Recommendations from the Association for European Paediatric and Congenital Cardiology for training in diagnostic and interventional electrophysiology.
The field of electrophysiology (EP) in paediatric cardiology patients and adults with congenital heart disease is complex and rapidly growing. The current recommendations for diagnostic and invasive electrophysiology of the working group for Cardiac Dysrhythmias and Electrophysiology of the Association for European Paediatric and Congenital Cardiology acknowledges the diveristy of European countries and centers. These training recommendations can be fulfilled in a manageable period of time, without compromising the quality of training required to become an expert in the field of paediatric and congenital EP and are for trainees undergoing or having completed accredited paediatric cardiologist fellowship. Three levels of expertise, the training for General paediatric cardiology EP, for non-invasive EP and invasive EP have been defined. This Association for European EP curriculum describes the theoretical and practicsal knowledge in clinical EP; catheter ablation, cardiac implantable electronic devices, inherited arrhythmias and arrhythmias in adults with congenital heart defects for the 3 levels of expertise.


The treatment of craniosynostosis: an ethical perspective.
The parents of children with craniofacial deformity have expectations that cannot always be reasonably met in a world of clinical uncertainty. In order to bridge the "reality gap," the members of the cranofacial team must be open and honest in discussing the known harms and benefits of a proposed treatment, so that a relationship of trust evolves between the health care professional and the patient/parent. It is only through this trust that a truthful implementation of consent, within its moral framework, can be achieved. This, in turn, requires an analysis of the outcomes of the various options for treatment as well as evidence that the cranofacial team is able to provide high standards of care. All this leads to the ethical imperative of respecting the right of parents to make an informed choice and allowing them to see that their child is treated in a way that provides maximum benefit and minimum harm.


Egg consumption and risk of type 2 diabetes in a Mediterranean cohort; the sun project.
The prevalence of diabetes is increasing at an alarming rate in nearly all countries. Some studies from non-Mediterranean populations suggest that higher egg consumption is associated with an increased risk of diabetes. The aim of our study was to prospectively assess the association between egg consumption and the incidence of type 2 diabetes in a large cohort of Spanish university graduates. In this prospective cohort including 15,956 participants (mean age: 38.5 years) during 6.6 years (median), free of diabetes mellitus at baseline. Egg consumption was assessed at baseline through a semiquantitative food-frequency questionnaire repeatedly validated in Spain. Incident diabetes mellitus diagnosed by a doctor was assessed through biennial follow-up questionnaires and confirmed subsequently by medical reports or records, according to the American Diabetes Association criteria. Analyses were performed through multivariable non-conditional logistic regression. After adjustment for confounders, egg consumption was not associated with the development of diabetes mellitus, comparing the highest versus the lowest quartile of egg consumption (<4 eggs/week vs >1 egg/week): odds ratio = 0.7; 95% CI 0.3-1.7. Egg consumption was not associated with the development of diabetes mellitus in this Mediterranean cohort.


Evaluation of an Unloading Concept for Knee Osteoarthritis: A Pilot Study in a Small Patient Group.
Joint compressive forces have been identified as a risk factor for osteoarthritis disease progression. Therefore, unloader braces are a common treatment with the aim of relieving pain, but their effects are not clearly documented in the literature. A knee brace concept was tested with the aim of reducing joint loads and pain in knee osteoarthritis patients by applying an extension moment exclusively during the stance phase. The ideal effects were evaluated during gait based on musculoskeletal modeling of six patients, and experimental tests with a prototype brace were conducted on one patient. The effects were evaluated using electromyography measurements and musculoskeletal models to evaluate the muscle activation and knee compressive forces, respectively. The ideal brace simulations revealed a varying reduction of the first peak knee force between 3.5% and 33.8% across six patients whereas the second peak was unaffected. The prototype reduced the peak vasti muscle activation with 7.9% and musculoskeletal models showed a reduction of the first peak knee compressive force of up to 26.3%. However, the prototype brace increased the knee joint force impulse of up to 17.1% and no immediate pain reduction was observed. The reduction of the first peak knee compressive force, using a prototype on a single patient, indicates a promising effect from an applied knee extension moment for reducing knee joint loads during normal gait. However, further clinical experiments with this brace method are required to evaluate the long-term effects on both pain and disease progression in knee osteoarthritis patients.


Nursing management of second stage labor.
Despite considerable research into nursing management of second stage labor, traditional approaches continue to predominate. Women are still encouraged to deliver in a recumbent position using sustained, closed-glottis pushing. Current research suggests that utilizing an upright position with pushing that is open glottis and complementary with the involuntary bearing-down reflex produces good maternal/fetal outcomes. Issues such as position, second stage phases, and bearing-down techniques are discussed in view of recent research findings. Gaps in knowledge are identified and practice implications are clearly defined. Now is the time to apply research-based knowledge to nursing management of second stage labor.


A bead-based multiplex assay covering all coronaviruses pathogenic for humans for sensitive and specific surveillance of SARS-CoV-2 humoral immunity.
Serological assays measuring antibodies against SARS-CoV-2 are key to describe the epidemiology, pathobiology or induction of immunity after infection or vaccination. Of those, multiplex assays targeting multiple antigens are especially helpful as closely related coronaviruses or other antigens can be analysed simultaneously from small sample volumes, hereby shedding light on patterns in the immune response that would otherwise remain undetected. We established a bead-based 17-plex assay detecting antibodies targeting antigens from all coronaviruses pathogenic for humans: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV strains 229E, OC43, HKU1, and NL63. The assay was validated against five commercial serological immunoassays, a commercial surrogate virus neutralisation test, and a virus neutralisation assay, all targeting SARS-CoV-2. It was found to be highly versatile as shown by antibody detection from both serum and dried blot spots and as shown in three case studies. First, we followed seroconversion for all four endemic HCoV strains and SARS-CoV-2 in an outbreak study in day-care centres for children. Second, we were able to link a more severe clinical course to a stronger IgG response with this 17-plex-assay, which was IgG1 and IgG3 dominated. Finally, our assay was able to discriminate recent from previous SARS-CoV-2 infections by calculating the IgG/IgM ratio on the N antigen targeting antibodies. In conclusion, due to the comprehensive method comparison, thorough validation, and the proven versatility, our multiplex assay is a valuable tool for studies on coronavirus serology.


Non-Invasive Evaluation of Retinal Vascular Alterations in a Mouse Model of Optic Neuritis Using Laser Speckle Flowgraphy and Optical Coherence Tomography Angiography.
Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.


Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction.
Extracellular superoxide dismutase (Ec-SOD) may protect the heart against myocardial infarction (MI) because of its extended half-life and capacity to bind heparan sulfate proteoglycans on cellular surfaces. Accordingly, we used direct gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy could protect against MI. The cDNA for human Ec-SOD was incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus produced a high level of Ec-SOD in the liver, which was redistributed to the heart and other organs by injection of heparin. Untreated rabbits (group I) underwent a 30-minute coronary occlusion and 3 days of reperfusion. For comparison, preconditioned rabbits (group II) underwent a sequence of six 4-minute-occlusion/4-minute-reperfusion cycles 24 hours before the 30-minute occlusion. Control-treated rabbits (group III) were injected intravenously with Ad5/CMV/nls-LacZ, and gene-therapy rabbits (group IV) were injected with Ad5/CMV/Ec-SOD 3 days before the 30-minute occlusion. Both groups treated with Ad5 received intravenous heparin 2 hours before the 30-minute occlusion. Infarct size (percent risk area) was similar in groups I (57+/-6%) and III (58+/-5%). Ec-SOD gene therapy markedly reduced infarct size to 25+/-4% (P<0.01, group IV versus group III), a protection comparable to that of the late phase of ischemic preconditioning (29+/-3%, P<0.01 group II versus group I). Direct gene transfer of the cDNA encoding membrane-bound Ec-SOD affords powerful cardioprotection, providing proof of principle for the effectiveness of antioxidant gene therapy against MI.


[Establishment of a method for determining the association between Legionella sp. and Amoeba sp. using polymerase chain reaction].
With two pairs of primers for the amplification of the MIP- (macrophage infectivity potentiator) and the 5S rDNA-fragment, it was possible to establish a DNA extraction and a PCR method for the detection of Legionella sp. in water-samples and, after cultivation, in Amoeba sp. Therefore, water-samples from a warm water-system in a hospital were taken. In all samples, legionellae were detected by the PCR method and identified by cultivation and a direct immunofluorescence-method as L. pneumophila (serogroup 1). Legionellae and amoebae of the same water sample were cocultured. Legionellae were also adherent at the outer-membrane. To separate the amoebae from the legionellae, the amoebae were sedimented selectively by centrifugation at 200 x g. This washing procedure had to be repeated seven times in order to eliminate the extraamoebale legionellae for sure. After DNA-extraction of water samples and heat treatment of the intraamoebale legionellae respectively, the amplification was performed with the MIP- and 5S rDNA-primers. In 14 of 16 cocultivations growth of legionellae was found. This result and the detection of legionellae and amoebae in the same water samples suggest that an infection of amoebae may also take place in the water system of the hospital. This is important for the disinfection as a procedure to eliminate legionellae, since intraamoebale bacteria are more resistant to environmental manipulation. Because in two of the cocultivations no growth of legionellae in amoebae was found, it can be assumed that only specific subtypes of legionellae can infect amoebae species.


Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.
ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/-) mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/-) mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/-) animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.


Neprilysin deficiency-dependent impairment of cognitive functions in a mouse model of amyloidosis.
Alzheimer's disease, responsible for the vast majority of dementia cases in the elderly population, is caused by accumulation of toxic levels of amyloid beta peptide (A beta) in the brain. Neprilysin is a major enzyme responsible for the degradation of A beta in vivo. We have previously shown that elevation of neprilysin levels in the brain delays the deposition of A beta-plaques in a mouse model of amyloidosis and that lack of neprilysin leads to increased A beta generation and to signs of incipient neurodegeneration in mouse brains. This study was designed to test whether low brain levels of neprilysin affect the amyloid pathology or perturb the learning and memory performance of mice. Double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein (APP), exhibited a reinforced amyloid pathology in comparison with their APP transgenic littermates. Moreover, in contrast to their parental lines, these mice were impaired in the Morris water maze learning and memory paradigm and showed facilitated extinction in the conditioned taste aversion test. These data suggest that even a partial neprilysin deficiency, as is found during aging, exacerbates amyloid pathology and may impair cognitive functions.


Cyclic nucleotides in ascites from ovarian carcinoma.
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were assayed in ascitic fluid from 27 patients with ovarian carcinoma and 23 patients with liver cirrhosis. The value of these cyclic nucleotides was correlated with standard methods for the clinical evaluation of tumors. No change in the cGMP levels was found in either of these groups. The cAMP content, however, was increased in 23 of the 27 cases of ovarian carcinoma. The high cAMP level was correlated with the cytological findings in only 13 (48.1%) of these cases.


Hair metabolomics: identification of fetal compromise provides proof of concept for biomarker discovery.
Analysis of the human metabolome has yielded valuable insights into health, disease and toxicity. However, the metabolic profile of complex biological fluids such as blood is highly dynamic and this has limited the discovery of robust biomarkers. Hair grows relatively slowly, and both endogenous compounds and environmental exposures are incorporated from blood into hair during growth, which reflects the average chemical composition over several months. We used hair samples to study the metabolite profiles of women with pregnancies complicated by fetal growth restriction (FGR) and healthy matched controls. We report the use of GC-MS metabolite profiling of hair samples for biomarker discovery. Unsupervised statistical analysis showed complete discrimination of FGR from controls based on hair composition alone. A predictive model combining 5 metabolites produced an area under the receiver-operating curve of 0.998. This is the first study of the metabolome of human hair and demonstrates that this biological material contains robust biomarkers, which may lead to the development of a sensitive diagnostic tool for FGR, and perhaps more importantly, to stable biomarkers for a range of other diseases.


Comparison of stapled and hand-sutured gastrectomies.
We reviewed 585 Billroth II gastrectomies to compare the results of stapled and hand-sutured cases. In 385 patients who had the duodenal stump handled by conventional methods, 18 (4.7%) leaked, compared with four (2.5%) leaks in 160 patients who had the duodenal stump stapled. In 474 hand-sutured anastomoses, there were 12 complications (leaks, hemorrhage, or obstruction), whereas there were no complications in 71 stapled anastomoses. We conclude that stapling provides an expedient way of performing gastrectomies that is at least as safe if not safer than conventional hand suture.


Successful treatment of a patient with hairy cell leukemia and pentostatin-induced autoimmune thrombocytopenia with rituximab.
The treatment of choice for hairy cell leukemia (HCL) are the purine analogs pentostatin and cladribine. They induced complete remissions in up to 85% of patients. Purine analogs are known to induce autoimmune phenomena, but there are no reports of autoimmune thrombocytopenia after treatment with pentostatin. This case report describes the very rare association of pentostatin-treated hairy cell leukemia and autoimmune thrombocytopenia. Encouraged by first reports of promising activity of the anti-CD20 monoclonal antibody rituximab in patients with autoimmune disorders, we decided to treat our patient with rituximab in the conventional dose of 375 mg/m(2) i.v. weekly for 4 cycles. One week after the first administration, the peripheral blood count has recovered with a normal platelet count. 22 weeks after completion of therapy, the patient is still in complete hematologic remission without further medication. In conclusion, rituximab seems to be a new, promising drug in the treatment of refractory autoimmune thrombocytopenia even in patients with underlying lymphoproliferative disorders.


Decreasing the Hours That Anesthesiologists and Nurse Anesthetists Work Late by Making Decisions to Reduce the Hours of Over-Utilized Operating Room Time.
In this special article, we evaluate how to reduce the number of hours that anesthesiologists and nurse anesthetists work beyond the end of their scheduled shifts. We limit consideration to surgical suites where the hours of cases in each operating room (OR) average 8 hours or more per day. Let "allocated hours" refer to the hours into which cases are scheduled, calculated months in advance for each combination of service and day of the week. Over-Utilized time is the OR workload exceeding allocated time. Reducing Over-Utilized time is the key to reducing the hours that anesthesia providers work late. Certain decisions that reduce Over-Utilized time and reduce the hours that anesthesiologists and nurse anesthetists work late are made by the surgical committee or perioperative medical director months in advance. Such decisions include increasing the number of first case starts and planning staffing for turnovers and lunch breaks during the busiest times of the day. However, most decisions substantively influencing Over-Utilized OR time are made within 1 workday before the day of surgery and on the day of surgery, because only then are ORs sufficiently full that changes can be made to minimize Over-Utilized time. Decisions to reduce Over-Utilized time on the day of surgery include targeting ORs with expected Over-Utilized time and taking steps to reduce it, including making effective staff assignments and appropriately scheduling add-on cases.


Phage based electrochemical detection of Escherichia coli in drinking water using affinity reporter probes.
The monitoring of drinking water for indicators of fecal contamination is crucial for ensuring a safe supply. In this study, a novel electrochemical method was developed for the rapid and sensitive detection of Escherichia coli (E. coli) in drinking water. This strategy is based on the use of engineered bacteriophages (phages) to separate and concentrate target E. coli when conjugated with magnetic beads, and to facilitate the detection by expressing gold binding peptides fused alkaline phosphatase (GBPs-ALP). The fusion protein GBPs-ALP has both the enzymatic activity and the ability to directly bind onto a gold surface. This binding-peptide mediated immobilization method provided a novel and simple approach to immobilize proteins on a solid surface, requiring no post-translational modifications. The concentration of E. coli was determined by measuring the activity of the ALP on gold electrodes electrochemically using linear sweep voltammetry (LSV). This approach was successfully applied in the detection of E. coli in drinking water. We were able to detect 105 CFU mL-1 of E. coli within 4 hours. After 9 hours of preincubation, 1 CFU of E. coli in 100 mL of drinking water was detected with a total assay time of 12 hours. This approach compares favorably to the current EPA method and has the potential to be applied to detect different bacteria in other food matrices.


Abdominal fibromatosis in a young child: a case study and review of the literature.
Fibromatoses comprise many different entities of well-differentiated fibroblastic proliferation with variable collagen production and form a firm nodular mass. Abdominal fibromatosis is distinguishable from other forms of fibromatosis because of its location and its tendency to occur in women of childbearing age during or following pregnancy. Abdominal fibromatosis in children is an extremely rare condition. A 15-month-old boy presented with an abdominal wall mass that had recently increased in size. Mass excision was perfomed. The tumor was 4.3×4.1 cm and partly circumscribed. Histologically, the tumor was composed of parallel long fascicles of spindle-cells with a uniform appearance. The edges of the resected mass were infiltrative, and the surgical margins were positive. Mitotic figures were <1/10 high power fields. No cellular atypia or necrosis was present. The tumor cells were positive for vimentin and nuclear β-catenin staining.


Rapid antimicrobial susceptibility testing by sensitive detection of precursor rRNA using a novel electrochemical biosensing platform.
Precursor rRNA (pre-rRNA) is an intermediate stage in the formation of mature rRNA and is a useful marker for cellular metabolism and growth rate. We developed an electrochemical sensor assay for Escherichia coli pre-rRNA involving hybridization of capture and detector probes with tail sections that are spliced away during rRNA maturation. A ternary self-assembled monolayer (SAM) prepared on gold electrode surfaces by coassembly of thiolated capture probes with hexanedithiol and posttreatment with 6-mercapto-1-hexanol minimized the background signal and maximized the signal-to-noise ratio. Inclusion of internal calibration controls allowed accurate estimation of the pre-rRNA copy number per cell. As expected, the ratio of pre-rRNA to mature rRNA was low during stationary phase and high during log phase. Pre-rRNA levels were highly dynamic, ranging from 2 copies per cell during stationary phase to ~1,200 copies per cell within 60 min of inoculation into fresh growth medium. Specificity of the assay for pre-rRNA was validated using rifampin and chloramphenicol, which are known inhibitors of pre-rRNA synthesis and processing, respectively. The DNA gyrase inhibitor, ciprofloxacin, was found to act similarly to rifampin; a decline in pre-rRNA was detectable within 15 min in ciprofloxacin-susceptible bacteria. Assays for pre-rRNA provide insight into cellular metabolism and are promising predictors of antibiotic susceptibility.


