Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation.
Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors.


Measurement techniques, modeling strategies and pitfalls to avoid when implementing a mini MLC in a non dedicated planning system.
Ghent University Hospital investigated the feasibility of the Pinnacle system for planning intracranial stereotactic treatments. The aim was to perform precise dose computation using the collapsed cone engine for treatment delivery with the Moduleaf mini-MLC mounted on an Elekta accelerator. The Moduleaf was commissioned using dose rate corrected data recorded by a diamond detector and using data measured by cylindrical chambers each limited to restricted field sizes. Automatic modeling resulted in clinical relevant dose errors up to 10%. Using manual modeling in Pinnacle, for clinical applicable fields a 2%/2 mm agreement between modeled data and measurements was obtained. The overall accuracy of the collapsed cone algorithm is within tolerances for single fraction stereotactic treatments.


Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer.
Cervical cancer remains a serious health problem till now, with nearly 500,000 women cases diagnosed each year around the world. Long noncoding RNA (lncRNA) is a novel class of RNA transcripts (>200 nucleotides in length) participating in gene transcription, cell proliferation, differentiation, and drug resistance. This study aimed to explore the regulatory relationship among lncRNA NCK1-AS1, miR-134-5p, and MutS protein homolog 2 (MSH2), so that the resistance against cisplatin in cervical cancer treatment could be better understood. Comprehensive lncRNA profiling analysis was performed to screen lncRNAs differentially expressed in cervical cancer. The expression patterns of miR-134-5p, NCK1-AS1, and MSH2 were evaluated in cancerous tissues and adjacent normal tissues obtained from 75 cervical cancer patients. Subsequently, anti-NCK1-AS1 small interfering RNA, miR-134-5p mimics, and miR-134-5p inhibitors were transfected into cervical cancer cells, and the effects of these transcripts on cisplatin resistance and cell apoptosis were investigated. The regulatory relationship among NCK1-AS1, miR-134-5p, and MSH2 was identified using a dual-luciferase reporter gene assay, and the results were further validated by RNA pull-down and RNA immunoprecipitation assays. Based on the microarray data of GSE63514 and GSE27678, NCK1-AS1 was upregulated in cervical cancer. Increased expression of NCK1-AS1, MSH2, and decreased expression of miR-134-5p were observed in cervical cancer tissues. In addition, NCK1-AS1 competitively bound to miR-134-5p to regulate MSH2. Therefore, si-NCK1-AS1 and miR-134-5p mimic both reduced MSH2 activity and increased cisplatin-induced apoptosis in cervical cancer cells. Taken together, NCK1-AS1 may become a novel target in improving the chemotherapeutic response and survival of cervical cancer patients.


Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.
Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-β/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.


Residual limb shear strain during gait is correlated with patient reported outcomes for persons with transfemoral amputation.
The purpose of this study was to measure residual limb skin strain and strain rate within the socket during gait in individuals with a transfemoral amputation and to determine if skin strain during gait is related to patient-reported comfort and function. It was hypothesized that greater skin strain and skin strain rate would correlate to worse patient-reported outcomes. It was also hypothesized that skin strain would progressively increase from the distal to the proximal end of the residuum and maximum strain would occur shortly after heel strike. Dynamic biplane radiography (DBR), combined with conventional motion capture, was used to measure skin deformation within the socket during treadmill walking for 10 persons with unilateral transfemoral amputation. The questionnaire for persons with a transfemoral amputation (Q-TFA) was administered to assess prosthetic use, mobility, health problems, and global health. Q-TFA Prosthetic Use score and Problem score were negatively correlated with the peak shear strains in the proximal and distal regions of the residuum, respectively. Maximum shear strain increased progressively from proximal to distal regions of the residual limb. Within-subject variability in shear strain waveforms during gait was 0.7% or less, but between-subject variability was 3.3% to 5.0% shear. This study demonstrates that skin shear within the socket of persons with transfemoral amputation can be measured during gait using DBR and the results suggest that greater skin shear in the proximal region of the socket is related to decreased prosthetic use.


Predictors of a clinical high risk status among individuals with a family history of psychosis.
Risk for psychosis can be assessed on the basis of genetic risk, referred to in the literature as family high risk (FHR) or through the presence of clinical high risk symptoms (CHR). Recent studies have also shown that certain risk factors (i.e. trauma, cannabis, migration) may play a role in the development of psychosis, possibly in combination with one another and in particular in combination with a family history of psychosis. It is unknown which risk factors may play a role in the prediction of CHR status among individuals whom are already genetically vulnerable. This study compared FHR individuals who also met CHR criteria to FHR individuals who did not on various risk factors, psychopathology and functioning. Participants were 25 who met FHR and CHR criteria (FHR + CHR) as determined by Structured Interview for Prodromal Syndromes, 25 who met only FHR criteria (FHR-non-CHR), and 25 healthy controls. A binary logistic regression was performed to determine the best predictors of belonging to the FHR + CHR group. FHR + CHR and FHR-non CHR were significantly different on measures of age first tried cannabis (F = 3.65, p < 0.05) and IQ (F = 3.32, p < 0.05). FHR groups also differed on self-reported anxiety (F=11.79, p < 0.001) and current scores of social (F = 19.74, p < 0.0001) and role (F = 17.71, p < 0.0001) functioning. The most significant predictor of belonging to the FHR + CHR group was an earlier age of cannabis use (OR = 0.44, p = 0.05). These preliminary results are promising in determining potential risk factors for the development of psychosis in those who are at risk for psychosis on the basis of a family history.


Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells.
The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor present in most cell types. Upon ligand binding, the GR is activated and translocates into the nucleus where it transmits the anti-inflammatory actions of glucocorticoids. Here, we describe the ligand-independent activation of GR by the beta2-adrenergic receptor (beta2-AR) agonists, salbutamol and salmeterol, in primary human lung fibroblasts and vascular smooth muscle cells. Immunohistochemistry demonstrated expression of GR and the beta2-AR by fibroblasts and vascular smooth muscle cells. Treatment of the cells with the beta2-AR agonists, salbutamol or salmeterol, resulted in translocation of GR into the nucleus beginning at 30 min, as shown by immunohistochemistry and Western blotting of cytosolic and nuclear cell extracts. In comparison, activation of GR induced by the corticosteroids dexamethasone and fluticasone occurred at the same time after treatment (30 min) but resulted in a more complete depletion of GR from the cytosolic compartment. Electrophoretic mobility shift assays confirmed that nuclear GR, activated by both beta2-AR agonists and glucocorticoids, actively bound to the GR consensus sequence (GR element). Functional activation of the GR was confirmed by a Luciferase reporter gene assay, using a GR driven promoter fragment from the p21((WAF1/CIP1)) gene. The effects of the beta2-AR agonists, salbutamol and salmeterol, were dependent upon binding to the beta2-AR, because blocking of beta2-AR with propranolol abrogated GR activation. GR activation appeared to involve cAMP. In summary, these data show that beta2-AR agonists are potent activators of GR. Ligand-independent activation of GR by beta2-AR agonists may substantially mediate the anti-inflammatory actions of these drugs observed in vitro and in vivo.


Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer.
We hypothesized that radiation-induced thoracic toxicity (RITT) of the lung, esophagus and pericardium share a similar mechanism, and aimed to examine whether genetic variation of transforming growth factor-beta1 (TGFβ1), tissue plasminogen activator (tPA) and angiotensin converting enzyme (ACE), are associated with RITT in patients with non-small-cell lung cancer (NSCLC). Patients with stage I-III NSCLC were enrolled and received radiotherapy (RT). Blood samples were obtained pre-RT and at 4 to 5 weeks during RT, and plasma TGF-β1 was measured using an enzyme-linked immunosorbent assay. The DNA samples extracted from blood pre-RT were analyzed for the following frequent genetic variations: TGFβ1 509C/T, tPA -7351 C/T, and ACE I/D. RITT score was defined as the sum of radiation-induced toxicity grades in esophagus, lung, and pericardium. Seventy-six NSCLC patients receiving definitive RT were enrolled. Patients with TGFβ1 509CC had higher mean grade of esophagitis (1.4 ± 0.2 versus 0.8 ± 0.2, p = 0.019) and RITT score (2.6 ± 0.3 versus 1.6 ± 0.3, p = 0.009) than T allele carriers. Although no significant relationship was observed between RITT and the tPA or ACE variants individually, patients with any high-risk alleles (tPA CC or ACE D or TGFβ1 509CC) had significantly higher grade of developing combined RITT (p < 0.001). Patients with TGFβ1 509CC had greater increase of plasma TGF β1 levels at 4 to 5 weeks during RT than T allele carriers did (CC 1.2 ± 0.2 versus T 0.7 ± 0.1, p = 0.047). This exploratory study demonstrated that sensitivity of radiation toxicity may be determined by genomic factors associated with TGFβ1 and genes involved in TGFβ1 pathway.


Sterile splenic abscesses in systemic Weber-Christian disease. Unique source of abdominal pain.
A patient with Weber-Christian disease and relapsing abdominal pain due to sterile splenic abscesses is presented. Histologically, acute and chronic inflammation with focal suppurative infiltrates of phagocytosed fat was detected in the absence of vascular or embolic disease, infection, or other apparent cause. Abdominal discomfort, an uncommon manifestation of Weber-Christian disease, usually is related to mesenteric panniculitis. Sterile splenic abscesses represent a previously undescribed complication of Weber-Christian disease, and another source of abdominal pain in this disorder. Although the precise pathophysiology of sterile splenic abscess formation in Weber-Christian disease is unknown, splenectomy is an effective means of alleviating pain.


