The time and spatial effects of bystander response in mammalian cells induced by low dose radiation.
Bystander effects induced by low dose of ionizing radiation have been shown to widely exist in many cell types and may have a significant impact on radiation risk assessment. Though many studies have been reported on this phenomenological observation, the mechanisms underlying this process are not clear, especially on the questions of how soon after irradiation the bystander effects can be initiated and how far this bystander signal can be propagated once it is started. DNA double-strand breaks (DSBs) induced by ionizing radiation or carcinogenic chemicals can be visualized in situ using gamma-H2AX immunofluorescent staining. Our previous studies have shown that in situ visualization of DSBs could be used to assess irradiation-induced extranuclear/extracellular (bystander) effect at an early stage after irradiation. In the present studies, we used this method to investigate the time and spatial effects of damage signals on unirradiated bystander cells. The results showed that increased DSBs in irradiated and unirradiated bystander areas could be visualized 2 min after radiation and reached its maximum 30 min after radiation. The average levels of DSB formation at 30 min post-1cGy irradiation in the irradiated and unirradiated bystander areas were 3-fold and 2-fold higher than those of the sham-irradiated control cells, respectively. Afterwards, the formation of DSBs declined with incubation time and remained steady for at least 6 h at a level that was statistically higher than their controls. The results also showed that the bystander signal derived from irradiated cells could be transferred to anywhere in the dish and the percentage of DSBs in the unirradiated bystander cells was not dependent on the dose delivered. Moreover, the fraction of DSB positive cells in unirradiated bystander areas showed a time-dependent increase based on its distance to the irradiated area at very early stage post-irradiation. Both lindane and DMSO significantly suppressed the yield of DSBs in the cells of unirradiated bystander areas, which suggest that gap junctional intercellular communication and reactive oxygen species played important roles in the induction of the bystander effects, both in irradiated and unirradiated bystander areas.


Molecular-dynamics simulations of cold antihydrogen formation in strongly magnetized plasmas.
Employing a high-order symplectic integrator and an adaptive time-step algorithm, we perform molecular-dynamics simulations of antihydrogen formation, in a cold plasma confined by a strong magnetic field, over time scales of microseconds. Sufficient positron-antiproton recombination events occur to allow a statistical analysis for various properties of the formed antihydrogen atoms. Giant-dipole states are formed in the initial stage of recombination. In addition to neutral atoms, we also observe antihydrogen positive ions (H(+)), in which two positrons simultaneously bind to an antiproton.


Forensic fingerprinting of diamondoids for correlation and differentiation of spilled oil and petroleum products.
Diamondoids (adamantanes and diamantanes) are rigid, three-dimensionallyfused cyclohexyl-ring alkane compounds that can be found in almost all crude oils and in most petroleum products. Forforensic environmental investigations, the most commonly used biomarkers are high molecular weight (MW) tri- to pentacyclic terpanes and steranes. Most of these high MW biomarkers, however, are removed from the original crude oil feedstocks during the refining processes, while smaller biomarkers including diamondoids are concentrated in petroleum products. Fingerprinting diamondoids could thus provide another diagnostic means for correlation and differentiation of spilled oils and be particularly valuable for light to midrange distillates, such as jet and diesel fuels, the source of which may be difficult to identify using routine biomarker techniques. In this work, a reliable GC-MS analytical method has been developed for characterization and quantitation of diamondoids. The method detection limits for five target diamondoids were determined to be in the range of 0.06-0.14 microg/g oil. Distributions of diamondoids in over 100 different oils and refined products were quantitatively compared. The concentrations of four groups of target biomarkers were found, in general, to decrease in the order of sesquiterpanes > terpanes and steranes > adamantanes > diamantanes in both crude oils and refined products. A number of indices of admantanes and diamantanes have been developed and assessed as source indicators using their diagnostic powers (DP). The effects of evaporative weathering and biodegradation on alteration of diamondoid distributions have been quantitatively investigated. Finally, a spill case study by statistical evaluation of diagnostic ratios using the "two-tailed" Student's tapproach is presented to illustrate the unique utility of diamondoids for correlation and differentiation of unknown spilled diesels.


Characteristics and turnover of exopolymeric substances in a hypersaline microbial mat.
The properties and microbial turnover of exopolymeric substances (EPS) were measured in a hypersaline nonlithifying microbial mat (Eleuthera, Bahamas) to investigate their potential role in calcium carbonate (CaCO(3)) precipitation. Depth profiles of EPS abundance and enzyme activities indicated that c. 80% of the EPS were turned over in the upper 15-20 mm. Oxic and anoxic mat homogenates amended with low-molecular-weight (LMW) organic carbon, sugar monomers, and different types of EPS revealed rapid consumption of all substrates. When comparing the consumption of EPS with that of other substrates, only marginally longer lag times and lower rates were observed. EPS (5-8%) were readily consumed during the conversion of labile to refractory EPS. This coincided with a decrease in glucosidase activity and a decrease in the number of acidic functional groups on the EPS. Approximately half of the calcium bound to the EPS remained after 10 dialyses steps. This tightly bound calcium was readily available to precipitate as CaCO(3). We present a conceptual model in which LMW organic carbon complexed with the tightly bound calcium is released upon enzyme activity. This increases alkalinity and creates binding sites for carbonate and allows CaCO(3) to precipitate. Therefore, this model explains interactions between EPS and CaCO(3) precipitation, and underscores the critical role of aerobic and anaerobic microorganisms in early diagenesis and lithification processes.


Esophageal carcinoma following bariatric procedures.
The long-term success of bariatric operations for weight reduction has been well documented, but their potential effects on the risk of esophageal cancer have not been evaluated. We performed operations on 3 patients for esophageal cancer following bariatric operations: 2 had Roux-en-Y gastric bypass, and 1 underwent vertical banded gastroplasty. All of these patients had adenocarcinoma at the gastroesophageal junction; 1 involved the entire intrathoracic esophagus. The intervals between the weight-loss operations and cancer diagnoses were 21, 16, and 14 years. All 3 patients had symptoms of reflux for many years before dysphagia developed and cancer was diagnosed. We performed a limited esophagogastrectomy, a classic Ivor-Lewis procedure, and a total esophagectomy with jejunal free-tissue transfer from stomach to cervical esophagus. Two patients had positive lymph nodes. One patient is alive at 6 years; 2 died at 13 and 15 months after undergoing operation for recurrent cancer. The effect of bariatric operations on gastroesophageal reflux is not known, although gastric bypass has been advocated as the "ultimate antireflux procedure." The presence of esophageal cancer in these 3 patients years after the weight loss operation is worrisome. We believe that patients who develop new symptoms should have endoscopic evaluation and that epidemiologic studies on the incidence of esophageal cancer occurring years after bariatric operation should be performed.


Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules.
Although the role of liganded nuclear receptors in mediating coactivator/corepressor exchange is well-established, little is known about the potential regulation of chromosomal organization in the 3-dimensional space of the nucleus in achieving integrated transcriptional responses to diverse signaling events. Here, we report that ligand induces rapid interchromosomal interactions among specific subsets of estrogen receptor alpha-bound transcription units, with a dramatic reorganization of nuclear territories, which depends on the actions of nuclear actin/myosin-I machinery and dynein light chain 1. The histone lysine demethylase, LSD1, is required for these ligand-induced interactive loci to associate with distinct interchromatin granules, long thought to serve as "storage" sites for the splicing machinery, some critical transcription elongation factors, and various chromatin remodeling complexes. We demonstrate that this 2-step nuclear rearrangement is essential for achieving enhanced, coordinated transcription of nuclear receptor target genes.


AHNS series: Do you know your guidelines? Management of head and neck cancer in the era of human papillomavirus: Educating our patients on human papillomavirus.
Human papillomavirus (HPV) has changed the face of head and neck cancer over the past 2 decades. No longer is this solely a disease of older patients with a history of heavy tobacco and alcohol use. Patients with HPV-related head and neck cancers tend to be younger, healthier, and have an improved prognosis, compared with those with HPV-negative tumors. As more patients are diagnosed with HPV-related head and neck cancer, physicians have important topics to consider. These include prevalence, transmission, and natural history of HPV, the role of screening, vaccines, and HPV testing in head and neck cancer. This article continues a series developed by the American Head and Neck Society's Education Committee entitled "Do you know your guidelines?" and is intended to provide guidance for navigating common questions and concerns patients may have about HPV infection and HPV-related head and neck cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 833-839, 2017.


Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses.
The present study focuses on the design and synthesis of a cage-like organic skeleton containing two triazole rings jointed via imine linkage. These molecules can act as urease inhibitors. The in-vitro urease inhibition screening results showed that the combination of the two triazole skeleton in the cage-like morphology exhibited comparable urease inhibition activity to that of the reference thiourea while the metallic complexation, especially with copper, nickel, and palladium, showed excellent activity results with IC50 values of 0.94 ± 0.13, 3.71 ± 0.61, and 7.64 ± 1.21 (3a⁻c), and 1.20 ± 0.52, 3.93 ± 0.45, and 12.87 ± 2.11 µM (4a⁻c). However, the rest of compounds among the targeted series exhibited a low to moderate enzyme inhibition potential. To better understand the compounds' underlying mechanisms of the inhibitory effect (3a and 4a) and their most active metal complexes (3b and 4b), we performed an enzymatic kinetic analysis using the Lineweaver⁻Burk plot in the presence of different concentrations of inhibitors to represent the non-competitive inhibition nature of the compounds, 3a, 4a, and 4b, while mixed type inhibition was represented by the compound, 3b. Moreover, molecular docking confirmed the binding interactive behavior of 3a within the active site of the target protein.