[Radioisotopic localization of the sentinel lymph node in breast cancer. Preliminary results].
The aim of this preliminary work is to show the results of the radioisotopic localization of the sentinel node in breast cancer and the surgical resection using a gamma probe. We studied 10 patients with breast cancer without primary chemotherapy and 3 patients with primary chemotherapy before surgery. A lymphoscintigraphy was made after injection of 111 MBq of Tc99m-nanocolloid in a volume of 3 ml. The scans were performed after 30 minutes, 2 hours, 4 hours and 24 hours after injection. We detected the node and then a skin mark was made. The next day, surgical resection of this node was performed, guided by a gamma probe. We detected all sentinel nodes but one: 12 sentinel nodes and 7 second echelon nodes. The mean time for a surgical detection was about 16 minutes. In our experience this technique allows an accurate localization of the sentinel node in patients with breast cancer. We are able to localize the node in the surgical room guided with gamma probe. The peroperatory evaluation by anatomopathological techniques shown the status of this node. All this, does not delay the surgical time.


Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation.
The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a complex process involving more than 20 components. So far, functional investigations have mainly been performed in Saccharomyces cerevisiae. Here, we have analyzed the role of the human cysteine desulfurase Nfs1 (huNfs1), which serves as a sulfur donor in biogenesis. The protein is located predominantly in mitochondria, but small amounts are present in the cytosol/nucleus. huNfs1 was depleted efficiently in HeLa cells by a small interfering RNA (siRNA) approach, resulting in a drastic growth retardation and striking morphological changes of mitochondria. The activities of both mitochondrial and cytosolic Fe/S proteins were strongly impaired, demonstrating that huNfs1 performs an essential function in Fe/S protein biogenesis in human cells. Expression of murine Nfs1 (muNfs1) in huNfs1-depleted cells restored both growth and Fe/S protein activities to wild-type levels, indicating the specificity of the siRNA depletion approach. No complementation of the growth retardation was observed, when muNfs1 was synthesized without its mitochondrial presequence. This extramitochondrial muNfs1 did not support maintenance of Fe/S protein activities, neither in the cytosol nor in mitochondria. In conclusion, our study shows that the essential huNfs1 is required inside mitochondria for efficient maturation of cellular Fe/S proteins. The results have implications for the regulation of iron homeostasis by cytosolic iron regulatory protein 1.


Atmospheric bismuth-212: measurement and some geophysical applications.
The concentrations of lead-212 and its short-lived daughter bismuth-212 in air near the ground were determined simultaneously by adaptation of the immersed-filter, delayed-coincidence technique of Assaf and Gat to measurement of the 3 x 10-(7)-second bismuth-212 and polonium-212 pair. The radioactive disequilibrium between lead-212 and bismuth-212 depends strongly on the efficiency of the ground in acting as a sink for these nuclides. This efficiency is low under dry conditions.


Island biology and morphological divergence of the Skyros wall lizard Podarcis gaigeae: a combined role for local selection and genetic drift on color morph frequency divergence?
Patterns of spatial variation in discrete phenotypic traits can be used to draw inferences about the adaptive significance of traits and evolutionary processes, especially when compared to patterns of neutral genetic variation. Population divergence in adaptive traits such as color morphs can be influenced by both local ecology and stochastic factors such as genetic drift or founder events. Here, we use quantitative color measurements of males and females of Skyros wall lizard, Podarcis gaigeae, to demonstrate that this species is polymorphic with respect to throat color, and the morphs form discrete phenotypic clusters with limited overlap between categories. We use divergence in throat color morph frequencies and compare that to neutral genetic variation to infer the evolutionary processes acting on islet- and mainland populations. Geographically close islet- and mainland populations of the Skyros wall lizard exhibit strong divergence in throat color morph frequencies. Population variation in throat color morph frequencies between islets was higher than that between mainland populations, and the effective population sizes on the islets were small (Ne:s < 100). Population divergence (FST) for throat color morph frequencies fell within the neutral FST-distribution estimated from microsatellite markers, and genetic drift could thus not be rejected as an explanation for the pattern. Moreover, for both comparisons among mainland-mainland population pairs and between mainland-islet population pairs, morph frequency divergence was significantly correlated with neutral divergence, further pointing to some role for genetic drift in divergence also at the phenotypic level of throat color morphs. Genetic drift could not be rejected as an explanation for the pattern of population divergence in morph frequencies. In spite of an expected stabilising selection, throat color frequencies diverged in the islet populations. These results suggest that there is an interaction between selection and genetic drift causing divergence even at a phenotypic level in these small, subdivided populations.


Level-adjusted perioperative risk of sacral amputations.
Sacral amputations above the S2 body often involve increased surgical complexity leading to long-term morbidity. The purpose of this study was to determine whether proximal sacral amputations have substantially higher perioperative morbidity compared with more distal sacral amputations. We evaluated the effect of sacral amputation level on perioperative outcomes within 90 days of surgery. Outcome measures included blood loss, intensive care unit (ICU) and hospital stay, hospital cost, and incidence of a major and minor morbidity. Survival analyses were adjusted for the level of resection and histological appearance. Thirteen proximal and 14 distal resections were performed. In comparing proximal versus distal resections, median estimated blood loss was 4 L versus 1 L (P < 0.001), ICU stay was 4 days versus 0 days (P = 0.012), hospital stay was 19 days versus 8 days (P = 0.001), hospital cost was 28,800 dollars versus 7,500 dollars (P = 0.003), with one or more major complications in 85% versus 29% (P = 0.011). Survival analysis demonstrated that the sacral resection level did not influence survival (P = 0.936), whereas the type of tumor did influence survival (P = 0.012). Tumor resections above S2 demonstrate increased perioperative morbidity, suggesting that proximal osteotomies be reserved for patients with a realistic cure potential.


Response of serum triglycerides of endogenous origin to the administration of triglyceride-rich lipid particles.
Studies were performed in rats to quantitate the changes in the concentration of serum triglycerides (TGs) of endogenous and exogenous origin after the acute intravenous injection of TG-rich emulsion particles. Emulsions were prepared to approximate chylomicrons and to contain a TG with a single fatty acid that could be traced during its clearance from the serum. After injection of emulsions, there was a rapid increase of not only the emulsion TG but TGs that contained a variety of other fatty acids of endogenous origin. Endogenous TGs were cleared from the serum at a slower rate than the emulsion TG and accounted for the major increase in serum TGs, especially during the latter phase of the clearance period. The increase in endogenous TGs was completely abolished by hepatectomy, which had no effect on the clearance of the emulsion TG. Results thus show that TGs of hepatic origin accumulate in the serum in response to the introduction of new TG-rich lipoproteins. Feeding rats a specific TG produced a similar result, with a pronounced rise in endogenous TGs that, like the changes after emulsion administration, was particularly evident once the TG that was fed was largely cleared from the serum. These findings are consistent with a process in which the preferential clearance of chylomicron TGs interrupts the clearance of very low density lipoprotein TGs that are produced by the liver. Consequently, the composition of serum TGs that accumulate after a meal may not reflect the composition of the meal itself.


Tissue damage caused by activated complement and granulocytes in shock lung, post perfusion lung, and after amniotic fluid embolism: ramifications for therapy.
The complement system evolved as a beneficial antimicrobial system. However when activated during extracorporeal perfusion, as with hemodialysis or cardiopulmonary bypass, modest pulmonary dysfunction associated with granulocyte aggregation and embolization can occur. When complement activation is more massive and prolonged as with severe sepsis, trauma and acute pancreatitis or during infusions of amniotic fluid or other lipid-rich suspensions, severe pulmonary damage which we often recognize as shock lung may occur. Therapeutic ramifications of these conclusions are evident. Thus, high doses of corticosteroids (or of non-steroidal anti-inflammatory agents, such as ibuprofen--herein not discussed) have the ability to prevent aggregation and embolization of stimulated granulocytes to patent vessels downstream and also inhibit their production of toxic oxygen radicals. These beneficial properties suggest the use of these agents may be appropriate in shock states, particularly shock lung or during suspected amniotic fluid infusion. Appropriate clinical trials to substantiate this suggestion are awaited with interest.