Computational tools for the analysis of heteroatom groups and their neighbours in protein tertiary structure.
A number of Protein Data Bank (PDB) entries contain heteroatoms defined as HETATM. These include the atomic co-ordinates mainly for heteroatom groups, such as cofactors, coenzymes, prosthetic groups, metal ions, sugars, drugs, peptides, heavy-atom derivatives, non-standard amino acid residues/nucleotides, water molecules and so on. In order to evaluate the different heteroatom (Het) groups and their distribution in protein tertiary structure, we have extracted these from all proteins in the PDB and provided the data in an easily accessible format at the following website. The data can be queried on the PDB code, protein name/description, Het Group code or Het Group name. Further, we have also developed a web-based software application that reports neighbouring atoms evaluated by a "user-defined" distance cut-off value (in Angstrom units), either between a specific Het Group or all Het Groups in a given PDB with amino acid residues and water molecules in the corresponding protein, or neighbours for only all the amino acid residues in the given PDB with respect to Het Groups and water molecules. Together, the database and software applications are useful to gather information that can be further analyzed in order to obtain insights into the preferred interactions of heteroatom groups in proteins, study their binding mode, design novel molecules or to annotate protein function.


A procedure to design a Permeable Adsorptive Barrier (PAB) for contaminated groundwater remediation.
A procedure to optimize the design of a Permeable Adsorptive Barrier (PAB) for the remediation of a contaminated aquifer is presented in this paper. A computer code, including different routines that describe the groundwater contaminant transport and the pollutant capture by adsorption in unsteady conditions over the barrier solid surface, has been developed. The complete characterization of the chemical-physical interactions between adsorbing solids and the contaminated water, required by the computer code, has been obtained by experimental measurements. A case study in which the procedure developed has been applied to a tetrachloroethylene (PCE)-contaminated aquifer near a solid waste landfill, in the district of Napoli (Italy), is also presented and the main dimensions of the barrier (length and width) have been evaluated. Model results show that PAB is effective for the remediation of a PCE-contaminated aquifer, since the concentration of PCE flowing out of the barrier is everywhere always lower than the concentration limit provided for in the Italian regulations on groundwater quality.


Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions.
Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation sites, and greater sensitivity of SIRT3-targeted sites to chemical acetylation in vitro and fasting-induced acetylation in vivo, suggest a nonenzymatic mechanism of acetylation. Our data indicate that most mitochondrial acetylation occurs as a low-level nonenzymatic protein lesion and that SIRT3 functions as a protein repair factor that removes acetylation lesions from lysine residues.


Osteoarthritis year in review 2017: genetics and epigenetics.
The purpose of this review is to describe highlights from original research publications related to osteoarthritis (OA), epigenetics and genomics with the intention of recognising significant advances. To identify relevant papers a Pubmed literature search was conducted for articles published between April 2016 and April 2017 using the search terms 'osteoarthritis' together with 'genetics', 'genomics', 'epigenetics', 'microRNA', 'lncRNA', 'DNA methylation' and 'histone modification'. The search term OA generated almost 4000 references. Publications using the combination of descriptors OA and genetics provided the most references (82 references). However this was reduced compared to the same period in the previous year; 8.1-2.1% (expressed as a percentage of the total publications combining the terms OA and genetics). Publications combining the terms OA with genomics (29 references), epigenetics (16 references), long non-coding RNA (lncRNA) (11 references; including the identification of novel lncRNAs in OA), DNA methylation (21 references), histone modification (3 references) and microRNA (miR) (79 references) were reviewed. Potential OA therapeutics such as histone deacetylase (HDAC) inhibitors have been identified. A number of non-coding RNAs may also provide targets for future treatments. There continues to be a year on year increase in publications researching miRs in OA (expressed as a percentage of the total publications), with a doubling over the last 4 years. An overview on the last year's progress within the fields of epigenetics and genomics with respect to OA will be given.


Targeting mitochondrial function and proteostasis to mitigate dynapenia.
Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age. One key mechanism to maintain proteostasis is protein turnover, which is an energetically costly process. When there is a mismatch between cellular energy demands and energy provision, inelastic processes related to metabolism are maintained, but there is competition for the remaining energy between the elastic processes of somatic maintenance and growth. With aging, mitochondrial dysfunction reduces ATP generation capacity, constraining the instantaneous supply of energy, thus compromising growth and somatic maintenance processes. Further, with age the need for somatic maintenance increases because of the accumulation of protein damage. In this review, we highlight the significant role mitochondria have in maintaining skeletal muscle proteostasis through increased energy provision, protein turnover, and substrate flux. In addition, we provide evidence that improving mitochondrial function could promote a cellular environment that is conducive to somatic maintenance, and consequently for mitigating dynapenia. Finally, we highlight interventions, such as aerobic exercise, that could be used to improve mitochondrial function and improve outcomes related to dynapenia.


Biological characterization of two marine Bdellovibrio-and-like organisms isolated from Daya bay of Shenzhen, China and their application in the elimination of Vibrio parahaemolyticus in oyster.
Bdellovibrio-and-like organisms (BALOs) are a group of highly motile delta-proteobacteria that prey on other gram-negative bacteria. However, nothing is known of the application potential of marine BALOs in safeguarding seafood safety. Here, biological characterization of two marine BALOs strains and their application in the elimination of Vibrio parahaemolyticus in oyster (Crassostrea ariakensis) at the laboratory scale were investigated. BALOs strains BDH12 and BDHSH06 were isolated from sediment of Daya bay in Shenzhen of China, with Shewanella putrefaciens strain 12 and V. parahaemolyticus strain SH06 as preys, respectively, when using double layer agar technique. They were identified as BALOs morphologically by transmission electron microscopy, while partial 16S rDNA sequencing analysis revealed that they showed no close relationships with members of the known genera Bdellovibrio, Bacteriolyticum, Bacteriovorax, or Peredibacter. Biological characterizations revealed that both strains had the optimal pH, salinity and temperature at 7.2, 3% and 30 °C, correspondingly. They could not utilize autoclaved, dead cells as hosts. Prey range analysis revealed that individually, BDH12 and BDHSH06 lysed 82.5% (47 strains) and 84.2% (48 strains) of the total 57 preys tested respectively. In combination, they lysed 98.2% (56 of 57) strains. All strains of V. parahaemolyticus, Vibrio cholerae and Vibrio alginolyticus tested could be lysed by both strains. A 7-day laboratory-scale V. parahaemolyticus elimination experiment in oyster showed that in the control, the cell counts of total vibrios and V. parahaemolyticus strain Vp plus in water and in oyster intestines were on the rise, whereas in the BALOs treated groups, their numbers were down from 8.09±0.05 log CFU/ml and 8.02±0.04 log CFU/ml to 2.39±0.01 log CFU/ml and 2.33±0.01 log CFU/ml, respectively. The same patterns could also be observed in oyster intestines. Results of this study indicate the feasibility of using BALOs to biologically control or even eliminate V. parahaemolyticus in seafood oyster.


Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells.
Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.


Subjective cognitive decline in Brazil: Prevalence and association with dementia modifiable risk factors in a population-based study.
Subjective cognitive decline (SCD) may be an early symptom of Alzheimer's disease. We aimed to estimate the prevalence of SCD in Brazil and its association with dementia modifiable risk factors. We used data of 8138 participants from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a population-based study that included clinical and demographic variables of individuals across the country. We calculated the prevalence of SCD and its association with dementia modifiable risk factors. We found that the prevalence of SCD in Brazil was 29.21% (28.22%-30.21%), varying according to region, sex, and age. SCD was strongly associated with hearing loss, low education, psychological distress, Brown/Pardo and Black races. The prevalence of SCD in Brazil is higher than in high-income countries. Brown/Black races and dementia modifiable risk factors were associated with SCD. Public strategies that target SCD may help mitigate the incidence of dementia.


Effects of treatment in the levels of circulating cytokines and growth factors in cystic fibrosis and dialyzed patients by multi-analytical determination with a biochip array platform.
Chronic inflammatory diseases need non-invasive sensitive, reliable and predictive clinical biomarkers for diagnosis and monitoring therapy. Since inflammation is a complex phenomenon, simultaneous evaluation of different analytes in the same sample may help in defining this complexity and in developing specific anti-inflammatory intervention strategies. In this study, we used a biochip array system capable of measuring 12 cytokines and growth factors (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1 α, IL-1 β, IFN-γ, TNF-α, MCP-1, VEGF, and EGF) in three groups: 97 control subjects; 24 cystic fibrosis (CF) patients before and during the antibiotic treatment (6 and 15days) for acute pulmonary exacerbation as well as 15days after the withdrawal of therapy; 22 children and young adults on chronic hemodialysis (HD) at the beginning and at the end of a standard HD session. CF patients in acute exacerbation displayed higher IL-2, IL-6, VEGF and MCP-1 levels than the control subjects. IL-6 significantly decreased during therapy (P<0.01) but not 15days after the withdrawal of therapy. IL-8 and EGF levels were significantly lower after 15days from the interruption of therapy (P<0.05 and P<0.01 respectively). Regression analysis showed that IL-4 and IL-6 correlated with the amelioration of the respiratory function during therapy. Patients on HD displayed higher IL-6 but lower IL-2, IL-4, IL-8, IFN-γ and EGF levels than control subjects. Serum levels of IL-8, IL-10 and IFN-γ were significantly higher at the end of the HD session (P<0.05 for all three). A biochip array allowed to define a pattern of cytokines/growth factors associated with an acute exacerbation in CF patients and IL-4 and IL-6 as predictors of response to therapy. In younger HD patients, we identified a biomarker pattern which is different from that of older patients. Finally, further studies are warranted to examine the role of these biomarkers in the pathogenesis of complications in HD patients.


