CO2 gas exchange and transpiration of Welwitschia mirabilis Hook. fil. in the central Namib desert.
The diurnal course of CO2 gas exchange, 14CO2 incorporation, malate and citrate content, and traspiration of Welwitschia mirabilis were measured in one of its natural habitats, the Welwitschia-Vlakte in the central Namib desert (Namibia), in order to decide which CO2 fixation pathway is used by this gymnosperm.The CO2 gas exchange of Welwitschia is that of a C3 plant under arid conditions. Younger leaf parts show a two-peaked pattern of photosynthetic CO2 uptake whereas in older parts the morning peak is followed by net CO2 release during the rest of the day. The maximum rates of net photosynthesis decrease from 3.4 μmol m-2 s-1 in 1-year-old parts to 1 μmol m-2 s-1 in 7-year-old parts. No net CO2 uptake was detected during the night. The diurnal CO2 balance indicates that the old leaf parts live at the expense of the younger ones. Irrigation of Welwitschia plants resulted in an increased CO2 uptake throughout the light period with maximum rate of 4.1 μmol m-2 s-1. 14CO2 was only incorporated during the day.The water loss of Welwitschia by transpiration is considerable, reaching a peak value of 1.9 mmol m-2 s-1 around noon. Leaf conductance corresponds with the twopeaked pattern of CO2 uptake.Although there is no sign of a crassulacean acid metabolism in Welwitschia the leaf contains rather high amounts of malate (up to 200 μmol g-1 dry matter) and citrate (up to 250 μmol g-1 dry matter), which depend on leaf age but do not show any significant day-night oscillation.In spite of all this the δ13C values are in the range of-17.77 to-19.64‰. Possible reasons for such a high 13C content in a C3 plant are discussed.


Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations.
Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10μM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development.


A case of T-cell chronic lymphocytic leukemia with an unusual phenotype and central nervous system involvement.
A case of T-cell chronic lymphocytic leukemia is reported. The leukemic cells had the morphologic features of medium-sized, mature-looking lymphocytes, and had an affinity for the central nervous system. Cytochemically, they were positive for alpha-naphthyl acetate esterase and acid phosphatase. They formed E-rosettes (E+) and reacted with OKT11 but not with OKT3/Leu-4, OKT4/Leu-3, OKT8/Leu-2, or OKM1, and did not possess IgG-Fc receptors (Fc gamma R). Functionally, they did not respond to phytohemagglutinin or concanavalin A, were not natural killer cells or antibody-dependent as well as alloantigen-reactive killer cells. Furthermore, they did not possess a helper or suppressor T-cell function for immunoglobulin synthesis. Results of immunologic studies suggest that the leukemic cells were derived from a normal counterpart of a lymphocyte subset present as a minor component of the peripheral blood, namely an E+, OKT3-, OKM1-, Fc gamma R- subset, the function of which is not yet identified.


Raman spectroscopic and structural investigation of 1,4-diphenylbuta-1,3-diene and selected monomethyl and dimethyl substituted homologues.
The Raman and mass spectra of 1,4-diphenylbuta-1,3-diene and several of its monomethyl and dimethyl homologues are reported and discussed, with a view to developing a spectroscopic protocol for detecting the presence and position of a methyl group in these compounds. Raman spectroscopy and mass spectrometry are shown to provide complementary information, by which the four available monomethyl homologues may be readily distinguished from each other and 1,4-diphenylbuta-1,3-diene itself. The utility of these 1,4-diarylbutadienes as model compounds for carotenoids and related materials, which may serve as indicators of extinct or extant extraterrestrial life, is considered.


PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.
The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein. The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties. Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a k(inact)/K(i) value of 112,000 M(-1)s(-1) and lipophilic efficiency (LipE) of 8.53. The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency.


Regulation of extrinsic apoptotic signaling by c-FLIP: towards targeting cancer networks.
The extrinsic pathway is mediated by death receptors (DRs), including CD95 (APO-1/Fas) or TRAILR-1/2. Defects in apoptosis regulation lead to cancer and other malignancies. The master regulator of the DR networks is the cellular FLICE inhibitory protein (c-FLIP). In addition to its key role in apoptosis, c-FLIP may exert other cellular functions, including control of necroptosis, pyroptosis, nuclear factor κB (NF-κB) activation, and tumorigenesis. To gain further insight into the molecular mechanisms of c-FLIP action in cancer networks, we focus on the structure, isoforms, interactions, and post-translational modifications of c-FLIP. We also discuss various avenues to target c-FLIP in cancer cells for therapeutic benefit.


Momentum spectroscopy of 1D phase fluctuations in Bose-Einstein condensates.
We measure the axial momentum distribution of Bose-Einstein condensates with an aspect ratio of 152 using Bragg spectroscopy. We observe the Lorentzian momentum distribution characteristic of one-dimensional phase fluctuations. The temperature dependence of the width of this distribution provides a quantitative test of quasicondensate theory. In addition, we observe a condensate length consistent with the suppression of density fluctuations, even when phase fluctuations are large.


Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet.
Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed. At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.


The relationship of anterior and rotatory laxity between surgical navigation and clinical outcome after ACL reconstruction.
Recently, a computer-assisted navigation system has been used for the quantitative evaluation not only of anterior-posterior (AP) laxity but also rotational laxity of the tibia intraoperatively. The purpose of this study was to investigate how intraoperative AP or rotational laxities measured by the navigation system could correlate with postoperative AP and rotational laxities of the patients. 125 patients who underwent primary isolated anatomical single- or double-bundle ACL reconstruction or augmentation using multistranded autologous hamstring tendons were included in the study after a minimum of 2-year follow-up. Clinically, absolute value and side-to-side difference (SSD) of AP translation of the tibia were measured by KT-2000 preoperatively and postoperatively. Intraoperative measurement of AP translation of the tibia and total range of tibial rotation of the ACL-injured knee were carried out using the computer-assisted navigation system. We have investigated the relationship between intraoperative measurements using the navigation system and AP laxity measurements using the KT-2000 knee arthrometer as well as rotational laxity measurements using the manual pivot shift test. There was a positive correlation between the SSD of preoperative AP translation of the tibia measured by KT-2000 arthrometer and the reduction in AP laxity following ACL reconstruction measured by the navigation system. However, we found no significant correlation between the reduction in AP laxity measured by the navigation system and the SSD of AP translation of the tibia measured by the KT-2000 arthrometer at final follow-up. Postoperatively, eight patients had a positive pivot shift test. Using the navigation system pre- and post-ACL reconstruction, these patients could not be identified by high absolute values for AP laxity nor rotational laxity. Although AP and rotational laxities vary largely among the patients, and AP and rotational stabilization are successfully achieved immediately after ACL reconstruction, intraoperative AP and rotational laxity measured by the navigation system did not influence the postoperative AP and rotational laxities after ACL reconstruction. III.


Phytol loaded PLGA nanoparticles regulate the expression of Alzheimer's related genes and neuronal apoptosis against amyloid-β induced toxicity in Neuro-2a cells and transgenic Caenorhabditis elegans.
Amyloid β (Aβ) induced neurotoxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration in Alzheimer's disease (AD). The nanoparticles based drug carrier system is considered as a promising therapeutic strategy to combat this incurable disease. It was also found to inhibit cholinesterase activity and apoptosis mediated cell death in Neuro-2a cells. The in vivo study further revealed that the Phytol and Phytol-PLGA NPs (Poly Lactic-co-Glycolic Acid Nanoparticles) was found to increase the lifespan, chemotaxis behavior and decrease Aβ deposition & ROS (Reactive oxygen species) production in transgenic Caenorhabditis elegans models of AD (CL2006, CL4176). Phytol and Phytol-PLGA NPs treatment downregulated the expression of AD associated genes viz Aβ, ace-1 and hsp-4 and upregulated the gene involved in the longevity to nematodes (dnj-14) and it also reduced the expression of Aβ peptide at the protein level. Our results of in vitro and in vivo studies suggest that Phytol and Phytol-PLGA NPs hold promising neuroprotective efficacy and targets multiple neurotoxic mechanisms involved in the AD progression.


Relationship between the flexibility and the motility of actin filaments: effects of pH.
Both the sliding velocity of fluorescently labeled actin filament and its persistence length as an index of the bending flexibility of the filament were examined in the motility assay as varying the pH values of the solution for preparing actin filaments. When the pH value was varied from 5.0 to 9.0 in the solution in which actin filaments were formed from the constituent monomers, the motile performance of Mg(2+) bound actin filaments (Mg-F-actin) was apparently suppressed compared to the case of Ca(2+) bound ones (Ca-F-actin). The persistence length for Ca-F-actin gradually increased with the increase of the pH value while the similar length for Mg-F-actin remained rather independent of the value. The largest sliding velocity of the filament, on the other hand, obtained at the persistence length of roughly 6 microm for both cases of Mg-F-actin and Ca-F-actin.