Towards high-throughput single cell/clone cultivation and analysis.
In order to better understand cellular processes and behavior, a controlled way of studying high numbers of single cells and their clone formation is greatly needed. Numerous ways of ordering single cells into arrays have previously been described, but platforms in which each cell/clone can be addressed to an exact position in the microplate, cultivated for weeks and treated separately in a high-throughput manner have until now been missing. Here, a novel microplate developed for high-throughput single cell/clone cultivation and analysis is presented. Rapid single cell seeding into microwells, using conventional flow cytometry, allows several thousands of single cells to be cultivated, short-term (72 h) or long-term (10-14 days), and analyzed individually. By controlled sorting of individual cells to predefined locations in the microplate, analysis of single cell heterogeneity and clonogenic properties related to drug sensitivity can be accomplished. Additionally, the platform requires remarkably low number of cells, a major advantage when screening limited amounts of patient cell samples. By seeding single cells into the microplate it is possible to analyze the cells for over 14 generations, ending up with more than 10 000 cells in each well. Described here is a proof-of-concept on compartmentalization and cultivation of thousands of individual cells enabling heterogeneity analysis of various cells/clones and their response to different drugs.


Empowering Foot Health: Harnessing the Adaptive Weighted Sub-Gradient Convolutional Neural Network for Diabetic Foot Ulcer Classification.
In recent times, DFU (diabetic foot ulcer) has become a universal health problem that affects many diabetes patients severely. DFU requires immediate proper treatment to avert amputation. Clinical examination of DFU is a tedious process and complex in nature. Concurrently, DL (deep learning) methodologies can show prominent outcomes in the classification of DFU because of their efficient learning capacity. Though traditional systems have tried using DL-based models to procure better performance, there is room for enhancement in accuracy. Therefore, the present study uses the AWSg-CNN (Adaptive Weighted Sub-gradient Convolutional Neural Network) method to classify DFU. A DFUC dataset is considered, and several processes are involved in the present study. Initially, the proposed method starts with pre-processing, excluding inconsistent and missing data, to enhance dataset quality and accuracy. Further, for classification, the proposed method utilizes the process of RIW (random initialization of weights) and log softmax with the ASGO (Adaptive Sub-gradient Optimizer) for effective performance. In this process, RIW efficiently learns the shift of feature space between the convolutional layers. To evade the underflow of gradients, the log softmax function is used. When logging softmax with the ASGO is used for the activation function, the gradient steps are controlled. An adaptive modification of the proximal function simplifies the learning rate significantly, and optimal proximal functions are produced. Due to such merits, the proposed method can perform better classification. The predicted results are displayed on the webpage through the HTML, CSS, and Flask frameworks. The effectiveness of the proposed system is evaluated with accuracy, recall, F1-score, and precision to confirm its effectual performance.


Magnitude and sign correlations in heartbeat fluctuations.
We propose an approach for analyzing signals with long-range correlations by decomposing the signal increment series into magnitude and sign series and analyzing their scaling properties. We show that signals with identical long-range correlations can exhibit different time organization for the magnitude and sign. We find that the magnitude series relates to the nonlinear properties of the original time series, while the sign series relates to the linear properties. We apply our approach to the heartbeat interval series and find that the magnitude series is long-range correlated, while the sign series is anticorrelated and that both magnitude and sign series may have clinical applications.


Cross-talk between probiotic bacteria and the host immune system.
Among the numerous purported health benefits attributed to probiotic bacteria, their capacity to interact with the immune system of the host is now supported by an increasing number of in vitro and in vivo experiments. In addition to these, a few well-controlled human intervention trials aimed at preventing chronic immune dysregulation have been reported. Even though the precise molecular mechanisms governing the cross-talk between these beneficial bacteria and the intestinal ecosystem remain to be discovered, a new and fascinating phase of research has been initiated in this area as demonstrated by a series of recent articles. This article summarizes the status and latest progress of the field in selected areas and aims at identifying key questions that remain to be addressed, especially concerning the translocation of ingested bacteria, the identification of major immunomodulatory compounds of probiotics, and specific aspects of the host-microbe cross-talk. The interaction with immunocompetent cells and the role of secretory IgA in gut homeostasis are also evoked. Finally, a brief overview is provided on the potential use of recombinant DNA technology to enhance the health benefits of probiotic strains and to unravel specific mechanisms of the host-microbe interaction.


Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting.
Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8-10 ng/m3), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Peq). IC50 values for viability were 5.7 and 3.0 nM B[a]Peq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 - Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2, COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.


Why older Australians participate in exercise and sport.
Research on variables that encourage older adults to exercise is limited. This study was carried out to identify the participation motives of older Australians involved in regular exercise and sport. The 815 participants (399 men, 416 women) ranged in age from 55 to 93 years (M = 63.6, SD = 7.8) and were participating in their activities of choice at least once per week. All participants completed the Participation Motivation Questionnaire for Older Adults. The most common exercise/sport activities that participants were involved in were walking, golf, lawn bowls, tennis, and swimming. The most highly reported motives for participation were to keep healthy, liking the activity, to improve fitness, and to maintain joint mobility. Principal-components analysis of the questionnaire revealed 6 factors: social, fitness, recognition, challenge/benefits, medical, and involvement. Analyses of variance showed significant differences in reasons for participation in exercise and sport based on gender, age, education level, and occupation.


Evaluation of plasma cortisol during fasting test in patients with endogenous hyperinsulinemic hypoglycemia. Fifteen years experience.
Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare clinical condition. The aim of this study was to evaluate baseline plasma cortisol concentration and its concentration during hypoglycemic crisis in fasting tests (FT) performed in our center. Secondarily, the aim was to establish the relationship between baseline cortisol and the time of evolution of EHH. A retrospective, observational, descriptive study was carried out which included patients with hypoglycemic disorder with positive FT. Of a total of 21 patients, 16 presented insulinoma, 1 nesidioblastosis, 2 malignant insulinoma and 2 EHH without pathological diagnosis. The time from the onset of symptoms to diagnosis was 2 years (Q1=1.5-Q2=5.5). The comparison between median baseline cortisol (BC)=11.8 mcg/dl (nmol/L 340.68) (Q1=9-Q3=14.1) and median cortisol during hypoglycemic episode (HC)=11.6 mcg/dl (nmol/L: 303.44) (Q1=7.8-Q3=16.1) showed no differences (Z=-0.08; P>.05). When correlating BC with HC, no significant relationship was observed (r=0.16; P>.05). When correlating the glycemic value in the crisis and the HC, a slight negative trend was found (r=-0.53; P=.01). In addition, we found that recurrent hypoglycemic disorder is associated with lower baseline cortisol values the longer the time of its evolution. We confirmed that cortisol values remain low during hypoglycemic episodes, reinforcing the hypothesis of lack of response of this counterregulatory hormone in cases of recurrent hypoglycemia.


Long poly(A) tracts in the human genome are associated with the Alu family of repeated elements.
Long poly(dA).poly(dT) tracts (poly(A) tracts), regions of DNA containing at least 20 contiguous dA residues on one strand and dT residues on the complementary strand, are found in about 2 X 10(4) copies interspersed throughout the human genome. Using poly(dA).poly(dA) as a hybridization probe, we identified recombinant lambda phage that contained inserts of human DNA with poly(A) tracts. Three such tracts have been characterized by restriction mapping and sequence analysis. One major poly(A) tract is present within each insert and is composed of from 28 to 35 A residues. In each case, the poly(A) tract directly abuts the 3' end of the human Alu element, indicating that the major class of poly(A) tracts in the human genome is associated with this family of repeats. The poly(A) tracts are also adjacent to A-rich sequences and, in one case, to a polypurine tract, having the structure GA3-GA3-GA4-GA6-GA5-GA4. We suggest that repetitive cycles of unequal crossing over may give rise to both the long poly(A) and polypurine tracts observed in this study.


GLUT1 contributes to impaired epithelial tight junction in the late phase of acute lung injury.
Dysfunction of epithelial barrier is crucial for the development of acute lung injury (ALI). This study was aimed to evaluate the role of glucose transporter 1 (GLUT1) in dysregulation of epithelial tight junction in ALI. GLUT1 was inhibited with specific antagonists WZB117 or BAY876 to see the effects on epithelial tight junction in a well-established LPS-induced mouse ALI model as well as in vitro cultured epithelial cells. Pharmacological inhibition of GLUT1 with WZB117 at either a low or high dose had no effects on lung injury and inflammation 24 h after LPS challenge, but significantly decreased the pulmonary inflammatory responses induced by LPS at 72 h with a high dose, which was verified by treatment with BAY876. WZB117 or BAY876 also recovered the expression of epithelial tight junction proteins ZO-1 and occludin. In cultured BEAS-2B and A549 cells, LPS induced increased GLUT1 expression, accompanied by decreased expression of tight junction protein ZO-1 and occludin. Blockade of GLUT1 restored LPS-induced disruption of ZO-1 and occludin in BEAS-2B rather than A549. Taken together, our results showed that GLUT1 is responsible for dysfunction of epithelial tight junctions in the late phase of LPS-induced ALI.


