Purchases by heavier drinking young people concentrated in lower priced beverages: Implications for policy.
Alcohol is an increasingly important risk factor in the global burden of disease. The acute harms experienced and persistence of drinking patterns established in adolescence motivate investigating influences on youth drinking. The aim is to examine association between heavier drinking in young people and their choice of beverage type, purchase outlet and price. A nationally representative sample of New Zealand drinkers (N = 1056) aged 16-19 years recruited using random digit dialling was surveyed in 2012 as part of the International Alcohol Control study. Typical quantities consumed and frequency of alcohol consumption categorised respondents into lower, medium and heavier consumption groups. Beverage choice, prices paid and on or off-premise purchase were related to consumption using univariate analysis. Logistic analysis was used to examine multivariate factors predicting membership of consumption groups. Twenty percent of the sample consumed six or more drinks at least once a week, increasing to 1 in 4 for those 18 years and older. Heavier drinkers consumed more alcohol in the form of ready to drinks (RTD) especially high-potency RTDs. Lower consumers drank greater proportion of wine. Heavier drinkers paid less than medium consumers who paid less than lower consumers. High-potency RTDs were cheaper per unit of alcohol than other beverages and chosen by heavier drinkers resulting in lower prices. Heavy consumption of alcohol remains common in New Zealand young drinkers. Heavier drinkers paid less to purchase alcohol and consumed more alcohol in the form of high-potency RTDs. [Wall M, Casswell S, Yeh L-C. Purchases by heavier drinking young people concentrated in lower priced beverages: Implications for policy. Drug Alcohol Rev 2017;36:352-358].


Studying the evolution of transcription factor binding events using multi-species ChIP-Seq data.
Recent technology advances make it possible to collect whole-genome transcription factor binding (TFB) profiles from multiple species through the ChIP-Seq data. This provides rich information to understand TFB evolution. However, few rigorous statistical models are available to infer TFB evolution from these data. We have developed a phylogenetic tree based method to model the on/off rates of TFB events. There are two unique features of our method compared to existing models. First, we mask nucleotide substitutions and focus on INDEL disruption of TFB events, which are rarer evolution events and more appropriate for divergent species and non-coding regulatory regions. Second, we correct for ascertainment bias in ChIP-Seq data by maximizing likelihood conditional on the observed (incomplete) data. Simulations show that our method works well in model selection and parameter estimation when there are sufficient aligned TFB events. When this method is applied to a ChIP-Seq data set with five vertebrates, we find that the instantaneous transition rates to INDELs are higher in TFB regions than in homologous non-binding regions. This is driven by an excess of alignment columns showing binding in one species but gaps in all other species. When we compare the inferred transition rates between the conserved and non-conserved regions, as expected, the conserved regions are estimated to have lower transition rates. The R package TFBphylo that implements the described model can be downloaded from http://bioinformatics.med.yale.edu/.


Seed Heteromorphism and Effects of Light and Abiotic Stress on Germination of a Typical Annual Halophyte Salsola ferganica in Cold Desert.
Seed heteromorphism is a common characteristic of halophyte and an adaptation to the spatial and temporal variations of natural habitats. Differences in dormancy and germination requirements have been documented in heteromorphic seeds of many species, but the mechanisms for maintenance between different status in various populations have not been well-understood. Salsola ferganica is a typical annual halophyte in Chenopodiaceae distributed in cold desert, in the present study, we found that it could produce three distinct types of seed according to the shape and size of winged perianth (WP), which differed in dispersal ability, dormancy and germination behaviors. Our further investigation revealed that light could significantly promote germination of heteromorphic seeds of S. ferganica, and WP inhibited while GA3 enhanced germination, which suggests that S. ferganica seeds possessed a photo-sensitive combined with morphological and non-deep physiological dormancy type, in which light was the dominant factor. Not like other desert plant species, the germinability of heteromorphic seeds of S. ferganica could not sustain for long (only 1-2 years), especially the small seeds, and was affected by storage time, temperature, salinity, even the environmental conditions of the maternal plant. Thus, the differences of characteristics existed among heteromorphic seeds and variations of heteromorphic ratio among different calendar years were presumed as diverse adaptation strategies integrated in the individual mother plant, and might apply important ecological significance for successful reproduction of the species in the unpredictable cold desert.


Endodontic Management of Maxillary First Molar With Two Palatal Canals Aided With Cone Beam Computed Tomography: A Case Report.
The success of endodontic therapy is based on having sufficient endodontic access, correct cleaning and shaping, and adequate root canal obturation. However, endodontic treatment is also dependent on having a sound knowledge of the internal anatomy of human teeth, especially when anatomic variations are present. Reporting these alterations is important for improving the understanding and expertise of endodontists. The aim of this case report is to describe a unique case of maxillary first molar with 2 palatal canals within a single root, as confirmed by cone-beam computed tomography (CBCT) scans. This article also reviews recent case reports of extra palatal root canals in the maxillary first molars and the role of CBCT analysis in successfully diagnosing them.


Anesthetic considerations for the oral surgery patient with hemophilia.
Hemophiliac patients undergoing oral surgical procedures can be a challenge for both dental and medical personnel involved in their care and treatment. Anesthetic management of hemophiliac patients may be safely attained by various pain control techniques including local anesthesia. Possible complications resulting from administration of anesthesia must be kept in mind at all times. Preparation, caution, and gentleness are necessities for administration of safe and effective anesthesia to the hemophiliac patient.


Exocrine pancreatic physiology: overview.
Exocrine pancreatic physiology has been actively investigated in Japan during the past 30 years. We selected three areas and reviewed them for this article. The selected areas are perfusion of the isolated pancreas, cholecystokinin (CCK)-releasing factor from pancreatic juice (monitor peptide), and genetically diabetic rats. The aim of this article is to present a brief overview of the selected areas of exocrine pancreatic physiology in Japan so that future research can be productively directed.


A blinded placebo-controlled randomized trial on the use of astaxanthin as an adjunct to splinting in the treatment of carpal tunnel syndrome.
Nutritional supplementation is a potential adjunct in the conservative management of carpal tunnel syndrome (CTS). This study investigated whether astaxanthin (a beta-carotenoid) increased the effectiveness of splinting in managing CTS. This is a triple-blinded randomized controlled trial where 63 patients with electrodiagnostically confirmed CTS were randomly allocated into either the experimental group (n = 32) (astaxanthin-4-mg capsules + splinting) or the control group (n = 31) (placebo + splinting). Medications were taken for 9 weeks followed by a 3-week washout. The primary outcome measure was the Symptom Severity Scale (SSS). Secondary outcome measures in the study included physical impairments, disability, and health status measures. Electrodiagnostic testing was performed before entry into the study and again at 12 weeks. All other outcomes were measured at baseline, 6, and 12 weeks. There was a reduction in symptoms as measured by the SSS over the course of treatment in both groups (p = 0.002), but no differences between the groups (p = 0.18). The Disability of Arm, Shoulder and Hand questionnaire and the Short Form 36-item Health Survey showed no effects over time or between treatment groups. The baseline difference between the groups in the level of total cholesterol and low-density lipoproteins remained constant over the course of the study. Impairment measures demonstrated no significant changes in grip, dexterity, or sensation. At present, the role for astaxanthin as an adjunct in conservative management of CTS has not been established.


Society of Skeletal Radiology- white paper. Guidelines for the diagnostic management of incidental solitary bone lesions on CT and MRI in adults: bone reporting and data system (Bone-RADS).
The purpose of this article is to present algorithms for the diagnostic management of solitary bone lesions incidentally encountered on computed tomography (CT) and magnetic resonance (MRI) in adults. Based on review of the current literature and expert opinion, the Practice Guidelines and Technical Standards Committee of the Society of Skeletal Radiology (SSR) proposes a bone reporting and data system (Bone-RADS) for incidentally encountered solitary bone lesions on CT and MRI with four possible diagnostic management recommendations (Bone-RADS1, leave alone; Bone-RADS2, perform different imaging modality; Bone-RADS3, perform follow-up imaging; Bone-RADS4, biopsy and/or oncologic referral). Two algorithms for CT based on lesion density (lucent or sclerotic/mixed) and two for MRI allow the user to arrive at a specific Bone-RADS management recommendation. Representative cases are provided to illustrate the usability of the algorithms.


Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations.
The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow-wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty-eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night-time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired-associate word list task, while procedural memory was tested using the mirror-tracing task. All participants underwent high-resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow-wave sleep as previously conceptualized.


Cardiovascular disease behavioral risk factors among Latinos by citizenship and documentation status.
Studies have observed that recent Latino immigrants tend to have a physical health advantage compared to immigrants who have been in the US for many years or Latinos who are born in the United States. An explanation of this phenomenon is that recent immigrants have positive health behaviors that protect them from chronic disease risk. This study aims to determine if trends in positive cardiovascular disease (CVD) risk behaviors extend to Latino immigrants in California according to citizenship and documentation status. We examined CVD behavioral risk factors by citizenship/documentation statuses among Latinos and non-Latino US-born whites in the 2011-2015 waves of the California Health Interview Survey. Adjusted multivariable logistic regressions estimated the odds for CVD behavioral risk factors, and analyses were stratified by sex. In adjusted analyses, using US-born Latinos as the reference group, undocumented Latino immigrants had the lowest odds of current smoking, binge drinking, and frequency of fast food consumption. There were no differences across the groups for fruit/vegetable intake and walking for leisure. Among those with high blood pressure, undocumented immigrants were least likely to be on medication. Undocumented immigrant women had better patterns of CVD behavioral risk factors on some measures compared with other Latino citizenship and documentation groups. This study observes that the healthy Latino immigrant advantage seems to apply to undocumented female immigrants, but it does not necessarily extend to undocumented male immigrants who had similar behavioral risk profiles to US-born Latinos.