Discretion and local health policy implementation: street-level bureaucrats and integrative and complementary therapies in Santos' local health units.
This research discusses contextual factors that influence the development of complementary and/or integrative therapies developed by local health units on street-level bureaucracy in Santos. Through a qualitative approach, the research verifies that street-level bureaucracy is free to suggest and implement the aforementioned therapies, even if they do not have formal support of the municipality; however, they need support from their immediate local supervisors so they can adjust and implement the practice's routine, or the practice might not occur. Additionally, this text also presents guidelines in order to further develop the research.


Affective Personality Traits in Olfactory Dysfunction: the Role of Dysthymia and Arousal.
Olfactory dysfunction can have a negative impact on emotional well-being. The aim of the present study was to examine associations between olfactory deficits and two affective personality characteristics (trait anxiety/trait depression). A questionnaire study was conducted with a total of 116 participants (33 classified as anosmic, 40 as hyposmic, and 39 as normosmic). All participants gave self-reports on two facets of trait depression (dysthymia, euthymia) and trait anxiety (arousal, worrying). Due to the fact that in all three groups, trait depression and anxiety were substantially correlated, analyses of covariance were conducted. After controlling for trait depression, anosmic and hyposmic patients showed lower trait arousal compared to normosmic controls (partial η2 = .05). After controlling for trait anxiety, patients scored higher on dysthymia (partial η2 = .06). This study underlines the importance of statistically isolating specific associations between each of these affective personality characteristics and olfactory dysfunction. The present findings suggest that olfactory dysfunction can have opposite effects on facets of trait depression and trait anxiety.


Challenges and engineering application of landfill leachate concentrate treatment.
Landfill leachate concentrate (LLC) is a concentrated waste stream from landfill leachate treatment systems and has been recognized as a key challenge due to its high concentration of salts, heavy metals, organic matters, etc. Improper management of LLC (e.g. reinjection) would exacerbate the performance of upstream treatment processes and pose risks to the surrounding environments near landfill sites. Addressing the challenge and recovering resources from LLC have thus been attracting considerable attention. Although many LLC treatment technologies have been developed, a comprehensive discussion about the challenges still lacks. This review critically evaluates mainstream LLC treatment technologies, namely incineration, coagulation, advanced oxidation, evaporation and solidification/stabilization. We then introduce a geopolymer-based solidification (GS) process as a promising technology owning to its simple casting process and reusable final product and summarize engineering applications in China. Finally, we suggest investigating hybrid systems to minimize LLC production and achieve the on-site reuse of LLC. Collectively, this review provides useful information to guide the selection of LLC treatment technologies and suggests a sustainable alternative for large-scale application, while also highlighting the need of joint efforts in the industry to achieve efficient, ecofriendly and economical on-site management of landfill waste streams.


Regional myocardial blood flow and coronary vascular reserve in unanesthetized ponies during pacing-induced ventricular tachycardia.
To examine the effects of tachycardia on coronary circulation, transmural distribution of myocardial blood flow (MBF, 15-micron diameter radionuclide-labeled microspheres) was studied in six healthy adult ponies at rest (heart rate = 60 +/- 7 beats . min-1), during ventricular pacing at 150 and 200 beats . min-1, as well as with ventricular pacing at 250 beats . min-1 before and during maximal coronary vasodilatation (iv adenosine infusion; 4 mumole . kg-1 . min-1). Mean aortic pressure and cardiac output were unchanged from control values with ventricular pacing. Whereas ventricular pacing at 150 and 200 beats . min-1 resulted in a progressive uniform increase in transmural MBF and well-maintained endo:epi perfusion ratio, pacing at 250 beats . min-1 did not result in a further increase in MBF compared to pacing at 200 beats . min-1 and the left ventricular (LV) subendocardial:subepicardial (endo:epi) perfusion ratio was significantly less than 1.00 (0.87 +/- 0.05). Blood flow to the LV papillary muscles and subendocardium was significantly less than that recorded at 200 beats . min-1. The LV endo:epi perfusion ratio with ventricular pacing at 250 beats . min-1 during adenosine infusion resulted in a decrease in mean aortic pressure (63% of control value) and a marked further reduction in blood flow to the LV papillary muscles as well as the LV subendocardium, while MBF increased dramatically in the LV subepicardium compared to values observed during ventricular pacing at 250 beats . min-1 alone. This resulted in a LV endo:epi perfusion ratio of 0.39 +/- 0.09. By contrast, transmural right ventricular (RV) MBF increased significantly and the RV endo:epi perfusion ratio was well maintained. These data demonstrate that coronary vasomotion functions to maintain LV subendocardial blood flow in the pony myocardium at a heart rate of 200 beats . min-1, while at 250 beats . min-1 exhaustion of coronary vasodilator reserve in the deeper layers limits further increase in MBF.


Reducing the risk of surgical site infections: does chlorhexidine gluconate provide a risk reduction benefit?
Chlorhexidine gluconate (CHG) has been available as a topical antiseptic for over 50 years, having broad clinical application throughout the health care environment. Evidence-based clinical studies have shown chlorhexidine gluconate to be a safe and effective perioperative skin-prepping agent. Renewed interest has emerged for use of the antiseptic bath/shower to reduce the microbial skin burden prior to hospital admission. Recent clinical studies have documented that multiple applications of 2% or 4% CHG using a standardized protocol results in high skin surface concentrations sufficient to inhibit/kill skin colonizing flora, including methicillin-resistant Staphylococcus aureus. A new focus for the use of CHG in surgical patients involves irrigation of the wound prior to closure with 0.05% CHG followed by saline rinse. Recent laboratory studies suggest that, following a 1-minute exposure, 0.05% CHG produces a >5-log reduction against selective health care-associated pathogens and reduces microbial adherence to the surface of implantable biomedical devices. General, orthopedic, cardiothoracic, and obstetrical surgical studies have documented the safety of selective CHG formulations in elective surgical procedures. The following discussion will address both the evidence-based literature and preliminary findings suggesting that CHG has a broad and safe range of applications when used as an adjunctive interventional strategy for reducing the risk of postoperative surgical site infections (SSI).


Impact of Green financing, FinTech, and financial inclusion on energy efficiency.
In modern times, enhancing energy efficiency is one of the core agenda items for the economies to progress the world. United Nations general assembly has recommended increasing energy efficiency by considering the SDG-7 guidelines. In the contemporary period, E7 economies are deficient in producing the financial resources to ensure the availability of funds for the acquisition of energy efficiency. COVID-19 crises, lack of resilience in economies, devastating fiscal burdens, and tight monetary conditions of E7 economies are the major barriers. To resolve such issues, some innovative financing techniques, such as green financing, financial inclusion, and FinTech, were suggested to investigate. However, this research tested the empirical role of financial inclusion, green financing, and FinTech on the energy efficiency of E7 economies. Study findings have shown a significant role of such financing techniques on energy efficiency. Comparatively, green financing is found most fitting and highly supportive financing tool for energy efficiency among the three. The differences in attributes, financing mechanism, funds flow system, transection systems, and variation in support by the financial institution are the main reasons that lessen the role of financial inclusion and FinTech for energy efficiency. However, theorists must revisit the transaction system of FinTech and financial inclusion parameters like green bonds for energy efficiency attainment. Policymakers are suggested to develop viable and energy system-friendly policies to grant green finance to the energy systems of E7 economies, as conveniently as possible.


Cytomegalovirus infections in pregnant women as a risk of congenital deafness in a child.
One per cent of live births are affected by cytomegalovirus infection, but 90% of neonates with perinatal infection do not show symptoms of disease. Symptomatic cytomegalovirus (CMV) is present in 5-10% of children. Typical clinical signs of congenital cytomegalovirus infection are microcephalia, mental retardation, progressive major amblyacousia, and neuromuscular infection. Hypoacusis is present in 30-60% of children with congenital symptomatic CMV - in most cases it is bilateral and applies to high-frequency hearing loss. A group of 70 children had serological and genetic screening of viral DNA using the polymerase chain reaction method in urine and blood. In this group, 52 children were diagnosed with congenital CMV, and 10 children were diagnosed with acquired CMV. Audiological examinations including pure-tone audiometry, auditory brainstem response, transiently evoked otoacoustic emission, and immittance audiometry were performed. Bilateral sensorineural hearing loss was in 9 children associated with mental and physical retardation, brain malformation, and microcephalia. Unilateral hearing loss was observed in 3 children. In 40 cases, we did not observe hearing loss, although the level of bilirubin was high, as well as splenomegaly, hepatomegaly, and facial nerve paralysis. Congenital cytomegalovirus infection often caused hearing loss. Children with congenital and acquired CMV should be under the permanent care of an audiologist. The growing problem of CMV infections and their late diagnosis suggests the need to prepare screening tests and increase the education of gynaecologists, neonatologists, paediatricians, and general practice doctors about CMV problems.