Experimental models of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by the progressive loss of motor neurons, leading to profound weakness and eventual death of affected individuals. For the vast majority of patients with ALS, the etiology of the disorder is unknown, and although multiple clinical trials of various therapeutic agents have been undertaken, truly effective therapy is not currently available for the disease. The selection of treatments used in ALS clinical trials frequently has its basis in promising data obtained from experimental model systems in which the proposed agent has shown some effect in protecting motor neurons from a particular insult. The likelihood of a successful clinical outcome for a given treatment in ALS would therefore depend on two principal factors, including the similarity of the model to the disease and the biologic action of the potential therapeutic agent. Partly because early experimental models of ALS failed to replicate the disease process, treatment success in these models did not carry over into human trials. Recently, however, a variety of newer model systems have been developed and utilized to investigate motor neuron degeneration as related to ALS. For example, in this issue, Corse et al. use a rat spinal cord organotypic slice subjected to glutamate excitotoxicity as a model system to test the effectiveness of neurotrophic factors in preventing motor neuron degeneration. This review will assess the strengths and weaknesses of differing ALS model systems that have been used to preclinically test potential drug efficacy in ALS.


The effect of alcohol intoxication on inflammation of the cornea.
New Zealand albino rabbits received daily intraperitoneal injections of alcohol (ethyl alcohol), 1.6 g/kg and the effect of short-term (three days) and long-term (six weeks) administration on corneal inflammation was studied. Both regimens produced an average peak serum concentration of more than 0.200 g/dL, a level consistent with gross intoxication in the majority of humans. Clinical signs of intoxication were present in all animals, manifested by a gross disturbance of equilibrium and gait. Neither regimen produced measurable liver damage. Nonetheless, following both regimens of alcohol administration, significantly fewer polymorphonuclear leukocytes invaded the corneas of animals receiving alcohol than invaded the corneas of simultaneously run controls receiving intraperitoneal saline. These data provide a mechanism to explain why an alcoholic individual might not cope with a corneal infection as well as a nonalcoholic person, an observation long thought to be true clinically.


Increased myocardial blood flow during acute exposure to simulated altitudes.
Although only poor data exist on changes in myocardial blood flow (MBF) under acute hypoxia, patients with known coronary artery disease are advised not to exceed a moderate altitude exposure of about 2000 m above sea level. We measured MBF with positron emission tomography using O-15--labeled water in 8 healthy human volunteers (aged 26 +/- 3 years [mean +/- SD]) at baseline (450 m above sea level, Zurich, Switzerland) and during acute hypoxic hypoxemia induced by inhalation of 2 hypoxic gas mixtures corresponding to altitudes of 2000 and 4500 m. MBF remained unchanged at 2000 m (increase of 10%, not significant) but increased significantly at 4500 m (62%, P <.001), exceeding the relative increase in rate pressure product. Our results may explain why exposure to an altitude of 2000 m (corresponding to the cabin pressure in most airplanes during flight) is clinically well tolerated, even by patients with reduced coronary flow reserve, such as those with coronary artery disease. However, at an altitude of 4500 m, MBF increases significantly, supporting the recommendation that patients with impaired flow reserve avoid exposure to higher altitudes.


[Sling suspension: a new technique of treating uterine prolapse].
To report a novel surgical technique of laparoscopic extraperitoneal sling suspension for uterine prolapse and evaluate its efficacy. A total of 21 consecutive patients of symptomatic uterovaginal prolapse with POP-Q (pelvic organ prolapse quantification system) stage ≥ 2 and aged 59 (42-76) years were enrolled for this procedure between September 2011 and December 2012. In brief, uterus was suspended to anterior abdominal wall fascia using an inelastic nonabsorable mesh extraperitoneally under laparoscopic guidance. The outcomes of interest included total operative duration, estimated blood loss, surgical length of stay POP-Q score change and quality of life questionnaire in pelvic floor distress inventor [PFDI-20] and pelvic floor impact questionnaire [PFIQ-7]. Follow-ups were scheduled at 1, 6 and 12 months and then annually. Comparisons were made between at preoperation and 6 and 12 months. The surgical success was defined as both subjective cure and significant improvement of POP-Q. This procedure was performed successfully in all patients. The estimated blood loss 10 (10-40) ml, operative duration 30 (25-90) minutes and postoperative hospital stay 1 (1-5) day. There were no major intraoperative or postoperative complications. The median follow-up was 20 (12-26) months. There were significant improvements in POP-Q measurements of Ba and C (P < 0.01) and quality-of-life scores (P < 0.01) at 6 and 12 months. The subjective cure rate was 100% and surgical success rate at 12 months 100%. This new sling suspension technique for uterine prolapse is safe, well-tolerated and effective so that it offers a simple alternative of laparoscopic uterine suspension.


A measurement of the fast-neutron sensitivity of a Geiger-Müller detector in the pulsed neutron beam from a superconducting cyclotron.
The kU value of a commercially available miniature energy compensated Geiger-Müller (GM) detector has been determined using the modified lead attenuation method of Hough. The measurements were made in a d(48.5)-Be neutron beam produced by the superconducting cyclotron based neutron therapy facility at Harper Hospital. The unique problems associated with making measurements in a 2 ms duration pulsed beam with a 20% duty cycle are discussed. The beam monitoring system, which allows the beam pulse shape at low beam intensities to be measured, is described. By gating the GM output with a discriminator pulse derived from the beam pulse shape, the gamma-ray count rates and dead-time corrections within the 2 ms pulse and between pulses can be measured separately. The kU value of (0.0245 +/- 0.0015) determined for this GM detector is consistent with the values measured by other workers with identical and similar detectors in neutron beams with comparable, but not identical, neutron spectra.


TRENDS IN COMPLETE DENTURE IMPRESSIONS IN PAKISTAN.
Multiple materials and techniques have been reported for complete denture impressions in literature. The aim of the study was to assess the trends in complete denture impression materials and techniques among general dental practitioners (GDP) and specialists (SP) in Pakistan. In this cross-sectional study, self-designed-structured questionnaires were distributed among 500 dentists in Pakistan. The three-part questionnaire enquired about the demographic features, preferred impression materials, impression techniques and related procedures commonly used in their clinical practice. A comparison between the responses of SP and GDP was also drawn. Frequency distribution and Chi-square test were performed to compare the responses. A total of 294 questionnaires were completed at a response rate of 58.8%. 75% of GDP used alginate for primary impressions and 66% of SP preferred impression compound for the same. A majority of both SP and GDP favoured the used of custom trays (SP 81%, GDP 85%) and selective pressure technique (SP 84%, GDP 53%) for final impression. However, 85% of GDP used zinc-oxide eugenol and 62% of SP favoured elastomeric materials for the same. Most of the SP and GDP used chemical cured resin custom trays (SP 54%, GDP 75%), however, 86% of SP used spaced trays and almost 60% of GDP preferred close-fitting trays. The practice of GDP and SP with regards to CD impression materials and techniques differed significantly. Continued education and training for GDP and SP with respect to procedures and techniques related to CD is recommended.


Risk Factors for the Development of High-risk Stigmata in Branch-duct Intraductal Papillary Mucinous Neoplasms.
Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS [odds ratio, 14.2; 95% confidence interval (CI), 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014]. Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.


BALD-2: a mutation affecting the formation of doublet and triplet sets of microtubules in Chlamydomonas reinhardtii.
The mutant strain bald-2 is unique among "flagellaless" strains of Chlamydomonas reinhardtii isolated to date, in that it possesses a mutant basal body: it is only capable of forming a ring of nine singlet microtubules, 180 nm in diameter, instead of the usual triplet basal body which is 225 nm in diameter. This singlet basal body lacks structural stability and the ability to associate with striated fiber material but retains two critical properties of basal bodies, namely, information specifying the length to which it should elongate and the ability to induce, albeit rarely, a flagellar transition region, a short, singlet-containing axoneme, and a specialized tunnel in the cell wall through which flagella normally emerge. The mutation seems to be specific for B- and C-microtubule synthesis or assembly since all other cytoplasmic sets of microtubules appear normal in numbers, orientation, and stability.


The Prevalence and Clinical Implications of Comorbid Back Pain in Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.
Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty. The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures. Cross-sectional study; Level of evidence, 3. As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients consented to participate in pre- and intraoperative data collection. Demographic characteristics, injury history, preoperative PRO scores, and radiologic and intraoperative findings were recorded for patients undergoing surgical shoulder stabilization. Patients were also asked, whether they had any back pain. The study cohort consisted of 1001 patients (81% male; mean age, 24.1 years). Patients with comorbid back pain (158 patients; 15.8%) were significantly older (28.1 vs 23.4 years; P < .001) and were more likely to be female (25.3% vs 17.4%; P = .02) but did not differ in terms of either preoperative imaging or intraoperative findings. Patients with self-reported back pain had significantly worse preoperative pain and shoulder-related PRO scores (American Shoulder and Elbow Surgeons score, Western Ontario Shoulder Instability Index) (P < .001), more frequent depression (22.2% vs 8.3%; P < .001), poorer mental health status (worse scores for the RAND 36-Item Health Survey Mental Component Score, Iowa Quick Screen, and Personality Assessment Screener) (P < .01), and worse preoperative expectations (P < .01). Despite having similar physical findings, patients with comorbid back pain had more severe preoperative pain and self-reported symptoms of instability as well as more frequent depression and lower mental health scores. The combination of disproportionate shoulder pain, comorbid back pain and mental health conditions, and inferior preoperative expectations may affect not only the patient's preoperative state but also postoperative pain control and/or postoperative outcomes.


