Constructed wetlands and duckweed ponds as a treatment step in liquid manure handling - A life cycle assessment.
Life cycle assessment (LCA) was applied to evaluate duckweed ponds and constructed wetlands as polishing steps in pig manure liquid fraction treatment. Using nitrification-denitrification (NDN) of the liquid fraction as the starting point, the LCA compared direct land application of the NDN effluent with different combinations of duckweed ponds, constructed wetlands and discharge into natural waterbodies. Duckweed ponds and constructed wetlands are viewed as a viable tertiary treatment option and potential remedy for nutrient imbalances in areas of intense livestock farming, such as in Belgium. As the effluent stays in the duckweed pond, settling and microbial degradation reduce the remaining phosphorous and nitrogen concentrations. Combined with duckweed and/or wetland plants that take up nutrients in their plant body, this approach can reduce over-fertilisation and prevent excessive nitrogen losses to aquatic environments. In addition, duckweed could serve as an alternative livestock feed and replace imports of protein destined for animal consumption. The environmental performance of the overall treatment systems studied was found to depend greatly on assumptions about the possible avoidance of potassium fertiliser production through the field application of effluents. If it is assumed that the potassium contained in the effluent replaces mineral fertiliser, direct field application of the NDN effluent performed best. If the application of NDN effluent does not lead to mineral fertiliser savings or if the replaced K fertiliser is of low grade, duckweed ponds seem to be a viable additional step in the manure treatment chain. Consequently, whenever background concentrations of N and/or P in fields allow for effluent application and potassium fertiliser substitution, direct application should be favoured over further treatment. If direct land application of the NDN effluent is not an option, the focus should be on long residence times in duckweed ponds to allow for maximum nutrient uptake and feed production.


Strengthen the purification of eutrophic water and improve the characteristics of sediment by functional ecological floating bed suspended calcium peroxide and sponge iron jointly.
To overcome the shortcomings of conventional ecological floating bed (CEFB) in purifying landscape water, this study constructed a functional ecological floating bed (FEFB) through the suspension of calcium peroxide (CP) and sponge iron (SI) jointly below the CEFB. The purification effect of water quality and influence of sediment were compared in control check, CEFB, and FEFB systems, which were loaded the same sediment and reclaimed water in a field experiment. Results showed that the FEFB suspended with CP and SI had evident purification effect on the quality of landscape water supplied with reclaimed water and can maintain stably the nutrient status of the water body at mesotrophic levels and low turbidity. The FEFB promoted the degradation of humus, thus eliminating the chroma risk in water body caused by the decay of plants from the CEFB. Moreover, the FEFB can control the sediment mass produced, reduce the total nitrogen (TN) mass of sediment, and decrease the transformable TN (TTN) content in the sediment. The FEFB enhanced the stability of phosphorus (P) in the sediment, where the relative content of Ca-P and stable P reached 42.18% and 64.27%, respectively. To sum up, the FEFB suspended with SI and CP can not only effectively control the eutrophication and sensory index of landscape water but also change the TTN content and P forms in sediment, making the sediment more stable. Thus, the FEFB provides an innovative approach to reduce endogenous nutrient release for landscape water along with recharging with reclaimed water.


Caregiving Status and Health of Heterosexual, Sexual Minority, and Transgender Adults: Results From Select U.S. Regions in the Behavioral Risk Factor Surveillance System 2015 and 2016.
Insufficient research attention has been paid to the diversity of informal caregivers, including sexual and gender minority caregivers. This study examined health effects of caregiving separately from sexual orientation or gender identity status, while stratifying by gender among cisgender adults. We hypothesized that compared with heterosexual cisgender noncaregivers, heterosexual caregivers and lesbian/gay/bisexual (LGB), and transgender (T) noncaregivers would report poorer health outcomes (i.e., self-reported health, and poor mental health days and poor physical health days), and LGBT caregivers would report the worst health outcomes. This is a secondary data analysis of the 2015 and 2016 Behavioral Risk Factor Surveillance System data from 19 U.S. states. After adjusting for covariates and stratifying by gender among the cisgender sample, heterosexual caregivers, LGB noncaregivers and LGB caregivers had significantly higher odds of self-reported fair or poor health (adjusted odds ratios [aORs] 1.3-2.0 for women and 1.2 for men), poor physical health days (aORs 1.2-2.8 for women and 1.3-2.8 for men), and poor mental health days (aORs 1.4-4.7 for women and 1.5-5.6 for men) compared with heterosexual noncaregivers (reference group). By contrast, transgender caregivers did not have significantly poorer health than cisgender noncaregivers. LGB caregivers reported the worst health compared with other groups on multiple measures, signifying they are an at-risk population. These results suggest the necessity to develop LGB appropriate services and programs to prevent poor health in LGB caregivers. Existing policies should also be inclusive of LGBT individuals who are caregivers.


Rational addiction and time-consistency: An empirical test.
This paper addresses one of the main empirical problems associated with rational addiction theory, namely, that its derived demand equation is not empirically distinguishable from those of models with forward-looking behavior but with time-inconsistent preferences. Using an encompassing general specification of the rational addiction model we derive a microfounded test of time-consistency. The test allows us to distinguish between time-consistent versus time-inconsistent naïve agents. The results obtained from a panel of Russian individuals conform to the theoretical predictions of the rational addiction model and the proposed test for time-consistency does not reject the hypothesis that Russian cigarette consumers are time-consistent.


In vitro fermentation characteristics of the dietary fiber in bamboo (Phyllostachys edulis) shoots and its regulatory effects on the intestinal microbiota and metabolites.
The effects of bamboo (Phyllostachys edulis) shoot dietary fiber (BSDF-1) on ulcerative colitis (UC) are unclear. Therefore, we performed an in vitro glycolysis study of intestinal microbiota samples, based on 16S rDNA sequencing and determining the metabolites in non-targeted colonic fecal fermentation broth. After a 48 h fermentation, the pH of the fermentation broth decreased significantly (p < 0.05) with the dextran sulfate sodium group (referred to here as the Mod group). The carbohydrate utilization rate was 26.59 %, and the total short-chain fatty acid content was 16.46 ± 0.71 mmol/L. The abundances of Alistipes and Lactobacillus increased after BDSF-1 fermentation, whereas those of Escherichia-Shigella, Enterococcus, and Proteus significantly decreased. BSDF-1 altered the levels of 17 metabolites in the Mod group after fermentation for 48 h, which reduced the cadaverine increasing induced by DSS. These results indicate that BSDF-1 can regulate the metabolism of the intestinal microbiota and the host, suggesting its use as a promising therapeutic strategy.


Study on the biological effect of fast neutrons 1. Effect of fast neutrons on germinability of barley seeds and on the chlorophyll content of the seedlings according to the dose used.
Barley seeds were irradiated in the active zone of the reactor at 500 watt, at favourable flux of fast neutrons in the dose interval of 823--2144 rad. Seeds after irradiation were "cooled" for 48 hours, then germinated, and the length of shoots of the seven days old seedings was measured. The value of the half lethal dose is 1130 rad, estimated from the growth curve. There is a well-defined relation of chlorophyll content (calculated for fresh weight unit) to the dose used. It was concluded from the phenotype of the leaves that the decrease of chlorophyll content was due first of all to the presence of chlorophyll-less cells and cell lines and not to the decrease of chlorophyll content of the individual cells. Irradiation yielded genetically defected cells.


Adjustment of the human melatonin and cortisol rhythms to shortening of the natural summer photoperiod.
Fifteen human subjects were exposed to natural outdoor summer light from 0415 h until 2000 h for 4 days and then from 0800 h until 1600 h for another 4 days. Following shortening of the natural summer photoperiod, times of the morning salivary melatonin decline and cortisol rise did not change whereas the time of the evening melatonin rise phase advanced by about 1.5 h within 1 day and further did not change significantly. Consequently, the melatonin signal duration extended markedly within 1 day. The data show that the compressed melatonin rhythm waveform in humans experiencing a long natural summer photoperiod from sunrise until sunset may change rapidly following a shortening of the photoperiod.


Pediatric renal transplantation: comparative study with renal transplantation in the adult population.
To retrospectively review our experience with pediatric renal transplantation and to compare the results with the adult population. Between January 1981 and August 2003, 74 renal transplants were performed in patients < or =18 years at the time of the transplant--the pediatric group versus 1153 patients in the adult group. We analyzed various risk factors for actuarial kidney graft and patient survivals using the Kaplan-Meier method. Median ages were 13.8 +/- 3.5 and 42.6 +/- 2.4 years, respectively. There was no statistically significant difference in the human leukocyte antigen matching or immunosuppression. There was, however, a younger donor age and shorter ischemia time in the pediatric group. Overall, kidney transplant survival rates for patients < or =18 years at 1, 2, 5, and 10 years were 94.4%, 91.3%, 70.6%, and 58.2%, respectively, with no significant difference for patients older than 18 (91.2%, 89.3%, 78.8%, 60.5%, P = .4325). There was a significantly decreased graft survival in the adult group at 10 years when the donor age was over 60 years and when the ischemia time was > or =20 hours. The incidence of delayed graft function and the creatinine levels of functioning grafts did not differ between the two groups. During the follow-up, acute rejections were more frequent in the younger group. Patient survival in the pediatric group at 1, 2, 5, and 10 years was 98.6%, 98.8%, 98.6%, and 90.3%, respectively, significantly lower in the adult group (95.3%, 94.0%, 87.9%, 76.8%, P < .02). Renal transplantation may be successfully performed in the pediatric patients with end-stage renal disease. Overall graft survival at 10 years did not differ significantly between the two groups. There is a higher incidence of acute rejections but longer patient survival in the pediatric population.


Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study.
Most NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain. The aim of the study was to estimate population event rates for NSAID-associated ALFT METHODS: This was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY). In the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose). Event rates per MTY were 1.59 (95 % CI 1.1-2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2-3.9) for ibuprofen, 1.9 (95 % CI 0.8-3.7) for nimesulide, 1.6 (95 % CI 0.6-3.4) for diclofenac and 1.6 (95 % CI 0.3-4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6-4.1) without overdoses and 7.8 (95 % CI 6.8-9.0) including overdoses. ALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.


Effect of ascorbate on acrolein modification of very low density lipoprotein and uptake of oxidized apolipoprotein e by hepatocytes.
Acrolein modification of apolipoprotein (apo) E in human very low density lipoprotein (VLDL) was suppressed by ascorbate. Acrolein-modified apoE in VLDL was not taken up by human hepatoma cell whereas unmodified apoE in the presence of ascorbate was taken up. These results suggest that ascorbate can play an important role in maintaining proper lipoprotein metabolism by the antioxidant effect.


Novel platinum(IV) complexes conjugated with a wogonin derivative as multi-targeted anticancer agents.
Platinum-based complexes like cisplatin and oxaliplatin are well known the mainstay of chemotherapy regimens on clinic. Wogonin, a natural product that possesses wide biological activities, is now in phase I clinical test as an anticancer agent in China. Herein reported are a series of novel Pt(IV) complexes that conjugated a wogonin derivative (compound 3) to the axial position via a linker group. After being tethered to the platinum(IV) complexes, the wogonin derivative provided multiple anticancer effects, especially in compound 10, a fusion containing wogonin and cisplatin units. Compound 10 not only inherited the genotoxicity from cisplatin, but also obtained the COX inhibitory property from the wogonin derivative. Further mechanistic investigation revealed that compound 10 caused the accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and then activated the p53 pathway. Overall, the research demonstrates that the "integrative" prodrug can be an effective strategy to promote the anticancer potency of Pt-based drugs for cancer treatment.


Contemplative pedagogy as a framework for education about ageism.
Current education in gerontology focuses on sharing knowledge and promoting intergenerational contact in order to shift students' attitudes about aging and elders. Existing interventions, however, may be less effective in modifying students' emotional reactions and implicit ageism. Contemplative pedagogy includes practices that help students notice cognitive and emotional patterns and that may serve to reduce bias. Suggestions are made for ways to incorporate contemplative pedagogy in the gerontology classroom.


Assessment of water supply as an ecosystem service in a rural-urban watershed in southwestern Mexico City.
Studies from the ecosystem services perspective can provide a useful framework because they allow us to fully examine the benefits that humans obtain from socio-ecological systems. Mexico City, the second largest city in the world, has faced severe problems related to water shortages, which have worsened due to increasing population. Demand for space has forced changes in land cover, including covering areas that are essential for groundwater recharge. The city has 880 km(2) of forest areas that are crucial for the water supply. The Magdalena River Watershed was chosen as a model because it is a well-preserved zone within Mexico City and it provides water for the population. The general aim of this study was to assess the ecosystem service of the water supply in the Magdalena River Watershed by determining its water balance (SWAT model) and the number of beneficiaries of the ecosystem services. The results showed that the watershed provides 18.4 hm(3) of water per year. Baseflow was dominant, with a contribution of 85%, while surface runoff only accounted for 15%. The zone provides drinking water to 78,476 inhabitants and could supply 153,203 potential beneficiaries. This work provides an example for understanding how ecosystem processes determine the provision of ecosystem services and benefits to the population in a rural-urban watershed in Mexico City.


Cardiorespiratory fitness and risk of site-specific cancers: a long-term prospective cohort study.
Based on self-reported physical activity, there is epidemiologic evidence for a beneficial relation between physical activity and colon cancer in men, but findings for other cancers are inconclusive. Measured cardiorespiratory fitness (CRF) can provide knowledge about the cancer-preventive value of physical activity. We aimed to assess relationships between CRF and risk of site-specific cancers. A cohort of 1997 healthy Norwegian men, aged 40-59 years at inclusion in 1972-1975, was followed for cancer throughout 2012 using data from the Cancer Registry of Norway. CRF was measured by a maximal exercise bicycle test at inclusion. Relationships between CRF and site-specific cancers were estimated using Cox regression, adjusted for age, body mass index, and smoking. During follow-up, 898 cancer cases were diagnosed in 758 men. When comparing men in CRF tertile 1 with men in tertiles 2 and 3, respectively, we found decreased risk of proximal colon cancer in tertile 2 (HR: 0.30, 95% CI: 0.13-0.73) and decreased risk of cancers of lung (0.39 95% CI: 0.22-0.66), pancreas (0.32 95% CI: 0.10-1.00), and bladder (HR: 0.40 95% CI: 0.21-0.74) in tertile 3. Furthermore, a significant trend for lower risk by increasing CRF tertile was found for cancers of proximal colon, lung, and bladder (P-value for trend <0.05). For other cancer sites, no significant association was found. Our results indicate that high midlife CRF may have cancer-preventive value.


Mitochondrial dysfunction induced by honokiol.
Honokiol has shown the ability to induce the apoptosis of several different cancer cell lines. Considering that mitochondria are involved in apoptosis, the aim of the present work was to investigate the effects of honokiol on mitochondria. The effects of honokiol on the permeability of H⁺ and K⁺, membrane potential, membrane fluidity, respiration and swelling of mitochondria isolated from the rat liver were assessed. The results show that honokiol can significantly induce mitochondrial swelling, decrease membrane potential and affect the respiration of mitochondria. Meanwhile, honokiol does not have a direct effect on the mitochondrial permeability transition pore.


[Familial incidence of juvenile diabetes mellitus and primary optic atrophy (author's transl)].
The syndrome of juvenile diabetes mellitus, primary optic atrophy and hydronephrosis, hydroureter and megacystis was observed in two brothers. One patient showed consistent elevation of the plasma creatine phosphokinase activity (isoenzymes MM 71%, MB 29%), without any sign of myocardial or skeletal muscle disease. This rare syndrome is inherited in an autosomal recessive manner. It has not yet been reported in Austria, to our knowledge.


The histochemistry of glycoconjugates in the colonic epithelium of the chicken.
In the colonic epithelium of the chicken, glycoconjugates have been studied by means of selected histochemical methods of light and electron microscopy. According to the results obtained, most of the colonic goblet cells contained acidic and neutral glycoconjugates with sulphate and vicinal diol groupings, alpha-D-mannose and alpha-D-glucose residues and sialic acid-galactose dimers. These goblet cells were found to undergo changes in histochemical reactivity during upward migration along the crypts; alpha-D-mannose and alpha-D-glucose residues and terminal sialic acid-galactose dimers increased in amount. The striated border of the colonic columnar cells has, likewise, been found to contain such glycoconjugates as were similar in reactivity to those of the goblet cells. The histophysiological significances of glycoconjugates involved in the chicken colonic epithelium have been discussed with special reference to the functional activities of the carbohydrates.


[Demonstration of circulating soluble immune complexes in the sera of psoriatic patients using the 125I-C1q deviation test].
The sera from 50 psoriatic patients, 130 patients with other skin diseases and from 24 healthy blood donors were tested for the presence of circulating immune complexes. By means of the 125I-C1q deviation test a positive result was obtained in 70% of the sera from psoriatic patients as compared to 8% in the healthy controls.


Quantifying alignment bias during the fabrication and fitting of ankle-foot orthoses: A single center study.
The sagittal plane alignment of ankle-foot orthoses (AFO) and AFO footwear combinations (AFO-FC) has been shown to influence gait outcomes. As such, clinicians often target a particular alignment during the fabricating and fitting of an AFO to maximize outcomes. How does the alignment of an AFO change during the fabrication and fitting process with respect to the intended, benchmark sagittal plane alignment identified by the consulting orthotist? Prospective METHODS: The assessment of AFO alignment was performed using a convenience sample of 125 custom molded AFOs from 68 individuals fabricated at our center (57 bilateral AFOs, 11 unilateral AFOs). The alignment of each AFO was measured at 5 distinct steps during the fabrication and fitting process using a recently validated method to measure AFO neutral angle using differential inclinometers. Prior to fabrication, the intended, benchmark alignment set by the consulting orthotist was 90 degrees for 92% of AFOs, was between 1 and 7 degrees of dorsiflexion for 7% of AFOs and was 5 degrees of plantarflexion for 1% of AFOs. Repeated measures ANOVA showed that AFO alignment changed between all fabrication and fitting steps. Overall, paired t-tests confirmed that AFO alignment was consistently 2-5 degrees more dorsiflexed than the benchmark alignment. Prior to fitting shoes, 55% of fabricated AFOs measured more than 2 degrees from the benchmark alignment. After fitting shoes, nearly 87% of AFO-FCs were more than 2 degrees from the benchmark alignment. The finding of systematic dorsiflexion bias and changes in AFO alignment throughout the fabrication and fitting process indicates the need to improve AFO fabrication precision. The neutral angle measurement methodology - using differential inclinometers - provides a means to improve this precision by enabling orthotists to precisely quantify and make appropriate adjustments to AFO alignment throughout the entire fabrication and fitting process.


A longitudinal cephalometric study of postorthodontic craniofacial changes.
Although the orthodontist focuses great efforts on diagnosis and treatment of the patient, less attention is paid to posttreatment changes that occur because of relapse and continued growth, especially over the long term. This cephalometric study describes 36 patients who were recalled x = 5.5 years after treatment and again x = 14.4 years after treatment. Most linear dimensions increased significantly from the end of treatment to first recall (ca. 16 to 21 years), presumably as a result of continued adolescent growth, but few changes achieved significance thereafter (ca. 21 to 30 years). Arch relationships (eg, ANB, NAP, AOBO, Y-axis) continued to improve after treatment, probably as a result of late growth of the mandible producing a more orthognathic profile. There was little change from first to second recall in any of the variables. Results suggest that if relapse occurs, it is likely to be evident soon after treatment and diminish thereafter and that continued craniofacial growth generally augments the orthodontic correction.