Influence of gender, ASA physical status, the location of a tumor and stage of the disease on the survival rate in patients with rectal cancer after surgery.
There are limited data describing different factors that influence survival rate of patients with rectal cancer. Our aim was to determine the influence of patient gender, American Society of Anesthesiologists (ASA) physical status, the location of the tumor and stage of the disease on the patient survival rates after excision of rectal cancer. We included 385 patients who were operated between 2004 and 2014 in the University Clinical Center Maribor. The patients were treated due to rectal adenocarcinoma. We assessed survival rates according to gender, ASA physical status, the location of the tumor and stage of the disease with different statistical methods. To find the extent of correlation between factors and survival rate, we used means and medians, Log Rank test, Breslow test and Tarone-Ware test. According to patient gender, survival rate did not differ significantly (P > 0.05), however ASA physical status (P < 0.05), location of the tumor (P < 0.05) and stage of the disease (P < 0.05) significantly affected the survival rates. Our study showed that gender does not have a significant impact on survival rate as oposed to ASA physical status, the location of the tumor and stage of the disease.


Enhanced removal of bio-refractory dissolved organic matter from cassava distillery wastewater by powdered activated carbon-ballasted coagulation: Detailed study of separation characteristics and mechanisms.
Efficient removal of bio-refractory dissolved organic matter (DOM) and colorants is essential for discharging or reusing the distillery wastewater. An important part of recalcitrant DOM still exists in the effluent of regular coagulation though the ferric coagulant has been found to be effective in decoloration. The present work adopted powdered activated carbon (PAC) as ballasting agent to achieve robust separation effect and efficiency of bio-refractory DOM from the bio-chemically treated cassava distillery wastewater (BTDWW). More than 90% of DOC could be removed at the PAC and Fe(III)-coagulant dosage of 1.40 g/L and 0.84 g/L as Fe when the BTDWW was neutral. PAC should be dosed before coagulant in order to mix well with the DOM in the BTDWW. The analyses of DOM in effluent reveal that PAC facilitated the removal of lignin breakdown products which could not be well eliminated by regular coagulation; the removal of DOM with MW < 5 kDa was mostly enhanced. The characteristics of flocs demonstrate that PAC reinforced the interaction between Fe(III) species and DOM by providing more reaction sites. The sedimentation could be completed within the initial 5 min, and the highest settling velocity was almost 8 times higher than that of the only Fe(III)-involved flocs. The large size and favorable robustness of PAC-involved flocs enabled decent sedimentation even though their stretched structure might not be desirable in regular coagulation. The PAC-ballasted coagulation is recommended as tertiary treatment of BTDWW considering its high efficiency and sound economic feasibility.


Preliminary experience in the use of ultrafast computed tomography to diagnose aortic valve stenosis.
Eight patients, mean age 72 years, with aortic valve stenosis were studied by ultrafast CT 1 day after cardiac catheterization. After injection of radiographic contrast material through a peripheral vein, two contiguous eight-level R wave-triggered cine mode scans in the short axis were acquired, starting above the aortic valve and continuing through the apex of the left ventricle. Seven of eight patients, all with calcified aortic valves, had a detectable central orifice. Catheterization-derived aortic valve areas were within 0.25 cm2 of the CT valve areas in six of seven. LV mass was measured by ultrafast CT in the eight patients with aortic valve stenosis (121.6 +/- 18.2 gm/m2) and was found to be significantly higher (p less than 0.0001) than that in a group of eight subjects with normal LV function, no history of hypertension, and normal ECGs (73.0 +/- 13.1 gm/m2). It is concluded that in selected cases ultrafast CT can contribute to the assessment of severity of calcific aortic stenosis by measurement of LV mass and valve area.


Recommendations for Services in a FAIR Data Ecosystem.
The development and growing adoption of the FAIR data principles and associated standards as a part of research policies and practices place novel demands on research data services. This article highlights common challenges and priorities and proposes a set of recommendations on how data infrastructures can evolve and collaborate to provide services that support the implementation of the FAIR data principles, in particular in the context of building the European Open Science Cloud (EOSC). The recommendations cover a broad area of topics, including certification, infrastructure components, stewardship, costs, rewards, collaboration, training, support, and data management. These recommendations were prioritized according to their perceived urgency by different stakeholder groups and associated with actions as well as suggested action owners. This article is the output of three workshops organized by the projects FAIRsFAIR, RDA Europe, OpenAIRE, EOSC-hub, and FREYA designed to explore, discuss, and formulate recommendations among stakeholders in the scientific community. While the results are a work-in-progress, the challenges and priorities outlined provide a detailed and unique overview of current issues seen as crucial by the community that can sharpen and improve the roadmap toward a FAIR data ecosystem.


Prophylactic Catheter Ablation of Ventricular Tachycardia in Ischemic Cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials Electrophysiology Collaborative Consortium for Metaanalysis - ELECTRAM Investigators.
Catheter ablation is an effective strategy for drug-refractory ventricular tachycardia (VT) in ischemic cardiomyopathy. We aimed to perform a systematic review and meta-analysis of outcomes of prophylactic catheter ablation (PCA) of Ventricular Tachycardia (VT) in ischemic cardiomyopathy patients. We performed a comprehensive literature search through February 10, 2020, for all eligible randomized controlled trials that compared "PCA" versus "No PCA" for VT. Primary efficacy outcomes included - appropriate ICD therapy (composite of anti-tachycardia pacing and ICD shock), appropriate ICD shocks, electrical storm, cardiac mortality, and all-cause mortality. The primary safety outcome was any adverse events. Four randomized controlled trials (N = 505) met inclusion criteria. Prophylactic catheter ablation was associated significant reduction in appropriate ICD therapies (RR 0.70; 95% CI 0.55 - 0.89, p = 0.004), appropriate ICD shocks (RR 0.57 95% CI 0.40 - 0.80, p = 0.001) with a trend towards reduced risk of electrical storm (RR 0.64; CI 0.39 - 1.05; p = 0.075) compared to "No PCA". There was no significant difference in cardiac mortality (RR 0.66, 95% CI 0.31 - 1.43, p = 0.29) and all-cause mortality (RR 0.98, 95% CI 0.52 - 1.82, p = 0.94) with similar adverse events (RR 1.46, 95% CI 0.73 - 2.95, p = 0.29) between two groups. Prophylactic catheter ablation in ischemic cardiomyopathy patients was associated with a lower risk of ICD therapies, including ICD shocks and VT storm with no difference in cardiac and all-cause mortality.


Identification of hub proteins in cerebrospinal fluid as potential biomarkers of Alzheimer's disease by integrated bioinformatics.
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with complex pathophysiology. Therefore, the identification of novel effective fluid biomarkers is essential for Alzheimer's disease diagnosis and drug development. This study aimed to identify potential candidate hub proteins in cerebrospinal fluid for precise Alzheimer's disease diagnosis using bioinformatics methods. A total of 29 co-significant differentially expressed proteins were identified by differential protein expression analysis in four different cohorts. Functional enrichment analysis revealed that most of these proteins were enriched in pathways related to glycometabolism. Using the Least Absolute Shrinkage and Selection Operator (LASSO) and random forest feature selection methods, six hub proteins [14-3-3 protein zeta/delta (YWHAZ), SPARC-related modular calcium-binding protein 1 (SMOC1), aldolase A (ALDOA), pyruvate kinase isoenzyme type M2 (PKM), chitinase-3-like protein 1 (CHI3L1), and secreted phosphoprotein 1 (SPP1)] were identified. These six hub proteins were upregulated in the cerebrospinal fluid of patients with Alzheimer's disease compared with cognitively unimpaired control individuals. Meanwhile, SMOC1, ALDOA, and PKM were specifically upregulated in the cerebrospinal fluid of patients with Alzheimer's disease but not in other neurodegenerative diseases. Build AD diagnostic models showed that a single hub protein or six hub proteins combination had an excellent ability to discriminate Alzheimer's disease. In conclusion, our study suggests that these identified hub proteins, which are related to glycometabolism, may be potential biomarkers for further basic and clinical research in Alzheimer's disease.


