The effect of increased functional load on the activation of satellite cells in the skeletal muscle of adult rats.
The comparison of the number of satellite cells in the fast oxidative glycolytic muscle fibers of m. quadriceps femoris in males of normal Wistar rats aged 16-17 weeks (5 animals) and rats trained for endurance (5 animals) was made. After six weeks of treadmill running at a speed of 35 m/min in an increasing regimen, the number of satellite cells in trained animals (9.59 +/- 1.09%) increased over 2.5-fold in comparison to controls (3.41 +/- 0.26%) within 24 hours. At the ultrastructural level complete and focal injuries of some muscle fibers and the partial denervation of individual muscle fibers were recorded in trained rats. It was proposed that the focal functional denervation of muscle fibers could be one of the factors for the activation of satellite cells in endurance exercise. Some trained rats demonstrated small groups of extra- and perisynaptic satellite cells under the basal membrane of muscle fibres, partial detachment of satellite cells from the surface of muscle fiber and presence in the interstitial space cell containing filaments.


Inflammatory bowel disease and risk of severe COVID-19: A nationwide population-based cohort study in Sweden.
There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD). This population-based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969-2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD-unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory-confirmed COVID-19 as the primary diagnosis, and (ii) severe COVID-19 (composite outcome consisting of (a) COVID-19 intensive care admission, or (b) death from COVID-19 or (c) death within 30 days of COVID-19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities. Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID-19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19-1.72). The corresponding numbers for severe COVID-19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81-1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score-matched model taking comorbidity into account until 2016, the increased risk for COVID-19 hospital admission remained (aHR = 1.32; 1.12-1.56), but there was no increased risk of severe COVID-19 (aHR = 1.12; 0.85-1.47). While individuals with IBD were more likely to be admitted to hospital for COVID-19 than the general population, the risk of severe COVID-19 was not higher.


Transfer of children with isolated linear skull fractures: is it worth the cost?
OBJECTIVE Children with skull fractures are often transferred to hospitals with pediatric neurosurgical capabilities. Historical data suggest that a small percentage of patients with an isolated skull fracture will clinically decline. However, recent papers have suggested that the risk of decline in certain patients is low. There are few data regarding the financial costs associated with transporting patients at low risk for requiring specialty care. In this study, the clinical outcomes and financial costs of transferring of a population of children with isolated skull fractures to a Level 1 pediatric trauma center over a 9-year period were analyzed. METHODS A retrospective review of all children treated for head injury at Riley Hospital for Children (Indianapolis, Indiana) between 2005 and 2013 was performed. Patients with a skull fracture were identified based on ICD-9 codes. Patients with intracranial hematoma, brain parenchymal injury, or multisystem trauma were excluded. Children transferred to Riley Hospital from an outside facility were identified. The clinical and radiographic outcomes were recorded. A cost analysis was performed on patients who were transferred with an isolated, linear, nondisplaced skull fracture. RESULTS Between 2005 and 2013, a total of 619 pediatric patients with isolated skull fractures were transferred. Of these, 438 (70.8%) patients had a linear, nondisplaced skull fracture. Of these 438 patients, 399 (91.1%) were transferred by ambulance and 39 (8.9%) by helicopter. Based on the current ambulance and helicopter fees, a total of $1,834,727 (an average of $4188.90 per patient) was spent on transfer fees alone. No patient required neurosurgical intervention. All patients recovered with symptomatic treatment; no patient suffered late decline or epilepsy. CONCLUSIONS This study found that nearly $2 million was spent solely on transfer fees for 438 pediatric patients with isolated linear skull fractures over a 9-year period. All patients in this study had good clinical outcomes, and none required neurosurgical intervention. Based on these findings, the authors suggest that, in the absence of abuse, most children with isolated, linear, nondisplaced skull fractures do not require transfer to a Level 1 pediatric trauma center. The authors suggest ideas for further study to refine the protocols for determining which patients require transport.


Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner.
Physical forces arising in the extra-cellular environment have a profound impact on cell fate and gene regulation; however the underlying biophysical mechanisms that control this sensitivity remain elusive. It is hypothesized that gene expression may be influenced by the physical deformation of the nucleus in response to force. Here, using 3T3s as a model, we demonstrate that extra-cellular forces cause cell nuclei to rapidly deform (<1 s) preferentially along their shorter nuclear axis, in an anisotropic manner. Nuclear anisotropy is shown to be regulated by the cytoskeleton within intact cells, with actin and microtubules resistant to orthonormal strains. Importantly, nuclear anisotropy is intrinsic, and observed in isolated nuclei. The sensitivity of this behaviour is influenced by chromatin organization and lamin-A expression. An anisotropic response to force was also highly conserved amongst an array of examined nuclei from differentiated and undifferentiated cell types. Although the functional purpose of this conserved material property remains elusive, it may provide a mechanism through which mechanical cues in the microenvironment are rapidly transmitted to the genome.


Clinical experience in the management of pulmonary opportunist infection and rejection in recipients of heart-lung transplants.
The main clinical problems that follow heart-lung transplantation are opportunist infections of the lungs and pulmonary rejection. Of 23 patients undergoing heart-lung transplantation, eight had opportunist infections and 12 had at least one episode of pulmonary rejection. Cardiac rejection occurred in only one patient, who did not need treatment. Of the 12 patients who had pulmonary rejection, nine recovered fully after augmented immunosuppression with high dose corticosteroids, although one patient required additional low dose corticosteroids for eight months before making a full recovery. Fatal opportunist lung infection followed treatment for rejection in two patients. One patient developed obliterative bronchiolitis. Of the eight patients with opportunist infections, five had primary cytomegalovirus pneumonitis, acquired from the donor. All three patients treated with acyclovir died, whereas the two treated with hyperimmune globulin and dihydroxy proxymethylguanine recovered fully. Two patients developed Pneumocystis carinii pneumonia, which was treated successfully in one patient with intravenous sulphadimidine and trimethoprim. The other patient died after a further episode of rejection and aspergillus bronchitis. One patient developed a tuberculous empyema. The calculated actuarial survival at one year was 78% and at two years 67.2%. Although it is still in its innovative stage heart-lung transplantation appears to have complications and results similar to those of transplantation of other organs.


Recent Technical Developments in ASL: A Review of the State of the Art.
This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.


Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty.
This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure. Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted. We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed. Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%). Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH.


Must insurance payments made in error be returned?
Healthcare organizations sometimes receive payments made in error from insurance companies. Such payments may occur when insurance companies do not determine that a person receiving care was not covered until after the care has been provided and the bill has been paid. A review of pertinent cases in this area suggests that a legal precedent exists for viewing a healthcare organization as an innocent third-party creditor, thus absolving it of the responsibility to return the mistaken payment.


Multifunctional acetyl-CoA carboxylase 1 is essential for very long chain fatty acid elongation and embryo development in Arabidopsis.
Acetyl-CoA carboxylase (ACCase) catalyses the carboxylation of acetyl-CoA, forming malonyl-CoA, which is used in the plastid for fatty acid synthesis and in the cytosol in various biosynthetic pathways including fatty acid elongation. In Arabidopsis thaliana, ACC1 and ACC2, two genes located in a tandem repeat within a 25-kbp genomic region near the centromere of chromosome 1, encode two multifunctional ACCase isoforms. Both genes, ACC1 and ACC2, appear to be ubiquitously expressed, but little is known about their respective function and importance. Here, we report the isolation and characterisation of two allelic mutants disrupted in the ACC1 gene. Both acc1-1 and acc1-2 mutations are recessive and embryo lethal. Embryo morphogenesis is impaired and both alleles lead to cucumber-like structures lacking in cotyledons, while the shortened hypocotyl and root exhibit a normal radial pattern organisation of the body axis. In this abnormal embryo, the maturation process still occurs. Storage proteins accumulate normally, while triacylglycerides (TAG) are synthesised at a lower concentration than in the wild-type seed. However, these TAG are totally devoid of very long chain fatty acids (VLCFA) and consequently enriched in C18:1, like all lipid fractions analysed in the mutant seed. These data demonstrate, in planta, the role of ACCase 1 in VLCFA elongation. Furthermore, this multifunctional enzyme also plays an unexpected and central function in embryo morphogenesis, especially in apical meristem development.


Neisseria meningitidis accumulate in large organs during meningococcal sepsis.
Neisseria meningitidis (Nm) is the cause of epidemic meningitis and fulminant meningococcal septicemia. The clinical presentations and outcome of meningococcal septic shock is closely related to the circulating levels of lipopolysaccharides (LPS) and of Neisseria meningitidis DNA (Nm DNA). We have previously explored the distribution of Nm DNA in tissues from large organs of patients dying of meningococcal septic shock and in a porcine meningococcal septic shock model. 1) To explore the feasibility of measuring LPS levels in tissues from the large organs in patients with meningococcal septic shock and in a porcine meningococcal septic shock model. 2) To evaluate the extent of contamination of non-specific LPS during the preparation of tissue samples. Plasma, serum, and fresh frozen (FF) tissue samples from the large organs of three patients with lethal meningococcal septic shock and two patients with lethal pneumococcal disease. Samples from a porcine meningococcal septic shock model were included. Frozen tissue samples were thawed, homogenized, and prepared for quantification of LPS by Pyrochrome® Limulus Amoebocyte Lysate (LAL) assay. N. meningitidis DNA and LPS was detected in FF tissue samples from large organs in all patients with meningococcal septic shock. The lungs are the organs with the highest LPS and Nm DNA concentration followed by the heart in two of the three meningococcal shock patients. Nm DNA was not detected in any plasma or tissue sample from patients with lethal pneumococcal infection. LPS was detected at a low level in all FF tissues from the two patients with lethal pneumococcal disease. The experimental porcine meningococcal septic shock model indicates that also in porcinis the highest LPS and Nm DNA concentration are detected in lungs tissue samples. The quantification analysis showed that the highest concentration of both Nm DNA and LPS are in the organs and not in the circulation of patients with lethal meningococcal septic shock. This was also shown in the experimental porcine meningococcal septic shock model. Our results suggest that LPS can be quantified in mammalian tissues by using the LAL assay.


[Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010].
Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4). Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.


Entacapone and prostate cancer risk in patients with Parkinson's disease.
The association between Parkinson's disease (PD) and prostate cancer, both common in elderly men, is disputable. In the STRIDE-PD study, prostate cancer developed in 9 patients (3.7%) receiving levodopa/carbidopa with entacapone, a catechol-O-methyltransferase inhibitor, versus 2 cases (0.9%) without entacapone. The current pharmacoepidemiological study aimed to determine whether entacapone increases prostate cancer incidence or mortality in PD patients and whether cumulative exposure affects these rates. We performed a retrospective cohort study using population-wide health care registers with patient-level linkage. Prostate cancer incidence and mortality were modeled by Cox's proportional hazards models. Use of entacapone with l-dopa/dopa decarboxylase inhibitor caused no increased risk of prostate cancer incidence (hazard ratio [HR]: 1.05; 95% confidence interval: 0.76-1.44) or mortality (0.93; 0.43-1.98). The HR for cumulative entacapone use of >360 days versus never-use was 0.82 (0.56-1.18) for prostate cancer incidence and 1.27 (0.60-2.72) for prostate cancer mortality.


Energy homeostasis and gastrointestinal endocrine differentiation do not require the anorectic hormone peptide YY.
The gastrointestinal hormone peptide YY is a potent inhibitor of food intake and is expressed early during differentiation of intestinal and pancreatic endocrine cells. In order to better understand the role of peptide YY in energy homeostasis and development, we created mice with a targeted deletion of the peptide YY gene. All intestinal and pancreatic endocrine cells developed normally in the absence of peptide YY with the exception of pancreatic polypeptide (PP) cells, indicating that peptide YY expression was not required for terminal differentiation. We used recombination-based cell lineage trace to determine if peptide YY cells were progenitors for gastrointestinal endocrine cells. Peptide YY(+) cells gave rise to all L-type enteroendocrine cells and to islet partial differential and PP cells. In the pancreas, approximately 40% of pancreatic alpha and rare beta cells arose from peptide YY(+) cells, suggesting that most beta cells and surprisingly the majority of alpha cells are not descendants of peptide YY(+)/glucagon-positive/insulin-positive cells that appear during early pancreagenesis. Despite the anorectic effects of exogenous peptide YY(3-36) following intraperitoneal administration, mice lacking peptide YY showed normal growth, food intake, energy expenditure, and responsiveness to peptide YY(3-36). These observations suggest that targeted disruption of the peptide YY gene does not perturb terminal endocrine cell differentiation or the control of food intake and energy homeostasis.


46,XY Sex Development Defect due to a Novel Homozygous (Splice Site) c.673_1G>C Variation in the HSD17B3 Gene: Case Report
The enzyme 17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the biosynthesis of testosterone (T) from Δ4-androstenedione, and plays an important role in the final steps of androgen synthesis. 17β-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46,XY sex developmental disorder (DSD). Patients with 46,XY karyotype can exhibit a wide phenotypic spectrum, varying from complete external female genitalia to male genitalia with hypospadias. Here we report a case of 17β-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel HSD17B3 gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum T, a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The consanguineous parents were sequenced, and both were heterozygous for the same mutation. This variation has not been previously reported in the literature. In conclusion, a 46,XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age. Furthermore, in patients with insufficient T synthesis and high levels of androstenedione, 17β-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.


Statistical inference and model selection for the 1861 Hagelloch measles epidemic.
A stochastic epidemic model is proposed which incorporates heterogeneity in the spread of a disease through a population. In particular, three factors are considered: the spatial location of an individual's home and the household and school class to which the individual belongs. The model is applied to an extremely informative measles data set and the model is compared with nested models, which incorporate some, but not all, of the aforementioned factors. A reversible jump Markov chain Monte Carlo algorithm is then introduced which assists in selecting the most appropriate model to fit the data.


Perception of Biomedical Engineering Students' Contribution to Course Projects During Pandemic.
One of the main challenges in the team-based project assessment is to evaluate the student's individual contributions, especially when the students work remotely during the Covid-19 pandemic. In this study, the student's perception of their teammates' contribution to the course project will be examined. This study will focus on assessing the soft skills aspect, such as the student's role, commitment, responsibility and awareness in a team. 42 students that are participated in the course will fill out an end-semester questionnaire. In general, students assess themselves in a more lenient than their teammates. Furthermore, the students tend to have a low profile in assessing themselves. It can be interpreted that they tend to have low self-confidence about their role in a team. Therefore, the results of this study can be used to improve the course project implementation, especially to assist the students in having higher confidence in their ability, capability and role in a group-based project. In addition, this study also shows that the instructor should not only rely on student peers' assessment and self-assessment.


Hepatitis C incidence--a comparison between injection and noninjection drug users in New York City.
Hepatitis C virus (HCV) burdens injection drug users (IDUs) with prevalence estimated from 60-100% compared to around 5% among noninjection drug users (non-IDUs). We present preliminary data comparing the risk for HCV among IDUs and non-IDUs to inform new avenues of HCV prevention and intervention planning. Two cohorts, new IDUs (injecting < or =3 years) and non-IDUs (smoke/sniff heroine, crack or cocaine < or =10 years), ages 15-40, were street-recruited in New York City. Participants underwent risk surveys and HCV serology at baseline and 6-month follow-up visits. Person-time analysis was used to estimate annual HCV incidence. Of 683 non-IDUs, 653 were HCV seronegative, 422 returned for at least 1 follow-up visit, and 1 became HCV seropositive. Non-IDUs contributed 246.3 person-years (PY) yielding an annual incident rate of 0.4/100 PY (95% Confidence Interval [CI]=0.0-1.2). Of 260 IDUs, 114 were HCV seronegative, 62 returned for at least 1 follow-up visit, and 13 became HCV seropositive. IDUs contributed 36.3 PY yielding an annual incidence rate of 35.9/100 PY (95%CI=19.1-61.2). Among IDUs, HCV seroconverters tended to be younger (median age 25 vs. 28, respectively), and inject more frequently (61.5% vs. 34.7%, respectively) than non-seroconverters. These interim data suggest that IDUs may have engaged in high-risk practices prior to being identified for prevention services. Preventing or at least delaying transition into injection could increase opportunity to intervene. Identifying risk factors for transition into injection could inform early prevention to reduce onset of injection and risk of HCV.


PLBD: protein-ligand binding database of thermodynamic and kinetic intrinsic parameters.
We introduce a protein-ligand binding database (PLBD) that presents thermodynamic and kinetic data of reversible protein interactions with small molecule compounds. The manually curated binding data are linked to protein-ligand crystal structures, enabling structure-thermodynamics correlations to be determined. The database contains over 5500 binding datasets of 556 sulfonamide compound interactions with the 12 catalytically active human carbonic anhydrase isozymes defined by fluorescent thermal shift assay, isothermal titration calorimetry, inhibition of enzymatic activity and surface plasmon resonance. In the PLBD, the intrinsic thermodynamic parameters of interactions are provided, which account for the binding-linked protonation reactions. In addition to the protein-ligand binding affinities, the database provides calorimetrically measured binding enthalpies, providing additional mechanistic understanding. The PLBD can be applied to investigations of protein-ligand recognition and could be integrated into small molecule drug design. Database URL https://plbd.org/.


Angiotensin-converting enzyme inhibitors and change in aortic valve calcium.
Calcium accumulation in the aortic valve is a hallmark of aortic sclerosis and aortic stenosis. Because lipoproteins, angiotensin-converting enzyme, and angiotensin II colocalize with calcium in aortic valve lesions, we hypothesized an association between angiotensin-converting enzyme inhibitor (ACEI) use and lowered aortic valve calcium (AVC) accumulation, as measured by electron beam computed tomography. Rates of change in volumetric AVC scores were determined retrospectively for 123 patients who had undergone 2 serial electron beam computed tomographic scans. The mean (+/-SD) interscan interval was 2.5 (+/-1.7) years; 80 patients did not receive ACEIs and 43 received ACEIs. The relationship of ACEI use to median rates of AVC score change (both unadjusted and adjusted for baseline AVC scores and coronary heart disease risk factors) was determined. We also examined the relationship of ACEI use to the likelihood of and adjusted odds ratio for definite progression (AVC change >2 times the median interscan variability). Unadjusted and adjusted median rates of AVC score change were significantly higher in the no-ACEI group than in the ACEI group (adjusted median AVC changes [95% confidence interval]: relative, 28.7%/y [18.9%-38.5%/y] vs 11.0%/y [-1.9% to 24.0%/y], P = .04; absolute: 25.1/y [19.7-30.5/y] vs 12.2/y [4.5-19.9/y], P = .02). The adjusted odds ratio (95% confidence interval) for definite AVC progression was significantly lower for patients who received ACEIs (0.29 [0.11-0.75], P = .01). This retrospective study finds a significant association between ACEI use and a lower rate of AVC accumulation. The results support the need for prospective, randomized trials of ACEIs in calcific aortic valve disease.