Layer-by-layer electrochemical biosensors configuring xanthine oxidase and carbon nanotubes/graphene complexes for hypoxanthine and uric acid in human serum solutions.
A selective biosensing platform for the determination of hypoxanthine (Hx) and uric acid (UA) concentrations in both buffer and human serum sample solutions was developed. The biosensor features the layer-by-layer (LbL) self-assembly of negatively charged xanthine oxidase (XOD) and positively charged poly(diallyldimethyl ammonium chloride) (PDDA) wrapped oxidized multi-walled carbon nanotubes and graphene (CNTs-G) complexes (PDDA-CNTs-G) on screen printed carbon electrode (SPCE) surfaces. Catalytic responses of the XOD modified biosensor with the chosen optimum number of layers for LbL assembly on SPCE towards Hx in buffer solutions were first investigated using both cyclic and square wave voltammetries. The peak current at around 0.08 V (vs. Ag/AgCl) associated with the production of UA increased as a function of the Hx concentration due to the surface selective catalytic reaction of XOD and Hx. A linear dynamic range of 5-50 µM Hx with a detection limit of 4.40 µM was obtained and the sensor was further applied to the analysis of Hx in normal human serum solutions in addition to myocardial infarction (MI) patient serum sample solutions from a local hospital. Since untreated serum solutions contain a certain amount of UA, a XOD free SPCE biosensor consisted of only PDDA-CNTs-G was also employed to evaluate the native concentration of UA in the serum and further assist the determination of Hx concentration when using the developed LbL biosensor. Our sensing results for the real biological fluidic solutions were finally validated by comparing to those using liquid chromatography-mass spectrometry(LC-MS).


High failure rates following ligation of the intersphincteric fistula tract for transsphincteric anal fistulas: are preoperative MRI measurements of the fistula tract predictive of outcome?
Treatment of transsphincteric fistulas (TSFs) with fistulotomy after an indwelling seton is tempered by risks of incontinence and litigation. Thus, ligation of the TSF tract has been popularized as an alternative option. We previously reported on 107 patients who underwent ligation of the intersphincteric fistula tract (LIFT), with a 46% failure rate. Posterior fistula was the only predictor of recurrence. The aim of the present work was to investigate whether the length, width or depth of the fistula measured on preoperative MRI was correlated with recurrence. Following institutional review board approval, a retrospective analysis of our prospective Complex Anal Fistula Database from 1 January 2011 to 31 August 2019 was performed. Patients with TSF who underwent preoperative MRI and LIFT were included. Fistula location was classified as anterior, posterior or lateral. MRI measurements of fistula length, width and depth (in the intersphincteric groove) were performed. The type and rate of postoperative recurrence were analysed. 173 patients underwent MRI for an anal fistula; of these 40 underwent LIFT and 22/40 (55%) had preoperative MRI. There was no difference in the length, width or depth of anterior (n = 9), posterior (n = 7) or lateral (n = 6) fistula tracts. The overall recurrence rate was 9/22 (41%). Posterior TSFs had the highest recurrence rate (5/7, 71%). The mean length, width, and depth of the fistula tract, measured at the preoperative site of LIFT in the intersphincteric groove, did not correlate with recurrence regardless of fistula location.


Funding resources for rare disease research.
Research is an expensive venture requiring multiple sources of funding for small projects that test new theories, large projects to make major advancements, training the next generation of researchers and facilitating meetings to share findings and support collaboration. For rare conditions, such as Batten disease, research funds can be difficult to find. To see how investigators supported their work in the past, we did a key word search of the Acknowledgement Section of peer-reviewed literature published in Batten disease in the last 6.5 years. Interestingly, we discovered 193 separate funding sources. The authors hope that, by showing where funds are available, we will enable Batten disease researchers to continue their pursuits and expand their studies; moving key findings from discovery to application phases. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.


The permeability of uncoupled heart mitochondria to potassium ion.
Isolated heart mitochondria retain matrix K+ in a K+-free medium and exchange matrix 42K+ with external K+ only slowly. This low permeability to K+ is maintained when the proton motive force is dissipated by addition of an uncoupler, but can be increased markedly in uncoupled mitochondria when (a) NADPH becomes oxidized and (b) a Ca2+ chelator or ruthenium red is added (Jung, D. W., and Brierley , G. P. (1981) J. Biol. Chem. 256, 10490-10496). This latter requirement suggests that decreased Ca2+ binding or alteration of the Ca2+ uniporter may be involved in the induction of permeability to K+ in these mitochondria. The present studies establish that La3+ (k0.5 = 1.8 nmol X mg-1 of protein) also induces K+ permeability in uncoupled mitochondria in which NADPH has been oxidized. The amount of net K+ loss or passive 42K+/K+ exchange induced by La3+ corresponds to that produced by ruthenium red or EGTA and appears to vary from preparation to preparation as a function of the endogenous adenine nucleotide (AN) content of the mitochondria. The permeability to K+ induced by all three reagents is increased by depletion of endogenous AN with PPi and strongly inhibited by low levels of exogenous AN. The optimum passive permeability to K+ develops at pH 7.5, is inhibited by Nupercaine , quinine, and dicyclohexylcarbodiimide, and is increased in a sucrose, as opposed to a KCl medium. The increased permeability to K+ appears to result from the opening of one or more K+-conducting uniport pathways, rather than K+/H+ exchange. Since Ca2+ efflux remains sensitive to ruthenium red when K+ efflux is induced, it seems unlikely that the Ca2+ uniporter itself can provide a pathway for K+ flux. The presence of such latent pathways for passive K+ permeability must be considered when defining the properties of the putative K+/H+ antiporter and during isolation and reconstitution protocols involving mitochondrial K+ transport components.


Differentiation of IncL and IncM Plasmids Associated with the Spread of Clinically Relevant Antimicrobial Resistance.
blaOXA-48, blaNDM-1 and blaCTX-M-3 are clinically relevant resistance genes, frequently associated with the broad-host range plasmids of the IncL/M group. The L and M plasmids belong to two compatible groups, which were incorrectly classified together by molecular methods. In order to understand their evolution, we fully sequenced four IncL/M plasmids, including the reference plasmids R471 and R69, the recently described blaOXA-48-carrying plasmid pKPN-El.Nr7 from a Klebsiella pneumoniae isolated in Bern (Switzerland), and the blaSHV-5 carrying plasmid p202c from a Salmonella enterica from Tirana (Albania). Sequencing was performed using 454 Junior Genome Sequencer (Roche). Annotation was performed using Sequin and Artemis software. Plasmid sequences were compared with 13 fully sequenced plasmids belonging to the IncL/M group available in GenBank. Comparative analysis of plasmid genomes revealed two distinct genetic lineages, each containing one of the R471 (IncL) and R69 (IncM) reference plasmids. Conjugation experiments demonstrated that plasmids representative of the IncL and IncM groups were compatible with each other. The IncL group is constituted by the blaOXA-48-carrying plasmids and R471. The IncM group contains two sub-types of plasmids named IncM1 and IncM2 that are each incompatible. This work re-defines the structure of the IncL and IncM families and ascribes a definitive designation to the fully sequenced IncL/M plasmids available in GenBank.


Mean platelet volume and platelet distribution width in the neonate.
Normal values for mean platelet volume (MPV) and platelet distribution width (PDW) have not been firmly established for term and preterm neonates. Cord blood samples from 143 healthy newborns (78 full term and 65 premature) were analyzed with the Coulter counter. Platelet count and MPV were significantly greater (p less than 0.05 and p less than 0.001, respectively) in term versus preterm infants, while PDW was significantly less in term infants (p less than 0.001). Platelet count and MPV correlated with gestational age, and platelet count also correlated with birth weight. There was a significant (p less than 0.001) negative correlation of PDW with gestational age and birth weight. These data represent normal reference ranges for neonates and demonstrate significant variation with gestational age.


Protocol for using autoclaved intertidal sediment as a medium to enrich marine cable bacteria.
Cable bacteria (CB) are non-isolated filamentous bacteria in the family of Desulfobulbaceae, known for fostering centimeter-long electron transfer in sediments with pronounced redox zonation. This protocol details steps to extract CB filaments from cultured natural sediment, inoculate autoclaved sediment with extracted filaments, and subsequently evaluate the growth and enrichment of CB. We also describe the approaches for collecting suitable sediment, preparing autoclaved sediment, and manufacturing glass needles and hooks for the extraction of CB.


Effects of dopamine depletion from the caudate-putamen and nucleus accumbens septi on the acquisition and performance of a conditional discrimination task.
Three experiments compared the effects of dopamine depletion from the caudate-putamen (CAUD; dorsal striatum) or nucleus accumbens septi (NAS; ventral striatum), or a systemically administered dopamine receptor antagonist (alpha-flupenthixol) on the acquisition and performance of a conditional discrimination task involving temporal frequency. In Expt. 1, rats receiving 6-hydroxydopamine (6-OHDA) lesions of the CAUD were impaired in the acquisition of a visual version of the task, and rats with 6-OHDA lesions of the NAS were not reliably impaired. Even when the rats with CAUD lesions had acquired the discrimination, they were still significantly slower to collect earned food pellets. Both CAUD and NAS lesions reduced a bias to respond to the faster of the two discriminative stimuli. In Expt. 2, rats with 6-OHDA lesions of CAUD were markedly impaired in their accuracy and speed of responding when they had been trained to criterion preoperatively. These effects could not be mimicked in controls by prefeeding (which had only minor effects on performance). Rats with 6-OHDA-induced lesions of the NAS were unimpaired in either visual or auditory discrimination performance, but were slower to extinguish responding than controls. In Expt. 3, alpha-flupenthixol (0.1-0.56 mg/kg, i.p.) produced dose-dependent impairments in both latency to respond and choice accuracy in visual and auditory versions of the task. In conjunction with other results, these data suggest that (1) dopamine receptor blockade and central dopamine depletion can impair discrimination performance under certain conditions (2) dopamine depletion from the ventral and dorsal striatum, respectively, have dissociable effects on behaviour controlled by conditioned reinforcers and discriminative stimuli and (3) the disruption of discrimination performance by dorsal striatal dopamine depletion is probably attributable to several factors.