Comparing patterns of care and outcomes after operative management of complications after bariatric surgery at MBSAQIP accredited bariatric centers and non-bariatric facilities.
Many operations for complications after bariatric surgery are performed by surgeons without bariatric expertise at centers without teams who routinely care for bariatric patients. This study sought to evaluate whether bariatric expertise affects patterns of care and perioperative outcomes among patients undergoing operative intervention for complications after bariatric surgery. Administrative claims data from the Kentucky Office of Health Policy were queried for inpatients undergoing operative intervention for complications related to bariatric surgery between 2015 and 2018. Patients were stratified with respect to whether or not they underwent surgery at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) accredited bariatric surgery center (BCE) or not (non-BCE). Groups were compared with respect to demographic, procedural, and outcome variables. BCE patients were more often Caucasian than non-BCE patients (p < 0.001) and have either private insurance or Medicare coverage (p = 0.02). Regarding operative approach, operations were more likely to be performed laparoscopically in BCE (88.5% BCE vs. 80.9% non-BCE, p = 0.007). Length of stay was significantly shorter for BCE patients (median 2 days BCE vs. 3 days non-BCE, p < 0.001), and BCE patients were more likely to be discharged home (85.4% BCE vs. 78.5% non-BCE, p = 0.02). Inpatient mortality and average total charges per patient did not differ significantly between the two groups CONCLUSIONS: Surgical management of complications after bariatric surgery at BCE is associated with greater utilization of minimally invasive techniques, shorter hospital stay, and increased likelihood of routine home discharge. These findings should prompt a review and standardization of care patterns for patients with complications after bariatric surgery aimed at optimizing outcomes and improving value.


Low-power XiX decoupling in MAS NMR experiments.
Low-power XiX proton decoupling under fast magic-angle spinning is introduced. The method is applicable if the MAS frequency exceeds the proton-proton interactions. For rigid organic solids this is the case for MAS frequencies above approximately 40 kHz. It is shown that the quality of the decoupling as well as the sensitivity to frequency offsets can be improved compared to low-power continuous-wave decoupling. The decoupling efficiency is somewhat reduced compared to optimized high-power decoupling: in a peptide sample investigated at an MAS frequency of 50 kHz a loss of about 10% in signal intensity for CH3 and CH groups, and of about 40% for CH2 groups was observed. Taking into consideration, that the rf amplitude in the low-power XiX was about 15 times lower than in high-power XiX decoupling, such a reduction in line intensity is sometimes tolerable.


[Ultrastructure, metabolism and function of the white blood cells in the process of the formation of an immune response and in exposure to glucocorticoids. II. The effect of immunization on the number and sub-microscopic structure of granulocytes in rabbits].
The absolute count of different types of granulocytes was determined and their ultrastructure was studied in the blood of rabbits immunized with bovine serum albumin. Both the primary and repeated antigen administration were followed by regular quantitative and qualitative changes in neutrophils, basophils, and eosinophils whose degree and character were determined by the stage of the immune response formation.


A self-targeting and controllable drug delivery system constituting mesoporous silica nanoparticles fabricated with a multi-stimuli responsive chitosan-based thin film layer.
Surface modification and functionalization of nanomaterials have been adopted widely in devising smart drug delivery systems. This work examines the fabrication of multi-stimuli responsive surfaces on mesoporous silica nanoparticles (MSN) for environmentally sensitive site specific drug delivery with reduced risk of premature drug leakage. Chitosan cross-linked via disulfide bonds was applied to form a thin film on drug-loaded MSN, realizing a capsulation and stimuli-sensitive regulating gate membrane; that was further conjugated with folate for site specific targeting toward cancer cells. The chitosan thin film was very stable under neutral conditions and could effectively prevent drug leakage, but was sensitive to both pH and GSH stimulations to reach rapid drug release. Thus, drug release could be triggered by changes in such factors that are common to cancer cells. However, complete and accelerated release could only be realized when triggered simultaneously by both acidic pH and GSH. Moreover, tests with HepG-2 cells confirmed that folate-receptor mediated endocytosis successfully enhanced the cellular uptake of the nanoparticle and antitumor activity toward cancer cells. It is expected that this surface chemical modification strategy promises a powerful approach constructing smart drug delivery systems for efficient and safe chemotherapy.


Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K).
Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. ClinicalTrials.gov, NCT04799067.


In situ control of root-bacteria interactions using optical trapping in transparent soil.
Bacterial attachment on root surfaces is an important step preceding the colonization or internalization and subsequent infection of plants by pathogens. Unfortunately, bacterial attachment is not well understood because the phenomenon is difficult to observe. Here we assessed whether this limitation could be overcome using optical trapping approaches. We have developed a system based on counter-propagating beams and studied its ability to guide Pectobacterium atrosepticum (Pba) cells to different root cell types within the interstices of transparent soils. Bacterial cells were successfully trapped and guided to root hair cells, epidermal cells, border cells, and tissues damaged by laser ablation. Finally, we used the system to quantify the bacterial cell detachment rate of Pba cells on root surfaces following reversible attachment. Optical trapping techniques could greatly enhance our ability to deterministically characterize mechanisms linked to attachment and formation of biofilms in the rhizosphere.


Possible further reduction in coronary flow velocity reserve in angina pectoris patients after oral glucose loading.
Previous studies have suggested an increase in myocardial oxygen demand as a cause of postprandial angina. The purpose of this study was to assess coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) before and after glucose ingestion in patients with known significant LAD stenosis. Fourteen patients with significant LAD stenosis and 20 subjects without LAD stenosis were enrolled. Transthoracic Doppler echocardiography was performed to measure the average peak diastolic coronary flow velocity (APDV) in the LAD at rest and during adenosine infusion. CFVR was calculated as APDV during adenosine infusion (APDVATP) divided by APDV at rest (APDVrest). APDVrest, APDVATP, and CFVR were assessed during fasting and 30, 60, and 120 min after a 75-g oral glucose loading. In patients with LAD stenosis, APDVrest at 30 min after glucose loading was the highest at any time point. However, significant differences were not found in the APDVATP among time points in the patients or controls. Consequently, the CFVR in the patients was the lowest at 30 min after glucose loading (fasting, 1.77 ± 0.19; 30 min, 1.48 ± 0.16; 60 min, 1.69 ± 0.17; and 120 min, 1.76 ± 0.19; p < 0.01, ANOVA), as in the controls. These findings suggested that the value of CFVR in the LAD was reduced after glucose loading. Myocardial risk area supplied by a stenosed coronary artery may be exposed to myocardial ischemia more frequently during oral glucose loading than during fasting in patients with significant coronary artery stenosis.


Proximal Humeral Bone Loss in Revision Shoulder Arthroplasty.
Proximal humeral bone loss in revision shoulder arthroplasty poses a significant obstacle to achieving stable and reliable fixation of the humeral stem. It is important to identify and classify this bone loss preoperatively, which can range from epiphyseal to substantial diaphyseal bone loss. There are several reconstructive options that can address the varying levels of bone loss, including cemented long-stem fixation, a composite construct using proximal humeral allograft or femoral allograft, proximal humeral endoprosthetic replacement, or total humeral replacement. All of these are viable reconstructive options that have demonstrated adequate to good outcomes.


The nature and sources of the emotional distress felt by intensivists and the burdens that are carried: A qualitative study.
Work in intensive care units is often traumatic and emotionally distressing, sometimes leading to growth but at other times to negative outcomes such as worker burnout and mental illness. The type and origin of distresses to intensivists has been poorly characterised in the literature. This evidence gap makes it difficult to develop tailored educational process or cultural interventions for all who work within the specialty. The aim of this study was to elicit the nature and sources of workplace emotional distress in an international sample of intensivists. Interviews were undertaken with experienced intensivists in Australia and Israel related to the basis of workplace distress. These were transcribed and qualitatively thematically analysed. In 2018, 19 intensivists participated in the study. Several key themes emerged from data analysis, some relating to clinical work, such as catastrophic patient outcomes, and some relating to interpersonal and systems-level challenges. Navigating complex interpersonal dynamics with carers and staff, both within and outside the intensive care unit team, caused substantial emotional burden. Many factors contribute to workplace stress for doctors in the intensive care setting. In elucidating common reactions to these stressors, we have attempted to normalise responses. We further note that the skill sets relevant to the many challenges identified are generally missing in medical training curricula. It may be prudent to consider their inclusion in the future.