[Effect of calcium-independent phospholipase A(2) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance].
Objective: To investigate the effect of calcium-independent phospholipase A(2) (iPLA(2)) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance. Methods: A total of 28 male Sprague-Dawley rats were randomly divided into the following three groups: 12 rats in group I (normal control group) were given normal diet for 18 weeks; 8 rats in group II (non-alcoholic fatty liver disease model group) were given high-fat diet for 18 weeks; 8 rats in group III (iPLA(2) inhibitor group) were given high-fat diet for 18 weeks and intraperitoneal injection of the iPLA(2) inhibitor bromoenol lactone 150 μg/kg once every other day since week 15 (14 times of injection in total). All the rats were sacrificed at the same time, and body weight and liver weight were measured. Blood lipids, serum enzymes, fasting blood glucose, fasting insulin, free fatty acid, and serum iPLA(2) concentration were measured in each group, and liver pathological changes were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the level of hepatocyte apoptosis and the apoptotic index was calculated. Quantitative PCR was used to measure the mRNA expression of iPLA(2). The Student-Newman-Keuls test and the chi-square test were used for comparison of parameters between groups I, II, and III. P < 0.05 was considered statistically significant. Results: Compared with group I, group II had significant increases in triglyceride (0.75±0.05 mmol/L vs 1.20±0.13 mmol/L, P < 0.05), cholesterol (1.50±0.12 mmol/L vs 2.94±0.34 mmol/L, P < 0.05), low-density lipoprotein (0.65±0.06 mmol/L vs 1.30±0.16 mmol/L, P < 0.05), free fatty acid (0.58±0.09 mEq/L vs 0.80±0.20 mEq/L, P < 0.05), fasting blood glucose (4.85±0.22 mmol/L vs 6.94±0.65 mmol/L, P < 0.05), and fasting insulin (0.89±0.52 mmol/L vs 1.29±0.52 mmol/L, P < 0.05), and a significant reduction in the insulin sensitivity index (0.52±0.21 vs 0.27±0.11, P < 0.05); group II also had significant inflammation and fatty degeneration shown by liver pathology, and compared with group I, group II had significant increases in apoptotic cells and apoptotic index (0.58%±0.17% vs 39.69%±4.96%, P < 0.05). Compared with group I, group II had significant increases in serum iPLA(2) concentration (2.92±0.08 ng/ml vs 3.28±0.14 ng/ml, P < 0.05) and the mRNA expression of iPLA(2) in the liver (1.07±0.18 vs 7.68±0.49, P < 0.05). Compared with group II, group III had a lower level of hepatocyte apoptosis, a significant reduction in apoptotic index (39.69%±4.96% vs 24.80%±2.53%, P < 0.05), significant reductions in serum iPLA(2) concentration (3.28±0.14 ng/ml vs 2.64±0.24 ng/ml, P < 0.05) and the mRNA expression of iPLA(2) in the liver (7.68±0.49 vs 2.60±0.36, P < 0.05), significant reductions in fasting insulin (1.29±0.52 mmol/L vs 0.80±0.09 mmol/L, P < 0.05) and fasting blood glucose (6.94±0.65 mmol/L vs 5.18±0.35 mmol/L, P < 0.05), and a significant increase in insulin sensitivity index (0.27±0.11 vs 0.45±0.09, P < 0.05). Conclusion: There is a significant increase in the expression of iPLA(2) in rats with non-alcoholic fatty liver disease, and iPLA2 inhibitor can reduce hepatocyte lipoapoptosis and improve insulin resistance.


Patient experiences of receiving a diagnosis of Parkinson's disease.
To report patients' own experiences of receiving a diagnosis of Parkinson's disease (PD) and to identify factors influencing this experience. A survey by the European Parkinson's Disease Association in 11 European countries. 1775 patients with an average age of 69.7 years participated of whom 54% were male. Those living in rural areas reported having waited longer to seek medical help (p < 0.05). A possible diagnosis of PD was made at the first appointment in a third of respondents. When the diagnosis was made, only 50% reported that the diagnosis was communicated sensitively. 38% of patients reported having been given enough time to ask questions and discuss concerns, but 29% did not. 98% of participants reported having been given information about PD at the time of diagnosis but 36% did not find the information given helpful. Patient satisfaction with the diagnostic consultation was positively associated with more sensitive delivery of diagnosis, the helpfulness and quantity of the information provided and time to ask questions (all p < 0.001). Where diagnosis was given by a specialist, participants reported greater perceived satisfaction with the diagnostic consultation, greater sensitivity of communicating the diagnosis, time to ask questions, provision and helpfulness of information, and earlier medication prescription (all p < 0.0001). There is a need to improve how the diagnosis of PD is communicated to patients, the opportunity to ask questions soon after diagnosis, and the amount, timing and quality of life information provided, as this is associated with greater satisfaction with the diagnostic process.


Pamidronate in the treatment of childhood SAPHO syndrome.
SAPHO syndrome is increasingly recognized within the paediatric population. Conventional therapeutic approaches have often not been effective. Pamidronate is a second-generation bisphosphonate that affects bone turnover and demonstrates anti-inflammatory properties. In small case series it has given symptomatic relief to adults with this condition. To report the clinical experience with pamidronate in childhood SAPHO syndrome. A retrospective observational study of all children with SAPHO syndrome treated with pamidronate between 1996 and 2003 at a tertiary rheumatology centre. The standard dosing regime for pamidronate was 1 mg/kg to a maximum of 30 mg, administered daily for three consecutive days, repeated 3-monthly as required. Response to treatment was determined by clinical observation, patient subjective response and reduction in other treatments Seven girls were treated, with a median (range) age at diagnosis of 11 yr (9-15 yr). All patients demonstrated a beneficial clinical response, with relief of pain, increased activity and improved well-being. Subsequent courses of pamidronate were used in all patients. Other medications including corticosteroids and methotrexate could subsequently be stopped. Transient symptoms were associated with the initial course of pamidronate in some patients. No serious adverse events were reported. Pamidronate was associated with a marked improvement in function and well-being, and a reduction of pain and use of other medications in all patients, with no significant adverse effects. This study represents preliminary clinical data. A prospective multicentre study is necessary to assess the role and long-term safety of pamidronate in the management of childhood SAPHO syndrome


Charge separation in ground-state 1,2,4,5-tetra-substituted benzene derivatives.
The conditions required for a formal biradical to exist in a zwitterionic form in the ground state are discussed following the recent experimental observation of zwitterionic structure in the ground state of a quinoid molecule (di-tert-butyl derivative of 2,5-diamino-1,4-benzoquinonediimine, I). A unique characteristic of molecules of this class is the fact that they may be considered as being formed by the union of two radicals, each having an odd number of pi electrons. In the case of I, one fragment carries the two amino group having 7 pi electrons; it acts as the electron donor. The other fragment carries the two oxygen atoms (carrying 5 pi electrons) and acts as an electron acceptor. A model that predicts the properties of these systems is presented, based on previous work on non-Kekule hydrocarbons(2,3) and on the electron donating and attracting properties of the donor and acceptor groups, respectively. The zwitterion is formed by an electron transfer leading to two subunits carrying 6 pi electrons each and may become more stable than the triplet biradical even in the gas phase (i.e., in the absence of an external field) if the ionization potential of the donor is small (of the order of 3-4 eV). In some cases solvation in a polar solvent is required to make the zwitterionic form the lowest energy species on the ground-state surface. The 'spacer' between the donor and acceptor groups (which need not be necessarily derived from an aromatic structure) can be varied and influences the overall dipole moment that is calculated in some cases to be quite large (over 20 D in the gas phase).


Headache children with temporomandibular disorders have several types of pain and other symptoms.
The aim was to investigate the association between temporomandibular disorders (TMD) and overall muscle tenderness, depressive symptoms, sleep difficulties, headache frequency and related symptoms in children with primary headache in comparison with controls. Based on an unselected population sample of 1135 Finnish schoolchildren classified according to the type of headache at age 12, altogether 297 children aged 13-14 from different headache groups and healthy controls were randomly selected for an interview and clinical examinations. Children with migraine had more TMD signs than children with nonmigrainous headaches or healthy controls. High TMD total scores were associated with palpation tenderness in other parts of the body and with frequent headache attacks. We conclude that children with overall headache, migraine in particular, and high total TMD scores showed an increased overall tenderness to muscle palpation and multiply manifested hypersensitivity pain.


Biophysical Characterization of the Type III Secretion System Translocator Proteins and the Translocator Proteins Attached to Bacterium-Like Particles.
Diarrhea caused by Shigella, Salmonella, and Yersinia is an important public health problem, but development of safe and effective vaccines against such diseases is challenging. A new antigen delivery platform called bacterium-like particles (BLPs) was explored as a means for delivering protective antigens from the type III secretion systems (T3SS) of these pathogens. BLPs are peptidoglycan skeletons derived from Lactococcus lactis that are safe for newborns and can carry multiple antigens. Hydrophobic T3SS translocator proteins were fused to a peptidoglycan anchor (PA) for BLP attachment. The proteins and protein-BLP complexes associated with BLPs were characterized and the resulting data used to create three-index empirical phase diagrams (EPDs). On the basis of these EPDs, IpaB (Shigella) and SipB (Salmonella) behave distinctly from YopB (Yersinia) under different environmental stresses. Adding the PA domain appears to enhance the stability of both the PA and translocator proteins, which was confirmed using differential scanning calorimetry, and although the particles dominated the spectroscopic signals in the protein-loaded BLPs, structural changes in the proteins were still detected. The protein-BLPs were most stable near neutral pH, but these proteins' hydrophobicity made them sensitive to environmental stresses.


[Interferon production-stimulating factor].
A factor stimulating interferon production (FSIP) has been isolated from cells treated once or twice (at an interval of 6-8 hours) with poly(rI).poly(rC) followed by actinomycin D (2 microgram/ml) or dehydrorifampicin (50 microgram/ml). In a dilution 1:512 the preparation stimulated interferon production 4-fold. In higher concentrations, the preparation induced interferon yields of 1280-2560 IE50/ml, i.e. exceeded the control values 16-fold. The factor does not affect the antiviral activity of interferon and has the tissue specificity. Its stimulating effect was not manifested with inducers of other nature. All the properties of FSIP studied show it to be similar with homologous interferon and repressor of its production but, unlike the latter, it was thermolabile and sensitive to acid pH.


PREP: present requirements for nurses and future possibilities.
All nurses know the requirements for PREP, with its practice, continuing professional development and re-registration standards. However, the system relies on nurses' honesty in completing their PREP record and does not assess a person's fitness to practice as a nurse. Would a system such as the medical re-accreditation process be more appropriate?