Salicylic Acid Biosynthetic Genes Expressed in Pseudomonas fluorescens Strain P3 Improve the Induction of Systemic Resistance in Tobacco Against Tobacco Necrosis Virus.
ABSTRACT Application of salicylic acid induces systemic acquired resistance in tobacco. pchA and pchB, which encode for the biosynthesis of salicylic acid in Pseudomonas aeruginosa, were cloned into two expression vectors, and these constructs were introduced into two root-colonizing strains of P. fluorescens. Introduction of pchBA into strain P3, which does not produce salicylic acid, rendered this strain capable of salicylic acid production in vitro and significantly improved its ability to induce systemic resistance in tobacco against tobacco necrosis virus. Strain CHA0 is a well-described biocontrol agent that naturally produces salicylic acid under conditions of iron limitation. Introduction of pchBA into CHA0 increased the production of salicylic acid in vitro and in the rhizosphere of tobacco, but did not improve the ability of CHA0 to induce systemic resistance in tobacco. In addition, these genes did not improve significantly the capacity of strains P3 and CHA0 to suppress black root rot of tobacco in a gnotobiotic system.


Antibiotic prescribing trends in a paediatric sub-population in Ireland.
Little is known about antibiotic prescribing in Irish children. This study aims to examine antibiotic prescribing patterns in Irish children and associated costs and to compare this with European findings. A retrospective analysis of the Irish Health Services Executive (HSE) pharmacy claims database 2004-2009 for the General Medical Services (GMS) scheme for dispensed medications. This represents 28% of Irish children but over-represents lower socio-economic groups. Overall prescribing rates were reported over time (2004-2009), age (0-4, 5-11, 12-15 years) and gender. Statistical comparison is made using negative binomial regression. Overall prescribing rates for the most commonly prescribed drugs were calculated. Associated cost of prescribing also was calculated. European prescribing data were retrieved from the literature. Rates remained stable from 2004 (631/1000 GMS population; 95%CI 628-634) to 2009 (621/1000; 95%CI 618-624). An interaction effect emerged between gender and age. Rates were generally higher for girls, except for the boys aged 0-4 years. The preferred choice of agents changed across years, with co-amoxiclav becoming the most prescribed drug in 2009 (308/1000; 95%CI 306-310). The total cost of antibiotics increased from €4.4 million in 2004 to €6.0 million in 2009. Higher overall rates of antibiotic prescribing emerged compared with available European data. Differences were observed between prescribing of some first-line and second-line drugs. Age and gender trends are consistent with international literature. However, Ireland has higher overall prescribing rates relative to some European countries. This suggests that a quality improvement in prescribing intervention is warranted.


A study of six cases of de Lange Amsterdam dwarf syndrome, with special attention to voice, speech and language characteristics.
From a survey of southern Scotland, six severly handicapped subjects (age-range 8 to 22 years) were established by firm criteria as suffering from the de Lange Amsterdam Dwarf syndrome. They showed a high incidence of behaviour disturbance. Language development was retarded and all but one of the subjects were dysphonic. A connection may exist between the glottal "fry" (an unperiodical phonation of the vocal folds in a frequency below the normal pitch register) observed in the cries of the younger non-speaking cases and the hoarseness in the speech of the older subjects.


Helium-based cold atmospheric plasma-induced reactive oxygen species-mediated apoptotic pathway attenuated by platinum nanoparticles.
Plasma is generated by ionizing gas molecules. Helium (He)-based cold atmospheric plasma (CAP) was generated using a high-voltage power supply with low-frequency excitation (60 Hz at 7 kV) and He flow at 2 l/min. Platinum nanoparticles (Pt-NPs) are potent antioxidants due to their unique ability to scavenge superoxides and peroxides. These features make them useful for the protection against oxidative stress-associated pathologies. Here, the effects of Pt-NPs on He-CAP-induced apoptosis and the underlying mechanism were examined in human lymphoma U937 cells. Apoptosis was measured after cells were exposed to He-CAP in the presence or absence of Pt-NPs. The effects of combined treatment were determined by observing the changes in intracellular reactive oxygen species (ROS) and both mitochondrial and Fas dependent pathway. The results indicate that Pt-NPs substantially scavenge He-CAP-induced superoxides and peroxides and inhibit all the pathways involved in apoptosis execution. This might be because of the SOD/catalase mimetic effects of Pt-NPs. These results showed that the Pt-NPs can induce He-CAP desensitization in human lymphoma U937 cells.


High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans.
Combat veterans are at high risk for the development of posttraumatic stress disorder (PTSD) and substance use disorders. Ketamine has been shown to be an effective treatment for numerous mental health disorders, although research on its efficacy in combat-related PTSD in veterans is very limited. The study population consisted of 30 US military veterans with combat-related PTSD. Participants underwent a standard induction series of six 1-hour ketamine infusions with the goal of obtaining a transpersonal dissociative experience. Participants were given a series of self-report questionnaires to assess for changes in symptoms of depression, PTSD, and substance use prior to the first and sixth infusions. Symptoms of depression as measured by change in score on the Patient Health Questionnaire decreased significantly from an average of 18.9 to 9.5 (P < .001). Similarly, symptoms of PTSD as measured by change in score on the PSTD Checklist for DSM-5 dropped significantly from an average of 56.2 to 31.3 (P < .001). Self-reported levels of substance use did not significantly decrease during the study period, although the level of use trended down. This observational study suggests that high-dose ketamine infusion therapy, which induced a transpersonal dissociative experience, could be a valuable tool in the treatment of combat-related PTSD. Further study is needed to better elucidate ketamine's mechanism of action with regards to the treatment of PTSD.


Qualitative Description of Global Health Nursing Competencies by Nursing Faculty in Africa and the Americas.
to analyze qualitative comments from four surveys asking nursing faculty to rate the importance of 30 global health competencies for undergraduate nursing programs. qualitative descriptive study that included 591 individuals who responded to the survey in English (49 from Africa and 542 from the Americas), 163 who responded to the survey in Spanish (all from Latin America), and 222 Brazilian faculty who responded to the survey in Portuguese. Qualitative comments were recorded at the end of the surveys by 175 respondents to the English survey, 75 to the Spanish survey, and 70 to the Portuguese survey. Qualitative description and a committee approach guided data analysis. ten new categories of global health competencies emerged from the analysis. Faculty also demonstrated concern about how and when these competencies could be integrated into nursing curricula. the additional categories should be considered for addition to the previously identified global health competencies. These, in addition to the guidance about integration into existing curricula, can be used to guide refinement of the original list of global health competencies. Further research is needed to seek consensus about these competencies and to develop recommendations and standards to guide nursing curriculum development.


Preparation and characterization of a hierarchical porous char from sewage sludge with superior adsorption capacity for toluene by a new two-step pore-fabricating process.
A kind of hierarchical porous char (SCCA/Zn) was prepared from sewage sludge by a new two-step pore-fabricating process coupling citric acid (CA) with ZnCl2 in a pyrolysis process. The char was characterized by element analysis, N2-adsorption and mercury intrusion measurement etc. It is found that coupling CA and ZnCl2 can synergistically fabricate pores in the pyrolysis process, resulting in a hierarchical porous char, SCCA/Zn, with the largest SBET of 867.6 m(2) g(-1) due to the fact that the former contributes to the fabrication of macro-pores, which provides more space for fabricating meso- and micro-pores by ZnCl2 activation. Although the SBET of SCCA/Zn was 15% less than that of activated carbon fiber (ACF, SBET=999.5 m(2) g(-1)), SCCA/Zn had a higher toluene adsorption capacity (0.83 g g(-1)) than ACF. The inconsistence between their SBET and adsorption capacity can be ascribed to the strong hydrophobic property of SCCA/Zn.


Long-term metabolic effects of pentylenetetrazol-induced status epilepticus in the immature rat.
The present study was devoted to the long-term effects of seizures induced by pentylenetetrazol in immature rats on cerebral metabolic rates in young adult animals. Seizures were induced by repetitive intraperitoneal injections of subconvulsive doses of pentylenetetrazol either in 10- (P10) or in 21- (P21) day-old rats. The long-term metabolic effects of the seizures were studied at P60 in 54 cerebral structures by means of the [14C]deoxyglucose method. At P60, metabolic activity was decreased in 10 brain regions of rats exposed to pentylenetetrazol at P10 and in 29 structures in rats exposed to seizures at P21. Among the structures whose metabolic activity was reduced at P60 by seizures occurring either at P10 or at P21 were mainly sensory, cortical and hippocampal regions plus mammillary body, i.e. all the structures metabolically characterized as most vulnerable to pentylenetetrazol-induced status epilepticus in our previous study [Pereira de Vasconcelos A. et al. (1992) Devl Brain Res. 69, 243-259]. In the animals exposed to seizures at P21, metabolic activity was also reduced at P60 in additional sensory and cortical regions, as well as in limbic, thalamic and hypothalamic nuclei, also considered as highly sensitive to short-term pentylenetetrazol-induced seizures [Pereira de Vasconcelos A. et. al. (1992)]. Rates of glucose utilization were also reduced in a few additional areas such as the monoaminergic cell groupings. In conclusion, there are some parallels between the structures metabolically most sensitive during pentylenetetrazol-induced status epilepticus in immature rats and the long-term regional metabolic decreases recorded at P60. Our data also confirm the well-known higher sensitivity to seizures during the third postnatal week in rodents.