Effect of clinical photography on postprocedure patient satisfaction in female patients who underwent nonsurgical rhinoplasty.
A prospective clinical study. To the best of our knowledge, there is no study in the literature that addresses the effect of showing comparative photographs in the follow-up period to patients who had undergone nonsurgical rhinoplasty on patient satisfaction. To examine the effect of showing preprocedure and postprocedure photographs to patients in the follow-up period on patient satisfaction. It was a nonsimultaneous prospective study that included patients suitable for nonsurgical rhinoplasty. Photographs were taken during routine follow-up after 1 month of the procedure, and patients were asked to fill the Derriford Appearance Scale 24 (DAS24) and Rhinoplasty Outcome Evaluation (ROE) questionnaires. Next, after the preprocedure and postprocedure photographs were shown to the patients, they were asked to complete the DAS24 and ROE questionnaires again. The study included 265 female patients. The mean age of the patients was 35.11 ± 8 (18-61 years). Before the preprocedure and postprocedure photographs were shown, the DAS24 score was 52.2 ± 14.26 and the ROE score was 75.91 ± 11.91. After the photographs were shown, the DAS24 score was found to be 40.80 ± 13.25 and the ROE score as 87.722 ± 8.56. Therefore, significant improvement in DAS24 and ROE scores and an increase in patient satisfaction were observed after the preprocedure and postprocedure photographs were shown (p = 0.01, p < 0.05). Showing preprocedure and postprocedure photographs in the follow-up period to patients who underwent nonsurgical rhinoplasty leads to greater patient satisfaction with the surgery and their self-image.


Comparative in vitro activity of carbapenems against major Gram-negative pathogens: results of Asia-Pacific surveillance from the COMPACT II study.
Resistance rates amongst Gram-negative pathogens are increasing in the Asia-Pacific region. The Comparative Activity of Carbapenem Testing (COMPACT) II study surveyed the carbapenem susceptibility and minimum inhibitory concentrations (MICs) of doripenem, imipenem and meropenem against 1260 major Gram-negative pathogens isolated from hospitalised patients at 20 centres in five Asia-Pacific countries (New Zealand, the Philippines, Singapore, Thailand and Vietnam) during 2010. Pseudomonas aeruginosa (n=625), Enterobacteriaceae (n=500), and other Gram-negative pathogens including Acinetobacter baumannii (n=135) were collected from patients with bloodstream infection (32.2%), nosocomial pneumonia including ventilator-associated pneumonia (58.1%), and complicated intra-abdominal infection (9.7%), with 36.7% being isolated from patients in an Intensive Care Unit. As high as 29.8% of P. aeruginosa and 73.0% of A. baumannii isolates were not susceptible to at least a carbapenem, whereas the majority of Enterobacteriaceae (97.2%) were susceptible to all carbapenems. Respective MIC(50)/MIC(90) values (MICs for 50% and 90% of the organisms, respectively) of doripenem, imipenem and meropenem were: 0.38/8, 1.5/32 and 0.38/16 mg/L for P. aeruginosa; 0.023/0.094, 0.25/0.5 and 0.032/0.094 mg/L for Enterobacteriaceae; and 32/64, 32/128 and 32/64 mg/L for A. baumannii. Doripenem and meropenem had comparable activity against P. aeruginosa, both being more active than imipenem. All carbapenems were highly potent against Enterobacteriaceae, although imipenem demonstrated higher MIC values than doripenem and meropenem. The three carbapenems showed less activity against A. baumannii. The high prevalence of carbapenem resistance amongst important nosocomial pathogens (P. aeruginosa and A. baumannii) warrants rigorous infection control measures and appropriate antimicrobial use in the Asia-Pacific region.


A review of the clinical performance of the Aptima HPV assay.
This comprehensive review compiles published data from 62 original articles comparing different HPV tests and one meta-analysis on the clinical performance of the Aptima HR HPV (AHPV) assay in either screening or referral populations as well as for the purpose of test of cure. A number of publications with technical issues were also considered. Besides a brief introduction in the development of E6/E7 mRNA testing, the review summarizes data on analytical sensitivies and specificities, as well as on clinical sensitivity, specificity, NPV and PPV with histological endpoints CIN2+ and CIN3+, where available. Although most studies were of cross-sectional design, five studies with a longitudinal prospective design or component were identified. In addition to the study design, sample size, age and CIN2/3+ prevalence of the respective cohort are listed. This allows direct comparison of the published data in the respective groups. One major outcome of this review is the remarkably stable similar sensitivities of AHPV and HC2 independent from study design for detection of CIN2/3+ combined with a higher specificity of the AHPV. The second outcome was the longitudinal predictive value derived from registry linkage and other prospective studies that would support the applicability of the AHPV test in primary screening with at least a three year screening interval.


Comparison between ELISA and gel-filtration assay for the quantitation of airway mucins.
In this study, we developed immunoassay methods for the more convenient and effective detection of rat tracheal mucin and the results were compared with those of [3H]glucosamine based gel-filtration method. A monoclonal anti-rat tracheal mucin antibody, mAbRT03, which specifically recognizes rat tracheal mucins, was used throughout in this study. To induce mucin secretion, varying concentrations of ATP (0-2 mM) were applied to the primary rat tracheal surface epithelial (RTSE) cell culture which had been metabolically radiolabeled with [3H]glucosamine and the secretion of mucin was analyzed both by the immunoassay and the gel-filtration chromatography methods. For the immunoassay, the following two procedures were employed. 1) Simple ELISA; the culture spent media were directly coated onto the assay plate and the immunoreactivity with mAbRT03 was assessed from the standard curve generated with the purified rat mucin. 2) Inhibition ELISA; A known amount of the purified rat mucin was coated onto the assay plate and then ATP-stimulated culture spent media were added to inhibit the immunoreactivity with mAbRT03. The contents of mucin in the sample were calculated from the standard inhibition curve which was generated with the purified rat mucin. The assay results obtained from the immunoassays were identical with those from the gel-filtration methods. The present result indicates that ELISA can be substituted for the laborious, time-consuming gel-filtration assay in studying the regulation of airway mucin release from cultured airway epithelial cells.


Predicting breakthrough of vanadium in fixed-bed absorbent columns with complex groundwater chemistries: A multi-component granular ferric hydroxide-vanadate-arsenate-phosphate-silicic acid system.
Granular ferric hydroxide (GFH) is often used for fixed bed adsorbent (FBA) columns in groundwater purification units around the world to remove arsenate contaminations. Groundwater can contain also other toxic (e.g., antimonite and vanadate) and non-toxic oxo-anions (phosphate and silicic acid) that are known to affect FBA lifetimes. Therefore, understanding the breakthrough of toxic compounds intended for removal by FBA is essential to their design, and is important to predict accurately breakthrough curves (BTCs) for FBAs in waterworks to plan future operating costs. Rapid small-scale column tests (RSCCT) and pilot-scale FBA were used to simulate vanadate BTCs for complex groundwater chemistries. The BTCs were simulated successfully using a homogeneous surface diffusion model (HSDM) combining equilibrium chemical adsorption and kinetic mass transfer. Adsorption parameters for various groundwater compositions were predicted using the CD-MUSIC surface complexation model, which was set up for the first time for akaganéite-based granular ferric hydroxide with a competitive multi-solute system. The results indicated that V(V) is less prone to competitive adsorption effects, and use of the homogeneous surface diffusion model to predict the BTCs requires then the kinetic mass transfer Biot number to be used as the only fitting parameter. On the other hand, a concentration overshoot could be observed for the two weaker absorbed oxo-anions arsenate and phosphate because of displacement by the vanadate. Results of pilot scale test column BTCs of vanadate for three waterworks with different groundwater compositions could be favorably extrapolated with a unique Freundlich constant kF of 3.2 derived on basis of the multi-solute CD-MUSIC model, and a unique Biot number of 37 fixed for all three different test sites.


Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse Models.
Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, is regulated by different forms of cell death, including apoptosis and autophagy. However, the role in ADPKD of ferroptosis, a recently discovered form of cell death mediated by iron and lipid metabolism, remains elusive. To determine a pathophysiologic role of ferroptosis in ADPKD, we investigated whether the absence of Pkd1 (encoding polycystin-1) affected the expression of key factors involved in the process of ferroptosis, using Western blot and qRT-PCR analysis in Pkd1 mutant renal cells and tissues. We also examined whether treatment with erastin, a ferroptosis inducer, and ferrostain-1, a ferroptosis inhibitor, affected cyst growth in Pkd1 mutant mouse models. We found that kidney cells and tissues lacking Pkd1 exhibit extensive metabolic abnormalities, including reduced expression of the system Xc- amino acid antiporter (critical for import of cystine), of iron exporter (ferroportin), and of GPX4 (a key and negative regulator of ferroptosis). The abnormalities also include increased expression of iron importers (TfR1, DMT1) and HO-1, which in turn result in high iron levels, low GSH and GPX4 activity, increased lipid peroxidation, and propensity to ferroptosis. We further found that erastin increased, and ferrostatin-1 inhibited ferroptotic cell death and proliferation of Pkd1-deficient cells in kidneys from Pkd1 mutant mice. A lipid peroxidation product increased in Pkd1-deficient cells, 4HNE, promoted the proliferation of survived Pkd1 mutant cells via activation of Akt, S6, Stat3, and Rb during the ferroptotic process, contributing to cyst growth. These findings indicate that ferroptosis contributes to ADPKD progression and management of ferroptosis may be a novel strategy for ADPKD treatment.