Transcriptomic discovery of a theranostic signature (SERPINE1/MMP3/COL1A1/SPP1) for head and neck squamous cell carcinomas and identification of antrocinol as a candidate drug.
Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC.


Acid base and electrolyte disturbance in diarrhoea.
The present study was undertaken to study the frequency of electrolyte imbalance in children with diarrhoea and the relationship between electrolyte abnormalities and mortality. This is a retrospective, observational hospital based study. Fifty seven children admitted to paediatric ward with diarrhoea and dehydration was evaluated for electrolyte and acid base status at presentation. The variables were analyzed using chi-square and student t- test. Majority (70%) of patients were below 2 years of age. There were 37 (65%) males and 20(35%) females. Electrolyte disturbance was observed in 46 (80%) patients while acid base disturbance was observed in all (100%) where the estimations were done. The major electrolyte disturbances noted were hyponatremia (56%), which was either isolated (26%) or associated with hypokalemia (26%). The second common abnormality was hypokalemia (46%) which was again either isolated (14%) or associated with hyponatremia (26%). About 10% patient had hypernatremia and about 3% had hyperkalemia. Twenty one (37 %) patients had mixed electrolyte imbalance. ABG analysis was performed only in 16 patients. Arterial blood gas analysis could be performed only in 16 patients. Metabolic acidosis was present in 15 (94%) while one (6%) had metabolic alkalosis. Out of 57, five patients (8.7%) expired. All of them had electrolyte abnormalities. Out of five patients who died one had isolated hyponatremia, 2 had hyponatremia + hypokalemia, while one each had hypernatremia + hypokalemia and hypernatremia+ hyperkalemia. Statistically significant mortality was observed in patients presenting with either hyponatremia or hypokalemia as compared to the group with normal electrolytes. Hyponatremia, hypokalemia and metabolic acidosis are common electrolyte and acid-base abnormalities in children with diarrhoea and dehydration and often responsible for mortality.


The causes and prevention of maceration of the skin.
Maceration can interfere with the normal healing response of a wound. Nurses caring for patients with wounds need expertise in detecting and preventing this condition. This paper examines the risk factors for exudate production, methods of controlling exudate levels and the selection of appropriate dressings in order to avoid maceration.


[Effects of a smoking cessation education on smoking cessation, endothelial function, and serum carboxyhemoglobin in male patients with variant angina].
The aim of this study was to evaluate the effects of a smoking cessation education on endothelial function and carboxyhemoglobin levels in smokers with variant angina. A nonequivalent control group pretest-posttest design was used. Participants were 60 male smokers with variant angina admitted to one hospital: the control group (30) between September and December, 2009, and the experimental group (30) between February and May, 2010. Endothelial function, as defined by flow-mediated vasodilation (FMD) of the brachial artery, and serum carboxyhemoglobin (COHb) were determined at baseline and at 3 months after the initiation of education in both groups. Three months after the program, smoking cessation was successful in 22 of the 30 smokers in the experimental group, but only in 4 of 30 smokers in the control group (p<.001). After the education, the experimental group showed a significant increase in FMD, and a significant decreased in serum COHb compared with the control group. The findings indicate that this smoking cessation education program is effective for hospitalized smokers with variant angina.


Differentiation of Naegleria fowleri and other Naegleriae by polymerase chain reaction and hybridization methods.
In order to detect and identify Naegleria fowleri strains an assay based on the Polymerase Chain Reaction (PCR) was evaluated. The amplified DNA fragments were detected by gel electrophoresis and ethidium bromide staining, followed by Southern blot hybridization with an internal digoxigenin-labeled probe. A set of primers (B1B2) which flank a 678-bp region within a virulence-associated gene, allowed for the highly specific identification of N. fowleri, since Naegleriae (N. lovaniensis, N. australiensis, N. gruberi, N. andersoni and N. jadini) and other Protozoa did not react. These primers did not detect amplification products from various organisms: Gram-positive bacteria, Gram-negative bacteria, algae, yeasts and human DNA. Whereas a second set of primers (A1A2), which flank a different sequence, detected various Naegleriae and Acanthamoebae strains. After 40 amplification cycles, the limit of detection was a single cell (cyst or trophozoite). Thus, the PCR appears to be a rapid and powerful tool for identification and detection of N. fowleri.


[The impact of iodine prophylaxis programme on thyroid gland morphology and function in children and adolescents from the Mazowieckie Voivodship].
The project was realised within the multicentre research programme no PBZ038-08. In all, 2967 children aged 11-18 years were examined, including 1712 girls and 1255 boys. The tested children came from the Mazowieckie Voivodship. Each child was assessed by thyroid ultrasound examination and the level of TSH, FT4 hormones, antithyroid antibodies ATM and ATGL in the blood serum. The level ofFT3 hormone in blood serum was assessed in every fourth child. The aim of this work was to determine the influence of obligatory iodine preventive treatment programme on the morphological and functional status of the thyroid gland in children and teenagers from the Mazowieckie Voivodship. The tested children were divided into three groups: 525 children examined in 1997, living in an area of moderate iodine deficiency, 1477 children tested in 1998 after a few months of iodine supplementation and 965 children examined in 1999 who were well supplemented by iodine longer than one year. The average thyroid volume and the incidence of focal changes in the thyroid gland were determined by ultrasonography, the mean of the TSH, FT4, FT3, hormone level was defined in blood serum in girls and in boys examined in consecutive years. In children tested in 1999 a reduction of the average thyroid volume and a statistically significant decrease of the percentage of children with goitre and with focal changes in the thyroid gland were observed in comparison to children tested in 1997. The results depended on iodine prophylaxis. A statistically significant lower level of FT3 hormone in blood serum was recorded in children tested in 1999 than in 1997. The largest number of children with high levels of ATM and ATGL antibodies in blood serum, exceeding 100 IIJ7ml, were found in 1997 (ATM in 8.6% of cases, ATGL in 17.3% of cases). The high level of ATGL antibodies was observed more frequently in children tested in 1999 than in 1998.


Synchronizing chaotic dynamics with uncertainties based on a sliding mode control design.
The synchronization of two chaotic systems with uncertainties is studied in this paper. A feedback controller is provided based on a sliding mode control design. A kind of extended state observer is used to compensate for the systems' uncertainties, such as the structure difference or parameter mismatching, using only the available synchronizing error. Then the feedback controller becomes physically realizable based on the states of the observer, and can be used to synchronize two continuous chaotic systems. Illustrative examples of the synchronization of Duffing and Van der Pol oscillators as well as two Lorenz systems with parameter mismatching are proposed to show the effectiveness of this method.


[Fronto- and laterobasal injuries in childhood and adolescence].
Within a period of 5 years, the author treated, among 106 children and adolescents up to 15 years of age with craniocerebral injuries, 12 who had frontobasal and laterobasal lesions. These were extended comminuted fractures, impression fractures, linear fractures (fissures), ethmoidal fractures, as well as a petrosal bone fracture. Principal signs were rhinoliquorrhoea or otoliquorrhoea, traumatic disturbances of consciousness and intracranial air accumulations. Less frequently, traumatic shock, signs of CSF infection and concomitant eye injuries were seen. Surgical care (treatment of the dural defect and plastic occlusion by means of Lyodura, galea-periosteal flap or fascia lata) was mostly effected transfrontally, in two cases transethmoidally and in one case with combined technique. In two cases, primary frontal decomminution had to be followed by a transethmoidal second intervention to close a lesion of the dura in the region of the sphenoid sinus. Surgery was carried out as an immediate operation in case of open injuries and in massive liquorrhoea if the general condition of the patient was good. In all other cases, operation was delayed until the second week after injury.


Visceral Adipose Tissue and Skeletal Muscle Index Distribution Predicts Severe Pancreatic Fistula Development After Pancreaticoduodenectomy.
In this study, we investigated the effect of body composition on pancreatic fistula (PF) development after pancreaticoduodenectomy (PD). All consecutive patients with pancreatic and extrahepatic biliary malignancy following PD who were treated between 2006 and 2016 were enrolled. PF developed in 30.3% of cases (30/99 patients), including a grade B PF in 25.3% of cases (25/99 patients) and a grade C PF in 5.1% of cases (5/99 patients). Univariate analysis identified that body mass index ≥25 kg/m2, visceral adipose tissue area (VATA)/skeletal muscle index (SMI) ≥2.0, pancreatic duct diameter ≤3 mm, and drain amylase concentration (Amy) on postoperative day (POD) 1 ≥5000 U/L were significantly associated with PF (grade B, C) after PD. Multivariate analysis indicated that VATA/SMI ≥2.0 (p=0.009), pancreatic duct diameter ≤3 mm (p=0.003), and drain Amy on POD1 ≥5000 U/L (p=0.032) were independent risk factors for PF. Elevated VATA/SMI was the only preoperative key factor for PF after PD.


