OX-42 positive resting microglial cells were observed in the ventral part of the external capsule. We suggest that the paraclaustral reservoir is a place of accumulation of astroglia and microglia during brain development and may possibly serve as source of glial cells for neighboring structures. Alternatively, these glial populations may perform local developmental functions.


Exploring the opinions of registered nurses working in a clinical transfusion environment on the contribution of e-learning to personal learning and clinical practice: results of a small scale educational research study.
To explore the opinions of registered nurses on the Learnbloodtransfusion Module 1: Safe Transfusion Practice e-learning programme to meeting personal learning styles and learning needs. A qualitative research methodology was applied based on the principles of phenomenology. Adopting a convenience sampling plan supported the recruitment of participants who had successfully completed the e-learning course. Thematic analysis from the semi-structured interviews identified common emerging themes through application of Colaizzis framework. Seven participants of total sample population (89) volunteered to participate in the study. Five themes emerged which included learning preferences, interactive learning, course design, patient safety and future learning needs. Findings positively show the e-learning programme captures the learning styles and needs of learners. In particular, learning styles of a reflector, theorist and activist as well as a visual learner can actively engage in the online learning experience. In an attempt to bridge the knowledge practice gap, further opinions are offered on the course design and the application of knowledge to practice following completion of the course. The findings of the small scale research study have shown that the e-learning course does meet the diverse learning styles and needs of nurses working in a clinical transfusion environment. However, technology alone is not sufficient and a blended approach to learning must be adopted to meet bridging the theory practice gap supporting the integration of knowledge to clinical practice.


Sterols and fatty acid biomarkers as indicators of changes in soil microbial communities in a uranium mine area.
Included in the 2nd tier of a site specific risk assessment that is being carried out in an abandoned uranium mine (Cunha Baixa uranium mine, Central Portugal), fatty acids biomarkers and sterols were analyzed to assess the impact of soil contamination with metals and radionuclides in the structure of the microbial community in seven sampling sites located at different distances from the mine. Surface soil samples were collected in those sampling sites in the four different seasons of the year. Principal component analysis (PCA) was performed on fatty acid biomarkers and sterols. Subsequently PCA scores obtained for both components were used to test the effect of sites and seasons, on soil samples collected in the Cunha Baixa uranium mine, through bi-factorial ANOVAs. Through PCA analysis, two distinct groups were set apart along the first two components. One group included sites at a great distance from the mine which were negatively correlated with higher contents of iC15:0 and iC17:0, both indicators of Gram-positive bacteria, as well as with ergosterol, cholestanol and cholesterol. The second group, in turn, was composed of the sampling sites most impacted by ore exploration, in situ leaching of poor ore, and spread of sludge from the effluent treatment pond. These sites were positively correlated with higher levels of iC16:0 (Gram-positive bacteria indicator), cyC17:0 (generally common in gram negative bacteria) and C18:0 and C17:0 biomarkers of non-specific bacteria. The profile of fatty acids obtained in the sampling sites revealed variable predominance of groups of bacteria which are a clear indication of differences in the soil microbial communities that are directly related to the environmental conditions prevailing in the uranium mine area.


Size constrains oxygen delivery capacity within but not between bumble bee castes.
Bumble bees are eusocial, with distinct worker and queen castes that vary strikingly in size and life-history. The smaller workers rely on energetically-demanding foraging flights to collect resources for rearing brood. Queens can be 3 to 4 times larger than workers, flying only for short periods in fall and again in spring after overwintering underground. These differences between castes in size and life history may be reflected in hypoxia tolerance. When oxygen demand exceeds supply, oxygen delivery to the tissues can be compromised. Previous work revealed hypermetric scaling of tracheal system volume of worker bumble bees (Bombus impatiens); larger workers had much larger tracheal volumes, likely to facilitate oxygen delivery over longer distances. Despite their much larger size, queens had relatively small tracheal volumes, potentially limiting their ability to deliver oxygen and reducing their ability to respond to hypoxia. However, these morphological measurements only indirectly point to differences in respiratory capacity. To directly assess size- and caste-related differences in tolerance to low oxygen, we measured critical PO2 (Pcrit; the ambient oxygen level below which metabolism cannot be maintained) during both rest and flight of worker and queen bumble bees. Queens and workers had similar Pcrit values during both rest and flight. However, during flight in oxygen levels near the Pcrit, mass-specific metabolic rates declined precipitously with mass both across and within castes, suggesting strong size limitations on oxygen delivery, but only during extreme conditions, when demand is high and supply is low. Together, these data suggest that the comparatively small tracheal systems of queen bumble bees do not limit their ability to deliver oxygen except in extreme conditions; they pay little cost for filling body space with eggs rather than tracheal structures.