Unusual severe radiation-induced toxicity in a patient with discoid lupus erythematosus: A case report and critical review of the literature.
Data on the incidence and severity of radiation-induced toxicity in patients with systemic and/or cutaneous lupus erythematosus (SLE/CLE) are very limited. After reporting the case of a patient who experienced major toxicity and CLE flare in the irradiated area following breast irradiation, we conducted a comprehensive literature review of available data in this setting. The few retrospectives studies which have evaluated both the risk of toxicity in SLE/CLE patients and/or the potential induction or reactivation of SLE/CLE with radiotherapy have not shown differences between SLE/CLE patients and controls. Several other factors such as concurrent chemotherapy, a particular genetic background, or lupus treatments (essentially hydroxychloroquine) can explain severe radiation-induced toxicity. Therefore, patients with SLE/CLE should be irradiated like patients without SLE/CLE, with close monitoring during radiotherapy if other risk factors exist. Further studies examining a larger number of patients would probably allow a better understanding of the radiosensitivity of these patients.


Increasing consolidation in healthcare markets: what are the antitrust policy implications?
To discuss the implications of the rapid transformation of the healthcare financing and delivery system for competition, social welfare, and antitrust policy. Horizontal and vertical consolidations can enhance efficiency but can also be anticompetitive in markets characterized by entry barriers. Active enforcement of the antitrust laws is essential to ensure that competition in healthcare markets will lead to procompetitive, rather than anticompetitive effects. However, healthcare antitrust enforcement policy must be flexible enough to allow efficient new forms of organization and practice to emerge.


Tryptophan metabolite norharman secreted by cultivated Lactobacillus attenuates acute pancreatitis as an antagonist of histone deacetylases.
Patients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation. In AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC-MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman. AP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman's activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages' activation. The enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation.


High cumulative doxorubicin dose for advanced soft tissue sarcoma.
The recommended cumulative doxorubicin dose in soft tissue sarcoma (STS) treatment was based on cardiotoxicity data from retrospective studies of breast cancer patients. However, the treatment and prognosis of STS and breast cancer are quite different, and reference to breast cancer data alone may not reflect the efficacy of doxorubicin treatment in STS. This study, thus, aimed to review and analyze clinical data of STS patients treated with a high cumulative doxorubicin dose, to provide a reference for treatment selection and clinical trial design. We retrospectively collected and analyzed clinical data of patients with advanced STS who received doxorubicin-based chemotherapy from January 2016 to January 2020. The patients were divided into a standard-dose group (who received ≤6 cycles of doxorubicin after the initial diagnosis) and an over-dose group (who were re-administered doxorubicin [doxorubicin-rechallenge] after receiving 6 cycles of doxorubicin therapy discontinuously). Patient characteristics, cumulative doxorubicin dose, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), cardiotoxicity incidence, and treatment effectiveness were evaluated in both groups. A total of 170 patients with advanced STS were recruited (146 in the standard-dose group and 24 in the over-dose group). The average cumulative doxorubicin dose was 364.04 ± 63.81 mg/m2 in the standard-dose group and 714.38 ± 210.09 mg/m2 in the over-dose group. The ORR, DCR, and median PFS were 15.07, 58.9%, and 6 (95% confidence interval [CI]: 5.8-6.5) months in the standard-dose group and 16.67, 66.67%, and 4 (95%CI: 2.0-5.8) months in the over-dose group, respectively. Symptomatic heart failure occurred in five patients (3.42%) of the standard-dose group and in one patient (4.17%) of the over-dose group. In these patients with cardiotoxicity, doxorubicin was discontinued, and all of them died of uncontrolled tumor growth. No drug-related deaths occurred. The continuation of or rechallenge with doxorubicin beyond the recommended cumulative dose could be a promising therapeutic option in the treatment of chemotherapy-sensitive advanced sarcomas. Further evaluation is necessary in prospective trials.


An analysis of assessment outcomes from eight years' operation of the Australian border weed risk assessment system.
The majority of Australian weeds are exotic plant species that were intentionally introduced for a variety of horticultural and agricultural purposes. A border weed risk assessment system (WRA) was implemented in 1997 in order to reduce the high economic costs and massive environmental damage associated with introducing serious weeds. We review the behaviour of this system with regard to eight years of data collected from the assessment of species proposed for importation or held within genetic resource centres in Australia. From a taxonomic perspective, species from the Chenopodiaceae and Poaceae were most likely to be rejected and those from the Arecaceae and Flacourtiaceae were most likely to be accepted. Dendrogram analysis and classification and regression tree (TREE) models were also used to analyse the data. The latter revealed that a small subset of the 35 variables assessed was highly associated with the outcome of the original assessment. The TREE model examining all of the data contained just five variables: unintentional human dispersal, congeneric weed, weed elsewhere, tolerates or benefits from mutilation, cultivation or fire, and reproduction by vegetative propagation. It gave the same outcome as the full WRA model for 71% of species. Weed elsewhere was not the first splitting variable in this model, indicating that the WRA has a capacity for capturing species that have no history of weediness. A reduced TREE model (in which human-mediated variables had been removed) contained four variables: broad climate suitability, reproduction in less or than equal to 1year, self-fertilisation, and tolerates and benefits from mutilation, cultivation or fire. It yielded the same outcome as the full WRA model for 65% of species. Data inconsistencies and the relative importance of questions are discussed, with some recommendations made for improving the use of the system.


Traveling Wave Ion Mobility-Mass Spectrometry to Enhance the Detection of Low Abundance Features in Untargeted Lipidomics.
Ion mobility has become a valuable tool in mass spectrometry-based lipidomics workflows, thanks to its ability to separate ions in the gas phase based on their size and conformation. Over the last years, it was demonstrated that the comparative analysis of ion mobility data has the potential to highlight the presence of low abundance species in untargeted lipidomics. The present chapter illustrates the background of the topic and guides the reader from the sample preparation to the data analysis of an untargeted lipidomics experiment performed using ion mobility.


Mindfulness-based interventions in epilepsy: a systematic review.
Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined.


Huaier extract suppresses non-small cell lung cancer progression through activating NLRP3-dependent pyroptosis.
Recent studies have reported the anticancer activity of huaier extract in various human malignancies. However, little is known about the effect of huaier extract in non-small cell lung cancer (NSCLC) and its underlying mechanism. The current study aimed to investigate whether huaier extract affects the progression of NSCLC. mRNA and proteins expression of pyroptotic-related genes (NLRP3, caspase-1, IL-1β, and IL-18) in NSCLC tissues and cells were, respectively, detected by qRT-PCR and western blot. The effects of huaier extract on NSCLC cell viability and cytotoxicity were evaluated by CCK-8 assay, colony formation assay, and LDH detection kit. Besides, we established a xenograft model to assess the antitumor effect of huaier extract on tumor growth in vivo. Our results showed that the expression of pyroptotic-related genes was downregulated in NSCLC tissues and cell lines. Huaier extract pretreatment inhibited cell viability and the percentage of colony formation of H520 and H358 cells, and upregulated the expression of pyroptotic-related genes. Mechanistically, huaier extract exhibited antitumor effect in NSCLC via inducing NLRP3-dependent pyroptosis in vitro and in vivo. In conclusion, our finding confirmed that huaier extract played an antitumor role in NSCLC progression through promoting pyroptotic cell death, which provided a new potential strategy for NSCLC clinical treatment.


Climate considerations in long-term safety assessments for nuclear waste repositories.
For a deep geological repository for spent nuclear fuel planned in Sweden, the safety assessment covers up to 1 million years. Climate scenarios range from high-end global warming for the coming 100 000 years, through deep permafrost, to large ice sheets during glacial conditions. In contrast, in an existing repository for short-lived waste the activity decays to low levels within a few tens of thousands of years. The shorter assessment period, 100 000 years, requires more focus on climate development over the coming tens of thousands of years, including the earliest possibility for permafrost growth and freezing of the engineered system. The handling of climate and climate change in safety assessments must be tailor-made for each repository concept and waste type. However, due to the uncertain future climate development on these vast time scales, all safety assessments for nuclear waste repositories require a range of possible climate scenarios.