Magnetic noise in structured hard magnets.
The anomalous Hall effect of wires patterned from (Co{90}Fe{10}/Pt){n} multilayers, with 10<or=n<or=50, is used to determine the magnetization process in a small volume of maze domains. Time-independent 1/f noise appears in samples with a quality factor Q<1 at points on the hysteresis loop where the magnetization reverses continuously. The magnetic noise is associated with reversible excursions of segments of a domain wall approximately 100 nm long. Barkhausen jumps are observed close to either the switching field or the saturation field where the noise power spectrum varies as 1/f{1.7}, and its magnitude decays with time.


Photoacoustic thermorelaxation microscopy for thermal diffusivity measurement.
Thermal diffusivity is one of the main parameters to characterize the thermo-physical properties of materials, and advances in its measurement technique will have significant impact on materials science and related applications. Here a photoacoustic (PA) thermorelaxation microscopy is proposed as a new noncontact method to measure the thermal diffusivity. By delivering co-focused heating/probing laser pulse pairs with tunable time delays, the sample's in situ thermal relaxation behavior after the heating pulse excitation can be photoacoustically monitored based on the temperature-dependent property of the Grueneisen parameter. We theoretically deduced the dependence of the obtained PA thermorelaxation time on the thermal diffusivity, and the results coincided well with simulations. The feasibility of this method was validated by various industrial and biological samples. This method provides a new strategy for high-resolution thermal diffusivity measurement with flexible measurement conditions, prefiguring great potential for material and biological applications.


Bacillus "next generation" diagnostics: moving from detection toward subtyping and risk-related strain profiling.
The highly heterogeneous genus Bacillus comprises the largest species group of endospore forming bacteria. Because of their ubiquitous nature, Bacillus spores can enter food production at several stages resulting in significant economic losses and posing a potential risk to consumers due the capacity of certain Bacillus strains for toxin production. In the past, food microbiological diagnostics was focused on the determination of species using conventional culture-based methods, which are still widely used. However, due to the extreme intra-species diversity found in the genus Bacillus, DNA-based identification and typing methods are gaining increasing importance in routine diagnostics. Several studies showed that certain characteristics are rather strain-dependent than species-specific. Therefore, the challenge for current and future Bacillus diagnostics is not only the efficient and accurate identification on species level but also the development of rapid methods to identify strains with specific characteristics (such as stress resistance or spoilage potential), trace contamination sources, and last but not least discriminate potential hazardous strains from non-toxic strains.


A new approach to fluorescence "turn-on" sensing of alpha-amino acids.
For the first time, a conjugated fluorescent polymer was utilized to probe alpha-amino acids, sensitively and selectively, through a new approach. First the strong fluorescence of the prepared polyfluorene (P1) was quenched by trace copper ions, and then the quenched fluorescence was recovered upon the addition of alpha-amino acids, making P1 a new and sensitive biosensor toward alpha-amino acids. The experimental results demonstrated that the alpha-amino acid selective nature of P1 over other analytes was relatively good. Thus, the work reported here might open up a new avenue for developing new biosensors.


The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation.
To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.


Conversion of chronic staphylococcal mastitis to acute gangrenous mastitis after neutropenia in blood and bone marrow produced by an equine anti-bovine leukocyte serum.
A stock strain of Staphylococcus aureus of mastitis origin, characterized by alpha-, beta-, and delta-toxins, was used to produce chronic mastitis of 20 to 300 days' duration in 6 lactating mammary quarters of 4 cows. Early acute Streptococcus agalactiae mastitis was produced in 1 additional mammary quarter of 1 cow. Equine anti-bovine leukocyte serum (EABLS) was administered to all cows by continuous intravascular drip for 12 to 32 hours. Neutropenia in blood and partial depletion of neutrophil reserve in bone marrow were produced. Chronic subclinical staphylococcal mastitis in 2 quarters of 1 cow changed to gangrenous mastitis by the 40th hour after EABLS administration and led to death of the cow. The disappearance of neutrophil leukocytes from the milk was followed by uninhibited multiplication of S aureus. Probably, staphylococcal leukocidins accelerated the destruction of neutrophils in the milk as S aureus multiplication became intensified. In another quarter of the same cow that was infected with Str agalactiae, neutrophil leukocytes were present in milk as long as 3 days after their disappearance from blood and bone marrow. This may give some indication of the extravascular life-span of the neutrophil in the udder in mastitis. The 2nd cow died at the 16th hour from the start of EABLS administration and at a time when gangrenous mastitis was in the initial stages of development. The S aureus-infected quarters of the 2 remaining cows did not become gangrenous. Administration of EABLS to these 2 cows did not significantly reduce the numbers of neutrophil leukocytes entering the milk of the 3 S aureus-infected quarters. It is concluded that continuous diapedesis of neutrophil leukocytes into the milk in chronic staphylococcal mastitis protects the gland against the development of gangrenous mastitis in the presence of a strain of S aureus capable of alpha-toxin production.


Combinations of serum prostate-specific antigen and plasma expression levels of let-7c, miR-30c, miR-141, and miR-375 as potential better diagnostic biomarkers for prostate cancer.
In the current study, expression levels of let-7c, miR-30c, miR-141, and miR-375 in plasma from 59 prostate cancer (PC) patients with different clinicopathological characteristics and two groups of controls: 16 benign prostatic hyperplasia (BPH) samples and 11 young asymptomatic men (YAM) were analyzed to evaluate their diagnostic and prognostic value in comparison to prostate-specific antigen (PSA). miR-375 was significantly downregulated in 83.5% of patients compared to BPH controls and showed stronger diagnostic accuracy (area under the curve [AUC]=0.809, 95% CI: 0.697-0.922, p=0.00016) compared with PSA (AUC=0.710, 95% CI: 0.559-0.861, p=0.013). Expression levels of let-7c showed potential to distinguish PC patients from BPH controls with AUC=0.757, but the result did not reach significance. Better discriminating performance was observed when combinations of studied biomarkers were used. Sensitivity of 86.8% and specificity of 81.8% were reached when all biomarkers were combined (AUC=0.877) and YAM were used as calibrators. None of the studied microRNAs (miRNAs) showed correlation with clinicopathological characteristics. PSA levels were significantly correlated with the Gleason score, tumor stage, and lymph node metastasis with Spearman correlation coefficients: 0.612, 0.576, and 0.458. In conclusion, the combination of the studied circulating plasma miRNAs and serum PSA has the potential to be used as a noninvasive diagnostic biomarker for PC screening outperforming the PSA testing alone.


β-catenin inhibitors in cancer therapeutics: intricacies and way forward.
β-catenin is an evolutionary conserved, quintessential, multifaceted protein that plays vital roles in cellular homeostasis, embryonic development, organogenesis, stem cell maintenance, cell proliferation, migration, differentiation, apoptosis, and pathogenesis of various human diseases including cancer. β-catenin manifests both signaling and adhesive features. It acts as a pivotal player in intracellular signaling as a component of versatile WNT signaling cascade involved in embryonic development, homeostasis as well as in carcinogenesis. It is also involved in Ca2+ dependent cell adhesion via interaction with E-cadherin at the adherens junctions. Aberrant β-catenin expression and its nuclear accumulation promote the transcription of various oncogenes including c-Myc and cyclinD1, thereby contributing to tumor initiation, development, and progression. β-catenin's expression is closely regulated at various levels including its stability, sub-cellular localization, as well as transcriptional activity. Understanding the molecular mechanisms of regulation of β-catenin and its atypical expression will provide researchers not only the novel insights into the pathogenesis and progression of cancer but also will help in deciphering new therapeutic avenues. In the present review, we have summarized the dual functions of β-catenin, its role in signaling, associated mutations as well as its role in carcinogenesis and tumor progression of various cancers. Additionally, we have discussed the challenges associated with targeting β-catenin molecule with the presently available drugs and suggested the possible way forward in designing new therapeutic alternatives against this oncogene.


Can we predict diatoms herbicide sensitivities with phylogeny? Influence of intraspecific and interspecific variability.
Diatoms are used as indicators of freshwater ecosystems integrity. Developing diatom-based tools to assess impact of herbicide pollution is expected by water managers. But, defining sensitivities of all species to multiple herbicides would be unattainable. The existence of a phylogenetic signal of herbicide sensitivity was shown among diatoms and should enable prediction of new species sensitivity. However, diatoms present a cryptic diversity that may lead to variation in their sensitivity to herbicides that would need to be taken into account. Using bioassays, the sensitivity to four herbicides (Atrazine, Terbutryn, Diuron, Isoproturon) was evaluated for 11 freshwater diatom taxa and intraspecific variability was assessed for two of them (Nitzschia palea and Achnanthidium spp.). Intraspecific variability of herbicide sensitivity was always smaller than interspecific variability, but intraspecific variability was more important in N. palea than in Achnanthidium spp. Indeed, one species showed no intraspecific phylogenetic signal (N. palea) whereas the other did (Achnanthidium spp.). On one hand, species boundaries are not set properly for Achnanthidium spp. which encompass several taxa. On the other hand, there is a higher phenotypic plasticity for N. palea. Finally, a phylogenetic signal of herbicide sensitivity was measured at the interspecific level, opening up prospects for setting up reliable biomonitoring tools based on sensitivity prediction, insofar as species boundaries are correctly defined.