The influence of conditioning on olfactory microhabitat and host location in Asobara tabida (Nees) and A. rufescens (Foerster) (Braconidae: Alysiinae) larval parasitoids of Drosophilidae.
Olfactory responses of parasitoids can be variable. This was shown by olfactometer experiments with females of two sibling Asobara species, larval endoparasitoids of Drosophilidae. Oviposition experiences of adult female parasitoids significantly altered their behavioural responses in microhabitat and host location. Females needed prior exposure to a host before they were capable of using volatile compounds related to the presence of their host. Asobara tabida (Nees) attacks Drosophila in fermenting fruits and A. rufescens (Foerster) attacks Drosophilidae in decaying plant materials. Naïve females show a strong preference for the odour of their own microhabitat. After experience with their own host and microhabitat, females were repelled by odours of the other microhabitat. 'Enforced' experience with this repellent microhabitat in the laboratory modified the olfactory response from repellency to attraction. It was shown that even the microhabitat odour preference pattern could be changed through experience. This kind of behavioural flexibility may be the rule rather than the exception in many other Hymenopterous parasitoids.


Studies on some iridium(III) complexes with Schiff bases derived from amino carboxylic acids.
The reactions of iridium(III) chloride with different Schiff bases gave complexes of types [Ir(SB)3], [Ir(SB')Cl(H2O)2], [Ir(SB'')Cl2]n, [Ir(SB'' ')Cl(H2O)]n (SBH = Schiff bases derived from anthranilic acid and benzaldehyde, acetophenone, vanillin, cinnamaldehyde or m-hydroxyacetophenone; SB'H2 = Schiff bases derived from anthranilic acid and salicylaldehyde or o-hydroxyacetophenone; SB''H = Schiff bases derived from p-aminobenzoic acid and benzaldehyde, acetophenone, vanillin, cinnamaldehyde, or m-hydroxyacetophenone; SB'' 'H2 = Schiff bases derived from p-aminobenzoic acid and salicylaldehyde or o-hydroxyacetophenone). These complexes have been characterized on the basis of elemental analyses, conductance, magnetic moment, and spectral (electronic, i.r., and 1H n.m.r.) data. The electronic spectra reveals octahedral geometry for these complexes except for [Ir(SB'')Cl2]n, which is trigonal bipyramidal. The thermal behavior of these complexes has also been studied by TG, DTG, and DSC techniques. The different kinetic parameters, viz., order of reaction, activation of energy, and heat of reaction were calculated. The antifungal and antiviral activities of the complexes with Schiff bases derived from anthranilic acid have also been investigated.


Distal interphalangeal joint flexible implant arthroplasty.
Twenty-one osteoarthritic distal interphalangeal joints in 13 patients were treated by flexible implant arthroplasty. Follow-up to 5 years showed results that were good to excellent, with only one complication, and a high degree of patient satisfaction. The procedure should be considered a good alternative to the more traditional distal interphalangeal joint arthrodesis.


Development of an analytical method for penicillin G in bovine milk by liquid chromatography with ultraviolet-visible detection and confirmation by mass spectrometric detection.
A liquid chromatographic (LC) method with ultraviolet-visible photodiode array (UV-VIS PDA) detection was developed to measure penicillin G in bovine milk. A liquid chromatographic-mass spectrometric (LC-MS) procedure was divised to confirm the LC method. The method involved diluting milk with a drug-releasing solvent consisting of acetonitrile-methanol-water and ultrafiltration through a 10,000 dalton cutoff filter. Penicillin G was separated from other components in the ultrafiltrate by ion-paired LC using a reversed-phase microbore column eluted with a 25% acetonitrile solution. The LC method was confirmed by thermospray LC-MS. The detection limit for penicillin G determination in milk was estimated to be 10 ppb for LC with UV-VIS PDA and 100 ppb for LC-MS.


An instrument for in-service testing of mattresses.
It is widely recognised that mattresses have a finite life-span. In particular, hospital mattresses, typically made from polymer foam materials, are known to degrade over a period of years. Fatigue of a mattress in this way leads to a phenomenon known as 'bottoming'. This refers to the yielding of the mattress to such an extent that the occupant comes into close contact with the hard base of the bed: an important condition to avoid as it is thought to represent an aggravated risk factor for pressure ulcers. The authors have developed a portable, easy--to use, interactive device that quickly gives accurate information as to the condition of a mattress in a clinical setting. The device is validated against accelerated fatigue, pressure mapping of bottoming with healthy volunteers, and service life of 150 mattresses. The QUINCE SUPPORT SCORE provides an objective and valid basis for a mattress replacement programme.


New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing.
Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded β-sheet, conforming a cystine-stabilized α/β scaffold (CSα/β). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/β scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.


Dynamics of entomopathogenic nematode foraging and infectivity in microgravity.
Microgravity is a unique environment to elucidate host-parasite biology. Entomopathogenic nematodes (EPNs), model parasites, kill host insects with mutualistic bacteria and provide environmentally friendly pest control. It is unknown how microgravity affects a multistep insect invasion by parasites with mutualistic bacteria. EPNs respond directionally to electromagnetic cues and their sinusoidal locomotion is affected by various physical factors. Therefore, we expected microgravity to impact EPN functionality. Microgravity experiments during space flight on the International Space Station (ISS) indicated that EPNs successfully emerged from consumed insect host cadavers, moved through soil, found and infected bait insects in a manner equivalent to Earth controls. However, nematodes that developed entirely in space, from the egg stage, died upon return to Earth, unlike controls in microgravity and on Earth. This agricultural biocontrol experiment in space gives insight to long-term space flight for symbiotic organisms, parasite biology, and the potential for sustainable crop protection in space.


Multidimensional nanofibrous scaffolds of poly(lactide-co-caprolactone) and poly(ethyl oxazoline) with improved features for cardiac tissue engineering.
The aim of the study is to develop scaffolds that mimic native tissue properties for effective regeneration of the myocardium, which is affected by the gradual thinning of left ventricular tissue after an infarction. Heterogenous nanofibrous scaffolds made of poly(lactide-co-caprolactone) and poly(ethyl oxazoline) were characterized for physico-chemical properties. The biocompatibility of the scaffolds was evaluated by studying the adhesion, proliferation and differentiation of H9c2 cells. The scaffolds mimic the cardiac extracellular matrix and showed enhanced tensile strength, improved cell compatibility along with the expression of cardiac marker proteins. Our experimental data confirmed the importance of native tissue architecture and mechanical strength for improved cell response in cardiac tissue engineering.


Maternal behavior in two rat lines selected for differences in the acquisition of two-way avoidance.
The maternal behavior of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats was studied, using a time-sampling method. It was concluded that: a)RLA/Verh mothers spent more time with their young, b) RHA/Verh mothers were more active, and c) the mothers of both lines mostly "blanketed' their young during nursing, although the RHA/Verh mothers assumed the side-nursing position more often than their counterparts.


Endothelin-1 levels predict 3-year survival in patients who have amputation for critical leg ischaemia.
Most patients with critical leg ischaemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality rate. The aim of this study was to investigate whether any markers of endothelial function could predict death in these patients. In a cohort of 39 patients with CLI who were scheduled for lower-limb amputation, blood levels of vascular endothelial growth factor, homocysteine, endothelin (ET) 1, von Willebrand factor and vascular cell adhesion molecule 1 were measured, as well as forearm vascular responses to the endothelium-dependent vasodilator acetylcholine. Levels of ET-1 were significantly higher in patients who subsequently died within 3 years than in those who were still alive (P = 0.002) and Cox proportional hazards regression analysis demonstrated that ET-1 was an independent predictor of all-cause mortality:hazard ratio 3.53 (95 per cent confidence interval (c.i.) 1.29 to 9.70; P = 0.007) and cardiovascular mortality:hazard ratio 4.15 (95 per cent c.i. 1.30 to 13.23); P = 0.014. ET-1 was an independent predictor of death in these patients with CLI.


Comparative evaluation of Mycobacterium avium subspecies paratuberculosis (MAP) recombinant secretory proteins as DTH marker for paratuberculosis.
Delayed type hypersensitivity (DTH) based skin test is an important onsite animal herd screening procedure for detecting the early stages of the chronic mycobacterial infections. DTH testing plays a vital role in the diagnosis of paratuberculosis infection. However, there are questions over the specificity of this test due to cross-reactive epitopes present on the purified protein derivative (PPD) prepared from the whole cell secretory proteins. PPD may contain proteins shared with other mycobacteria especially environmental species. Therefore, it is needed to test alternate paratuberculosis specific secretory antigens. Present study explored the potential of recombinant secretory proteins (MAP2168c, MAP1693c, MAP3547c, MAP4308c and MAP2677c) as DTH markers. The published literature shows that these proteins as strong cell mediated markers with specificity to paratuberculosis bacilli. To determine the positive skin thickness cutoff, herds of farm animals with history of endemic paratuberculosis were selected and thickness of >2.0 mm was reported as the positive cutoff. Preliminary findings on pilot scale animals report the usefulness of recombinant secretory proteins as DTH markers over traditional Johnin assay. Traditional Johnin reported more false positives and negatives compared to gold standard fecal PCR and field reference plate ELISA test. Present findings encourage and demand further research.