Maturity-onset diabetes of the young (MODY): genetic and clinical characteristics.
Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of familial diabetes mellitus characterized by early onset, autosomal dominant inheritance and primary defects of insulin secretion. Mutations in six genes cause most of the MODY cases. These genes encode the enzyme glucokinase and the transcription factors hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 1alpha, insulin promoter factor-1, hepatocyte nuclear factor 1beta and neuroD1. Additional MODY genes remain to be identified. The study of families with MODY has shown that the different MODY subtypes present different metabolic and clinical profiles.


Accumulation rate of advanced glycation end products in recent onset psychosis: A longitudinal study.
Schizophrenia is associated with excessive oxidative stress. Production of advanced glycation end products (AGEs) in the skin is strongly associated with oxidative stress. Increased skin AGE-levels have been demonstrated at cross-sectional level in recent onset psychosis and chronic schizophrenia, indicating increased cardiovascular risk. We aimed to investigate factors underlying AGE-accumulation and accumulation rate of AGEs in recent onset psychosis. From December 2016 through May 2017, 66 patients and 160 (highly educated) healthy controls from a previous case-control study of AGE-levels were assessed for a follow-up measurement 12-24 months after baseline. Possible determinants of AGE-accumulation were analyzed. AGE-accumulation rates in patients and controls were compared adjusted for relevant confounders. In healthy controls, a significant association of AGE-accumulation with ethnicity and tobacco exposure was found. An indication of a markedly higher AGE-accumulation rate was found in patients suffering from recent onset psychosis compared to healthy controls, independent of ethnicity and tobacco smoking, but not independent of cannabis use (more prevalent in patients than controls), although results were not significant.


Gender Differences in Physical Activity Associated with Urban Neighborhood Parks: Findings from the National Study of Neighborhood Parks.
Urban neighborhood parks are designed to provide easy access to recreation and physical activity. We analyzed data from the first National Study of Neighborhood Parks, which assessed the characteristics and use of a representative sample of U.S. urban neighborhood parks. This article compares factors associated with active commuting (e.g., walking) to parks among men and women and park characteristics associated with observed moderate-to-vigorous physical activity (MVPA) within neighborhood parks. We used systematic direct observation to quantify parks visitors of all ages in 162 U.S. neighborhood parks in 25 cities in 2016 and surveyed a sample of adult visitors (877 women and 793 men). We used descriptive statistics to identify park facilities, amenities, and park management practices associated with park use. We also conducted multivariate regressions to identify factors most closely associated with observed park-based MVPA among all age groups and with self-reported levels of active commuting to parks among adults. Reasons to visit parks varied by gender, with women more likely than men to bring children (59% vs 42% for men; p < .001), and men more likely than women to go to parks to relax (38% vs 29%; p = .01). Bringing children to parks was associated with more motorized transport among women, but not among men. Active commuting to parks was associated with living closer to parks (β = -0.92; p < .0001), a greater frequency of park use (β = 0.99; p < .0001), and the park having a working drinking fountain (β = 0.62; p = .01), with no significant differences between men and women. Men and boys used park facilities very differently than women and girls. Men and boys engaged in the most MVPA in soccer fields, gyms, and skate parks, whereas for women and girls the top three sites were pools, playgrounds, and walking paths. Significant gender differences in why men and women visit parks and how parks are used likely reflect cultural determinants of gender roles. Our findings suggest that park management practices should be adjusted to mitigate the lower use of parks and lower levels of park-based MVPA among women and girls compared with men and boys.


A de novo microdeletion in a patient with inner ear abnormalities suggests that the 10q26.13 region contains the responsible gene.
Microdeletions in the 10q26.1 region are related to intellectual disability, growth delay, microcephaly, distinctive craniofacial features, cardiac defects, genital abnormalities and inner ear abnormalities. The genes responsible for inner ear abnormalities have been narrowed to fibroblast growth factor receptor 2 gene (FGFR2), H6 family homeobox 2 gene (HMX2) and H6 family homeobox 3 gene (HMX3). An additional patient with distinctive craniofacial features, congenital deafness and balance dysfunctions showed a de novo microdeletion of 10q26.11q26.13, indicating the existence of a gene responsible for inner ear abnormalities in this region.


Pre-manipulative testing: predicting risk or pretending to?
Clinical practice guidelines should be evidence-based and useful. Unfortunately, the APA guidelines largely are not. Their recommendations include.


Linear regression analysis of ultrasound follicular growth series: evidence for an abnormality of follicular growth in endometriosis patients.
Follicular diameter growth is a highly linear function of time. Recently, the potential utility of linear regression-derived parameters for describing and comparing cycles of follicular growth was described. The linearity of growth, growth rate constant (K), calculated date of growth onset (Do), total growth period (TGP), menstrual age at apparent ovulation (MAov), and peak follicular diameter (PFD) have been calculated from the follicular growth series of a group of patients with laparoscopically diagnosed endometriosis (n = 46). These parameters were compared with those of a group of normal volunteers (n = 18). The authors found significant differences between endometriosis patients and controls in follicular growth rate and total growth period. The effect of patients' clomiphene citrate usage on growth parameters in these patients was examined. Abnormalities in interrelationships between the growth parameters were detected, suggesting the possibility of subtle defects in the regulation of follicular growth in these patients.


Clozapine modulation of zebrafish swimming behavior and gene expression as a case study to investigate effects of atypical drugs on aquatic organisms.
Mental illnesses affect more than 150 million people in Europe and lead to an increasing consumption of neuroactive drugs during the last twenty years. The antipsychotic compound, clozapine, is one of the most used psychotropic drugs worldwide, with potentially negative consequences for the aquatic environment. Hence, the objectives of the study presented here were the quantification of clozapine induced changes in swimming behavior of exposed Danio rerio embryos and the elucidation of the molecular effects on the serotonergic and dopaminergic systems. Yolk-sac larvae were exposed to different concentrations (0.2 mg/L, 0.4 mg/L, 0.8 mg/L, 1.6 mg/L, 3.2 mg/L and 6.4 mg/L) of clozapine for 116 h post-fertilization, and changes in the swimming behavior of the larvae were assessed. Further, quantitative real-time PCR was performed to analyze the expression of selected genes. The qualitative evaluation of changes in the swimming behavior of D. rerio larvae revealed a significant decrease of the average swimming distance and velocity in the light-dark transition test, with more than a 36% reduction at the highest exposure concentration of 6.4 mg/L. Furthermore, the total larval body length was reduced at the highest concentration. An in-depth analysis based on expression of selected target genes of the serotonin (slc6a4a) and dopamine (drd2a) system showed an upregulation at a concentration of 1.6 mg/L and above. In addition, a lower increase in expression was detected for biomarkers of general stress (adra1a and cyp1a2). Our data show that exposure to clozapine during development inhibits swimming activity of zebrafish larvae, which could, in part, be due to disruption of the serotonin- and dopamine system.


Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue.
DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology.


Tissue specific expression of the splice variants of the mouse vacuolar proton-translocating ATPase a4 subunit.
We have identified splicing variants of the mouse a4 subunit which have the same open reading frame but have a different 5'-noncoding sequence. Further determination of the 5'-upstream region of the a4 gene in mouse indicated the presence of two first exons (exon 1a and exon 1b) which include the 5'-noncoding sequence of each variant. The mRNAs of both splicing variants (a4-I and a4-II) show a similar expression pattern in mouse kidney by in situ hybridization. However, tissue and developmental expression patterns of the variants are different. In addition to strong expression in kidney, a4-I expression was detected in heart, lung, skeletal muscle, and testis, whereas a4-II is expressed in lung, liver, and testis. During development, a4-I was expressed beginning with the early embryonic stage, but a4-II mRNA was detected from day 17. These results suggest that each a4 variant has both a tissue and developmental stage specific function.


A new pyoverdin from Pseudomonas aeruginosa R'.
From a Pseudomonas aeruginosa hospital isolate a new pyoverdin was isolated. It is identical with that of Pseudomonas aeruginosa strain R except that in the peptide chain L-Gln is missing.


Smoking cessation and the risk of hospitalization for pneumonia.
Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% CI 0.31-0.74), while former smokers had no difference in (adjusted HR 0.83, 95% CI 0.63-1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% CI 0.45-0.95). However, this lower risk was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41-0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD.


[Severe hemorrhage intestinal in a child with ileal duplication and brief entity review].
Intestinal duplications are very uncommon congenital malformations located in the mesenteric edge of the small bowel, particularly in the ileum. Over 60% of the patients become symptomatic during the first year of life whereas the remainder demonstrates symptoms at school age or adulthood. The wide spectrum of symptoms and unspecific signs frequently simulate other diseases. Gastrointestinal hemorrhage is the most noteworthy complication, which can cause severe anemia and shock. In the case we describe an 11-year-old girl experienced massive intermittent intestinal hemorrhage, anemic syndrome and intense abdominal pain over 15 months. In this patient, hemoglobin levels rose up to 6 g/dL necessitating several hemotransfusion. Multiple diagnosis and examinations were carried out until finally the gammagram with Tc99m disclosed an ectopic gastric mucosa. Using a laparotomy an intestinal duplication was found in the terminal ileum. In this paper the intestinal duplication is analyzed and the importance of considering it as a differential diagnosis in any kind of bleeding of the digestive tube is discussed.