Evaluation of the agreement between lingual and thoracic limb noninvasive blood pressure with invasive blood pressure measurements in anaesthetized horses.
To evaluate the agreement between noninvasive arterial blood pressure (NIBP) measured from the tongue and thoracic limb with invasive blood pressure (IBP), and to compare NIBP measured from the tongue and thoracic limb in anaesthetized horses. Prospective clinical study. A group of eight client-owned healthy horses anaesthetized for scheduled procedures, American Society of Anesthesiologists classification I-II, weighing (mean ± standard deviation) 498 ± 91 kg and aged 7.8 ± 6.75 years. Animals were premedicated with intravenous (IV) romifidine (0.04-0.08 mg kg-1) and methadone (0.1 mg kg-1). General anaesthesia was induced IV with ketamine (2.5 mg kg-1) and midazolam (0.05 mg kg-1) and maintained with isoflurane. The facial artery was catheterized for IBP measurements. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were recorded from the NIBPtongue, NIBPlimb and IBP every 20 minutes during the procedure. Agreement between NIBP and IBP was evaluated based on the American College of Veterinary Internal Medicine criteria and American Association for Medical Instrumentation criteria using the Bland-Altman method. The mean bias and precision between IBP and NIBP measured from the tongue met the standards for all pressure ranges (< 10 mmHg and < 15 mmHg, respectively). NIBP measurements from the tongue and thoracic limb tended to underestimate IBP measurements. During hypotension, MAPtongue and DAPtongue overestimated IBP, but both precision and accuracy met the criteria. The overall accuracy and precision of NIBPlimb was poorer than NIBPtongue. The percentage of NIBPtongue that differed from IBP by < 10 mmHg was higher than that recorded with NIBPlimb for SAP (46% versus 25%), MAP (77% versus 28%) and DAP (79% versus 19%). The tongue is a clinically suitable alternative for assessing arterial blood pressure compared with the thoracic limb and can reliably detect hypotension in healthy anaesthetized horses.


Avian neural crest cell migration on laminin: interaction of the alpha1beta1 integrin with distinct laminin-1 domains mediates different adhesive responses.
In the present study, to further elucidate the molecular events that control neural crest cell migration, we have analyzed in vitro the adhesive and locomotory response of avian trunk neural crest cells to laminin-1 and searched for the integrin receptors involved in this process. Adhesion of crest cells on laminin-1 was comparable to that found on fibronectin or vitronectin. By contrast, migration was significantly greater on laminin-1 than on the other substrate molecules. Interaction of crest cells with laminin-1 involved two major cell-binding domains situated in different portions of the molecule, namely the E1' and E8 fragments, which elicited different cellular responses. Cells were poorly spread on the E1' fragment whereas, on E8, they were extremely flattened and cohesive. Either fragment supported cell locomotion, albeit not as efficiently as laminin-1. Immunoprecipitation and immunocytochemistry analyses revealed that crest cells expressed the alpha1beta1, alpha3beta1, alpha6beta1 and alpha vbeta3 integrins, as well as beta8 integrins, as presumptive laminin-1 receptors, but not alpha6beta4 and alpha2beta1. Immunofluorescence labeling of cultured cells showed that the alpha1, alpha v, beta1 and beta3 subunits were diffuse on the cell surface and in focal contacts. In contrast, alpha3 and beta8 were diffuse, while alpha6 was mostly intracytoplasmic and, secondarily, in focal contacts. Inhibition assays of cell adhesion and migration with function-perturbing antibodies demonstrated that alpha1beta1 played a predominant role in both adhesion and migration on laminin-1 and interacted with either binding sites in the E1' and E8 fragments. Alpha vbeta3 was also implicated in neural crest cell migration. In contrast, alpha3beta1, alpha6beta1 and the beta8 integrins appeared to play only subsidiary roles in cell adhesion and migration. Finally, the ability of neural crest cells to interact with laminin-1 was found to increase with time in culture, possibly in correlation with changes in alpha3 distribution on the cell surface. In conclusion, our study indicates that (1) the preferential migration of neural crest cells along basal laminae can be accounted for by the ability of laminin-1 to promote migration with great efficiency; (2) interaction with laminin-1 involves two major cell binding domains that are both recognized by the alpha1beta1 integrin; (3) alpha1beta1 integrin can elicit different cellular responses depending on the laminin-1 domains with which it interacts; and (4) changes in the repertoire of integrins expressed by neural crest cells are consistent with the modulations of cell-substratum adhesion occurring throughout migration.


In situ growth of a CaAl-NO3--layered double hydroxide film directly on an aluminum alloy for corrosion resistance.
In this study, a calcium-aluminum-layered double hydroxide (CaAl-LDH) thin film was grown on an AA6082 aluminum alloy, for the very first time, by using a facile in situ growth method in an effort to investigate the CaAl-LDH structural geometry and corresponding corrosion resistance properties. The structure and surface morphologies of the CaAl-LDH thin film were studied using a scanning electron microscope (SEM) equipped with an EDS detector, a transmission electron microscope (TEM), an X-ray diffractometer (XRD), and a Fourier transform infrared spectrometer (FT-IR), while the electron impendence spectra (EIS) and potentiodynamic curves were recorded to understand the LDH anticorrosion behavior. The findings demonstrated that thin, well-developed CaAl-LDH coatings with different surface morphologies can be prepared with eminent corrosion resistance properties. Specifically, the CaAl-LDH thin film synthesized at 140 °C-24 h synthetic conditions showed a large impedance modulus of 7.3 Ω cm2 at 0.01 Hz (|Z|f = 0.01 Hz), along with a low corrosion current density (Icorr) of 0.0007 μA cm-2, while a vertically orientated rod like structure with a uniform surface morphology was observed.


Initial Outcomes of Cyanoacrylate Closure, VenaSeal System, for the Treatment of the Incompetent Great and Small Saphenous Veins.
Cyanoacrylate closure of the saphenous vein with the VenaSeal system is a new technique just approved on December 2016 in Korea. Therefore, there are seldom reports about postprocedural outcomes of VenaSeal system in Asian countries. We report the initial outcomes of VenaSeal system for the treatment of great saphenous veins (GSVs) and small saphenous veins (SSVs) as a first report in Korea. Thirty-four patients with incompetent saphenous veins (47 GSVs and 16 SSVs) were treated at a single session. Concomitant phlebectomy was performed in 15 (44.1%) of 34 patients. All procedures were started with local anesthesia with music therapy and switched to intravenous sedation if patient requested. Patients revisited the clinic on 10 days, 1 month, and 3 months after surgery. Postprocedural evaluations including numerical pain rating score, revised Venous Clinical Severity Scores (rVCSS), and Aberdeen Varicose Vein Questionnaires were checked. Duplex ultrasound was performed on 10 days, 1 month, and 3 months. All treated veins (47 GSVs and 16 SSVs; 100%) had complete closure by duplex ultrasound during the follow-up period. Mean numerical pain rating scale of 6 hours after procedure was 2.7. The rVCSS was improved during the follow-up period. Phlebitis-like "abnormal skin reaction" in the treatment area was occurred in 8 (23.5%) of 34 patients and recovered fully in 2 weeks. Cyanoacrylate closure, VenaSeal system, is safe and effective for the treatment of incompetent saphenous veins.


Point-of-care assessment of medical trainee competence for independent clinical work.
Clinical supervisors make frequent assessments of medical trainees' competence so they can provide appropriate opportunities for trainees to experience clinical independence. This study explored context-specific assessments of trainees' competence for independent clinical work. In Phase One, 88 teaching team members from internal and emergency medicine were observed during clinical activities (216 hours), and 65 participants completed brief interviews. In Phase Two, 36 in-depth interviews were conducted using video vignettes. Data collection and analysis employed grounded theory methodology. Supervisors' assessments of trainee trustworthiness for independent clinical work involved consideration of four dimensions: knowledge/skill, discernment of limitations, truthfulness, and conscientiousness. Supervisors' reliance on language cues as a source of trustworthiness data was revealed. This study provides an initial exploration of context-specific competence assessments, which affect both patient safety and education, and provides a novel framework for study of the links between language use and competence.


Structural and cellular characterization of electrospun recombinant human tropoelastin biomaterials.
An off-the-shelf vascular graft biomaterial for vascular bypass surgeries is an unmet clinical need. The vascular biomaterial must support cell growth, be non-thrombogenic, minimize intimal hyperplasia, match the structural properties of native vessels, and allow for regeneration of arterial tissue. Electrospun recombinant human tropoelastin (rTE) as a medial component of a vascular graft scaffold was investigated in this study by evaluating its structural properties, as well as its ability to support primary smooth muscle cell adhesion and growth. rTE solutions of 9, 15, and 20 wt% were electrospun into sheets with average fiber diameters of 167 ± 32, 522 ± 67, and 735 ± 270 nm, and average pore sizes of 0.4 ± 0.1, 5.8 ± 4.3, and 4.9 ± 2.4 µm, respectively. Electrospun rTE fibers were cross-linked with disuccinimidyl suberate to produce an insoluble fibrous polymeric recombinant tropoelastin (prTE) biomaterial. Smooth muscle cells attached via integrin binding to the rTE coatings and proliferated on prTE biomaterials at a comparable rate to growth on prTE coated glass, glass alone, and tissue culture plastic. Electrospun tropoelastin demonstrated the cell compatibility and design flexibility required of a graft biomaterial for vascular applications.