[Popper and the problem of induction in epidemiology].
In this article we are discussing a few of the contributions by the Austro-British philosopher Karl R. Popper, one of our most influential contemporary thinkers, whose epistemological and socio-political theories have also penetrated the sphere of epidemiology. We are focusing mainly on the so-called problem of induction. We sustain, in line with Popper, that the scientific method does not use inductive reasoning, but rather hypothetical-deductive reasoning. Although the movement from the data evaluating a hypothesis to a conclusion on the latter goes from the specific to the general, that is, in an inductive direction, the induction does not exist as a reasoning process or inference. That is, there is no method that enables us to infer or to verify hypotheses or theories (we cannot explore all of the possible situations to see whether the theory stands up), or even to render them very probable. Besides, scientists look for highly informative theories, not highly probable ones. What we actually do is to propose a hypothesis as a tentative solution to a problem, to confront the prediction deduced from the hypothesis with actual experience, and evaluate whether the hypothesis is rejected or not by the facts. As theories cannot be verified, we can only accept them if they withstand an attempt to reject them. Consequently, the test of a theory consists of criticism or a serious attempt at falsification, that is, the elimination of error within a theory, in order to reject it if it is false. The objective is, thus, the search for true theories. For this purpose, the scientific method uses a systematic set of methodological (not logical) rules, that is, decisions. These methodological rules or principles can be summed up in two: [symbol: see text]be inventive and critical!, that is, propose bold hypotheses and subject them to severe tests of experience. Logic plays its role mainly by allowing us to deduce from a hypothesis the predictions to be confronted with the facts or evidence. This is applicable both to statistical inference as well as to causal inference. We argue that the criteria of causality used in epidemiology are none other than rules of the method designed for the same purpose: they are concerned with eliminating or reducing errors (chance, bias...) on testing a causal hypothesis. Consequently, the so-called ausal inference, the step from evidence to causal theory, is not a logical inductive or probabilistic process but rather a decision based on the evaluation of a causal hypothesis thanks to methodological rules such as the criteria of causality. We believe that the interest of the debate between the Popperian and the inductivist epidemiologists is not merely a matter of words, as, if we are aware that we do not operate inductively, that we cannot establish firmly hypotheses, not even affirm them probabilistically, we will presumably adopt a humbler attitude and look more for the errors in our theories than for their facile examples of confirmation.


Latino beliefs about biomedical research participation: a qualitative study on the U.S.-Mexico border.
Latinos are under-represented in biomedical research conducted in the United States, impeding disease prevention and treatment efforts for this growing demographic group. We gathered perceptions of biomedical research and gauged willingness to participate through elicitation interviews and focus groups with Latinos living on the U.S.-Mexico border. Themes that emerged included a strong willingness to participate in biomedical studies and suggested that Latinos may be under-represented due to limited formal education and access to health information, not distrust. The conflation of research and clinical care was common and motivated participation. Outreach efforts and educational interventions to inform Latinos of participation opportunities and clarify harms and benefits associated with biomedical research participation will be essential to maintain trust within Latino communities.


An aqueous formulation of gamma-linolenic acid with anti-proliferative action on human pancreatic cancer cell lines.
Essential fatty acids, especially gamma-linolenic acid (GLA), have been shown to directly inhibit the growth of cancer cell lines in culture. The aim of this study was to see whether an aqueous formulation of GLA works as well as the lithium-based salt. We evaluated the effect of the 1-deoxy-1-methylamino-D-glucitol salt of GLA (MeGLA) on the growth of two human pancreatic cancer cell lines (Panc-1 and MIA PaCa-2) in vitro, and compared its effects with a previously studied formulation, lithium GLA (LiGLA). The effect of time exposure (2-7 days) and difference in concentration (0-1000 micromol/l) were studied using 96-well culture plates. Cell growth was assessed by MTT assay. Control experiments were performed with meglumine alone in similar concentrations. MeGLA had cytostatic and cytotoxic effects on pancreatic cancer cell lines with 50% growth inhibition at 30-100 micromol/l and cytotoxic effects at 60-250 micromol/l. The degree of growth inhibition increased with time of exposure to MeGLA. The anti-proliferative effects of MeGLA were similar to those previously observed with LiGLA. We conclude that MeGLA has equivalent anti-proliferative activity to LiGLA when tested in vitro against pancreatic cancer cell lines and is therefore a suitable alternative to LiGLA for investigation of the in vivo activity of GLA against pancreatic adenocarcinomas.