Utility of covered stents for extracranial internal carotid artery stenosis.
To our knowledge, the utility of coronary covered stents in the treatment of atherosclerotic carotid artery stenosis has not been defined in the English-language literature. Covered stents may prevent microembolic complications in select atherosclerotic carotid lesions, as they exclude the atherosclerotic lesion from the circulation by pressing the plaque against the vessel wall. Our early clinical experience has shown that use of these stents can be a therapeutic option in select cases of atherosclerotic stenosis of the cervical internal carotid artery.


Effect of lectin on nodulation by wild-type Bradyrhizobium japonicum and a nodulation-defective mutant.
The nodulation characteristics of wild-type Bradyrhizobium japonicum USDA 110 and mutant strain HS111 were examined. Mutant strain HS111 exhibits a delayed-nodulation phenotype, a result of its inability to initiate successful nodulation promptly following inoculation of the soybean root. Previously, we showed that the defect in initiation of infection leading to subsequent nodulation which is found in HS111 can be phenotypically reversed by pretreatment with soybean root exudate or soybean seed lectin. This effect is not seen after pretreatment with root exudates and lectins obtained from other plant species. Treatment of strain HS111 with as little as 10 soybean seed lectin molecules per bacterium (3.3 X 10 (-12) M) resulted in enhancement of nodule formation. Pretreatment of wild-type B. japonicum USDA 110 with soybean root exudate or seed lectin increased nodule numbers twofold on 6-week-old plants. Wild-type strain USDA 110 cells inoculated at 10(4) cells per seedling exhibited a delay in initiation of infection leading to subsequent nodulation. Wild-type cells pretreated in soybean root exudates or seed lectin did not exhibit a delay in nodulation at this cell concentration. Mutant strain HS111 pretreated in seed lectin for 0 or 1 h, followed by washing with the hapten D-galactose to remove the lectin, exhibited a delay in initiation of nodulation. Phenotypic reversal of the delayed-nodulation phenotype exhibited by strain HS111 was seen if incubation was continued for an additional 71 h in plant nutrient solution following 1 h of lectin pretreatment. Reversal of the delayed-nodulation phenotype of HS111 through lectin pretreatment was prevented by chloramphenicol or rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)


Muscle atrophy in mechanically-ventilated critically ill children.
ICU-acquired muscle atrophy occurs commonly and worsens outcomes in adults. The incidence and severity of muscle atrophy in critically ill children are poorly characterized. To determine incidence, severity and risk factors for muscle atrophy in critically ill children. A single-center, prospective cohort study of 34 children receiving invasive mechanical ventilation for ≥48 hours. Patients 1 week- 18 years old with respiratory failure and without preexisting neuromuscular disease or skeletal trauma were recruited from a tertiary Pediatric Intensive Care Unit (PICU) between June 2015 and May 2016. We used serial bedside ultrasound to assess thickness of the diaphragm, biceps brachii/brachialis, quadriceps femoris and tibialis anterior. Serial electrical impedance myography (EIM) was assessed in children >1 year old. Medical records were abstracted from an electronic database. Respiratory failure requiring endotracheal intubation for ≥48 hours. The primary outcome was percent change in muscle thickness. Secondary outcomes were changes in EIM-derived fat percentage and "quality". Of 34 enrolled patients, 30 completed ≥2 ultrasound assessments with a median interval of 6 (IQR 6-7) days. Mean age was 5.42 years, with 12 infants <1 year (40%) and 18 children >1 year old (60%). In the entire cohort, diaphragm thickness decreased 11.1% (95%CI, -19.7% to -2.52%) between the first two assessments or 2.2%/day. Quadriceps thickness decreased 8.62% (95%CI, -15.7% to -1.54%) or 1.5%/day. Biceps (-1.71%; 95%CI, -8.15% to 4.73%) and tibialis (0.52%; 95%CI, -5.81% to 3.40%) thicknesses did not change. Among the entire cohort, 47% (14/30) experienced diaphragm atrophy (defined a priori as ≥10% decrease in thickness). Eighty three percent of patients (25/30) experienced atrophy in ≥1 muscle group, and 47% (14/30)-in ≥2 muscle groups. On multivariate linear regression, increasing age and traumatic brain injury (TBI) were associated with greater muscle loss. EIM revealed increased fat percentage and decreased muscle "quality". In children receiving invasive mechanical ventilation, diaphragm and other skeletal muscle atrophy is common and rapid. Increasing age and TBI may increase severity of limb muscle atrophy. Prospective studies are required to link muscle atrophy to functional outcomes in critically ill children.


Therapy of radiation injury.
It is apparent from preclinical and clinical research to date that continued evaluation of new and alternative treatment strategies is required to eliminate the obligate periods of neutropenia and thrombocytopenia after acute high-dose irradiation. Future treatment strategies may involve new combinations of cytokines to affect hematopoietic stem cell proliferation and "engineered" cellular grafts to provide short-term in vivo expansion of neutrophils and platelets in an effort to bridge the cytopenic gap until endogenous or transplanted stem cells regenerate the hematopoietic and immune systems. Cytokine-mobilized peripheral blood and cord blood will provide alternative sources of allogeneic stem and progenitor cells in support of primary engraftment, delayed engraftment or secondary failure of the initial graft, as well as starting populations for various ex vivo expansion protocols. Further insights into the relative quality of stem cell populations and the factors that regulate their survival and self renewal, and the identification and roles of adhesion molecules in stem cell mobilization, engraftment, and interaction with the adult marrow microenvironment will provide the basis for future treatment strategies for the radiation-induced hematopoietic syndrome. As our ability to treat the hematopoietic syndrome improves, damage to other organ systems such as the skin, lung, and/or gastrointestinal tissue will emerge as dose-limiting. At the same time, the characterization of receptors for inflammatory cytokines, cytokine receptor antagonists, and anti-endotoxin antibodies has allowed significant insights into the mechanisms and pathogenesis of sepsis. However, translation of this knowledge into a treatment modality for septic patients is precluded by the lack of any clear-cut beneficial effect from the many clinical trials. The research and clinical results presented in this volume and recent conferences reflect the body of knowledge that will lead to further developments in assessment, prophylaxis, and treatment of radiation injuries in the areas of infectious disease and the hematopoietic, gastrointestinal, and cutaneous syndromes.


A modified technique for inferior turbinate reduction: the integration of coblation technology.
Many procedures have been described for the surgical management of inferior turbinate hypertrophy. Coblation is a relatively new technology that uses radiofrequency energy to ablate hypertrophied tissues. The standard method of using this technology has been shown to be effective; however, it only partially relieves symptoms of obstruction. The authors present a modified hybrid technique for the surgical reduction of inferior turbinate hypertrophy using a combination of coblation and turbinate outfracture to maximize the nasal airway patency. A review was performed of operating room video files to evaluate the senior author's (J.L.E.) technique for performing inferior turbinate reduction using the modified coblation and outfracture technique. The videos were edited to present the technique. The senior author has found this modified hybrid technique to be both efficacious and safe. This Video Plus article presents both the operative technique and postoperative management for cases of inferior turbinate hypertrophy that fail medical management. This modified hybrid technique is the mainstay of the senior author's treatment of inferior turbinate hypertrophy reduction and can be a useful surgical tool to achieve adequate outcomes when dealing with patients who have hypertrophied inferior turbinates that fail medical management.


Phosphorus release from a biosolids-amended sandy spodosol.
Most regulations governing biosolids land application do not consider that phosphorus (P) solubility can vary widely among biosolids. Current regulations typically group all biosolids together in one category or group biosolids together with manures. Research has shown that not all biosolids have the same potential to affect the environment when land applied, but the database is limited. The purpose of this study was to characterize P release from several biosolids produced and/or marketed in Florida. A small soil column dynamic laboratory incubation was conducted to assess P release potential. Eleven biosolids and a mineral fertilizer (triple super phosphate) were individually mixed with a typical low-P sorbing Florida soil (Immokalee fine sand) at 56 and 224 kg P ha(-1). Columns were periodically leached over 5.5 mo to attain 60 mL (1/2 pore volume) of drainage in each leaching. Soluble reactive P was determined and summed over the eight leachings to represent total P source release. Cumulative P release (as a percentage of P applied) was greatest from biological P removal (BPR) and BPR-like biosolids and least from heat-dried materials. Phosphorus release from biosolids depends on biosolids treatment type (digestion) and P chemistry, suggesting that biosolids regulations must account for differences in P lability to accurately gauge environmental risk.