Abnormal intrahepatic portal vasculature in native and allograft liver biopsies: a comparative analysis.
Abnormal portal vessels in small portal tracts can be seen in association with various causes of portal hypertension, such as noncirrhotic portal hypertension (NCPH) and cirrhosis. Very little has been reported about the presence of abnormal portal vessels in livers with normal portal pressure. Little attention has also been given to the presence of abnormal vessels in liver allografts outside the setting of transplant vasculopathy/chronic rejection. This study reports on the portal vasculature abnormalities, many similar to those described in NCPH, encountered in routine native liver biopsies (n = 46) and allograft liver biopsies (n = 48). A classification scheme for the abnormal portal vasculature was adapted from the literature, and the portal vessels were divided into five groups (types 0-IV). Abnormal vessels were present in greater than 25% of the portal tracts in 88% of all the biopsies studied; there was no significant difference between the native and allograft biopsies. In the allograft biopsy group, there were correlations between vascular abnormalities and severity of a concurrent acute cellular rejection episode, the presence of prior rejection episodes, and length of time after transplant. Biopsies from patients with viral hepatitis C infection (HCV) showed more type IV lesions (absent or sclerosed portal vessels) with fragmentation when compared with biopsies obtained for other reasons. The number of portal tracts with abnormal portal veins and fragmented vessels correlated positively with increasing fibrosis. This is the first study to demonstrate the presence of abnormal portal vessels, some of the type seen in NCPH, in a significant number of both native and allograft liver biopsies in patients without evidence of portal hypertension. Abnormal portal vasculature tends to be associated with HCV and increased fibrosis, and, within the transplant group, with the severity of rejection, presence of prior rejection episodes, and increased time posttransplantation.


Position specificity in Chitonomyces (Ascomycota, Laboulbeniomycetes) on Laccophilus (Coleoptera, Dytiscidae): a molecular approach resolves a century-old debate.
The occurrence of Laboulbeniomycete species consistently on a precise portion of beetle integument was investigated in 13 species of Chitonomyces ectoparasitic on the aquatic diving beetle Laccophilus maculosus (Coleoptera, Dytiscidae). The phenomenon was called "position specificity" by Roland Thaxter in 1896, yet the mechanism has remained unknown. By using molecular analysis of the nucSSU rRNA gene and the 5.8S and partial ITS1 rRNA regions, 13 species of Chitonomyces reported to exhibit position specificity on Laccophilus maculosus were placed neatly into pairs of morphotypes, resulting in synonomies and recognition of six phylogenetic species (one species is a triplet). Each phylogenetic species was located at corresponding positions on male and female beetles that make contact during mating. In addition, ecological data and video footage of the mating behaviors of Laccophilus confirmed that sexual transmission is the mechanism behind this enigmatic phenomenon.


Barriers to effective pain/symptom control.
We have a challenging call to provide compassionate care and comfort in a changing and varied clinical, social and financial setting. Multiple variables including race, creed, age, and sex of the patient can impact the decision-making process. It is hoped that consideration by professional caregivers of the above barriers will improve and provide consistent care to those put in our charge.


Osteoporosis in patients with a low-energy fracture: 3 years of screening in an osteoporosis outpatient clinic.
The prevalence of osteoporosis in the Netherlands is 52 per 1,000 men and 166 per 1,000 women (age >55 years). Previous results of an osteoporosis screening program showed that 55%, 41%, and 37.1% had osteoporosis. This study aims to evaluate the incidence of osteoporosis after low-energy fractures and to describe the care program for osteoporosis screening. The second endpoint was to investigate the incidence of risk factors in the whole study population and a subgroup analysis from the three major groups with osteoporotic fractures. All female and male patients older than 50 years with a low-energy fracture were included for the osteoporosis screening program. Patients with a fracture of the vertebrae were also included if the age was less than 50 years. All patients underwent a bone mineral density measurement by means of dual-energy X-ray film absorptiometry. All obtained data were registered by a nurse specialist in osteoporosis, in a computerized database. The incidence of osteoporosis in patients with low-energy fractures is high, 46.4%. At the time of fracture presentation, there were 33.2% of the patients with a low body weight (<67 kg), almost all osteoporotic patients (96%) had a low-energy fracture occurred after their 50th year. In patients diagnosed with osteoporosis, the hip fracture is the most common fracture site (34%), followed by the humerus (20.1%). In conclusion, a screening program for osteoporosis is necessary and should be a tool in the armamentarium of every traumatology department.


Delayed rupture of the radial artery caused by catheter-related sepsis.
Arterial catheter-related sepsis was detected in six adult patients during 45 months by prospective surveillance of blood culture results. In two of the patients, infection of the radial artery caused delayed arterial rupture and either hemorrhage or pseudoaneurysm formation despite prompt catheter removal and antibiotic treatment. Features present in these two cases but not in the four uncomplicated cases were infection caused by Staphylococcus aureus and persistence of systemic signs of infection for more than 2 days after catheter removal. A review of the literature showed that these two features have been noted in almost all adult patients previously reported to develop arterial rupture as a complication and not in patients with uncomplicated arterial catheter-related sepsis. Identification of patients at increased risk for this complication may facilitate prompt diagnosis of arterial rupture or exploration and possible resection of an infected segment of artery before rupture occurs.


Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening.
The primary objective was to compare the performance of 3 different abbreviated MRI (AMRI) sets extracted from a complete gadoxetate-enhanced MRI obtained for hepatocellular carcinoma (HCC) screening. Secondary objective was to perform a preliminary cost-effectiveness analysis, comparing each AMRI set to published ultrasound performance for HCC screening in the USA. This retrospective study included 237 consecutive patients (M/F, 146/91; mean age, 58 years) with chronic liver disease who underwent a complete gadoxetate-enhanced MRI for HCC screening in 2017 in a single institution. Two radiologists independently reviewed 3 AMRI sets extracted from the complete exam: non-contrast (NC-AMRI: T2-weighted imaging (T2wi)+diffusion-weighted imaging (DWI)), dynamic-AMRI (Dyn-AMRI: T2wi+DWI+dynamic T1wi), and hepatobiliary phase AMRI (HBP-AMRI: T2wi+DWI+T1wi during the HBP). Each patient was classified as HCC-positive/HCC-negative based on the reference standard, which consisted in all available patient data. Diagnostic performance for HCC detection was compared between sets. Estimated set characteristics, including historical ultrasound data, were incorporated into a microsimulation model for cost-effectiveness analysis. The reference standard identified 13/237 patients with HCC (prevalence, 5.5%; mean size, 33.7 ± 30 mm). Pooled sensitivities were 61.5% for NC-AMRI (95% confidence intervals, 34.4-83%), 84.6% for Dyn-AMRI (60.8-95.1%), and 80.8% for HBP-AMRI (53.6-93.9%), without difference between sets (p range, 0.06-0.16). Pooled specificities were 95.5% (92.4-97.4%), 99.8% (98.4-100%), and 94.9% (91.6-96.9%), respectively, with a significant difference between Dyn-AMRI and the other sets (p < 0.01). All AMRI methods were effective compared with ultrasound, with life-year gain of 3-12 months against incremental costs of US$ < 12,000. NC-AMRI has limited sensitivity for HCC detection, while HBP-AMRI and Dyn-AMRI showed excellent sensitivity and specificity, the latter being slightly higher for Dyn-AMRI. Cost-effectiveness estimates showed that AMRI is effective compared with ultrasound. • Comparison of different abbreviated MRI (AMRI) sets reconstructed from a complete gadoxetate MRI demonstrated that non-contrast AMRI has low sensitivity (61.5%) compared with contrast-enhanced AMRI (80.8% for hepatobiliary phase AMRI and 84.6% for dynamic AMRI), with all sets having high specificity. • Non-contrast and hepatobiliary phase AMRI can be performed in less than 14 min (including set-up time), while dynamic AMRI can be performed in less than 17 min. • All AMRI sets were cost-effective for HCC screening in at-risk population in comparison with ultrasound.


[A Chinese girl with cleidocranial dysplasia (CCD) caused by the recurrent R190W mutation in RUNX 2].
Cleidocranial dysplasia (CCD) is a rare skeletal disease with autosomal dominant inheritance associated with mutation in RUNX 2. The authors report a Chinese girl with CCD in whom the mutation in RUNX 2 was identified. Clinical diagnosis was based on physical examination, radiological findings, and biochemical tests. For mutation detection, genomic DNA was extracted from peripheral blood using standard method. All 7 coding exons of RUNX 2 and their flanking intronic sequences were amplified by polymerase chain reaction (PCR), and the PCR products were then subjected to automatic DNA sequencing. The affected girl showed typical clinical manifestations of CCD, including patent fontanelles, absent clavicles, short stature and dental anomalies. Direct sequencing of PCR-amplified fragments revealed a recurrent missense mutation, R190W (568 C > T), in RUNX 2. The mutation was further confirmed by Hae III restriction analysis. A Chinese case of CCD was confirmed and the disease-causing mutation was linked to a recurrent point mutation in RUNX 2.


Di-μ-oxo dimetal core of Mn(IV) and Ti(IV) as a linker between two chiral salen complexes leading to the stereoselective formation of different M- and P-helical structures.
Because of restricted rotational freedom along the metal-metal axis, a di-μ-oxo dimetal core could be an excellent building block to create dinuclear compounds with well-defined stereochemistry, but their stereoselective synthesis remains a challenge. We herein report the formation of di-μ-oxo dimanganese(IV) complexes with tetradentate salen ligands bearing different degrees of steric bulk, in order to study stereochemical aspects of the dimerization reaction that potentially generates multiple stereoisomers. X-ray crystallography shows that the di-μ-oxo dimanganese(IV) complex with salen, where salen is (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine, adopts a unique structure in which two salen complexes are arranged in an M-helical fashion. According to the solution study using (1)H, (2)H NMR, and circular dichroism spectroscopies, the dimerization reaction is highly diastereoselective in the presence of the tert-butyl group at the 3/3' position as a determinant steric factor. In contrast, the di-μ-oxo dititanium(IV) complex with the same salen ligand was previously reported to afford an opposite P-helical dimer. The present DFT study clarifies that a less-covalent Ti-O bonding causes a distortion of the di-μ-oxo dititanium(IV) core structure, generating a completely different framework for interligand interaction. The present study provides a solid basis to understand the stereochemistry for the formation of the di-μ-oxo dimetal core.


[Experience with the use of short dental implants in the literature].
According to the literature short dental implants have often been used for the replacement of teeth in the daily praxis. The implantation of short dental implants raise a lot of questions. The autors's aim is to collect the most important experiences of current literature on the mentioned theme to oral implantologists. In the article 33 reviews and clinical studies have been overviewed. The analysis of the different studies suggest that the use of short implants--taking into account of indications and contraindications--decreases the incidence of complications and the patient's discomfort as well as the cost of treatment. The use of short dental implants is proposed as an alternative method in the daily dental praxis.