Resistance to apoptosis is increased during metastatic dissemination of colon cancer.
Apoptosis dysfunction in metastases has been suggested to participate in their poor response to conventional anticancer treatments. To address this question, we have analyzed the sensitivity to cell death induced by non-steroid anti-inflammatory drug, Sulindac, the most common drug used in colon cancer chemotherapy, 5-fluorouracil (5-FU) and the short chain fatty acid, butyrate (Bu) in cell lines derived from a primary colorectal tumor (ALT-I) as well as the liver (ALT-F) and the lymph-node (ALT-G) metastases. We have previously shown both in vitro by analyzing anchorage-independent cell proliferation and in vivo by subcutaneous injection into athymic nude mice that the ALT-F and ALT-G cells were more tumorigenic than the primary ALT-I cells. All these cell lines, derived from an untreated patient, were highly resistant to apoptosis induced by 5-FU and Sulindac but were sensitive to Bu-induced apoptosis. The resistance to apoptosis was, as quantified by the induction of caspase activity and the relative percentage of apoptotic cells, higher in the metastatic cell lines, than in the ALT cell line. When compared to the primary tumor, more anti-apoptotic bcl-2 and less pro-apoptotic bax were expressed in the liver and lymph node metastatic cell lines. Quite remarkably, the expression of bax was up-regulated during Bu-treatment, a feature that could explain its powerful pro-apoptotic activity.


Empyema thoracis in patients undergoing emergent closed tube thoracostomy for thoracic trauma.
The vast majority of thoracic trauma victims require only observation or tube thoracostomy for definitive treatment of their thoracic injury. Although tube thoracostomy is generally considered a limited intervention, 2 to 25 percent of patients who undergo this procedure develop infectious complications. To determine the incidence and risk factors for the development of empyema thoracis after tube thoracostomy, a retrospective study was undertaken. We found that the development of empyema thoracis was increased in patients whose pleural space was incompletely drained and whose thoracic catheters were in place for a prolonged period.


Effects of 780 SE on lipid metabolism in rabbit aorta.
Pretreatment of rabbits with Benfouorex (780 SE) 50 mg/kg p.o. for 10 days strongly inhibited the incorporation of a 20 muCi tracer dose of 4-14C-cholesterol (given i.v. 24 h earlier) into various segments of the aorta. Incorporation of specific activity into the liver, intestine, lung or plasma was not affected. 1 h after i.v. injection of a 100 muCi tracer dose of 2-14C-acetate, a significant reduction in the radioactivity of total lipids of the aorta and liver was seen in rabbits pretreated with 780 SE. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free fatty acids, free and esterfied cholesterol, phospholipids and especially triglycerides). Incorporation of acetate into triglyceride fractions of liver and intestine and into hepatic cholesterol was also significantly decreased. The results indicate that 780 SE may have anti-atherogenic properties which could be valuable in the clinical treatment of atherosclerosis.


Gross anatomical investigation of the muscular head between the vastus lateralis and intermedius in the Japanese population: a cadaver study.
Unlike the general understanding of the quadriceps femoris, the existence of a new muscular head between the vastus lateralis and the vastus intermedius was reported, and named the tensor of the vastus intermedius in the Swedish population. The purpose of this study was to investigate the presence and form of the muscular head in the Japanese population and to clarify its structure by gross anatomical approaches. A total of 35 thighs of 20 Japanese cadavers were investigated. We searched for the muscular head and classified it into four types. In addition, nerve fiber analysis was performed for each classification type. Regarding classification, 11% were the independent type, 29% were the common type, 37% were the vastus lateralis type, and 23% were the vastus intermedius type. Based on nerve fiber analysis, in the common type, the muscular head was under dual nerve supply from the vastus lateralis and intermedius. The other three types were innervated only by nerves from the vastus lateralis. The target muscular head may always be present in Japanese. The nerves from the vastus lateralis were always distributed in the target muscular head based on nerve fiber analysis; therefore, this muscular head may be most closely related to the vastus lateralis. The name of this muscular head should be "the accessory head of the vastus lateralis" rather than "the tensor of the vastus intermedius."


Pituitary adenomas: long-term results for radiotherapy alone and post-operative radiotherapy.
Analysis of prognostic factors and long-term results of treatment of pituitary adenomas. The study involved a retrospective review of outcome in a series of 268 patients with pituitary adenomas, treated at the Queensland Radium Institute from January 1962 to December 1986. The study population included 108 patients treated with radiotherapy alone and 160 patients treated by surgery and post-operative radiotherapy. In each group, univariate and multivariate analyses were conducted of possible prognostic factors including age, sex, performance status, tumor type, tumor extent, visual disturbance, radiotherapy dose, and field size. For radiotherapy alone, the 10-year progression-free survival rate was 60%, and overall tumor control was obtained in 77%. Univariate analysis suggested that tumor type and radiotherapy field size were of prognostic significance. Multivariate analysis confirmed that Prolactinoma subtype and increasing radiotherapy field size were independently predictive of reduced progression-free survival. Long-term visual complications occurred in 1% of patients treated by radiotherapy alone. In patients treated by surgery and post-operative radiotherapy, the 10-year progression-free survival rate was 77%, and overall tumor control was achieved in 83%. Univariate analysis suggested that tumor type, completeness of surgical excision, and radiotherapy dose were predictive of outcome. However, on multivariate analysis, only the extent of surgical excision predicted prognosis independently. Long-term visual sequelae were noted in 3% of patients treated by surgery and post-operative radiotherapy. Both radiotherapy alone and post-operative radiotherapy are effective in long-term control of pituitary adenomas, and produce acceptably low complication rates.


Neuro-oncology at the American Society for Clinical Oncology 2022 Annual Meeting.
In the following brief report, we highlight the advances in the neuro-oncology space from the ASCO 2022 Annual Meeting. We put into context the phase 2 and 3 trials and how these may alter the standard of care going forward. In addition, we highlight some other earlier work that will lead to future and potentially practice-changing trials.


Empowering nurses in a practical way.
Practical approaches to increasing autonomy and participation will be required to underpin the rhetoric of 'empowerment', says James Buchan in his monthly column.


Surveillance programme for multidrug-resistant bacteria in healthcare-associated infections: an urban perspective in South Brazil.
Multidrug-resistant bacteria (MDRB) have emerged as a public health problem and the World Health Organization recommends actions to control MDRB in healthcare-associated infections (HCAIs). This study describes a surveillance programme for MDRB in HCAIs at Curitiba, Brazil. MDRB in pneumonia, bloodstream, urinary tract and surgical site infections has been surveyed since January 2010. Carbapenem-resistant Acinetobacter baumannii and third generation resistant Klebsiella pneumoniae were the most frequent MDRB in HCAIs. Infection control strategies enrolling hospitals and public health have been developed. The data presented describe MDRB prevalence and the feasibility of this municipal MDRB surveillance programme in Brazil.


Reconstruction of the distal radius using a double-barrel vascularized fibula flap: A case series.
Treatment of distal radius tumor sometimes requires sacrificing the epiphysis. We propose adding to currently available reconstruction options a technique using a double-barrel vascularized fibula flap fixed distally to the first carpal row, conserving midcarpal mobility. We monitored 4 cases of Campanacci III giant-cell tumor and 2 cases of osteosarcoma. After en-bloc tumor resection, a double-barrel vascularized fibula flap was lodged distally in the scaphoid and lunate and proximally in the radius. Follow-up was clinical and radiological, using DASH, PRWE and MSTS functional scores. At a median 3 years' follow-up, there were no cases of recurrence or non-union. Median ranges of motion were 23° flexion, 28° extension, 90° pronation and 62° supination. Median grip strength proportional to the contralateral side was 67%. Median DASH and PRWE functional scores were respectively 13.7 and 17 points. Median MSTS was 83%. Although this technique is challenging, with difficulties in double-barrel flap placement and in pedicle plication, the double-barrel vascularized fibula flap provided a stable and mobile wrist.


Long-term mortality of patients ablated for atrial fibrillation: a retrospective, population-based epidemiological study in Apulia, Italy.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Data on long-term risk and mortality after catheter ablation for AF are lacking. The aim of this study was to evaluate all-cause mortality and the long-term risk of death in patients who underwent catheter ablation for AF compared with the general population. Retrospective, population-based epidemiological study. We analysed data from patients residing in Apulia region who underwent AF ablation between January 2009 and June 2019. 1260 patients (914 male, mean age 60±11 years). Vital status and dates of death to 31 December 2019 were obtained by using regional Health Information System. The expected number of deaths was derived using mortality rates from the general regional population by considering age-specific and gender-specific death probability provided for each calendar year by the Italian National Institute of Statistics. Standardised mortality ratios (SMRs) were calculated by dividing the observed number of deaths among patients by the expected number of deaths estimated from the general population. During follow-up (6449 person-years), 95 deaths were observed (1.47 deaths per 100 person-years). Although overall long-term mortality after AF ablation was not different to that of the general population (SMR 1.05 (95% CI 0.86 to 1.28; p=0.658)), the number of observed events was significantly increased in patients with heart failure (HF) at baseline or who developed HF during follow-up (SMR 2.40 (1.69 to 3.41; p<0.001) and 1.75 (1.17 to 2.64; p=0.007), respectively) and reduced in those without (SMR 0.63 (0.47 to 0.86; p=0.003)). Long-term mortality of patients undergoing AF ablation is similar to that of the general population. Patients with HF had an increased risk while those without seem to have a better risk profile.