Traumatic thoracic aortic injury caused by a sharp edge of left fractured rib on body position change: case report.
Aortic injury caused by penetration of a fractured rib is very rare. We present a patient with aortic injury demonstrated using serial imaging studies. A 66-year-old woman fell from a ladder and sustained multiple left-side rib fractures. There was a small left hemothorax and widened mediastinum on the initial chest roentgenogram in the emergency department. Chest computed tomography (CT) revealed a posterior segmental fracture of the sixth rib on the left side with a sharp edge penetrating into the posterior aspect of the thoracic aorta. It was initially missed. More than 1000 cc of fresh blood suddenly gushed out of the chest tube 7 hours after the traumatic event. After resuscitation, an aortogram was performed which showed blood extravasation from the thoracic aorta at the rib fracture site. Unfortunately, surgical intervention was delayed and she died. Early detection and early surgical intervention are necessary in patients with a widened mediastinum and positive results on imaging studies.


A mathematical computer stimulation model for the development of colonic polyps and colon cancer.
Currently known information about the development and progression of colon polyps and cancer is summarized and organized into a mathematical computer simulation model that successfully predicts the natural history of colon polyp and cancer development for an average patient with (1) familial polyposis coli (2) genetic susceptibility as measured by a positive family history, and (3) negative family history with a high fat diet. The mathematical model uses four distinct types of cells (normal, transformed, polypoid, and cancerous) and two kinetic processes (mutation and promotion). Arachidonic acid metabolites play a role in the model in the promotion of cancer from polyps, and account for that promotion through: (1) their effect on encouraging more polypoid cells in mitosis to move toward cancer; and (2) their immunosuppressive effect over time. The model also shows that one defect in allowing more cells to mutate to the transformed state is sufficient to account for the chain of events leading to the clinical sequelae of familial polyposis coli. A second genetic effect at another point in the process is unnecessary. The mechanism of action of Sulindac on colon polyps is explained by the model through inhibition of production of arachidonic acid metabolites, most notably prostaglandin E.


Abortion law reforms in Colombia and Nicaragua: issue networks and opportunity contexts.
This article analyses two instances of abortion law reform in Latin America. In 2006, after a decades-long impasse, the highly controversial issue of abortion came to dominate the political agenda when Colombia liberalized its abortion law and Nicaragua adopted a total ban on abortion. The article analyses the central actors in the reform processes, their strategies and the opportunity contexts. Drawing on Htun's (2003) framework, it examines why these processes concluded with opposing legislative outcomes. The authors argue for the need to understand the state as a non-unitary site of politics and policy, and for judicial processes to be seen as a key variable in facilitating gender policy reforms in Latin America. In addition, they argue that 'windows of opportunity' such as the timing of elections can be critically important in legislative change processes.


Restless Legs Syndrome in Aircrew.
INTRODUCTION: Restless legs syndrome (RLS) is characterized by an uncomfortable sensation on the legs, which causes the urge to move the legs. The main cause is unknown but there are many risk factors, including geographical properties and high altitude. Our objective was to explore the frequency of RLS in aircrew.METHODS: There were 301 Turkish aircrew who were admitted to Istanbul Medipol University Hospital Neurology Department for periodic examinations and 272 healthy (non-aircrew) subjects included in the study. The International RLS Study Group's Questionnaire and the International RLS Study Group Rating Scale (IRLSSGRS) were used to evaluate RLS. The participants filled the RLS questionnaire and then both groups were divided into two subgroups as having RLS or not. The subjects years in the profession, average flight duration in a month, daily sleep duration, smoking, and coffee consumption were recorded. None of the subjects had previously been diagnosed with RLS.RESULTS: The frequency of RLS was 6.7% in the aircrew group and 7.9% in the control group, and there was no significant difference between the two groups. Age, gender, daily duration of sleep, smoking, coffee consumption, family history of RLS, being a pilot or a flight attendant, years in profession, and monthly flight hours were similar in aircrew with and without RLS.DISCUSSION: The RLS frequency in aircrew was similar to that of the control group. We can conclude flying at high altitude wasnt a risk factor for RLS.Düz OA, Yilmaz NH, Olmuscelik O. Restless legs syndrome in aircrew. Aerosp Med Hum Perform. 2019; 90(11):934937.


Design and synthesis of dihydrofolate reductase inhibitors encompassing a bridging ester group. Evaluation in a mouse colitis model.
Crohn's disease is a chronic inflammatory bowel disease characterized by inflammation of both the small and large intestines. Methotrexate (MTX), a classical dihydrofolate reductase (DHFR) inhibitor, has been used as a therapeutic agent in the treatment of patients with Crohn's disease in recent years. We sought to develop antifolates similar in structure to MTX that would be effective in reducing inflammation in a mouse disease model of colitis. Four classical DHFR inhibitors encompassing ester bridges in the central parts of the molecules were synthesized. These antifolates were efficient inhibitors of the DHFR enzyme derived from rat. They were also tested in vitro for their ability to inhibit induced proliferation of lymphocytes from mouse spleen. Inhibition of cell proliferation was achieved only in the micromolar range, whereas MTX was effective at low nanomolar concentrations. One of the DHFR inhibitors (1), with an IC(50) value for rlDHFR approximately 8 times higher than that of methotrexate, was selected for in vivo experiments in an experimental colitis model in mice. This compound demonstrated a clear antiinflammatory effect after topical administration, comparable to the effect achieved with the glucocorticoid budesonide. Three parameters were evaluated in this model: myeloperoxidase activity, colon weight, and inflammation scoring. A favorable in vivo effect of compound 1 (15 mg/(kg.day)) was observed in all three inflammatory parameters. However, the results cannot be explained fully by DHFR inhibition or by inhibition of lymphocyte cell proliferation, suggesting that other yet unidentified mechanisms enable reduction of inflammation in the colitis model. The mechanism of action of methotrexate analogues encompassing a bridging ester group is not well understood in vivo but seems to lend itself well to further development of similar compounds.


Cytological effects of cellulases in the parasitism of Phytophthora parasitica by Pythium oligandrum.
The ubiquitous oomycete Pythium oligandrum is a potential biocontrol agent for use against a wide range of pathogenic fungi and an inducer of plant disease resistance. The ability of P. oligandrum to compete with root pathogens for saprophytic colonization of substrates may be critical for pathogen increase in soil, but other mechanisms, including antibiosis and enzyme production, also may play a role in the antagonistic process. We used transmission electron microscopy and gold cytochemistry to analyze the intercellular interaction between P. oligandrum and Phytophthora parasitica. Growth of P. oligandrum towards Phytophthora cells correlated with changes in the host, including retraction of the plasma membrane and cytoplasmic disorganization. These changes were associated with the deposition onto the inner host cell surface of a cellulose-enriched material. P. oligandrum hyphae could penetrate the thickened host cell wall and the cellulose-enriched material, suggesting that large amounts of cellulolytic enzymes were produced. Labeling of cellulose with gold-complexed exoglucanase showed that the integrity of the cellulose was greatly affected both along the channel of fungal penetration and also at a distance from it. We measured cellulolytic activity of P. oligandrum in substrate-free liquid medium. The enzymes present were almost as effective as those from Trichoderma viride in degrading both carboxymethyl cellulose and Phytophthora wall-bound cellulose. P. oligandrum and its cellulolytic enzymes may be useful for biological control of oomycete pathogens, including Phytophthora and Pythium spp., which are frequently encountered in field and greenhouse production.


Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples.
Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of IB is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. Although serotyping requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV, and it is inefficient at detecting multiple viruses in a single sample. We describe herein a MinION-based, amplicon-based sequencing (AmpSeq) method that genetically categorized IBV from clinical samples, including samples with multiple IBVs. Total RNA was extracted from 15 tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer's instructions into a 1D MinION sequencing library, and then sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in 3 of 5 samples containing 2 IBV lineages. Additionally, 1 sample contained 3 IBV lineages, and AmpSeq accurately detected 2 of the 3 lineages. Strain identification, including detection of different IBVs from the same lineage, was also possible with this AmpSeq method. Our results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.


Cellular responses to thermoresponsive stiffness memory elastomer nanohybrid scaffolds by 3D-TIPS.
Increasing evidence suggests the contribution of the dynamic mechanical properties of the extracellular matrix (ECM) to regulate tissue remodeling and regeneration. Following our recent study on a family of thermoresponsive 'stiffness memory' elastomeric nanohybrid scaffolds manufactured via an indirect 3D printing guided thermally-induced phase separation process (3D-TIPS), this work reports in vitro and in vivo cellular responses towards these scaffolds with different initial stiffness and hierarchically interconnected porous structure. The viability of mouse embryonic dermal fibroblasts in vitro and the tissue responses during the stiffness softening of the scaffolds subcutaneously implanted in rats for three months were evaluated by immunohistochemistry and histology. Scaffolds with a higher initial stiffness and a hierarchical porous structure outperformed softer ones, providing initial mechanical support to cells and surrounding tissues before promoting cell and tissue growth during stiffness softening. Vascularization was guided throughout the digitally printed interconnected networks. All scaffolds exhibited polarization of the macrophage response from a macrophage phenotype type I (M1) towards a macrophage phenotype type II (M2) and down-regulation of the T-cell proliferative response with increasing implantation time; however, scaffolds with a more pronounced thermo-responsive stiffness memory mechanism exerted higher inflammo-informed effects. These results pave the way for personalized and biologically responsive soft tissue implants and implantable device with better mechanical matches, angiogenesis and tissue integration. Statement of Significance This work reports cellular responses to a family of 3D-TIPS thermoresponsive nanohybrid elastomer scaffolds with different stiffness softening both in vitro and in vivo rat models. The results, for the first time, have revealed the effects of initial stiffness and dynamic stiffness softening of the scaffolds on tissue integration, vascularization and inflammo-responses, without coupling chemical crosslinking processes. The 3D printed, hierarchically interconnected porous structures guide the growth of myofibroblasts, collagen fibers and blood vessels in real 3D scales. In vivo study on those unique smart elastomer scaffolds will help pave the way for personalized and biologically responsive soft tissue implants and implantable devices with better mechanical matches, angiogenesis and tissue integration.