Rational Design, Pharmacomodulation, and Synthesis of [68Ga]Ga-Alb-FAPtp-01, a Selective Tumor-Associated Fibroblast Activation Protein Tracer for PET Imaging of Glioma.
Dynamic changes in the tumor-associated fibroblast activation protein (FAP) expression in tumors of different stages may be helpful for prognostic evaluation and treatment response monitoring, making this protein a promising surveillance biomarker for timely diagnosis of malignant tumors and effective planning of patient care. To prospectively verify the diagnostic efficacy value of the developed FAP tracers, [68Ga]Ga-FAPtp and [68Ga]Ga-Alb-FAPtp-01, dynamic/static positron emission tomography (PET)/computed tomography scans were acquired for tumor-targeting studies in vivo and in comparison with the well-established clinically used tracer [68Ga]Ga-FAPI-04. The optimized rationally designed FAP-targeting PET tracer, [68Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the [68Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.


Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section*.
In a randomised, double-blinded study, we compared boluses of phenylephrine 100 microg with ephedrine 10 mg for treating hypotension (systolic blood pressure < 100 mmHg) in 204 patients having non-elective Caesarean section under spinal anaesthesia. Umbilical arterial (UA) and venous (UV) pH and base excess were similar between groups. In the ephedrine group, UA lactate concentration was higher (median 2.6 [interquartile range 2.3-3.3] vs 2.4 [1.9-3.0] mmolxl(-1), p = 0.002) and UV lactate concentration was higher (2.5 [2.2-3.2] vs 2.3 [1.9-2.8] mmolxl(-1), p = 0.016) and more patients had nausea or vomiting (12.7% vs 3.9%, p = 0.02). Clinical neonatal outcome was similar. Of the protocol-compliant patients (n = 148), UA Po(2) and UV Po(2) were lower in the phenylephrine group although oxygen content was similar. We conclude that phenylephrine and ephedrine are both suitable vasopressors for use in non-elective Caesarean sections.


Effects of retinoic acid on the human lymphocyte response to mitogens.
Nontoxic concentrations of retinoic acid enhance DNA synthesis of human peripheral blood lymphocytes in response to phytohemagglutinin or rabbit-antihuman thymocyte globulin, whereas the response to concanavalin A or pokeweed mitogen remained unaffected. Retinoic acid-induced stimulation of lymphocyte reactivity to phytohemagglutinin or antithymocyte globulin was most evident in T cell-enriched subpopulations and required the near-concurrent addition of retinoic acid and mitogens. Retinoic acid-mediated enhancement of lymphocyte proliferation in response to phytohemagglutinin or antithymocyte globulin was paralleled by a concomitant suppression of immune interferon production of lymphocytes stimulated with these mitogens. These findings allow further studies on the immunoregulatory action of retinoids in vitro.


Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery.
Estrogen deprivation has a profound effect on the female brain. One of the most obvious examples of this condition is hot flushes. Although estrogens relieve these typical climacteric symptoms, many women do not want to take them owing to unwanted side-effects impacting, for example, the uterus, breast and blood. Therefore, there is a need for developing safer estrogen therapies. We show here that treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a novel brain-targeting bioprecursor prodrug of the main human estrogen, 17β-estradiol, alleviates hot flushes in rat models of thermoregulatory dysfunction of the brain. Oral administration of DHED elicits a significant reduction of tail skin temperature (TST) rise representing hot flushes in the morphine-dependent ovariectomized rat model and results in the restoration of estrogen deprivation-induced loss of diurnal rhythm in TST. These beneficial effects occur without detrimental peripheral hormonal exposure; thus, the treatment avoids potentially harmful stimulation of estrogen-sensitive peripheral organs, including the uterus and the anterior pituitary, or the proliferation of MCF-7a breast cancer cell xenografts. Our promising preclinical assessments warrant further considerations of DHED for the development of a brain-selective 17β-estradiol therapy to relieve hot flushes without undesirable peripheral side-effects.


Expression of VEGFR and PDGFR-α/-β in 187 canine nasal carcinomas.
Radiotherapy represents the standard of care for intranasal carcinomas. Responses to tyrosine kinase inhibitors (TKIs) have been reported but data on expression of target receptor tyrosine kinases (rTKs) is limited. This study characterizes the expression of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β in canine intranasal carcinomas. Histological samples from 187 dogs were retrieved. Immunohistochemistry was performed using commercially available antibodies. Expression of rTKs was classified into weak, moderate or intense and additionally recorded as cytoplasmic, membranous, cytoplasmic-membranous, nuclear or stromal. VEGFR was expressed in 158 dogs with predominantly moderate expression (36.9%) and a cytoplasmic-membranous expression pattern (70.9%). PDGFR-α was detected in 133 with predominantly weak expression (57.9%) and cytoplasmic pattern (87.9%). PDGFR-β was identified in 74 patients with a predominantly moderate expression (17.6%) and cytoplasmic expression pattern (63.5%). Co-expression of rTKs was common. These results confirm expression of VEGFR, PDGFR-α and PDGFR-β in canine intranasal carcinomas and support the utility of TKIs.


Evaluation of the complete Sniffin Sticks Test versus its subtests in differentiating Parkinson's disease patients from healthy controls.
Hyposmia is one of the most common, as well as the first nonmotor condition in Parkinson disease (PD). The sniffin sticks test (SST) evaluates three different aspects of olfactory function: threshold (T), discrimination (D), and identification (I). The sum of the scores of these three subtests produce a global score of olfaction, the Threshold-Discrimination-Identification (TDI) score. The aim of this study was to investigate if the TDI score or one of its subtests is better to discriminate PD patients from controls. We recruited 27 PD patients and 17 healthy age-matched controls (HC) who were evaluated through a clinical interview, the Montreal Cognitive Assessment and Movement Disorders Society - Unified Parkinson Disease Rating Scale. The olfaction was assessed using the complete SST. The performance of PD patients on the olfactory test was significantly worse when compared with the HC (T: 3.0 vs. 6.5, p < 0.001; D: 8.1 vs. 11.2, p < 0.001; I: 7.3 vs. 11.7, p < 0.001; TDI: 18.8 vs. 29.9, p < 0.001). The prevalence of olfaction impairment in our study (PD: 100%, and HC: 56%) was greater than that found in the literature. Cognition influenced the performance on TDI. The olfactory subtests were impaired proportionally between patients and controls. Furthermore, D and I were correlated, but only in PD patients. The TDI showed a tendency to better discriminate PD patients from HC, when compared with its subtests. Although the complete olfactory evaluation is time consuming, it seems to be a superior tool to identify olfaction impairment in PD patients, when compared with the isolated subtests.


First spatially resolved measurements of the D-3He α-particle source with the upgraded JET gamma-ray camera.
The Joint European Torus (JET) gamma-ray camera has been recently upgraded with the installation of new gamma-ray detectors, based on LaBr3(Ce) scintillation crystals, which add spectroscopic capability to the existing system allowing measurements with good energy resolution (5% at 0.622 MeV), a dynamic range from hundreds of keV up to about 30 MeV, and high counting rate capabilities of MCps. First gamma-ray measurements during the C38 campaign of the JET have been successfully carried out, in particular, in D-3He plasmas from three-ion ion cyclotron resonance heating experiments, where the detection of 16.4 MeV γ-rays from D + 3He → γ + 5Li reactions with the gamma-ray camera upgrade allowed determining the spatial profile of alpha particles born in D + 3He fusion reactions.


Alcohol-induced liver injury in signalling pathways and curcumin's therapeutic potential.
Confronting the profound public health concern of alcohol-induced liver damage calls for inventive therapeutic measures. The social, economic, and clinical ramifications are extensive and demand a comprehensive understanding. This thorough examination uncovers the complex relationship between alcohol intake and liver damage, with a special emphasis on the pivotal roles of the Toll-like receptor 4 (TLR4)/NF-κB p65 and CYP2E1/ROS/Nrf2 signalling networks. Different alcohol consumption patterns, determined by a myriad of factors, have significant implications for liver health, leading to a spectrum of adverse effects. The TLR4/NF-κB p65 pathway, a principal regulator of inflammation and immune responses, significantly contributes to various disease states when its balance is disrupted. Notably, the TLR4/MD-2-TNF-α pathway has been linked to non-alcohol related liver disease, while NF-κB activation is associated with alcohol-induced liver disease (ALD). The p65 subunit of NF-κB, primarily responsible for the release of inflammatory cytokines, hastens the progression of ALD. Breakthrough insights suggest that curcumin, a robust antioxidant and anti-inflammatory compound sourced from turmeric, effectively disrupts the TLR4/NF-κB p65 pathway. This heralds a new approach to managing alcohol-induced liver damage. Initial clinical trials support curcumin's therapeutic potential, highlighting its ability to substantially reduce liver enzyme levels. The narrative surrounding alcohol-related liver injury is gradually becoming more intricate, intertwining complex signalling networks such as TLR4/NF-κB p65 and CYP2E1/ROS/Nrf2. The protective role of curcumin against alcohol-related liver damage marks the dawn of new treatment possibilities. However, the full realisation of this promising therapeutic potential necessitates rigorous future research to definitively understand these complex mechanisms and establish curcumin's effectiveness and safety in managing alcohol-related liver disorders.


Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves.
Cefoxitin pharmacokinetics and bioavailability were studied in unweaned calves. The antibiotic was administered to nine calves intravenously (i.v.), to seven calves intramuscularly (i.m.) at 20 mg/kg and to eight calves i.m. at 20 mg/kg together with probenecid at 40 mg/kg. Serum concentration versus time data were analysed using statistical moment theory (SMT). The i.v. data were also fitted by a linear, open two-compartment model. The elimination half-life (t1/2) was 66.9 +/- 6.9 min (mean +/- SD) after i.v. and 81.0 +/- 10.9 min after i.m. administration. The t1/2 increased to 125.5 +/- 15.6 min by the co-administration of probenecid. The total body clearance (ClT) was 4.88 +/- 1.71 ml/min/kg and the volume of distribution (Vss) 0.3187 +/- 0.0950 l/kg. The mean residence time (MRT) was 68.2 +/- 12.3 min after i.v. and 118.6 +/- 16.8 min after i.m. injection and increased to 211.5 +/- 16.8 min by the co-administration of probenecid. The mean absorption time (MAT) was 50.6 min and the estimated bioavailability (F) of cefoxitin after i.m. administration was 73.8%. The cefoxitin protein binding ranged from 55.0 to 42.0% at concentrations from 2 to 50 micrograms/ml. The MIC90 values for cefoxitin were 6.25 micrograms/ml for E. coli and Salmonella group B isolates, 3.13 micrograms/ml for Salmonella group C and D and Pasteurella multocida. There were no statistically significant differences between the pharmacokinetic parameters calculated by SMT or compartmental analysis. SMT provided an additional independent parameter, the MRT, for characterization of drug disposition kinetics.