Anteroposterior difference in EEG sleep depth measure is reduced in apnea patients.
In the present work, mean frequencies of FFT amplitude spectra from six EEG derivations were used to provide a frontopolar, a central and an occipital sleep depth measure. Parameters quantifying the anteroposterior differences in these three sleep depth measures during the night were also developed. The method was applied to analysis of 30 all-night recordings from 15 healthy control subjects and 15 apnea patients. Control subjects showed larger differences in sleep depth between frontopolar and central positions than the apnea patients. The relatively reduced frontal sleep depth in apnea patients might reflect the disruption of the dynamic sleep process caused by apneas.


Racial/ethnic group differences in parenting attitudes among at-risk emerging adults: The roles of adversity, relationship quality, and caregiver involvement and attitudes.
Healthy parenting attitudes are foundational for positive parenting and child well-being. However, few studies explore their formation and mediators explaining racial/ethnic group differences. The present study prospectively examines potential mediators for racial/ethnic group differences in parenting attitudes in a diverse sample of emerging adults (EA). Participants are EA and their caregivers (N = 891) who participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Adverse childhood experiences (ACEs), parenting attitudes, and caregiver-child relationship quality and involvement were assessed. Mediators of racial/ethnic group differences were tested using Structural Equation Modeling with bias-corrected confidence intervals based on 1000 bootstrapped samples. Black EA had less appropriate developmental expectations and perceptions of family roles, empathy toward children, and rejection of physical punishment, compared to White EA. Latinx EA also had less empathy toward children compared to White EA. Caregivers' parenting attitudes mediated group differences, beyond ACEs and relationship quality and involvement. Significant mediation effects include: appropriate developmental expectations, R2 = 0.08, p < .05; rejection of physical punishment, R2 = 0.06, p < .05; appropriate family roles, R2 = 0.16, p < .05; and empathy toward children, R2 = 0.15, p < .05, for Black relative to White EA, as well as, empathy toward children, R2 = 0.12, p < .05, for Latinx relative to White EA. Findings highlight the mediating role of intergenerational transmission of parenting attitudes for explaining racial-ethnic differences and supporting positive parenting practices in diverse communities.


Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates.
Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.


Listening to neuropeptides by microdialysis: echoes and new sounds?
Neuropeptides represent the largest class of neuromessengers in the central nervous system. They are involved in the regulation of growth processes, reproduction, social behavior, emotion/motivation and cognition. Particularly in subcortical structures, neuropeptides act as neuromodulators, which reach their target sites via diffusion through the extracellular space. This route of information transfer together with the ability of neurons to release neuropeptides from their whole membrane surface predisposes neuropeptides for microdialysis experiments. This review outlines the special characteristics of neuropeptide signaling in relation to other classes of neuromessengers. It further provides a survey of the application of the microdialysis technique for monitoring neuropeptide release patterns in laboratory rodents exemplarily for the two neuropeptides arginine vasopressin and oxytocin, discusses pros and cons of such experiments and outlines perspectives for future neuroendocrine studies in rats and mice.


Illustrating How to Use the Validated Alsayed_v1 Tools to Improve Medical Care: A Particular Reference to the Global Initiative for Asthma 2022 Recommendations.
The current research aimed to illustrate a real case using the validated Alsayed_v1 tools as tutorial training to improve the knowledge and skills of healthcare practitioners in the clinical problem-solving process necessary to implement medical and pharmaceutical care. The Alsayed_v1 instruments consist of principal components: data collection, assessment of treatments, the medical problem oriented plan (MPOP), as well as a care plan and patient education. This study illustrated a real case of asthma patient using the validated Alsayed_v1 tools. These validated and clinically tested tools provide a coding system for the MPOP that permits easy documentation with an open hierarchical structure where higher levels are broad and lower levels are particular, and the possibility to enter free text. The section dedicated to treatment assessments is intended to synthesize patient information to facilitate the identification of the MPOPs. Effective management requires the development of a partnership between the patient with asthma (or the patient's caregivers) and his healthcare professional(s). This partnership aims to allow the patient to control his condition with guidance from the healthcare professional(s), discuss and agree on therapy goals, and develop a personalized, written, self-management asthma care plan. By implementing Alsayed_v1 tools, the clinical practitioner can actively give the best practice for optimal patient outcomes.


Tracing the source of difficult to settle fine particles which cause turbidity in the Hitotsuse Reservoir, Japan.
A unique method to trace the source of "difficult-to-settle fine particles," which are a causative factor of long-term turbidity in reservoirs was developed. This method is characterized by cluster analysis of XRD (X-ray diffraction) data and homology comparison of major component compositions between "difficult-to-settle fine particles" contained in landslide soil samples taken from the upstream of a dam, and suspended "long-term turbid water particles" in the reservoir, which is subject to long-term turbidity. The experiment carried out to validate the proposed method, demonstrated a high possibility of being able to make an almost identical match between "difficult-to-settle fine particles" taken from landslide soils at specific locations and "long-term turbid water particles" taken from a reservoir. This method has the potential to determine substances causing long-term turbidity and the locations of soils from which those substances came. Appropriate countermeasures can then be taken at those specific locations.


Social support and health status in spinal cord injury.
In a mailed survey, 125 persons with spinal cord injury responded to questions on the SCI Quality of Life Index (QOLI), and the Reciprocal Social Support Scale. The results indicated that people with SCI who believe that they receive support from the community, compared to those who believed they received less support (1) perceived themselves to be better adjusted to their injury, and (2) had significantly fewer health problems (fewer spinal cysts, lower blood pressure, shorter recovery time from decubitus ulcers, less pain below the level of injury, and fewer hospital admissions). The results also showed that people who believe that they contribute to the community in some way, compared to those who believed they contributed little or nothing (1) perceived themselves to be better adjusted to their injury, and (2) had significantly fewer health problems (fewer urinary tract infections, fewer decubitus ulcers, less severe decubiti, less pain above the level of injury, and fewer hospital admissions). A community support score, a summary score of support given and received, was also related to adjustment and health.


Antitumor efficacy of AAV-mediated systemic delivery of interferon-beta.
Type I interferons (alpha/beta) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. An alternative dosing schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while maintaining its antitumor efficacy. We have tested a gene therapy approach in murine tumor models to treat malignancies that have shown responsiveness to interferon in clinical trials. The tumor cell lines used were moderately sensitive to the direct effects of human interferon-beta (hIFN-beta) in vitro. For in vivo testing, systemic delivery of hIFN-beta was generated following liver-targeted delivery of adeno-associated virus (AAV) vector carrying the hIFN-beta transgene. This prevented engraftment of subcutaneous human gliomas, and orthotopic, localized (intrarenal) and disseminated (primarily pulmonary) human renal cell carcinomas; and caused regression of established tumors at these sites. In a syngeneic, immunocompetent model of melanoma, AAV IFN-beta treatment limited subcutaneous tumor growth and prevented disseminated disease. A significant decrease in mean intratumoral vessel density was demonstrated in hIFN-beta-treated tumors, suggesting that in addition to a direct tumoricidal effect, the antitumor efficacy of AAV IFN-beta in this study was due to its ability to inhibit angiogenesis.


Quality of vision in endoscopy in the midst of a pandemic: Does PPE influence quality of vision during gastrointestinal endoscopy?
In the midst of the SARS-CoV-2 virus (COVID-19) pandemic, health professionals, specifically gastroenterologists, have had to use personal protective equipment (PPE) to reduce contact with droplets and aerosols generated during gastrointestinal endoscopy. To evaluate the impact of the use of two types of PPE on quality of vision during gastrointestinal endoscopy. A cross-sectional observational pilot study in gastroenterologists who undergo an ophthalmological examination of visual acuity and quality of vision when using two types of PPE. Type #1: 3M N95 1860 green respirator + 3M mono safety glasses + protective screen. Type #2: 3M 6800 full facepiece + 3M NIOSH 7093C HF/P100 filters. Visual acuity and quality of vison parameters while using the PPE that is routinely used when performing gastrointestinal endoscopy during the pandemic were evaluated. It was found that Modality #1 was associated with decreases of up to 37% in visual acuity, 25% in colour visualisation and 75% in contrast sensitivity among digestive endoscopists within minutes of placement. These figures worsened over the course of the procedure, rising to 75%, 60% and 100%, respectively. Modality #2 was not associated with any deterioration in quality of vision. The different PPE modalities used during gastrointestinal endoscopy could have an impact on the quality of endoscopy studies performed during the SARS-CoV-2 (COVID-19) pandemic.


Rigid congeners of arylpyridazinones. IV. Synthesis and activity of derivatives of the new heterocyclic system 9H-indeno[2,1-c]pyridazine.
Representative terms of the new heterocyclic system 9H-indeno[2,1-c]pyridazine have been synthesized. Their antiinflammatory, analgesic and antipyretic activities were evaluated, in order to compare the pharmacological profiles with those of the isomeric series of 5H-indeno[1,2-c]pyridazine previously investigated. The new compounds were, in general, equiactive as analgesic but less active as antiinflammatory and antipyretic agents with respect to their 5H-isomers.


