Variation of urinary protein to creatinine ratio during the day in women with suspected pre-eclampsia.
To investigate the stability throughout the day of the protein to creatinine ratio (PCR) in spot urine, to demonstrate whether the PCR is a valid alternative for 24-hour protein investigation in pregnant women. Prospective study. Tertiary referral university centre. Women suspected of having pre-eclampsia, admitted to the Erasmus Medical Centre. Twenty-four-hour urine collections and simultaneously three single voided 5-ml aliquots were obtained at 8 a.m., 12 a.m. (noon) and 5 p.m. A PCR was measured in each specimen and compared with the 24-hour protein excretion. The 24-hour proteinuria and PCR measured in spontaneous voids. The PCRs correlated strongly with each other and with the 24-hour protein excretion but did show variation throughout the day (mean coefficient of variation 36%; 95% confidence interval 31-40%). The coefficient of variation was unrelated to the degree of 24-hour proteinuria. Receiver operating characteristics curves to discriminate between values below and greater than or equal to the threshold of 0.3 g protein per 24-hour had an area under the curve of respectively 0.94 (8 a.m.), 0.96 (noon) and 0.97 (5 p.m.). Sensitivities at 8 a.m., noon and 5 p.m. were respectively 89%, 96% and 94%; specificities were 75%, 78% and 78% with the proposed PCR cut-off of 30 mg/mmol (0.26 g/g) (National Institute for Health and Care Excellence guidelines).There is no evidence of a difference between the three measurement times regarding the sensitivities and specificities. The PCR determined in spot urine varies throughout the day but is a valid alternative for 24-hour urine collections in pregnant women. It is especially useful to rapidly identify clinically relevant proteinuria.


Alteration of gene expression in intervertebral disc degeneration of passive cigarette- smoking rats: separate quantitation in separated nucleus pulposus and annulus fibrosus.
We constructed a passive cigarette-smoking model with rats to investigate the molecular mechanism of intervertebral disc degeneration, and found by gene expression analysis that passive cigarette smoking stimulated the stress-responsive signal pathway and inhibited the apoptotic pathway. In this study, to clarify that these changes were derived from either nucleus pulposus (NP) or annulus fibrosus (AF), we separately collected NP and AF and quantitatively analyzed gene expression. Total RNA was extracted from NP and AF of the lumbar intervertebral discs from rats which were kept in a smoking box for 4 and 8 weeks. Gene expression was measured by real-time PCR of cDNA synthesized from the total RNA. Stress-responsive protein, heat shock protein 70, was expressed similarly in NP and AF, and was upregulated to the same degree after 8 weeks of passive cigarette smoking. The protein tyrosine phosphatase gene was expressed more strongly in AF than in NP, and was upregulated after 8 weeks of smoking in both tissue parts. The type II collagen and aggrecan genes were predominantly expressed in AF and NP, respectively. These results indicate that passive cigarette smoking stimulates both NP and AF, and induces the stress-responsible genes such as heat shock protein 70 and protein tyrosine phosphatase in both.


A Dose Relationship Between Brain Functional Connectivity and Cumulative Head Impact Exposure in Collegiate Water Polo Players.
A growing body of evidence suggests that chronic, sport-related head impact exposure can impair brain functional integration and brain structure and function. Evidence of a robust inverse relationship between the frequency and magnitude of repeated head impacts and disturbed brain network function is needed to strengthen an argument for causality. In pursuing such a relationship, we used cap-worn inertial sensors to measure the frequency and magnitude of head impacts sustained by eighteen intercollegiate water polo athletes monitored over a single season of play. Participants were evaluated before and after the season using computerized cognitive tests of inhibitory control and resting electroencephalography. Greater head impact exposure was associated with increased phase synchrony [r (16) > 0.626, p < 0.03 corrected], global efficiency [r (16) > 0.601, p < 0.04 corrected], and mean clustering coefficient [r (16) > 0.625, p < 0.03 corrected] in the functional networks formed by slow-wave (delta, theta) oscillations. Head impact exposure was not associated with changes in performance on the inhibitory control tasks. However, those with the greatest impact exposure showed an association between changes in resting-state connectivity and a dissociation between performance on the tasks after the season [r (16) = 0.481, p = 0.043] that could also be attributed to increased slow-wave synchrony [F (4, 135) = 113.546, p < 0.001]. Collectively, our results suggest that athletes sustaining the greatest head impact exposure exhibited changes in whole-brain functional connectivity that were associated with altered information processing and inhibitory control.


Delayed presentation of spinal cord injury without radiographic abnormality (SCIWORA): a case report.
Spinal Cord Injury without Radiographic Abnormality (SCIWORA) is an unprecedented event to occur in adults but may lead to serious complications including permanent neurological impairments and death. In this article, we report a case of a 60-year-old male presenting to the emergency for a head and neck trauma after a motorbike accident, who reported only a neck ache and a normal primary neurological exam. The evolution was marked by the occurrence of paraplegia with a diminished sphincter tone and hypoesthesia beneath the T12 dermatome level after six hours, confirmed by the Magnetic Resonance Imaging (MRI). He underwent a deferred laminectomy within 30 days after receiving methylprednisolone, with partial neurological improvement after two months. An early recognition of the diagnosis was challenge for the emergency physician, given the wide variability of clinical presentations. Magnetic resonance imaging (MRI) is a key examination to guide the diagnosis and the management of these patients.


Association between the Use of Antibiotics and the Development of Acute Renal Injury in Patients Hospitalized for COVID-19 in a Hospital in the Peruvian Amazon.
Introduction: A significant antibiotic prescribing pattern associated with the COVID-19 pandemic has been described. Multiple protocols included empirical antimicrobials, leading to a substantial increase in antimicrobial consumption in medical care. A higher mortality rate is described among patients diagnosed with COVID-19 who received antibiotics. Objectives: To determine the association between the use of antibiotics and the development of acute renal injury in patients infected with SARS-CoV-2 in patients treated at the Hospital II EsSalud de Ucayali, 2021. Methods: A cross-sectional-analytical study was conducted, evaluating the medical records of patients admitted to the intensive care unit between July 2020 and July 2021. For the statistical analysis, measures of central tendency and dispersion, statistical hypothesis contrast tests were used in relation to acute kidney injury (AKI), antibiotic use and associated factors, derived from linear regression models. Results: The factors that were positively associated with the development of AKI were sepsis (aPR: 2.86; 95% CI: 1.26-6.43), shock (aPR:2.49; 95% CI: 1.28-4.86), mechanical ventilation (aPR:9.11; 95% CI: 1.23-67.57), and use of vancomycin (aPR: 3.15; 95% CI: 1.19-8.27). Conclusions: In the Peruvian Amazon, there is a high consumption and inadequate prescription of antibiotics. The drugs most commonly used for the treatment of COVID-19 were: aminoglycosides, vancomycin, ivermectin, azithromycin, tocilizumab, and corticosteroids. The development of AKI among hospitalized patients was found to be related to vancomycin administration. In addition, an association was found with the use of mechanical ventilation, a high body mass index, and the presence of complications such as sepsis or shock. Therefore, inappropriate antibiotic use for COVID-19 has been associated with multiple negative outcomes and consequences.


Cerebrovascular risk factors and MRI abnormalities in migraine.
Case series have demonstrated an increased incidence of white matter lesions (WMLs) in patients with migraine. It is controversial whether the evidence of subclinical brain lesions relates to a higher risk of cerebrovascular disease. The objective of this study was to evaluate the association between magnetic resonance imaging (MRI) subclinical brain lesions and cerebrovascular risk factors (hyperhomocysteinaemia, MTHFR genotype, patent foramen ovale, hypertension, smoking and hypercholesterolaemia). From our database of 1201 patients followed at our Headache Clinic since September 2003 we analysed the MRI findings of 253 individuals. All MRI were blindly analysed by a second neuroradiologist (C.A.) and patients with WMLs (study group) were evaluated. In order to assess the association of WMLs with specific vascular risk factors, patients with WMLs were matched, according to age, sex and ICHD II diagnosis, with an equal number of individuals with normal MRI (control group). Headache was classified by the International Classification of Headache Disorders (ICHD 2004) criteria. We did not find any statistically significant difference between the two groups with regard to the presence of the cerebrovascular disease risk factors considered. Our results confirm that the WMLs are not related to the cerebrovascular disease risk factors.


Early and late deaths after elective end of therapies for childhood cancer in Italy.
The first cohort of subjects treated for cancer during childhood is now entering adulthood, and it is necessary to determine whether treatment has been sufficient to completely eradicate the neoplastic clone, and whether the cancer itself or treatment-related toxicity may have increased the risk of premature death. For these reasons, long-term survival and causes of death were evaluated in a cohort of subjects treated for childhood cancer who reached the elective end of therapy in continuous remission and were registered until 1992 in the Italian Registry of off-therapy subjects (OTR). The vital status of OTR subjects was ascertained in 1996 by a postal survey through census bureaux; for deceased subjects, the cause of death was defined and compared with the expected rates in the general population. At follow-up, out of 6402 eligible and evaluable subjects, 890 were found to have died; the estimated overall survival at 20 years was 80.7% (95% CI 79.3-82.1). Most of the patients (84.6%) died due to recurrence of the primary cancer, usually within the first 5 years after the OT. The cumulative incidence of death due to recurrence of the primary tumor was greater among subjects treated for solid tumor than among those treated for leukemia/lymphoma (p = 0.0001); in contrast, OT subjects after leukemia and lymphoma were more likely to die due to of medical complications of therapy (p < 0.02). Second cancers were the second most frequent cause of death, with a 12-fold risk compared with the general population; the figures were similar in the 2 cancer groups. Compared with the general population, OT subjects were 32 times more likely than same-age subjects to die. The SMR decreased to 6.1 when only non-cancer deaths were considered. Deaths due to external or avoidable causes occurred among survivors at a rate similar to that of the general population.


Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination.
Ab-targeted vaccination involves targeting a receptor of choice expressed by dendritic cells (DCs) with Ag-coupled Abs. Currently, there is little consensus as to which criteria determine receptor selection to ensure superior Ag presentation and immunity. In this study, we investigated parameters of DC receptor internalization and determined how they impact Ag presentation outcomes. First, using mixed bone marrow chimeras, we established that Ag-targeted, but not nontargeted, DCs are responsible for Ag presentation in settings of Ab-targeted vaccination in vivo. Next, we analyzed parameters of DEC205 (CD205), Clec9A, CD11c, CD11b, and CD40 endocytosis and obtained quantitative measurements of internalization speed, surface turnover, and delivered Ag load. Exploiting these parameters in MHC class I (MHC I) and MHC class II (MHC II) Ag presentation assays, we showed that receptor expression level, proportion of surface turnover, or speed of receptor internalization did not impact MHC I or MHC II Ag presentation efficiency. Furthermore, the Ag load delivered to DCs did not correlate with the efficiency of MHC I or MHC II Ag presentation. In contrast, targeting Ag to CD8(+) or CD8(-) DCs enhanced MHC I or MHC II Ag presentation, respectively. Therefore, receptor expression levels, speed of internalization, and/or the amount of Ag delivered can be excluded as major determinants that dictate Ag presentation efficiency in setting of Ab-targeted vaccination.


Cloning and identification of human syntaxin 5 as a synaptobrevin/VAMP binding protein.
Syntaxins are transmembrane proteins that function in regulating transport vesicle docking and fusion with target membranes in neuronal and nonneuronal cells. Vesicle docking is thought to be regulated in part by the specific interactions of syntaxin with a vesicle-associated membrane protein termed synaptobrevin/VAMP. We have cloned a 1557-bp cDNA that encodes the human syntaxin 5 isoform, using a combination of PCR and colony-screening methods. The deduced 301 amino-acid sequence of human syntaxin 5 shares 96% identity with rat syntaxin 5. Like rat syntaxin 1A, human syntaxin 5 binds to synaptobrevin/VAMP in vitro. The identification of human syntaxin 5 as a synaptobrevin/VAMP-binding protein supports the hypothesis that syntaxin 5 regulates protein transport by binding to vesicle-associated membrane proteins.


Diabetes and nephropathy.
Diabetic nephropathy is the single most common disorder leading to renal failure. Its annual incidence has more than doubled in the past decade to reach 44% of all end-stage renal disease, despite recent therapeutic advances. Thus, research into diabetic nephropathy pathophysiology that could lead to new treatment approaches is urgently needed and this review aims to summarize the work performed in this area in the past year. There have been advances in the understanding of diabetic nephropathy pathology. Clearly, structural changes may be advanced before any clinical findings are apparent. Not all functional consequences of the condition are explained by current structural analyses. Genetic studies have connected the disorder risk to multiple candidate genes and a few genetic loci, but the exact genetic predisposition or protectors are not fully described. Perturbations in multiple metabolic pathways are associated with diabetic nephropathy in animals and humans, but their relative importance requires further work. Glycemia and blood pressure control are crucial for diabetic nephropathy prevention and treatment, but new modalities are needed. Recent advances in molecular biology and genetics will bring new insights to the mechanisms involved in diabetic nephropathy development. This will allow early identification of patients at risk of, or safe from, diabetic nephropathy and will hopefully lead to preventive strategies, based on the understanding of the pathophysiology of the disorder. Meanwhile, aggressive implementation of proven therapies to prevent (glycemic control) and slow (antihypertensive therapy, especially with renin-angiotensin system blockers) the progression of diabetic nephropathy are strongly recommended.


A 2-Month Linear Periodized Resistance Exercise Training Improved Musculoskeletal Fitness and Specific Conditioning of Navy Cadets.
Vantarakis, A, Chatzinikolaou, A, Avloniti, A, Vezos, N, Douroudos, II, Draganidis, D, Jamurtas, AΖ, Kambas, A, Kalligeros, S, and Fatouros, IG. A 2-month linear periodized resistance exercise training improved musculoskeletal fitness and specific conditioning of navy cadets. J Strength Cond Res 31(5): 1362-1370, 2017-Major objectives of army and navy training are the development of readiness, performance, and injury prevention. Numerous studies have examined the effect of specific strength training (ST) programs on performance of Special Forces and military personnel. Although navy personnel have to address on-board conditions that require the development of strength, agility, speed, and task-specific endurance, there is no information regarding the effects of ST on navy-specific performance. Therefore, the purpose of this study was to investigate the effect of an 8-week ST on performance of navy cadets. Thirty-one cadets of the Hellenic Naval Academy volunteered to participate and were randomly assigned in 2 groups. Cadets in the Experimental Group participated in a linear periodized ST program in addition to their daily training schedule. Cadets in the control group participated only in pre- and post-measurements. Anthropometrics, maximal oxygen consumption, oxygen consumption during a Navy Obstacle Course (NOC), maximum strength in bench press and squat exercises, hand grip strength, repetitions in push-ups and abdominal test, time to complete a 30-m sprint, and time to complete NOC were measured before and after the intervention. A 2-way repeated-measures analysis of variance showed that ST induced favorable changes in bench press and squat 1 repetition maximum, push-ups, abdominal crunches, time to complete 30-m distance, and time to complete the NOC. These results indicate that an additional ST may induce positive alterations on readiness and performance of navy cadets. The study has the approval of university's institutional review board and ethical committee.


Evaluation of the Field Performance of ImmunoCard STAT!® Rapid Diagnostic Test for Rotavirus in Dadaab Refugee Camp and at the Kenya-Somalia Border.
AbstractRotavirus commonly causes diarrhea in children, leading to hospitalization and even death. Rapid diagnostic tests are feasible alternatives for determining rotavirus outbreaks in refugee camps that have inadequate laboratory capacity. We evaluated the field performance of ImmunoCard STAT!® Rotavirus (ICS-RV) in Dadaab Refugee Camp and at the Kenya-Somalia border. From May to December 2014, we prospectively enrolled children aged < 5 years hospitalized with acute diarrhea, defined as ≥ 3 episodes of loose stool in 24 hours for < 7 days. Stool samples were collected and tested by trained surveillance clerks using ICS-RV per manufacturer's instructions. The field performance characteristics of ICS-RV were evaluated against the gold standard test, Premier™ Rotaclone® enzyme immunoassay. The operational characteristics were evaluated using World Health Organization (WHO) ASSURED criteria to determine whether ICS-RV is appropriate as a point-of-care test by administering a standard questionnaire and observing surveillance clerks performing the test. We enrolled 213 patients with a median age of 10 months (range = 1-48); 58.2% were male. A total of 71 (33.3%) and 60 (28.2%) patients tested positive for rotavirus infection by immunoassay and ICS-RV, respectively. The sensitivity, specificity, and positive and negative predictive values of ICS-RV compared with the immunoassay were 83.1% (95% confidence interval [CI] = 72.3-91.0), 99.3% (95% CI = 96.1-100), 98.3% (95% CI = 91.1-100), and 92.1% (95% CI = 86.6-95.5), respectively. The ICS-RV fulfilled the WHO ASSURED criteria for point-of-care testing. ICS-RV is a field-ready point-of-care test with good field performance and operational characteristics. It can be useful in determining rotavirus outbreaks in resource-limited settings.


Modeling and analysis of ultrasound backscattering by spherical aggregates and rouleaux of red blood cells.
The present study concerns the modeling and analysis of ultrasound backscattering by red blood cell (RBC) aggregates, which under pathological conditions play a significant role in the rheology of blood within human vessels. A theoretical model based on the convolution between a tissue matrix and a point spread function, representing, respectively, the RBC aggregates and the characteristics of the ultrasound system, was used to examine the influence of the scatterer shape and size on the backscattered power. Both scatterers in the form of clumps of RBC aggregates and rouleaux were modeled. For all simulations, the hematocrit was kept constant at 10%, the ultrasound frequency was 10 MHz, the insonification angle was varied from 0 to 90 degrees , and the scatterer size (diameter for clumps and length for rouleaux) ranged from 4 mum to 120 mum. Under Rayleigh scattering by assuming a Poisson distribution of scatterers in space, the ultrasound backscattered power increased linearly with the particle volume. For non-Rayleigh scatterers, the intensity of the echoes diminished as the scatterer volume increased, with the exception of rouleaux at an angle of 90 degrees . As expected, the backscattered power was angularly dependent for anisotropic particles (rouleaux). The ultrasound backscattered power did not always increase with the size of the aggregates, especially when they were no longer Rayleigh scatterers. In the case of rouleaux, the anisotropy of the backscattered power is emphasized in the non-Rayleigh region.


Immunological and functional differences between human type I and II colony-stimulating factors.
Two distinct types of colony-stimulating factor (CSF) have recently been described in human tissues and cultured cell lines. Antisera to purified type I and II CSF were prepared in rabbits. Anti-CSF I antibody inhibits CSF I, but has no effect on CSF II. It cross-inhibits CSF I from several other human sources, but does not inhibit CSF from mouse lung or mouse L cells. Anti-CSF II antibody inhibits the activity of CSF II, but has no effect on CSF I. A radioimmunoassay for CSF I has been established. Competitive binding assay further demonstrated the immunological differences between CSF I and II. When CSF II is used to stimulate human marrow cells fractionated by sedimentation velocity, two populations of CFU-C are separated, one sedimenting at 8 mm/h and forming colonies by day 7, and a second sedimenting at 6.8 mm/h and forming colonies by day 13. In contrast, CSF I does nt stimulate colony growth by day 7 but does do so by day 13 in cells sedimenting between 7.2-8.5 mm/h. These results indicate that CSF I and II are distinct in their biochemical, immunological, and functional properties.


Exchange of carbon-bound hydrogen atoms ortho to the hydroxyl group in tyrosine.
The carbon-bound hydrogen atoms of tyrosine that exchange with solvent protons in strongly acid solutions at about 100 degrees C are not the methylene hydrogen atoms but a pair on the aromatic ring. Of the two pairs of protons on the aromatic ring, observed in the proton magnetic resonance spectra, the pair at higher field undergoes exchange in 2.4N DCI at 100 degrees C. Other hydrogen atoms, attached either to aliphatic or aromatic carbon atoms, exhibit no noticeable exchange under the same conditions. From a chemicalshift analysis the exchanging protons are assigned as those ortho to the hydroxyl group on the aromatic ring.


Genomic comparative analysis and gene function prediction in infectious diseases: application to the investigation of a meningitis outbreak.
Next generation sequencing (NGS) is being increasingly used for the detection and characterization of pathogens during outbreaks. This technology allows rapid sequencing of pathogen full genomes, useful not only for accurate genotyping and molecular epidemiology, but also for identification of drug resistance and virulence traits. In this study, an approach based on whole genome sequencing by NGS, comparative genomics, and gene function prediction was set up and retrospectively applied for the investigation of two N. meningitidis serogroup C isolates collected from a cluster of meningococcal disease, characterized by a high fatality rate. According to conventional molecular typing methods, all the isolates had the same typing results and were classified as outbreak isolates within the same N. meningitidis sequence type ST-11, while full genome sequencing demonstrated subtle genetic differences between the isolates. Looking for these specific regions by means of 9 PCR and cycle sequencing assays in other 7 isolates allowed distinguishing outbreak cases from unrelated cases. Comparative genomics and gene function prediction analyses between outbreak isolates and a set of reference N. meningitidis genomes led to the identification of differences in gene content that could be relevant for pathogenesis. Most genetic changes occurred in the capsule locus and were consistent with recombination and horizontal acquisition of a set of genes involved in capsule biosynthesis. This study showed the added value given by whole genome sequencing by NGS over conventional sequence-based typing methods in the investigation of an outbreak. Routine application of this technology in clinical microbiology will significantly improve methods for molecular epidemiology and surveillance of infectious disease and provide a bulk of data useful to improve our understanding of pathogens biology.


Assessment of intracranial pressure with ultrasonographic retrobulbar optic nerve sheath diameter measurement.
Ultrasonograpic retrobulbar optic nerve sheath diameter (ONSD) measurement is considered to be an alternative noninvasive method to estimate intracranial pressure,but the further validation is urgently needed. The aim of the current study was to investigate the association of the ultrasonographic ONSD and intracranial pressure (ICP) in patients. One hundred and ten patients whose intracranial pressure measured via lumbar puncture were enrolled in the study. Their retrobulbar ONSD with B-scan ultrasound was determined just before lumber puncture. The correlation between the ICP and the body mass index (BMI), ONSD or age was established respectively with the Pearson correlation coefficient analysis. The discriminant analysis was used to obtain a discriminant formula for predicting ICP with the ONSD、BMI、gender and age. Another 20 patients were recruited for further validation the efficiency of this discriminant equation. The mean ICP was 215.3 ± 81.2 mmH2O. ONSD was 5.70 ± 0.80 mm in the right eye and 5.80 ± 0.77 mm in the left eye. A significant correlation was found between ICP and BMI (r = 0.554, p < 0.001), the mean ONSD (r = 0.61, P < 0.001), but not with age (r = -0.131, p = 0.174) and gender (r = 0.03, p = 0.753). Using receiver operating characteristic (ROC) curve analysis, the critical value for the risk mean-ONSD was 5.6 mm from the ROC curve, with the sensitivity of 86.2% and specificity of 73.1%. With 200 mmH2O as the cutoff point for a high or low ICP, stepwise discriminant was applied, the sensitivity and specificity of ONSD predicting ICP was 84.5%-85.7% and 86.5%-92.3%. Ophthalmic ultrasound measurement of ONSD may be a good surrogate of invasive ICP measurement. This non-invasive method may be an alternative approach to predict the ICP value of patients whose ICP measurement via lumbar puncture are in high risk. The discriminant formula, which incorporated the factor of BMI, had similar sensitivity and higher specificity than the ROC curve.


Preoperative C-reactive protein predicts the need for repeated intracerebral brain abscess drainage.
To determine predicting factors for repeated surgical drainage in patients with intracerebral brain abscesses. Patients operated between 01/2008 and 10/2013 with a single-burr-hole technique to drain an intracerebral brain abscess were included from our prospective database. Clinical and radiological characteristics were analyzed retrospectively and compared between patients requiring a single surgical abscess drainage (S group) vs. patients requiring multiple surgical abscess aspirations (M group). Thirty-five patients (mean age 42.6 years, 14 females) including 27 patients in the S group and 8 in the M group were included in this study. Age, gender, causing bacterial agent, surgical technique and abscess volume were comparable for both groups. Preoperative mean C-reactive protein (CRP) (13.9 mg/l vs. 56.1 mg/l, p=0.015) was significantly higher in the M group. Preoperative mean leukocyte count (12.3×10(9)/l vs. 8.9×10(9)/l, p=0.050) was borderline significantly higher in the M group. Although the origin in the overall population was cryptogenic in 43% of the cases, this was never the case in the patient population needing multiple surgeries. Patients with multiple intracerebral brain abscess aspirations showed significantly higher preoperative CRP values than patients who needed surgery only once. Patients with high CRP values at admission and obvious origin of infection might need closer radiographic as well as clinical and laboratory exams after surgery to earlier select patients, which need repeated surgery.


Valence and Core Photoelectron Spectra of Aqueous I3- from Multi-Reference Quantum Chemistry.
The I3- molecule is known to undergo substantial structural reorganization upon solvation by a protic solvent, e.g., water. However, the details of this process are still controversially discussed in the literature. In the present study, we combined experimental and theoretical efforts to disentangle this controversy. The valence (5p), N4,5 (4d), and M4,5 (3d) edge photoelectron spectra were measured in an aqueous solution and computed using high-level multi-reference methods. Our previous publication mainly focused on obtaining reliable experimental evidence, whereas in the present article, we focused primarily on theoretical aspects. The complex electronic structure of I3- requires the inclusion of both static and dynamic correlation, e.g., via the multi-configurational perturbation theory treatment. However, the resulting photoelectron spectra appear to be very sensitive to problems with variational stability and intruder states. We attempted to obtain artifact-free spectra, allowing for a more reliable interpretation of experiments. Finally, we concluded that the 3d Photoelectron Spectrum (PES) is particularly informative, evidencing an almost linear structure with a smaller degree of bond asymmetry than previously reported.


An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry).
Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile-stratified model, and propensity score-matched model. The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank P<0.001). Using multivariable Cox proportional hazards analysis, home hemodialysis was associated with superior patient survival (hazard ratio for overall death, 0.47; 95% confidence interval, 0.38 to 0.59) as well as better on-treatment survival (hazard ratio for on-treatment death, 0.34; 95% confidence interval, 0.26 to 0.45), composite patient and technique survival (hazard ratio for death or technique failure, 0.34; 95% confidence interval, 0.29 to 0.40), and death-censored technique survival (hazard ratio for technique failure, 0.34; 95% confidence interval, 0.28 to 0.41). Similar results were obtained with the propensity score models as well as sensitivity analyses using competing risks models and different definitions for technique failure and lag period after modality switch, during which events were attributed to the initial modality. Home hemodialysis was associated with superior patient and technique survival compared with peritoneal dialysis.


Melting properties of AgxPt1-x nanoparticles.
At the nanoscale, materials exhibit unique properties that differ greatly from those of the bulk state. In the case of AgxPt1-x nanoalloys, we aimed to study the solid-liquid transition of nanoparticles of different sizes and compositions. This system is particularly interesting since Pt has a high melting point (2041 K compared to 1035 K for Ag) which could keep the nanoparticle solid during different catalytic reactions at relatively high temperatures, such as we need in the growth of nanotubes. We performed atomic scale simulations using a semi-empirical potential implemented in a Monte Carlo code at constant temperature and chemical composition in a canonical ensemble. We observed that the melting temperature decreases with decreasing size (pure systems and alloys) and increasing Ag content. We show that the melting systematically passes through an intermediate stage with a crystalline core (pure platinum or mixed PtAg depending on the composition) and a pure silver liquid skin, which strongly questions the idea of having a faceted solid particle in catalytic reactions for carbon nanotube synthesis.


Creating telehealth networks from existing infrastructures.
Implementing a telehealth program from the technical standpoint can be an engineering and financial challenge due to associated costs such as hardware, software, networking, administration and human expertise. To maximize potential and minimize costs, it makes sense to leverage existing telecommunications infrastructures and tailor the program based on what is available. This is especially critical in developing nations where funding is often limited.


Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial.
Late-onset sepsis frequently complicates prematurity, contributing to morbidity and mortality. Probiotics may reduce mortality and necrotizing enterocolitis (NEC) in preterm infants, with unclear effect on late-onset sepsis. This study aimed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis. A prospective multicenter, double-blinded, placebo-controlled, randomized trial compared daily administration of a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis, containing 1 × 10(9) total organisms) with placebo (maltodextrin) in infants born before 32 completed weeks' gestation weighing <1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis. Between October 2007 and November 2011, 1099 very preterm infants from Australia and New Zealand were randomized. Rates of definite late-onset sepsis (16.2%), NEC of Bell stage 2 or more (4.4%), and mortality (5.1%) were low in controls, with high breast milk feeding rates (96.9%). No significant difference in definite late-onset sepsis or all-cause mortality was found, but this probiotic combination reduced NEC of Bell stage 2 or more (2.0% versus 4.4%; relative risk 0.46, 95% confidence interval 0.23 to 0.93, P = .03; number needed to treat 43, 95% confidence interval 23 to 333). The probiotics B infantis, S thermophilus, and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants, but not definite late-onset sepsis or mortality. Treatment with this combination of probiotics appears to be safe.


Trabecular Bone Structure in the Distal Femur of Humans, Apes, and Baboons.
Trabecular bone structure has been used to investigate the relationship between skeletal form and locomotor behavior on the premise that trabecular bone remodels in response to loading during an animal's lifetime. The aim of this study is to characterize human distal femoral trabecular bone structure in comparison to three non-human primate taxa and relate the patterns of trabecular structural variation in the distal femur to knee posture during habitual locomotor behavior. A whole-epiphysis approach was applied using microCT scans of the distal femora of extant Homo sapiens, Pan troglodytes, Pongo pygmaeus, and Papio spp. (N = 48). Bone volume fraction (BV/TV) was quantified in the epiphysis and analyzed with both whole-condyle and a novel sector analysis. The results indicate high trabecular bone structural variation within and between species. The sector analysis reveals the most distinctive patterns in the stereotypically loaded human knee, with a pattern of high BV/TV distally. In general, Pan, Pongo, and Papio show evidence of flexed knee postures, typical of their locomotor behaviors, with regions of high BV/TV posteriorly within the condyles. The pairwise comparisons confirm the unique pattern in Homo and reveal a shared high BV/TV region in the patellar groove of both Homo and Papio. The distinct pattern found in Homo relative to the other primate taxa suggests a plastic response to unique loading patterns during bipedal locomotion. Results may facilitate resolving the antiquity of habitual bipedality in the hominin fossil record. This analysis also presents new approaches for statistical analysis of whole-epiphysis trabecular bone structure. Anat Rec, 2018. © 2018 American Association for Anatomy.


Fibrin mechanisms and functions in nervous system pathology.
In brain physiology, cerebrovascular interactions regulate both, vascular functions, such as blood vessel branching and endothelial cell homeostasis, as well as neuronal functions, such as local synaptic activity and adult neurogenesis. In brain pathology, including stroke, HIV encephalitis, Alzheimer Disease, multiple sclerosis, bacterial meningitis, and glioblastomas, rupture of the vasculature allows the entry of blood proteins into the brain with subsequent edema formation and neuronal damage. Fibrin is a blood-derived protein that is not produced by cells of the nervous system, but accumulates only after disease associated with vasculature rupture. This review presents evidence from human disease and animal models that highlight the role of fibrin in nervous system pathology. Our review presents novel experimental data that extend the role of fibrin, from that of a blood-clotting protein in cerebrovascular pathologies, to a component of the perivascular extracellular matrix that regulates inflammatory and regenerative cellular responses in neurodegenerative diseases.


Electrostatic properties of adsorbed polar molecules: opposite behavior of a single molecule and a molecular monolayer.
We compare the electrostatic behavior of a single polar molecule adsorbed on a solid substrate with that of an adsorbed polar monolayer. This is accomplished by comparing first principles calculations obtained within a cluster model and a periodic slab model, using benzene derivatives on the Si(111) surface as a representative test case. We find that the two models offer diametrically opposite descriptions of the surface electrostatic phenomena. Slab electrostatics is dominated by dipole reduction due to intermolecular dipole-dipole interactions that partially depolarize the molecules, with charge migration to the substrate playing a negligible role due to electric field suppression outside the monolayer. Conversely, cluster electrostatics is dominated by dipole enhancement due to charge migration to/from the substrate, with only a small polarization of the molecule. This establishes the important role played by long-range interactions, in addition to local chemical properties, in tailoring surface chemistry via polar molecule adsorption.


High-temperature requirement protein A4 (HtrA4) suppresses the fusogenic activity of syncytin-1 and promotes trophoblast invasion.
Cell-cell fusion and cell invasion are essential for placental development. Human cytotrophoblasts in the chorionic villi may undergo cell-cell fusion to form syncytiotrophoblasts to facilitate nutrient-gas exchange or differentiate into extravillous trophoblasts (EVTs) to facilitate maternal-fetal circulation. The placental transcription factor glial cells missing 1 (GCM1) regulates syncytin-1 and -2 expression to mediate trophoblast fusion. Interestingly, GCM1 and syncytin-1 are also expressed in EVTs with unknown physiological functions. In this study, we performed chromatin immunoprecipitation-on-chip (ChIP-chip) analysis and identified the gene for high-temperature requirement protein A4 (HtrA4) as a GCM1 target gene, which encodes a serine protease facilitating cleavage of fibronectin and invasion of placental cells. Importantly, HtrA4 is immunolocalized in EVTs at the maternal-fetal interface, and its expression is decreased by hypoxia and in preeclampsia, a pregnancy complication associated with placental hypoxia and shallow trophoblast invasion. We further demonstrate that HtrA4 interacts with syncytin-1 and suppresses cell-cell fusion. Therefore, HtrA4 may be crucial for EVT differentiation by playing a dual role in prevention of cell-cell fusion of EVTs and promotion of their invasion into the uterus. Our study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia.


Endometrial endometrioid adenocarcinoma of the uterine corpus involving the cervix: some cases probably represent independent primaries.
The majority of endometrial endometrioid adenocarcinomas involving the cervix have tumor morphology that is similar in the endometrium and the endocervix. There are, however, some cases in which the morphology of the tumor in the endocervix is different from the endometrial carcinoma, in which it is more invasive than the endometrial carcinoma, or in which invasion only occurs in the endocervix while there is no or only minimal myometrial invasion. The goal of this study was to investigate whether tumors involving the endometrium and the endocervix are similar or 2 independent primaries by hematoxylin and eosin stain, immunohistochemistry (IHC), human papillomavirus (HPV) DNA in situ hybridization, RNA reverse transcriptase in situ polymerase chain reaction (PCR) analyses to reveal HPV, and DNA clonality studies. We selected 14 cases of endometrial endometrioid adenocarcinomas involving the cervix with complete pathology material available from the years between 1968 and 2004. Immunohistochemical studies for vimentin, carcinoembryonic antigen, estrogen receptor, progesterone receptor, and p16 were performed in 12 cases; HPV DNA/RNA analyses in 4 cases; and clonality studies in 9 cases. The patients' ages ranged from 42 to 81 years (mean: 62 y). Follow-up information was obtained in 11 patients. Histologic features varied between the tumors in the endometrium and the endocervix in 8 cases, and 5 of these cases had uniform, dilated glands having a microcystic appearance in the cervix. In 6 cases, the tumors in the endometrium and the endocervix had similar histologic features. The immunohistochemical studies showed some differences between the endometrial and endocervical adenocarcinomas in 8 of the 12 cases, independent of differing or similar histologic features. HPV testing in 4 of the cases (3 with similar and 1 with different histology) yielded similar results in the endometrium and endocervix: 2 cases were negative, 1 was positive and 1 was equivocal for HPV DNA/RNA analyses. Clonality studies showed differences between the adenocarcinoma in the endometrium and the endocervix in 7 cases, including 5 cases with different histologic appearances; 2 cases had similar loss of heterozygosity patterns. In conclusion, as suggested by clonality studies, coexisting endometrial and endocervical carcinomas with different histologic features are most likely independent neoplasms. Endometrial and endocervical carcinomas that have similar appearances can represent either the same neoplasm or independent primaries. Clonality tests may help determine their relationship. IHC studies may not be helpful for synchronous endometrial and endocervical tumors, especially those of endometrioid type. It is possible that IHC identifies cell differentiation, rather than site of origin. HPV studies are important to identify endocervical tumors associated with high-risk HPV. However, endometrial tumors involving the cervix and endocervical tumors unrelated to HPV are both negative for high-risk HPV.


Cross reactivity studies with platinum group metal salts in platinum-sensitised rats.
Hooded Lister rats were sensitised to the halide salt of platinum ammonium tetrachloroplatinate(II)[(NH4)2PtCl4] in its conjugated form with ovalbumin. Sensitisation was achieved by intraperitoneal injection with Bordetella pertussis vaccine as adjuvant, followed 21 days later by a further injection in saline. The presence of specific anti-platinum IgE antibody was determined by passive cutaneous anaphylaxis (PCA) and radioallergosorbent test (RAST) using the platinum halide salt conjugated to a heterologous carrier. Sera exhibiting positive reactions were pooled and PCA tests performed on the titrated pooled sera with 3 conjugated platinum group metal salts, 5 platinum group metals in their free salt form and 6 platinum salts with differing ligands. PCA challenges with these compounds resulted in significant cross reactivity between ammonium tetrachloroplatinate(II), ammonium hexachloroplatinate(IV) and the conjugated tetrachloroplatinate. There was very limited cross reactivity with other platinum or platinum group metal salts in either free or conjugated forms. Furthermore, these results were confirmed by RAST inhibition studies.