[Effect of anti-aging drug on DNA methylase of brain in rats].
DNA methylase activity of brain in Wistar rats treated with Shenfang Bushen Shengxue Drug (SBSD) was observed using 3H-labelled methyl group of S-adenosyl-methionine incorporated into DNA. It was found that the SBSD has a marked effect on anti-aging. After SBSD treatment the specific activity of DNA methylase increased, the thermostability and salt-tolerance of it improved slightly, its optional pH changed from 7.5 to 8.0. A and a difference was found between the electrophoresgram of partially purified product of DNA methylase in SBSD treated rats and that in normal rats, suggesting SBSD could change the activity and characteristics of DNA methylase so as to affect the level of DNA methylation, which might be one pathway of SBSD effects on anti-aging.


Modulation of gut microbiota from obese individuals by in vitro fermentation of citrus pectin in combination with Bifidobacterium longum BB-46.
This study aimed to evaluate the effects of three treatments, i.e., Bifidobacterium longum BB-46 (T1), B. longum BB-46 combined with the pectin (T2), and harsh extracted pectin from lemon (T3) on obesity-related microbiota using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). The effects of the treatments were assessed by the analysis of the intestinal microbial composition (using 16S rRNA gene amplicon sequencing) and the levels of short-chain fatty acids (SCFAs) and ammonium ions (NH4+). Treatments T2 and T3 stimulated members of the Ruminococcaceae and Succinivibrionaceae families, which were positively correlated with an increase in butyric and acetic acids. Proteolytic bacteria were reduced by the two treatments, concurrently with a decrease in NH4+. Treatment T1 stimulated the production of butyric acid in the simulated transverse and descending colon, reduction of NH4+ as well as the growth of genera Lactobacillus, Megamonas, and members of Lachnospiracea. The results indicate that both B. longum BB-46 and pectin can modulate the obesity-related microbiota; however, when the pectin is combined with B. longum BB-46, the predominant effect of the pectin can be observed. This study showed that the citric pectin is able to stimulate butyrate-producing bacteria as well as genera related with anti-inflammatory effects. However, prospective clinical studies are necessary to evaluate the anti/pro-obesogenic and inflammatory effects of this pectin for future prevention of obesity.


Maximum-likelihood image estimation using photon-correlated beams.
A theory is presented addressing the fundamental limits of image estimation in a setup that uses two photon-correlated beams. These beams have the property that their photon arrivals, as a point process, are ideally synchronized in time and space. The true image represents the spatial distribution of the optical transmittance (or reflectance) of an object. In this setup, one beam is used to probe the image while the other is used as a reference providing additional information on the actual number of photons impinging on the object. This additional information is exploited to reduce the effect of quantum noise associated with the uncertainty in the number of photons per pixel. A stochastic model for the joint statistics of the two observation matrices is developed and used to obtain a local maximum-likelihood estimator of the image. The model captures the nonideal nature of the correlation between the photons of the beams by means of a simple random translation model. The mean-square error of the estimator is evaluated and compared to the corresponding conventional techniques. Conditions for the performance advantage of the proposed estimator are examined in terms of key system parameters. The theoretical predictions are demonstrated by means of simulation.


Health, wealth, and happiness: financial resources buffer subjective well-being after the onset of a disability.
We examined the hypothesis that the relationship between financial status and subjective well-being, typically found to be very small in cross-sectional studies, is moderated by health status. Specifically, we predicted that wealth would buffer well-being after the onset of a disability. Using data from the Health and Retirement Study, a longitudinal study of people at and approaching retirement age, we employed within-subjects analyses to test whether wealth measured prior to the onset of a disability protected participants' well-being from some of the negative effects of a new disability. We found support for this hypothesis: Participants who were above the median in total net worth reported a much smaller decline in well-being after a new disability than did participants who were below the median. We also found some evidence that the buffering effect of wealth faded with time, as below-median participants recovered some of their well-being.


The placebo effect: advances from different methodological approaches.
There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.


Seasonal activity of Trechnites insidiosus (Hymenoptera: Encyrtidae) and its host Cacopsylla pyricola (Hemiptera: Psyllidae) in pear.
Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is the most expensive and challenging insect pest of commercial pear trees in the Pacific Northwest. Integrated pest management (IPM) programs are working toward relying more heavily on natural enemies to reduce insecticide use. Trechnites insidiosus (Crawford) (Hymenoptera: Encyrtidae) is the main parasitoid of C. pyricola, but little is known about its biology in the region. Developing sampling tools is important for the deployment of IPM programs, including monitoring of natural enemies. In this study, we examined 2 conventional monitoring methods: beat trays and yellow sticky cards, in addition to screened sticky cards and 3D-printed cylinder traps. Additionally, we tested an overwintering trap for the collection of parasitized C. pyricola. The trapping methods were tested in orchards in Oregon and Washington. Unscreened cards caught the most T. insidiosus and C. pyricola, followed by screened cards, cylinder traps, and then beat trays. Beat trays sometimes failed to catch any T. insidiosus, even when it was found in abundance via other methods. Screened cards and cylinder traps reduced bycatch and increased ease of identifying T. insidiosus. Specimens from the cylinder traps were also more suitable for use in molecular analysis. The overwintering traps were effective at capturing parasitized C. pyricola, but were highly variable year to year. The ideal trapping method will vary based on research needs (e.g., DNA preservation, reducing bycatch, catching higher numbers), but both screened sticky cards and cylinder traps were viable methods for monitoring T. insidiosus and its host.


Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist.
Exposure to heavy metals, such as vanadium, poses an ongoing environmental and health threat, heightening the risk of neurodegenerative disorders. While several compounds have shown promise in mitigating vanadium toxicity, their efficacy is limited. Effective strategies involve targeting specific subunits of the NMDA receptor, a glutamate receptor linked to neurodegenerative conditions. The potential neuroprotective effects of ZA-II-05, an NMDA receptor antagonist, against vanadium-induced neurotoxicity were explored in this study. Organotypic rat hippocampal slices, and live mice, were used as models to comprehensively evaluate the compound's impact. Targeted in vivo fluorescence analyses of the hippocampal slices using propidium iodide as a marker for cell death was utilized. The in vivo study involved five dams, each with eight pups, which were randomly assigned to five experimental groups (n = 8 pups). After administering treatments intraperitoneally over six months, various brain regions were assessed for neuropathologies using different immunohistochemical markers. High fluorescence intensity was observed in the hippocampal slices treated with vanadium, signifying cell death. Vanadium-exposed mice exhibited demyelination, microgliosis, and neuronal cell loss. Significantly, treatment with ZA-II-05 resulted in reduced cellular death in the rat hippocampal slices and preserved cellular integrity and morphological architecture in different anatomical regions, suggesting its potential in countering vanadium-induced neurotoxicity.


Longitudinal associations between reading and mathematics achievement.
The association between early reading skills and changes in mathematics was examined in a large, low-income sample to determine whether students who have a greater level of reading skills in early elementary school exhibit more rapid gains in tests of mathematics. The longitudinal associations between third grade reading comprehension and changes in three components of mathematics achievement (Problem Solving and Data Interpretation, Mathematical Concepts and Estimation, Mathematical Computation) from third through eighth grade were examined. Latent growth models were fit to the repeated assessments of each mathematics component and the students' third grade reading and global mathematics scores were included as predictors of the intercept and slope. Gender, poverty status, and ethnicity were included in the models as control variables. The results showed males and African-American students tended to have shallower rates of change than females and non-African-American/non-Hispanic students. In terms of the effect of reading on changes in mathematics, third grade reading comprehension was found to be a positive significant predictor of change for each component of mathematics, suggesting students with a greater level of reading achievement in early elementary school change more rapidly in mathematics skills controlling for prior mathematics skills and student characteristics. The largest effects were shown for the Problem Solving and Data Interpretation test, a test focused on the applications of mathematics knowledge, and the Mathematical Concepts and Estimation test. Negligible effects were found for changes in Mathematical Computation. Thus, early reading comprehension was shown to be related to a conceptual understanding of mathematics and the application of mathematics knowledge. These findings lend support for the notion that early reading skills are important for success in mathematics.