Role of leukotriene B4 receptors in rheumatoid arthritis.
The purpose of this review is to summarize the role that murine models of arthritis are playing in the understanding of human rheumatoid arthritis and how leukotriene B(4) (LTB(4)) is emerging as an important target in this field. Both the collagen-induced arthritis (CIA) model and the K/BxN serum transfer arthritis model have contributed to outline the potential mechanisms involved in inflammatory arthritis. Indeed, the CIA model has contributed to the development of effective anti-TNFalpha and anti-IL-1beta based treatments for RA that are currently in the clinic. Many recent studies in mouse models have suggested a critical role for LTB(4) and its receptors in the development of inflammatory arthritis. Inhibitors of LTB(4) biosynthesis as well as LTB(4) receptors are protective in mouse models of RA and mice deficient in the LTB(4) biosynthetic enzymes or LTB(4) receptors are resistant to disease development suggesting several promising targets for RA in this pathway.


Characteristics and first-year mortality, by lesion level, among infants with spina bifida in the New York State Birth Defects Registry, 2008-2017.
Spina bifida is the most common neural tube defect. It has been associated with increased mortality, disability, and may require lifelong medical care. Higher-level lesions have been shown to be associated with increased mortality in infants with spina bifida. A study was conducted using data from infants with myelomeningocele and related spina bifida reported to the New York State Birth Defects Registry for birth years 2008 through 2017. Descriptive statistics were conducted. Cox regression was used to calculate adjusted hazard ratios for mortality by age one, by lesion level. Hazard ratios were adjusted for birthweight and maternal race/ethnicity. Overall survival at age one was 90.7%. Cervical-level lesions had an increased risk of mortality compared to lumbar-level lesions (HR 8.32; 95% CI: 2.56, 27.05). No statistically significant associations were found for sacral-level lesions compared to lumbar-level lesions. These results suggest that infants with cervical-level spina bifida have a higher risk of death by age one than those with other lesion levels.


Heated air humidification versus cold air nebulization in newly tracheostomized patients.
After tracheostomy, the airway lacks an essential mechanism for warming and humidifying the inspired air with the consequent functional impairment and discomfort. The purpose of this study was to compare airway hydration with cold-air nebulization versus heated high-flow humidification on medical interventions and tracheal ciliary beat frequency (CBF). Newly tracheostomized patients (n = 20) were treated either with cold-air nebulization or heated humidification. The number of required tracheal suctioning procedures to clean the trachea and tracheal CBF were assessed. The number of required suctions per day was significantly lower in the heated humidification group with medians 3 versus 5 times per day. Mean CBF was significantly higher in the heated humidification group (6.36 ± 1.49 Hz) compared to the cold-air nebulization group (3.99 ± 1.39 Hz). The data suggest that heated humidification enhanced mucociliary transport leading to a reduced number of required suctioning procedures in the trachea, which may improve postoperative patient care.


t-Butyl hydroperoxide stimulates alveolar macrophage biosynthesis of cyclooxygenase products.
Rat alveolar macrophages, labeled with 3H-arachidonic acid, were treated with t-butyl hydroperoxide (tBOOH). Treatment of cells with 100 microM tBOOH led to a rapid increase in 12-hydroxyheptadecatrienoic acid (12-HHT) within 2.5 minutes. At 15 minutes, 12-HHT levels appeared to plateau as there was no further increase at 30 minutes. TxB2 levels increased in a similar manner to that found with 12-HHT; however, only the level at 15 minutes was statistically increased. TxB2 levels also appeared to plateau at 15 minutes. Indomethacin, at a concentration of 1 microM, significantly inhibited TxB2 and 12-HHT production by approximately 90%. Desferal, an iron chelator, had no effect on alterations of biosynthesis of cyclooxygenase products by macrophages treated with tBOOH. No evidence of lipoxygenase products was found. Thus, these results suggest that tBOOH rapidly and selectively stimulated arachidonic acid metabolism through the cyclooxygenase pathway in rat alveolar macrophages. The stimulation of cyclooxygenase activity was transient with a maximum rate observed at 100 microM tBOOH.


Association of Polysomnographic Sleep Parameters With Neuroimaging Biomarkers of Cerebrovascular Disease in Older Adults With Sleep Apnea.
Our objective was to determine whether polysomnographic (PSG) sleep parameters are associated with neuroimaging biomarkers of cerebrovascular disease (CVD) related to white matter (WM) integrity in older adults with obstructive sleep apnea (OSA). From the population-based Mayo Clinic Study of Aging, we identified participants without dementia who underwent at least 1 brain MRI and PSG. We quantified 2 CVD biomarkers: WM hyperintensities (WMHs) from fluid-attenuated inversion recovery (FLAIR)-MRI, and fractional anisotropy of the genu of the corpus callosum (genu FA) from diffusion MRI. For this cross-sectional analysis, we fit linear models to assess associations between PSG parameters (NREM stage 1 percentage, NREM stage 3 percentage [slow-wave sleep], mean oxyhemoglobin saturation, and log of apnea-hypopnea index [AHI]) and CVD biomarkers (log of WMH and log of genu FA), respectively, while adjusting for age (at MRI), sex, APOE ε4 status, composite cardiovascular and metabolic conditions (CMC) score, REM stage percentage, sleep duration, and interval between MRI and PSG. We included 140 participants with FLAIR-MRI (of which 103 had additional diffusion MRI). The mean ± SD age was 72.7 ± 9.6 years at MRI with nearly 60% being men. The absolute median (interquartile range [IQR]) interval between MRI and PSG was 1.74 (0.9-3.2) years. 90.7% were cognitively unimpaired (CU) during both assessments. For every 10-point decrease in N3%, there was a 0.058 (95% CI 0.006-0.111, p = 0.030) increase in the log of WMH and 0.006 decrease (95% CI -0.012 to -0.0002, p = 0.042) in the log of genu FA. After matching for age, sex, and N3%, participants with severe OSA had higher WMH (median [IQR] 0.007 [0.005-0.015] vs 0.006 [0.003-0.009], p = 0.042) and lower genu FA (median [IQR] 0.57 [0.55-0.63] vs 0.63 [0.58-0.65], p = 0.007), when compared with those with mild/moderate OSA. We found that reduced slow-wave sleep and severe OSA were associated with higher burden of WM abnormalities in predominantly CU older adults, which may contribute to greater risk of cognitive impairment, dementia, and stroke. Our study supports the association between sleep depth/fragmentation and intermittent hypoxia and CVD biomarkers. Longitudinal studies are required to assess causation.


Long-term effects of polychlorinated biphenyls and dioxins on pregnancy outcomes in women affected by the Yusho incident.
Maternal exposure to polychlorinated biphenyls (PCBs) is associated with increased proportions of spontaneous abortion and stillbirth in animal studies. In Japan in 1968, accidental human exposure to rice oil contaminated with PCBs and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to the development of what was later referred to as Yusho oil disease. The aim of this study was to investigate the association of maternal PCB and dioxin exposure with adverse pregnancy outcomes in Yusho women. In 2004, we interviewed 214 Yusho women (512 pregnancies) about their pregnancy outcomes over the past 36 years. Pregnancy outcomes included induced abortion, spontaneous abortion, preterm delivery, and pregnancy loss. In pregnancy years 1968-1977 (within the first 10 years after exposure), the proportions of induced abortion [odds ratio adjusted for age at delivery (ORadj) = 5.93; 95% confidence interval (CI), 2.21-15.91; two-tailed p < 0.001) and preterm delivery (ORadj = 5.70; 95% CI, 1.17-27.79; p = 0.03) were significantly increased compared with the proportions in pregnancy years 1958-1967 (10 years before the incident). Spontaneous abortion (ORadj = 2.09; 95% CI, 0.84-5.18), and pregnancy loss (ORadj = 2.11; 95% CI, 0.92-4.87) were more frequent (OR = 2.18; 95% CI, 1.02-4.66), but these were not significant (p = 0.11 and p = 0.08, respectively) in pregnancy years 1968-1977. We found no significant increases in the proportions of these adverse pregnancy outcomes in pregnancies occurring during 1978-1987 or 1988-2003 compared with those in pregnancies before 1968. High levels of PCB/PCDF exposure had some adverse effects on pregnancy outcome in Yusho women.


An elevated neutrophil-to-lymphocyte ratio predicts a poor postoperative survival in primary hepatocellular carcinoma patients with a normal preoperative serum level of alpha-fetoprotein.
Although alpha-fetoprotein (AFP) is a useful prognostic marker in patients with hepatocellular carcinoma (HCC), a recent study has shown that the preoperative neutrophil-to-lymphocyte ratio (NLR) is also associated with the postoperative survival in such patients. To investigate the significance of the NLR in patients with primary HCC (p-HCC) showing a normal preoperative AFP. Among 478 p-HCC patients undergoing curative surgery, 112 who had a normal AFP (< 8 ng/ml) were enrolled. The patients were divided into two groups: group A, who did not have an elevated NLR (≤ 3.2); and group B, who had an elevated NLR (> 3.2). Uni- and multivariate analyses were performed to compare clinical features with the overall survival (OS). A multivariate analysis of the clinical features showed that the NLR (> 3.2/≤ 3.2) (hazard ratio 2.366; 95% CI 1.069-5.235; P = 0.034) was closely associated with the OS, along with the age (> 65/≤ 65 years) (P = 0.033). Group B had a significantly lower survival ratio than group A in terms of not only the OS (P = 0.013), but also the cancer-specific survival (P = 0.002) and relapse-free survival (P = 0.039). An elevated NLR (> 3.2) is predictive of a poor survival in patients with primary HCC (p-HCC) showing normal AFP levels.


In defense of 'niche modeling'.
There is a growing awareness of problems with the estimation of the ecological tolerances of species through correlative modeling approaches. These problems have led some investigators to argue for abandoning terms such as 'ecological niche model' and 'environmental niche model' in favor of the ostensibly more value-neutral 'species distribution model', as the models are thought to frequently be poor estimators of the niche. Here, I argue that most applications to which these models are put require the assumption that they do estimate the niche, however imperfectly, and that obscuring this inescapable and potentially flawed assumption in the terminology may only serve to hinder the development of the field.


Diagnostic value of EUS-guided SF6 pancreatography for pancreatic cystic lesions on cyst communication with the pancreatic duct.
ERCP remains the reliable method to determine whether pancreatic cystic lesions (PCLs) and pancreatic duct communicate when other modalities (computed tomography, magnetic resonance imaging, and EUS) fail. However, complications after ERCP are still a risk that should not be ignored. In this study, we evaluated the value of EUS-guided SF6 pancreatography (ESP) for the diagnosis of PCLs focusing on pancreatic cyst communication with the pancreatic duct. We reviewed the database of medical records to retrieve the clinicopathological data of the patients with PCLs who had undergone ESP, and analyzed the diagnostic value of ESP to determine communication between the cyst and the pancreatic duct. The inclusion criteria were as follows: (1) PCLs were pathologically diagnosed by postsurgery specimen or through-the-needle biopsy and (2) ESP was performed to determine communication between the pancreatic cyst and the pancreatic duct. Pathological diagnosis confirmed communication with the pancreatic duct in all eight patients with positive pancreatography, among whom seven were branch-duct-intraductal papillary mucinous neoplasm (BD-IPMN) and one was the main duct-IPMN. Pathological diagnosis confirmed noncommunication with the pancreatic duct in 20 of the 21 patients with negative pancreatography, among whom 11 were mucinous cystic neoplasm, 7 were serous cystic neoplasm, 1 was solid pseudopapillary neoplasm, 1 was pancreatic pseudocyst, and 1 was BD-IPMN. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of ESP to determine communication between the pancreatic cyst and the pancreatic duct were 96.6% (28/29), 88.9% (8/9), 100% (20/20), 100% (8/8), and 95.2% (20/21), respectively. ESP achieved high accuracy to determine communication between the pancreatic cyst and the pancreatic duct.


Sudden painless visual loss: optic nerve and circulatory disturbances.
There are many causes of sudden painless visual loss in older adults. This article reviews the causes that are based on disturbances of the optic nerve and disorders of the circulatory system of the eye. Clinical clues to the recognition of these disorders and treatment (if available) are reviewed.


Lung point-of-care (POCUS) ultrasound in a pediatric COVID-19 case.
The World Health Organization categorized coronavirus disease 2019 (COVID-19) as a pandemic due to its high contagion rate and widespread infectivity in February 2020. In the United States, one of the public health concerns is the adequacy of resources to treat infected cases. We describe a case of a previously well, 9-year-old obese boy who presented to the emergency department with shortness of breath, fever, abdominal pain, and cough with chest pain. He was diagnosed with COVID-19 through significant family contact, confirmed by polymerase chain reaction and found to be at high risk of venous thromboembolism due to abnormal d-dimer. Lung point-of-care ultrasound (POCUS) in the emergency department observed significant lung pathology, including pleural thickening, consolidation, and B lines. A chest X-ray found bilateral ground glass opacities and interstitial prominences consistent with viral pneumonia. Our case suggests that lung POCUS can provide adequate and rapid imaging to assess lung pathology of COVID-19 in a pediatric patient. As there is limited literature on use of lung POCUS in pediatric patients infected with SARS-CoV-2, our case emphasizes its function as a potentially efficient modality in bedside assessment.


Using cost-effectiveness analysis to improve the efficiency of allocating funds to clinical trials.
This study applied a cost-effectiveness model to seven randomized trials. The model demonstrates the effect of design choices made in the planning stages of a clinical trial on the costs and benefits derived from conducting the trial. The study focused on one parameter used to calculate sample size: the minimum clinically important difference in event rates between control and experimental therapies. The study shows that the model can be operationalized to these trials. A computerized software package and manual has been developed to simplify the calculations. While there was some variation in the incremental cost-effectiveness ratios across the seven trials in this study, all ratios may be below the funding threshold. This analytical technique can be used to demonstrate explicitly the resource consequences of the design of randomized trials and perhaps to set funding priorities.


Origin of dendrite-free lithium deposition in concentrated electrolytes.
The electrolyte solvation structure and the solid-electrolyte interphase (SEI) formation are critical to dictate the morphology of lithium deposition in organic electrolytes. However, the link between the electrolyte solvation structure and SEI composition and its implications on lithium morphology evolution are poorly understood. Herein, we use a single-salt and single-solvent model electrolyte system to systematically study the correlation between the electrolyte solvation structure, SEI formation process and lithium deposition morphology. The mechanism of lithium deposition is thoroughly investigated using cryo-electron microscopy characterizations and computational simulations. It is observed that, in the high concentration electrolytes, concentrated Li+ and anion-dominated solvation structure initiate the uniform Li nucleation kinetically and favor the decomposition of anions rather than solvents, resulting in inorganic-rich amorphous SEI with high interface energy, which thermodynamically facilitates the formation of granular Li. On the contrary, solvent-dominated solvation structure in the low concentration electrolytes tends to exacerbate the solvolysis process, forming organic-rich mosaic SEI with low interface energy, which leads to aggregated whisker-like nucleation and growth. These results are helpful to tackle the long-standing question on the origin of lithium dendrite formation and guide the rational design of high-performance electrolytes for advanced lithium metal batteries.


Exploring expert variability in defining pseudoparalysis: an international survey.
There is currently disagreement among experts in the field of shoulder surgery when attempting to define the term "pseudoparalysis." Multiple surgical techniques to address this condition have been investigated; however, many studies have recruited heterogeneous patient populations and have used varying definitions of pseudoparalysis. This makes it difficult to compare outcomes among various techniques. To our knowledge, no previous study has surveyed international experts regarding the definition of pseudoparalysis using a questionnaire and video-based patient assessment. The purpose of this study was to evaluate the level of agreement among shoulder surgeons in defining and applying the term "pseudoparalysis." We hypothesized that inter-rater agreement for classifying patients as having pseudoparalysis would be poor. Members of the American Shoulder and Elbow Surgeons, the European Society for Surgery of the Shoulder and the Elbow, and our national shoulder and elbow society were surveyed on 2 occasions using an electronic questionnaire. All surgeons were asked to identify their preferred definition of pseudoparalysis from 1 of 4 options. The surgeons then viewed video examinations of 10 patients and labeled them as having pseudoparalysis or not. Inter-rater reliability and intrarater reliability were calculated as κ coefficients. The Pearson χ2 test was used to detect associations between the preferred definition and demographic information. A total of 246 surgeons responded to at least 1 survey. Overall inter-rater agreement on classifying patients as having pseudoparalysis based on video consultation showed a κ value of 0.59 (95% confidence interval [CI], 0.58-0.60). The same verbal definition was selected by 56.1% of surgeons. The surgeons were not internally consistent in their choice of definition, with intrarater reliability showing a κ value of 0.64 (95% CI, 0.48-0.81). Intrarater reliability for classifying patients as having pseudoparalysis was better, with a κ value of 0.78 (95% CI, 0.72-0.83). An association was observed between how surgeons defined pseudoparalysis and their age (P = .03), as well as their shoulder caseload percentage (P = .04). Shoulder surgeons do not agree on how best to define pseudoparalysis of the shoulder. Inter-rater agreement based on video consultation was weak overall and improved with the elimination of an outlier video. Intrarater agreement was less frequent when selecting a preferred definition compared with classifying patients as having pseudoparalysis based on video examinations. Surgeons may rely less on explicit criteria and more on a conceptual framework when assigning a "pseudoparalytic" label. Care should be taken with use of the term "pseudoparalysis" in clinical outcome studies when there is clearly a lack of consensus among experts in defining this term.


Stimulation of ornithine decarboxylase activity by luteinizing hormone in rat testicular interstitial cells in vitro is age dependent.
The developmental pattern of ornithine decarboxylase (ODC) responsiveness to luteinizing hormone (LH) in isolated rat testicular interstitial cells in vitro was examined and correlated with testosterone production by the same cells. LH caused a 60-100% stimulation of ODC activity in cells from 60-day-old rats but produced no response in cells from 30, 37, 41, 50 and 55-day-old animals. Interstitial cells from 25-day-old rats responded with a moderate (40%) but statistically significant enhancement of ODC activity to the highest LH dose (100.0 ng/ml) only. Testosterone production by control cells was low until day 41 (0.15-0.30 ng/10(6) cells per 4 h), and then markedly increased to adult levels (2.12 +/- 0.03 10(6) cells per 4 h). LH in all concentrations (0.1 - 100.0 ng/ml) employed caused a consistent 4 to 7-fold stimulation of testosterone production in interstitial cells at all ages studied. This study shows age-dependent stimulation by LH of ODC activity in rat testicular interstitial cells in vitro and no apparent correlation with testosterone production by the same cells.


Role of osteopontin in modulation of hydroxyapatite formation.
The presence of osteopontin (OPN) at high levels in both mineralized tissues such as bone and ectopic calcifications such as atherosclerotic plaque presents a conundrum: is OPN a promoter or inhibitor of hydroxyapatite (HA) formation? In vitro studies show that OPN adsorbs tightly to HA and is a potent inhibitor of crystal growth. Although the mechanism of the OPN-HA interaction is not fully understood, it is probably electrostatic in nature. Phosphorylation enhances OPN's ability to adsorb to and inhibit the growth of HA crystals, although other anionic groups also contribute to these properties. Recent findings suggest that OPN is an intrinsically unordered protein and that its lack of folded structure facilitates the protein's adsorption by allowing multiple binding geometries and the sequential formation of ionic bonds with Ca(2+) ions of the crystal surface. By analogy with other biominerals, it is likely that adsorption of OPN to HA results in "pinning" of growth steps. The abundance of OPN at sites of ectopic calcification reflects upregulation of the protein in response to crystal formation or even in response to elevated phosphate levels. Therefore, it appears that OPN is one of a group of proteins that function to prevent crystal formation in soft tissues. The role of OPN in bone mineralization, if any, is less clear. However, it is possible that it modulates HA formation, either by preventing crystal growth in "inappropriate" areas such as the osteoid seam or by regulating crystal growth habit (size and shape).


