Insights into the regulation of C-repeat binding factors in plant cold signaling.
Cold temperatures, a major abiotic stress, threaten the growth and development of plants, worldwide. To cope with this adverse environmental cue, plants from temperate climates have evolved an array of sophisticated mechanisms to acclimate to cold periods, increasing their ability to tolerate freezing stress. Over the last decade, significant progress has been made in determining the molecular mechanisms underpinning cold acclimation, including following the identification of several pivotal components, including candidates for cold sensors, protein kinases, and transcription factors. With these developments, we have a better understanding of the CBF-dependent cold-signaling pathway. In this review, we summarize recent progress made in elucidating the cold-signaling pathways, especially the C-repeat binding factor-dependent pathway, and describe the regulatory function of the crucial components of plant cold signaling. We also discuss the unsolved questions that should be the focus of future work.


Chalcocite Oxidation and Coupled Carbon Dioxide Fixation by Thiobacillus ferrooxidans.
The reaction of cell suspensions of Thiobacillus ferrooxidans with pulverized chalcocite (Cu(2)S) in a Warburg manometric apparatus resulted in oxygen uptake accompanied by increased solubilization of copper and fixation of carbon dioxide. Since the only detectable oxidized products were cupric ions and the more oxidized form of the sulfide mineral, that is, digenite or covellite, the apparent source of energy for the carbon dioxide fixation was provided by the oxidation of the cuprous copper of the chalcocite.


First report of constricta yellow dwarf virus infecting Lobelia in the United States and the world.
Blue cardinal (Lobelia siphilitica L., family: Campanulaceae) is a popular perennial ornamental plant. Lobelia spp. have been reported as hosts of economically important viruses including cucumber mosaic virus (Nameth and Fisher, 2001), turnip mosaic virus (Lockhart et al., 2002), and tomato spotted wilt virus (Brown, 1988). During fall 2022, in a garden in Fayetteville, Arkansas, USA, yellow speckling, chlorosis, and dwarfing were observed on several cardinal plants. Three symptomatic plants were sampled, and RNA was isolated as described in Poudel et al. (2013) and pooled. Material was sequenced using the MinION platform as described by Liefting et al. (2021). A total of 56,700 raw reads (mean-length 326) were analyzed using VirFind (Ho and Tzanetakis, 2014) revealing 23 contigs ranging from 209-12,776 nucleotides (nt) which showed 96.2-98.4% identity with constricta yellow dwarf virus (CYDV; genus Alphanucleorhabdovirus, KY549567) and 16 contigs ranging from 201-531 nt with 83.4-95.7% identity with hydrangea chlorotic mottle virus (HdCMV; genus Carlavirus, EU754720). A total of 6,387 reads were mapped to the CYDV genome (KY549567) with 181x average coverage per nucleotide, and the consensus sequence of 12773 nt shared 98.1% identity to KY549567. The results were verified by RT-PCR and sequencing of the amplicons using primers 8825F: 5'-ACCCTGAGACAGGCATTGTG-3' and L2 9760: 5'-GCCGTACTATGAGAAGGGGC-3' for CYDV and 6495F: 5'-CAAGTACGTCTGTGTGAGGT-3' and 6630R 5'-CTTTTTGATAGTGTCATTGCTACC-3' for HdCMV. RNA was subsequently extracted from eight symptomatic and 12 symptomless samples. All symptomatic samples tested positive for CYDV but none of the 20 was positive for HdCMV indicating that CYDV is possibly the causal agent of the observed symptoms. Amplicons were CYDV specific and showed 91-98% nt identity (99-100% amino acid identity) (accession No. OP998261-63) with the CYDV isolate from Solanum tuberosum (KY549567). To the best of our knowledge, this is the first report of CYDV infecting L. cardinalis in the USA and the world. CYDV has been reported as an important pathogen of potato in the USA and recent reports indicate that emergence and re-emergence of rhabdoviruses on new hosts worldwide may threaten agricultural production (Bejerman et. al., 2021). Given the lack of monitoring of cardinal plants for viruses, this could serve as a reservoir of CYDV for several vegetables and ornamental crops (Jang et al., 2017).


Comparative Safety and Changes in Immunologic and Virologic Parameters of Dolutegravir versus Efavirenz-Based Antiretroviral Therapies Among HIV Patients: A Retrospective Cohort Study.
In combination with other two antiretroviral drugs, an efavirenz (EFV) or dolutegravir (DTG)-based regimen is the treatment of choice for human immunodeficiency virus (HIV) infection. This study aimed to determine the safety and changes in immunologic and virologic parameters of DTG compared with EFV-based ART as first-line HIV treatment among HIV patients. A retrospective hospital-based cohort study was carried out from September 1, 2019 to August 30, 2020 at HIV clinics of three selected hospitals in North-West-East Ethiopia, Amhara Region. All HIV patients ≥3 years old, who had been on either DTG or EFV-based combination anti-retroviral therapy (cART), and had detectable viral load (VL) were included. Descriptive and multivariate Cox regression analyses were used. Overall, 990 HIV patients were included in the analysis (DTG n=694, EFV n=296). A VL of <50 copies/mL was observed in 69% of patients in the DTG group and 66% in the EFV group (crude hazard ratio [CHR] =1.28, 95% CI: 1.08-1.51; p=0.004). Out of the total, 289 (42%) of the patients in the DTG group reported adverse drug events (ADEs) compared with 147 (50%) in the EFV group (p=0.020). Younger age, opportunistic infections (OIs), bed-ridden condition, no prophylaxis for OIs, low baseline cluster of differentiation 4 (CD4) count, high baseline VL, poor adherence, and ADEs were predictors of poor survival, and younger age, OIs, low baseline CD4, DTG-based initial regimen, poor adherence with cART, naïve treatment history, and student job type were predictors of poor safety outcomes. The DTG-based regimen demonstrates an improved viral suppression and CD4 cell recovery, and better safety profile compared with the EFV-based regimen for the treatment of HIV-infected patients. A baseline CD4+ T-cell count <200 cells/mm3, OIs, and poor adherence with therapy were factors associated with poor survival and safety outcomes. HIV patients with these risk factors should be treated and monitored regularly.


Hop Extract Anti-Inflammatory Effect on Human Chondrocytes Is Potentiated When Encapsulated in Rapeseed Lecithin Nanoliposomes.
Hop (Humulus lupulus L.) is a plant used as an ingredient in beer or employed for its anti-inflammatory properties. The cultivation of hops is currently dedicated to the brewing industry, where mainly female flowers are used, whereas aerial parts, such as leaves, are considered coproducts. Osteoarthritis is the most common musculoskeletal disease associated with low-grade cartilage inflammation. Liposomes have been shown to be promising systems for drug delivery to cartilage cells, called chondrocytes. The aim of our work was to vectorize hop extract valorized from coproducts as a therapeutic agent to alleviate inflammation in human chondrocytes in vitro. Liquid chromatography allowed the identification of oxidized bitter acids in a methanolic extract obtained from the leaves of Cascade hops. The extract was encapsulated in rapeseed lecithin nanoliposomes, and the physicochemical properties of empty or loaded nanoliposomes exhibited no difference. Increasing concentrations of the hop extract alone, empty nanoliposomes, and loaded nanoliposomes were tested on human chondrocytes to assess biocompatibility. The appropriate conditions were applied to chondrocytes stimulated with interleukin-1β to evaluate their effect on inflammation. The results reveal that encapsulation potentiates the hop extract anti-inflammatory effect and that it might be able to improve joint inflammation in osteoarthritis. Furthermore, these results also show that a "zero waste" chain is something that can be achieved in hop cultivation.


Bariatric Surgery and Metabolic Dysfunction-Associated Fatty Liver Disease: a 2022 Update.
Non-alcoholic fatty liver disease (NAFLD) has been recently termed metabolic dysfunction-associated fatty liver disease (MAFLD) to address the strong association with the metabolic syndrome. The prevalence of MAFLD is significantly increased in obese individuals and treatment of obesity is currently the cornerstone of management of MAFLD. Bariatric and metabolic surgery nowadays emerges as a key therapeutic strategy for the treatment of the MAFLD. This review aims to provide an update on the novel studies reporting the outcomes of bariatric surgery on the spectrum of MAFLD, from hepatic steatosis to cirrhosis.


Significance of incidentally thick endometrial echo on transvaginal ultrasound in postmenopausal women.
Postmenopausal bleeding is "cancer until proven otherwise." A thin distinct endometrial echo on transvaginal ultrasound has a risk of malignancy of 1 in 917 and does not require an endometrial biopsy. If the endometrial echo is poorly visualized, then in such women, saline infusion sonohysterography is an appropriate next step. The prevalence of asymptomatic endometrial thickening (mostly due to inactive polyps) is high, approximately 10% to 17% of postmenopausal women. The risk of malignancy in such polyps is low (approximately 0.1%), and in structures that mimic polyps, it is also low (0.3%). The incidence of serious complications from an operative intervention in such postmenopausal women is not insignificant (1.3%-3.6%). Thus, automatic intervention in such women, without any high-risk status, is not warranted.


Return to productivity following traumatic brain injury: cognitive, psychological, physical, spiritual, and environmental correlates.
The purpose of this study was to investigate the determinants and correlates of return to productivity (RTP) defined here as return to paid employment and/or school four years following traumatic brain injury (TBI). Participants included 46 people with TBI, part of a prospective, cohort study, and 14 friend/family member controls all employed and/or in school at time of injury or inception into the study. Variables were selected for investigation based on two models of recovery. Demographic and injury severity data including time to recover free recall were collected at time of injury, on admission to a trauma unit. Data on other variables (neuropsychological, psychological, physical, spiritual, environmental) were collected concurrent with productivity status at a mean of 4.3 years post-TBI. Time to recover free recall (measured acutely), neuropsychological status, pain severity, depression, and the use of maladaptive coping behaviours were all related to productivity status (p < 0.05). When these variables were entered into exploratory, planned hierarchical logistic regression models time to free recall, pain, and maladaptive coping remained in the models with depression only dropping out because of the high correlation with pain (r > 0.80). Injury severity (time to free recall), physical status (pain), and psychological status (depression, coping) are important to understanding differences in productivity outcomes. Addressing pain, depression and coping in rehabilitation programs may have a positive impact on outcomes.