The use of mucolysed induced sputum for the identification of pulmonary pathogens associated with human immunodeficiency virus infection.
We describe a system for diagnosis of pulmonary disease in the human immunodeficiency virus-infected patient using induced sputum and other diagnostic procedures. This system has been successfully used at San Francisco (Calif) General Hospital for more than 2 years. It utilizes outpatient facilities and reduces the need for bronchoscopy. Sputum induced by inhalation of 3% saline mist, mucolysed, concentrated by centrifugation, and stained by a rapid modified Giemsa stain was the first diagnostic specimen examined in 404 episodes of suspected human immunodeficiency virus-associated pulmonary disease in 358 patients. Pneumocystis carinii was found in 222 (55%) sputum specimens. In 118 episodes in which the sputum did not contain P carinii, bronchoscopy with transbronchial biopsy and/or bronchoalveolar lavage was performed and P carinii was found in 50 (42%). These 118 bronchoscopy results, as well as evaluation of the subsequent clinical course of those patients who accounted for 64 episodes of lung disease and who did not have bronchoscopy following examination of nondiagnostic induced sputum, indicated a range of sensitivity for detection of P carinii in induced sputum of 74% to 77% and a negative predictive value of 58% to 64%. Mycobacteria were recovered from 11 (6%) of the induced sputum and 6 (12%) of the bronchoscopic specimens containing P carinii. However, only oral or environmental fungi were recovered from P carinii-containing induced sputum or bronchoscopic specimens. For those patients in whom P carinii was not detected, only the bronchoscopic specimens were cultured for Mycobacteria and fungi. Potentially pathogenic Mycobacteria and fungi were recovered from 16 (23.5%) and 34 (50%), respectively, of these P carinii-negative specimens. Analysis of these results, obtained under routine practice conditions, indicates that bronchoscopy should be reserved for those patients whose induced sputum examinations do not show P carinii and that mycobacterial and fungal cultures be performed only on bronchoscopic specimens in which P carinii is not detected.


Difference of molecular alterations in HER2-positive and HER2-negative gastric cancers by whole-genome sequencing analysis.
The aim of this study was to compare the molecular profiling, including somatic mutation and somatic copy number variation (SCNV), between human epidermal growth factor receptor 2 (HER2)-positive (HER2+) and HER2-negative (HER2-) gastric cancer patients. Tumor samples were collected from 15 gastric cancer patients, including 10 HER2+ samples and five HER2- samples, which were diagnosed by immunohistochemistry. Whole-genome sequencing was performed by Illumina HiSeq PE150 instrument, along with somatic single nucleotide variant (SNV), somatic structural variation (SV) and SCNV analyses. The average number of somatic SNVs and mutation spectrum were similar between HER2+ and HER2- samples. Transition of C>T was the main type of mutation. For somatic SV, number of intrachromosomal translocation (2,850.3±1,260.4 vs 1,157±586.6, P=0.015) and insertion of large fragment (1,125.6±457.4 vs 500±138.9, P=0.002) in HER2+ samples were higher than those in HER2- samples. For all samples, lysine methyltransferase 2C (KMT2C), ZNF91, TAF1 and MAP4 genes were identified as new significant mutated driver genes. KMT2C gene mutations were mainly detected in HER2+ samples (7/10), which were correlated with the lysine degradation pathway. SERF2 gene mutations were more common in HER2- samples (3/5) than in HER2+ samples (1/10). Copy number gain was the major type of SCNV in both groups, and the average number of SCNVs was similar. In the HER2+ samples, by using the GISTIC algorithm, amplification of known driver genes cyclin-dependent kinase 12 (CDK12, 6/10) and RARA (5/10) was mainly observed, and other amplifications including JUP, GJD3, KRT39, CDC6, RAPGEFL1, WIPF2, FAM65C, KLF5, DACH1 and PIBF1 genes were also observed. Amplifications of solute carrier family 12 member 7 (SLC12A7, 5/5), TTC40 (4/5) and GALNT9 (4/5) genes were mainly detected in HER2- samples. Differences in genomic landscape between HER2+ and HER2- gastric cancer samples were revealed in this study. KMT2C mutation and CDK12 amplification were mainly detected in HER2+ gastric cancer, whereas SERF2 mutation and SLC12A7 amplification were detected in HER2- gastric cancer.


Archeological Investigations in East Central Arizona.
A blend of traditional and new methodologies is being employed to analyze extinct cultural systems up to 4000 years old. A Univac computer was used to demonstrate a functional attribute of ceramics, and sociological inferences were made from spatial distributions of pottery designs.


The Incidence of Marine Toxins and the Associated Seafood Poisoning Episodes in the African Countries of the Indian Ocean and the Red Sea.
The occurrence of Harmful Algal Blooms (HABs) and bacteria can be one of the great threats to public health due to their ability to produce marine toxins (MTs). The most reported MTs include paralytic shellfish toxins (PSTs), amnesic shellfish toxins (ASTs), diarrheic shellfish toxins (DSTs), cyclic imines (CIs), ciguatoxins (CTXs), azaspiracids (AZTs), palytoxin (PlTXs), tetrodotoxins (TTXs) and their analogs, some of them leading to fatal outcomes. MTs have been reported in several marine organisms causing human poisoning incidents since these organisms constitute the food basis of coastal human populations. In African countries of the Indian Ocean and the Red Sea, to date, only South Africa has a specific monitoring program for MTs and some other countries count only with respect to centers of seafood poisoning control. Therefore, the aim of this review is to evaluate the occurrence of MTs and associated poisoning episodes as a contribution to public health and monitoring programs as an MT risk assessment tool for this geographic region.


[Primary and secondary prevention of stroke].
The basis for primary and secondary prevention of stroke (and also TIA) are both a healthy lifestyle with a healthy diet, non smoking, weight reduction and regular exercise, and consistent treatment of arterial hypertension with a target of < 140 /90 mmHg. The choice of the antihypertensive is depending on concomitant diseases, more important than the class of antihypertensive is treatment to target. Reduction of cholesterol with statins in primary prevention is dependant on total cardiovascular risk, in secondary prevention statins are integral part of modern treatment in non cardioembolic stroke. Atrial fibrillation is one of the major causes of stroke and should be treated with anticoagulation depending on the CHA2DS2-VASc score. Platelet inhibition is mandatory lifelong in all non cardioembolic strokes, in primary prevention only for patients with high total cardiovascular risk. Treatment of asymptomatic carotid artery stenosis should be determined on an individual basis. Symptomatic carotid artery stenosis should be treated immediately after the index stroke.


Molecular Tumor Boards: Ethical Issues in the New Era of Data Medicine.
The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with "genomic medicine" nor with "precision medicine", but with "data medicine" (DM) (big data, data mining). The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The "transformation" of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision of care. Molecular tumor boards (MTB) are one response to these changes and are now providing better access to next-generation sequencing (NGS) and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent (IC) documents at all academic medical centers and to introduce dynamic and electronic informed consent (e-IC).


Rib Bone Graft Adjusted to Fit the Facial Asymmetry: A Frame Structure Graft.
The authors introduce the concept of a "frame structure graft" in which a harvested rib bone was adjusted to fit facial asymmetry. On the costochondral junction of the sixth or seventh rib, a 5 cm incision was made. Through a subperiosteal dissection, the rib bone was harvested. Using a reciprocating saw, the harvested rib was scored on its anterior surface as well as its posterior surface with a partial depth at different intervals. The harvested rib bone was placed on the skin surface of the unaffected side of the face and a curvature was created exactly matching that of the unaffected side by bending the bone using a greenstick fracture. Thereafter, the graft was adjusted to conceal the asymmetry of the deficient side. The adjusted "frame structure" was transferred to the defect through the incisions on the affected side, and the "frame structure" graft was placed on the mandible or zygoma. The graft fixation was done externally with at least 2 Kirschner wires (K-wires). From January 2005 to August 2013, a total of 30 patients (13 men, 17 women, mean age 25.6 years) received a frame structure graft. All 30 patients achieved good healing at the operation site without complications. Donor-site morbidity as pneumothorax from the rib bone harvest was not found. Merits of this frame structure graft, the authors think, are that this method could allow a similar curvature to the normal side. In addition, the procedure itself is easy.


[Chest circumference of East German children in mathematical analysis].
Determinations of chest circumference for GDR children and youth in the years 1956 to 1958 as compiled by Marcusson and Oehmisch ( Marcusson 1961) are submitted to nonlinear regressions using a growth function proposed by the author. In addition the puberal growth spurt and growth velocities are calculated and represented in tables and graphs. Finally specific properties of growth development in chest circumference are confronted with those of the foot, tibia and radius as well as head circumference and body height. Possible changes due to acceleration will scarcely effect the latter considerations.