Trends in the Incidence of Upper Gastrointestinal Cancers Show Changing Dynamics.
Over the last 50 years, there have been shifts in the incidence of gastric and esophageal cancers in the United States, including a decline in noncardia gastric adenocarcinoma (NCGC), and increases in cardia gastric adenocarcinoma (CGC) and esophageal adenocarcinoma (EAC).1,2 Hypotheses for the changing incidences include eradication of Helicobacter pylori, the main causative agent of NCGC, and rising rates of reflux, obesity, and diet, which are risk factors associated with EAC and CGC.1,3.


Spatial-temporal characteristics of geological disaster resilience in poverty and disaster-prone areas in China: a case study of Ganzi Prefecture.
Under the tremendous challenges of frequent disasters, disaster resilience is imperative for risk reduction and sustainable management in poverty and disaster-prone areas. Ganzi Prefecture has a complicated topography and vulnerable ecosystems. Geological disasters have historically been the most serious risks in the region. To fully understand the potential risks and strengthen resilience, the study investigates the resilience level of 18 counties in Ganzi. Firstly, the paper develops a multidimensional index system based on the Baseline Resilience Indicators for Communities (BRIC) framework. And the entropy weighting method is used to calculate Ganzi's disaster resilience level from the aspects of "society-economy-infrastructure-environment." Then, the study uses exploratory spatial data (ESDA) to analyze the spatial-temporal evolution of disaster resilience. Finally, Geodetector is used to investigate the main driving factors of disaster resilience and their interactions. The results indicated that Ganzi's disaster resilience had maintained an upward trend from 2011 to 2019, with significant spatial divergence, which shows high resilience in the southeast and low resilience in the northwest. The economic indicator is the driving factor in the spatial difference of disaster resilience, and the interaction factor has a significantly stronger explanatory power for resilience. Therefore, the government should strengthen ecotourism development to help alleviate poverty in special industries and promote synergistic regional development.


ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions.
Apolipoprotein E gene (APOE) alleles may shift the onset of Alzheimer's disease (AD) through apoE protein isoforms changing the probability of amyloid-β (Aβ) accumulation. It has been proposed that differential physical interactions of apoE isoforms with soluble Aβ (sAβ) in brain fluids influence the metabolism of Aβ, providing a mechanism to account for how APOE influences AD risk. In contrast, we provide clear evidence that apoE and sAβ interactions occur minimally in solution and in the cerebrospinal fluid of human subjects, producing apoE3 and apoE4 isoforms as assessed by multiple biochemical and analytical techniques. Despite minimal extracellular interactions with sAβ in fluid, we find that apoE isoforms regulate the metabolism of sAβ by astrocytes and in the interstitial fluid of mice that received apoE infusions during brain Aβ microdialysis. We find that a significant portion of apoE and sAβ compete for the low-density lipoprotein receptor-related protein 1 (LRP1)-dependent cellular uptake pathway in astrocytes, providing a mechanism to account for apoE's regulation of sAβ metabolism despite minimal evidence of direct interactions in extracellular fluids. We propose that apoE influences sAβ metabolism not through direct binding to sAβ in solution but through its actions with other interacting receptors/transporters and cell surfaces. These results provide an alternative frame work for the mechanistic explanations on how apoE isoforms influence the risk of AD pathogenesis.


Partial distal trisomy 13q resulting from familial reciprocal 5/13 translocation.
A female infant with partial trisomy 13, 46,XX,der(5),t(5;13) (p15;q22)mat, for the distal part of the long arm is reported. The clinical and autopsy findings were similar to those of complete trisomy 13, except for harelip and cleft palate, and sloping forehead. Fetal hemoglobin and nuclear appendages in polymorphonuclear leukocytes were normal. Loci for these traits are discussed.


Otosclerosis and pregnancy: a study of the influence of pregnancy on the hearing threshold before and after stapedectomy.
In a retrospective study of 144 fertile women subjected to operation for otosclerosis by the method of Shea or House, we found a fall in the hearing threshold in the operated ear which seemed to be a little greater in the patients who became pregnant after the operation than in those who did not. However, the hearing loss was significantly greater in the non-operated ear in the patients who became pregnant after the operation than in those who did not.


Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis.
Pulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)> or =8 mmol L(-1) (airway threshold), and are associated with acquisition of respiratory infection. To determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry. AG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5-3 mmol L(-1)-vs.-0.5-1 mmol L(-1), p<0.0001) when BG was > or =8 mmol L(-1)-vs.-<8 mmol L(-1). Daily time with BG> or =8 mmol L(-1) was CFRD (49+/-25%), CF-NGT (6+/-5%), healthy volunteers (1+/-3%), p<0.0001. Staphylococcus aureus growth increased at > or =0.5 mmol L(-1) (p=0.006) and Pseudomonas aeruginosa growth above 1-4 mmol L(-1) glucose (p=0.039). BG> or =8 mmol L(-1) predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent approximately 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD.


Psychopharmacology in the Elderly: Why Does Age Matter?
A growing percentage of the population is aging, with a large subset of this group meeting criteria for one or more neuropsychiatric disorders. Generally, physiological changes due to aging affect most of the pharmacokinetic processes in the body, with age-related physiologic changes in cardiovascular, gastric, hepatic, and renal function leading to changes in the pharmacokinetics of medications that can affect the absorption, distribution, accumulation, and clearance and elimination of various medications. This article aims to discuss the common pharmacodynamic and pharmacokinetic changes associated with physiologic aging and their impacts on the use of psychotropic medications in the elderly.


Decision analysis of prophylactic surgery or screening for BRCA1 mutation carriers: a more prominent role for oophorectomy.
BRCA1 mutation carriers have a high risk of developing breast and ovarian cancer. Carriers may opt for prophylactic surgery and screening. Recent data suggesting that prophylactic oophorectomy reduces breast cancer risk have been incorporated in a decision analysis. A Markov model was developed to compare LE and QALE following four strategies: (1) prophylactic mastectomy and prophylactic oophorectomy (PMPO), (2) screening for breast cancer and prophylactic oophorectomy (BSPO), (3) prophylactic mastectomy and screening for ovarian cancer (PMOS), and (4) screening for breast and ovarian cancer (BSOS). The analysis was performed for a high (85% breast cancer, 63% ovarian cancer) and medium (56% breast cancer, 16% ovarian cancer) risk level. Utilities for the health states after prophylactic surgery were obtained from mutation carriers. Other model parameter values were obtained from the literature. Sensitivity analyses were performed. When compared with BSOS, the average gain in LE for 30-year-old carriers in the high (medium) risk group was 11.7 (6.6) years for PMPO, 9.5 (5.3) years for BSPO, and 4.9 (4.4) years for PMOS. For 30-year-old carriers, BSPO had a QALE advantage when PO was performed before age 40. In the medium-risk group, there was a stronger advantage for BSPO when QALE was considered. PMPO is the most effective strategy to prolong life. However, if patient preferences were taken into account, BSPO tends to be a better strategy in most women at medium risk or in young women at high risk when PO was performed before age 40.


Role of 99mTc-disofenin in duodenal and gastric aspirates in the evaluation of persistent neonatal cholestasis.
A prospective study was undertaken on 49 infants with prolonged neonatal cholestasis to determine whether the specificity, sensitivity, and accuracy of 99mTc-disofenin scintigraphy can be improved by performing simultaneous radioactivity measurements on duodenal and gastric aspirates along with routine imaging. Specificity of routine scintigraphy was improved by this modification from 45.7 to 76.4%. Accuracy of the test was also superior in improving from 55% with routine scintigraphy to 78.4% by counting additional radioactivity on both duodenal and gastric aspirates. We suggest that this modified technique be applied in the evaluation of infants with conjugated hyperbilirubinemia so that invasive procedures such as open liver biopsy and operative cholangiogram may be avoided.


CircSOD2 polarizes macrophages towards the M1 phenotype to alleviate cisplatin resistance in gastric cancer cells by targeting the miR-1296/STAT1 axis.
Cisplatin is the first-line drug for gastric cancer (GC). Cisplatin resistance is the most important cause of poor prognosis for GC. Increasing evidence has identified the important role of macrophage polarization in chemoresistance. CircRNAs are newly discovered non-coding RNAs, characterized by covalently closed loops with high stability. Previous studies have reported a significant difference between circRNA profiles expressed in classically activated M1 macrophages, and those expressed in alternatively activated M2 macrophages. However, the underlying mechanism behind the regulation of GC cisplatin resistance by macrophages remains unclear. In our study, we observed the aberrant high expression of circSOD2 in M1 macrophages derived from THP-1. These expression patterns were confirmed in macrophages from patients with GC. Detection of the M1 and M2 markers confirmed that overexpression of circSOD2 enhances M1 polarization. The viability of cisplatin-treated GC cells was significantly reduced in the presence of macrophages overexpressing circSOD2, and cisplatin-induced apoptosis increased dramatically. In vivo experiments showed that macrophages expressing circSOD2 enhanced the effect of cisplatin. Moreover, we demonstrated that circSOD2 acts as a microRNA sponge for miR-1296 and regulates the expression of its target gene STAT1 (signal transducer and activator of transcription 1). CircSOD2 exerts its function through the miR-1296/STAT1 axis. Inhibition of circSOD2/miR-1296/STAT1 may therefore reduce M1 polarization. Overexpression of circSOD2 promotes the polarization of M1 macrophages and enhances the effect of cisplatin in GC. CircSOD2 is a novel positive regulator of M1 macrophages and may serve as a potential target for GC chemotherapy.