[Molecular and immunological approach to hematological disease: detection and analysis of intracellular modified nucleosides by flow cytometry].
Modified nucleosides are components of ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). 1-methyladenosine and pseudouridine are members of those modified nucleosides. The urinary concentration of 1-methyladenosine and pseudouridine of cancer patients are higher than that of healthy controls, and those compounds were reduced after effective chemotherapy. Thus those compounds might be expected to use as tumor markers. In this study cellular origin of 1-methyladenosine and pseudouridine were analysed about two tumor cell lines (HUT-102, THP-1), peripheral blood lymphocytes (PBL) from healthy adult and PBL under the phytohemagglutinin stimulation, by flow cytometric analysis and immunofluorescent staining of cellular RNA using monoclonal antibodies specific for 1-methyladenosine (AMA) and pseudouridine (APU). Both 1-methyladenosine and pseudouridine were detected in more than 90% of tumor cells above the thresholds of flow cytometric detection (Spectrum III, Ortho). The PBL under the PHA stimulation also tended to take the same way of the tumor cell lines, whereas few of the PBL contained 1-methyladenosine above the thresholds. According to the DNA analysis of those cell lines, high contents of the modified nucleosides in the cell might follow DNA synthesis, this leads to one reason for high levels of the urinary excretion of the modified nucleosides in cancer patient.


Oral vaccination against raccoon rabies: landscape heterogeneity and timing of distribution influence wildlife contact rates with the ONRAB vaccine bait.
Aerial distribution of oral vaccine baits is one of the available strategies for controlling the spread of infectious wildlife diseases. This technique has commonly been used to control rabies in wild carnivores and, together with other techniques, was used to immunize wild populations of raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) after the detection of the first rabid raccoon in the province of Quebec, Canada, in 2006. Vaccine bait distribution was conducted over large areas where agricultural land is dominant but interspersed with residual forest patches. Our objective was to evaluate the effect of habitat (forest vs. agricultural crops) in space and time on the contact rate between wildlife and the ONRAB(®) vaccine bait, a recent alternative to the V-RG(®). Four transects of eight vaccine baits each were installed parallel to, and at different distances from, the forest's edge (under forest cover, at field-forest edge, and at 50 and 200 m from forest edge in agricultural crops) at three sites composed of various crop types interspersed with forest patches. This experiment was conducted during three periods (late spring, 1-7 June; summer, 27 July-2 August; and fall, 24-30 October) in 2009. Contact rates with vaccine baits were monitored for 7 days in each period to evaluate the potential temporal variations generated within the habitat types. Contact rates with ONRAB vaccine baits were highest under forest cover and in the fall. Of 13 species observed in proximity to the vaccine baits, raccoons were the most frequent (49.5%, n=55 visits). Our study underlines the importance of taking into account landscape heterogeneity and timing of distribution when planning the distribution of vaccine baits to control rabies in raccoons.


A Paper-Based Analytical Device Integrated with Smartphone: Fluorescent and Colorimetric Dual-Mode Detection of β-Glucosidase Activity.
In this work, indoxyl-glucoside was used as the substrate to develop a cost-effective, paper-based analytical device for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity through a smartphone. The β-glucosidase can hydrolyze the colorless substrate indoxyl-glucoside to release indoxyl, which will be self-oxidized to generate green products in the presence of oxygen. Meanwhile, the green products emit bright blue-green fluorescence under ultraviolet-visible light irradiation at 365 nm. Fluorescent or colorimetric images were obtained by a smartphone, and the red-green-blue channels were analyzed by the Adobe Photoshop to quantify the β-glucosidase activity. Under the optimum conditions, the relative fluorescent and colorimetric signals have a good linear relationship with the activity of β-glucosidase, in the range of 0.01-1.00 U/mL and 0.25-5.00 U/mL, and the limits of detection are 0.005 U/mL and 0.0668 U/mL, respectively. The activities of β-glucosidase in a crude almond sample measured by the fluorescent and colorimetric methods were 23.62 ± 0.53 U/mL and 23.86 ± 0.25 U/mL, respectively. In addition, the spiked recoveries of normal human serum and crude almond samples were between 87.5% and 118.0%. In short, the paper-based device, combined with a smartphone, can provide a simple, environmentally friendly, and low-cost method for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity.


Ecological Risk Assessment and Influencing Factors of Heavy-Metal Leaching From Coal-Based Solid Waste Fly Ash.
In order to promote and broaden the utilization of fly ash as a resource, the fly ash from a 2,660-MW coal-fired power plant in Huainan (China) was investigated. The physical and chemical properties of fly ash were characterized by scanning electron microscopy, energy spectrum analysis, and XRD. The content and different forms of the heavy metals Cd, Cr, Cu, Co, and Ni were determined by acid digestion, oscillation leaching, and Tessier five-step extraction. The effect of pH, temperature, and particle size on the leached amount of heavy metals was studied. Finally, the ecological risk index was calculated for each heavy metal via the risk assessment coding (RAC) method and Hakanson ecological risk assessment method, allowing the ecological risk of fly ash to be determined under different environmental conditions. Results showed that the average concentrations of Cd, Cr, Co, and Ni were all below the risk screening values reported for environmental pollutants (pH > 7.5). Under varying pH, temperature, and particle size conditions, the leached amounts (oscillation leaching) were below the soil risk screening values for agricultural land in China. An RAC-Cd value of >50% indicates a high ecological risk, while the RAC values of Co and Ni were between 10 and 30%, indicating a medium ecological risk, and the RAC values of Cr and Cu were <10%, indicating a low ecological risk. With increasing pH, the potential ecological risk index (RI) decreased, with a maximum RI of 59.62 observed at pH 2.8. With increasing temperature, the potential ecological RI increased initially to a maximum of 27.69 at 25°C and then decreased thereafter. With increasing particle size, the ecological RI decreased, with the highest RI of 4.06 occurring at <0.075 mm. The Hakanson ecological RI value was below 150, indicating a slight ecological risk. Therefore, fly ash can be considered as a soil additive and conditioner that is suitable for use in the improvement of reclamation soil in coal mining subsidence areas.


[Preoperative preparation and the quality of postoperative recovery in surgery patients: an experimental study].
The authors describe the methods, content and main effects of an experimental program in education of surgical patients. The material used was obtained in a study of 32 patients who had been admitted for cholecystectomy at the Surgical Ward of Veterans Hospital, Split. The program has been organized according to basic principles of a communication approach in controlling surgical stress via informing and teaching patients in pain control and other active coping skills. Informed patients (n = 16), in contrast to the control group (n = 16), showed better psychophysiological condition and less situational anxiety while facing the episode, and later, in the course of 5-day follow-up, they showed shorter, and overall better quality of post-operational recovery. In discussion, the authors call attention to the need of further systematic investigations concerning the quality and effects of patient education programs at surgical wards in Yugoslavia as necessary basis for implementation and standardization of such programs in everyday clinical practice.


Early stages of trachea healing process: (immuno/lectin) histochemical monitoring of selected markers and adhesion/growth-regulatory endogenous lectins.
Tracheotomy may be associated with numerous acute and chronic complications including extensive formation of granulation tissue. The emerging functional versatility of the adhesion/growth-regulatory galectins prompted us to perform a histochemical study of wound healing using rat trachea as model. By using non-cross-reactive antibodies and the labelled tissue lectins we addressed the issue of the presence and regulation of galectin reactivity during trachea wound healing. Beside localization of high-molecular-weight keratin, wide-spectrum cytokeratin, keratins 10 and 14, α-smooth muscle actin, vimentin, fibronectin, and Sox-2, galectins -1, -2, and -3 and their reactivity profiles were measured in frozen sections of wounded and control trachea specimens 7, 14, and 28 days after trauma. A clear trend for decreased galectin-1 presence and increased reactivity for galectin-1 was revealed from day 7 to day 28. Sox-2-positive cells were present after seven days and found in the wound bed. Interestingly, several similarities were observed in comparison to skin wound healing including regulation of galectin-1 parameters.


Giant Ovarian Cyst in a Term Pregnancy Simulating a Massive Ascites: A Case Report.
The diagnosis of ovarian mass during pregnancy may be missed if early ultrasonographic assessments of pregnancy are not done, resulting in late detection and management. Hence, this case report is aimed at underscoring the possibility of misdiagnosis of a giant ovarian mass for massive ascites in pregnancy. We present the case of a 35-year-old unbooked multigravida woman who was referred to our centre on account of polyhydramnios in labour, misdiagnosed as a massive ascites on admission. The incidental intraoperative diagnosis of a right giant ovarian cyst resulted in the right salpingo-oophorectomy of a huge cyst with the histological diagnosis of a benign ovarian serous cystadenoma. Huge cystic ovarian tumours coexisting with a normal pregnancy may simulate massive ascites resulting in a misleading diagnosis as reported in this case study. We report this case to awaken the suspicion index of a giant ovarian cyst in any patient presenting with massive ascites in pregnancy.


A Comparative Study of Nitroxide-Based Biradicals for Dynamic Nuclear Polarization in Cellular Environments.
Dynamic nuclear polarization (DNP) is a powerful tool to enhance the NMR signals of molecules by transferring polarization from unpaired electron spins to nuclei through microwave irradiation. The resulting signal enhancements can enable the analysis of samples that have previously been intractable by NMR spectroscopy, including proteins, nucleic acids, and metabolites in cells. To carry out DNP, the sample is doped with a polarization agent, a biradical containing two nitroxide moieties. DNP applications in cells, however, present significant challenges as nitroxides are often susceptible to the reducing cellular environment. Here, we introduce a novel polarization agent, POPAPOL, that exhibits increased lifetimes under reducing conditions. We also compare its bioresistance and DNP performance with three popular, commercially available polarization agents. Our work indicates that pyrrolidine-based nitroxides can outperform piperidine-based nitroxides in cellular environments, and that future polarization agent designs must carefully balance DNP performance and stability for cellular applications.


Seven Foundational Principles of Population Health Policy.
In 2016, Keyes and Galea issued 9 foundational principles of population health science and invited further deliberations by specialists to advance the field. This article presents 7 foundational principles of population health policy whose intersection with health care, public health, preventive medicine, and now population health, presents unique challenges. These principles are in response to a number of overarching questions that have arisen in over a decade of the authors' collective practice in the public and private sectors, and having taught policy within programs of medicine, law, nursing, and public health at the graduate and executive levels. The principles address an audience of practitioners and policy makers, mindful of the pressing health care challenges of our time, including: rising health-related expenditures, an aging population, workforce shortages, health disparities, and a backdrop of inequities rooted in social determinants that have not been adequately translated into formal policies or practices among the key stakeholders in population health. These principles are meant to empower stakeholders-whether it is the planner or the practitioner, the decision maker or the dedicated caregiver-and inform the development of practical tools, research, and education.


The effect of training volume and intensity on competitive cyclists' efficiency.
The impact of different intensity training on cycling efficiency in competitive cyclists is unknown. Twenty-nine endurance-trained competitive male cyclists completed 3 laboratory visits during a 12-week training period. At each visit, their cycling efficiency and maximal oxygen uptake were determined. After the first visit, cyclists were randomly split into 2 groups (A and B). Over the first 6 weeks, between tests 1 and 2, group A was prescribed specific high-intensity training sessions, whereas group B was restricted in the amount of intensive work undertaken. After test 2 and for the second 6-week period, group B was allowed to conduct high-intensity training. Gross efficiency (GE) increased in group A (+1.6 +/- 1.4%; p < 0.05) following the high-intensity training, whereas no significant change was seen in group B (+0.1 +/- 0.7%; p > 0.05). Group B cyclists increased their GE between tests 2 and 3 (+1.4 +/- 0.8%; p < 0.05) but no changes in GE were observed in group A over this period (+0.4 +/- 0.4%; p > 0.05). Delta efficiency (DE) did not change significantly in either group across the study period. This study demonstrates that GE is increased following high-intensity training in competitive male cyclists after 12 weeks.


Valorisation of the invasive alga Rugulopteryx okamurae through the production of monomeric sugars.
Rugulopteryx okamurae is an invasive brown alga causing severe environmental and economic problems on the western Mediterranean coasts. Thus, in addition to the difficulties caused to the fishing and tourism sectors, there is a need to manage its accumulation on the beaches. This work aims to valorise this waste by using it as raw material for producing monosaccharides through a two-stage sequential process. These sugars could be used for different fermentative processes to obtain high-value-added bioproducts. In this work, biological pretreatment of the previously conditioned seaweed with the fungus Aspergillus awamori in solid-state fermentation (SSF), followed by enzymatic hydrolysis with a commercial enzyme cocktail, was performed. The effect of the extension of the biological pretreatment (2, 5, 8 and 12 days) on the subsequent release of total reducing sugars (TRS) in the enzymatic hydrolysis stage was studied. To analyse this effect, experimental data of TRS produced along the hydrolysis were fitted to simple first-order kinetics. Also, the secretion of cellulase and alginate lyase by the fungus, along with the biological pretreatment, was determined. The results suggest that 5 days of biological pretreatment of the macroalgae with A. awamori followed by enzymatic saccharification for 24 h with Cellic CTec2® (112 FP units/g of dry biomass) are the best conditions tested, allowing the production of around 240 g of TRS per kg of dried biomass. The main sugars obtained were glucose (95.8 %) and mannitol (1.5 %), followed by galactose (1 %), arabinose (0.9 %) and fucose (0.5 %). KEY POINTS: • Five-day SSF by A. awamori was the best condition to pretreat R. okamurae. • Five-day SSF was optimal for alginate lyase production (1.63 ±0.011 IU/g biomass). • A maximum yield of 239 mg TRS/g biomass was obtained (with 95.8 % glucose).


Photodynamic therapy of Pheophorbide a inhibits the proliferation of human breast tumour via both caspase-dependent and -independent apoptotic pathways in in vitro and in vivo models.
Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)(50) of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5 µm. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer.


Antimicrobial Resistance: Physicians' and Pharmacists' Perspective.
Aims: The aim of this study was to evaluate pharmacists' and physicians' attitudes and knowledge about antimicrobial treatment and resistance and based on the results to identify possible gaps and suggest opportunities for collaboration between the two professions. Methods: The physician's questionnaire consisted of 47 items and the pharmacists' questionnaire consisted of 50 items. Participants were asked to identify situations in which they were more likely to prescribe/dispense an antimicrobial without a firm indication, to identify the greatest contributors to antimicrobial resistance (AMR) among health care workers, to rate statements related to AMR, how frequently they used different sources of information and to rate the possible causes of AMR. Furthermore, preparedness for specific actions in practice was self-rated and knowledge was evaluated. The questionnaires were anonymous and participation in the study was voluntary. Results: This research included 180 community pharmacists and 181 physicians. As many as 76 (42.0%) physicians stated they would prescribe an antimicrobial when unsure whether the infection was of viral or bacterial etiology. More than half of the participants considered family medicine doctors the greatest contributors to AMR (N = 216, 59.8%), followed by patients (N = 175, 48.5%). In questions focusing on knowledge, physicians scored significantly higher compared with pharmacists (4.06 ± 1.01 vs. 3.71 ± 1.08, p = 0.001). Conclusion: This research revealed practices among pharmacists and physicians that should be improved and it highlighted gaps in knowledge by both professions. More attention should be given to patient consultation when dispensing and prescribing an antimicrobial as this may reduce their contribution to AMR.


Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.
Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature's development, breeding, and homeostasis. Lately, some researchers have reported that both pathological hypoxia and environmental hypoxia might affect bone health. Adaptation to hypoxia is a pivotal cellular event in normal cell development and differentiation and in pathological settings such as ischemia. As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair. From this perspective, we summarized the role of HIF-1 and HIF-2 in signaling pathways implicated in bone development and skeletal repair and outlined the molecular mechanism of regulation of downstream growth factors and protein molecules such as VEGF, EPO, and so on. All of these present an opportunity for developing therapies for bone regeneration.


Measurement properties of the WHO Disability Assessment Schedule 2.0 for evaluating functional status after inpatient surgery.
Expert recommendations propose the WHO Disability Assessment Schedule (WHODAS) 2.0 as a core outcome measure in surgical studies, yet data on its long-term measurement properties remain limited. These were evaluated in a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) prospective cohort. Participants were adults (40 years of age or older) who underwent inpatient non-cardiac surgery. The 12-item WHODAS and EQ-5DTM-3L questionnaires were administered preoperatively (in person) and 1 year postoperatively (by telephone). Responsiveness was characterized using standardized response means (SRMs) and correlation coefficients between change scores. Construct validity was evaluated using correlation coefficients between 1-year scores and comparisons of WHODAS scores across clinically relevant subgroups. The analysis included 546 patients. There was moderate correlation between changes in WHODAS and various EQ-5DTM subscales. The strongest correlation was between changes in WHODAS and changes in the functional domains of the EQ-5D-3L-for example, mobility (Spearman's rho 0.40, 95 per cent confidence interval [c.i.] 0.32 to 0.48) and usual activities (rho 0.45, 95 per cent c.i. 0.30 to 0.52). When compared across quartiles of EQ-5D index change, median WHODAS scores followed expected patterns of change. In subgroups with expected functional status changes, the WHODAS SRMs ranged from 'small' to 'large' in the expected directions of change. At 1 year, the WHODAS demonstrated convergence with the EQ-5D-3L functional domains, and good discrimination between patients with expected differences in functional status. The WHODAS questionnaire has construct validity and responsiveness as a measure of functional status at 1 year after major surgery.


A single nucleotide polymorphism in an IgA1 protease gene determines Streptococcus pneumoniae adaptation to the middle ear during otitis media.
Factors facilitating the chronicity of otitis media (OM) in children are, to date, not fully understood. An understanding of molecular factors aiding bacterial persistence within the middle ear during OM could reveal pathways required for disease. This study performed a detailed analysis of Streptococcus pneumoniae populations isolated from the nasopharynx and middle ear of one OM case. Isolates were assessed for growth in vitro and infection in a mouse intranasal challenge model. Whole genome sequencing was performed to compare the nasopharyngeal and middle ear isolates. The middle ear isolate displayed a reduced rate of growth and enhanced potential to transit to the middle ear in a murine model. The middle ear population possessed a single nucleotide polymorphism (SNP) in the IgA1 protease gene igA, predicted to render its product non-functional. Allelic exchange mutagenesis of the igA alleles from the genetic variant middle ear and nasopharyngeal isolates was able to reverse the niche-adaptation phenotype in the murine model. These results indicate the potential role of a SNP in the gene encoding the IgA1 protease, in determining S. pneumoniae adaptation to the middle ear during chronic OM. In contrast, a functional IgA1 protease was associated with increased colonisation of the nasopharynx.


Observational Application Comparing Problem-Based Learning with the Conventional Teaching Method for Clinical Acupuncture Education.
Although the problem-based learning (PBL) teaching method was introduced in 1969, its rapid and widespread application in Malaysia started in 1979. This study aimed to evaluate satisfaction with PBL compared to that of conventional learning, using satisfaction surveys and the Rosenberg Self-Esteem scores, of students learning clinical acupuncture at the School of Traditional Chinese Medicine (TCM), Xiamen University Malaysia. The participants of this study (N=36) were registered for a bachelor's degree program in TCM in 2016 and enrolled in the Science of Acupuncture and Moxibustion course beginning in September 2018. The students were randomly allocated into two groups: PBL group and conventional group. A self-administered learning satisfaction survey and the Rosenberg Self-Esteem scores were used for data collection. An independent sample t-test was used to compare the results between the two groups. A p-value <0.05 was considered significant. The results of the learning satisfaction survey and Rosenberg Self-Esteem scores were significantly better in the PBL group than in the conventional group (p<0.05). PBL appears to be more effective for clinical acupuncture education than the conventional teaching method. However, further studies are needed to identify the mechanisms by which PBL excels in clinical acupuncture education, as well as other related TCM fields.


Potential Role of Neutrophil Extracellular Traps in Cardio-Oncology.
Cardiovascular toxicity has emerged as the leading cause of death in patients undergoing cancer treatment. Thus, cardio-oncology (CO) care must also focus on the prevention and management of related cardiovascular (CV) complications caused by cancer therapy. Neutrophil extracellular traps (NETs)-entities with released DNA, proteases, proinflammatory and prooxidative substances from blasted neutrophils-play an important role in cancer proliferation, propagation metastasis, and incident CV events (acute coronary syndrome, thromboembolic events, and heart failure). Although NETs have been shown to be involved in cancer progression and incident CV events, little is known about their relationship with cardio-oncology, especially on cancer treatment-related cardiovascular toxicity (CTRCT). This review aims to explore the evidence of the impact of NETs on cancer, CV events, and CTRCT, and the possible solutions based on the mechanism of NETs activation and NETs released toxic substances.


Endocarditis caused by Actinobacillus actinomycetemcomitans.
The first two cases of Actinobacillus actinomycetemcomitans endocarditis in Israel are reported. One involved a 67 year old woman with mitral insufficiency and the other, a 48 year old alcoholic male with bioprosthetic mitral valve. The organism grew in three of seven and seven of fourteen blood culture specimens, taken during the first two or three days of hospitalization respectively. Blood cultures became positive after incubation for seven days. The first patient recovered after therapy with penicillin and an aminoglycoside, and the second one is still being treated. Previously described cases of Actinobacillus actinomycetemcomitans endocarditis are reviewed.


Accuracy of Blood Glucose Measurement and Blood Glucose Targets.
To summarize new evidence regarding the methodological aspects of blood glucose control in the intensive care unit (ICU). We reviewed the literature on blood glucose control in the ICU up to August 2019 through Ovid Medline and Pubmed. Since the publication of the Leuven studies, the benefits of glycemic control have been recognized. However, the methodology of blood glucose control, notably the blood glucose measurement accuracy and the insulin titration protocol, plays an important but underestimated role. This may partially explain the negative results of the large, pragmatic multicenter trials and made everyone realize that tight glycemic control with less-frequent glucose measurements on less accurate blood glucose meters is neither feasible nor advisable in daily practice. Blood gas analyzers remain the gold standard. New generation point-of-care blood glucose meters may be an alternative when using whole blood of critically ill patients in combination with a clinically validated insulin dosing algorithm. When implementing blood glucose management in an ICU one needs to take into account the interaction between aimed glycemic target and blood glucose measurement methodology.


HLA-DR antigens have polymorphic light chains and invariant heavy chains as assessed by lysine-containing tryptic peptide analysis.
HLA-DR antigens were isolated from B lymphoblastoid cells labeled with either [3H]- or [14C]lysine. Double-label comparisons of the tryptic peptides by microbore ion-exchange chromatography led to the following conclusions: The heavy and light chains share few peptides, one of which is free lysine that is liberated from the polypeptide chains by trypsin. The heavy chains of different HLA-DR allospecificities are virtually identical in all cell lines examined. In contrast, the light chains of different HLA-DR allospecificities are nonidentical and, thus, must bear the alloantigenic determinant.


Conventional Total Thyroidectomy Using a Novel Single Retractor: Technical Note for Apollo®.
Despite the increasingly innovative techniques developed in thyroid surgery to offer patients minimally invasive and scarless interventions, conventional open procedures still account for most of the interventions performed in this field. The surgical incision length has been significantly reduced, from 6-9 cm to 3 cm, and therefore patients perceive the scar to be highly acceptable. In this technical note, we present the use of a new single retractor (APOLLO®; AFS MEDICAL GmbH, Teesdorf, Austria) for conventional open thyroidectomies with intraoperative neuromonitoring. This device offers several advantages: a) better exposure of the surgical field; b) less traction on skin flaps and neck muscles; and c) protection of the skin edges from the heat generated by energy-based devices/coagulating instruments, with consequent better healing.


Thyroid hormone decreases thyrotropin subunit mRNA levels in rat anterior pituitary.
Recombinant DNA clones containing sequences for the subunits of rat thyrotropin have been isolated, characterized, and used to examine the hormonal regulation of subunit mRNA levels. A library of rat cDNA sequences cloned in plasmid pBR322 was constructed and screened for thyrotropin sequences using cloned bovine cDNAs which had been previously identified. The identity of rat thyrotropin subunit cDNAs was confirmed by nucleotide sequence analysis. The cloned cDNAs were then used as hybridization probes to examine the effects of triiodothyronine on the levels of the alpha- and beta-subunit mRNAs of thyrotropin. The results demonstrate that treatment with thyroid hormone decreases the levels of both alpha- and beta-subunit mRNA in rat anterior pituitary.


High-level disinfection of gastrointestinal endoscope reprocessing.
High level disinfection (HLD) of the gastrointestinal (GI) endoscope is not simply a slogan, but rather is a form of experimental monitoring-based medicine. By definition, GI endoscopy is a semicritical medical device. Hence, such medical devices require major quality assurance for disinfection. And because many of these items are temperature sensitive, low-temperature chemical methods, such as liquid chemical germicide, must be used rather than steam sterilization. In summarizing guidelines for infection prevention and control for GI endoscopy, there are three important steps that must be highlighted: manual washing, HLD with automated endoscope reprocessor, and drying. Strict adherence to current guidelines is required because compared to any other medical device, the GI endoscope is associated with more outbreaks linked to inadequate cleaning or disinfecting during HLD. Both experimental evaluation on the surveillance bacterial cultures and in-use clinical results have shown that, the monitoring of the stringent processes to prevent and control infection is an essential component of the broader strategy to ensure the delivery of safe endoscopy services, because endoscope reprocessing is a multistep procedure involving numerous factors that can interfere with its efficacy. Based on our years of experience in the surveillance of culture monitoring of endoscopic reprocessing, we aim in this study to carefully describe what details require attention in the GI endoscopy disinfection and to share our experience so that patients can be provided with high quality and safe medical practices. Quality management encompasses all aspects of pre- and post-procedural care including the efficiency of the endoscopy unit and reprocessing area, as well as the endoscopic procedure itself.


Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine.
The availability of the cannabinoid antagonist, SR 141716A, to precipitate withdrawal following repeated cannabinoid administration provides a model to investigate the mechanisms underlying cannabinoid dependence as well as potential treatments to alleviate withdrawal symptoms. The goal of the present study was to determine whether SR 141716A-precipitated withdrawal symptoms in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant mice could be alleviated by either readministration of Delta(9)-THC or clonidine, an alpha(2)-receptor agonist. SR 141716A elicited paw tremors in Delta(9)-THC-tolerant mice, but produced a significant increase in head shakes independently of repeated Delta(9)-THC treatment. Readministration of Delta(9)-THC, following SR 141716A-precipitated withdrawal, reversed paw tremors (ED(50)=9.9 mg/kg), but failed to reduce head shaking behavior. Clonidine reversed SR 141716A-precipitated paw tremors (ED(50)=0.18 mg/kg) and blocked head shakes at all doses tested. The reversal effects did not appear to be the result of motor impairment because neither decreases in spontaneous locomotor activity nor motor incoordination, as assessed in the inverted screen test, could account for the effects. These findings suggest that SR 141716A precipitates paw tremors in mice by competing with Delta(9)-THC at the CB(1) receptor, though it also produced head shaking in nondependent animals. Finally, the observation that clonidine alleviated SR 141716A-precipitated paw tremors suggests its potential as a treatment for cannabinoid dependence.


The effectiveness of community health nursing interventions: a literature review.
As the devastating impact of many public health problems becomes more evident nationwide, a need exists for effective programs aimed at community-oriented health promotion. Escalating health care costs, however, severely limit available health care resources, threatening the demise of many public health efforts. During this time of imminent reform in our national health care system, it is imperative for community health nurses to elicit support by demonstrating the efficacy of their interventions (Oda & Boyd, 1987). This article describes services provided by community health nurses and documents the effectiveness of these interventions based on available literature. The programs reviewed represent community health nursing strategies developed in response to the needs of high-risk families, geographic communities, and vulnerable population groups. Both descriptive analyses and outcome-evaluation studies are used to support the effectiveness of home-based and community-centered community health nursing interventions. Recommendations eliciting support for community health nursing practice from legislators, policy makers, practice agencies, professional organizations, educators, and research institutions are included.


Changes in the fine structure of the human dental pulp subsequent to carious exposure.
Sections of human pulp tissue taken from the region of a carious exposure in four young patients each having a clinical history of spontaneous dental pain were examined with the electron microscope. All the tissues examined exhibited a generalized edema, and an infiltration with lymphocytes, plasma cells, polymorphonuclear leukocytes and macrophages. Varying degree of lysis of pulp and inflammatory cells were evident. The unmyelinated nerve axons of the pulp appeared to be least affected. Extracellular lysosomes were present in many of the necrotic areas. Edematous vacuoles were noted in two of the pulp specimens. In some of the sections these vacuoles appeared to be responsible for a physical distortion of adjacent unmyelinated nerve axons. It was postulated that such distortion may be a contributing factor to the pain of pulpitis. In another of the pulp specimens, micro-organisms were found intracellularly and extracellularly. Intracellularly they were present within the cytoplasm of polymorphonuclear leukocytes and macrophages and exhibited evidence of lysis. Only two morphological forms, a gram positive rod, and a gram positive coccus were identified.


Analysis of Perceptions and Emotional Repercussions in Twitter Users in Colombia During the COVID-19 Pandemic.
The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population. We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorised them in an inductive way to analyse them qualitatively. Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism. The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises.


Cellulose Nanofiber-Reinforced MXene Membranes as Stable Friction Layers and Effective Electrodes for High-Performance Triboelectric Nanogenerators.
In this work, MXene films incorporating cellulose nanofibers (CNFs) with a spider-web-like structure were fabricated using a facile vacuum-assisted filtration method. The CNFs significantly improved the flexibility and stability of the MXene membranes. The resulting composites functioned well as electrodes and friction layers in triboelectric nanogenerators (TENGs) when paired with either polytetrafluoroethylene (PTFE) as an electropositive material or nylon as an electronegative material. A membrane containing 20 wt % CNFs in conjunction with PTFE was extremely effective during the prolonged operation of a TENGs, generating an output voltage in excess of 1120 V at a frequency of 3.5 Hz. The surface charge density of this device was as high as 100 μC m-2. When paired with nylon, the MXene/CNF film produced a surface charge density of over 60 μC m-2. The microstructures on the rough surface of these membranes, together with the presence of -F and other polar terminations on the MXene, are responsible for the high performance of the nanocomposite. This work demonstrates that MXenes are not necessarily equivalent to PTFE within the triboelectric series and suggests that the MXene-based friction layer could greatly enhance the performance of TENGs.


Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin.
Ovarian cancer (OC) is a refractory cancer that shows recurrence due to the acquisition of resistance to anticancer drugs, including cisplatin. However, the molecular mechanism underlying the acquisition of cisplatin resistance by cancer cells remains largely unknown. In the present study, two sets of ovarian endometrioid carcinoma cell lines were used: The parental A2780 cell line, the OVK18 cell line, and their derived cisplatin‑resistant cells. It was found that cisplatin could induce ferroptosis in these parental cells by enhancing mitochondrial membrane potential and lipid peroxidation as assessed by flow cytometric analysis, and that expression of Ferredoxin1 (Fdx1), an iron‑sulfur protein localized to the mitochondria, could be upregulated in cisplatin‑resistant cells in the absence of cisplatin. Intriguingly, it was shown that the siRNA‑mediated depletion of Fdx1 in cisplatin‑resistant cells resulted in enhanced ferroptosis by increasing the mitochondrial membrane potential and lipid peroxidation induced by cisplatin. By examining Fdx1 expression with immunohistochemical analysis in clinical specimens from patients with OC, higher expression of Fdx1 was detected in cisplatin‑resistant specimens than in cisplatin‑sensitive specimens. Collectively, these results indicated that Fdx1 may be a novel and suitable diagnostic/prognostic marker and therapeutic molecular target for the treatment of cisplatin‑resistant OC.


[Effectiveness of etofibrate in arteriosclerosis obliterans. Pilot study in hyperlipidemic patients with arteriosclerosis obliterans].
In a pilot study the therapeutic effect of 2 x 500 mg etofibrate (Lipo Merz retard) on lipids and lipoproteins, fibrinolytic activity and clinical parameters was studied for four weeks in hyperlipidemic patients suffering from arteriosclerosis obliterans (Fontaine stage II/III). The study parameters were evaluated prior to and after the four weeks of treatment. Administration of etofibrate resulted in a significant decrease in serum cholesterol and triglyceride levels, the decrease in LDL-/HDL-cholesterol-ratio due mainly to an elevation of the HDL-cholesterol fraction, an increase in plasma fibrinolytic activity, an increased peripheral blood flow in the ischemic leg, and an increase in the pain-free walking distance. Thus, etofibrate applied twice daily might be recommended for the treatment of hyperlipidemic patients with signs of arteriosclerosis obliterans, Fontaine stage II/III.


PR10 expression in maize and its effect on host resistance against Aspergillus flavus infection and aflatoxin production.
Maize (Zea mays L.) is a major crop susceptible to Aspergillus flavus infection and subsequent contamination with aflatoxins, the potent carcinogenic secondary metabolites of the fungus. Protein profiles of maize genotypes resistant and susceptible to A. flavus infection and/or aflatoxin contamination have been compared, and several resistance-associated proteins have been found, including a pathogenesis-related protein 10 (PR10). In this study, RNA interference (RNAi) gene silencing technology was employed to further investigate the importance of PR10. An RNAi gene silencing vector was constructed and introduced into immature Hi II maize embryos through both bombardment and Agrobacterium infection procedures. PR10 expression was reduced by 65% to more than 99% in transgenic callus lines from bombardment. The RNAi-silenced callus lines also showed increased sensitivity to heat stress treatment. A similar reduction in PR10 transcript levels was observed in seedling leaf and root tissues developed from transgenic kernels. When inoculated with A. flavus, RNAi-silenced mature kernels produced from Agrobacterium-mediated transformation showed a significant increase in fungal colonization and aflatoxin production in 10 and six, respectively, of 11 RNAi lines compared with the non-silenced control. Further proteomic analysis of RNAi-silenced kernels revealed a significant reduction in PR10 production in eight of 11 RNAi lines that showed positive for transformation. A significant negative correlation between PR10 expression at either transcript or protein level and kernel aflatoxin production was observed. The results indicate a major role for PR10 expression in maize aflatoxin resistance.


Crystal structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc substrate complex.
MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas aeruginosa performing one of the key membrane steps of peptidoglycan synthesis catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP-GlcNAc and compared it with the previously solved complex from E. coli. The structure reveals a large-scale conformational change in the relative orientations of the N- and C-terminal domains, which has the effect of widening the cofactor binding site and displacing the UDP-GlcNAc donor. These results suggest new opportunities to design potent inhibitors of peptidoglycan biosynthesis.


Character Strengths and Resilience in Older Adults during the COVID-19 Pandemic.
During the pandemic, older adults were perceived as a vulnerable group without considering their various strengths. This study explored the associations between character strengths and resilience, and verified if some of these could predict resilience during the COVID-19 pandemic. A sample of 92 participants (women = 79.1%), ≥ 70 years of age (mean = 75.6 years), completed an online version of the Values in Action Inventory of Strengths - Positively keyed (VIA-IS-P) to assess 24 character strengths (grouped under six virtues) and the Connor and Davidson Resilience Scale. Results showed that 20 of the 24 strengths correlated positively and significantly with resilience. A multiple regression analysis revealed that the virtues of courage and transcendence, as well as attitudes toward aging, uniquely predicted the level of resilience. Interventions should be developed to improve certain strengths (e.g., creativity, zest, hope, humor, and curiosity), while reducing ageism, in order to promote resilience.


Nucleotide sequence preservation of human mitochondrial DNA.
Recombinant DNA techniques have been used to quantitate the amount of nucleotide sequence divergence in the mitochondrial DNA population of individual normal humans. Mitochondrial DNA was isolated from the peripheral blood lymphocytes of five normal humans and cloned in M13 mp11; 49 kilobases of nucleotide sequence information was obtained from 248 independently isolated clones from the five normal donors. Both between- and within-individual differences were identified. Between-individual differences were identified in approximately 1/200 nucleotides. In contrast, only one within-individual difference was identified in 49 kilobases of nucleotide sequence information. This high degree of mitochondrial nucleotide sequence homogeneity in human somatic cells is in marked contrast to the rapid evolutionary divergence of human mitochondrial DNA and suggests the existence of mechanisms for the concerted preservation of mammalian mitochondrial DNA sequences in single organisms.


Focal thinning of the posterior corpus callosum: normal variant or post-traumatic?
The corpus callosum (CC) can be affected by childhood traumatic brain injury (TBI), through focal lesions, reductions in size and arrested development. Little is known, however, about what constitutes normal CC shape and appearance and how it may be affected in the long-term after early TBI. In this study, the appearance of the CC was investigated in individuals with TBI assessed 10 years post-injury (n = 52, mean age = 16.82 years, SD = 3.55 years, 24 male) and compared to age-matched healthy controls (n = 44, mean age = 15.77 years, SD = 1.21 years, 18 male). A simple visual analysis technique was used to code the appearance of the CC according to location of focal thinning and severity of thinning and results between groups were compared using Chi-square analysis. A significantly higher proportion of patients with childhood TBI had focal posterior thinning of the CC than age-matched controls (p = 0.001). The findings call into question previous conclusions that focal posterior thinning is a normal variant of development. Instead, attenuations of the posterior portion of the CC in the long-term may reflect altered cortical and callosal development as a result of early brain injury, although the functional significance of this remains to be determined.


Brown Recluse Spider Bite Resulting in Coombs Negative Hemolytic Anemia in a Young Male Requiring Blood Transfusion.
Spider bites, including the bites of recluse spiders (Loxosceles, also known as brown spiders), usually lead to local symptoms; however, severe systemic symptoms have also been reported in the literature. Management of spider bites is based on symptoms. In severe cases involving the development of angioedema, hemolytic anemia, skin necrosis with superimposed bacterial infection or disseminated intravascular coagulation, antibiotics, steroids, blood transfusions, and plasma exchange may also play a role. We present a case of a brown recluse spider bite resulting in symptomatic hemolytic anemia and jaundice requiring blood transfusion.


[Psychosocial rehabilitation and monitored foster home.].
Studies on the concept of psychosocial adaptation related to the concept of social competency allow to propose a link between the level of social adaptation and this trait of personality that is the focus of control. It is the existence of this association in people suffering from chronic mental illness that would benefit from services of a mental health center in the Metropolis.


The neurobiology of psychopathy: recent developments and new directions in research and treatment.
Psychopathic individuals account for substantial predatory and impulsive violence. To the present, the principal intervention used to decrease the harm inflicted by psychopaths has been confinement. Nevertheless, most confined psychopathic persons return to the community. Recent advances in the understanding of the neurobiology of psychopathy hold promise for new research directions and more effective treatments. In this article, we will explore recent advances in genetics, electrophysiology, brain imaging, and psychopharmacology, as well as, in brief, their implications for new directions in research and treatment.


A screen of maternally inherited microbial endosymbionts in oribatid mites (Acari: Oribatida).
We determined the distribution of microbial endosymbionts as possible agents of parthenogenesis in Oribatida. We screened mites from 20 species of 14 families suspected to be parthenogenetic from the absence or rarity of males. Our research included parthenogenesis-inducing bacteria Wolbachia spp., Cardinium spp., Rickettsia spp., and additionally Arsenophonus, Spiroplasma and microsporidia that can also manipulate host reproduction. We detected the endosymbionts by PCR-based methods and transmission electron microscopy (TEM) observation of fixed and stained preparations of host cells. We detected Wolbachia only in one Oribatida species, Oppiella nova, by identifying Wolbachia genes using PCR. TEM observations confirmed infection by the endosymbiont in O. nova and its lack in other Oribatida species. Sequence analysis of hcpA and fbpA genes showed that the Wolbachia strain from O. nova was different from strains characterized in some insects, crustaceans (Isopoda), mites (Tetranychidae), springtails (Hexapoda) and roundworms (Nematoda). The analysis strongly suggested that the Wolbachia sp. strain found in O. nova did not belong to supergroups A, B, C, D, E, F, H or M. We found that the sequences of Wolbachia from O. nova were clearly distantly related to sequences from the bacteria of the other supergroups. This observation makes O. nova a unique Wolbachia host in terms of the distinction of the strain. The role of these micro-organisms in O. nova remains unknown and is an issue to investigate.


The Antimicrobial Potential of Bacteria Isolated from Honey Samples Produced in the Apiaries Located in Pomeranian Voivodeship in Northern Poland.
The principal objective of this study was to determine whether the honeys produced in apiaries located in Pomeranian Voivodeship (Northern Poland) contain bacteria producing metabolites with growth inhibition potential against important human and animal pathogens. The pathogens included Staphylococcus aurues, Staphyloccocus epidermidis, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Candida albicans. From 12 samples of honey, 163 strains of bacteria were isolated. Activity against reference staphylococci: S. aurues ATCC 25923; S. aureus ATCC 29213; S. epidermidis 12228 was observed in 33 (20.3%), 38 (23.3%), and 41 (25.1%) isolates, respectively. High inhibitory activity was also found against Listeria monocytogenes ATCC 7644 in 34 strains (20.9%). Activity against Candida albicans ATCC 10231 and especially Gram-negative bacteria: Pseudomonas aeruginosa ATCC 27857 and Escherichia coli ATCC 25922 was rarely observed. Production of metabolites exhibiting activity against the three pathogens mentioned above was confirmed for 13 (7.8%), 3 (1.8%), and 2 (1.2%) isolates, respectively. Forty-six isolates were selected for further analysis. Within this group, metabolites synthesized by 18 producing strains (39.13%) inhibited growth of only one of the reference strains of pathogenic microorganisms. However, 14 (30.44%), 8 (17.39%), and 6 (13.04%) strains produced agents active against three, two, and four pathogens, respectively. Sequencing of the 16S rRNA gene revealed that 80.4% of these 46 producing strains belong to the genus Bacillus. However, some producing strains belonging to the genus of Peanibacillus, Lysinibacillus, Microbacterium, and Staphylococcus were also identified. Furthermore, the analysis of the sequences of 16S rRNA, as well as RAPD-PCR, exhibited a significant diversity in the strains tested, even in the case of bacteria isolated from the same honey (and classified to the same genus, usually Bacillus spp.). This observation suggests environmental origin (nectar, water, or pollen) of the producing strains. The research carried out confirmed that honey produced in Northern Poland is a promising source of strains of bacteria producing metabolites with antimicrobial activity.


Induced inflammation and apoptosis in femtosecond laser-assisted capsulotomies and manual capsulorhexes: an immunohistochemical study.
To evaluate cellular inflammation and apoptosis induced in the central portion of capsulorhexes/capsulotomies during cataract surgery, comparing a conventional manual technique and a femtosecond laser-assisted procedure at different energy settings using two laser systems. Fifty-six capsulorhexes/capsulotomies were divided into four groups: the manual group (14 capsulorhexes) performed with the manual technique; the 7.0-µJ group (14 capsulotomies) (LensAR laser system; Lensar, Inc., Orlando, FL); the 10-µJ group (14 capsulotomies) (LenSx laser system; Alcon Laboratories, Inc., Fort Worth, TX); and the 13.0-µJ group (14 capsulotomies) (LenSx laser system). All samples were stained for cellular apoptosis analysis (TUNEL assay) and cellular induced inflammation (NF-κB). One-way analysis of variance indicated a statistically significant difference in the percentage of NF-κB and TUNEL positive cells between the four groups, (F [3.52] = 14.717, P < .001) and (F [3.52] = 139.561, P < .001), respectively. Post-hoc analysis indicated a statistically significant difference in the percentage of NF-κB positive cells between the 13.0-µJ group and the manual, 7.0-µJ, and 10-µJ groups (P < .001, = .037, and < .001, respectively). Post-hoc analysis of differences in TUNEL positive cells indicated a significant difference between the 7.0-µJ and 10-µJ groups (P <.017) and between the 13.0-µJ group and the manual, 7.0-µJ, and 10-µJ groups (P < .001, < .001, and < .001, respectively). The results show a higher percentage of NF-κB and TUNEL positive cells in the 13.0-µJ group compared to the 7.0-µJ, 10-µJ, and manual groups. Therefore, inflammatory response and cell death increased at increasing energies. An effective capsulotomy in femtosecond laser-assisted cataract surgery with minimal detrimental apoptotic and inflammatory effects is possible if the laser system is set to use the minimum energy level.


The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis.
Tail resorption during amphibian metamorphosis has been thought to be controlled mainly by a cell-autonomous mechanism of programmed cell death triggered by thyroid hormone. However, we have proposed a role for the immune response in metamorphosis, based on the finding that syngeneic grafts of tadpole tail skin into adult Xenopus animals are rejected by T cells. To test this, we identified two tail antigen genes called ouro1 and ouro2 that encode keratin-related proteins. Recombinant Ouro1 and Ouro2 proteins generated proliferative responses in vitro in T cells isolated from naive adult Xenopus animals. These genes were expressed specifically in the tail skin at the climax of metamorphosis. Overexpression of ouro1 and ouro2 induced T-cell accumulation and precocious tail degeneration after full differentiation of adult-type T cells when overexpressed in the tail region. When the expression of ouro1 and ouro2 were knocked down, tail skin tissue remained even after metamorphosis was complete. Our findings indicate that Ouro proteins participate in the process of tail regression as immune antigens and highlight the possibility that the acquired immune system contributes not only to self-defense but also to remodeling processes in vertebrate morphogenesis.


Spectral analysis of cyclic symptoms in late luteal phase dysphoric disorder.
Fifty-eight subjects self-referred for premenstrual difficulty were evaluated for late luteal phase dysphoric disorder through a spectral analysis technique applied to prospective symptom ratings. Data from the Schedule for Affective Disorders and Schizophrenia--Life-time Version were used to group the subjects according to the absence or presence of past or present psychiatric disorders. The two psychiatric groups were compared with regard to both patterns of significant symptom change and premenstrual symptom severity. Differences between the groups are used to discuss issues regarding the reliable identification of late luteal phase dysphoric disorder and the impact of other psychiatric disorders on this syndrome.


Predicting recurrence of nonfunctioning pituitary adenomas.
Nonfunctioning pituitary adenomas are commonly diagnosed as large tumors. Most are detected incidentally during imaging studies or as a result of neurological manifestations. Depending on severity, most patients with large tumors require surgery and adjunctive therapies because of the high rate of tumor recurrence. The ability to predict the recurrence of a tumor at the time of the initial surgery would be helpful in deciding whether adjunctive therapy is necessary and decreasing morbidity. We investigated the use of several cellular markers for predicting the recurrence of nonfunctioning pituitary adenomas. A tissue array block was made using tissue from 35 cases of nonfunctioning pituitary adenomas (16 cases with early recurrence <or=4 yr after surgery, 10 cases with late recurrence >4 yr after surgery, and nine cases without recurrence). Levels of tumor tissue cellular markers associated with cell proliferation or apoptosis were analyzed, and immunohistochemical study of cellular markers was conducted using sectioned slides from the tissue array block. High Ki-67 and TUNEL labeling indexes were associated with recurrent nonfunctioning pituitary adenomas. Tumors with a high level of expression of phospho-Akt, phospho-p44/42 MAPK, and PTTG1 were associated with early recurrence. However, high levels of expression of phospho-CREB and ZAC1 were inversely associated with recurrence. Tumors with high levels of expression of phospho-Akt and phospho-p44/42 MAPK and low levels of expression of phospho-CREB and ZAC1 should be followed closely and may require adjunctive therapy to prevent tumor recurrence.


Unique secretory dynamics of tissue plasminogen activator and its modulation by plasminogen activator inhibitor-1 in vascular endothelial cells.
We analyzed the secretory dynamics of tissue plasminogen activator (tPA) in EA.hy926 cells, an established vascular endothelial cell (VEC) line producing GFP-tagged tPA, using total internal reflection-fluorescence (TIR-F) microscopy. tPA-GFP was detected in small granules in EA.hy926 cells, the distribution of which was indistinguishable from intrinsically expressed tPA. Its secretory dynamics were unique, with prolonged (> 5 minutes) retention of the tPA-GFP on the cell surface, appearing as fluorescent spots in two-thirds of the exocytosis events. The rapid disappearance (mostly by 250 ms) of a domain-deletion mutant of tPA-GFP possessing only the signal peptide and catalytic domain indicates that the amino-terminal heavy chain of tPA-GFP is essential for binding to the membrane surface. The addition of PAI-1 dose-dependently facilitated the dissociation of membrane-retained tPA and increased the amounts of tPA-PAI-1 high-molecular-weight complexes in the medium. Accordingly, suppression of PAI-1 synthesis in EA.hy926 cells by siRNA prolonged the dissociation of tPA-GFP, whereas a catalytically inactive mutant of tPA-GFP not forming complexes with PAI-1 remained on the membrane even after PAI-1 treatment. Our results provide new insights into the relationship between exocytosed, membrane-retained tPA and PAI-1, which would modulate cell surface-associated fibrinolytic potential.


Electrochemical detection and counting of Escherichia coli in the presence of a reducible coenzyme, lipoic acid.
Reduction of lipoic acid by bacteria coupled to oxygen consumption during glucose absorption can be followed potentiometrically with a pair of gold and reference electrodes in a minimal culture medium. The variations in potential as a function of time have the shape of a wave. A theoretical expression was derived relating the size of the original inoculum to the time preceding the appearance of the wave. The validity of that relation was experimentally verified with Escherichia coli, and the time needed for a drop of 100 mV was determined. Detection of small inocula, e.g., down to a range of 10 viable E. coli per liter, is possible in about 11 h by yeast extract stimulation. The method, technically simple and adequately sensitive, suggests the possibility of automated detectors of bacterial contaminations.


Update on the pharmacogenomics of proton pump inhibitors.
Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease as well as other acid-related disorders. PPIs are metabolized primarily via the CYP2C19 and CYP3A4 isoenzymes; their activity is influenced both by exogenous and endogenous (pharmacogenetic) factors. The CYP2C19 polymorphism affects the metabolism of PPIs, causing large individual pharmacokinetic variations. Differences in the CYP2C19-mediated metabolism can produce marked interpatient variability in acid suppression, in drug-interaction potential and in clinical efficacy. Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic alterations may help clinicians optimize PPI therapy and administer individual treatment, especially to nonresponder patients with gastroesophageal reflux disease or ulcer or after failed eradication therapy.


Initial force systems during bodily tooth movement with plastic aligners and composite attachments: A three-dimensional finite element analysis.
To describe, using a three-dimensional finite element (FE) model, the initial force system generated during bodily movement of upper canines with plastic aligners with and without composite attachments. A CAD model of an upper right canine, its alveolar bone and periodontal ligament, thermoformed plastic aligner, and two light-cured composite attachments were constructed. A FE model was used to analyze the effects of imposing a distal movement condition of 0.15 mm on the aligner (simulating the mechanics used to produce a distal bodily movement) with and without composite attachments. In terms of tension and compression stress distribution, without composite attachments a compression area in the cervical third of the distal root surface and a tension area in the apical third of the mesial surface were observed. With composite attachments, uniform compression areas in the distal root surface and uniform tension area in the mesial root surface were observed. Compression areas in the active surfaces of the composite attachments were also observed. In terms of movement patterns, an uncontrolled distal inclination, with rotation axis between the middle and cervical root thirds, was observed without composite attachment. Distal bodily movement (translation) was observed with composite attachment. In a three-dimensional FE analysis of a plastic aligner system biomechanically supplementary composite attachments generate the force system required to produce bodily tooth movement; the absence of biomechanically supplementary composite attachments favors the undesired inclination of the tooth during the translation movements.


Biological importance of residual leukaemic cells after BMT for CML: does the polymerase chain reaction help?
The fate of the leukaemic clone after bone marrow transplantation (BMT) for patients with chronic myeloid leukaemia (CML) may determine the long-term prognosis. Several groups have reported the use of the polymerase chain reaction (PCR), a highly sensitive technique for detecting residual leukaemia, to study blood and bone marrow of patients in apparent cytogenetic and clinical remission at various intervals after BMT. The limitations of the technique relate to the need in CML to use mRNA rather than DNA as test material, the undefined sensitivity of the assay, the lack of knowledge of cell lineage when the test is positive and the high risk with present techniques of false positive and false negative findings. These points notwithstanding, the collected data suggest that most longterm survivors have no evidence of leukaemia detectable by PCR; in contrast many of the patients transplanted within the last 5 years do have evidence of residual leukaemia. This suggests that in a significant number of patients the leukaemic clone may survive for several years after BMT before it is eradicated (or falls below the threshold for detection by PCR). If this is confirmed the finding of residual leukaemia by PCR in the first few years post-BMT would have limited prognostic significance.


A Comparison of the Efficacy of Once-Daily Fluticasone Furoate/Vilanterole with Twice-Daily Fluticasone Propionate/Salmeterol in Elderly Asthmatics.
Asthma in the elderly population has been focused because it affects quality of life and results in a higher hospitalization rate and mortality. Fluticasone furoate (FF)/vilanterole (VI) is a novel inhaled corticosteroids (ICS)/long-acting β2 agonist (LABA) combination being developed for once-daily administration for asthma with greater anti-inflammatory activity and longer duration of bronchidilation. The ElliptaTM dry powder inhaler (DPI) has also been available as a new device with high levels of satisfaction and preference. A 12-week, randomized, open-label cross-over, pilot study was conducted in 18 elderly patients with bronchial asthma to compare the effectiveness of once-daily FF/VI 200/25 µg via the ElliptaTM DPI vs. twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 µg via the DiskusTM DPI. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) scores were measured 0, 4, and 8 weeks after randomization. Preferences for their device were also assessed using a self-completed questionnaire. Spirometric paramters, FeNO levels and ACT scores were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period. FF/VI treatment via the ElliptaTM DPI was preferred to the FP/SAL treatment via the DiskusTM DPI (p<0.01). These data indicate that FF/VI treatment via the ElliptaTM DPI is preferred in elderly patients with asthma based on its ease-of-use, suggesting the potential to improve patient adherence and, as a result, overall disease management.


Psychometric properties of the Spanish Version of the Diabetes Self-management Assessment Report Tool.
The purpose of this study is to evaluate the psychometric properties of a Spanish-language version of the Diabetes Self-management Assessment Report Tool (D-SMART) for Hispanics with type 2 diabetes. Participants were 174 Hispanics from the Worcester Family Health Center diagnosed with type 2 diabetes. Reliability testing was conducted to determine the internal consistency and stability of the newly revised Spanish-language version of the D-SMART. Psychometric findings support the reliability of the newly translated Spanish-language version of the D-SMART. The newly revised Spanish-language version of the D-SMART provides educators with a culturally relevant measure of diabetes self-management along with a better understanding about how Hispanics perceive their diabetes and self-management practices.


Including the Voice of Older Adults in Research.
The authors of this paper discuss the use of participatory and visual research methods with older adults with daily care needs in the United Kingdom. The comments made by older adults and their caregivers in focus groups provided the narrative for this paper. The authors also discuss how to engage older adults in participatory research. Nursing research and practice both involve evaluating processes to gain a holistic understanding of patients through multiple means of data collection. In other words, how do nurses give voice to otherwise silent older adults, even in cases when their strength and recall is failing?


Evaluation of in vitro anticancer potential of pharmacological ethanolic plant extracts Acacia modesta and Opuntia monocantha against liver cancer cells.
Acacia modesta (AM) and Opuntia monocantha (OM) are distributed in Pakistan, Afghanistan and India. Both of these plants have different pharmacological properties. This study was designed to evaluate anticancer potential of Acacia modesta (AM) and Opuntia monocantha (OM). Liver cancer cell line HepG2 was used for assessment of anticancer activity. For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of apoptosis ELISA of p53 performed. Furthermore, LDH assay to find out the ability of malignant cells to metabolize pyruvate to lactate and antioxidant enzymes activity (GSH, CAT and SOD) at the end HPLC was performed to find active compound of AM and OM. Cytotoxicity (MTT), Viability assays (trypan blue, crystal viability, MUSE analysis) showed more dead, less live cells in plant treated groups with increase of concentration. Scratch assay for the anti-migratory effect of these plants showed treated groups have not ability to heal scratch/wound. ELISA of p53 for cellular apoptosis showed more release of p53 in treated groups. Antioxidant assay via glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) showed less anti-oxidative potential in treated cancer groups. LDH assay showed more lactate dehydrogenase release in treated groups compared with untreated. HPLC analysis showed the presence of phytochemicals such as steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and amino acids in AM and OM plant extracts. Based on all these findings, it can be concluded that ethanolic extracts of Acacia modesta and Opuntia monocantha have promising anti-cancer potential.


CDK inhibitor Palbociclib targets STING to alleviate autoinflammation.
Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.


Spontaneous and induced chromosome damage in somatic cells of sporadic and familial Alzheimer's disease patients.
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly with a complex etiology due to the interaction between genetic and environmental factors. At least 15% of cases are inherited as an autosomal dominant mutation, but the majority are sporadic. We evaluated cytogenetic alterations, both spontaneous and chemical-induced [aluminium (Al) and griseofulvin (GF)], by means of the micronucleus (MN) test in lymphocytes or skin fibroblasts of 14 patients with sporadic and eight with familial Alzheimer's disease (FAD), respectively. The spontaneous MN frequencies of sporadic (20.8 +/- 9.2) and familial (20.7 +/- 4.6) AD patients are significantly higher than those of the respective control groups (9.0 +/- 6.8 and 6.7 +/- 3.4). In all AD patients, GF significantly increased the spontaneous MN frequency of somatic cells to a lesser extent (P < 0.05) as compared with the control group. Al treatment did not induce MN in AD patients. The results of the present study indicate that different types of somatic cells from sporadic and familial AD patients show comparable levels of spontaneous cytogenetic anomalies, and MN induction is partially reduced or lacking according to the type of chemical treatments.


Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥ 3 cm.
The optimal locoregional treatment for non-resectable hepatocellular carcinoma (HCC) of ≥ 3 cm in diameter is unclear. Transarterial chemoembolization (TACE) is the initial intervention most commonly performed, but it rarely eradicates HCC. The purpose of this study was to measure survival in HCC patients treated with adjuvant stereotactic body radiotherapy (SBRT) following TACE. A retrospective study of patients with HCC of ≥ 3 cm was conducted. Outcomes in patients treated with TACE alone (n = 124) were compared with outcomes in those treated with TACE + SBRT (n = 37). There were no significant baseline differences between the two groups. The pre-TACE mean number of tumours (P = 0.57), largest tumour size (P = 0.09) and total tumour diameter (P = 0.21) did not differ significantly between the groups. Necrosis of the HCC tumour, measured after the first TACE, did not differ between the groups (P = 0.69). Local recurrence was significantly decreased in the TACE + SBRT group (10.8%) in comparison with the TACE-only group (25.8%) (P = 0.04). After censoring for liver transplantation, overall survival was found to be significantly increased in the TACE + SBRT group compared with the TACE-only group (33 months and 20 months, respectively; P = 0.02). This retrospective study suggests that in patients with HCC tumours of ≥ 3 cm, treatment with TACE + SBRT provides a survival advantage over treatment with only TACE. Confirmation of this observation requires that the concept be tested in a prospective, randomized clinical trial.


Rectangle and [2]catenane from cluster modular construction.
Reaction of [Et4N][Tp*WS3] (1) with [Cu(MeCN)4]PF6, CsCl, isonicotinic acid and CuCN, and treatment of [Et4N][Tp*WS3(CuCl)3] (2)/[Et4N][{Tp*WS3Cu3Cl}2(μ-Cl)2(μ4-Cl)] (3) with AgOTf and bpp (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate; bpp = 1,3-di(4-pyridyl)propane) give rise to [Et4N]2[{Tp*WS3Cu3(CN)0.5}2(μ-Cl)2(μ4-Cl)]2(PF6)2 (4) and [(Tp*WS3Cu3)2(μ3-Cl)2(bpp)3]2(OTf)4 (5), respectively. Compounds 4 and 5 feature cluster-based rectangle and [2]catenane architecture, and both exhibit enhanced third-order nonlinear optical responses relative to those of 1.


The Concept of Successful Aging: A Review Article.
With the increasing number of elderly people in the world, usage of concepts and terminology related to this phenomenon has substantially increased. One concept in this context is successful aging. The purpose of the present study is to extract and introduce a common concept to be used in studies on measuring successful aging. This is a review study. First, by searching the databases of Magiran, Noormags, Medlib, Irandoc, Iranmedex, Barakat Knowledge Network System, Civilica, SID, ISI Web Of Science, PubMed, Scopus, Science Direct and search engines, Google Scholar and Elmnet as well as using standard keywords such as elder, elderly, aging, and successful aging, all related published articles during the period 1995 to 2017 were retrieved. A total of 3417 documents were retrieved. By removing 3390 unrelated, duplicate and unusable documents, 27 articles were included in the study after quality control. The findings of the study were categorized in three areas: "defining successful aging by focusing on dimensions", "successful aging principles" and "factors influencing successful aging". Reviewing various studies, we found that the definition of successful aging deals with cognitive action, perception, control, life satisfaction, and ethics. Successful aging is also defined as having inner feelings of happiness and satisfaction with life for the present and the past. Sometimes successful aging is also considered to be survival with health. Health care professionals as community health supporters can use the results from the present study for providing the grounds for successful aging. Then, they can use the designed successful aging program for preserving and promoting active and healthy aging for every elderly person in old age.


Clinical Effect of Endoscopic Vidian Neurectomy on Bronchial Asthma Outcomes in Patients with Coexisting Refractory Allergic Rhinitis and Asthma.
Background The prevalence of both allergic rhinitis and bronchial asthma is high throughout the world; their mutual influence on each other has been documented in many studies. However, studies regarding surgical intervention are limited. Objective To evaluate the clinical significance of endoscopic vidian neurectomy on bronchial asthma outcomes in patients with coexisting refractory allergic rhinitis and asthma. Methods A total of 109 patients with moderate to severe persistent intractable allergic rhinitis and mild/moderate asthma were allocated to the bilateral endoscopic vidian neurectomy group (group 1) or conservative medication group (group 2) according to the patients' self-selection. The Rhinoconjunctivitis Quality of Life Questionnaire, Visual Analog Scale, Asthma Quality of Life Questionnaire, Total Asthma Symptom Score, and medication scores were evaluated at six months, one year, and three years after undergoing the initial treatments. Multivariate analysis was performed to determine which triggers of asthma attacks were associated with improved asthma outcomes in patients. Results Ninety-five patients were followed up for at least three years. Postoperative scores of Rhinoconjunctivitis Quality of Life Questionnaire and Visual Analog Scale were significantly lower than preoperative scores during follow-up in group 1 and were significantly lower than those of group 2. Postoperative scores of Asthma Quality of Life Questionnaire at the three follow-up time points were higher than the preoperative scores in group 1. The Total Asthma Symptom Score was not significantly decreased in group 1. The medication scores for allergic rhinitis and asthma were gradually reduced after surgery. At the end of the follow-up, the improvement rates for allergic rhinitis and asthma were 90.6% and 45.3%, respectively. Asthma outcomes were significantly improved by controlling rhinitis symptoms in patients whose asthma attacks were induced by "rhinitis onset" or "weather change." Conclusion Controlling allergic rhinitis symptoms by bilateral endoscopic vidian neurectomy can significantly improve asthma outcomes in patients whose asthma attacks are induced by rhinitis onset and/or cold air.


Novel blood derived hemostatic agents for bleeding therapy and prophylaxis.
Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic challenges. Early, aggressive administration of blood-derived products with hypothesized increased clotting potency has been proposed. A series of early- and late-phase clinical trials testing the safety and/or efficacy of lyophilized plasma and new forms of platelet products in humans have provided light on the future of alternative blood component therapies. This review intends to contextualize and provide a critical review of the information provided by these trials. The beneficial effect of existing freeze-dried plasma products may not be as high as initially anticipated when tested in randomized, multicenter clinical trials. A next-generation freeze dried plasma product has shown safety in an early phase clinical trial and other freeze-dried plasma and spray-dried plasma with promising preclinical profiles are embarking in first-in-human trials. New platelet additive solutions and forms of cryopreservation or lyophilization of platelets with long-term shelf-life have demonstrated feasibility and logistical advantages. Recent trials have confirmed logistical advantages of modified plasma and platelet products in the treatment or prophylaxis of bleeding. However, their postulated increased potency profile remains unconfirmed.


The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2.
The E1B-55K and E4orf6 oncoproteins of adenovirus type 5 are involved in the export of viral mRNAs. Previously, it was suggested that a complex composed of E1B-55K and E4orf6 serves as a nucleocytoplasmic transporter for viral mRNAs in which the E4orf6 protein directs both nuclear import and export. We now demonstrate that the E1B-55K protein itself shuttles efficiently in the absence of E4orf6. In addition, E1B-55K trafficking was independent of the defined shuttle proteins Mdm2 or p53, which interacts with E1B-55K. The identified N-terminal E1B-55K leucine-rich nuclear-export signal (NES) conferred rapid nuclear export even in a heterologous system in contrast to the postulated E4orf6NES. Interestingly, although shuttling was blocked by inhibitors of the CRM1 mediated export pathway, E1B-55K inhibited neither the activity nor the trafficking of the retroviral shuttle proteins HIV-1 Rev and HTLV-1 Rex. In contrast, Rev or Rex blocked the nuclear export of E1B-55K, most likely by competing for essential export factors. Our results provide new insights into the regulation of the adenovirus mRNA export system and the processes of adenovirus mediated transformation. Oncogene (2000) 19, 850 - 857.


[Coronary radiography in patients with valvular cardiopathies and stenocardia].
Seventy patients with valvular cardiopathies were performed selective coronarography besides the routine hemodynamic examination during the period 1973-1983. Those 70 patients could be subdivided in the following way: 46 with aortic, 17 - with mitral-aortic and 7 with mitral valvular lesion. Their average age is 46,15 +/- 1,42. Considerable changes (stenosis over 50% of at least one artery of the three main ones) were established in 9 patients (12,85%). The average age of the patients with the changes is 47,44 +/- 1,64. Angina pectoris had 57 out of 70 patients (81,42%). The mean telediastolic pressure of left ventricle of the patients with coronary alterations was 3,94 +/- 0,63 kPa (29,6 +/- 4,71 mm Hg) whereas the others, with intact coronary arteries had a mean telediastolic pressure of 2,6 +/- 0,43 kPa (19,43 +/- 3,26 mm Hg). Out of the nine patients with coronary changes--6 were males and 3--females. All had aortic valvular lesions--four with high degree stenosis, there--with high degree insufficiency and two--with mixed defect. The authors think that the systematic coronarographic investigations of the patients that are to have valvular prosthetization, is not necessary.