Post diagnosis diet quality and colorectal cancer survival in women.
Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival. 1201 women diagnosed with stage I-III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman. During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles = 0.71, 95% CI 0.52-0.98, p trend = 0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1 = 0.72, 95% CI = 0.43-1.21, p trend = 0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5-15 g/d = 1.30, 95%CI = 1.05-1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving = 1.11, 95% CI = 1.01-1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality. Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations.


[Amiodarone associated optic neuropathies--two cases reports].
We described two cases with papilledema within the first months of amiodarone treatment. The particular aspects of these cases are, on one hand the development of the optic neuropathy before any toxic change of the cornea and on the other hand the daily and weekly doses prescribed in both cases. We reviewed the meta-analysis studies on the subject and the different pathogenic mechanisms described until now.


Mechanistic analysis of the contributions of DNA and protein damage to radiation-induced cell death.
Protein oxidation can contribute to radiation-induced cell death by two mechanisms: (1) by reducing the fidelity of DNA repair, and (2) by decreasing cell viability directly. Previously, we explored the first mechanism by developing a mathematical model and applying it to data on Deinococcus radiodurans . Here we extend the model to both mechanisms, and analyze a recently published data set of protein carbonylation and cell survival in D. radiodurans and Escherichia coli exposed to gamma and ultraviolet radiation. Our results suggest that similar cell survival curves can be produced by very different mechanisms. For example, wild-type E. coli and DNA double-strand break (DSB) repair-deficient recA- D. radiodurans succumb to radiation doses of similar magnitude, but for different reasons: wild-type E. coli proteins are easily oxidized, causing cell death even at low levels of DNA damage, whereas proteins in recA- D. radiodurans are well protected from oxidation, but DSBs are not repaired correctly even when most proteins are intact. Radioresistant E. coli mutants survive higher radiation doses than the wild-type because of superior protection of cellular proteins from radiogenic oxidation. In contrast, wild-type D. radiodurans is much more radioresistant than the recA- mutant because of superior DSB repair, whereas protein protection in both strains is similar. With further development, the modeling approach presented here can also quantify the causes of radiation-induced cell death in other organisms. Enhanced understanding of these causes can stimulate research on novel radioprotection strategies.


Effect of different physical activity training methods on epilepsy: A protocol for systematic review and meta-analysis.
Over the past few decades, people with epilepsy were advised not to engage in sports based on the fear that sporting activity may cause injuries, potentially induce seizures, and have a negative effect on disease course. However, in recent years, numerous studies have indicated a positive role of physical exercise in reducing the frequency of seizures and improving health condition of patients with epilepsy. The purpose of this study was to compare the effects of different physical exercise programs on the symptomatology and health condition of individuals with epilepsy and provide guidance for selecting the optimal modality of physical exercise for patients with epilepsy via a meta-analysis of available literature. A literature search was carried out in MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI), and Wan fang databases to gather relevant data about different physical exercise modalities and epilepsy. We will use Endnote X9 software for studies selection and Stata16.0 software for the data analysis. This present study aimed to provide the most up to date evidence and recommendations for clinicians and epilepsy patients to choose an optimal type of exercise. Aerobic exercise and resistance exercises both had a positive effect on epilepsy patients. Persons with epilepsy should be encouraged to participate in sports activities.INPLASY registration number: INPLASY202220070.


Massive Hemoptysis in Children.
Rationale. Hemoptysis is a rare but often life-threatening condition in pediatric patients. Massive hemoptysis can easily lead to asphyxia, respiratory failure, shock, and even death. The most common causes of severe hemoptysis are lower respiratory tract infection, vascular malformation, and bronchial foreign body. We present an unusual case of massive hemoptysis caused by malformation of the bronchial artery, which includes bronchial artery hypertrophy, bronchial-pulmonary artery fistula, and ectopic bronchial artery. Patient. An 11-year-old boy was admitted to the hospital with mild hemoptysis lasting for the two preceding days. He did not report any discomfort, such as fever or chest pain. His complete blood count and coagulation function were normal. Chest X-ray documented lower right pneumonia. Massive hemoptysis occurred on the night of the admission. Diagnosis. Bronchial arteriography revealed that the right lower bronchial artery and the ectopic bronchial artery from the renal artery were the responsible vessels for hemoptysis. Interventions. The boy underwent a successful bronchial artery embolization and bronchoscopy to remove the blood clot from the airway. Outcomes. After bronchial artery embolization and bronchoscopy, the boy recovered without complications. Hemoptysis and chest pain disappeared, and chest radiographs returned to normal. Lessons. Bronchial arterial bleeding often presents as life-threatening massive hemoptysis. Patients should immediately receive hemostatic treatment and undergo chest CTA, bronchial arteriography, BAE, and bronchoscopy according to their condition. Rapid identification of the etiology and symptomatic treatment are critical to saving the lives of children.


Human recombinant interleukin-1 beta stimulates glycosaminoglycan production in human synovial fibroblast cultures.
Human recombinant interleukin-1 beta (rIL-1 beta) stimulated glycosaminoglycan (GAG) production in human synovial fibroblast cultures. A dose-dependent increase in GAG production was found, to a maximum of 500%. Increase was detected at doses as low as 1 pg/ml of rIL-1 beta, reached a maximum at 10-100 pg/ml, and was apparent 10 hours after addition of rIL-1 beta. Stimulation of GAG was always accompanied by increased accumulation of prostaglandin E (PGE) in culture media and by increased collagenase production in approximately one-half the experiments. Indomethacin (5 micrograms/ml) completely inhibited PGE stimulation by rIL-1 beta, but only partially inhibited that of GAG overproduction and had no effect on collagenase production. Hydrocortisone (2 micrograms/ml) inhibited stimulation of all 3 parameters. Stimulation of hyaluronate in synovial cultures prevailed over that of sulfated GAG, which occurred to a lesser extent. Our results support earlier suggestions that interleukin-1 is a major active mononuclear cell factor that is capable of inducing profound changes in connective tissue cell function.


Theoretical explanation of uneven frequency response of time-domain acoustic contrast control method.
Acoustic contrast control (ACC) is one of the most commonly utilized sound zone control methods, which maximizes the ratio of the average squared sound pressure in two control zones. The time-domain formulation of ACC (TACC) is usually preferred since it can optimize the whole bandwidth in a single step and the resulting control filter is guaranteed to be causal. Many researchers have noted that TACC suffers from uneven frequency response. However, a convincing theoretical explanation of this problem is yet to be investigated. In this letter, an asymptotically equivalent frequency-domain form of TACC is constructed, based on which it can be proven that TACC has the tendency of extracting the specific frequency component with the highest contrast. Simulation results validate the efficacy of this theoretical analysis.


Phylogenetic analysis of the CDGSH iron-sulfur binding domain reveals its ancient origin.
The iron-sulfur (2Fe-2S) binding motif CDGSH appears in many important plant and animal proteins that regulate iron and reactive oxygen metabolism. In human it is found in CISD1-3 proteins involved in diabetes, obesity, cancer, aging, cardiovascular disease and neurodegeneration. Despite the important biological role of the CDGSH domain, its origin, evolution and diversification, are largely unknown. Here, we report that: (1) the CDGSH domain appeared early in evolution, perhaps linked to the heavy use of iron-sulfur driven metabolism by early organisms; (2) a CISD3-like protein with two CDGSH domains on the same polypeptide appears to represent the ancient archetype of CDGSH proteins; (3) the origin of the human CISD3 protein is linked to the mitochondrial endosymbiotic event; (4) the CISD1/2 type proteins that contain only one CDGSH domain, but function as homodimers, originated after the divergence of bacteria and archaea/eukaryotes from their common ancestor; and (5) the human CISD1 and CISD2 proteins diverged about 650-720 million years ago, and CISD3 and CISD1/2 share their descent from an ancestral CISD about 1-1.1 billion years ago. Our findings reveal that the CDGSH domain is ancient in its origin and shed light on the complex evolutionary path of modern CDGSH proteins.


Effect of Sixteen Weeks Combined Training on FGF-23, Klotho, and Fetuin-A Levels in Patients on Maintenance Hemodialysis.
Fibroblast growth factor 23 (FGF-23) and its cofactor alfa klotho, are one of the most important factors, directly and indirectly, involved in the process of calcification and atherosclerosis. This study aimed to evaluate the efficacy of a combination of regular exercise during dialysis on quality of life and markers including FGF-23, alfa klotho, and fetuin-A levels. Forty-five hemodialysis patients aged 61 ± 9.02 years and weight 69 ± 11.25 kg were randomly divided into two training, EX (n = 24) and control groups, CON (n = 21). The EX group patients participated in a 16-week combined aerobic and resistance exercise program during dialysis. Bone markers including, FGF-23, klotho, fetuin-A, were measured before and at the end of the study in both groups. Statistical analysis for comparing data change during study by SPSS software and the P value was set at .05. In the control group in the secondary assessment, reduction in quality of life was observed (P < .05). Significant change in growth factor 23, CRP, and fetuin-A was not observed in exercise and control groups (P > .05), however significant rising of klotho was observed in treated patients (P < .05). Also, combined training reduced the amount of phosphorus, parathyroid hormone; significantly (P < .05). This study showed that regular exercise during dialysis improves quality of life and physical functions. No significant change in FGF-23 and CRP were observed during the study. However significant rising of klotho and reduction of iPTH and phosphorous levels were observed in treated patients.