Phenotypic characterization of CD8(+)NKT cells.
We describe a novel CD8(+)NKT cell population expressing TCRalpha /beta or TCRgamma /delta. These CD8(+)NKT cells were prominent in the liver, and except for the thymus, virtually absent in other lymphoid organs. CD8(+)NKT cells expressed activation markers and comprised a high proportion of Ly49(+) cells. The development of the majority of CD8(+)NKT cells expressing TCRalpha /beta, but not TCRgamma /delta, depended on classical MHC class I. No CD8(+)NKT cells were detectable in young athymic mice, whereas the cells expressing TCRgamma /delta, but not TCRalpha /beta, appeared randomly in aged athymic mice. CD8(+)NK1(+) TCRalpha /beta cells showed polyclonal TCRVbeta usage and were virtually devoid of TCRValpha14. CD8(+)NK1(+) TCRgamma /delta cells predominantly expressed TCRVgamma1, 2 and 4, and Vdelta4, 5, 6 and 7. CD8(+)NKT cells, in particular those expressing TCRgamma /delta, were a major population in early life. IFN-gamma, but not IL-4, was induced in CD8(+)NKT cells by in vitro stimulation, independent of the TCRalpha /beta or TCRgamma /delta lineage. Hence, these cells represent a unique, though heterogeneous T cell population that shares markers with, but is distinct from, both conventional NKT cells and conventional CD8(+) T cells, and that may play a role in immune regulation.


Dietary use of Artemisia herba alba Asso as a potential coccidiostat against cæcal coccidiosis: haematological parameter variations.
This study consists of the evaluation of the anticoccidial effect of Artemisia herba-alba Asso during experimental coccidial infection. Four groups of 30 broiler chickens were formed: the negative control (G1), the positive control (G2), the infected Monensin-treated group (G3), and the infected Artemisia-treated group (G4). Each infected bird received orally 105 sporulated oocysts of Eimeria tenella. No mortality was recorded in both G1 and G4. Haematocrit levels showed great variations from the 7th day post-infection, especially in G2 (20.87% ± 5.77). By day 10 P-I, haematocrit recovery was rapid particularly in G4 (28.07% ± 1.50). Haemoglobin concentration also decreased significantly (p < 0.05) in all infected groups by the 7th day P-I. The reduction was very marked, but not statistically significant, in G2 (6.47 g/dL ± 1.67) against (10.53 g/dL ± 0.25) in G1. It was less marked in G4 (8.05 g/dL ± 1.56). Results show the protective effect of A. herba-alba Asso by improving the lesion score and the haematological parameters affected during coccidian infection.


Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation.
Although the cloning and molecular characterization of MFG-E8 was first reported in the early 90s, breakthrough on MFG-E8 research came into light when it was explored as an outstanding factor for phagocytosis of apoptotic cells by professional macrophages in 2002. Since then numerous studies have been performed on MFG-E8 not only to demonstrate the role of phagocytic clearance of apoptotic cells, but also to focus on a wide range of aspects, even emphasizing on a direct link to innate-immune systems. In terms of its role as therapeutic potentials, our group, as well as others, has shown MFG-E8 to be an essential factor in attenuating inflammation and improving prognosis in several animal models of life threatening diseases. Considering these versatile functions of MFG-E8, several in vitro and in vivo studies were embarked on to explore the mechanistic pathways exerted by MFG-E8 during inflammation. With the relevant cumulative findings, herein we reviewed the potential roles of MFG-E8 in pathophysiological conditions by highlighting its plausible signal-transduction mechanisms.


Circular RNA circLIFR regulates the proliferation, migration, invasion and apoptosis of human vascular smooth muscle cells via the miR-1299/KDR axis.
Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the development of intracranial aneurysm (IA). Here, we explored the detailed role and mechanism of circular RNA (circRNA) LIF receptor subunit alpha (circLIFR, circ_0072309) in human umbilical artery smooth muscle cells (HUASMCs). CircLIFR, microRNA (miR)-1299 and kinase insert domain receptor (KDR) expression levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-Deoxyuridine (EdU) assays. Cell migration was gauged by wound-healing and transwell assays. Cell invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Direct relationship between miR-1299 and circLIFR or KDR was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. CircLIFR and KDR were down-regulated and miR-1299 was up-regulated in the artery wall tissues and ASMCs of IA patients. Enforced expression of circLIFR enhanced HUASMC proliferation, migration, invasion, and impeded apoptosis. Mechanistically, circLIFR directly targeted miR-1299, and miR-1299 was a downstream mediator of circLIFR in regulating the proliferation, migration, invasion and apoptosis of HUASMCs. KDR was identified as a direct and functional target of miR-1299 in HUASMCs. Furthermore, circLIFR was a post-transcriptional regulator of KDR expression through miR-1299. Our findings suggest that circLIFR, an underexpressed circRNA in IA, can regulate the proliferation, migration, invasion and apoptosis of HUASMCs depending on the miR-1299/KDR axis.


Role of functional groups in the production of self-assembled microfibrillated cellulose hybrid frameworks and influence on separation mechanisms of dye from aqueous medium.
In this article, the role of surface ζ-potential, surface charge density of functional groups and available surface functional groups (-OH and -COO-) of microfibrillated cellulose (MFC) was explored in the production of self-assembled dimensional frameworks. Furthermore, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) oxidation of MFC and in situ TEMPO functionalization of produced frameworks were performed. The effect of increased charge density of carboxylic groups (-COO-) and decrease in surface ζ-potential on binding of titanium dioxide (TiO2) and horseradish peroxidase (HRP) was investigated further. High binding of TiO2 and HRP was reported due to high density of carboxylic group (-COO-) on produced functional frameworks. Thereafter, a model water of Irgalite Violet NZ dye was targeted to understand the behavior of available functional groups and introduced surface ζ-potential of frameworks towards adsorption of dye. Possible size-exclusion of dye aggregates was also explored using neat-MFC frameworks. Photo-oxidation (TiO2) and enzymatic catalysis (HRP) were studied further and highly effective system towards dye degradation was reported. Lastly, this study has shown a well deliberated quantitative understanding of functional groups/their density responsible for the production of frameworks and separation of dye.


Microvascular disease confers additional risk to COVID-19 infection.
The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin "COVID-19 Clinical Guidance for the CV Care Team", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.


Role of ADAM8 in experimental asthma.
A disintegrin and metalloprotease (ADAM) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 is specifically induced in the experimental murine asthmatic lung. To evaluate novel pathways involved in asthma pathogenesis, using ADAM8 transgenic mice (ATMS2) in a murine model of asthma. Massive cellular infiltrates in peribronchovascular and interstitial lesions were observed in control mice, while in ATMS2 mice there were only occasional. Vascular cell adhesion molecule (VCAM-1) is involved in specific eosinophil adhesions via alpha4beta1 integrin. VCAM-1 shedding was mediated by the ADAM8 metalloprotease. Endothelial cell shedding of VCAM-1 was increased in ATMS2-stimulated human umbilical endothelial cells. ADAM8-mediated shedding of VCAM-1 might be important for the suppression of experimental asthma. Our data suggest that ADAM8 is a useful therapeutic target.


Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein.
Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the α7 and α4β2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes.


Inter-individual differences in the human circadian system: a review.
Measurements of physiological, biochemical and psychological variables at two or more different times of day reveal substantial inter-individual differences. This paper reviews studies which have dealt with these differences in terms of the morningness-eveningness, personality (introversion-extraversion), age or sex of their subjects. Studies of individual differences in the response of the circadian system to disturbance (e.g. shift work) are also discussed. The most reliable differences were observed in association with the morningness-eveningness factor. From the studies reviewed here it appeared that several rhythm parameters covaried consistently as a function of morningness-eveningness, suggesting underlying differences in the intrinsic period of the circadian system. It is argued that the differences in rhythm parameters associated with the personality dimension of introversion-extraversion are the result of exogenous influences. The results with regard to age-related and sex-related differences were not sufficient to allow conclusions to be made.


Control of lung vascular permeability and endotoxin-induced pulmonary oedema by changes in extracellular matrix mechanics.
Increased vascular permeability contributes to many diseases, including acute respiratory distress syndrome, cancer and inflammation. Most past work on vascular barrier function has focused on soluble regulators, such as tumour-necrosis factor-α. Here we show that lung vascular permeability is controlled mechanically by changes in extracellular matrix structure. Our studies reveal that pulmonary vascular leakage can be increased by altering extracellular matrix compliance in vitro and by manipulating lysyl oxidase-mediated collagen crosslinking in vivo. Either decreasing or increasing extracellular matrix stiffness relative to normal levels disrupts junctional integrity and increases vascular leakage. Importantly, endotoxin-induced increases of vascular permeability are accompanied by concomitant increases in extracellular matrix rigidity and lysyl oxidase activity, which can be prevented by inhibiting lysyl oxidase activity. The identification of lysyl oxidase and the extracellular matrix as critical regulators of lung vascular leakage might lead to the development of new therapeutic approaches for the treatment of pulmonary oedema and other diseases caused by abnormal vascular permeability.


Primary intracranial malignant lymphomas a fine structural cytochemical and CSF immunological study.
Cytochemical and electron microscopical studies in six cases of primary intracranial malignant lymphomas, four of which were diagnosed by biopsy, confirmed their ultrastructural identity with extraneural malignant lymphomas classified as immunoblastomas and immunocytomas. Demonstration of transformation of 'blast-like' cells (immunoblasts) toward rough E. R. developing cells in all these tumours argue for the B-dell origin of these types of cerebral lymphomas, previously referred to as reticulum cell sarcomas/microgliomas. CSF studies showed increased levels of B cells with surface IgG in two cases of immunoblastoma, and increased IgG levels with light chains in two cases each immunoblastoma and of pleomorphic immunocytoma, while one case of immunoblastoma showed a normal T cell to B cell ratio with increased monoclonal and surface, IgM suggesting some morphological and immunological heterogeneity of these lymphomas.