Synthesis of Sialyl LewisX Mimetics with E- and P-Selectin Binding Properties and Immunosuppressive Activity.
E- and P-selectins are adhesion proteins implicated in immune cell recruitment at sites of infection, making them important drug targets for diseases involving excessive and uncontrolled inflammation. In this study, we developed an efficient strategy to synthesize bicyclic galactopyranosides through a key stereoselective equatorial C4-propiolate addition and TMSCN axial C-glycosidation. The nitrile group can then be converted to the carboxyl and different bioisosteres at a late stage in the synthesis, allowing for various derivatizations to potentially enhance biological activity. The sialyl LewisX glycomimetic featuring this rigidified bicyclic galactopyranoside moiety prevents neutrophil adhesion to endothelial cells in vitro by binding to both E- and P-selectins. We show here that the axial carboxyl analogue blocks immune cell recruitment in vivo, demonstrating its potential as an immunomodulator.


An instrument for dissecting the esophagus.
We describe an instrument for mobilizing the normal esophagus without thoracotomy. It is essentially a metal ring introduced through the neck that encircles the esophagus, separating it from surrounding tissues. Preliminary studies of 12 cadavers were followed by clinical application in 18 patients with esophageal carcinoma and two with benign esophageal lesions. Pneumothorax occurred in 20%, recurrent laryngeal nerve palsy in 25% (4 of 5 were transient), and thoracotomy for postoperative bleeding from the tumor bed in two cases. No anastomotic leakage occurred. Mortality rate at 30 days after operation was 15%, with an in-hospital mortality rate of 20%. Use of the instrument did not cause any of the described complications. In one patient the esophageal carcinoma was adherent to the trachea, which was injured. No incidence of hypotension or arrhythmia was observed during thoracic esophageal dissection. Blood loss from the mediastinum wa unremarkable. The treatment by stripping is a palliative treatment and precludes a radical curative attempt. The use of this instrument is contraindicated in lesions of the upper and middle parts of the esophagus, and it is not intended to strip a bulky esophagus as in achalasia. The esophageal dissector made mobilization of the normal thoracic esophagus easier and less time consuming, and yielded no episodes of hypotension or arrythmia.


In-utero stem cell transplantation: clinical use and therapeutic potential.
Early evidence suggests that in-utero stem cell transplantation represents a new therapeutic strategy for different congenital disease. Moreover, gene therapy constitutes one of the most promising new approach to treat a wide spectrum of genetic disorders. It was shown that the fetus could represent an ideal recipient because of his immunologic early naiveté in gestation that reduces the risk of immunoreactions. Clinical experience in human fetus was performed in order to treat immunodeficiency and metabolic disorders, hemoglobinopathies and some other genetic diseases. Use of alternative source (i.e., cord blood, placenta, membrane, amniotic fluid, fetal tissue) of stem cell transplanted has been only one of the several strategies to improve donor cell advantages on host stem cell. The present review focused on the clinical use and therapeutic potential of in-utero stem cell transplantation, reporting the outcome of human cases treated and the limits of this therapy and possible future applications.


Changes in white matter functional networks across late adulthood.
The aging brain is characterized by decreases in not only neuronal density but also reductions in myelinated white matter (WM) fibers that provide the essential foundation for communication between cortical regions. Age-related degeneration of WM has been previously characterized by histopathology as well as T2 FLAIR and diffusion MRI. Recent studies have consistently shown that BOLD (blood oxygenation level dependent) effects in WM are robustly detectable, are modulated by neural activities, and thus represent a complementary window into the functional organization of the brain. However, there have been no previous systematic studies of whether or how WM BOLD signals vary with normal aging. We therefore performed a comprehensive quantification of WM BOLD signals across scales to evaluate their potential as indicators of functional changes that arise with aging. By using spatial independent component analysis (ICA) of BOLD signals acquired in a resting state, WM voxels were grouped into spatially distinct functional units. The functional connectivities (FCs) within and among those units were measured and their relationships with aging were assessed. On a larger spatial scale, a graph was reconstructed based on the pair-wise connectivities among units, modeling the WM as a complex network and producing a set of graph-theoretical metrics. The spectral powers that reflect the intensities of BOLD signals were found to be significantly affected by aging across more than half of the WM units. The functional connectivities (FCs) within and among those units were found to decrease significantly with aging. We observed a widespread reduction of graph-theoretical metrics, suggesting a decrease in the ability to exchange information between remote WM regions with aging. Our findings converge to support the notion that WM BOLD signals in specific regions, and their interactions with other regions, have the potential to serve as imaging markers of aging.


Overground-Propulsion Kinematics and Acceleration in Elite Wheelchair Rugby.
Maximal acceleration from standstill has been identified as a key performance indicator in wheelchair rugby; however, the impact of classification and kinematic variables on performance has received limited attention. This study aimed to investigate kinematic variables during maximal acceleration, with level of activity limitation accounted for using sport-classification scores. Based on their sporting classification scores, which reflect combined trunk, arm, and hand function, 25 elite wheelchair rugby players were analyzed in high-, mid-, and low-point groups before completing five 5-m sprints from a stationary position. Inertial measurement units and video analysis were used to monitor key kinematic variables. Significant differences in kinematic variables were evident across the classification groups, particularly for the first stroke-contact angle (1-way ANOVA F2,122 = 51.5, P < .05) and first stroke time (F2,124 = 18.3, P < .05). High-point players used a first stroke-contact angle that was closer to top dead center of the wheel than either other group, while also using a shorter overall stroke time than low-point players. A linear mixed-effects model was used to investigate how kinematic variables influenced performance, with results suggesting that increased release angles (ie, farther around the wheel) and decreased stroke angles resulted in larger peak accelerations. Further investigation revealed that these results are likely influenced by strong relationships for the high-point group, as there was often no clear trend evident for midpoint and low-point groups. Findings show that various propulsion approaches exist across classification groups, with this information potentially informing individual wheelchair setups and training programs.


Torque-angle-velocity Relationships and Muscle Performance of Professional and Youth Soccer Players.
Soccer matches consist of a variety of different activities, including repeated sprints. Time to attain velocity (TTAV), load range (LR) and the torque-angle-velocity relationship (TAV3D) represent an important measurement of muscle performance, however there are few related studies. The aim of this study was to compare these outcomes between soccer players of different age category. 17 professional (PRO) and 17 under-17 (U17) soccer players were assessed for concentric knee flexion/extension at 60, 120 and 300°/s. For the extensor muscles, differences were found in favor of the U17 group for TTAV and LR outcomes at 120°/s, however, the PRO group maintained higher torques in both movement directions in comparison to the U17 in TAV3D evaluation. These results suggest that muscle performance of the PRO group is more efficient than the U17 group.


[Radiocardiographic evaluation of the hemodynamics in combined acquired heart defects].
One hundred and twenty eight subjects were examined, 77 of them with acquired combined valvular defects, with an average age of 42,2 as well as 51 healthy subjects. Depending on the degree of cardiac insufficiency, the patients were grouped into three stages, I, II A and II B. The hemodynamics was studied by quantitative radiocardiography. Indices, characterizing the heart pump function, the intracardial transit time, pulmonary circulation, etc. were followed up. The data obtained from the follow up of more than 20 parameters reveal that insignificant hemodynamic disorders develop during the initial stage of compensation and subcompensation of the cardiovascular system. In case of cardiac insufficiency, stages II A and II B the values of cardiac output was markedly and progressively decreased, the intracardial transit times were prolonged, the values of pulmonary circulation and those of the peripheral hemodynamics were considerably increased.


Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor.
Brain-derived neurotrophic factor (BDNF) is a key regulator of hippocampal synaptic plasticity in the developing and adult nervous system. It can be released from pyramidal neuron dendrites in an activity-dependent manner and has therefore been suggested to serve as a signal that provides the retrograde intercellular communication necessary for Hebbian plasticity and hippocampal-dependent learning. Although much has been learned about BDNF function by field stimulation of hippocampal neurons, it is not known whether moderate action potential-independent depolarization of single cells is capable of releasing sufficient BDNF to influence transmission at individual synapses. In this study, we show directly at the single-cell level that such modulation can occur. By using K-252a, anti-BDNF antibody, and interruption of regulated release, we confirm a model in which postsynaptic depolarization elicits calcium-dependent release of BDNF that diffuses retrogradely and enhances presynaptic transmitter release.


[Current therapy concepts in cutaneous T-cell lymphomas].
Cutaneous T-cell-lymphomas (CTCL) include a group of rare diseases that are characterized by an accumulation of clonal T-lymphocytes in skin. The various disease entities may be classified by an adapted Kiel classification. For staging purposes the TNM system is most commonly used. Treatment modalities depend on the extent and the aggressiveness of the disease (low- or high-grade lymphoma) and on the individual situation of the patient. Stage-adapted therapy is currently recommended. Early stages of low-grade CTCL are successfully treated with PUVA, retinoids or interferon-alpha. Extracorporeal photopheresis is the treatment of choice in stage III patients with Sézary syndrome. Alternative therapeutic modalities for CTCL, such as radiotherapy, chemotherapy or various experimental protocols, are discussed.


Intramolecular Homolytic Substitution Enabled by Photoredox Catalysis: Sulfur, Phosphorus, and Silicon Heterocycle Synthesis from Aryl Halides.
Aryl radical generation and manipulation constitutes a long-standing challenge in organic synthesis. Photocatalytic single-electron reduction of aryl halides has been established as a premier activation pathway to reach these intermediates. The current study integrates the conceptual simplicity of the classical intramolecular homolytic substitution with the practicality of the modern photocatalytic approach. Predicated on an efficient metal-free dehalogenation of aryl halides under mild organo-photoredox conditions, sulfur, phosphorus, and silicon heteroatoms capture the C(sp2)-centered radical in an intramolecular fashion.


Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the Liliaceae family.
Plants belonging to the Liliaceae family have been the topic of research in many phytochemical and pharmacological laboratories because they contain structurally complex and biologically fascinating steroidal alkaloids. This review, citing 153 references, summarises the chemistry, bioactivity and geographical diversity of steroidal alkaloids isolated from Veratrum and Fritillaria species, so as to illustrate the chemo-diversity and biological significance of these alkaloids, along with their geographical distribution where this is discernible.


Studies on the effects of oxamniquine on autonomic transmissions.
The effects of oxamniquine have been investigated on parasympathetic and sympathetic transmissions using in vitro and in vivo laboratory models. Oxamniquine (3.6 X 10(-5)-5.5 X 10(-4) M) depressed or abolished electrically-evoked contractions of the isolated chick esophagus and isolated vas deferens muscle preparations. At the same concentration (3.6 X 10(-5)-5.5 X 10(-4) M) levels, the drug also reduced or abolished the indirect, electrically-provoked twitches of the rat isolated phrenic nerve-hemidiaphragm muscle preparations and contractions of the cat nictitating membrane induced by pre-ganglionic cervical sympathetic nerve trunk electrical stimulation in vivo. These results strongly suggest blockade of sympathetic and parasympathetic transmissions by oxamniquine.


Orientation dependent misalignments in a visual alignment task.
Subjects performed a three-dot alignment in the frontoparallel plane. We found systematic deviations in alignment, especially for diagonally oriented stimuli. The biases did not depend on the angular size of the stimuli which was varied between 0.8 and 20 deg. We put forward a tentative explanation based on saccade trajectories. Extending the task to judgements of the straightness of virtual lines consisting of a varying number of dots showed that the biases decrease gradually when the number of dots increases. This suggests that there are two different and competing mechanisms to judge the straightness of virtual lines.


Self-Relay Gold(I)-Catalyzed Pictet-Spengler/Cyclization Cascade Reaction for the Rapid Elaboration of Pentacyclic Indole Derivatives.
Gold-catalyzed cascade reactions allow the rapid elaboration of pentacyclic indolo[2,3-a]quinolizidines from N-allyl tryptamines and ortho-alkynylarylaldehydes. The tandem process combines a gold-catalyzed Pictet-Spengler reaction and a cyclization occurring concomitantly with an allyl transfer from the nitrogen atom to the stilbene function. Various substituted allyls were successfully transferred, furnishing the products in yields typically ranging from 60-98 % in high diastereoselectivity. Tryptamines bearing a butenol chain undergo an additional cyclization to chiral hemiaminals in high diastereoselectivities.


Intra- vs intermuscular injections in swine.
In order to determine the exact localization (intra- vs intermuscular) in which a drug is injected when administered by a so-called intramuscular injection technique, a radiopaque test article (2 ml) was injected into the cervical musculature (2 sites), the loins and the gluteal mass in anaesthesized pigs. Immediately after this, the pigs were euthanized and deep-frozen. Then they were cut into slices, which were X-rayed to determine the exact localization of the test material. Semi-quantitative scores were given to each injection site according to the amount of test article found in or out of muscle mass and also to the absence or the presence of test article subcutaneously. The loins area obtained the highest score for intramuscular location, but in this site, injections were almost always followed by a flowing back of the test article to the subcutaneous' area. It was shown that an injection in the neck perpendicular to the skin surface just behind the base of the ear was the most appropriate site for intramuscular injection in pigs.


Developing Online Communities with LAMP (Linux, Apache, MySQL, PHP) - the IMIA OSNI and CHIRAD Experiences.
Many health informatics organisations do not seem to use, on a practical basis, for the benefit of their activities and interaction with their members, the very technologies that they often promote for use within healthcare environments. In particular, many organisations seem to be slow to take up the benefits of interactive web technologies. This paper presents an introduction to some of the many free/libre and open source (FLOSS) applications currently available and using the LAMP - Linux, Apache, MySQL, PHP architecture - as a way of cheaply deploying reliable, scalable, and secure web applications. The experience of moving to applications using LAMP architecture, in particular that of the Open Source Nursing Informatics (OSNI) Working Group of the Special Interest Group in Nursing Informatics of the International Medical Informatics Association (IMIA-NI), in using PostNuke, a FLOSS Content Management System (CMS) illustrates many of the benefits of such applications. The experiences of the authors in installing and maintaining a large number of websites using FLOSS CMS to develop dynamic, interactive websites that facilitate real engagement with the members of IMIA-NI OSNI, the IMIA Open Source Working Group, and the Centre for Health Informatics Research and Development (CHIRAD), as well as other organisations, is used as the basis for discussing the potential benefits that could be realised by others within the health informatics community.


Direct stimulatory effect of histamine on aldosterone secretion of the perfused dog adrenal gland.
The left adrenal gland of the hypophysectomized-nephrectomized dog was perfused in situ with the blood from the femoral artery of the hypophysectomized-nephrectomized donor dog. After infusion of histamine (0.1 mg/min for 5 min) into the arterial inflow circuit, the rates of secretion of aldosterone, corticosterone and cortisol (ng/100 mg adrenal wt. each min) increased from the basal level of 0.66+/-0.21 (mean+/-S.E.M.) to 2.24+/-0.45 at 10 min, from 4+/-1 to 20+/-4 at 5 min and from 19+/-5 to 64+/-15 at 5 min, respectively. The maximal increments above the basal value after the infusion of histamine in the secretory rates of aldosterone, corticosterone and cortisol were 51, 16, and 13% that of the respective steroid after the infusion of ACTH (20mIU/min for 5 min). The results indicate that histamine has a direct stimulatory effect on the secretion of aldosterone by the adrenal gland as well as on that of corticosterone and cortisol.


How will mosquitoes adapt to climate warming?
The potential for adaptive evolution to enable species persistence under a changing climate is one of the most important questions for understanding impacts of future climate change. Climate adaptation may be particularly likely for short-lived ectotherms, including many pest, pathogen, and vector species. For these taxa, estimating climate adaptive potential is critical for accurate predictive modeling and public health preparedness. Here, we demonstrate how a simple theoretical framework used in conservation biology-evolutionary rescue models-can be used to investigate the potential for climate adaptation in these taxa, using mosquito thermal adaptation as a focal case. Synthesizing current evidence, we find that short mosquito generation times, high population growth rates, and strong temperature-imposed selection favor thermal adaptation. However, knowledge gaps about the extent of phenotypic and genotypic variation in thermal tolerance within mosquito populations, the environmental sensitivity of selection, and the role of phenotypic plasticity constrain our ability to make more precise estimates. We describe how common garden and selection experiments can be used to fill these data gaps. Lastly, we investigate the consequences of mosquito climate adaptation on disease transmission using Aedes aegypti-transmitted dengue virus in Northern Brazil as a case study. The approach outlined here can be applied to any disease vector or pest species and type of environmental change.


A change in the prevalence and the etiological factors of chronic wounds in Helsinki metropolitan area during 2008-2016.
The prevalence of chronic wounds in the Helsinki metropolitan area in 2008 was investigated. Thereafter, a specialised wound care team was founded as part of the City of Helsinki Health Services, aiming for early diagnoses of chronic wounds. In the current study, we have repeated the prevalence study to analyse the changes in the prevalence of chronic wounds. A questionnaire on wound patients was sent to all units of social and health care in the Helsinki metropolitan area. We asked about the number of patients with wounds treated during a 24-hour period, as well the aetiology and location of the wounds. A total of 911 patients had, altogether, 1021 wounds. Thus, prevalence was 0.08%. Pressure and multifactorial ulcers were the most common aetiological groups, whereas wound without defined aetiology had diminished greatly (61%) The prevalence of chronic wound decreased when compared with 2008 (0.08% vs 0.1%). The number of elderly people aged over 65 years had increased 35%, and the age-adjusted prevalence had decreased. Wounds are treated mostly in primary care units and as outpatients. Therefore, the following conclusion may be reached: diagnostic process and implementation of treatment paths are strengthened within primary care units, yet prevalence of wounds has decreased.


Accuracy of detecting vertical root fractures in non-root filled teeth using cone beam computed tomography: effect of voxel size and fracture width.
To investigate simultaneously the effect of voxel size and fracture width on the accuracy of detecting vertical root fractures (VRFs) in non-root filled teeth when using cone beam computed tomography. Fifty-one of 161 extracted human permanent teeth (16 anterior teeth, 132 premolars and 13 mandibular molars) were selected randomly for VRF induction with two fracture widths. All teeth were scanned with four CBCT units at different voxel sizes provided by the units. Three observers classified the presence or absence of VRF using a 5-point scale. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the ROC curve (AUC) were calculated. AUCs amongst voxel sizes and between the fracture widths were compared using the Z test. Intra- and inter-observer agreement was assessed using weighted Cohen kappa. For the NewTom VGi and ProMax 3D Mid CBCT unit, no significant differences were found amongst voxel sizes for the AUCs, irrespective of the fracture width (P > 0.05). There were significant differences between images scanned with voxel size 250 and 160 μm (P = 0.02), and images scanned with voxel size 250 and 80 μm for AUCs in the narrow VRF group for the 3D Accuitomo 170 unit (P = 0.03). For i-CAT FLX, significant differences were found between the voxel protocols of 300 μm and of the other three voxel sizes for AUC, sensitivity and NPV (P < 0.05). Significant differences between the wide and the narrow VRF groups for AUCs were found for 3D Accuitomo 170 (P = 0.01) and ProMax 3D Mid (P < 0.01). Cone beam computed tomography was accurate for detecting VRF in non-root filled teeth. Fracture width had an effect on the detection of VRF. The effect of the voxel size on the detection of VRF depended on the CBCT unit used.


Computational analysis of the vibrational spectra and structure of aqueous cytosine.
The recently developed efficient protocol for the explicit quantum mechanical modeling of the structure and IR spectra of liquids and solutions [Katsyuba et al., J. Phys. Chem. B, 2020, 124, 6664-6670] is used to describe aqueous solutions of cytosine. The same cluster model of a solute surrounded by the first solvation shell of solvent molecules was shown to be sufficient to reproduce experimental vibrational frequencies and relative IR and Raman intensities. An equally good quality of Raman spectra was provided by B3LYP-D3/def2-TZVP and B3LYP-D3/aug-cc-pVDZ simulations. Computations using the PBE functional were sufficient for modeling of the IR spectra but failed in the simulations of Raman scattering. It is shown that strong changes of frequencies and relative intensities of Raman and IR bands of cytosine, caused by its hydration, cannot be completely assigned to the influence of hydrogen bonds (HBs) with 7 or 8 closest water molecules. They are rather ascribed to the combined effect of solute-solute and solute-solvent HBs with the participation of at least 30 water molecules separating cytosine from the bulk solvent. This suggests that the vibrational modes and derivatives of the polarizability and dipole moment of the solute are mainly locally influenced by its first hydration shell, while the influence of bulk water is rather modest.


[Immunology and interferons (author's transl)].
The general function of the immune system is discussed in the present review paper. In addition to the discussion of 'specific' and 'non-specific' defence mechanisms, particular attention is paid to the important role played by macrophages in the two systems. Macrophages are found to have a specific regulatory function both in the induction and the effector phase of the immune response. The part dealing with the effector phase of the immune response is concerned with the action of sensitized T lymphocytes on the one hand and provides a review of the present state of knowledge of (sub)classes of immunoglobulins in domestic animals on the other. In the section on interferon, efforts are made to answer a number of questions concerning the properties and chemical composition of interferons as well as the induction of interferons and the use of interferon inducers in veterinary practice. Moreover, a number of theories on the possible mechanism of action of interferons are discussed. The antitumour effect of interferons is examined more closely, the relationship with the antitumour activity of the immune system being a central feature. The part played by 'killer' and 'natural killer' cells is discussed. Finally, a look is taken into the future, and efforts are made to present an actual picture of the future possibilities of the use of interferons in therapy and prevention. A central question is whether it will be possible to produce interferons in sufficient amounts by particular bacteria (recombinant DNA studies) within a certain period.


SEX RATIO SELECTION AND THE EVOLUTION OF ENVIRONMENTAL SEX DETERMINATION IN LABORATORY POPULATIONS OF MENIDIA MENIDIA.
What happens when a population with environmental sex determination (ESD) experiences a change to an extreme environment that causes a highly unbalanced sex ratio? Theory predicts that frequency-dependent selection would increase the proportion of the minority sex and decrease the level of ESD in subsequent generations. We empirically modeled this process by maintaining five laboratory populations of a fish with temperature-dependent sex determination (the Atlantic silverside, Menidia menidia) in extreme constant temperature environments that caused highly skewed sex ratios to occur initially. Increases in the minority sex consistently occurred from one generation to the next across all five populations, first establishing and then maintaining a balanced sex ratio until termination of the experiment at 8 to 10 generations. The extent to which the level of ESD changed as balanced sex ratios evolved, however, was not consistent. Two populations that experienced high temperatures each generation displayed a loss of ESD, and in one of these ESD was virtually eliminated. This suggests that temperature-insensitive, sex-determining genes were being selected. In populations maintained in low temperature environments, however, the level of ESD did not decline. Instead, the response of sex ratio to temperature was adjusted upward or downward, perhaps by selection of sex-determining genes sensitive to higher (or lower) temperatures. The two different outcomes at low versus high temperatures occurred independent of the geographic origin of the founding population. Our results demonstrate that ESD is capable of evolving in response to selection.


Positive Emotional Traits and Ambitious Goals among People at Risk for Mania: The Need for Specificity.
Recent psychosocial theories implicate disturbances in reward pursuit among individuals putatively at risk for mania. The present study examined associations of a measure of risk for mania (the Hypomanic Personality Scale; HPS) with both four trait positive emotions (joy, pride, compassion, and love) and ambitious life goals in five domains (fame, wealth, political influence, family, and friends) among 302 participants from two university settings. Findings indicated that higher HPS scores were related to reward (joy) and achievement-focused (pride) positive emotions, with weaker relations to prosocial (compassion, love) positive emotions. HPS scores were more robustly related to extrinsic (fame, politics) as compared to other-oriented (friends, family) ambitious life goals, with the exception of wealth. These effects were independent of current symptoms of mania and depression. Discussion focuses on the implications of elevated reward and achievement-related positive emotions and goals in understanding risk factors for mania.


Acute effects of a single exercise class on appetite, energy intake and mood. Is there a time of day effect?
This study aimed to investigate the acute effects of a single exercise class on appetite sensations, energy intake and mood, and to determine if there was a time of day effect. Twelve healthy, young, normal weight females, who were non-regular exercisers, participated in four trials: morning control, morning exercise, evening control and evening exercise. Exercise trials were a one-hour class of aerobic and muscle conditioning exercise of varying intensities, to music. Control trials were a one-hour rest. Ratings of perceived exertion were significantly greater during the warm-up and muscle conditioning parts of the morning exercise trial compared to those of the evening exercise trial. Although both exercise trials, compared to control trials, produced an increase in appetite sensations, they did not alter energy intake and produced a decrease in 'relative' energy intake. In relation to mood, both exercise trials increased positive affect and decreased negative affect. These results suggest that a single exercise class, representative of that offered by many sports centres, regardless of whether it is performed in the morning or evening produces a short-term negative energy balance and improves mood in normal weight women. However, when this type of exercise was performed in the morning it was perceived to require more effort.


Attitudes towards abortion among physicians working at obstetrical and paediatric departments in Denmark.
The purpose of this study was to describe the attitudes among physicians working in perinatal medicine towards abortion for social reasons or because of abnormal prenatal diagnostic results. A questionnaire was sent to all physicians registered as employed at obstetrical or paediatric departments in Danish hospitals with a neonatal function. Of 994 questionnaires, 687 (69 per cent) were completed and returned. There was strong consensus among all participants that abortion is acceptable until week 21 in the case of trisomy 13 and at least until week 19 in the case of cystic fibrosis. Furthermore, there was strong consensus that abortion in the first trimester is acceptable in the case of an unwanted pregnancy in a 16-year-old girl and in the case of Down syndrome. Major controversy was found in connection with abortion in the case of Turner syndrome until week 21, abortion in week 13 in the case of polycystic kidney disease, abortion in week 24 in the case of Down syndrome, and abortion for social reasons in week 21.


Silver stain for ringed sideroblasts. A sensitive method that differs from Perls' reaction in mechanism and clinical application.
A modified silver stain is described for the demonstration of ringed sideroblasts in bone marrow. It is more sensitive than Perls' reaction for that purpose, especially when iron stores of marrow are low or absent. Ringed sideroblasts may still be demonstrable by silver stain in cases of sideroblastic anemia without ringed sideroblasts, for which severe iron deficiency prevents detection of the abnormal sideroblasts by Perls' reaction. As iron has been reported to be present in mitochondria of ringed sideroblasts in the form of ferric phosphate, it is possible that the silver stain demonstrates the phosphate moiety and not the iron, thus explaining its greater sensitivity in iron deficiency as compared to Perls' reaction. Further study is necessary to confirm the staining mechanism, to elucidate the composition of iron deposits, and to explain the pathophysiology of sideroblastic anemia.


Improvement of NADPH-dependent bioconversion by transcriptome-based molecular breeding.
Transcriptome data for a xylitol-producing recombinant Escherichia coli were obtained and used to tune up its productivity. Structural genes of NADPH-dependent D-xylose reductase and D-xylose permease were inserted into an Escherichia coli chromosome to construct a recombinant strain producing xylitol from D-xylose for use as a model system for NADPH-dependent bioconversion. Transcriptome analysis of xylitol-producing and nonproducing conditions for the recombinant revealed that xylitol production down-regulated 56 genes. These genes were then selected as candidate factors for suppression of the NADPH supply and were disrupted to validate their functions. Of the gene disruptants, that resulting from the deletion of yhbC showed the best bioconversion rate. Also, the deletion accelerated cell growth during log phase. The features of the mutant could be maintained in jar fermenter-scale production of xylitol. Thus, our novel molecular host strain breeding method using transcriptome analysis was fully effective and could be applied to improving various industrial strains.


Canine visceral leishmaniasis: study of methods for the detection of IgG in serum and eluate samples.
The Brazilian Ministry of Health recommends the culling and euthanasia of dogs with a positive serological test for canine visceral leishmaniasis (CVL). In the Municipality of Rio de Janeiro, the technique used for the diagnosis of CVL is the indirect fluorescent antibody test (IFAT), using blood samples eluted on filter paper (eluate). A dog survey was conducted over a period of one year in the region of Carapiá, in order to evaluate the diagnosis of CVL in this region. All animals underwent clinical examination, and blood samples (serum and eluate) were collected for analysis by enzyme immunoassay (ELISA) and IFAT. A skin biopsy was obtained for parasitological examination (culture). A total of 305 animals were studied and Leishmania chagasi was isolated from nine animals. Sensitivity and specificity were 100% and 96.6% for ELISA, respectively, 100% and 65.5% for IFAT (cut-off at a 1:40 dilution), 100% and 83.4% for IFAT (cut-off at a 1:80 dilution), and 22.2% and 97.0% for eluate IFAT. In conclusion, ELISA was the best tool for the diagnosis of CVL among the serological techniques tested. The present results suggest the need for a better evaluation of filter paper IFAT as the only diagnostic method for CVL in the Municipality of Rio de Janeiro.


Auditory masking patterns in bottlenose dolphins (Tursiops truncatus) with natural, anthropogenic, and synthesized noise.
Auditory masking occurs when one sound (usually called noise) interferes with the detection, discrimination, or recognition of another sound (usually called the signal). This interference can lead to detriments in a listener's ability to communicate, forage, and navigate. Most studies of auditory masking in marine mammals have been limited to detection thresholds of pure tones in Gaussian noise. Environmental noise marine mammals encounter is often more complex. In the current study, detection thresholds were estimated for bottlenose dolphins with a 10 kHz signal masked by natural, anthropogenic, and synthesized noise. Using a band-widening paradigm, detection thresholds exhibited a pattern where signal thresholds increased proportionally to bandwidth for narrow band noise. However, when noise bandwidth was greater than a critical band, masking patterns diverged. Subsequent experiments demonstrated that the auditory mechanisms responsible for the divergent masking patterns were related to across-channel comparison and within-valley listening.