[A new approach to the treatment of patients with circulatory encephalopathy].
Effects were studied of vincamin and tanakan in 68 patients with stage I, II and III discirculatory encephalopathy (as per WHO classification 1981). In 52% of the patients atherosclerosis of brain vessels was associated with arterial hypertension (group I), in 48 per cent venous discirculatory encephalopathy was diagnosable against the background of arterial hypertension (group IIA-20%) and arterial hypotension (group IIB-26%). Both tanakan and vincamin were found to be effective in group I patients; however, in stage III condition their effectiveness was no better than 42 and 15% respectively, which fact might be due to organic changes in the vascular wall. Tanakan appeared to be more beneficial in group II patients since venous dystonia is considered to be the main pathogenetic link in this context, and tanakan is known to improve the venous outflow from the cranial cavity. Almost in one-third of group IIB patients vincamin worsened general health status, especially so in stage III discirculatory encephalopathy, which fact may be related to peculiar effect of the drug on the arterial link of brain blood supply.


A precise map of splice junctions in the mRNAs of minute virus of mice, an autonomous parvovirus.
We have determined the exact splicing patterns of the mRNAs of the minute virus of mice by a combination of cDNA sequencing and S1 nuclease protection analysis. There are four virus-specific mRNA species, each coding for one of the four polypeptides identified by in vitro translation. The R1 mRNA comprises sequences from nucleotide approximately 200 to 2281 and from 2378 to approximately 4800 and codes for the NS1 protein. The R2 mRNA is derived from nucleotides approximately 200 to 515, 1991 to 2281, and 2378 to approximately 4800 and codes for the NS2 protein. Between nucleotides 1991 and 2281, the coding sequence for NS2 overlaps that of NS1, but in a different reading frame. R3 covers nucleotides approximately 2007 to 2281 and 2378 to approximately 4800 and codes for VP2. The fourth species, R3', differs from R3 by using an alternative splice donor and acceptor in the region around 47 map units (nucleotide 2400); it extends from nucleotide approximately 2007 to 2317 and from 2400 to approximately 4800 and almost certainly codes for VP1. The R2 transcript is unusual in that the intron that was removed from it (nucleotides 516 to 1990) starts with GC rather than the canonical GU. With the exception of the splice acceptor at position 2378, which is found only in rodent parvoviruses, the splice junctions are highly conserved among autonomous parvoviruses. These results show that minute virus of mice, like other small DNA viruses, uses multiple strategies to compress the coding information for several viral proteins into a short (5,104 nucleotide) genome.


Domestic violence: the response of healthcare.
This article discusses domestic violence and the role of the healthcare professional in dealing with it. The author provides advice on screening, assessing, documenting, and then intervening to help victims of domestic violence. There is also a special section on dealing with the problem of elderly abuse/violence.


Effective Photocatalytic Ethanol Reforming into High-Value-Added Multicarbon Compound Coupled with H2 Production Over Pt-S3 Sites at PtSA -ZnIn2 S4 Interface.
Selective photocatalytic production of high-value acetaldehyde concurrently with H2 from bioethanol is an appealing approach to meet the urgent environment and energy issues. However, the difficult ethanol dehydrogenation and insufficient active sites for proton reduction within the catalysts, and the long spatial distance between these two sites always restrict their catalytic activity. Here, guided by the strong metal-substrate interaction effect, an atomic-level catalyst design strategy to construct Pt-S3 single atom on ZnIn2 S4 nanosheets (PtSA -ZIS) is demonstrated. As active center with optimized H adsorption energy to facilitate H2 evolution reaction, the unique Pt single atom also donates electrons to its neighboring S atoms with electron-enriched sites formed to activate the O─H bond in * CH3 CHOH and promote the desorption of * CH3 CHO. Thus, the synergy between Pt single atom and ZIS together will reduce the energy barrier for the ethanol oxidization to acetaldehyde, and also narrow the spatial distance for proton mass transfer. These features enable PtSA -ZIS photocatalyst to produce acetaldehyde with a selectivity of ≈100%, which will spontaneously transform into 1,1-diethoxyethane via acetalization to avoid volatilization. Meanwhile, a remarkable H2 evolution rate (184.4 µmol h-1 ) is achieved with a high apparent quantum efficiency of 10.50% at 400 nm.


Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes.
To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA(1c) and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose </= 0.3 U/kg/24 h and HbA(1c) within the normal range, was analysed in relation to characteristics at diagnosis. Remissions were seen in 43% of the patients with a median duration of 8 months (range 1-73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab(+)), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m(2)) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab(+) remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.


MicroRNA-214 protects cardiac myocytes against H2O2-induced injury.
Reactive oxygen species (ROS)-induced cardiac myocyte injury resulting from changes in the expression levels of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in hydrogen peroxide (H2O2)-mediated gene regulation in cardiac myocytes. In this study, we used quantitative real-time RT-PCR (qRT-PCR) to demonstrate that miR-214 was upregulated in cardiac myocytes after treatment with H2O2. We transfected cells with pre-miR-214 to upregulate miR-214 expression and transfected cells with a miR-214 inhibitor (anti-miR-214) to downregulate miR-214 expression. H2O2-induced cardiac cell apoptosis was detected by flow cytometry. The level of apoptosis was increased by the miR-214 inhibitor and decreased by pre-miR-214. Therefore, we believe that miR-214 plays a positive role in H2O2-induced cardiac cell apoptosis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is constitutively active and is considered to be the primary downregulator of the pro-oncogenic PI3K/Akt pathway. Western blot analysis revealed that the expression of the PTEN protein in cardiac myocytes decreased after H2O2 induction. Anti-miR-214 increased PTEN protein expression level, in contrast, pre-miR-214 decreased the PTEN protein expression level in cultured cardiac myocytes. These results indicate that PTEN is regulated by miR-214 and serves as an important target of miR-214 in cardiac myocytes. In conclusion, miR-214 is sensitive to H2O2 stimulation, and miR-214 protects cardiac myocytes against H2O2-induced injury via one of its targets, PTEN.


The use of the term 'radiosensitivity' through history of radiation: from clarity to confusion.
The term 'radiosensitivity' appeared for the first time at the beginning of the 20th century, few years after the discovery of X-rays. Initially used by French and German radiologists, it illustrated the risk of radiation-induced (RI) skin reactions. From the 1950s, 'radiosensitivity' was progressively found to describe other features of RI response such as RI cancers or cataracts. To date, such confusion may raise legal issues and complexify the message addressed to general public. Here, through an historical review, we aimed to better understand how this confusion appeared. To support our historical review, a quantitative and qualitative wording analysis of the 'radiosensitivity' occurrences and its derived terms was performed with Google books, Pubmed, Web of Science™ databases, and in all the ICRP publications. While 'radiosensitivity' was historically related to RI adverse tissue events attributable to cell death, the first efforts to quantify the RI risk specific to each organ/tissue revealed some different semantic fields that are not necessarily compatible together (e.g. adverse tissue events for skin, cataracts for eyes, RI cancer for breast or thyroid). To avoid such confusion, we propose to keep the historical definition of 'radiosensitivity' to any clinical and cellular consequences of radiation attributable to cell death and to introduce the term 'radiosusceptibility' to describe the RI cancers or any feature that is attributable to cell transformation.


Predictors of Caregiver Burden in Huntington's Disease.
Huntington's disease (HD) is a genetic neurodegenerative condition that is characterized by cognitive, motor, and psychiatric dysfunction. The purpose of this study was to explore which disease characteristics influence caregiver burden in HD. Fifty participants with HD and 50 of their caregivers participated in the study at the University of South Florida. Participants were administered a neuropsychological battery, the Unified Huntington's Disease Rating Scale (UHDRS) motor exam, and the Frontal Systems Behavior Scale (FrSBe) self-report. Caregivers completed the Caregiving Appraisal Scale and the FrSBe family-report. There were significant correlations between caregiver burden and caregiver age and sex, UHDRS motor scores, cognitive functioning, and self and caregiver-reported FrSBe scores. The significant variables were entered into a regression model and explained 63.1% of the variance in caregiver burden scores. Caregiver age, cognitive functioning, and caregiver-reported FrSBe scores continued to be significant predictors of caregiver burden, whereas the other variables were no longer significant. There were significant relationships between caregiver burden, cognitive functioning, and frontally mediated behaviors, but not motor scores. The results suggest that possible interventions for caregivers may include education to caregivers on how to cope with apathy/executive dysfunction and cognitive decline. Caregiver age was associated with burden, with younger age being associated with increased burden when controlling for symptom severity. This has implications for this population in that HD typically has a younger age of onset than other neurodegenerative diseases and therefore, these caregivers may be particularly at risk for caregiver burden.


Flotation of the Bivalve Corbicula fluminea as a Means of Dispersal.
Small specimens of the Asiatic bivalve Corbicula c.f. fluminea (Müller) secrete long mucous threads through their exhalent siphons that act as draglines to buoy the animal into a water column. These mucous strands, secreted in response to water current stimuli, are produced by dense accumulations of ctenidial mucocytes and may help in the downstream or interstream dispersal of this rapidly spreading exotic clam.


Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus.
Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site. In the presence of high thrombin concentrations, clots from Pros1lox/loxPf4-Cre- mice contract, but not clots from Pros1lox/loxPf4-Cre+ mice, because of highly dense fibrin networks. Thus, PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries.