Multiscale determinants of Pacific chorus frog occurrence in a developed landscape.
Pacific chorus frog (Pseudacris regilla) populations have persisted despite urban and rural development throughout the species' range; yet it is possible that P. regilla, like other anurans with which it historically co-occurred, will become extirpated from cities and suburbs if urbanization intensifies as predicted. An improved understanding of the conditions that enable this species to persist in developed landscapes is needed to identify and conserve suitable habitats. We investigated species-habitat relationships for P. regilla in a mixed urban-rural landscape in southwestern British Columbia, Canada, to identify potential criteria for habitat suitability. We conducted repeat auditory surveys of chorusing males at 52 potential breeding wetlands and modeled occupancy at 26 of these sites using local and landscape variables representing competing hypotheses and spatial scales of influence. The models that best explained P. regilla occupancy included a combination of terrestrial habitat and connectivity factors and the presence of non-native predators. We found that the proportion of impervious cover within 250 m of a wetland had the strongest negative impact on occupancy. Our findings suggest that availability of terrestrial habitat adjacent to breeding sites is the primary driver of species presence in the developed landscape. Conservation efforts should seek to limit impervious cover to less than 20% within a 250-m buffer around breeding wetlands. Further, restored and created wetlands in urban and rural areas may be more likely to support P. regilla if they are designed with a seasonal hydroperiod that excludes non-native aquatic predators and are placed in an area of high pond density.


Enhanced binding of fibronectin-coated latex beads to quiescent 3T3-L1 cells is correlated with escape from growth arrest.
The possible involvement of fibronectin receptors in growth stimulation was investigated by an analysis of fibronectin-coated latex bead binding to 3T3-L1 cells under various conditions. 3T3-L1 cells, growth-arrested in a medium with a low concentration of calf serum, bound few fibronectin-coated beads. After addition of serum at concentrations of 1.0% or higher, there was a rapid and transient increase in the number of cells with bound beads and a subsequent increase in the incorporation of bromodeoxyuridine (BrdU) into cell nuclei. Incorporation of BrdU was observed in about 60% of the cells with bound beads. Fibroblast growth factor and platelet-derived growth factor at concentrations of 5 ng/ml or higher also enhanced binding of fibronectin-coated beads to cells. Stimulation of bead binding by epidermal growth factor and insulin was weak. Fibroblast growth factor, but not epidermal growth factor, increased the incorporation of BrdU into nuclei. These results indicate a relationship between stimulation of cell proliferation in quiescent cells and increased binding by cells of fibronectin-coated latex beads.


Diversity of Coronaviruses with Particular Attention to the Interspecies Transmission of SARS-CoV-2.
In December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China with serious impacts on global health and economy that is still ongoing. Although interspecies transmission of coronaviruses is common and well documented, each coronavirus has a narrowly restricted host range. Coronaviruses utilize different receptors to mediate membrane fusion and replication in the cell cytoplasm. The interplay between the receptor-binding domain (RBD) of coronaviruses and their coevolution are determinants for host susceptibility. The recently emerged SARS-CoV-2 caused the coronavirus disease 2019 (COVID-19) pandemic and has also been reported in domestic and wild animals, raising the question about the responsibility of animals in virus evolution. Additionally, the COVID-19 pandemic might also substantially have an impact on animal production for a long time. In the present review, we discussed the diversity of coronaviruses in animals and thus the diversity of their receptors. Moreover, the determinants of the susceptibility of SARS-CoV-2 in several animals, with special reference to the current evidence of SARS-CoV-2 in animals, were highlighted. Finally, we shed light on the urgent demand for the implementation of the One Health concept as a collaborative global approach to mitigate the threat for both humans and animals.


Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1.
Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.


Improved electrochemical analysis of neuropathy target esterase activity by a tyrosinase carbon paste electrode modified by 1-methoxyphenazine methosulfate.
A graphite-paste tyrosinase biosensor was improved by adding 1-methoxyphenazine methosulfate as a mediator. Mediator modification enhanced sensitivity to phenol 4-fold and long-term stability 3-fold. Phenol could be detected at 25 nM (S/N = 2) using an Ag/AgCl reference electrode. The biosensor was used to measure the activity of a toxicologically significant enzyme, neuropathy target esterase (NTE), which yields phenol by hydrolysis of the substrate, phenyl valerate. Using the new biosensor, blood and brain NTE inhibition by organophosphorus (OP) compounds with different neuropathic potencies were well correlated (r = 0.990, n = 7), supporting the use of blood NTE as a biochemical marker of exposure to neuropathic OP compounds.


Textural analysis of a mesophase with banana shaped molecules.
Observed under the polarizing microscope, the B7bis phase in the banana compound D14F3 [J.P. Bedel et al., Liq. Cryst. 27, 1411 (2000)] displays two types of textures of defects, namely (a): helical ribbons, that nucleate in large quantities when the samples are quenched from a sufficiently high temperature in the isotropic phase (b)- shapes with no helicity having the structure of developable domains much akin to those observed in columnar phases, either resulting from the annealing of the helical ribbons or nucleating under slow cooling processes. The existence of these two kinds of defects points toward the complex nature of the structure of the B7 phase, which is at the same time a columnar and a smectic phase. Our observations fit the model [M. Kleman, J. Phys. France 46, 1193 (1985)] according to which the geometry of a helical ribbon is that one of the central region of a screw dislocation with a giant Burgers vector, split into two helical disclination lines of strength k = 1/2 which bound the ribbon. Textures and defects, already partly documented, and growth features and annealing processes, not yet reported in the literature, are analyzed. We conclude that the helical ribbons and the developable domains with no helicity are textures of two different B7 states, namely a metastable state and the ground state respectively. Comparative textural analysis is performed for two other banana compounds exhibiting B2 phases.


The effect of different methods of stability assessment on fixation rate and complications in supination external rotation (SER) 2/4 ankle fractures.
Distinguishing stable supination-external rotation (SER) 2 from unstable SER 4 ankle fractures, using standard radiographs, is controversial. Examination under anaesthesia (EUA), gravity-stress (GS) and weight-bearing (WB) radiographs can aid surgical decision-making. We evaluated the effect of three methods of fracture stability assessment. Radiographs and case-notes of 312 consecutive patients with SER 2/4 fractures were reviewed. We recorded ankle stability assessment (plain film (PF) and EUA vs. GS vs. WB radiographs), management (conservative vs. operative), unplanned surgery and complications. Forty five percent assessed with GS underwent surgery (6% for PF/EUA, 4% for WB; P=0.0001). Amongst GS patients, 11% underwent additional surgery (0.1% PF/EUA, 0% WB; P=0.0001). Complications occurred in 2% of the WB group (8% for PF/EUA, 22% for GS; P=0.007). This study associates GS assessment with higher rates of surgery and complications. Subsequent studies may determine the longer term effect stability assessments have on post-traumatic arthritis.


Nd:YAG laser photodisruption of the lens nucleus before phacoemulsification.
We studied the use of Q-switched Nd:YAG laser pulses to soften sclerotic lens nuclei before phacoemulsification. We obtained 105 lens nuclei from extracapsular cataract extractions, graded them for degree of sclerosis, and randomized them into laser treatment (53 lenses) or control groups (52 lenses). The treated lenses received laser pulses until confluent pits and clefts were visible. All lenses were phacoemulsified and the times recorded. Nd:YAG laser pretreatment decreased phacoemulsification time in all grades. In moderately sclerotic nuclei, average phacoemulsification time was reduced from 40.1 to 23.9 seconds (40.4%). The nuclei of ten lenses obtained from intracapsular cataract extractions were treated intracapsularly, and the posterior capsule was inadvertently ruptured in five.


Modulation of fibril formation by a beta-sheet breaker peptide ligand: an electrochemical approach.
The development of generic inhibitors in order to control the formation of amyloid fibrils and early oligomers is still an unmet medical need. Here, we demonstrate the applicability of electrochemical analysis for the detection of β-sheet breaker peptide ligands that act as excellent inhibitors of Alzheimer's disease (AD) amyloid-β (Aβ) fibrils and oligomers in vitro. As the case study, a well-defined β-sheet breaker pentapeptide (LPFFD, FibIII) was utilized with Aβ(1-42) peptides. Square wave voltammetry (SWV) measurements were confirmed with simultaneous fluorescence analysis of the same incubated Aβ samples using a well-known fluorescent marker of β-sheet formation, Thioflavin T (ThT). Significant changes in the electrochemical signals were observed for the interaction of the Aβ oligomers with FibIII at the early stages of aggregation. The electrochemical approach, in principle, allowed monitoring β-sheet breaker-Aβ interactions on the time scale of aggregation in a label-free and cost-effective format using screen-printed carbon strip (SPCS) electrodes.


Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer.
We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.


Interfacial tension in phase-separated aqueous cationic/anionic surfactant mixtures.
Interfacial tensions in two aqueous phase-separated cationic/anionic surfactant mixtures, CTAB/AS and 12-3-12/AS, without and with NaBr added were determined by the spinning drop method at 318.15 K. CTAB, 12-3-12 and AS are the abbreviations for cetyltrimethylammonium bromide, 1,3-propanediyl-bis(dodecyldimethylammonium bromide) and sodium dodecyl sulfonate, respectively. The interfacial tension sigma was found to be in the range of 0.06-21 microNm(-1). Toward a better understanding of the influence of the concentration difference between the separated phases in aqueous two-phase systems (ATPS) to interfacial tension, compositions of equilibrium phases were determined by elemental analysis coupled with material balance and electroneutrality. The investigation indicates that the concentration differences of surfactant ions between the separated phases and the adsorption of surfactant ions at the interface are the decisive factors determining the magnitude of interfacial tension.


Effect of a pescetarian and vegan diet on fatty acid composition in blood and spermatozoa in young healthy men.
There is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men. Four groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content. Main findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group. Higher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men.


Overview of the fracture healing cascade.
Fracture healing is a dynamic process being governed by a variety of cellular elements and stimulating agents. Our knowledge in understanding the molecular and cellular processes occurring in healing fractures has vastly expanded as a result of the advances made in all aspects of medicine. The ability to manipulate mesenchymal stem cells and to deliver locally growth factors in order to create new bone has led to a proliferation of research papers. The purpose of this article is to provide a brief overview of the current level of understanding of the physiological processes regulating the healing of fractures.


Why are young Canadians afraid of birth? A survey study of childbirth fear and birth preferences among Canadian University students.
to examine attitudes towards birth that may be common among young adults who have been socialised into a medicalised birth culture. Specifically, we were interested in examining factors that might be associated with fear of birth and preferences for elective obstetric interventions among the next generation of maternity care consumers. secondary analysis of an online survey of university students. British Columbia, Canada. students from the University of British Columbia (n=3680). A quarter of the sample comprised Asian students, which allowed for analysis of cultural differences in attitudes towards birth. Both male and female students participated in the study; results are reported for the full sample, and by gender. a six item fear of childbirth scale was developed, as well as a 4 item index that measures students' concerns over physical changes following pregnancy and birth and a 2 item scale that assesses students' attitudes towards obstetric technology. as we hypothesised, students who were more fearful of birth preferred epidural anaesthesia and birth by CS. Worries over physical changes following pregnancy and birth, favourable attitudes towards obstetric technology, and exposure to pregnancy and birth information via the media were also significantly associated with a preference for CS. Fear of birth scores were highest among students who reported that the media had shaped their attitudes towards pregnancy and birth. Asian students had significantly higher fear of birth scores and were more likely to prefer CS, compared to Caucasian students. young adults are contemplating pregnancy and birth in an increasingly technology-dependent society. Educational programmes aimed at reducing fear of childbirth and concerns over physical changes following pregnancy and childbirth might contribute to vaginal birth intentions among young adults. Midwives may use the findings to identify and counsel nulliparas who exhibit fear of birth and other childbirth attitudes that may predispose them to choose elective obstetric interventions.


Decision making in treatment of symptomatic severe aortic stenosis: a survey study in Dutch heart centres.
To provide insight into the basic characteristics of decision making in the treatment of symptomatic severe aortic stenosis (SSAS) in Dutch heart centres with specific emphasis on the evaluation of frailty, cognition, nutritional status and physical functioning/functionality in (instrumental) activities of daily living [(I)ADL]. A questionnaire was used that is based on the European and American guidelines for SSAS treatment. The survey was administered to physicians and non-physicians in Dutch heart centres involved in the decision-making pathway for SSAS treatment. All 16 Dutch heart centres participated. Before a patient case is discussed by the heart team, heart centres rarely request data from the referring hospital regarding patients' functionality (n = 5), frailty scores (n = 0) and geriatric consultation (n = 1) as a standard procedure. Most heart centres 'often to always' do their own screening for frailty (n = 10), cognition/mood (n = 9), nutritional status (n = 10) and physical functioning/functionality in (I)ADL (n = 10). During heart team meetings data are 'sometimes to regularly' available regarding frailty (n = 5), cognition/mood (n = 11), nutritional status (n = 8) and physical functioning/functionality in (I)ADL (n = 10). After assessment in the outpatient clinic patient cases are re-discussed 'sometimes to regularly' in heart team meetings (n = 10). Dutch heart centres make an effort to evaluate frailty, cognition, nutritional status and physical functioning/functionality in (I)ADL for decision making regarding SSAS treatment. However, these patient data are not routinely requested from the referring hospital and are not always available for heart team meetings. Incorporation of these important data in a structured manner early in the decision-making process may provide additional useful information for decision making in the heart team meeting.


Application of genetically engineered microbial whole-cell biosensors for combined chemosensing.
The progress of genetically engineered microbial whole-cell biosensors for chemosensing and monitoring has been developed in the last 20 years. Those biosensors respond to target chemicals and produce output signals, which offer a simple and alternative way of assessment approaches. As actual pollution caused by human activities usually contains a combination of different chemical substances, how to employ those biosensors to accurately detect real contaminant samples and evaluate biological effects of the combined chemicals has become a realistic object of environmental researches. In this review, we outlined different types of the recent method of genetically engineered microbial whole-cell biosensors for combined chemical evaluation, epitomized their detection performance, threshold, specificity, and application progress that have been achieved up to now. We also discussed the applicability and limitations of this biosensor technology and analyzed the optimum conditions for their environmental assessment in a combined way.


Urinary concentrations of triclosan in the U.S. population: 2003-2004.
Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware. This study was designed to assess exposure to triclosan in a representative sample > or = 6 years of age of the U.S. general population from the 2003-2004 National Health and Nutrition Examination Survey (NHANES). We analyzed 2,517 urine samples using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We detected concentrations of total (free plus conjugated) triclosan in 74.6% of samples at concentrations of 2.4-3,790 microg/L. The geometric mean and 95th percentile concentrations were 13.0 microg/L (12.7 microg/g creatinine) and 459.0 microg/L (363.8 mug/g creatinine), respectively. We observed a curvilinear relation between age and adjusted least square geometric mean (LSGM) concentrations of triclosan. LSGM concentrations of triclosan were higher in people in the high household income than in people in low (p < 0.01) and medium (p = 0.04) income categories. In about three-quarters of urine samples analyzed as part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations differed by age and socioeconomic status but not by race/ethnicity and sex. Specifically, the concentrations of triclosan appeared to be highest during the third decade of life and among people with the highest household incomes.


Neuromodulation in Dystonia - Harnessing the Network.
Adult-onset isolated focal dystonia (AOIFD) is a network disorder characterised by abnormalities of sensory processing and motor control. These network abnormalities give rise to both the phenomenology of dystonia and the epiphenomena of altered plasticity and loss of intracortical inhibition. Existing modalities of deep brain stimulation effectively modulate parts of this network but are limited both in terms of targets and invasiveness. Novel approaches using a variety of non-invasive neuromodulation techniques including transcranial stimulation and peripheral stimulation present an interesting alternative approach and may, in conjunction with rehabilitative strategies, have a role in tailored therapies targeting the underlying network abnormality behind AOIFD.


Transcription fidelity and its roles in the cell.
Accuracy of transcription is essential for productive gene expression, and the past decade has brought new understanding of the mechanisms ensuring transcription fidelity. The discovery of a new catalytic domain, the Trigger Loop, revealed that RNA polymerase can actively choose the correct substrates. Also, the intrinsic proofreading activity was found to proceed via a ribozyme-like mechanism, whereby the erroneous nucleoside triphosphate (NTP) helps its own excision. Factor-assisted proofreading was shown to proceed through an exchange of active centres, a unique phenomenon among proteinaceous enzymes. Furthermore, most recent in vivo studies have revised the roles of transcription accuracy and proofreading factors, as not only required for production of errorless RNAs, but also for prevention of frequent misincorporation-induced pausing that may cause conflicts with fellow RNA polymerases and the replication machinery.


Essential histidyl residues at the active site(s) of sucrose-phosphate synthase from Prosopis juliflora.
Chemical modification of sucrose-phosphate synthase (EC 184.108.40.206) from Prosopis juliflora by diethyl pyrocarbonate (DEP) and photo-oxidation in the presence of rose bengal (RB) which modify the histidyl residues of the protein resulted in the inactivation of the enzyme activity. This inactivation was dependent on the concentration of the modifying reagent and the time of incubation and followed pseudo-first order kinetics. For both the reagents, the inactivation was maximum at pH 7.5, which is consistent with the involvement and presence of histidine residues at the active site of the enzyme. Substrates, UDPG and F6P protected the enzyme against the inactivation by the modifying reagents suggesting that the histidine residues may be involved in the binding of these substrates and are essential for the catalytic activity. Specificity of DEP was indicated by an increase in absorbance at 240 nm along with concomitant inactivation of the enzyme and reactivation of the modified enzyme by hydroxylamine. These results strongly suggest the presence of histidine residue(s) at or near the active site of the enzyme.


Premature osteoarthritis of the knee associated with cartilage hypertrophy and phalangeal dysgenesis.
A woman presented with premature knee osteoarthritis associated with marked femoral cartilage hypertrophy. She also exhibited phalangeal dysgenesis, suggesting this may be an unrecognised syndrome that may predispose to knee osteoarthritis.


[Influence of basic fibroblast growth factors on the migration, proiferation of osteoblasts and periodontal ligament fibroblasts].
In order to determine the influence of bFGF on the biological characteristics of osteoblasts and periodontal ligament cells, the author investigate the influence of bFGF on the migration, proliferation of osteoblasts and periodontal ligament fibroblasts between osteoblasts and fibroblasts. The forth generation of osteoblasts and periodontal ligament fibroblast were obtained and the wounding model in vitro of them was founded. The cells were cultured in mediums with or without bFGF. Their migration and proliferation were observed and measured. Osteoblasts migrated faster than fibroblasts in common culture medium without bFGF and the periodontal ligament fibroblasts in culture medium with bFGF had higher migration rate than other groups. bFGF promoted the proliferation of both two kinds of cells. bFGF could accelerate periodontal fibroblasts' proliferation and migration.


Effects of nitric oxide system and osmotic stress on Aquaporin-1 in the postnatal heart.
Aquaporin-1 (AQP1) is expressed in the heart and its relationship with NO system has not been fully explored. The aims of this work were to study the effects of NO system inhibition on AQP1 abundance and localization and evaluate AQP1 S-nitrosylation in a model of water restriction during postnatal growth. Rats aged 25 and 50days (n=15) were divided in: R: water restriction; C: water ad libitum; RL: L-NAME (4mg/kgday)+water restriction; CL: L-NAME+water ad libitum. AQP1 protein levels, immunohistochemistry and S-nitrosylation (colocalization of AQP1 and S-nitrosylated cysteines by confocal microscopy) were determined in cardiac tissue. We also evaluated the effects of NO donor sodium nitroprusside (SNP) on osmotic water permeability of cardiac membrane vesicles by stopped-flow spectrometry. AQP1 was present in cardiac vascular endothelium and endocardium in C and CL animals of both ages. Cardiac AQP1 levels were increased in R50 and RL50 and appeared in cardiomyocyte plasma membrane. No changes in AQP1 abundance or localization were observed in R25, but RL25 group showed AQP1 presence on cardiomyocyte sarcolemma. AQP1 S-nitrosylation was increased in R25 group, without changes in the 50-day-old group. Cardiac membrane vesicles expressing AQP1 presented a high water permeability coefficient and pretreatment with SNP decreased water transport. Age-related influence of NO system on AQP1 abundance and localization in the heart may affect cardiac water homeostasis during hypovolemic state. Increased AQP1 S-nitrosylation in the youngest group may decrease osmotic water permeability of cardiac membranes, having a negative impact on cardiac water balance.


Cigarettes, alcohol, coffee, and caffeine as risk factors for colorectal adenomatous polyps.
The possible association of colorectal adenomatous polyps, a precursor lesion for colorectal cancer, with cigarette smoking, alcohol consumption, and coffee and caffeine consumption was investigated in a case-control study. Between April 1986 and March 1988, 271 cases of patients with pathologically confirmed incident colorectal adenomatous polyps and 457 control subjects were collected from three colonoscopy practices in New York City. Information on exposure was obtained by structured interviews. After adjustment of age, statistically significant odds ratios (highest-lowest quartile) were found for cigarette smoking in males (2.2; 95% confidence interval (CI), 1.2 to 3.8) and coffee consumption in females (2.0%; 95% CI, 1.0 to 3.9). No significant associations were obtained for cigarette smoking in females, for coffee consumption in males, or for alcohol or caffeine consumption. After adjustments for alcohol, coffee, and caffeine consumption, the association of adenomas with cigarette smoking remained in males and significant associations were also observed in subcategory analysis for both left-side and right-side adenomatous polyps. Adjustment for cigarette smoking eliminated the association between colorectal adenomatous polyps and coffee consumption in females. Cigarette smoking appears to be a significant risk factor for colorectal adenomatous polyps in males.


Rewiring a Rab regulatory network reveals a possible inhibitory role for the vesicle tether, Uso1.
Ypt1 and Sec4 are essential Rab GTPases that control the early and late stages of the yeast secretory pathway, respectively. A chimera consisting of Ypt1 with the switch I domain of Sec4, Ypt1-SW1Sec4, is efficiently activated in vitro by the Sec4 exchange factor, Sec2. This should lead to its ectopic activation in vivo and thereby disrupt membrane traffic. Nonetheless early studies found that yeast expressing Ypt1-SW1Sec4 as the sole copy of YPT1 exhibit no growth defect. To resolve this conundrum, we have analyzed yeast expressing various levels of Ypt1-SW1Sec4 We show that even normal expression of Ypt1-SW1Sec4 leads to kinetic transport defects at a late stage of the pathway, with secretory vesicles accumulating near exocytic sites. Higher levels are toxic. Toxicity is suppressed by truncation of Uso1, a vesicle tether required for endoplasmic reticulum-Golgi traffic. The globular head of Uso1 binds to Ypt1 and its coiled-coil tail binds to the Golgi-associated SNARE, Sed5. We propose that when Uso1 is inappropriately recruited to secretory vesicles by Ypt1-SW1Sec4, the extended coiled-coil tail blocks docking to the plasma membrane. This putative inhibitory function could serve to increase the fidelity of vesicle docking.


Preference and uptake of different community-based HIV testing service delivery models among female sex workers along Malaba-Kampala highway, Uganda, 2017.
Female Sex workers (FSW) and their clients accounted for 18% of the new HIV infections in 2015/2016. Special community-based HIV testing service delivery models (static facilities, outreaches, and peer to peer mechanism) were designed in 2012 under the Most At Risk Populations Frame work and implemented to increase access and utilization of HIV care services for key populations like female sex workers. However, to date there is no study that has been done to access the preference and uptake of different community-based HIV testing service delivery models used to reach FSW. We assessed preference and uptake of the current community-based HIV testing services delivery models that are used to reach FSW and identified challenges faced during the implementation of the models. We conducted a cross-sectional study design using quantitative (interview with the health workers in facilities providing services to female sex workers and interviews with FSWs) and qualitative (interviews with Ministry of Health staff, health workers, district health team members, program staff at different levels involved in delivery of HIV care services, FSWs and political leaders to assess for the enabling environment created to deliver the different community-based HIV testing services to FSWs along the Malaba-Kampala highway. Malaba - Kampala high way is one of the major high ways with many different hot spots where the actual buying and selling of sex takes place. We defined FSWs as any female, who undertakes sexual activity after consenting with a man for money or other items/benefits as an occupation or as a primary source of livelihood irrespective of site of operation within the past six months. We assessed the preference and uptake of different community based HIV testing services delivery model among FSWs based on two indicators, i.e., the proportion of FSWs who had an HIV Counseling and Testing (HCT) in the last 12 months and the proportion of FSWs who were positive and linked to care. Overall, 86% (390/456) of the FSWs had taken an HIV test in the last 12 months. Of the 390 FSWs, 72% (279/390) had used static facilities, 25% (98/390) had used outreaches, and 3.3% (13/390) used peer to peer mechanisms to have an HIV test. Overall, 35% (159/390) of the FSWs who had taken an HIV test were HIV positive. Of the 159, 83% (132/159) were successfully linked into care. Ninety one percent (120/132) reported to have been linked into care by static facilities. Challenges experienced included; lack of trust in the results given during outreaches, failure to offer other testing services including hepatitis B and syphilis during outreaches, inconsistent supply of testing kits, condoms, STI drugs, and unfriendly health services due to the infrastructure and non-trained health workers delivering KP HIV testing services. Most of the FSWs had HCT services and were linked to care through static facilities. Community-based HIV testing service delivery models are challenged with inconsistent supply of HIV testing commodities and unfriendly services.. We recommended strengthening of all HIV testing community-based HIV testing service deliverymodels by ensuring constant supply of HIV testing/AIDS care commoditiesoffering FSW friendly services, and provision of comprehensive HIV/AIDS health care package.


Bacterial contamination of 'Venflon' intravenous cannulae with valved injection sideport.
Eighty-eight intravenous cannulae with valved injection sideports were examined bacteriologically after approximately three days (64-80 h) normal clinical use. Three methods of culture of the cannulae were used, which distinguished contamination of the outer and inner surfaces as well as detecting bacteria remaining on the inner cannula surface following a washing procedure of the lumen. Of the cannulae sampled, 40.9 per cent were found to be contaminated on their inner surfaces and no correlation was obtained between use of the sideport and contamination of the cannulae at this site. It was concluded that contamination of a cannula lumen did not necessarily result in bacteraemia.


PARK2 variability in Polish Parkinson's disease patients--interaction with mitochondrial haplogroups.
A new pathomechanism of Parkinson's disease (PD) involving regulation of mitochondrial functions was recently proposed. Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, which is abolished by PARK2 gene mutations. We have previously shown that mitochondrial haplogroups/clusters and TFAM common variation influenced PD risk. We investigate the role of PARK2 polymorphisms on PD risk and their interactions with mitochondrial haplogroups/clusters as well as with TFAM variability. 104 early-onset PD patients (EOPD, age at onset ≤ 50 years) were screened for PARK2 coding sequence changes including gene dosage alterations. Three selected PARK2 polymorphisms (S167N, V380L, D394N) were genotyped in 326 PD patients and 315 controls using TaqMan allelic discrimination assay. PARK2 screen revealed two heterozygous changes in two EOPD patients: exon 2 deletion and one novel synonymous variation (c.999C > A, P333P). In association study no differences in genotype/allele frequencies of S167N, V380L, D394N were found between analyzed groups. Stratification by mitochondrial clusters revealed higher frequency of V380L G/G genotype and allele G in PD patients, within HV cluster (p = 0.040; p = 0.022, respectively). Moreover, interaction between genotypes G/G V380L of PARK2 and G/G rs2306604 of TFAM, within HV cluster was significant (OR 2.05; CI 1.04-4.04; p = 0.038). Our results indicate that co-occurrence of G/G V380L PARK2 and G/G rs2306604 TFAM on the prooxidative HV cluster background can contribute to PD risk. We confirm low PARK2 mutation frequency in Polish EOPD patients.


Type I interferon during viral infections: multiple triggers for a multifunctional mediator.
Type I interferons (IFN-I) orchestrate numerous biological and cellular processes and are essential elements during host antiviral defense. After recognition of highly conserved virus signatures, a complex network of signaling events is rapidly initiated and leads to IFN-I synthesis. These cytokines directly induce a strong antiviral state and exert several immune-regulatory actions aimed at preventing virus spread. On the other hand, viruses evolved to evade or subvert the IFN-I system for their own benefit. In the present article, we review selective aspects of IFN-I induction and functions during several viral infections and discuss the beneficial and detrimental roles of IFN-I illustrated during lymphocytic choriomeningitis virus (LCMV) infection in its natural host, the mouse.


Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products.
Rat liver folylpolyglutamate synthetase was partially purified and its reaction and products were characterized. The preparation contained no conjugase activity. Gel filtration analysis revealed a molecular weight of 69,000. The synthetase was optimally active at pH 8.4 (37 degrees C), required mercaptoethanol and a monovalent cation, and was highly specific for L-glutamate. Only purine nucleoside triphosphates served as the energy source for the reaction; ATP and dATP gave the best activity. All naturally occurring folates (including 5-methyl-tetrahydrofolic acid) as well as a number of folate analogs (including methotrexate) served as substrates. The unnatural diastereoisomer of at least one folate, 5,6,7,8-tetrahydrofolic acid, was also a substrate. Modifications of the terminal, acceptor glutamate led to loss of substrate activity, as well as loss of binding. High pressure liquid chromatography analysis, conjugase digestion, double radiolabel studies, and amino acid analysis of acid-hydrolyzed product confirmed that folylpoly-gamma-glutamates were synthesized. High concentrations of (dl)-5,6,7,8-tetrahydrofolic acid favored accumulation of short chain (predominantly diglutamate) products while low concentrations favored accumulation of longer chains (predominantly tetraglutamate). This inverse relationship between concentration and chain length may be of regulatory significance. Synthesis of pentaglutamate forms, the predominant chain length of rat liver folates in vivo, was detected at low (dl)-5,6,7,8-tetrahydrofolic acid, but hexaglutamate was not detected. Synthetic (l)-5,6,7,8-tetrahydropteroylpentaglutamate was a poor substrate for the synthetase but it inhibited formation of polyglutamates from monoglutamates. These observations indicate that the predominant chain length of folates in rat liver may be determined solely by the substrate specificity of the rat liver synthetase. Inhibition by the specificity of the rat liver synthetase. Inhibition by the pentaglutamate derivative offers a means by which folylpolyglutamates could regulate their own synthesis.


Climate-driven tree growth and mortality in the Black Forest, Germany-Long-term observations.
Episodic tree mortality can be caused by various reasons. This study describes climate-driven tree mortality and tree growth in the Black Forest mountain range in Germany. It is based on a 68-year consistent data series describing the annual mortality of all trees growing in a forest area of almost 250 thousand ha. The study excludes mortality caused by storm, snow and ice, and fire. The sequence of the remaining mortality, the so-called "desiccated trees," is analyzed and compared with the sequence of the climatic water balance during the growing season and the annual radial growth of Norway spruce in the Black Forest. The annual radial growth series covers 121 years and the climatic water balance series 140 years. These unique time series enable a quantitative assessment of multidecadal drought and heat impacts on growth and mortality of forest trees on a regional spatial scale. Data compiled here suggest that the mortality of desiccated trees in the Black Forest during the last 68 years is driven by the climatic water balance. Decreasing climatic water balance coincided with an increase in tree mortality and growth decline. Consecutive hot and dry summers enhance mortality and growth decline as a consequence of drought legacies lasting several years. The sensitivity of tree growth and mortality to changes in the climatic water balance increases with the decreasing trend of the climatic water balance. The findings identify the climatic water balance as the main driver of mortality and growth variation during the 68-year observation period on a landscape-scale including a variety of different sites. They suggest that bark beetle population dynamics modify mortality rates. They as well provide evidence that the mortality during the last 140 years never was as high as in the most recent years.


Assessing incident depression among older people with and without HIV in U.S.
Despite substantially higher prevalence of depression among people living with HIV/AIDS (PLWHA), few data exist on the incidence and correlates of depression in this population. This study assessed the effect of HIV infection, age, and cohort period on the risk of developing depression by sex among older U.S. Medicare beneficiaries. We constructed a retrospective matched cohort using a 5% nationally representative sample of Medicare beneficiaries (1996-2015). People with newly diagnosed (n = 1309) and previously diagnosed (n = 1057) HIV were individually matched with up to three beneficiaries without HIV (n = 6805). Fine-Gray models adjusted for baseline covariates were used to assess the effect of HIV status on developing depression by sex strata. PLWHA, especially females, had higher risk of developing depression within five years. The relative subdistribution hazards (sHR) for depression among three HIV exposure groups differed between males and females and indicated a marginally significant interaction (p = 0.08). The sHR (95% CI) for newly and previously diagnosed HIV (vs. people without HIV) were 1.6 (1.3, 1.9) and 1.9 (1.5, 2.4) for males, and 1.5 (1.2, 1.8) and 1.2 (0.9, 1.7) for females. The risk of depression increased with age [sHR 1.3 (1.1, 1.5), 80 + vs. 65-69] and cohort period [sHR 1.3 (1.1, 1.5), 2011-2015 vs. 1995-2000]. HIV infection increased the risk of developing depression within 5 years, especially among people with newly diagnosed HIV and females. This risk increased with older age and in recent HIV epidemic periods, suggesting a need for robust mental health treatment in HIV primary care.


Novel application of vinylpolysiloxane hearing aid impression mold as patient-specific bolus for head and neck cancer radiotherapy.
Hearing aid impression material composed of vinylpolysiloxane is an ideal bolus material which may be used to aid in delivery of adjuvant radiation to complex surgical defects of the head and neck. It is affordable, easily accessed, and efficient.


Hypervitaminosis A resulting in DNA aberration in fetal transgenic mice (Muta Mouse).
Treatment with excessive amounts of Vitamin A during maternity induces fetal malformations. However, it is unclear whether these malformations are due to gene mutations or not. Using transgenic mice (containing lacZ gene showing beta-galactosidase enzymatic activity), we planned to observe whether gene mutations occur in the fetal tissues after treatment during maternity with Vitamin A (retinol palmitate). On the 11th day of pregnancy, mothers were given 30 mg (group 2), 150 mg (group 3) and 300 mg (group 4) of Vitamin A/kg body weight orally. Fetuses obtained on the 18th day of gestation showed malformations, such as cleft palate, origodactyly, brachydactyly and ectromeria. Most notably, cleft palate occurred dose dependently. The incidental rates were 100% in group 4, 58% in group 3 and 6% in group 2. The number of dead and absorbed fetuses also increased dose dependently with the treatments. DNA (integrated vectors containing lacZ genes) extracted from each fetus showed Vitamin A-induced lacZ mutations, especially in the malformed fetuses. The mutation frequencies were 4.99x10(-5) in group 4, 5.28x10(-5) in group 3 and 4.26x10(-5) in group 2. The frequencies of group 3 were significantly higher (p<0.05) than that of the controls (group 1), 2.79x10(-5). Maternal treatment with Vitamin A (150 mg/kg of body weight) was carried out on the 11th day of pregnancy. Fetuses obtained on the 14th day of gestation showed a much higher incidence of mutation, approximately 8.91x10(-5) (group 6) that was significantly higher (p<0.0001) than those from the controls (group 5), 2.94x10(-5). The present study indicates a possibility that hypervitaminosis A-induced fetal malformation and death might be caused by gene mutations.


The influence of tonsillectomy on allergic diseases in pediatric patients.
The influence of tonsillectomy on allergic airway diseases is not well known. In the present study, the influence of tonsillectomy on perennial allergic rhinitis (PAR) and bronchial asthma (BA) among pediatric subjects was prospectively investigated. The tonsillectomy (surgery group) and the age-matched non-surgical subjects (control group) were examined and followed prospectively. In addition, immunological analysis was conducted. After in vitro allergen stimulation, the production of a small number of allergen-specific Th2 cells was induced in the tonsillar cells, even in sensitized subjects. Flow cytometry analysis detected more effector regulatory T cells (Tregs) in the tonsils than in peripheral blood. Clinically, after surgery, the PAR and BA symptoms improved in the surgery group but not in the control group. The total IgE in the surgery group was significantly lower than in the control group; after surgery, IgE levels slightly increased but remained lower. The postoperative Dermatophagoides farina (Der f)-specific IgE level increased in the sensitized subjects but not in the non-sensitized subjects. Tonsillectomy did not improve the underlying mechanisms of the allergy, however the decreased risk of infection and upper airway obstruction could lead to improved symptoms of allergic airway diseases.


A highly efficient preparative-scale generic immunoaffinity chromatography method for the purification of antibodies to hydrophobic haptens: purification procedure and monitoring tests.
A generic affinity chromatography purification protocol for the isolation of preparative quantities of pure and stable polyclonal antibodies to hydrophobic haptenic analytes is described together with a panel of tests to monitor the purification process and assess the functional and structural purity of isolated antibodies. The purification method is based on the use of a mixture of acetonitrile and propionic acid to elute bound antibodies from Sepharose 4B-based immunoabsorbent gels. Highly specific and pure antibodies to steroid estrogens, pentachlorophenol and Irgarol 1051 were isolated in 50-150 mg quantities per preparation in a batch-wise method using appropriate ligands linked to the solid phase via a hydrophilic chemical arm, tetraethylene pentamine. The panel of ELISA tests together with SDS-PAGE enabled the monitoring of the absorption and elution steps and provided data relevant to the assessment of the degree of structural and functional purity of the isolated antibody preparations. The study demonstrates that the affinity purification procedure is practical, simple, generic for antibodies to hydrophobic haptens and suitable for scaling up. In addition, the study showed that the functional properties of the affinity-purified antibodies indicated improvements on the operational properties (specificity and assay detection limits) of the source antisera. The isolated IgG antibodies showed near 100% functional and structural purity and no deterioration of activity on storage for long periods. The method provides critical reagents for labelled-antibody immunoassays and immunosensors and antibody-dependent sample purification techniques.


Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator.
In Drosophila, signalling by the protein Hedgehog (Hh) alters the activity of the transcription factor Cubitus interruptus (Ci) by inhibiting the proteolysis of full-length Ci (Ci-155) to its shortened Ci-75 form. Ci-75 is found largely in the nucleus and is thought to be a transcriptional repressor, whereas there is evidence to indicate that Ci-155 may be a transcriptional activator. However, Ci-155 is detected only in the cytoplasm, where it is associated with the protein kinase Fused (Fu), with Suppressor of Fused (Su(fu)), and with the microtubule-binding protein Costal-2. It is not clear how Ci-155 might become a nuclear activator. We show here that mutations in Su(fu) cause an increase in the expression of Hh-target genes in a dose-dependent manner while simultaneously reducing Ci-155 concentration by some mechanism other than proteolysis to Ci-75. Conversely, eliminating Fu kinase activity reduces Hh-target gene expression while increasing Ci-155 concentration. We propose that Fu kinase activity is required for Hh to stimulate the maturation of Ci-155 into a short-lived nuclear transcriptional activator and that Su(fu) opposes this maturation step through a stoichiometric interaction with Ci-155.


Reliability of a markerless motion capture system to measure the trunk, hip and knee angle during walking on a flatland and a treadmill.
Markerless motion capture system (MLS) using an infrared sensor such as Microsoft Kinect has been used for gait analysis. Several studies have shown that kinematic measurements of trunk and lower limb joint angles during walking measured by MLS are valid. However, the reproducibility, presence of systematic error, or degree of random error of kinematic measurements during walking using MLS with Kinect v2 were not demonstrated. This study was made to confirm the reliability of kinematic measurements using Kinect v2 during gait. Twenty-two young, injury-free individuals volunteered to participate. Walks were made at 2 miles per hour (mph) on both the flatland and the treadmill. Intra-class correlation coefficients (ICCs) were calculated, systematic errors identified, and minimal detectable changes (MDCs) were estimated to assess the reliability of kinematic measurements of trunk, hip, and knee joint angles during walking. For trunk angles measured on the flatland, ICC was higher than 0.6, systematic error was smaller, and MDC was 2.2° smaller than that in gait on the treadmill (6.6°). In hip joint angles measured on the flatland, although systematic error was slight, ICC was not higher than on the treadmill and MDC exceeded 5°. The results for the knee joint were similar to those of the hip joint. Kinect can detect kinematic abnormalities of the trunk during slow walking on the flatland easier than on the treadmill.


Imaging of the lumbar plexus: Optimized refocusing flip angle train design for 3D TSE.
To study the effects of refocusing angle modulation with 3D turbo spin echo (TSE) on signal and sharpness of small oblique nerves embedded in muscle and suppressed fat in the lumbar plexus. Flip angle trains were generated with extended phase graphs (EPG) for a sequence parameter subspace. Signal loss and width broadening were simulated for a single-pixel nerve embedded in muscle and suppressed fat to prescribe a flip angle modulation that gives the best compromise between signal and sharpness of small nerves. Two flip angle trains were defined based on the simulations of small embedded nerves: design denoted A, predicting maximum global signal, and design denoted B, predicting maximum signal for minimum width broadening. In vivo data of the lumbar plexus in 10 healthy volunteers was acquired at 3.0T with 3D TSE employing flip angle trains A and B. Quantitative and qualitative analyses of the acquired data were made to assess changes in width and signal intensity. Changing flip angle modulation from A to B resulted in: 1) average signal losses of 23% in (larger) L5 nerves and 9% in (smaller) L3 nerves; 2) average width reductions of 4% in L5 nerves and of 16% in L3 nerves; and 3) statistically significant sharpness improvement (P = 0.005) in L3 nerves. An optimized flip angle train in 3D TSE imaging of the lumbar plexus considering geometry-specific blurring effects from both the nerve and the surrounding tissue can improve the delineation of small nerves.


Improved methods for fMRI studies of combined taste and aroma stimuli.
Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.


Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex.
Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain.


Imaging of Trauma in Pregnancy.
A pregnant patient with acute trauma is not commonly encountered by clinicians and radiologists. A multidisciplinary approach is key. Although radiography and ultrasound examination are frequently used modalities in the setting of maternal-fetal trauma, the fear of radiation should not preclude from carrying out a thorough diagnostic workup of the patient with a computed tomography scan. MRI mainly serves as a problem solving and follow-up modality. After stabilizing the mother, fetal well-being should be assessed with external fetal monitoring and a dedicated obstetric ultrasound examination. Radiologists should be familiar with the sonographic and computed tomography findings of catastrophic entities.


The knowledge and perceptions of the first year medical students of an International University on family planning and emergency contraception in Nicosia (TRNC).
Informing the individuals on family planning including emergency contraception is a significant step for preventing unintended pregnancies. Although there is a number of studies on family planning and emergency contraception globally and in Turkey, no such data are available in the Turkish Republic of Northern Cyprus. The objective of this study was to evaluate the knowledge and perceptions on family planning and emergency contraception of the first year students of an international medical school in Nicosia, Northern Cyprus and to increase awareness for developing new policies on the issue. The data of this cross-sectional study were collected in February 2016 by a questionnaire of 36 questions. Of the 229 students, 189 (82.5%) completed the questionnaire. The data were evaluated by SPSS 18.0 statistical program. The differences of variables were evaluated by Chi square test, p < 0.05 being accepted as significant. The distribution of participants from 23 countries according to nationality revealed three leading countries: Nigeria, Turkey and Syria. Of the students, 53.6% knew the definition of family planning. The sources of information were mainly school, the internet and media, with a total of 60.9% of the participants who stated having prior information on the subject. Awareness of contraceptive methods was indicated by more than 90% and emergency contraception by 66.1% of the participants. However, the students were unable to differentiate between modern and traditional family planning methods; 85.6% did not have knowledge of the most effective period for emergency contraception and 63.1%, of the definition of emergency contraceptive pills. In conclusion, the knowledge and awareness level of the first year medical students on family planning and emergency contraception was insufficient. Family planning and emergency contraception education should be provided for the students at the first year of all faculties as well as medical schools and relevant programs should be included in the curricula of medical education.


Accentuation of high susceptibility of hypertrophied myocardium to ischemia: complementary assessment of Gadophrin-enhancement and left ventricular function with MRI.
The aim of the study was to compare infarction size and left ventricular (LV) function in normal and hypertrophied hearts after brief ischemia using Gadophrin-enhancement and functional assessment by MRI. Rats (n = 20) were assigned to aortic banding to induce LV hypertrophy or control. Eight weeks later, rats were subjected to 25 min of regional myocardial ischemia followed by 3 hr of reperfusion. The necrosis-specific agent Gadophrin-3 was injected to delineate infarcted myocardium on MRI. Effects of aortic banding and ischemia on LV mass and function were determined. At postmortem, areas at risk and infarction were measured. Close correlation was found between LV mass measured with MRI and at postmortem (r = 0.98). LV mass measured with MRI was significantly greater (0.81 +/- 0.02 g) in animals with aortic banding compared to control (0.62 +/- 0.02 g; P < 0.001). Infarction size was larger in hypertrophied hearts (19.0 +/- 1.4% / 18.3 +/- 1.5%) than in control (9.8 +/- 1.7% / 9.2 +/- 2.0%) on Gadophrin-enhanced MRI and at postmortem, respectively. Similarly, greater impairment in ejection fraction was observed in hypertrophied hearts with MRI (39 +/- 4% vs. 49 +/- 2%; P = 0.02). Gadophrin-3 provides accurate estimation of infarct size in hypertrophied hearts. Hypertrophied hearts are more sensitive to ischemia than nonhypertrophied hearts. The complementary assessment of Gadophrin-enhancement and LV function with MRI provides unique information about myocardium sensitivity to ischemia.


Anesthetic considerations for patients with anterior mediastinal masses.
Anterior mediastinal tumors can cause severe airway and vascular compression, and these effects are exacerbated by general anesthesia. Tumor biopsy using a local anesthetic technique is preferable. General anesthesia for a biopsy procedure or resection of an anterior mediastinal mass should be undertaken only after a thorough preoperative assessment. Treatment protocols for surgery and anesthesia vary from institution to institution, and management remains operator dependent. Some consider the maintenance of spontaneous respiration during anesthesia optimal. Others advocate airway stenting. Cardiopulmonary bypass, instituted at the outset of surgery under local anesthetic, may be used as a fall-back technique in extreme circumstances.


Cardiac output as a predictor in congenital heart disease: Are we stating the obvious?
Significant pulmonary regurgitation, declining right-sided ejection fraction, increased right ventricular (RV) volumes as well as left ventricular (LV) dysfunction have all been identified as predictors of poor outcomes in patients with congenital heart disease (CHD). The prognostic value of the cardiac output (CO) in these patients however has never been studied. All consecutive ambulatory adult patients with CHD referred for magnetic resonance imaging (MRI) at the Montreal Children's Hospital between June 2007 and May 2009 were included. Right ventricular (RV) and left ventricular (LV) variables including end diastolic and end systolic volumes (EDV, ESV respectively), ejection fractions (EF) and regurgitant volumes were obtained. Cardiac index (CI) was calculated. Patients were followed for cardiac-related hospitalizations and cardiac interventions. Ninety-six patients were included. Median follow up was 3.9 ± 1.4 years. Nineteen percent of patients had a systemic CI<2.4 l/min/m(2). LVEDV, LVEF and RVEF were significantly diminished in the low CI group with a significant increase in RVESV and total regurgitant volume. Best predictors of low CI were LVEF (AUC=0.74), RVEF (AUC=0.71), total RV regurgitant volume (AUC=0.64) and RVESV (AUC=0.563). Low systemic CI was the best predictor of cardiac-related hospitalizations (hazard ratio 3.5, 95% confidence interval 1.5-8.5) and cardiac interventions (hazard ratio 2.2, 95% confidence interval 1.3-4.0), superior to LVEF, RVEF, total regurgitant volume and RVESV parameters. In patients with congenital heart disease, cardiac index is the best predictor of cardiac hospitalizations and cardiac interventions.


T wave alternans in idiopathic long-QT syndrome: insight from body surface mapping.
Body surface mapping was recorded during T wave alternans in two patients with idiopathic long QT syndrome. Eighty-seven lead ECGs of two consecutive beats during T wave alternans demonstrated that alternating changes in the morphology and polarity of the T wave existed mainly in the left frontal chest. The QRST isointegral maps of the same two consecutive beats showed alternation of a large negative area appearing mainly in the left frontal chest. These results indicate that T wave alternans in the two patients were related to alternate heterogeneous prolongation of the action potential duration in this region.


Nomenclature of dyspepsia, dyspepsia subgroups and functional dyspepsia: clarifying the concepts.
There is international agreement that dyspepsia refers to pain or discomfort centered in the upper abdomen. However, the term 'discomfort' has been variably defined. While other symptoms may often be simultaneously present, gastro-oesophageal reflux disease can usually be clearly distinguished by the presence of predominant heartburn. Dyspepsia is a frequent reason for consultation in primary care and in gastrointestinal practice. With the widespread availability and utilization of endoscopy, it has become evident that a structural (or organic) explanation is found in only a minority of patients presenting with dyspepsia. Operationally, functional dyspepsia is defined as persistent or recurrent dyspepsia for 3 or more months in the absence of a clinically identifiable structural disease causing the symptoms. It has been proposed, based on symptoms, that functional dyspepsia be subdivided into symptom subgroups to promote patient homogeneity. The initially proposed 'clustering' of symptoms into ulcer-like and dysmotility-like functional dyspepsia has proved a dismal failure because of the considerable overlap observed, the lack of stability over time and the failure to identify robust pathophysiological abnormalities or responses to therapy. A subcategorization based upon the most bothersome symptom is theoretically more attractive but needs to be prospectively and rigorously tested.


Comfort Level of US Radiation Oncology Graduates: Assessment of Transition to Independent Clinical Practice.
Radiation training programs are designed to prepare graduates for independent practice, with metrics in place to assess appropriateness of clinical decision-making. Here, we investigated the self-assessed preparedness of US graduates during the transition to independent practice.An anonymous, Internet-based survey was distributed to recent graduates of radiation oncology residencies (2016-2017). A Likert scale was used to assess comfort with various aspects of practice, as well as "time" to development of comfort in independent practice.Responses were obtained from 70/210 (33%), the majority reported training in programs with 5-8 residents (n = 35). Most (77%) reported designing between 500 and 900 treatment plans during training (n = 54). Only 41% of respondents reported the opportunity to review treatment plans and make decisions about safety/adequacy without attending input > 50% of the time (n = 29). Thirty percent of residents reported being responsible for seeing/managing on-treatment visits (OTVs) ≤ 75% of the time. Aspects with which practitioners reported the least comfort were understanding of billing/application to practice (2.43, IQR 2-3), orthovoltage (superficial radiation) setup and field design (2.57, IQR 1-4), and planning/delivery of prostate implants (2.82, IQR 2-4). Increased mean comfort levels were reported by those designing > 700 treatment plans in training as well as those reporting an opportunity to evaluate plans and make clinical decisions prior to attending input > 50% of the time during residency. Comfort with the delivery of stereotactic body radiation (SBRT) correlated with caseload for liver, spine, prostate, and CNS disease sites but not lung.Variations in training experiences exist across institutions. Here, a lower than expected number of residents reported seeing/managing OTVs as well as reviewing treatment plans prior to attending input during training. Overall comfort was correlated with case volume and opportunities to independently review treatment plans prior to attending input. These data highlight areas of opportunity for improving resident education with implications for ease of transition to independent clinical practice.


Comprehensive investigations of 2-phenylethanol production by high 2-phenylethanol tolerating Meyerozyma sp. strain YLG18.
2-Phenylethanol (2-PE) production through bio-synthesis method has become an appealing option owning to the mild conditions and high product selectivity. However, 2-PE is toxic to cells, which is an important limiting factor for the biosynthesis of 2-PE. In this study, a novel 2-PE generating Meyerozyma sp. strain YLG18 was first isolated, which could produce 2-PE through both Ehrlich and Shikimate pathways. Moreover, the indigenous high 2-PE tolerance makes it a promising candidate for high 2-PE production. Response surface methodology and in situ product recovery technology could improve the final 2-PE production to 3.20 g/L, representing the highest 2-PE production by using Meyerozyma sp. Furthermore, genes involved in 2-PE synthesis were identified and their expression levels between Shikimate pathway and Ehrlich pathway were compared. Based on the genomic and transcriptional analysis, a penta-functional enzyme AroM and an aspartate aminotransferase (AAT) with the potential to convert phenylalanine into phenylpyruvate were identified. These findings would help broaden our knowledge and add the pool of known 2-PE generating microbes and genes.


Lessons Learned on Recruiting and Retaining Young Fathers in a Parenting and Repeat Pregnancy Prevention Program.
Research shows that mainstream parenting and repeat pregnancy prevention programs generally do not effectively engage with fathers and that young men's levels of participation in such services are low. To support practitioners in overcoming the barriers to recruiting and retaining young fathers, the current study aimed to gather lessons learned from one program's state administrators, case managers, and young fathers about the most effective strategies for engaging this population in intensive case management. Three focus groups were conducted. One focus group was held with the creators and managers of the Michigan Adolescent Pregnancy and Parenting Program MI-APPP at the state Department of Health and Human Services (n = 3). The other two groups were designed to jointly engage young fathers currently involved in intensive case management (n = 11) and their case managers (n = 5). A qualitative analysis of the focus group transcripts was conducted using a coding scheme developed from emerging themes in the transcripts and related literature. The findings highlight a selection of those strategies that focus group participants perceived to be most successful in improving male recruitment and retention in intensive ongoing case management. Among these strategies were centralizing feedback from young fathers in program decision making, offering opportunities for young fathers to connect, and challenging staff's negative stereotypes about young fathers. Despite the small sample size, the results of this study nevertheless contribute to debates in the field regarding appropriate strategies for engaging young fathers by informing professional practice.


New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductase.
The enzyme Δ24-dehydrocholesterol reductase (DHCR24) catalyzes the reduction of the Δ24-double bond in the side chain of cholesterol precursors. Recent biochemical investigations fuel the hope that inhibition of DHCR24, resulting in an accumulation of desmosterol, can open new therapeutic options for treating hepatitis C virus infections, certain forms of cancer and atherosclerosis. In turn, there is a high need for selective, potent and non-toxic inhibitors of DHCR24. Previous reports as well as our re-evaluation showed that established DHCR24 inhibitors are not suitable for this purpose. Based on the lathosterol-derived amide MGI-21 (IC50 823 nM for inhibition of overall cholesterol biosynthesis in HL-60 cells) we performed a systematic variation of the side chain functionality and identified the steroidal 3,22-diols 29 and 30, as well as several esters thereof, as extremely potent (IC50 < 5 nM), selective, and non-toxic DHCR24 inhibitors. In mice, diester 27 (SH-42) led to a significant increase in plasma desmosterol levels. The new inhibitors described here are valuable tools for investigating the therapeutic potential of DHCR24 inhibition.


Physiological mechanisms constraining ectotherm fright-dive performance at elevated temperatures.
Survival of air-breathing, diving ectotherms is dependent on their capacity to optimise the time available for obligate underwater activities, such as predator avoidance. Submergence times are thermally sensitive, with dive durations significantly reduced by increases in water temperature, deeming these animals particularly vulnerable to the effects of climate change. The physiological mechanisms underlying this compromised performance are unclear but are hypothesised to be linked to increased oxygen demand and a reduced capacity for metabolic depression at elevated temperatures. Here, we investigated how water temperature (both acute and chronic exposures) affected the physiology of juvenile estuarine crocodiles (Crocodylus porosus) performing predator avoidance dives (i.e. fright-dives). Diving oxygen consumption, 'fright' bradycardia, haematocrit and haemoglobin (indicators of blood oxygen carrying capacity) were assessed at two test temperatures, reflective of different climate change scenarios (i.e. current summer water temperatures, 28°C, and 'high' climate warming, 34°C). Diving oxygen consumption rate increased threefold between 28 and 34°C (Q10=7.4). The capacity to depress oxygen demand was reduced at elevated temperatures, with animals lowering oxygen demand from surface levels by 52.9±27.8% and 27.8±16.5% (means±s.e.m.) at 28°C and 34°C, respectively. Resting and post-fright-dive haematocrit and haemoglobin were thermally insensitive. Together these findings suggest decrements in fright-dive performance at elevated temperatures stem from increased oxygen demand coupled with a reduced capacity for metabolic depression.


Transmission of radiation-induced rearrangements through cell divisions.
A BrdU incorporation technique associated with heat denaturation, acridine orange staining and UV irradiation, was applied to G0-irradiated lymphocyte cultures. This made it possible both to obtain an R-banding, and to estimate the number of divisions undergone by each cell in mitosis irradiation. Cell survival and slowing down of the cell cycle could be distinguished. The frequency of various types of rearrangements, and their association was studied at each cell division. It is shown that the loss of cells carrying chromosomal rearrangements is determined by several parameters such as the presence of dicentric or multicentric chromosomes and above all the association of several rearrangements in the same cell.


KCNJ11 gene E23K variant and therapeutic response to sulfonylureas.
Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant. One hundred and one patients with type 2 diabetes who failed to achieve HbA1c<7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis. After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04±0.10 vs. 0.79±0.12%, p=0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01-0.32, p=0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n=55). Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.


Confucian virtues and Chinese adolescent development: a conceptual review.
Despite the fact that different Chinese communities have already undergone industrialization and urbanization, Confucian virtues are still regarded as developmental ideals in Chinese culture. Unfortunately, while Confucian virtues are commonly discussed under Chinese philosophies, they are rarely examined in the context of developmental research. In this paper, several key Confucian virtues are discussed, including loyalty ("zhong"), filial piety ("xiao"), benevolence ("ren"), affection ("ai"), trustworthiness ("xin"), righteousness ("yi"), harmony ("he"), peace ("ping"), propriety ("li"), wisdom ("zhi"), integrity ("lian") and shame ("chi"). These Chinese traditional virtues are also linked to the concepts of character strengths and positive youth development constructs highlighted in Western culture. It is argued that Confucian virtues provide an indigenous conceptual framework to understand character strengths and positive youth development in Chinese culture. Furthermore, when service leadership is considered in Chinese contexts, these virtues should be regarded as important cornerstones.


[Acute infection caused by the human immune deficiency virus (HIV) during the practice of safe sex].
On the basis of two cases of acute HIV infection, diagnosed in two patients who only employed "safe sex", HIV-infection prophylaxis in the high and low risk groups is discussed.


Type VI secretion requires a dynamic contractile phage tail-like structure.
Type VI secretion systems are bacterial virulence-associated nanomachines composed of proteins that are evolutionarily related to components of bacteriophage tails. Here we show that protein secretion by the type VI secretion system of Vibrio cholerae requires the action of a dynamic intracellular tubular structure that is structurally and functionally homologous to contractile phage tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the type VI secretion system cycle between assembly, quick contraction, disassembly and re-assembly. Whole-cell electron cryotomography further shows that the sheaths appear as long tubular structures in either extended or contracted conformations that are connected to the inner membrane by a distinct basal structure. These data support a model in which the contraction of the type VI secretion system sheath provides the energy needed to translocate proteins out of effector cells and into adjacent target cells.


The last step of kanamycin biosynthesis: unique deamination reaction catalyzed by the α-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH-dependent reductase KanK.
Mystery solved: using heterologous expression, the activities of two enzymes exclusively belonging to the kanamycin biosynthetic pathway have been identified in vitro. A distinctive reaction mechanism to produce kanamycin is proposed and the previously unknown catalytic deamination activity of KanJ dioxygenase is uncovered.


Iranian older adults women: The Impact of COVID-19 and Coping Strategies.
In the field of epidemics, some vulnerable groups, such as older adults, are at greater risk. Many psychological, social, economic and physical hazards have threatened older adults during the COVID-19 pandemic. Some threats can be managed with medical system interventions. However, social and psychological challenges cannot be controlled quickly. People will have a better quality of life if they can take appropriate action in critical situations. There is a strong theoretical and empirical background that a sense of control and self-efficacy can promote psychological well-being. The main questions of this study included the following: What were the main problems experienced by older Iranian women during the outbreak of COVID-19? What coping methods did they use to control the situation? What were their views on the future? This research was conducted in Kerman city, the capital of Kerman Province. A phenomenological method was used. We interviewed 15 women over 65 years old. We extracted five main themes from the interviews. These themes were health issues, persistent anxiety, economic and social pressures, identifying unique solutions to the current situation, and optimism versus pessimism: what is the future? From the participants' point of view, psychological, social and physical problems have disturbed them during the pandemic, especially at the beginning. However, they controlled their problems by using selective coping strategies. In Iran, planners can use the potential of the two institutions of family and religion to reduce the problems of older adults.


Endoscopic surgery in the skull base unit: experience in the first 72 cases.
A multidisciplinary team is essential to develop and expand the indications in endonasal endoscopic skull base surgery. The aim of this study was to present our experience in a group of patients with skull base lesions treated using endonasal endoscopic approach. From January 2008 to January 2012, 72 patients with skull base involvement were diagnosed and treated in our centre. The mean patient age was 53 years. The different pathologies included 36 pituitary adenomas, 10 cerebrospinal fluid leaks and 5 inverted papillomas as the most frequent pathologies. We performed a transsphenoidal transellar approach in 45 cases, a transmaxillary transpterygoid approach in 4 cases and a transnasal expanded approach in 6 cases. We performed an ethmoidal/sphenoidal approach in 12 patients and a Draf IIb/III procedure in four cases. Total resection was achieved in 61% of patients with pituitary adenomas, subtotal in 22% and partial in 17%. Successful repair was achieved in 86% of CSF leaks. No recurrences were observed in patients with inverted papilloma. Complications were observed in 21 patients (29%), 6 being major complications. Our centre stresses the importance of multidisciplinary collaboration in endoscopic endonasal skull base surgery.


Cardiac arrest in private locations: different strategies are needed to improve outcome.
A tremendous amount of public resources are focused on improving cardiac arrest (OHCA) survival in public places, yet most OHCAs occur in private residences. A prospective, observational study of patients transported to seven urban and suburban hospitals and the individuals who called 911 at the time of a cardiac arrest (bystander) was performed. Bystanders (N=543) were interviewed via telephone beginning 2 weeks after the incident to obtain data regarding patient and bystander demographics, including cardiopulmonary resuscitation (CPR) training. Of all arrests 80.2% were in homes. Patients who arrested in public places were significantly younger (63.2 vs. 67.2, P<0.02), more often had an initial rhythm of VF (63.0 vs. 37.7%, P<0.001), were seen or heard to have collapsed by a bystander (74.8 vs. 48.1%, P<0.001), received bystander CPR (60.2 vs. 28.6%, P<0.001), and survived to DC (17.5 vs. 5.5%, P<0.001). Patients who arrested at home were older and had an older bystander (55.4 vs. 41.3, P<0.001). The bystander was less likely to be CPR trained (65.0 vs. 47.4%, P<0.001), less likely to be trained within the last 5 years (49.2 vs. 17.9, P<0.001), and less likely to perform CPR if trained (64.2 vs. 30.0%, P<0.001). Collapse to shock intervals for public versus home VF patients were not different. Many important characteristics of cardiac arrest patients and the bystander differ in public versus private locations. Fundamentally different strategies are needed to improve survival from these events.


Optimization of ultrasound-assisted cellulase degradation method on the extraction of mulberry leaf protein and its effect on the functional characteristics.
The mulberry leaf protein extracted by ultrasound-assisted cellulase degradation (UACD) method was optimized with the protein dissolution amount (PDA) as the index. The Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy of extracted mulberry leaf protein were measured. The functional characteristics of protein extracted by the UACD method were evaluated. Results showed that the extraction condition was optimized and adjusted to the following parameters: pH value of 7.20, ultrasound temperature of 35.00 °C, enzyme dosage of 4.20% and ultrasound time of 10.00 min. Under these optimized conditions, the experimental verification value of PDA was 13.87 mg/mL, which was approaching to the predicted value of 13.54 mg/mL. The analysis results of FTIR showed that after extraction by the UACD method, the mulberry leaf protein with the vibrational peak of ester carbonyl (C = O) absorption peak (1734.66 cm-1) disappeared. The α-helix content of protein extracted by the UACD decreased by 8.13%, and the β-turn and random coil content of protein increased by 20.22% and 18.79%, respectively, compared to that of the blank. The microstructure of mulberry leaf protein showed that the UACD method could break the dense structure of protein raw materials, reduce the average size of proteins and increase the specific surface area and roughness of proteins. According to the results of functional characteristics, the mulberry leaf protein extracted by the UACD method presented the highest enzymolysis properties and solubility, which was beneficial for the application in the food industry. In conclusion, the UACD method was a very effective way to extract protein from mulberry leaf.


Neuropsychological outcomes following pediatric lung transplantation.
Lung transplantation (LTx) is a treatment option for eligible children with end-stage pulmonary diseases. Improving our understanding of longer-term developmental outcomes in pediatric LTx recipients is important for strategized interventions targeting cognitive difficulties. Neuropsychological assessments were completed for children who received LTx at our center (2009-2017). Assessments comprised tasks of general intellect, memory, visual-perception, academics, and executive functioning as well as caregiver questionnaires of adaptive, executive, emotional, and behavioral functioning. Results were compared to age-matched population norms. Between-group nonparametric tests were performed pre-LTx vs post-LTx and for children with a primary diagnosis of cystic fibrosis (CF) vs other diagnoses (non-CF). Neuropsychological outcomes were assessed for 21 children post-LTx, with a median age (interquartile range) at the time of transplant of 11.52 (6.89, 14.12) years. Eleven children completed pre- and post-transplant assessments and within this group, improvements for verbal learning (P = .02), aspects of mood, behavior, and adaptive functioning were observed over time (all P < .05). Post-transplant whole group analysis suggested age-appropriate abilities across most cognitive domains, with a relative weakness for executive functioning. Emotional or behavioral difficulties were not endorsed by caregivers. Across pulmonary diagnoses, higher levels of emotional, behavioral, and executive functioning difficulty were reported in the non-CF group (all P < .05). Overall, LTx has a positive impact on cognitive functioning, particularly learning, adaptive functioning, mood, and behavior. Children transplanted for non-CF related diseases demonstrated greater challenges, highlighting the need for targeted assessments and interventions across the transplant process to support the complex needs of this population.


Robotic-assisted laparoscopic Essure removal: a novel surgical approach.
Primary objective was to evaluate safety and feasibility of robotic-assisted Essure removal while describing the procedure. Secondary objective was to assess improvement of symptoms post-operatively. The design was retrospective cohort study. Patients included were those who underwent robotic-assisted Essure removal between June, 2015 and December, 2020 for symptomatic relief. Interventions are robotic-assisted laparoscopic removal of Essure devices. A retrospective chart review was conducted. Phone survey of pain scores and quality-of-life ratings were performed. Twenty-one women underwent robotic-assisted removal of Essure devices. Two cases were excluded from analysis due to concomitant procedures. All devices were removed intact (19/19). The mean time from placement to removal was 5.3 years. Safety and feasibility were demonstrated, mean operating time was 43.1 ± 12 min, mean length of stay (LOS) was 11 h, and no complications occurred. Mean pain scores (0-10) improved from 8.5 before surgery to 0.75 at 1 month after surgery (p < 0.005). Mean Quality-of-Life (QOL) scores (0-7) improved from 5.9 prior to surgery to 1.5 at 1 month after surgery (p < 0.005). To our knowledge, this is the first report of the use of robotic assistance for Essure removal. Robotic-assisted laparoscopic Essure removal appears safe, feasible, and potentially superior to other surgical approaches. Despite discontinuation of the device in 2018, Essure removal is likely to remain needed. Robotic-assisted laparoscopic Essure removal appears effective in treating pain and various other symptoms attributed to Essure devices.


Efficient secretion of the herpes simplex virus tegument protein VP22 from living mammalian cells.
Many studies show that a tegument protein, VP22, of herpes simplex virus possesses an unusual capacity for intercellular trafficking, while several studies have reported that the intercellular trafficking was observed only in cells after fixation. Therefore, the trafficking ability in living cells remains controversial. To settle the question, we first examined secretion of VP22 in living cells. In this report, we fused VP22 with beta-galactosidase (betaGal) and investigated the secretion of VP22-betaGal in living cells by monitoring betaGal activity in the culture medium. Under our conditions, a significant amount of VP22-betaGal was detected in the culture medium, and it increased with time. Particularly, 6 days after transfection, 72% of all VP22-betaGal expressed was detected in the culture medium. Lactate dehydrogenase assays revealed that leakage of VP22-betaGal from damaged cells was not the main cause of the high level of secretion. We thus conclude that VP22 possesses a remarkable ability to be secreted from living cells.


Measurement of 111in DTPA clearance during radionuclide cisternography.
A new preparation of 111In DTPA for intrathecal administration has been tested and found to be a safe and highly efficacious cisternographic agent. The rate of removal of 111In DTPA from the C.S.F. and from the whole body has been measured and has been found to be of no diagnostic value in the distinction between patients with cerebral atrophy and those with normotensive hydrocephalus. Long-term retention studies show no evidence of significant long-term retention of indium in the C.S.F. The absorbed radiation dose has been investigated and found to be in good agreement with previous estimates based upon extrapolated data.


Frailty in surgical patients.
To describe the current definitions, aetiology, assessment tools and clinical implications of frailty in modern surgical practice. Frailty is a critical issue in modern surgical practice due to its association with adverse health events and poor post-operative outcomes. The global population is rapidly ageing resulting in more older patients presenting for surgery. With this, the number of frail patients presenting for surgery is also increasing. Despite the identification of frailty as a significant predictor of poor health outcomes, there is currently no consensus on how to define, measure and diagnose this important syndrome. Relevant references were identified through keyword searches of the Cochran, MEDLINE and EMbase databases. Despite the lack of a gold standard operational definition, frailty can be conceptualised as a state of increased vulnerability resulting from a decline in physiological reserve and function across multiple organ systems, such that the ability to withstand stressors is impaired. Multiple studies have shown a strong association between frailty and adverse peri-operative outcomes. Frailty may be assessed using multiple tools; however, the ideal tool for use in a clinical setting has yet to be identified. Despite the association between frailty and adverse outcomes, few interventions have been shown to improve outcomes in these patients. Frailty encompasses a group of individuals at high risk of adverse post-operative outcomes. Further work exploring ways to optimally assess and target interventions towards these patients should be the focus of ongoing research.


Laparoscopic ileal pouch-anal anastomosis in patients with chronic ulcerative colitis and primary sclerosing cholangitis: a case-matched study.
This study was designed to compare short-term outcomes after laparoscopic ileal pouch-anal anastomosis with those of open ileal pouch-anal anastomosis in patients with both sclerosing cholangitis and ulcerative colitis. Sixteen patients with sclerosing cholangitis and ulcerative colitis undergoing laparoscopic ileal pouch-anal anastomosis were matched with 16 open ileal pouch control subjects by sex, American Society of Anesthesiologists' score, age, and body mass index. Operative mortality was zero. Operative time was longer in the laparoscopic group (500 +/- 125.8 vs. 381.8 +/- 60.9 minutes, P = 0.03). Thirty-day complications were not significantly different between groups (laparoscopic 25 percent vs. open 43.7 percent, P = 0.26). Length of stay was significantly shorter in the laparoscopic group (5.3 +/- 1.3 days vs. 9.9 +/- 3.3 days open, P < 0.001). Average return of gastrointestinal function was 2.5 days in the laparoscopic group and 4.8 days in the open group (P = 0.001). Time to soft diet was three days in the laparoscopic group and six days in the open group (P < 0.001). All patients were alive and all pouches were intact at last follow-up. Laparoscopic ileal pouch-anal anastomosis is feasible with apparent safety in patients with primary sclerosing cholangitis, resulting in shorter duration of hospital stay and quicker return of gastrointestinal function compared with the open procedure with no difference in perioperative complications, reoperations, and readmissions.


Designing a Clinical Ethics Education Program for Nurses Based on the ADDIE Model.
The ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model enables educators to create programs using a systematic approach designed to meet learner's needs. The purpose of this study was to develop and evaluate a clinical ethics education program for nurses to improve their ethical confidence, ethical competence, and moral sensitivity. The study was conducted in three steps. In the first step, a seven-session ethics program was developed using the ADDIE model. The themes of each session were as follows: (a) sharing individual ethical issues in clinical settings; (b) understanding a process involved in ethical decision-making; (c) identifying ethical issues in end-of-life care; (d) identifying ethical issues in family caregiving; (e) learning communication skills; (f) developing ethical leadership skills; and (g) reflecting to build self-awareness of the significance of practicing clinical ethics. The second step involved the delivery of the program. In the third step, using a mixed methods design, the effects of the program were evaluated through a quantitative survey administered both before and after completion of the program and focus group interviews. The seven-session ethics program based on the ADDIE model improved ethical confidence, ethical competence, and moral sensitivity in nurses. The ADDIE model can be an effective tool in nursing education, offering an established structure for developing educational programs. In order to validate the effectiveness of the ethics program, it is necessary to conduct repeated measure studies and further studies at the institutional level.


Listeriosis downregulates hepatic cytochrome P450 enzymes in sublethal murine infection.
Listeria monocytogenes (Lm) can cross the intestinal barrier in humans and then disseminates into different organs. Invasion of the liver occurs even in sublethal infections, however, knowledge of affected physiological processes is scarce. This study employed a sublethal murine infection model to investigate liver responses systematically by proteomics. Liver samples from three stages of the sublethal infection covering the initial invasion, the peak of infection, and the clearance phase (1, 3, 9 days postinoculation) were analyzed in comparison to samples from noninfected mice. Apart from flow cytometry and RT-PCRs for immune status control, liver responses were analyzed by quantitative peptide sequencing (HPLC-Orbitrap Fusion) using 4-plex iTRAQ-labeling. Accurate MS characterized about 3600 proteins and statistics revealed 15% of the hepatic proteome as regulated. Immunological data as well as protein regulation dynamics strongly indicate stage-specific hepatic responses in sublethal infections. Most notably, this study detected a comprehensive deregulation of drug metabolizing enzymes at all stages, including 25 components of the cytochrome P450 system. Sublethal Lm infection deregulates hepatic drug metabolizing pathways. This finding indicates the need to monitor drug administration along Lm infections, especially in all patients needing constant medication.


Birds gone wild: same-sex parenting in albatross.
Same-sex behavior in animals fascinates scientists as well as laypeople, partly because of implications about sexual orientation in humans. After all, if animals engage in homosexuality, can it be dismissed as 'unnatural'? A recent paper by Young and colleagues documents long-term female pairs in >30% of Laysan albatross on the Hawaiian island of Oahu. The unrelated females bred successfully, challenging ideas about cooperative breeding, alternative reproductive strategies and perhaps even the evolution of sexual orientation.