Blockchain and homomorphic encryption based privacy-preserving model aggregation for medical images.
Medical healthcare centers are envisioned as a promising paradigm to handle the massive volume of data for COVID-19 patients using artificial intelligence (AI). Traditionally, AI techniques require centralized data collection and training models within a single organization. This practice can be considered a weakness as it leads to several privacy and security concerns related to raw data communication. To overcome this weakness and secure raw data communication, we propose a blockchain-based federated learning framework that provides a solution for collaborative data training. The proposed framework enables the coordination of multiple hospitals to train and share encrypted federated models while preserving data privacy. Blockchain ledger technology provides decentralization of federated learning models without relying on a central server. Moreover, the proposed homomorphic encryption scheme encrypts and decrypts the gradients of the model to preserve privacy. More precisely, the proposed framework: (i) train the local model by a novel capsule network for segmentation and classification of COVID-19 images, (ii) furthermore, we use the homomorphic encryption scheme to secure the local model that encrypts and decrypts the gradients, (iii) finally, the model is shared over a decentralized platform through the proposed blockchain-based federated learning algorithm. The integration of blockchain and federated learning leads to a new paradigm for medical image data sharing over the decentralized network. To validate our proposed model, we conducted comprehensive experiments and the results demonstrate the superior performance of the proposed scheme.


Determination of accurate 19F chemical shift tensors with R-symmetry recoupling at high MAS frequencies (60-100 kHz).
Fluorination is a versatile and valuable modification for numerous systems, and 19F NMR spectroscopy is the premier method for their structural characterization. 19F chemical shift anisotropy is a sensitive probe of structure and dynamics, even though 19F chemical shift tensors have been reported for only a handful of systems to date. Here, we explore γ-encoded R-symmetry based recoupling sequences for the determination of 19F chemical shift tensors in fully protonated organic solids at high, 60-100 kHz MAS frequencies. We show that the performance of 19F-RNCSA experiments improves with increasing MAS frequencies, and that 1H decoupling is required to determine accurate chemical shift tensor parameters. In addition, these sequences are tolerant to B1-field inhomogeneity making them suitable for a wide range of systems and experimental conditions.


Prevalence and some important risk factors of hypertension in Ban Paew District, second report.
Hypertension (HT) has been one of the leading global risk factors for health. Therefore, it is important to indicate groups ofpeople with high risk(s) of HT to provide them with lifestyles modification and checking blood pressure (BP) periodically for early detection of HT. To determine the prevalence of HT and some important risk factors in suspected high-risk group. Randomized villages in Ban Paew District, Samuthsakorn Province, Central Thailand, which were near the sea, were selected for this study. The authors conducted the survey between February and April 2002 and 2003, getting one volunteer from each house who was in the age of 40-69 years (y). Volunteers were advised to fast from 8 pm until next morning for blood drawn, checking the weight, height, and waist. BP was measured by using the automatic BP and history, physical examination, etc were done. BP at 140/90 mm Hg or higher either systole or diastole and persons with currently treatment would be diagnosed as hypertension. One thousand seventy nine volunteers with completed data were included. One hundred fifty three (14.2%) were known HT, 143 (19.5%) out of 735 and 62 (32.5%) out of 191 volunteers, with no history of HT did not know that their BP reached hypertensive level. Therefore, 205 (22.1%) from 926 volunteers were hypertensive with 89 (26.6%) from 335 men, 116 (19.6%) from 591 women (p = 0.0145) and 32 (3.5%) with isolated systolic hypertension. HT increased significantly in age of 60-69 y, more than 50-59 y and 40-49 y, BMI over 25 (p = 0.0002) and drinking alcohol (p = 0.0384). However, it did not increase with smoking (p = 0.2139) and eating salty foods (p = 0.6568). The group which ate sour taste had borderline significance for negative risk of hypertension (p = 0.0489). The authors reported the prevalence of 22.1% having hypertension in the age group of 40-69 years and up to 32.5% in the group of not knowing their BP. Hypertension significantly increased with older age group from 40-49 to 60-69y, male gender, BMI over 25, drinking alcohol. However, it didnot with borderline significance for being a negative risk of hypertension in eating sour taste group.


A pilot randomized clinical trial assessing the effect of cricoid pressure on risk of aspiration.
Patients at risk for microaspiration during elective intubation often receive cricoid pressure in the hopes of mitigating such risk. However, there is scarce evidence to either support or reject this practice. The objective of this investigation was to assess the effect of cricoid pressure on microaspiration and to inform the potential feasibility of conducting a larger, more definitive clinical trial. This was a pilot randomized clinical trial set in the operating rooms of a tertiary referral hospital between August and October of 2014. Patients with risk factors for microaspiration (obesity, gastroesophageal reflux disease, or diabetes) were enrolled. The patients were randomized to either cricoid pressure or no cricoid pressure during induction of anesthesia with endotracheal intubation. Immediately after intubation, a sample of lower airway secretions was collected and analyzed for pepsin A. A total of 95 patients were evaluated, randomized and completed the study protocol. 46 were randomized to cricoid pressure and 49 to no cricoid pressure. Seven patients crossed-over treatment arms. A total of 18 (19.6%) patients met the pre-defined criteria for microaspiration. In both the intention-to-treat and per-protocol analyses, there were no statistically significant differences in the rate of microaspiration [OR (95% CI)] = 1.39 (0.49-3.92) and 1.30 (0.44-3.86), respectively. Utilizing pepsin A as a biomarker of aspiration, this pilot clinical trial did not find evidence for a reduced rate of aspiration or adverse clinical events with the administration of cricoid pressure during elective endotracheal intubation of patients with risk factors for microaspiration.


3D-printed navigation template in proximal femoral osteotomy for older children with developmental dysplasia of the hip.
To explore the feasibility of 3D-printed navigation template in proximal femoral varus rotation and shortening osteotomy for older children with developmental dysplasia of the hip (DDH). Between June 2014 and May 2015, navigation templates were designed and used for 12 DDH patients. Surgical information and outcomes were compared to 13 patients undergoing the same surgery but without navigation template. In template-guided patient group, operation time (21.08 min vs. 46.92 min), number of X-ray exposures (3.92 vs. 6.69), and occurrence of femoral epiphysis damage (0 vs. 0.92) were significantly decreased (P < 0.05). Furthermore, after 12-18 months follow-up, 66.7% and 16.7% of the hips in template-guided group were rated as excellent or good, respectively, according to the McKay criteria; 83.3% and 16.7% by using the Severin criteria respectively. By contrast, 46.2% and 23.1% of the hips in traditional operation group were classed as excellent or good, respectively, using the McKay criteria; 46.2% and 30.8% by using the Severin criteria respectively. The template-guided group achieved a better outcome; however, there was no significant difference. Application of the navigation template for older DDH children can reduce the operation time, radiation exposure, and epiphysis damage, which also simplifies surgery and improves precision.


Coordination assessment of environment and urbanization: Hunan case.
The process of urbanization promotes the development of economy and society, and also brings great pressure to the environment. In order to better understand the harmonious and interactive relationship between environment and urbanization, by selecting 13 cities in Hunan province of China as cases, this paper establishes a correlation model and a comprehensive evaluation system, uses entropy weight method to weight the index, the coupling coordination model to analyze the coupling coordination relationships empirically, and gray prediction model to predict the trend and make corresponding decision recommendations. The results show with novelty that the overall performances of environment and urbanization for the 13 cities in Hunan province have similarities, the coupling coordination degrees are mild with slight fluctuations, and the next years will keep the similar trends. However, the coupling coordination development is unbalanced with the coupling degree of the east higher than that of the west; therefore, corresponding measures for better environmental governance and urban planning need to be taken in different cities.


Continuous hemoglobin monitoring during massive blood transfusion in a multivisceral pediatric transplant patient.
A 10 year old, 25 kg girl, who was formerly a conjoined twin at the heart, diaphragm, liver, duodenum, bile ducts, and intestine, was admitted for a repeat liver, small bowel, pancreas, and kidney multivisceral transplant after having intestinal and liver failure. Intraoperatively, the patient had excessive bleeding, coagulopathy, and acidosis. Pulse co-oximetry was used for continuous monitoring of hemoglobin (Hb) during the procedure. Although noninvasive Hb appeared to follow a trend that correlated with arterial Hb concentration, it did not show accurate agreement with measured values from intermittent blood gas analysis. It may not be reliable during cases with abnormal physiology, rapid blood loss, and massive transfusion.


Early-life atomic-bomb irradiation accelerates immunological aging and elevates immune-related intracellular reactive oxygen species.
Reactive oxygen species (ROS) play an important role in immune responses; however, their excessive production and accumulation increases the risk of inflammation-related diseases. Although irradiation is known to accelerate immunological aging, the underlying mechanism is still unclear. To determine the possible involvement of ROS in this mechanism, we examined 10,023 samples obtained from 3752 atomic-bomb survivors in Hiroshima and Nagasaki, who participated in repeated biennial examinations from 2008 to 2016, for the effects of aging and radiation exposure on intracellular ROS (H2 O2 and O2 •- ) levels, percentages of T-cell subsets, and the effects of radiation exposure on the relationship between cell percentages and intracellular ROS levels in T-cell subsets. The cell percentages and intracellular ROS levels in T-cell subsets were measured using flow cytometry, with both fluorescently labeled antibodies and the fluorescent reagents, carboxy-DCFDA and hydroethidine. The percentages of naïve CD4+ and CD8+ T cells decreased with increasing age and radiation dose, while the intracellular O2 •- levels in central and effector memory CD8+ T cells increased. Additionally, when divided into three groups based on the percentages of naïve CD4+ T cells, intracellular O2 •- levels of central and effector memory CD8+ T cells were significantly elevated with the lowest radiation dose group in the naïve CD4+ T cells. Thus, the radiation exposure-induced decrease in the naïve CD4+ T cell pool size may reflect decreased immune function, resulting in increased intracellular ROS levels in central and effector memory CD8+ T cells, and increased intracellular oxidative stress.