Mechanical testing of a smart spinal implant locking mechanism based on nickel-titanium alloy.
Development and testing of a new spinal implant-locking mechanism based on the special properties of nickel-titanium alloy. To develop a new self-tightening locking mechanism to reduce fretting corrosion at implant junctions. All current implant locking involves tightening of a nut against the rod and screw head to form a coupling. Particulate debris is generated, and the coupling becomes loose because of wear between the rod and locking mechanism (fretting). To avoid this fretting, a new locking mechanism with an automatic retightening effect based on the superelastic and shape-memory properties of nickel-titanium alloy has been developed. The new coupling made of nickel-titanium alloy will tightly lock the rod when temperature increases to 50 degrees C (shape-memory effect). If fretting occurs, the coupling will further tighten itself around the rod (superelastic effect). This new coupling is mechanically tested against 4 current implant couplings. In axial compression, conventional couplings failed between 570 and 740 N, while the new coupling reached 800 N without loosening. In axial rotation, conventional devices failed between 1.8 and 5.3 Nm, while the new coupling reached 6.5 Nm without failure. During testing, the retightening effect could be seen on the force versus displacement plot. To our knowledge, the self-tightening coupling is a new concept not previously described and is attributable to the superior superelastic effect of the new coupling. This implant coupling has the potential to be used as a very low profile system and also in nonfusion technologies in which demands on the coupling would not higher without the protection of spinal fusion.


Midterm functional outcomes in operatively treated adolescent Lisfranc injuries.
This study evaluates the midterm outcomes of Lisfranc injuries in adolescents operatively treated with Kirschner wire or screw fixation. Eight adolescent patients with Lisfranc injuries operatively treated in a single institution were included in this study. The mean duration of follow-up was 3.8 years. Analysis of radiographs with respect to the degree of initial displacement and final reduction was carried out in terms of the intermetatarsal distances. All cases were scored functionally using the American Orthopaedic Foot and Ankle Society Midfoot Scale. We concluded that most operatively treated cases of adolescent Lisfranc injuries will do well at the midterm follow-up, with a mean American Orthopaedic Foot and Ankle Society Midfoot score of 93.4. Level 4 (Case series).


Endovascular Intervention with a Mobile C-Arm in the Operating Room.
Mobile C-arm fluoroscopic X-ray systems are used for various diagnostic imaging and minimally invasive endovascular procedures. One of the greatest advantages of a mobile C-arm is its ability to move around the patient. The purpose of this study was to address the optimal setting of the mobile C-arm and the operating table, as well as the proper position of the operator and assistants for each procedure. In addition, methods to minimize radiation exposure to the operator and medical staff are described. Both the optimal setting and the proper position were classified by 5 types. These include the setting for aortic and inferior vena caval procedures (type I); left lower extremity (LE) intervention with an up-and-over technique (type II); right LE intervention with up-and-over technique, or bilateral LE vascular intervention with antegrade access (type III); arteriovenous fistula/graft intervention (type IV); and central vein catheterization (type V).


Exposure to febrile-range hyperthermia potentiates Wnt signalling and epithelial-mesenchymal transition gene expression in lung epithelium.
As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (i) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (ii) HSF1 is activated at febrile temperatures (38-41 °C) and (iii) hypothermia (32 °C) activates and hyperthermia (39.5 °C) reduces expression of a subset of miRNAs that target protein kinase-Cα (PKCα) and enhance proliferation. We analysed the effect of hypo- and hyperthermia exposure on Wnt signalling by exposing human small airway epithelial cells (SAECs) and HEK293T cells to 32, 37 or 39.5 °C for 24 h, then analysing Wnt-3a-induced epithelial-mesenchymal transition (EMT) gene expression by qRT-PCR and TOPFlash reporter plasmid activity. Effects of miRNA mimics and inhibitors and the HSF1 inhibitor, KNK437, were evaluated. Exposure to 39.5 °C for 24 h increased subsequent Wnt-3a-induced EMT gene expression in SAECs and Wnt-3a-induced TOPFlash activity in HEK293T cells. Increased Wnt responsiveness was associated with HSF1 activation and blocked by KNK437. Overexpressing temperature-responsive miRNA mimics reduced Wnt responsiveness in 39.5 °C-exposed HEK293T cells, but inhibitors of the same miRNAs failed to restore Wnt responsiveness in 32 °C-exposed HEK293T cells. Wnt responsiveness, including expression of genes associated with EMT, increases after exposure to febrile-range temperature through an HSF1-dependent mechanism that is independent of previously identified temperature-dependent miRNAs. This process may be relevant to febrile fibrosing lung diseases, including the fibroproliferative phase of acute respiratory distress syndrome (ARDS) and exacerbations of idiopathic pulmonary fibrosis (IPF).


Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett's esophagus.
Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.


Improving the safety of shoulder arthroscopy in the beach chair position: a prospective randomized trial investigating the effect of compression stockings on cerebral desaturation events in obese patients.
Devastating transient and permanent postoperative neurocognitive complications in previously healthy, low-risk patients have been observed after elective shoulder arthroscopy in the beach chair position (BCP). Continuous monitoring of cerebral oxygen saturation has been recommended to identify cerebral desaturation events (CDEs) and improve patient safety. However, the relatively high cost and limited availability of monitoring may not be cost-effective. More cost-effective and available measures, including the use of thigh-high compression stockings (CS), have been investigated. However, efficacy data of CS usage is limited, especially for obese patients, who have been shown to be at increased risk for CDEs. The purpose of this was study was to determine if the intraoperative addition of thigh-high compression stockings decreases the incidence, frequency, and magnitude of CDEs in obese patients undergoing shoulder arthroscopy in the BCP. Thirty-three patients in the treatment group wore both thigh-high compression stockings (CS) and sequential compression devices (SCDs), and the remaining 33 patients in the control group wore SCDs alone. Cerebral oximetry was monitored during surgery using near-infrared spectroscopy. The incidence of CDEs was equal between groups, with 9 patients (27%) in each experiencing desaturation events. The median number of CDEs per patient was 3 for the control group and 1 for patients wearing CS (P = .29). There was no difference between groups in terms of median time from induction of anesthesia to onset of CDE (P = .79), median time from upright positioning to onset of CDE (P = .60), mean CDE duration per patient (P = .22), and median cumulative CDE duration (P = .19). The median maximal desaturation from baseline was also not different between groups: 27.6% in the control group and 24.3% in the treatment group (P = .35). The combination of thigh-high CS and SCDs did not decrease the incidence, frequency, or magnitude of CDEs in patients undergoing shoulder arthroscopy in the BCP. Twenty-seven percent of patients undergoing shoulder arthroscopy in the BCP demonstrated CDEs with or without the use of CS. Therefore, further research is required to identify cost-effective, minimally invasive, and universally available methods of decreasing the incidence of CDEs during this common surgical procedure.


Endoscopic transluminal necrosectomy in necrotising pancreatitis: a systematic review.
We performed a systematic review to assess the outcome of endoscopic transluminal necrosectomy in necrotising pancreatitis with additional focus on indication, disease severity, and methodological quality of studies. We searched the literature published between January 2005 and June 2013. Cohorts, including patients with (infected) necrotising pancreatitis, undergoing endoscopic necrosectomy were included. Indication, disease severity, and methodological quality were described. The main outcomes were mortality, major complications, number of endoscopic sessions, and definitive successful treatment with endoscopic necrosectomy alone. After screening 581 papers, 14 studies, including 455 patients, fulfilled the eligibility criteria. All included studies were retrospective analyses except for one randomized, controlled trial. Overall methodological quality was moderate to low (mean 5, range 2-9). Less than 50 % of studies reported on pre-procedural severity of disease: mean APACHE-II score before intervention was 8; organ failure was present in 23 % of patients; and infected necrosis in 57 % of patients. On average, four (range 1-23) endoscopic interventions were performed per patient. With endoscopic necrosectomy alone, definitive successful treatment was achieved in 81 % of patients. Mortality was 6 % (28/460 patients) and complications occurred in 36 % of patients. Bleeding was the most common complication. Endoscopic transluminal necrosectomy is an effective treatment for the majority of patients with necrotising pancreatitis with acceptable mortality and complication rates. It should be noted that methodological quality of the available studies is limited and that the combined patient population of endoscopically treated patients is only moderately ill.


Experimental isovolemic haemodilution-induced augmentation of carotid blood flow and oxygen transport through graded carotid stenoses.
The effect of haemodilution without volume expansion (isovolemic haemodilution) was assessed with respect to blood flow and oxygen transport across stenotic lesions of progressive severity in the dog carotid artery. As the mean haematocrit (Hct) was reduced from 40 +/- 1% (+/- SEM) to 32 +/- 0% (p less than 0.001), reductions in vascular resistance were significant across the 90% (p less than 0.001) and 95% (p less than 0.0003) relative carotid stenoses. Isovolemic haemodilution reduced fresh blood viscosity significantly by 27 +/- 3% (p less than 0.001) and 42 +/- 4% (p less than 0.001) at the low shear rates of 10 sec-1 and 1 sec-1 which are typical of low-flow states. Following a 20% reduction in Hct 30 to 35% increase (p less 0.001) in carotid blood flow occurred at non-critical degrees of stenosis while a mean 83% increase (p less than 0.001) occurred at the highly critical 95% relative stenosis. Oxygen transport after a 22% decrease in blood haemoglobin was significantly increased by 28% (p less than 0.01) at the 95% relative stenosis level. These data provide a physiologic rationale for the beneficial effects of haemodilution in acute cerebral ischaemia, cerebral vasospasm and cerebral revascularization or carotid endarterectomy.