Measuring the approximate number system.
Recent theories in numerical cognition propose the existence of an approximate number system (ANS) that supports the representation and processing of quantity information without symbols. It has been claimed that this system is present in infants, children, and adults, that it supports learning of symbolic mathematics, and that correctly harnessing the system during tuition will lead to educational benefits. Various experimental tasks have been used to investigate individuals' ANSs, and it has been assumed that these tasks measure the same system. We tested the relationship across six measures of the ANS. Surprisingly, despite typical performance on each task, adult participants' performances across the tasks were not correlated, and estimates of the acuity of individuals' ANSs from different tasks were unrelated. These results highlight methodological issues with tasks typically used to measure the ANS and call into question claims that individuals use a single system to complete all these tasks.


Primary care closed claims experience of Massachusetts malpractice insurers.
Despite prior focus on high-impact inpatient cases, there are increasing data and awareness that malpractice in the outpatient setting, particularly in primary care, is a leading contributor to malpractice risk and claims. To study patterns of primary care malpractice types, causes, and outcomes as part of a Massachusetts ambulatory malpractice risk and safety improvement project. Retrospective review of pooled closed claims data of 2 malpractice carriers covering most Massachusetts physicians during a 5-year period (January 1, 2005, through December 31, 2009). Data were harmonized between the 2 insurers using a standardized taxonomy. Primary care practices in Massachusetts. All malpractice claims that involved primary care practices insured by the 2 largest insurers in the state were screened. A total of 551 claims from primary care practices were identified for the analysis. Numbers and types of claims, including whether claims involved primary care physicians or practices; classification of alleged malpractice (eg, misdiagnosis or medication error); patient diagnosis; breakdown in care process; and claim outcome (dismissed, settled, verdict for plaintiff, or verdict for defendant). During a 5-year period there were 7224 malpractice claims of which 551 (7.7%) were from primary care practices. Allegations were related to diagnosis in 397 (72.1%), medications in 68 (12.3%), other medical treatment in 41 (7.4%), communication in 15 (2.7%), patient rights in 11 (2.0%), and patient safety or security in 8 (1.5%). Leading diagnoses were cancer (n = 190), heart diseases (n = 43), blood vessel diseases (n = 27), infections (n = 22), and stroke (n = 16). Primary care cases were significantly more likely to be settled (35.2% vs 20.5%) or result in a verdict for the plaintiff (1.6% vs 0.9%) compared with non-general medical malpractice claims (P < .001). In Massachusetts, most primary care claims filed are related to alleged misdiagnosis. Compared with malpractice allegations in other settings, primary care ambulatory claims appear to be more difficult to defend, with more cases settled or resulting in a verdict for the plaintiff.


Clinical viral infections and multiple sclerosis.
Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated "at risk" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses.


The huPBL-SCID mouse as a means to examine human immune function in vivo.
The transfer of human peripheral blood lymphocytes (huPBL) into mice with severe combined immune deficiency (SCID) has allowed for the generation of a model in which it is possible to examine human immune cell function in vivo. This model also provides the researcher an invaluable tool with which to examine human disease states and to evaluate potential therapies using human cells and reagents under more physiological conditions. However, it is clear that there are still significant obstacles that need to be addressed to optimize this model. The primary problem with the huPBL-SCID mouse is the tremendous variability in the extent of human cell engraftment which can vary from donor to donor and even from mouse to mouse using the same huPBL donor. This variability currently limits attempts to standardize this model among investigators and subsequently, various laboratories have employed different methods to optimize and ascertain the extent of human cell engraftment. In addition, there appears to be significant xenogeneic host-versus-graft and graft-versus-host reactions, as well as lethal EBV-induced B-cell lymphomas that can spontaneously arise which may further complicate the interpretation of human immunological studies performed in these mice. Despite these obstacles, the huPBL-SCID model has the potential to serve as a model for the examination of human lymphoid cells in an in-vivo setting and has been usefully applied to the study of various human disease states including AIDS, transplantations, autoimmunity and cancer.


Clinical Outcomes in Patients with Panurothelial Carcinoma Treated with Radical Nephroureterectomy Following Cystectomy for Metachronous Recurrence.
We report pathological, functional and oncologic outcomes in patients treated with radical nephroureterectomy following radical cystectomy. We identified patients who underwent radical cystectomy and then radical nephroureterectomy for metachronous urothelial recurrence at our institution between January 1995 and December 2014. Univariable Cox regression was used to assess the association between overall survival and age, grade, stage, lymph node metastasis and radiographic findings. Of the 3,173 patients treated with radical cystectomy 64 underwent subsequent radical nephroureterectomy for metachronous urothelial recurrence. Median age at radical cystectomy was 66 years (IQR 61-74). In the 64 patients who underwent radical nephroureterectomy median time from radical cystectomy to radical nephroureterectomy was 2.7 years (IQR 1.4-4.6). Among 37 patients who underwent ureteroscopy prior to radical nephroureterectomy 29 (78%) had a positive biopsy. Radical nephroureterectomy pathology findings revealed locally advanced disease (pT3/pT4) in 39% of cases and positive node status in 11% compared with locally advanced disease in 17% and positive node status in 6% on radical cystectomy pathology findings. The post-radical nephroureterectomy estimated glomerular filtration rate was less than 60 and less than 30 ml/minute/1.73 m2 in 96% and 40% of patients, respectively. Median overall survival after radical nephroureterectomy was 3.1 years (95% CI 2.4-4.3). Only lymph node involvement at radical nephroureterectomy was significantly associated with worse overall mortality (HR 2.73, 95% CI 1.04-7.15, p = 0.041). The prognosis is poor in patients with panurothelial carcinoma treated with nephroureterectomy following cystectomy with locally advanced disease in a large proportion. Renal function after these procedures diminished and almost all patients were ineligible for cisplatin based chemotherapy.


High Prevalence of Mansonella perstans Filariasis in Rural Senegal.
Large parts of African and American countries are colonized by Mansonella, a very common but poorly described filarial nematode. Bloodsucking flies of the genus Culicoides are suspected to be the vector of Mansonella perstans, but no study in Senegal has confirmed that Culicoides can transmit the parasite. Designed specific real-time quantitative polymerase chain reaction (qPCR) can be used to identify microfilaria in stained blood smears. This study was performed in July and December 2010 in the southeastern Senegal, which is known to be endemic for M. perstans. We analyzed 297 blood smears from febrile and afebrile resident people by qPCR. The global prevalence of M. perstans was approximately 14.5% in both febrile and afebrile individuals. The age group of > 30 years had the highest prevalence (22.0%). No Culicoides among 1,159 studied specimens was positive for M. perstans and its vector in Senegal still requires identification.


Emotion contagion and physiological synchrony: The more intimate relationships, the more contagion of positive emotions.
The study aimed to explore how interpersonal closeness (friends vs. strangers) and emotion type (positive vs. negative) influenced emotion contagion and physiological synchrony between interacting partners. Twenty-eight friend dyads (n = 56) and 29 stranger dyads (n = 58) participated in an emotion contagion laboratory task. In each dyad, one participant, the 'sender', was randomly asked to watch a film clip (neutral, positive, or negative), while their partner, the 'observer' passively observed the sender's facial expressions. Participants' electrocardiograms (ECG) and facial electromyography (EMG) signals were recorded using the BIOPAC system. Results revealed that observing the sender's facial expressions led to the observer's spontaneous mimicry and emotional contagion, accompanied by enhanced physiological synchrony between interacting partners. In the positive emotion condition, the observers reported more positive emotions and displayed stronger zygomaticus major activity in friend dyads than in stranger dyads. Greater physiological synchrony (heart rate and heart rate variability) between interacting partners was also observed in friend dyads than in stranger dyads in the positive emotion condition. These results indicate that positive emotion contagion is more likely to occur between close partners than negative emotion contagion.


Bold, Sedentary Fathead Minnows Have More Parasites.
Parasites that rely on trophic transmission can manipulate the behavior of an intermediate host to compromise the host's antipredator competence and increase the probability of reaching the next host. Selection for parasite manipulation is diminished when there is significant risk of host death to causes other than consumption by a suitable definitive host for the parasite. Consequently, behavioral manipulation by parasites can be expected to be subtle. Ornithodiplostomum ptychocheilus (Op) is a trematode parasite that has a bird-snail-fish host life cycle. Fathead minnows are a common intermediate host of Op, where metacercariae encyst in the minnow brain. In this study, we report a link between metacercarial intensity and behavior in fathead minnows. In the field, we found that roaming distance by free-living minnows over 24 h was negatively correlated with parasite intensity. In the laboratory, we found that boldness in an open field test was positively correlated with parasite intensity. These parasite-induced behavioral changes may render infected minnows more susceptible to predators, which would serve to facilitate trophic transmission of parasites to the bird host.


Morbidity and mortality among Egyptian neonates and infants: rates and associated factors.
Among 2,128 women residing in two Egyptian governorates with differing socio-economic backgrounds, who were interviewed after giving birth between 1994 and 1996, 181 experienced an early foetal death, 34 had stillbirths, and 1,908 each had a live birth. Among the live births, there were 35 neonatal deaths and 42 post-neonatal deaths. A high percentage of the women sought prenatal care, beginning early in pregnancy, from both government health facilities (GHF) and private physicians. Problem-based care was typically directed to private physicians whereas routine care was largely directed to GHF. Diagnostic procedures were not routinely performed at GHF. The women recognized symptoms which may be associated with adverse outcomes, but health-seeking based on this recognition was inconsistent. Most deliveries were conducted by Egyptian traditional birth attendants, in homes. Anaesthesia and medications to accelerate labour were commonly administered by all types of practitioners in home deliveries. Perinatal mortality was mid-range by global standards, with most deaths occurring at home rather than in hospitals. Although care was sought for most infants with diarrhoea, respiratory infections and fever, neonates with these symptoms were rarely given oral rehydration therapy or antibiotics.


The determinants of translational medicine success - a managerial contribution.
Scope of Translational Medicine is to speed the development of new compounds of medical protocols and/or treatments to improve patient's quality of life. Translational medicine represents the synergy between epidemiology, basic research and clinical trials, and is based upon Innovation Management and Research Development in medicine. Being the speed and progression up to the patient a key issue of Translational Medicine, the innovation process ought to be pursued according to rigorous protocols embedded on a research development path capable of decreasing the lead time at the most. Translational Medicine represents a goal to be pursued by all involved actors, from academic researchers to clinicians, patients and others than can be seen as a network of co-creating actors engaged for the ultimate patient benefit. To underpin Translational Medicine advantages and determinants, the paper approaches the issue by adopting a systems thinking perspective, capable of highlighting the key issues to be considered.


Left atrial mechanics evaluated by two-dimensional strain analysis: alterations in essential hypertension.
Hypertension is a cardiovascular risk factor that predisposes to cardiac structural alterations namely increased left ventricular (LV) wall thickness, reduced LV compliance and diastolic dysfunction, with consequent left atrial (LA) dilation and functional impairment. In this article, we evaluated differences in left atrial structure and function using two-dimensional speckle tracking echocardiography in patients with hypertension compared with controls. This was a retrospective cross-sectional study of 208 hypertensive patients and 157 controls who underwent a comprehensive transthoracic echocardiogram. Patients with hypertension were stratified by the presence of left ventricular hypertrophy (LVH). Non-LVH hypertension patients had lower left atrial reservoir strain (LAS RES ) (34.78 ± 29.78 vs. 29.78 ± 6.08; P = 0.022) and conduit strain (LAS CD ) (19.66 ± 7.29 vs. 14.23 ± 4.59; P = 0.014) vs. controls despite similar left atrial volumes (LAV) . Left atrial contractile strain (LAS CT ) was not significantly different between non-LVH hypertension patients and controls (15.12 ± 3.77 vs. 15.56 ± 3.79; P = 0.601). Left atrial mechanical dispersion was significantly higher in the LVH group compared with the non-LVH hypertension group (42.26 ± 13.01 vs. 50.06 ± 14.95; P = 0.009). In multivariate regression analysis, LVH correlated with left atrial mechanical dispersion ( P = 0.016). An age-hypertension interaction independently correlated with LAS CT ( P < 0.001). Hypertension results in functional left atrial changes even before development of LV hypertrophy and structural left atrial changes with increased left atrial volume. We demonstrate both a likely hypertension-associated left atrial myopathy that prevents age-related compensatory increase in left atrial contractile function, and impact of LVH in hypertension on left atrial dyssynchrony.


A longitudinal study of changes in provider-patient interaction in treatment of localized prostate cancer.
Whilst much is known as to the met and unmet communication needs of prostate cancer patients, few studies have been conducted on the changes in communication between provider and patient over time. Therefore, the aim of our study is to examine (a) whether there are changes over time in the quality of psychosocial care in long-term treatment of localized prostate cancer and (b) whether those changes are associated with the treatment decision. HAROW is a prospective, observational study designed to collect clinical data and patient reported outcomes (PROs) of different treatment options (hormonal therapy, active surveillance, radiation, operation, watchful waiting) for newly diagnosed patients with localized prostate cancer under real conditions. At 6-month intervals, general clinical data, PROs (e.g. quality of life, quality of physician-patient interaction) and individual costs are documented. We analysed data of N = 1,216 patients at the time of initial diagnosis (T1) and after 6 months (T2). There is a significant decline in shared decision-making behaviour of physicians for the group of patients undergoing a prostatectomy and for the hormonal therapy group at the time of initial diagnosis and after 6 months. In terms of emotional support by physicians, there is a significant difference between the treatment groups at the time of initial diagnosis with patients undergoing a prostatectomy reporting significantly less support than the hormonal therapy group. Future research from both, the providers' and the patients' perspective, will have to clarify if we can interpret our results as change in the communication behaviour once the treatment decision for prostatectomy or hormonal therapy is made.


New autoantibodies and their antigens in autoimmune diseases.
Autoimmune diseases are caused by failure to distinguish between host and foreign (e.g. microbial) antigens. We do not know why autoimmune disease occurs and what the relevant pathogenic mechanisms are. Autoantibodies might be considered as diagnostic markers, e.g. as "witnesses" to or "messengers" of autoimmune disease. Therefore, older and newer autoantibodies, as well as results on their respective antigens, will be considered.


ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization.
NMDA receptors (NMDARs) are key mediators of glutamatergic transmission and synaptic plasticity, and their dysregulation has been linked to diverse neuropsychiatric and neurodegenerative disorders. While normal NMDAR function requires regulated expression and trafficking of its different subunits, the molecular mechanisms underlying these processes are not fully understood. Here we report that the amyloid precursor protein intracellular domain associated-1 protein (AIDA-1), which associates with NMDARs and is encoded by ANKS1B, a gene recently linked to schizophrenia, regulates synaptic NMDAR subunit composition. Forebrain-specific AIDA-1 conditional knock-out (cKO) mice exhibit reduced GluN2B-mediated and increased GluN2A-mediated synaptic transmission, and biochemical analyses show AIDA-1 cKO mice have low GluN2B and high GluN2A protein levels at isolated hippocampal synaptic junctions compared with controls. These results are corroborated by immunocytochemical and electrophysiological analyses in primary neuronal cultures following acute lentiviral shRNA-mediated knockdown of AIDA-1. Moreover, hippocampal NMDAR-dependent but not metabotropic glutamate receptor-dependent plasticity is impaired in AIDA-1 cKO mice, further supporting a role for AIDA-1 in synaptic NMDAR function. We also demonstrate that AIDA-1 preferentially associates with GluN2B and with the adaptor protein Ca(2+)/calmodulin-dependent serine protein kinase and kinesin KIF17, which regulate the transport of GluN2B-containing NMDARs from the endoplasmic reticulum (ER) to synapses. Consistent with this function, GluN2B accumulates in ER-enriched fractions in AIDA-1 cKO mice. These findings suggest that AIDA-1 regulates NMDAR subunit composition at synapses by facilitating transport of GluN2B from the ER to synapses, which is critical for NMDAR plasticity. Our work provides an explanation for how AIDA-1 dysfunction might contribute to neuropsychiatric conditions, such as schizophrenia.


Ketorolac for postoperative pain management in children.
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic effects and a relatively low incidence of adverse effects. Numerous clinical trials of postoperative pain treatment in children have shown that ketorolac is as effective as the major opioid analgesics, such as morphine, and more effective than codeine. The pharmacokinetics of ketorolac differ in children compared with adult patients after surgery. In children, the volume of distribution (Vd) of ketorolac is increased by as much as 2-fold relative to that in adults. The plasma clearance (CL) of ketorolac is also higher in children, probably because of lower binding to plasma proteins. However, the elimination half-life (t 1/2 beta) of ketorolac is similar in children and adults because t 1/2 beta is directly proportional to Vd but inversely proportional to CL. These pharmacokinetic differences indicate that a higher relative dosage is required in children, but the dosage interval is similar in children and adults. Ketorolac can be administered intravenously, intramuscularly or orally. The intravenous route is preferred during the immediate postoperative period, until the patient can tolerate oral medication. Intramuscular injections are not recommended in children, unless the intravenous route is unavailable. The recommended intravenous dosage of ketorolac in children is 0.5 mg/kg, followed either by bolus injections of 1.0 mg/kg every 6 hours or an intravenous infusion of 0.17 mg/kg/h. The maximum daily dosage is 90mg, and the maximum duration of treatment is 48 hours. The recommended oral dosage is 0.25 mg/kg to a maximum of 1.0 mg/kg/day, with a maximum duration of 7 days. Older children may require somewhat lower dosages, while infants and young children may require slightly higher dosages to achieve the same level of pain relief. Ketorolac is not recommended for use in infants aged < 1 year. Unlike opioid analgesics ketorolac does not depress ventilation, and is not associated with nausea and vomiting, urinary retention or sedation. When combined with an opioid, ketorolac exhibits marked opioid-sparing effects, allowing a lower dosage of opioid to be used. Clinical studies in children and adults show that the synergistic action of ketorolac and opioids improves the degree and quality of pain relief, and reduces the incidence of opioid-related adverse effects such as respiratory depression, nausea/vomiting and ileus. Recovery of bowel function after abdominal surgery occurs sooner in ketorolac-compared with opioid-treated patients. Ketorolac reversibly inhibits cyclo-oxygenase, and decreases the hypersensitisation of tissue nociceptors that occurs with surgery. It also has reversible antiplatelet effects, which are attributable to the inhibition of thromboxane synthesis. Bleeding time is usually slightly increased, but in most patients it remains within normal values. There is conflicting evidence of the potential for increased surgical-site bleeding after tonsillectomy but, for other types of paediatric surgery, numerous clinical studies have confirmed that ketorolac is not associated with increased bleeding. Thus, ketorolac is well suited for the treatment of postoperative pain in children, either alone or in combination with opioids or local anaesthetics, because of its analgesic potency and relatively low incidence of adverse effects.


Leaching potential of persistent soil fumigant residues.
Persistent fumigant residues in soil resulting from agricultural pest-control practices may be released into water and leached to groundwater. In this study, the leaching potential of persistent soil fumigant residues was evaluated, and the effect of dissolved organic matter (DOM) and ammonium thiosulfate (ATS) amendment was investigated. A silt loam soil was incubated separately with the fumigants 1,3-dichloropropene (1,3-D), chloropicrin (CP), and methyl isothiocyanate (MITC) at 240-990 mg kg(-1) for 35 d, followed by 48 h of evaporation. The soil was packed into stainless steel columns (1.4 cm x 10 cm) and leached with water, 5 mM ATS, and DOM solution (DOC 250 mg L(-1)) by gravity. Residues of 1,3-D, CP, and MITC in the evaporated soil were 5.61, 11.38, and 1.83 mg kg(-1), respectively. Concentrations of 1,3-D, CP, and MITC in column effluents ranged from 0.05 to 0.73, 0.16 to 0.81, and 0.05 to 0.27 mg L(-1), respectively, when the soil was leached with 10 pore volumes of water. DOM did not promote the leaching of persistent fumigant residues, and ATS remarkably reduced the amount of 1,3-D and CP yet notably increased MITC recovered in the effluents. The results suggest that the leaching of persistent fumigant residues through soil to water is significant, and movement of fumigants in soil is not facilitated by DOM. Amending soil with ATS through irrigation is an effective method to remove persistent residues of halogenated fumigants. To reduce groundwater pollution risks posed by fumigation, persistent soil fumigant residues have to be considered.


Thymic regulation of hematopoiesis. III: Isolation of helper and suppressor populations using counterflow centrifugal elutriation.
We have evidence that thymic regulatory cells can either enhance or inhibit the growth of hematopoietic progenitors in vitro. We have suggested that two separate populations are responsible for this regulatory interaction but isolation of the cell types has proven difficult. We now report the isolation by counterflow centrifugal elutriation (CCE) of two separate populations of thymocytes which regulate erythropoiesis in coculture. We demonstrate that a minority population (less than 10%) of slow sedimenting elutriated thymocytes provide a helper function whereas the suppressor population is the majority population. Furthermore, some thymocytes of intermediate cell volume neither enhance nor inhibit erythroid colony growth. We conclude that isolation of thymic subsets can lead to identification of populations which induce cell-cell regulation of hematopoietic progenitors resulting in both a positive and negative feedback control of growth.


Independent gene phylogenies and morphology demonstrate a malagasy origin for a wide-ranging group of swallowtail butterflies.
Madagascar is home to numerous endemic species and lineages, but the processes that have contributed to its endangered diversity are still poorly understood. Evidence is accumulating to demonstrate the importance of Tertiary dispersal across varying distances of oceanic barriers, supplementing vicariance relationships dating back to the Cretaceous, but these hypotheses remain tentative in the absence of well-supported phylogenies. In the Papilio demoleus group of swallowtail butterflies, three of the five recognized species are restricted to Madagascar, whereas the remaining two species range across the Afrotropical zone and southern Asia plus Australia. We reconstructed phylogenetic relationships for all species in the P. demoleus group, as well as 11 outgroup Papilio species, using 60 morphological characters and about 4 kb of nucleotide sequences from two mitochondrial (cytochrome oxidase I and II) and two nuclear (wg and EF-1alpha) genes. Of the three endemic Malagasy species, the two that are formally listed as endangered or at risk represented the most basal divergences in the group, while the more common third endemic was clearly related to African P. demodocus. The fifth species, P. demoleus, showed little differentiation across southern Asia, but showed divergence from its subspecies sthenelus in Australia. Dispersal-vicariance analysis using cladograms derived from morphology and three independent genes indicated a Malagasy diversification of lime swallowtails in the middle Miocene. Thus, diversification processes on the island of Madagascar may have contributed to the origin of common butterflies that now occur throughout much of the Old World tropical and subtemperate regions. An alternative hypothesis, that Madagascar is a refuge for ancient lineages resulting from successive colonizations from Africa, is less parsimonious and does not explain the relatively low continental diversity of the group.


[The psychopathological dimension of female alcoholism].
In France, as in other countries, more and more women are affected by alcoholism. Progress needs to be made in the early detection and management of their physical and psychological dependence on alcohol, as well as their psychopathological comorbidities.


A Smartphone App for Self-Monitoring of Rheumatoid Arthritis Disease Activity to Assist Patient-Initiated Care: Protocol for a Randomized Controlled Trial.
Telemedicine based on self-measurement of disease activity could be one of the key components to create the health care system of the future. Previous publications in various medical fields have shown that it is possible to safely telemonitor patients while reducing the number of outpatient clinic visits. For this purpose, we developed a mobile phone app for patients with rheumatoid arthritis (RA), which allows them to self-monitor their disease. The objective of this study is to assess the safety and efficacy of self-initiated care assisted by a smartphone app in patients with RA. This is a randomized controlled trial that will be performed for 1 year. A total of 176 patients with RA will be randomized to either self-initiated care with only one scheduled follow-up consultation assisted by our app or usual care. The coprimary outcome measures are the number of outpatient clinic consultations with a rheumatologist taking place during the trial period and the mean disease activity score as measured by the disease activity score 28 (DAS28) at 12 months. The secondary outcomes are patient satisfaction, adherence, patient empowerment, and cost evaluation of health care assisted by the app. Recruitment started in May 2019, and up to 18 months will be required for completion of recruitment. Thus far, 78 patients have been randomized, and thus far, experiences with the app have been positive. The study results are expected to be published by the end of 2021. The completion of this study will provide important data regarding the following: (1) safety of self-initiated care supported by a smartphone app in terms of DAS28 and (2) efficacy of lowering health care usage with this new strategy of providing health care. Netherlands Trial Register NL7715; https://www.trialregister.nl/trial/7715. DERR1-10.2196/15105.


Is olanzapine better than haloperidol in resistant schizophrenia? A double-blind study in partial responders.
To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111).


Initial experience of video-assisted thoracic surgery lobectomy after neoadjuvant chemotherapy plus toripalimab in a patient with locally advanced non-small cell lung cancer: a case report.
Immune checkpoint inhibitors were used for patients with advanced non-small cell lung cancer (NSCLC) more and more frequently and the effects were thrilling. Toripalimab as a new immune checkpoint inhibitor has been shown to be effective in patients with advanced NSCLC. However, data regarding the safety and feasibility of surgical resection after treatment with toripalimab for NSCLC remain scarce. Here, we present a case with locally advanced NSCLC that received video-assisted thoracic surgery (VATS) lobectomy after treatment with toripalimab in combination with chemotherapy. A 62-year-old male patient with a history of coronary artery stenting operation for two times was found a 3.4 × 3.2 cm cavity mass in the upper lobe of the left lung and enlarged left hilar and mediastinal lymph nodes. Pathological results identified squamous cell carcinoma. The patient was diagnosed with a locally advanced NSCLC and received VATS left upper lobectomy and lymph node dissection after neoadjuvant chemotherapy plus toripalimab for 3 cycles. The postoperative pathological results showed complete tumor remission. Short-term follow-up results were excellent, and long-term results remain to be revealed. Our preliminary results showed that the use of neoadjuvant toripalimab and chemotherapy for the locally advanced NSCLC before surgical resection is safe and feasible.


Screening of potential key genes in esophageal cancer based on RBP and expression verification of HENMT1.
To screen key biomarkers of esophageal cancer (ESCA) by bioinformatics and analyze the correlation between key genes and immune infiltration. Expression profile data of ESCA was downloaded from TCGA database, and DEGs in ESCA were screened with R software. After the RNA binding proteins (RBPs) in DEGs were screened, the protein interaction network was constructed using tools such as STRING and Cytoscape and the key genes (HENMT1) were screened. Survival analysis of HENMT1 was performed by Kaplan-Meier method. Functional enrichment analysis of HENMT1 interacting proteins was performed using the DAVID website, and GSEA predicted the signal pathways involved by HENMT1. CIBERSORT algorithm was used to analyze the infiltration of immune cells in ESCA. The expression of HENMT1 in ESCA was detected by immunohistochemistry. A total of 105 RNA binding proteins (RBPs) were differentially expressed in ESCA, and a PPI network was constructed to screen the key gene HENMT1. The expression level of hemmt1 gene was closely related to the infiltration of B cells naive, T cells regulatory (Tregs), neutrophils, T cells CD4 memory activated, master cells resting and dendritic cells resting in ESCA tissues (P < .05). Immunohistochemical results showed that HENMT1 was highly expressed in ESCA tissues and was positively correlated with the expression of MKI67. HENMT1 is related to the occurrence and prognosis of ESCA, and is also related to the infiltration of immune cells in ESCA tissue, which may provide a new idea for the targeted treatment of ESCA.


[A present-day approach to surgery for the formation of crossed femoro-femoral shunts in unilateral occlusions of the ilio-femoral venous segment (indications, principles of the surgical technique)].
As distinct from the classical Palme-D'Esperon operation in which the anastomosis is established with the common femoral vein, the authors prefer to form the anastomosis in the region of the saphenofemoral communication in inadequate drainage in the iliofemoral segment in patients with the postthrombotic disease. Seven variants of crossed femorofemoral shunting (CFFS) were carried out. The anastomoses were formed by means of precision techniques; an operating microscope was used when the anastomosis measured less than 5 mm in diameter. The CFFS was found to be patent in follow-up periods of up to 2.5 years in all cases. From analysis of the late-term results of CFFS, the authors claim that functional block of venous drainage from the femoro-iliac segment, rather than anatomical occlusion, is the indication for this operation.


Combining nanotechnology with current biomedical knowledge for the vascular imaging and treatment of atherosclerosis.
Activation of vasa vasorum (the microvessels supplying the major arteries) at specific sites in the adventitia initiates their proliferation or 'angiogenesis' concomitant with development of atherosclerotic plaques. Haemorrhagic, leaky blood vessels from unstable plaques proliferate abnormally, are of relatively large calibre but are immature neovessels poorly invested with smooth muscle cells and possess structural weaknesses which may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. Weak neovascular beds in plaque intima as well as activated adventitial blood vessels are potential targets for molecular imaging and targeted drug therapy, however, the majority of tested, currently available imaging and therapeutic agents have been unsuccessful because of their limited capacity to reach and remain stably within the target tissue or cells in vivo. Nanoparticle technology together with magnetic resonance imaging has allowed the possibility of imaging of neovessels in coronary or carotid plaques, and infusion of nanoparticle suspensions using infusion catheters or implant-based drug delivery represents a novel and potentially much more efficient option for treatment. This review will describe the importance of angiogenesis in mediation of plaque growth and development of plaque instability and go on to investigate the possibility of future design of superparamagnetic/perfluorocarbon-derived nanoparticles for imaging of the vasculature in this disease or which could be directed to the adventitial vasa vasorum or indeed intimal microvessels and which can release active payloads directed against primary key external mitogens and intracellular signalling molecules in endothelial cells responsible for their activation with a view to inhibition of angiogenesis.


Stimulus representations in human Pavlovian conditioning: implications of missing negative transfer across response systems.
Three Pavlovian conditioning experiments with human participants are reported, which investigated whether common or separate stimulus representations are involved in solving nonlinear discrimination tasks in different response systems. In our experiments we made use of a negative transfer effect between positive and negative patterning. Experiment 1 specified the conditions under which such a negative transfer effect occurs in human eyelid conditioning. Experiments 2 and 3 investigated whether a similar effect also occurs if two response systems--the eyelid and the skin conductance response system--are trained with trials of both types being randomly interleaved. The presence or absence of a negative transfer effect indicates whether or not the stimulus representations involved in the two conditioning processes overlap. The findings are discussed within the framework of a neuropsychological model of hippocampal function. The results suggest that the representations are distinct and thus support the idea of acquired equivalence and distinctiveness of stimulus representations.


Artifact-Based Rendering: Harnessing Natural and Traditional Visual Media for More Expressive and Engaging 3D Visualizations.
We introduce Artifact-Based Rendering (ABR), a framework of tools, algorithms, and processes that makes it possible to produce real, data-driven 3D scientific visualizations with a visual language derived entirely from colors, lines, textures, and forms created using traditional physical media or found in nature. A theory and process for ABR is presented to address three current needs: (i) designing better visualizations by making it possible for non-programmers to rapidly design and critique many alternative data-to-visual mappings; (ii) expanding the visual vocabulary used in scientific visualizations to depict increasingly complex multivariate data; (iii) bringing a more engaging, natural, and human-relatable handcrafted aesthetic to data visualization. New tools and algorithms to support ABR include front-end applets for constructing artifact-based colormaps, optimizing 3D scanned meshes for use in data visualization, and synthesizing textures from artifacts. These are complemented by an interactive rendering engine with custom algorithms and interfaces that demonstrate multiple new visual styles for depicting point, line, surface, and volume data. A within-the-research-team design study provides early evidence of the shift in visualization design processes that ABR is believed to enable when compared to traditional scientific visualization systems. Qualitative user feedback on applications to climate science and brain imaging support the utility of ABR for scientific discovery and public communication.


Transradial approach for diagnostic selective cerebral angiography: results of a consecutive series of 166 cases.
Diagnostic selective cerebral angiography is commonly performed via transfemoral and transbrachial approaches. With these approaches, however, patients occasionally suffer serious complications. The purpose of this study was to evaluate the feasibility, efficacy, and safety of a transradial approach as an alternative to the transfemoral and transbrachial approaches. Between October 1998 and September 1999, transradial cerebral angiography was performed in 166 consecutive patients in a single center as a diagnostic procedure. Before the procedure, we confirmed the collateral blood supply to the hand from the ulnar artery using a modified Allen test. Regular catheterization techniques were practiced using our newly designed 120-cm-long 4F catheter. In 42 patients, anticoagulant and/or antiplatelet therapy was given perioperatively. Twelve of the 166 patients proved to be poor candidates for the transradial approach, owing to restlessness (n = 9), lack of collateral blood supply via the ulnar artery (n = 2), and brachial artery stenosis (n = 1). The radial artery was successfully punctured and cannulated in the remaining 154 patients. Selective catheterization of the intended vessels was obtained in all carotid and vertebral angiographic procedures with no major vascular complications. Compared with transfemoral and transbrachial approaches, the transradial approach is a less invasive and safer technique for selective cerebral angiography and may warrant consideration as a standard procedure. Anticoagulant or antiplatelet therapy need not be discontinued for this method.


NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and rabbit CB chemoreceptor cells.
The aim of the present work was to elucidate the role of NADPH oxidase in hypoxia sensing and transduction in the carotid body (CB) chemoreceptor cells. We have studied the effects of several inhibitors of NADPH oxidase on the normoxic and hypoxia-induced release of [3H]catecholamines (CA) in an in vitro preparation of intact CB of the rat and rabbit whose CA deposits have been labeled by prior incubation with the natural precursor [3H]tyrosine. It was found that diphenyleneiodonium (DPI; 0.2-25 microM), an inhibitor of NADPH oxidase, caused a dose-dependent release of [3H]CA from normoxic CB chemoreceptor cells. Contrary to hypoxia, DPI-evoked release was only partially Ca2+ dependent. Concentrations of DPI reported to produce full inhibition of NADPH oxidase in the rat CB did not prevent the hypoxic release response in the rat and rabbit CB chemoreceptor cells, as stimulation with hypoxia in the presence of DPI elicited a response equaling the sum of that produced by DPI and hypoxia applied separately. Neopterin (3-300 microM) and phenylarsine oxide (0.5-2 microM), other inhibitors of NADPH oxidase, did not promote release of [3H]CA in normoxic conditions or affect the response elicited by hypoxia. On the basis of effects of neopterin and phenylarsine oxide, it is concluded that NADPH oxidase does not appear to play a role in oxygen sensing or transduction in the rat and rabbit CB chemoreceptor cells in vitro and, in the context of the present study, that DPI effects are not related to NADPH oxidase inhibition.


Variation in Home Health Care Use by Dementia Status among a National Cohort of Older Adults.
Medicare-funded Home Health Care (HHC) delivers skilled nursing, therapy, and related services through visits to the patient's home. Nearly one-third (31%) of HHC patients have diagnosed dementia, but little is currently known regarding how HHC utilization and care delivery differs for Persons Living with Dementia (PLwD). We drew on linked 2012-2018 Health and Retirement Study and Medicare claims for a national cohort of 1,940 community-living older adults. We described differences in HHC admission, length of stay, and referral source by patient dementia status and used weighted, multivariable logistic and negative binomial models to estimate the relationship between dementia and HHC visit type and intensity while adjusting for sociodemographic characteristics, health and functional status, and geographic/community factors. PLwD had twice the odds of using HHC during a two-year observation period, compared to those without dementia (OR: 2.03; p<0.001). They were more likely to be referred to HHC without a preceding hospitalization (49.4% vs 32.1%; p<0.001) and incurred a greater number of HHC episodes (1.4 vs 1.0; p<0.001) and a longer median HHC length of stay (55.8 days vs 40.0 days; p<0.001). Among post-acute HHC patients, PLwD had twice the odds of receiving social work services (aOR: 2.15; p=0.008) and three times the odds of receiving speech-language pathology services (aOR: 2.92; p=0.002). Findings highlight HHC's importance as a care setting for community-living PLwD and indicate the need to identify care delivery patterns associated with positive outcomes for PLwD and design tailored HHC clinical pathways for this patient subpopulation.