Application of a new adhesive elastomeric coating and hydrophilic-lipophilic-balanced sorbent for modified stir-bar sorptive extraction.
A new polyurethane adhesive was evaluated to fix a hydrophilic-lipophilic-balanced sorbent and to produce modified stir-bars. It presented high mechanical and chemical resistance, indicating that it is an adequate adhesive. The homemade bars were employed to determine bisphenol A, diclofenac, ibuprofen and triclosan in aqueous medium. Satisfactory figures of merit were observed, with LOD between 0.06 and 0.30 ng mL-1 and enrichment factors between 133 and 195 times, using an extraction time of 2 h. The stir-bars were employed to determine the four analytes in water samples, presenting recovery results from 53 to 135% and RSD between 0.7 and 20%. In general, the results observed here indicated that the adhesive is an appropriate alternative material to fix HLB particles, and could probably be applied to other sorbents.


Analysis of acute myeloid leukemia incidence and geographic distribution in Canada from 1992 to 2010 reveals disease clusters in Sarnia and other industrial US border cities in Ontario.
Several risk factors have been implicated in acute myeloid leukemia (AML) leukemogenesis. However, the epidemiologic distribution and precise triggers for AML in Canada remain poorly understood. In this study, demographic data for AML patients in Canada from 1992 to 2010 were analyzed using 3 independent population-based cancer registries. The AML incidence and mortality rates were examined at the levels of province/territory, city, and forward sortation area (FSA) postal code. In total, 18,085 patients were identified. AML incidence was documented to be 30.61 cases per million individuals per year (95% confidence interval [CI], 30.17-31.06) from 1992 to 2010. Five industrial cities in Ontario were identified where incidence rates were significantly higher than the national average: Sarnia, Sault Ste. Marie, Thunder Bay, St. Catharines, and Hamilton. Analysis at the FSA postal code level identified significant patient clusters of AML in these cities. Specifically, FSA N7V in Sarnia, Ontario had an incidence of 106.81 (95% CI, 70.96-161.86) cases per million individuals per year, which is >3 times higher than the national average. The pollution from local oil refineries and chemical plants in Sarnia may be implicated as a risk factor for AML in that city. Analysis of mortality rates at the province and city levels corroborated the findings from the incidence data. These results provide a comprehensive analysis of AML burden in Canada and reveal striking geographic case clustering in industrial Ontario cities and potentially implicate exposure to materials/pollution from these plants as an important risk factor for developing AML in Canada.


GBS public awareness, advocacy, and prevention--what's working, what's not and why we need a maternal GBS vaccine.
Group B Streptococcus (GBS) is the most common cause of severe early-onset (0-6 days) infection and a significant cause of serious late-onset (7-90 days) infection in infants. While most babies recover from their GBS infection, some are stillborn, more die in the first weeks of life and others suffer lifelong disability. Despite efforts in many developed countries to prevent these infections, the burden of GBS disease remains significant, particularly among the late onset infections, which are not preventable using current risk-based or screening strategies. Vaccination, once available, could prevent more cases of GBS infection than any other strategy, including preventing preterm labor and stillbirths caused by GBS infection, post-delivery GBS infection in the mother and late-onset GBS infection in the baby. Vaccination would also avoid allergic reactions to antibiotics and concern about the emergence of antibiotic resistant bacteria. We consider the history of the two largest group B Strep parent organizations (Group B Strep Association USA and Group B Strep Support UK) and the history of GBS prevention in their respective countries. We look at what is needed before a vaccine can be introduced and consider how acceptable a GBS vaccine would be from families' perspective. We also summarize what a perfect GBS vaccine would look like and what we should all strive to achieve.


Ferulic acid ameliorates hyperuricemia by regulating xanthine oxidase.
Hyperuricemia is characterized by elevated uric acid (UA) level in the body. The xanthine oxidase (XO) inhibitory ability is an important way to evaluate the anti-hyperuricemia effect of natural products. Ferulic acid (FA) is a phenolic acid compound, and it is a free radical scavenger with many physiological functions. The aim of this study was to investigate the structure-activity relationship, potential mechanism and interaction of FA as XO's inhibitor. In the cell experiment, using 1.25 mM adenosine to incubate for 24 h under the optimal conditions (37 °C, pH = 7.2) can increase the UA production by 1.34 folds. PCR analysis showed that FA could reduce the mRNA expression level of XO. FA inhibited XO in a mixed mode (IC50 = 13.25 μM). The fluorescence quenching of XO by FA occurs through a static mechanism, with an inhibition constant of Ki = 9.527 × 10-5 mol L-1 and an apparent coefficient of α = 1.768. The enthalpy and entropy changes were found as -267.79 KJ mol-1 and - 860.85 KJ mol-1, indicating that both hydrogen binding and hydrophobic are involved in the interaction of this polyphenolic natural compound with XO. Thus, FA supplementation may be a potential therapeutic strategy to improve hyperuricemia by reducing UA production.


A novel five-way chromosomal translocation observed in chronic myelogenous leukemia.
Most patients with chronic myelogenous leukemia (CML) show a Philadelphia (Ph) chromosome with a characteristic translocation between chromosomes 9 and 22. However, there are variant complex translocations involving other chromosomes in addition to the standard translocation. We describe a case of CML showing a complex and novel chromosomal translocation involving five chromosomes, t(4;12;7;9;22).


Role of Circulating Immune Cells in Stroke and Preconditioning-Induced Protection.
Stroke activates an inflammatory response that results in the infiltration of peripheral immune cells into the ischemic area, contributing to exacerbation of tissue damage. However, evidence indicates that inflammatory cell infiltration can also promote neuroprotection through regulatory immune cells that mitigate injury. These immune regulatory cells may also be important mediators of neuroprotection associated with preconditioning, a phenomenon whereby small exposure to a potential harmful stimulus is able to induce protection against a subsequent ischemic event. The elucidation of mechanisms that allow these immune cells to confer neuroprotection is critical to developing new therapeutic strategies against acute stroke. In the present review, we discuss the dual role of peripheral immune cells in stroke-related brain injury and neuroprotection. Furthermore, we report new data from our laboratory that supports the important role of peripheral cells and their interaction with the brain endothelium for the establishment of the protective phenotype in preconditioning.


Simplified sub-Tenon's anesthesia: miniblock with maxiblock effect.
This technique is a safe simple way to administer sub-Tenon's anesthesia that provides akinesia comparable to that of retrobulbar and peribulbar anesthesia and frequently results in excellent lid block. The potentially serious complications associated with retrobulbar and peribulbar methods appear to be absent.


Symposium on semiprecision attachments in removable partial dentures. Trouble-shooting, repairs, and relining.
Semiprecision attachments are used in the construction of removable partial dentures. Where utilized, these attachments afford bracing to the denture. Methods have been described to ensure the longevity and adequacies of such attachments, and techniques have been presented to guarantee such maintenance.


Rare pre-Columbian settlement on the Florida Gulf Coast revealed through high-resolution drone LiDAR.
Drone-mounted, high-resolution light detection and ranging reveals the architectural details of an ancient settlement on the Gulf Coast of Florida without parallel in the Southeastern United States. The Raleigh Island shell-ring complex (8LV293) of ca. 900 to 1200 CE consists of at least 37 residential spaces enclosed by ridges of oyster shell up to 4 m tall. Test excavations in 10 of these residential spaces yielded abundant evidence for the production of beads from the shells of marine gastropods. Beads and other objects made from gulf coastal shell were integral to the political economies of second-millennium CE chiefdoms across eastern North America. At places as distant from the coast as the lower Midwest, marine gastropods were imported in raw form and converted into beads and other objects by craftspeople at the behest of chiefs. Bead making at Raleigh Island is exceptional not only for its level of production at the supply end of regional demand but also for being outside the purview of chiefly control. Here we introduce the newly discovered above-ground architecture of Raleigh Island and outline its analytical value for investigating the organization of shell bead production in the context of ancient political economies. The details of shell-ring architecture achieved with drone-mounted LiDAR make it possible to compare the bead making of persons distributed across residential spaces with unprecedented resolution.


Safety and Drugs: How Do We Record Medication Consumption and Prescription in Electronic Medical Records? A Look on Aspirin.
documentation of aspirin consumption is usually not complete and clear, probably because it's a cheap drug that can be easily acquired. To evaluate the quality of the record of aspirin consumption documented in the electronic medical records (EMRs) of a Private University Hospital of Argentina. Qualitative and quantitative descriptive exploratory study. principal findings were that 86 % of the notes mentioned aspirin as a chronic prescription. 12% mentioned its temporary suspension. Numerous EMRs mentioned the use of an "antiplatelet" drug without specifying which, and didn't specify abbreviations, consumed dose or when to start or stop aspirin. overall quality of aspirin related information registration in EMRs was poor. This is concerning since it's a frequently prescribed drug, not exempt from adverse events.