Leishmaniasis in Sri Lanka: spatial distribution and seasonal variations from 2009 to 2016.
Leishmaniasis is listed as one of the eight neglected tropical diseases by the World Health Organization and the number of cases in endemic areas has seen a sharp rise in the past decade. More alarmingly, reports have shown that leishmaniasis is spreading to non-endemic areas of the world due to co-infection with HIV. In Sri Lanka, leishmaniasis is considered as a notifiable disease from 2008 and has seen a rising trend of incidence since then. This is the first study describing the burden, seasonal variation and spatial distribution of leishmaniasis in Sri Lanka since the disease has been included as a notifiable disease. Data on health statistics from 2009 to 2016 were obtained from published databases maintained by the Epidemiology Unit of the Ministry of Health in Sri Lanka. Climatic data for Sri Lanka were obtained from the Department of Meteorology and the populations in administrative districts were obtained from the Department of Census and Statistics, Sri Lanka. Descriptive spatiotemporal analysis, correlation between leishmaniasis incidence and climatic variables were analyzed using SPSS statistical software. The total number of people reported with leishmaniasis during the study period was 8487. Cutaneous leishmaniasis is the prominent form in Sri Lanka while few visceral and muco-cutaneous cases were reported. Although leishmaniasis patients were identified from all 25 districts in the island, almost 90% of the total caseload was reported from Anuradhapura, Hambantota, Polonnaruwa, Kurunegala and Matara districts. The highest number of patients was reported from the Anuradhapura district and the highest incidence per 100,000 persons was reported from the Hambantota district. The disease has a seasonal trend, a peak of leishmaniasis occur in July to September in the north-central region and in October to December in the southern region. Maximum temperature, humidity and wind speed are significantly associated climatic variables with leishmaniasis in endemic regions. Leishmaniasis is an emerging public health problem in north-central and southern Sri Lanka. Public awareness programs for the prevention and control of the disease in endemic regions are essential to reduce the incidence of leishmaniasis.


Sample Size Calculation in Animal Studies Using Resource Equation Approach.
Animal research plays an important role in the pre-clinical phase of clinical trials. In animal studies, the power analysis approach to sample size calculation is recommended. Whenever it is not possible to assume the standard deviation and the effect size, an alternative to the power analysis approach is the 'resource equation' approach, which sets the acceptable range of the error degrees of freedom (DF) in an analysis of variance (ANOVA). The aim of this article is to guide researchers in calculating the minimum and maximum numbers of animals required in animal research by reformulating the error DF formulas.


The next generation of electron cyclotron emission imaging diagnostics (invited).
A 128 channel two-dimensional electron cyclotron emission imaging system collects time-resolved 16x8 images of T(e) profiles and fluctuations on the TEXTOR tokamak. Electron cyclotron emission imaging (ECEI) is undergoing significant changes which promise to revolutionize and extend its capabilities far beyond what has been achieved to date. These include the development of a minilens array configuration with increased sensitivity antennas, a new local oscillator pumping scheme, enhanced electron cyclotron resonance heating shielding, and a highly flexible optical design with vertical zoom capability. Horizontal zoom and spot size (rf bandwidth) capabilities are also being developed with new ECEI electronics. An interface module is under development to remotely control all key features of the new ECEI instrument, many of which can be changed during a plasma discharge for maximum flexibility.


The contribution of cis-elements to disease-associated repeat instability: clinical and experimental evidence.
Alterations in the length (instability) of gene-specific microsatellites and minisatellites are associated with at least 35 human diseases. This review will discuss the various cis-elements that contribute to repeat instability, primarily through examination of the most abundant disease-associated repetitive element, trinucleotide repeats. For the purpose of this review, we define cis-elements to include the sequence of the repeat units, the length and purity of the repeat tracts, the sequences flanking the repeat, as well as the surrounding epigenetic environment, including DNA methylation and chromatin structure. Gender-, tissue-, developmental- and locus-specific cis-elements in conjunction with trans-factors may facilitate instability through the processes of DNA replication, repair and/or recombination. Here we review the available human data that supports the involvement of cis-elements in repeat instability with limited reference to model systems. In diverse tissues at different developmental times and at specific loci, repetitive elements display variable levels of instability, suggesting vastly different mechanisms may be responsible for repeat instability amongst the disease loci and between various tissues.


Recent Developments in Total Syntheses of Cephalosporolides, Penisporolides, and Ascospiroketals.
The possible biogenetic connection of the 10-membered lactone (decanolide) and the tricyclic [5,5]-spiroacetal-cis-fused-γ-lactone (SAFL) natural products was proposed by Hanson in 1985. Mimicking such biosynthetic hypothesis led us to develop a general synthetic strategy for the total syntheses of both decanolide-type cephalosporolides and SAFL-type natural products. This biomimetic strategy features two key transformations: i) oxidative ring expansion of bicyclic β-hydroxy tetrahydropyrans to the decanolides and ii) ring contraction rearrangement of the decanolides to the tricyclic SAFLs. In particular, the phenol derivatives are exploited as the starting materials for the decanolides and then the SAFLs. The successful biomimetic total synthesis allows us to revise the structures and biosynthetic hypothesis of several natural products, along with development of an NMR analysis method for determination of the relative stereochemistry of SAFL-type compounds. In addition, this account will summarize recent synthetic work by other research groups.


Adiponectin deficiency rescues high-fat diet-induced hepatic injury, apoptosis and autophagy loss despite persistent steatosis.
Background &aims:Low levels of adiponectin (APN), an adipose-derived adipokine, are associated with obesity and non-alcoholic steatohepatitis although its role in high-fat diet-induced hepatic injury and steatosis remains unclear. Here we hypothesized that APN deficiency alters fat diet-induced hepatic function. To this end, we examined the effect of APN deficiency on high-fat diet-induced hepatic injury, apoptosis and steatosis. Adult wild type and APN knockout mice were fed a low- or high-fat diet for 20 weeks. Serum levels of liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, hepatic triglycerides, steatosis, pro-inflammatory cytokines, apoptosis and autophagy were examined. High-fat feeding led to elevated body (48.2%) and liver weights (18.8%), increased levels of ALT (87.8%), serum cholesterol (104.4%), hepatic triglycerides (305.6%) and hepatic fat deposition as evidenced by Oil Red O staining, along with a reduced AST/ALT ratio and unchanged AST. Although APN knockout itself did not affect hepatic function and morphology, it reconciled fat diet-induced hepatic injury (P<0.05 vs WT-HF group) without reversing changes in body and liver weights, serum cholesterol and hepatic steatosis. In addition, fat diet intake promoted AMPK phosphorylation, p62 accumulation and apoptosis, including elevated Bax and cleaved Caspase-3 and downregulated Bcl-2, along with suppressed phosphorylation of Akt, STAT3 and JNK, and the autophagy makers Atg7, Beclin-1 and LC3B (P<0.05 vs WT-LF group) without affecting hepatic interlelukin-6 and tumor necrosis factor-α levels, the effects were reversed or significantly attenuated by APN knockout (P<0.05 vs WT-HF group). In vitro study using HepG2 cells revealed that STAT3 activation rescued palmitic acid-induced cell injury whereas STAT3 inhibition nullified APN knockdown-offered beneficial effects. Our results revealed that high-fat diet intake promotes hepatic steatosis, apoptosis and interrupted autophagy. APN knockout elicits protective effect against hepatic injury possibly associated with autophagy regulation despite persistent hepatic steatosis.


Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping.
Autism spectrum disorder (ASD) is a group of the neurodevelopment disorders presenting as an isolated ASD or more complex forms, where a broader clinical phenotype comprised of developmental delay and intellectual disability is present. Both the isolated and complex forms have a significant causal genetic component and submicroscopic genomic copy number variations (CNV) are the most common identifiable genetic factor in these patients. The data on microarray testing in ASD cohorts are still accumulating and novel loci are often identified; therefore, we aimed to evaluate the diagnostic efficacy of the method and the relevance of implementing it into routine genetic testing in ASD patients. A genome-wide CNV analysis using the Agilent microarrays was performed in a group of 150 individuals with an isolated or complex ASD. Altogether, 11 (7.3%) pathogenic CNVs and 15 (10.0%) variants of unknown significance (VOUS) were identified, with the highest proportion of pathogenic CNVs in the subgroup of the complex ASD patients (14.3%). An interesting case of previously unreported partial UPF3B gene deletion was identified among the pathogenic CNVs. Among the CNVs with unknown significance, four VOUS involved genes with possible correlation to ASD, namely genes SNTG2, PARK2, CADPS2 and NLGN4X. The diagnostic efficacy of aCGH in our cohort was comparable with those of the previously reported and identified an important proportion of genetic ASD cases. Despite the continuum of published studies on the CNV testing in ASD cohorts, a considerable number of VOUS CNVs is still being identified, namely 10.0% in our study.


KCNE1 rs1805127 polymorphism increases the risk of atrial fibrillation: a meta-analysis of 10 studies.
Atrial fibrillation (AF) is one of the most common types of arrhythmia in humans. Recently, many studies have investigated the relationship between human atrial fibrillation and the single nucleotide polymorphism (SNP) of rs1805127 (A>G) in KCNE1 gene, but the results were still inconsistent and inconclusive. Electronic databases and bibliographies of retrieved studies were searched. We performed a meta-analysis of ten case-control studies, including 2099 cases and 2252 controls, to evaluate the association of rs1805127 polymorphism (A>G) with the risk of AF. Random-effects model was used when the heterogeneity was obvious; otherwise, fixed-effects model was applied. Meta-regression was performed to examine potential source of heterogeneity. Egger's test and Begg's test were used to detect publication biases. The results showed a significantly increased risk of AF in homozygote comparison (GG vs. AA:OR = 1.899, 95%CI: 1.568, 2.300; Pheterogeneity = 0.217), heterozygote comparison (GA vs. AA:OR = 1.436, 95% CI:1.190, 1.732; Pheterogeneity = 0.739), dominant model(GA /GG vs. AA: OR = 1.624, 95%CI: 1.361, 1.938; Pheterogeneity = 0.778) and recessive model (GG vs. GA/AA: OR = 1.394, 95%CI:1.152, 1.686; Pheterogeneity = 0.03). Meta-regression revealed that the sample size and the types of AF were the source of the heterogeneity. The rs1805127 polymorphism (A>G) of KCNE1 is associated with an increased risk of AF, which suggests the rs1805217 polymorphism of KCNE1 gene may play an important role in the pathogenesis of AF.