Distribution of type III collagen in the pulp parenchyma of the human developing tooth. Light and electron microscope immunotyping.
The distribution of collagen type III throughout the pulp tissue from human developing tooth was studied using specific antibodies, immuno-fluorescence as well as immuno-peroxidase labelling for electron microscopy. Our results indicate that type III and type I collagen are present in the pulp. The staining intensity seems to correlate with the relatively high proportions of type III collagen biochemically found in pulp. In addition, type III collagen and reticulin fibres are similarly distributed, except that the Von Korff fibres were never detected with anti-type III collagen antibodies. Correspondingly, at the ultrastructural level, type III collagen appears as fine, branched filaments or electron dense material distributed throughout the tissue and particularly in close association with the plasma membrane of pulp fibroblasts. In contrast, type I collagen appears as typical coarse cross banded fibres.


Inherent differences in keratinocyte function in hidradenitis suppurativa: Evidence for the role of IL-22 in disease pathogenesis.
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.


First detection of AmpC β-lactamase bla(CMY-2) on a conjugative IncA/C plasmid in a Vibrio parahaemolyticus isolate of food origin.
Vibrio parahaemolyticus is an important causative agent of gastroenteritis, with the consumption of contaminated seafood being the major transmission route. Resistance to penicillin is common among V. parahaemolyticus strains, whereas cephalosporin resistance remains rare. In an attempt to assess the current prevalence and characteristics of antibiotic resistance of this pathogen in common food samples, a total of 54 (17% of the total samples) V. parahaemolyticus strains were isolated from 318 meat and seafood samples purchased from supermarkets and wet markets in Shenzhen, China, in 2013. These isolates exhibited high-level resistance to ampicillin, yet they were mostly susceptible to other antimicrobials, except for two that were resistant to extended-spectrum cephalosporins. The β-lactamase gene blaPER-1 was detectable in one strain, V. parahaemolyticus V43, which was resistant to both third- and fourth-generation cephalosporins. Compared to other blaPER-1-positive V. parahaemolyticus strains reported in our previous studies, strain V43 was found to harbor an ∼200-kb conjugative plasmid carrying genes that were different from the antimicrobial resistance genes reported from the previous studies. The β-lactamase gene blaCMY-2 was detectable for the first time in another V. parahaemolyticus isolate, V4, which was resistant to third-generation cephalosporins. This blaCMY-2 gene was shown to be located in an ∼150-kb IncA/C-type conjugative plasmid with a genetic structure consisting of traB-traV-traA-ISEcp1-blaCMY-2-blc-sugE-encR-orf1-orf2-orf3-orf4-dsbC-traC, which is identical to that of other IncA/C conjugative plasmids in Enterobacteriaceae, albeit with a different size. These findings indicate that the transmission of extended-spectrum-β-lactamase (ESBL) and AmpC β-lactamase genes via conjugative plasmids can mediate the development of extended-spectrum cephalosporin resistance in V. parahaemolyticus, thereby posing a potential threat to public health.


Low doses of TRH analogue act in the dorsal motor nucleus to induce gastric protection in rats.
Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.


Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial.
SARS-CoV-2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4. Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.


Critical evaluation of in silico methods for prediction of coiled-coil domains in proteins.
Coiled-coils refer to a bundle of helices coiled together like strands of a rope. It has been estimated that nearly 3% of protein-encoding regions of genes harbour coiled-coil domains (CCDs). Experimental studies have confirmed that CCDs play a fundamental role in subcellular infrastructure and controlling trafficking of eukaryotic cells. Given the importance of coiled-coils, multiple bioinformatics tools have been developed to facilitate the systematic and high-throughput prediction of CCDs in proteins. In this article, we review and compare 12 sequence-based bioinformatics approaches and tools for coiled-coil prediction. These approaches can be categorized into two classes: coiled-coil detection and coiled-coil oligomeric state prediction. We evaluated and compared these methods in terms of their input/output, algorithm, prediction performance, validation methods and software utility. All the independent testing data sets are available at http://lightning.med.monash.edu/coiledcoil/. In addition, we conducted a case study of nine human polyglutamine (PolyQ) disease-related proteins and predicted CCDs and oligomeric states using various predictors. Prediction results for CCDs were highly variable among different predictors. Only two peptides from two proteins were confirmed to be CCDs by majority voting. Both domains were predicted to form dimeric coiled-coils using oligomeric state prediction. We anticipate that this comprehensive analysis will be an insightful resource for structural biologists with limited prior experience in bioinformatics tools, and for bioinformaticians who are interested in designing novel approaches for coiled-coil and its oligomeric state prediction.


Identification of Mutations in Cell-Free Circulating Tumor DNA in Adrenocortical Carcinoma: A Case Series.
The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices for diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA predicted tumor dynamics. The present pilot study included six patients. Next-generation sequencing (NGS) showed mutations in three ACC cases. From these patients, blood was drawn before (1 to 2 weeks) and after surgery and cell-free circulating DNA (cfDNA) was isolated. Tumor-specific mutations were found in the cfDNA of one of the three patients, with metastasized ACC at diagnosis. NGS of the tumor showed an NRAS mutation (c.182A>G:p.Q61R) in 78%, a TP53 mutation (c.856G>A:p.E286K) in 60%, and a TERT gene mutation (1295250C>T) in 28% of the reads. The preoperative cfDNA showed the same mutations at a frequency of 64%, 32%, and 2%, respectively. The postoperative cfDNA showed the same mutations but at lower frequencies (52%, 16%, and 3%, respectively). The patient was postoperatively treated with mitotane and chemotherapy. No mutations were detected in the corresponding leukocyte DNA or in the cfDNA from the two other patients. To the best of our knowledge, we report for the first time mutations occurring at high levels in cfDNA collected before and after surgery from one of three patients, after previous identification in the tumor. However, in the cfDNA from two patients with known mutations, we were unable to reliably detect mutations in the cfDNA. Our results indicate that mutation detection in cfDNA can vary among ACC patients, and other approaches might be required to detect the tumor response and monitor progressive disease.


Mechanical loading causes site-specific anabolic effects on bone following exposure to ionizing radiation.
During spaceflight, astronauts will be exposed to a complex mixture of ionizing radiation that poses a risk to their health. Exposure of rodents to ionizing radiation on Earth causes bone loss and increases osteoclasts in cancellous tissue, but also may cause persistent damage to stem cells and osteoprogenitors. We hypothesized that ionizing radiation damages skeletal tissue despite a prolonged recovery period, and depletes the ability of cells in the osteoblast lineage to respond at a later time. The goal of the current study was to test if irradiation prevents bone accrual and bone formation induced by an anabolic mechanical stimulus. Tibial axial compression was used as an anabolic stimulus after irradiation with heavy ions. Mice (male, C57BL/6J, 16 weeks) were exposed to high atomic number, high energy (HZE) iron ions ((56)Fe, 2 Gy, 600 MeV/ion) (IR, n=5) or sham-irradiated (Sham, n=5). In vivo axial loading was initiated 5 months post-irradiation; right tibiae in anesthetized mice were subjected to an established protocol known to stimulate bone formation (cyclic 9N compressive pulse, 60 cycles/day, 3 day/wk for 4 weeks). In vivo data showed no difference due to irradiation in the apparent stiffness of the lower limb at the initiation of the axial loading regimen. Axial loading increased cancellous bone volume by microcomputed tomography and bone formation rate by histomorphometry in both sham and irradiated animals, with a main effect of axial loading determined by two-factor ANOVA with repeated measure. There were no effects of radiation in cancellous bone microarchitecture and indices of bone formation. At the tibia diaphysis, results also revealed a main effect of axial loading on structure. Furthermore, irradiation prevented axial loading-induced stimulation of bone formation rate at the periosteal surface of cortical tissue. In summary, axial loading stimulated the net accrual of cancellous and cortical mass and increased cancellous bone formation rate despite prior exposure to ionizing radiation, in this case, HZE particles. Our findings suggest that mechanical stimuli may prove an effective treatment to improve skeletal structure following exposure to ionizing radiation.


Changes in early psychosis service provision: a file audit.
To measure change in services provided to young people with first-episode psychosis following the introduction of specialized early psychosis teams and staff training. A standardized tool was developed to audit services provided to young people with first-episode psychosis. The tool initially comprised 27 clinical indicators measuring aspects of optimal care derived from the Australian clinical guidelines for early psychosis. The first 12 months of treatment, as documented in the case records, were audited for all young people receiving their first treatment for psychosis during a 6-month period prior to the introduction of these service developments (n = 47). These subjects were compared with those who received treatment after the implementation of service development strategies (n = 70). A comparison was also made within the second group, between those receiving some treatment from a specialized early psychosis team and those being exclusively treated by other services. Inter-rater reliability was achieved for 24 of the 27 indicators. Improvements were found on 10 indicators which measured psychosocial interventions, prescribing practices, family interventions and continuity of care. There was no significant deterioration on any of the indicators. Clients who attended early psychosis teams were significantly more likely to receive psychoeducation. The services increased their provision of "guideline concordant" care for early psychosis. The audit proved useful to monitor performance, to demonstrate improvements in care and to identify those areas of service provision and documentation in need of improvement.


[Genome organization of the plasmid of IncQ/P4 group and its vector derivatives].
The genome organization and functioning of IncQ/P4 plasmids are reviewed. Based on these plasmids, cloning vectors have been constructed for broad host range of gram-negative bacteria. Together with one- and two-replicon vectors for cloning via insertion inactivation of markers, specialized plasmid vectors are described: cosmids, promoter-probe vectors, vectors for direct selection of recombinant molecules. Examples of using broad host range vectors for gene cloning and expression in non-enteric gram-negative bacteria are presented.


Decision analysis model comparing cost of multiparametric magnetic resonance imaging vs. repeat biopsy for detection of prostate cancer in men with prior negative findings on biopsy.
We compared cost of multiparametric magnetic resonance imaging (MP-MRI) vs. repeat biopsy in detection of prostate cancer (PCa) in men with prior negative findings on biopsy. A decision tree model compared the strategy of office-based transrectal ultrasound-guided biopsy (TRUS) for men with prior negative findings on biopsy with a strategy of initial MP-MRI with TRUS performed only in cases of abnormal results on imaging. Study end points were cost, number of biopsies, and cancers detected. Cost was based on Medicare reimbursement. Cost of sepsis and minor complications were incorporated into analysis. Sensitivity analyses were performed by varying model assumptions. The baseline model with 24% PCa found that the overall cost for 100 men was $90,400 and $87,700 for TRUS and MP-MRI arms, respectively. The MP-MRI arm resulted in 73 fewer biopsies per 100 men but detected 4 fewer cancers (16 vs. 20.4) than the TRUS arm did. A lower risk of PCa resulted in lower costs for the MP-MRI arm and a small difference in detected cancers. At lower cancer rates, MP-MRI is superior to TRUS over a wide range of sensitivity and specificity of MRI. A lower sensitivity of MP-MRI decreases the cost of the MP-MRI, as fewer biopsies are performed, but this also reduces the number of cancers detected. The use of MP-MRI to select patients for repeat biopsy reduced the number of biopsies needed by 73% but resulted in a few cancers being missed at lower cost when compared with the TRUS arm. Further studies are required to determine whether cancers missed represent clinically significant tumors.


Developing incrementality in filler-gap dependency processing.
Much work has demonstrated that children are able to use bottom-up linguistic cues to incrementally interpret sentences, but there is little understanding of the extent to which children's comprehension mechanisms are guided by top-down linguistic information that can be learned from distributional regularities in the input. Using a visual world eye tracking experiment and a corpus analysis, the current study investigates whether 5- and 6-year-old children incrementally assign interpretations to temporarily ambiguous wh-questions like What was Emily eating the cake with __? In the visual world eye-tracking experiment, adults demonstrated evidence for active dependency formation at the earliest region (i.e., the verb region), while 6-year-old children demonstrated a spill-over effect of this bias in the subsequent NP region. No evidence for this bias was found in 5-year-olds, although the speed of arrival at the ultimately correct instrument interpretation appears to be modulated by the vocabulary size. These results suggest that adult-like active formation of filler-gap dependencies begins to emerge around age 6. The corpus analysis of filler-gap dependency structures in adult corpora and child corpora demonstrate that the distributional regularities in either corpora are equally in favor of early, incremental completion of filler-gap dependencies, suggesting that the distributional information in the input is either not relevant to this incremental bias, or that 5-year-old children are somehow unable to recruit this information in real-time comprehension. Taken together, these findings shed light on the origin of the incremental processing bias in filler-gap dependency processing, as well as on the role of language experience and cognitive constraints in the development of incremental sentence processing mechanisms.


[Metabolic micromilieu in tumours].
Solid malignant tumours are characterized by a heterogeneous metabolic micromilieu with the intra-individual variability within single tumours being substantially smaller than the inter-individual differences between tumours. Despite this variability, there are some hallmarks which are characteristic for the majority of malignancies. They include hypoxia, tissue acidosis, and abnormal microcirculation. Peculiarities of the carbohydrate metabolism and specifically of glycolysis in tumours receive increasing attention in experimental and clinical research. As shown by our research with induced bioluminescence, different tumours from various entities exhibit a large spectrum of lactate accumulation. Interestingly, primary lesions with metastasis contain significantly higher amounts of lactate as compared to non-metastatic tumours. Classification into high and low lactate tumours according to the median lactate concentration in combination with a Kaplan-Meier analysis reveals that survival of patients with high lactate tumours is significantly worse than that with low lactate carcinomas. Furthermore, there is a positive correlation between tumour lactate content and radio-resistance. High lactate tumours are characterized by a higher degree of malignancy and therapeutic resistance.


Orthopaedic manifestations of Brachmann-de Lange syndrome: a report of 34 patients.
Brachmann-de Lange syndrome (BDLS) is a disorder of unknown cause that is recognized on the basis of characteristic facies in association with growth retardation, mental retardation and, in many cases, upper limb anomalies. Because of its association with skeletal anomalies, patients with the syndrome are often referred to the paediatric orthopaedic surgeon. Thirty-four patients with Brachmann-de Lange syndrome were evaluated for the prevalence and pattern of musculoskeletal involvement. The average age of the patients was 10.2 years (range, 1 month to 44 years). Both sexes were affected equally. The common orthopaedic manifestation affected the hand (100%), elbow (47%), and the heel cord (26%). Severe bony anomalies included complete absence of the hand in one case, and ulna hemimelia in two cases. In two patients bilateral Legg-Perthes-like changes were noted. Scoliosis presented in four cases, all before the age of 10 years. Surgery was performed in two patients with severe bilateral equinovarus feet. Despite the constellation of musculoskeletal findings, most of the patients did not have surgical intervention for their deformities.


Clonemate cotransmission supports a role for kin selection in a puppeteer parasite.
Host manipulation by parasites is a fascinating evolutionary outcome, but adaptive scenarios that often accompany even iconic examples in this popular field of study are speculative. Kin selection has been invoked as a means of explaining the evolution of an altruistic-based, host-manipulating behavior caused by larvae of the lancet fluke Dicrocoelium dendriticum in ants. Specifically, cotransmission of larval clonemates from a snail first host to an ant second host is presumed to lead to a puppeteer parasite in the ant's brain that has clonemates in the ant abdomen. Clonal relatedness between the actor (brain fluke) and recipients (abdomen flukes) enables kin selection of the parasite's host-manipulating trait, which facilitates transmission of the recipients to the final host. However, the hypothesis that asexual reproduction in the snail leads to a high abundance of clonemates in the same ant is untested. Clonal relationships between the manipulator in the brain and the nonmanipulators in the abdomen are also untested. We provide empirical data on the lancet fluke's clonal diversity within its ant host. In stark contrast to other trematodes, which do not exhibit the same host-manipulating behavioral trait, the lancet fluke has a high abundance of clonemates. Moreover, our data support existing theory that indicates that the altruistic behavior can evolve even in the presence of multiple clones within the same ant host. Importantly, our analyses conclusively show clonemate cotransmission into ants, and, as such, we find support for kin selection to drive the evolution and maintenance of this iconic host manipulation.


Polarized Mechanosensitive Signaling Domains Protect Arterial Endothelial Cells Against Inflammation.
Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, which supports an anti-inflammatory phenotype that protects them from atherosclerosis. High laminar shear stress also supports flow-aligned cell elongation and front-rear polarity, but whether this is required for athero-protective signaling is unclear. Here, we show that Caveolin-1-rich microdomains become polarized at the downstream end of ECs exposed to continuous high laminar flow. These microdomains are characterized by higher membrane rigidity, filamentous actin (F-actin) and lipid accumulation. Transient receptor potential vanilloid-type 4 (Trpv4) ion channels, while ubiquitously expressed, mediate localized Ca 2+ entry at these microdomains where they physically interact with clustered Caveolin-1. The resultant focal bursts in Ca 2+ activate the anti-inflammatory factor endothelial nitric oxide synthase (eNOS) within the confines of these domains. Importantly, we find that signaling at these domains requires both cell body elongation and sustained flow. Finally, Trpv4 signaling at these domains is necessary and sufficient to suppress inflammatory gene expression. Our work reveals a novel polarized mechanosensitive signaling hub that induces an anti-inflammatory response in arterial ECs exposed to high laminar shear stress.


Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway.
Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in cancer therapy. Statins are cholesterol-lowering drugs with an excellent safety profile and associated with a reduced incidence of various cancers including colorectal cancer (CRC). The authors have previously shown that statins act by activating tumour suppressive bone morphogenetic protein (BMP) signalling in CRC, increasing expression of BMP2. BMP2 is silenced by hypermethylation in gastric cancer. To investigate whether BMP2 is methylated in CRC, whether statins can reverse this, and what implications this has for the use of statins in CRC. Methylation-specific PCR, bisulphite sequencing, immunoblotting, reverse transcription PCR, quantitative PCR, fluorescence-activated cell sorting analysis, an in vitro DNA methyltransferase (DNMT) assay, and cell viability studies were performed on CRC cells. The effect of statins was confirmed in a xenograft mouse model. Results BMP2 is silenced by promoter hypermethylation in cell lines with the hypermethylator phenotype and in primary tumours. Treatment with lovastatin downregulates DNMT activity, leading to BMP2 promoter demethylation and to upregulation of expression of BMP2 as well as other genes methylated in CRC. Statins alter gene expression, indicating a shift from a stem-like state to a more differentiated state, thereby sensitising cells to the effects of 5-fluorouracil. In a xenograft mouse model, simvastatin treatment induces BMP2 expression, leading to differentiation and reduced proliferation of CRC cells. Statins act as DNMT inhibitors, demethylating the BMP2 promoter, activating BMP signalling, inducing differentiation of CRC cells, and reducing 'stemness'. This study indicates that statins may be able to be used as differentiating agents in combined or adjuvant therapy in CRC with the CpG island methylator phenotype.


HER2 shedding and serum HER2 extracellular domain: biology and clinical utility in breast cancer.
The transmembrane protein HER2 is over-expressed in approximately 15% of invasive breast cancers as a result of HER2 gene amplification. HER2 proteolytic cleavage (HER2 shedding) generates soluble truncated HER2 molecules that include only the extracellular domain and the concentration of which can be measured in the serum fraction of blood. HER2 shedding also generates a constitutively active truncated intracellular receptor of 95kDa (p95(HER2)). Another soluble truncated HER2 protein (Herstatin), which can also be found in serum, is the product of an alternatively spliced HER2 transcript. Recent preclinical findings may provide crucial insights into the biological and clinical relevance of increased sHER2 concentrations for the outcome of HER2-positive breast cancer and sensitivity to trastuzumab and lapatinib treatment. We present here the most recent findings about the role and biology of sHER2 based on data obtained using a standardized test, which has been cleared by FDA in 2000, for measuring sHER2. This test includes quality control assessments and has been already widely used to evaluate the clinical utility of sHER2 as a biomarker in breast cancer. We will describe in detail data concerning the assessment of sHER2 as a surrogate maker to optimize the evaluation of the HER2 status of a primary tumor and as a prognosis and predictive marker of response to therapies, both in early and metastatic breast cancer.


Development of a dental model hardener.
The paper presents a novel method of strengthening dental gypsum materials by infiltrating with a low-viscosity autopolymerising monomer. Gypsum specimens were infiltrated with diluted butyl-cyanoacrylate monomer at different concentrations. Nanoindentation was employed to measure their hardness and elastic modulus. A standard single-edge-notched beam (SENB) method was used to measure fracture toughness. Biaxial strength was measured using a universal test machine with a piston-on-ring jig. Scanning Electron Microscopy (SEM) and affiliated energy dispersive X-ray spectroscopy (EDX) were used to observe the fracture topography and the depth of infiltration. Infiltration and autopolymerisation of the cyanoacrylate improved the biaxial strength and fracture toughness of the gypsum by around 39% and around 30%, respectively. The hardness and elastic modulus for the treated specimens were also higher, albeit slightly. The proposed method provides a convenient way to strengthen and repair dental gypsum models in situ.


Trade-off between cancer and aging: what role do other diseases play? Evidence from experimental and human population studies.
The potential gain in life expectancy which could result from the complete elimination of mortality from cancer in the U.S. would not exceed 3 years if one were to consider cancer independently of other causes of death. In this paper, we review evidence of trade-offs between cancer and aging as well as between cancer and other diseases, which, if taken into account, may substantially increase estimates of gain in life expectancy resulting from cancer eradication. We also used the Multiple Causes of Death (MCD) data to evaluate correlations among mortalities from cancer and other major disorders including heart disease, stroke, diabetes, Alzheimer's, Parkinson's diseases, and asthma. Our analyses revealed significant negative correlations between cancer and other diseases suggesting stronger population effects of cancer eradication. Possible mechanisms of the observed dependencies and emerging perspectives of using dependent competing risks models for evaluating the effects of reduction of mortality from cancer on life expectancy are discussed.


Enantioselective Antiviral Activities of Chiral Zinc Oxide Nanoparticles.
Chiral nanoparticles (C-NPs) play a crucial role in biomedical applications, especially in their biological effects on cytotoxicity and metabolism. However, there are rare reports about the antivirus property of C-NPs and their working mechanism. Here, three different types of chiral ZnO NPs (l-ZnO, d-ZnO, and dl-ZnO) were prepared as enantioselective antivirals. Biocompatibility test results showed that the three different chiral ZnO NPs varied significantly in cytotoxicity. Evaluation of their effects against porcine reproductive and respiratory syndrome virus (PRRSV) indicated that compared with d-ZnO and dl-ZnO NPs, l-ZnO NPs exhibited stronger anti-PRRSV activity due to their higher cognate cell adhesion and uptake. Furthermore, the high concentration of l-ZnO NPs can obviously reduce cellular reactive oxygen species (ROS) in MARC-145 cells, thus effectively preventing PRRSV-induced oxidative damage. This study demonstrated the outstanding antiviral properties of l-ZnO NPs, which may facilitate the development and application of C-NPs in antiviral drugs and tissue engineering.


Microbial surface contamination after standard operating room cleaning practices following surgical treatment of infection.
At the authors' institution, some joint arthroplasty surgeons require the operating room to be terminally cleaned before using the room after infected cases, in theory to decrease exposure to excessive microbial contamination for the subsequent patient. The authors found no guidance in the literature to support this practice. To test this theory, the authors measured microbial surface contamination from 9 surfaces in operating rooms after standard operating room turnover following 14 infected cases vs 16 noninfected cases. A check was made for an association between organisms isolated intraoperatively from infected surgical patients immediately preceding standard cleaning and organisms isolated from common operating room surfaces. Colony counts were made at 24 and 48 hours, and organisms were identified. No significant difference was noted in colony counts between infected and noninfected cases, and no relationship was found between organisms isolated from infected cases and those from operating room surfaces. Furthermore, the largest colony count from both groups (0.08 cfu/cm(2)) was an order of magnitude less than the recently proposed 5 cfu/cm(2) threshold for surface hygiene in hospitals. This finding indicates that standard operating room turnover results in minimal surface contamination, regardless of the previous case's infection status, and that there is no need for a more extensive terminal cleaning after an infected case.


Descriptive morphometry and stereology in accessing the testis structure and function of the marsupial Philander frenatus (Olfers, 1818) (Didelphimorphia: Didelphidae).
Philander frenatus is an important marsupial for the maintenance and conservation of the Atlantic Rainforest, however, it has biological characteristics that are still little explored. The study of the reproductive biology is an important key to understand the species reproductive strategies and to improve the development of conservation and management activities. The present study aimed to conduct a histological and morphometric investigation of the testis structure and function of P. frenatus. The average body and testicular weight were 445 g and 0.74 g, respectively, with a gonadosomatic index of 0.17%. The seminiferous tubules occupying 64.95% of the organ, totalising 9.26 m per gram of testis. The tubulesomatic and epitheliumsomatic indexes were 0.10% and 0.07%, respectively. Philander frenatus showed cell loss of approximately 98% during the proliferative phase and the spermatogenic yield was 10.3 cells. The high loss during the mitotic phase contributed to the low spermatogenic yield. The testicular parenchyma was composed of 35% of intertubular components, one of the highest proportions observed in mammals. Leydig cells were responsible for approximately 25% of the testes, followed by lymphatic space (6.44%), blood vessels and connective tissue (4% together). The organisation of the intertubular components resembles the Fawcett III category. The volume and number of Leydig cell per gram of testis were 2,627.12 µm3 and 91.28 × 106 cells, respectively. High investment in the intertubular compartment, specifically number and volume of Leydig cells in P. frenatus is consistent with territorial behaviour and polygynic mating system, which have greater androgenic capacity.


Estimating in vivo potassium distribution and fluxes with stable potassium isotopes.
Extracellular potassium (K+) homeostasis is achieved by a concerted effort of multiple organs and tissues. A limitation in studies of K+ homeostasis is inadequate techniques to quantify K+ fluxes into and out of organs and tissues in vivo. The goal of the present study was to test the feasibility of a novel approach to estimate K+ distribution and fluxes in vivo using stable K+ isotopes. 41K was infused as KCl into rats consuming control or K+-deficient chow (n = 4 each), 41K-to-39K ratios in plasma and red blood cells (RBCs) were measured by inductively coupled plasma mass spectrometry, and results were subjected to compartmental modeling. The plasma 41K/39K increased during 41K infusion and decreased upon infusion cessation, without altering plasma total K+ concentration ([K+], i.e., 41K + 39K). The time course of changes was analyzed with a two-compartmental model of K+ distribution and elimination. Model parameters, representing transport into and out of the intracellular pool and renal excretion, were identified in each rat, accurately predicting decreased renal K+ excretion in rats fed K+-deficient vs. control diet (P < 0.05). To estimate rate constants of K+ transport into and out of RBCs, 41K/39K were subjected to a simple model, indicating no effects of the K+-deficient diet. The findings support the feasibility of the novel stable isotope approach to quantify K+ fluxes in vivo and sets a foundation for experimental protocols using more complex models to identify heterogeneous intracellular K+ pools and to answer questions pertaining to K+ homeostatic mechanisms in vivo.


Tubal surgery in the era of assisted reproductive technology: clinical options.
We reviewed the place of tubal surgery in the era of assisted reproductive technology. Reversal of tubal ligation is one of the main indications for tubal microsurgery. Adhesiolysis has the best results if the adhesion is the only factor responsible for infertility. There are no differences between adhesiolysis by laparoscopy or by laparotomy, and so laparoscopy must be preferred. Proximal tubal obstructions can be successfully treated by microsurgical tubocornual anastomosis. As far as distal tubal lesions are concerned, success rates depend strictly on the pre-existing tubal disease in distal tubal lesions and tubal surgery frequently fails; in-vitro fertilization (IVF) must therefore be considered in such circumstances. In conclusion, we think that IVF and tubal surgery must be considered to be complementary rather than competitive procedures. Adequate selection of patients is crucial to find the best therapeutic approach.


Older men manifest multifold synchrony disruption of reproductive neurohormone outflow.
Under a working clinical hypothesis that aging putatively disrupts neuroendocrine control mechanisms, here we test a specific corollary notion that transitions in sleep stage, oscillations in nocturnal penile tumescence (NPT; a neurogenically organized signal), and the rates of instantaneous secretion of LH and/or testosterone are jointly synchronous in healthy young, but not older, men. To this end, we evaluated 10 young (aged 21-31 yr) and 8 older (aged 65-74 yr) men by intensive overnight multisite monitoring, viz. simultaneous electro-encephalogram and NPT recordings (every 30 s) and remote blood sampling (every 2.5 min) to quantitate LH and testosterone release. Waveform-independent deconvolution and cross-correlation analyses of these neurohormone outflow measures revealed that healthy young men sustain four salient physiological linkages overnight: 1) a strong inverse (confirmatory) relationship between sleep stage and NPT activity, such that deeper sleep is accompanied by suppression of NPT; 2) consistent coupling between NPT and testosterone secretion, wherein heightened NPT activity respectively precedes and follows increased testosterone secretion by 12.5-32.5 and 50-60 min; 3) evident synchrony between sleep stage and testosterone secretion, in which testosterone secretion increases over a 30-min window (-2.5 to 25 min) while sleep deepens; and 4) a close temporal linkage between instantaneous LH release and NPT oscillations, whereby LH secretion increases 55-62.5 min before and again 5-30 min after NPT declines. In contrast, older men manifested global loss of expected young adult synchrony; namely, 1) abolition of the inverse relationship between sleep stage and NPT, 2) decorrelation of NPT oscillations and testosterone secretion, 3) decoupling of testosterone release and deep sleep, and 4) abrogation of the linkage between LH secretion and penile detumescence. In summary, high intensity overnight monitoring of multiple reproductive neuroendocrine outflow measures simultaneously in young men delineates prominent neurophysiological coupling among sleep transitions and NPT activity, LH and testosterone secretion or NPT oscillations, and testosterone secretion and deepening sleep stage. In contrast, healthy older men exhibit near-universal disruption of physiological young adult synchronicity. Thus, we conclude that male reproductive aging is marked by erosion of coordinate regulation among sleep transitions, central nervous system-directed NPT activity, and hypothalamically driven episodic GnRH/LH (and thereby Leydig cell testosterone) secretion. Whether analogous multifold uncoupling of neurohormone signals emerges in the course of reproductive aging in women or in nonhuman species is not yet known.


[Characteristics of early disorders of fatty-acid composition of kidney lipids in spontaneous (hereditary) arterial hypertension].
Fatty acid composition of kidney lipids from spontaneously hypertensive Okamoto-Aoki rats (SHR) and normotensive Wistar rats (NR) was investigated two days after birth by gas-liquid chromatography. In SHR kidney phospholipids, as compared to the respective NR values, the content of arachidonic acid (20:4n6) was decreased and the levels of oleic (18:1n9) and docosahexaenoic (22:6n3) acids were increased; in kidney triglycerides, the content of eicosatrionoic acid (20:3n9) and all fatty acids of the linoleic acid series was decreased, except the content of a polyunsaturated long-chain product of linoleic acid metabolism, docosapentaenoic acid (22:5n6) that was increased. These changes may have developed prenatally as a result of genetic peculiarities of SHR.


MRI findings of hepatic alveolar echinococcosis.
Diagnosis of liver infestation by alveolar echinococcosis (AE) is based on serologic, sonographic and computed tomography (CT) findings. Experience with magnetic resonance imaging (MRI) demonstrates that features of this disease are limited. CT and MRI findings of 14 cases with hepatic AE were compared in this report. We have described the MRI appearance of hepatic AE, which exhibits variable signal intensities on T1- and T2-weighted images. Fibrous and parasitic tissue showed low signal both on T1- and, generally, on T2-weighted images. In a few cases, a high signal on T2-weighted images may be observed, due either to central necrotic zones or to small peripheral cyst. MRI than by CT was more easily identified central necrosis. However, MRI seemed to be less effective than CT in allowing us to reach a positive diagnosis, due to its inability to show microcalcifications. In addition, MRI may not reveal small lesions. In most cases, T1-weighted images revealed more clearly than CT did the margins of the lesions and the hepatic extension, especially to hepatic veins, vena cava and perihepatic spaces.


Competition between intra-community and inter-community synchronization and relevance in brain cortical networks.
In this paper the effects of inter-community links on the synchronization performance of community networks, especially on the competition between individual community and the whole network, are studied in detail. The study is organized from two aspects: the number or portion of inter-community links and the connection strategy of inter-community links between different communities. A critical point is found in the competition of global network and individual communities. Increasing the number of inter-community links will enhance the global synchronizability but degrade the synchronization performance of individual community before this point. After that the individual community will synchronize better and better as part of the whole network because the community structure is not so prominent. The critical point represents a balance region where the individual community is maximally independent while the information transmission remains effective between different communities. Among various connection strategies, connecting nodes belonging to different communities randomly rather than connecting nodes with larger degrees are the most efficient way to enhance global synchronization of the network. However, the dynamical modularity is the reverse case. A preferential connection scheme linking most of the hubs from the communities will allow rather efficient global synchronization while maintaining strong dynamical clustering of the communities. Interestingly, the observations are found to be relevant in a realistic network of cat cortex. The synchronization state is just at the critical point, which shows a reasonable combination of segregated function in individual communities and coordination among them. Our work sheds light on principles underlying the emergence of modular architectures in real network systems and provides guidance for the manipulation of synchronization in community networks.


Desmoplastic fibroma of the mandible.
We report the imaging findings of a desmoplastic fibroma (DF) of the mandible in a 3 years old girl. DF of bone is a rare, no-metastasizing but locally aggressive tumor. Hypercellularity, nuclear pleomorphism, mitotic activity, and traces of odontogenic epithelium and bony tissue are absent. US exam showed a highly vascular and well delimited mass, with no necrotic/hemorrhagic areas. It appeared as a well-defined osteolytic region in RX and a multiloculated, hypodense mass, with no periosteal reaction signs, in CT scans. MRI showed hypointensity in T1w TSE sequence and hyperintensity both in T1w TSE SPIR and T2w ones with no restriction of the "apparent diffusion coefficient" (ADC). In conclusion, remaining histology the gold standard for the DF diagnosis, imaging features may strongly suggest it.


Appropriateness of hysterectomy in Taiwan.
Hysterectomy is among the most frequently performed surgical procedures in developed countries, but few studies from the Asia-Pacific region have assessed the appropriateness of hysterectomy. The purpose of this study was to examine the rate of inappropriate hysterectomy in Taiwan and its association with patient characteristics and indications for the procedure. A random sample of hysterectomies for which claims were submitted to the Taiwan Bureau of National Health Insurance from July 1, 1997 to June 30, 1998 was selected. A total of 658 charts were reviewed by an expert panel composed of 5 senior gynecologists. Overall, 74.2% of patients underwent hysterectomy for appropriate reasons, 5.6% for uncertain reasons, and 20.2% for inappropriate reasons. Inappropriate procedures were positively associated with younger age and premenopausal status. Primary indications that accounted for over 25% of inappropriate procedures were chronic pelvic pain (42.9%), abnormal uterine bleeding (37.5%), and endometriosis (27.7%). This study found a high rate of inappropriate hysterectomy in Taiwan. Gynecologists and physician organizations should take action to improve physician agreement on the use of hysterectomy, especially for indications associated with high rates of inappropriate procedures.


Use of an argatroban-based purge solution in a percutaneous ventricular assist device.
The use of an argatroban-based percutaneous ventricular assist device (pVAD) purge solution in a patient with suspected heparin-induced thrombocytopenia (HIT) is described. A 70-year-old woman in cardiogenic shock was admitted to a coronary care unit after being discovered unresponsive at home. A transthoracic echocardiogram revealed a low ejection fraction and findings consistent with takotsubo cardiomyopathy. Administration of multiple inotropes and vasopressors was initially required for hemodynamic support. The patient was implanted with an Impella pVAD (Abiomed, Inc., Danvers, MA) using a heparin-based purge solution; an i.v. heparin infusion was initiated for supplemental systemic anticoagulation. Over the next 24 hours, the patient's platelet count decreased from 168,000 to 37,000 cells/μL. Given a differential diagnosis that included HIT, the patient was transitioned to an argatroban-based purge solution. Due to prolonged activated partial thromboplastin times, a systemic argatroban infusion was not initiated, and the patient remained fully anticoagulated throughout pVAD support with only the argatroban-based purge solution. An HIT antibody test was negative. On hospitalization day 9 (day 6 of pVAD support with argatroban use), the patient became hemodynamically stable and was weaned off pVAD support. Three days later, the platelet count had recovered to 117,000 cells/μL (from a nadir of 21,000 cells/μL). During pVAD support, the patient developed hemolytic anemia with minimal bleeding complications. Argatroban was used as a purge solution anticoagulant in a patient with an Impella pVAD and found to be a safe and effective alternative to heparin.


Amycolatopsis regifaucium sp. nov., a novel actinomycete that produces kigamicins.
The taxonomic position of seven soil actinomycetes provisionally assigned to the genus Amycolatopsis was established in a polyphasic study. The isolates, which had identical 16S rRNA gene sequences, had closest similarity to the type strain of Amycolatopsis orientalis. A representative isolate, strain GY080T, had chemotaxonomic properties that were typical of the genus Amycolatopsis and could be distinguished from the type strain of A. orientalis using DNA-DNA relatedness data. All of the isolates shared a phenotypic profile that distinguished them from representatives of phylogenetically closely related species. Amplified rDNA restriction analysis showed that the isolates formed a homogeneous group that was distinctly separate from single-membered groups consisting of representative Amycolatopsis type strains, including that of A. orientalis. Based on the combined genotypic and phenotypic evidence, it is proposed that the seven isolates be classified as representatives of a novel species for which the name Amycolatopsis regifaucium sp. nov. is proposed. The type strain is GY080T (=DSM 45072T=NCIMB 14277T).


Dynamic characteristics of long-wavelength quantum dot vertical-cavity surface-emitting lasers with light injection.
This investigation experimentally demonstrates the dynamic characteristics of quantum dot vertical-cavity surface-emitting lasers (QD VCSEL) without and with light injection. The QD VCSEL is fully doped structure on GaAs substrate and operates in the 1.3 mum optical communication wavelength. The eye diagram, frequency response, and intermodulation distortion are presented. We also demonstrate that the frequency response enhancement by light injection technique allows us to improve the performance of subcarrier multiplexed system.