A Liver Index and its Relationship to Indices of HCC Aggressiveness.
A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness.


Potential use of rainwater as a tool for fire stations and firefighting: Literature review, environmental and cost assessments.
Few studies in the literature integrate rainwater harvesting and firefighting. Thus, the general objective of this paper was to evaluate the potential use of rainwater as a source of water for firefighting. To do so, two approaches were proposed for the assessment. The first approach was the analysis of the existing literature. Two databases were evaluated as references in engineering fields, of which 32 articles mentioned rainwater as an alternative for firefighting. The main result of the review was the scarcity of articles in the area under study, with some of the existing articles focusing on forest fires. In contrast, others analysed the use of rainwater within the scope of buildings or fire stations. The second approach involved a case study that started by analysing the fire statistics provided by the Military Fire Department of the state of Santa Catarina, Brazil. It was observed that, between 2017 and 2020, building fires represented 25 % of the state's fires and 50 % of the water consumption in firefighting, while the rest of the fire occurrences represented the other half of water consumption. Rainwater can be used not only to reduce the total consumption of potable water but also as a logistics tool towards better response time in the event of a fire. With the firefighting water demand obtained, a Life Cycle Assessment (LCA) approach was performed to assess the potential environmental optimisation in a simplified scope. It was performed in a cradle-to-gate approach, leaving the potential optimisations in transport and logistics apart. Also, a cost assessment was carried out, obtaining a much lower cost for firefighting and providing financial savings for fire stations. As a result, rainwater is expected to decrease environmental impacts, help logistics in fire and save money for fire supression.


Human computation as a new method for evidence-based knowledge transfer in Web-based guideline development groups: proof of concept randomized controlled trial.
Guideline developers use different consensus methods to develop evidence-based clinical practice guidelines. Previous research suggests that existing guideline development techniques are subject to methodological problems and are logistically demanding. Guideline developers welcome new methods that facilitate a methodologically sound decision-making process. Systems that aggregate knowledge while participants play a game are one class of human computation applications. Researchers have already proven that these games with a purpose are effective in building common sense knowledge databases. We aimed to evaluate the feasibility of a new consensus method based on human computation techniques compared to an informal face-to-face consensus method. We set up a randomized design to study 2 different methods for guideline development within a group of advanced students completing a master of nursing and obstetrics. Students who participated in the trial were enrolled in an evidence-based health care course. We compared the Web-based method of human-based computation (HC) with an informal face-to-face consensus method (IC). We used 4 clinical scenarios of lower back pain as the subject of the consensus process. These scenarios concerned the following topics: (1) medical imaging, (2) therapeutic options, (3) drugs use, and (4) sick leave. Outcomes were expressed as the amount of group (dis)agreement and the concordance of answers with clinical evidence. We estimated within-group and between-group effect sizes by calculating Cohen's d. We calculated within-group effect sizes as the absolute difference between the outcome value at round 3 and the baseline outcome value, divided by the pooled standard deviation. We calculated between-group effect sizes as the absolute difference between the mean change in outcome value across rounds in HC and the mean change in outcome value across rounds in IC, divided by the pooled standard deviation. We analyzed statistical significance of within-group changes between round 1 and round 3 using the Wilcoxon signed rank test. We assessed the differences between the HC and IC groups using Mann-Whitney U tests. We used a Bonferroni adjusted alpha level of .025 in all statistical tests. We performed a thematic analysis to explore participants' arguments during group discussion. Participants completed a satisfaction survey at the end of the consensus process. Of the 135 students completing a master of nursing and obstetrics, 120 participated in the experiment. We formed 8 HC groups (n=64) and 7 IC groups (n=56). The between-group comparison demonstrated that the human computation groups obtained a greater improvement in evidence scores compared to the IC groups, although the difference was not statistically significant. The between-group effect size was 0.56 (P=.30) for the medical imaging scenario, 0.07 (P=.97) for the therapeutic options scenario, and 0.89 (P=.11) for the drug use scenario. We found no significant differences in improvement in the degree of agreement between HC and IC groups. Between-group comparisons revealed that the HC groups showed greater improvement in degree of agreement for the medical imaging scenario (d=0.46, P=.37) and the drug use scenario (d=0.31, P=.59). Very few evidence arguments (6%) were quoted during informal group discussions. Overall, the use of the IC method was appropriate as long as the evidence supported participants' beliefs or usual practice, or when the availability of the evidence was sparse. However, when some controversy about the evidence existed, the HC method outperformed the IC method. The findings of our study illustrate the importance of the choice of the consensus method in guideline development. Human computation could be an acceptable methodology for guideline development specifically for scenarios in which the evidence shows no resonance with participants' beliefs. Future research is needed to confirm the results of this study and to establish practical significance in a controlled setting of multidisciplinary guideline panels during real-life guideline development.


Salivary acquired pellicle-inspired DpSpSEEKC peptide for the restoration of demineralized tooth enamel.
Salivary acquired pellicle (SAP) is a layer of proteins and glycoproteins of salivary origin that tightly coat the tooth surface. Statherin is an important part of the SAP. The initial six-peptide sequence DpSpSEEK (where pS denotes phosphorylated serine) of the N-terminus of statherin can be immobilized on a hydroxyapatite (HAP) surface and the negatively charged domains of the DpSpSEEK side chain can catch free Ca2+ in saliva due to the charge adsorption effect. In order to prepare more functional materials based on DpSpSEEK, we designed a cysteine-labeled peptide sequence DpSpSEEKC, which could conjugate other macromolecules by forming a sulfur-based linkage. In this work, we measured the adsorption of DpSpSEEKC to HAP by various methods. We also coated DpSpSEEKC on a demineralized tooth enamel surface to evaluate its biomineralization capacity. The DpSpSEEKC-coated samples were characterized after immersion in artificial saliva for 2 weeks. The results showed that DpSpSEEKC has a strong adsorption capacity to HAP and could induce remineralization on the demineralized tooth enamel surface due to its carboxyl and phosphate groups. Compared with the control samples, the mechanical properties of the DpSpSEEKC-coated samples were obviously improved. In conclusion, DpSpSEEKC can provide a potential method for restoring demineralized tooth enamel.


Taxonomy and physiology of Pseudoxanthomonas arseniciresistens sp. nov., an arsenate and nitrate-reducing novel gammaproteobacterium from arsenic contaminated groundwater, India.
Reductive transformation of toxic arsenic (As) species by As reducing bacteria (AsRB) is a key process in As-biogeochemical-cycling within the subsurface aquifer environment. In this study, we have characterized a Gram-stain-negative, non-spore-forming, rod-shaped As reducing bacterium designated KAs 5-3T, isolated from highly As-contaminated groundwater of India. Strain KAs 5-3T displayed high 16S rRNA gene sequence similarity to the members of the genus Pseudoxanthomonas, with P. mexicana AMX 26BT (99.25% similarity), P. japonensis 12-3T (98.9 0%), P. putridarboris WD-12T (98.02%), and P. indica P15T (97.27%) as closest phylogenetic neighbours. DNA-DNA hybridization study unambiguously indicated that strain KAs 5-3T represented a novel species that was separate from reference strains of P. mexicana AMX 26BT (35.7%), P. japonensis 12-3T (35.5%), P. suwonensis 4M1T (35.5%), P. wuyuanensis XC21-2T (35.0%), P. indica P15T (32.5%), P. daejeonensis TR6-08T (32.0%), and P. putridarboris WD12T (22.1%). The DNA G+C content of strain KAs 5-3T was 64.9 mol %. The predominant fatty acids were C15:0 (37.4%), C16:0 iso (12.6%), C17:1 iso ω9c (10.5%), C15:0 anteiso (9.5%), C11:0 iso 3-OH (8.5%), and C16:1 ω7c/ C16:1 ω6c (7.5%). The major polar lipids were diphosphatidylglycerol, phosphatidyldimethylethanolamine, phosphatidylcholine, and two unknown phospholipids (PL1, PL2). Ubiquinone 8 (Q8) was the predominant respiratory quinone and spermidine was the major polyamine of the strain KAs 5-3T. Cells of strain KAs 5-3T showed the ability to use O2, As5+, NO3-, NO2-, and Fe3+ as terminal electron acceptors as well as to reduce As5+ through the cytosolic process under aerobic incubations. Genes encoding arsenate reductase (arsC) for As-detoxification, nitrate- and nitrite reductase (narG and nirS) for denitrification were detected in the strain KAs 5-3T. Based on taxonomic and physiological data, strain KAs 5-3T is described as a new representative member of the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas arseniciresistens sp. nov. is proposed. The type strain is KAs 5-3T (= LMG 29169T = MTCC 12116T = MCC 3121T).


Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication.
Infection with coronavirus rearranges the host cell membrane to assemble a replication/transcription complex in which replication of the viral genome and transcription of viral mRNA occur. Although coexistence of nsp3 and nsp4 is known to cause membrane rearrangement, the mechanisms underlying the interaction of these two proteins remain unclear. We demonstrated that binding of nsp4 with nsp3 is essential for membrane rearrangement and identified amino acid residues in nsp4 responsible for the interaction with nsp3. In addition, we revealed that the nsp3-nsp4 interaction is not sufficient to induce membrane rearrangement, suggesting the participation of other factors such as host proteins. Finally, we showed that loss of the nsp3-nsp4 interaction eliminated viral replication by using an infectious cDNA clone and replicon system of SARS-CoV. These findings provide clues to the mechanism of the replication/transcription complex assembly of SARS-CoV and could reveal an antiviral target for the treatment of betacoronavirus infection.


Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser Syndrome in a girl with a 46, XX karyotype: A case report and review of literature.
Mayer-Rokitansky-Kuster-Hauser (MRKH) is a characteristic syndrome in which the Mullerian structures are absent or rudimentary. It is also associated with anomalies of the genitourinary and skeletal systems. Its association with gonadal dysgenesis is extremely rare and appears to be fortuitous, independent of chromosomal anomalies. We report such a case in a 21-year-old girl who presented primary amenorrhea and impuberism. The endocrine study revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46, XX. No chromosome Y was detected at the fluorescence in situ hybridization (FISH) analysis. Internal genitalia could not be identified on the pelvic ultrasound and pelvic magnetic resonance imaging. Laparoscopy disclosed concomitant ovarian dysgenesis and MRKH syndrome. There were no other associated malformations. Hormonal substitution therapy with oral conjugated estrogens was begun. The patient has been under regular follow-up for the last two years and is doing well.


Electron-beam writing of large-area Fresnel zone plates.
High-resolution X-ray microscopy requires advanced fabrication technology for Fresnel zone plates (FZPs). As the resolution of an FZP depends on the width of the outermost zone, fine zone patterns for objective lenses have to be replicated. On the other hand, to achieve highly condensed X-ray beams by using FZPs for condenser lenses, large-field replication is required. A method of pattern replication of FZPs for X-ray microscopy is reported. Utilizing a 30 keV electron-beam writing tool and an FZP-generation computer program, FZP patterns for a condenser lens 1 mm in diameter with an outermost-zone width of 0.2 micro m and for an objective lens 0.5 mm in diameter with an outermost-zone width of 0.1 micro m were replicated.


Mitochondrial complex 1 inhibition increases 4-repeat isoform tau by SRSF2 upregulation.
Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by intracellular aggregation of the microtubule-associated protein tau. The tau protein exists in 6 predominant isoforms. Depending on alternative splicing of exon 10, three of these isoforms have four microtubule-binding repeat domains (4R), whilst the others only have three (3R). In PSP there is an excess of the 4R tau isoforms, which are thought to contribute significantly to the pathological process. The cause of this 4R increase is so far unknown. Several lines of evidence link mitochondrial complex I inhibition to the pathogenesis of PSP. We demonstrate here for the first time that annonacin and MPP(+), two prototypical mitochondrial complex I inhibitors, increase the 4R isoforms of tau in human neurons. We show that the splicing factor SRSF2 is necessary to increase 4R tau with complex I inhibition. We also found SRSF2, as well as another tau splicing factor, TRA2B, to be increased in brains of PSP patients. Thereby, we provide new evidence that mitochondrial complex I inhibition may contribute as an upstream event to the pathogenesis of PSP and suggest that splicing factors may represent an attractive therapeutic target to intervene in the disease process.


Quantitative source identification of dioxin-like PCBs in Yokohama, Japan, by temperature dependence of their atmospheric concentrations.
The source and environmental behavior of dioxin-like polychlorinated biphenyls (PCBs) together with other PCBs and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) were evaluated based on analysis of variations in their atmospheric concentrations in Yokohama, Japan. Potential factors responsible for variations in the atmospheric concentrations of the congeners were investigated by principal component analysis and multiple regression analysis of the data. Two major variations were seen: one had strong temperature dependence, while the other had no significant temperature dependence. A possible explanation for this difference is that the former is related to congeners released by volatilization (e.g., volatilization from commercial PCB products and past polluted environments), while the latter is related to congeners emitted from thermal processes. The relative contributions of dioxin-like PCBs released by volatilization and those emitted from thermal processes were estimated based on the temperature dependence of the atmospheric concentrations. The results suggest that both dioxin-like PCBs emitted from thermal processes and those released by volatilization are significant sources of air pollution in this area in terms of the toxic equivalent (TEQ) for dioxin-like PCBs. We demonstrated that the present approach based on variations in atmospheric concentrations can be useful in providing a qualitative as well as quantitative understanding of source information.


Overview on the Surface Functionalization Mechanism and Determination of Surface Functional Groups of Plasma Treated Carbon Nanotubes.
The use of carbon materials for many applications is due to the unique diversity of structures and properties ranging from chemical bonds between the carbon atoms of the materials to nanostructures, crystallite alignment, and microstructures. Carbon nanotubes and other nanoscale carbonaceous materials draw much attention due to their physical and chemical properties, such as high strength, high resistance to corrosion, electrical and thermal conductivity, stability and a qualified adsorbent. Carbon-based nanomaterials, which have a relatively large specific area and layered structure, can be used as an adsorbent for efficient removal of organic and inorganic contaminants. However, one of the biggest obstacles to the development of carbon-based nanomaterials adsorbents is insolubility and the lack of functional groups on the surface. There are several approaches to introduce functional groups on carbon nanotubes. One of these approaches, plasma applications, now has an important place in the creation of surface functional groups as a flexible, fast, and environmentally friendly method. This review focuses on recent information concerning the surface functionalization and modification of plasma treated carbon nanotube. This review considers the surface properties, advantages, and disadvantages of plasma-applied carbon nanotubes. It also examines the reaction mechanisms involved in the functional groups on the surface.


Use of an internet "viral" marketing software platform in health promotion.
Health-related websites have become a common tool for public health authorities to inform the general public of their health promotion information and programs. However, building traffic in the cluttered health Internet universe is becoming increasingly complex, costly, and challenging for governmental health promotion websites. In 2006, the Canadian Health Network (CHN), a cooperative program made up of the Public Health Agency of Canada (PHAC) and some 20 health non-governmental organizations (NGOs), was looking for an affordable marketing tool for the promotion of its website and contents to specific populations. To test new and innovative marketing tools for a health promotion website in Canada. Within the context and constraints of a governmental health promotion website, an adaptation of a commercial Internet viral marketing software platform was developed and implemented under the name "The Crazy Race". This process was done interactively between seven NGOs and the CHN staff. The communication objectives were (a) to provide a meaningful visit that could communicate important public health messages, and (b) to increase subscriptions to its e-newsletter. A nine-step standardized Web-user experience (Internet path) was thus defined and experimented with under a pre-determined operating budget of less then Can$50,000, mainly paid for by participating organizations on a pay-per-performance basis. An initial group of 215 people were sent an invitation to participate in the campaign. Over its 15-day duration, the campaign generated by itself and without any media support a total of 110,200 Web user participants who registered and sent a total of 439,275 invitations (2% of the Canadian Web-user population of 21.8 million in 2006). The epidemic self-dissemination of the campaign occurred in both French and English populations and spread across all age groups. Two-thirds of the participants were women. The use of an Internet viral marketing platform proved to be effective in bringing thousands of Web users to discover and explore a governmental health promotion website. The exponential growth of the person-to-person dissemination generated by the campaign indicates that public health messages have high viral propagation potential on the Internet ("virulence") when they are presented in the context of an enjoyable online game. This could constitute a promising method to create affordable mass audience public health campaigns, both in Canada and internationally.


Optimization of Fermentation Condition for Echinacoside Yield Improvement with Penicillium sp. H1, an Endophytic Fungus Isolated from Ligustrum lucidum Ait Using Response Surface Methodology.
(1) Background: Application of echinacoside has become increasingly important for its significant biological activities. However, there are many disadvantages in existing synthesis methods such as contaminating the environment, harsh reaction conditions and so on. Therefore, it is urgent to invent a novel alternative method that can increase the yield of echinacoside. (2) Methods: In this study, we isolated and purified an endophyte from the leaves of Ligustrum lucidum Ait. Then, we improved the yield of echinacoside by optimizing the fermentation condition with an endophytic fungus. Penicillium sp. H1 was isolated from Ligustrum lucidum Ait. In addition, response surface methodology was used to optimize the fermentation condition. (3) Results: The results indicate that the maximal yield of echinacoside (37.16 mg/L) was obtained when inoculation rate, temperature and days were 13.98%, 27.85 °C and 26.06 days, respectively. The yield of echinacoside was 150.47 times higher under the optimal conditions than under the control conditions. The results indicate that the yield of echinacoside could be improved with endophytic fermentation by optimizing the fermentation condition. We provide an alternative method for echinacoside production by endophytic fermentation in this paper. It may have a profound effect on the application of echinacoside.