The impact of size of the adnexal mass on the accuracy of frozen section diagnosis.
We recently showed that frozen section diagnosis has an almost perfect specificity for the diagnosis of malignancy in an adnexal mass, whereas the sensitivity was, though good, not perfect. The aim of the present study was to examine whether the accuracy of frozen section diagnosis is affected by the size of the adnexal masses. We included women that underwent frozen section diagnosis for adnexal mass surgery. For each patient we recorded serum CA125 level, menopausal status, tumour size, and histologic classification both at frozen section diagnosis and at definite histological examination. We calculated sensitivity and specificity of frozen section diagnoses, both in tumours below and above 10 cm diameter. We included 257 patients, of whom 142 had a benign tumour, 28 had a borderline tumour and 87 had a malignant tumour at definitive histological assessment. In case frozen section diagnosis showed malignancy, this was always confirmed at final histological assessment. In women with a tumour <10 cm, there was only 1 false negative diagnosis in 50 women with a benign frozen section diagnosis, whereas there were 11 false negative diagnoses in 97 women in women with a tumour > or = 10 cm. The corresponding likelihood ratios of a benign diagnosis for presence of malignancy were .15 for tumours > or = 10 cm and 0.03 for tumours <10 cm, respectively. The accuracy of frozen section diagnosis is dependent on tumour size. In adnexal masses > or = 10 cm, a benign result of the frozen section diagnosis is less reliable than in women with a tumour <10 in cm.


Detection of Rickettsia helvetica in ticks collected from European hedgehogs (Erinaceus europaeus, Linnaeus, 1758).
The role of wild mammals in the dissemination and maintenance of Rickettsia in nature is still under investigation. European hedgehogs (Erinaceus europaeus) are often heavily infested by tick and flea species that are known to harbor and transmit different Rickettsia spp. We investigated ixodid ticks sampled from European hedgehogs for the presence of Rickettsia. A total of 471 Ixodes ricinus and 755 I. hexagonus were collected from 26 German and 7 British European hedgehogs. These were tested by a genus-specific real-time PCR assay targeting the citrate synthase gene (gltA). The rickettsia minimum infection rate was 11.7% with an increase detected with each parasitic tick stage. No significant difference in Rickettsia prevalence in the 2 Ixodes species was detected. Using sequencing of partial ompB, Rickettsia helvetica was the only species identified. More than half of the hedgehogs carried Rickettsia-positive ticks. In addition, tissue samples from 2/5 hedgehogs (where tissue DNA was available) were PCR-positive. These results show that European hedgehogs are exposed to R. helvetica via infected ticks and might be involved in the natural transmission cycle of this Rickettsia species.


Use of darbepoetin alfa and epoetin alfa in clinical practice in patients with cancer-related anemia.
Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs. The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products. Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA administration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients. We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 microg (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sensitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered. Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.


Knowledge domain and emerging trends in nanoparticles and plants interaction research: A scientometric analysis.
The potential releases of nanoparticles (NPs) into soil medium have drawn considerable attention due to the increasing production and application of NPs worldwide. Understanding the interactions between NPs and plants is particularly important to assess the risks of NPs in the soil ecosystem. Although important knowledge has been gained about the NPs-plants interactions, current results of numerous published articles are still scattered. Therefore, this paper reviews the scientific progress in the NPs-plants interactions via a scientometric analysis to identify the main gaps and to provide future perspectives. Scientific documents on the interaction of nanoparticles and plant research during the period January 2000-July 2020 have been collected from Web of Science core collection and analyzed using CiteSpace. Overall, 9 scientometric indicators, i.e. literature quantity and growth trend, contributing countries, authors, institutions, keywords, cited journals, cited authors, and cited articles, are employed to understand the results retrieved from the 961 documents collected. The number of studies on nano-plant interaction research has been growing at an average annual rate of 56%. 71 countries and around 3380 authors have contributed to this field. Among the cited journals, Environmental Science and Technology stands out as the most-cited journal followed by Science of the Total Environment and Environmental Pollution, respectively. Moreover, the keyword citation burst, an indicator of the most active area of research or emerging trend, indicates that the beneficial side of nanoparticles and the trophic transfer require further exploration. This paper will be beneficial for fully understanding the salient research themes and the research trends of nano-plant interaction in future.


Early Canadian results on the long-range transport of Chernobyl radioactivity.
The levels of Chernobyl-derived radionuclides were measured in several rain, snow and water filtration plant floc samples collected from various locations in Canada. The data indicate that the Chernobyl release had negligible effect on the radiological quality of Lake Ontario waters. The detection of some activation products in pre-Chernobyl samples, presumably arising from the accidental release of radioactivity during weapon testing at the Nevada site, is also reported. Some data from the ongoing measurements on rain samples are presented to discuss the possible use of Chernobyl radionuclides for delineating tropospheric transport processes. Fractionation factors for the major radionuclides are also reported.


Muscarinic receptor subtypes mediate vasorelaxation in isolated horse deep dorsal penile vein.
To investigate the effect of acetylcholine (ACh) on horse deep dorsal penile vein and to characterize the muscarinic receptor subtypes involved in this response. Vein rings were mounted in an organ bath chamber, and the isometric tension was recorded. In phenylephrine-contracted veins, ACh (1 nM to 1 microM) induced endothelium-dependent relaxation. The muscarinic receptor antagonist, atropine, produced parallel rightward shifts of the ACh response curves (pA2 = 10.04; pK(B) = 9.98). Carbachol (10 nM to 100 microM) also evoked relaxation in the vein segments, but showed a lower potency and similar relaxation to that induced by ACh. Pirenzepine, the high, intermediate, and low-affinity antagonist for M1, M3, and M2 receptors, respectively, inhibited ACh and carbachol-induced relaxation, yielding pA2 values of 7.51 and 7.37, and pK(B) values of 7.38 and 7.28, respectively. Methoctramine, a high-affinity M2 antagonist, showed no significant effect on the response to ACh. However, a high-affinity M3 antagonist, pFHHSiD, potently blocked the relaxation induced by carbachol and ACh, yielding pA2 and pK(B) values of 7.72 and 7.70 for pFHHSiD against ACh, respectively, and of 7.77 and 7.65 against carbachol, respectively. These results indicate that ACh induces an endothelium-dependent relaxation in horse deep dorsal penile vein. The antagonist profile suggests that M3 muscarinic receptors mediate ACh-induced relaxation in this tissue.


Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?
The aim of the study is to determine factors affecting ischaemic wound healing and role of the angiosome concept in bypass surgery. Single-centre, retrospective clinical study. A total of 249 consecutive critical ischaemic limbs with tissue loss in 228 patients who underwent distal bypasses from 2003 to 2009 were reviewed. A total of 81% of patients were diabetic, and 49% of patients had dialysis-dependent renal disease (end-stage renal disease, ESRD). Distal targets of bypasses were the crural artery (57%) and the pedal artery (43%). The complete healing of ischaemic wounds was achieved in 211 limbs (84.7%). ESRD (odds ratio (OR) 0.127, p < 0.001), diabetes (OR 0.216, p = 0.030), Rutherford category 6 (R6) with heel ulcer/gangrene (OR 0.134, p < 0.001), R6 except heel (OR 0.336, p = 0.025) and low albuminaemia (OR 0.387, p = 0.049) were negative predictors of wound healing. Regarding the angiosome, the healing rate in the indirect revascularisation (IR) group was slower than in the direct revascularisation (DR) group, especially in patients with ESRD (p < 0.001). However, the healing rates of the DR and IR groups were similar after minimising background differences with propensity score methods (p = 0.185). In the field of bypass surgery, the angiosome concept seems unimportant, at least in non-ESRD cases. The location and extent of ischaemic wounds as well as co-morbidities may be more relevant than the angiosome in terms of wound healing.


Is allograft sufficient for posterior atlantoaxial instrumented fusions with screw and rod constructs? A structured review of literature.
Iliac crest autograft remains the gold standard for spinal fusion operations. Given risk of donor site morbidity, many centers utilize allograft. We reviewed published series of C1-2 posterolateral instrumented fusions with allograft and autograft. Online databases were searched for English-language articles reporting quantifiable outcome data published between 1994 and 2011 of posterior atlantoaxial instrumented arthrodesis with C1 and C2 screws. Thirteen studies describing 652 patients having autograft and seven studies describing 60 patients having allograft serve as the basis of this report. All studies were retrospective case series (Class III evidence). There were no differences in complications or mortality between the groups. There were trends toward shorter operative times and less blood loss using allograft. A higher proportion of patients in the allograft group underwent sacrifice of the C2 nerve root and decortication and packing of the C1-2 joints (P<0.0001). There was no significant difference in the proportion of surviving patients who achieved solid fusion in the autograft (642 of 644 [99.7%]) and allograft patients (59 of 59 [100%]; P = 1.0). This review is limited by the retrospective data and inconsistent methodology of fusion determination used in most studies. Modern instrumentation and proper surgical techniques result in high rates of successful C1-2 arthrodesis. The use of allograft is a treatment option (Class III evidence) during posterior C1-2 instrumentation and fusion operations. Randomized, controlled trials using standardized radiographic assessments are needed across spinal arthrodesis studies to better determine the prevalence of radiographic fusion and establish technique superiority.