Discovery of renin inhibitors containing a simple aspartate binding moiety that imparts reduced P450 inhibition.
Discovery of potent renin inhibitors which contain a simplified alkylamino Asp-binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified.


New trends in immunocastration and its potential to improve animal welfare: a mini review.
Castration is frequently used to reduce aggressive behavior and improve the meat quality of animals. Traditionally, surgical and mechanical castration are used to sterilize the animals, but these approaches are associated with a high level of pain, stress, long recovery periods, and post-operative infections. Immunocastration is a new animal-friendly, painless alternative castration technique that is used to prevent undesired sexual behavior, reduce aggressive behavior, prevent unwanted pregnancy, control wildlife populations and wandering species, enhance growth performance, improve meat quality, and treat various sex hormone-dependent disorders. The mechanism of immunocastration includes the immunological block of the hypothalamic-pituitary-gonadal axis (HPG axis) which inhibits gonadotropin secretions, causes atrophy of gonadal tissues, and inhibits gametogenesis, resulting in infertility in both female and male mammals. By the mid-1990s, various immunocastration vaccines have been tested in different animal models to achieve successful castration effects. Recently, genetic immunocastration especially DNA vaccine has gained increasing attention due to its safety, being animal-friendly, and being easy to use. This review aims to evaluate the potential of traditional castration methods, as well as the current status of immunocastration vaccines, their effects, and future prospective.


Two-Stage Biventricular Repair of Complex Aortic Atresia.
We describe the successful 2-stage treatment of an infant with double-outlet right ventricle, aortic valve atresia, normally related great vessels, muscular outlet ventricular septal defect, and ductal arch origin of the cephalic vessels using a hybrid ductal stent and branch pulmonary artery banding followed by a comprehensive Yasui-type biventricular repair.


Evaluation of Preoperative Tamsulosin Role in Facilitating Ureteral Orifice Navigation for School-Age Pediatric Ureteroscopy.
To address whether preoperative tamsulosin increases the rate of successful ureteral orifice navigation for ureteroscopy (URS) without prestenting in school-age pediatric patients. We retrospectively reviewed all pediatric patients who had undergone ureteroscopy (URS) at our institution from 2013 to 2020. Patients were divided into two groups: those who had received tamsulosin 0.4 mg daily ≥48 hours preoperatively and those who had not. Statistical analysis was done using independent-sample t-tests and Mann-Whitney U tests for continuous variables, and χ2 and Fisher's exact tests were used for categorical variables. Multivariate analysis was done using binary logistic regression test. Overall, successful ureteral orifice navigation occurred in 44 of 50 patients (88%) who had received tamsulosin and 17 of 26 (65.4%) who had not (p=0.019). On further subanalysis based on stone location and instrumentation used, successful ureteral orifice navigation had occurred in 21 of 24 patients (87.5%) in the tamsulosin group and one of five (20%) in the no-tamsulosin group for semirigid ureteroscopy for mid-distal ureterolithiasis (p=0.007). For proximal ureteral and renal stones, successful ureteral orifice navigation with a flexible ureteroscope or ureteral access sheath had occurred in 23 of 26 patients (88.5%) in the tamsulosin group and 16 of 21 (76.2%) in the no-tamsulosin group (p=0.437). Multivariate analysis showed no significant difference between success rates in the two groups after controlling for patient weight, height, BMI, and stone location. We did not observe any adverse effects from tamsulosin. This is the first study to evaluate preoperative tamsulosin on successful ureteral orifice navigation in school-age pediatric patients. Although not reaching statistical significance, further evaluation should be done on larger cohorts. Patient height was found to be an independent predictor of successful ureteral orifice navigation.


Association between COVID-19 and Male Fertility: Systematic Review and Meta-Analysis of Observational Studies.
Whether COVID-19 reduces male fertility remains requires further investigation. This meta-analysis and systematic review evaluated the impact of COVID-19 on male fertility. The literature in PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library up to January 01, 2022 was systematically searched, and a meta-analysis was conducted to investigate the effect of COVID-19 on male fertility. Totally 17 studies with a total of 1,627 patients and 1,535 control subjects were included in our meta-analysis. Regarding sperm quality, COVID-19 decreased the total sperm count (p=0.012), sperm concentration (p=0.001), total motility (p=0.001), progressive sperm motility (p=0.048), and viability (p=0.031). Subgroup analyses showed that different control group populations did not change the results. It was found that during the illness stage of COVID-19, semen volume decreased, and during the recovery stage of COVID-19, sperm concentration and total motility decreased <90 days. We found that sperm concentration and total motility decreased during recovery for ≥90 days. Fever because of COVID-19 significantly reduced sperm concentration and progressive sperm motility, and COVID-19 without fever ≥90 days, the sperm total motility and progressive sperm motility decreased. Regarding disease severity, the moderate type of COVID-19 significantly reduced sperm total motility, but not the mild type. Regarding sex hormones, COVID-19 increased prolactin and estradiol. Subgroup analyses showed that during the illness stage, COVID-19 decreased testosterone (T) levels and increased luteinizing hormone levels. A potential publication bias may have existed in our meta-analysis. COVID-19 in men significantly reduced sperm quality and caused sex hormone disruption. COVID-19 had long-term effects on sperm quality, especially on sperm concentration and total motility. It is critical to conduct larger multicenter studies to determine the consequences of COVID-19 on male fertility.


The effect of aspirin on bleeding after extraction of teeth.
Acetylsalicylic acid (ASA) generically known as aspirin is used clinically as an analgesic, antipyretic, anti-inflammatory and as a medication to prevent platelet aggregation. Many studies have investigated bleeding associated with ASA. The aim of this study was to determine if ASA was associated with bleeding after dental extraction. One hundred and eighty-nine subjects were divided into four groups. Group 1A subjects who received ASA, underwent simple extraction. Group 1B subjects who received ASA, underwent surgical extraction. Group 2A subjects who did not receive ASA, underwent simple extraction which served as control group. Group 2B subjects who did not receive ASA, underwent surgical extraction which also served as control group. The results showed that Group 1B was the only group which showed bleeding after 24 h. All groups had similar results after 48 h and 5 days post-operatively. The study concluded that subjects who received 81 mg ASA daily could undergo dental extraction without bleeding risks.


Computational fluid dynamics and NOSE scale to assess nasal respiratory function, and correlation with linear maxillary measurements after surgically assisted rapid maxillary expansion.
Nasal obstruction is common in patients with a transverse maxillary deficiency. The aim of this study was to determine the variation in nasal airway resistance in adult patients with a transverse maxillary deficiency before and after surgically assisted rapid maxillary expansion (SARME) by computational fluid dynamics (CFD) using computed tomography scans, and to correlate this variation with maxillary linear measurements obtained by means of plaster models. The subjective symptoms of nasal obstruction were also analysed using a visual analogue scale (VAS) for nasal breathing and the Nasal Obstruction Symptom Evaluation (NOSE) scale. There was a median reduction of 21% in nasal airway resistance post SARME (P = 0.002). The NOSE scale score decreased (P < 0.001) and nasal breathing quality VAS scores increased in both nostrils (P < 0.001). Transverse measurements between the upper canines (C-C), premolars (PM-PM), and molars (M-M), and maxillary perimeter showed significant increases (P < 0.001), while the anteroposterior maxillary arch length showed a significant decrease (P = 0.016). An inverse proportional correlation was found between PM-PM and nasal airway resistance (r = -0.395; P = 0.034) and between M-M and nasal airway resistance (r = -0.383; P = 0.040). These results demonstrate that surgically expanding the posterior region of the maxilla results in decreased nasal airway resistance, decreased obstructive symptoms, and improved patient respiratory quality.


Antimony release from polyester textiles by artificial sweat solutions: A call for a standardized procedure.
Polyester fibres are usually contaminated by antimony because of its use as a catalyst in the production of polyethylene terephthalate and as a flame retardant synergist in a variety of new and recycled polymers. The present study determined the release of antimony (at total concentrations ranging from about 125 to 470 μg g-1) from polyester textile samples designed to be in contact with human skin using standard artificial sweat solutions (ISO 105-E04 and EN 1811). The study also examined the role of different experimental parameters on the release of the metalloid. Overall, and using the default parameters, between about 0.05 and 2% of total antimony (or 0.1-1 μg g-1) was mobilized into artificial sweat. A reduction in time (from 24 to 12 h) and temperature (from 37 to 20 or 4 °C) and an increase in pH (from 5.5 to 7) resulted in a decline in antimony mobilization from textiles, while altering textile mass to solution volume and the presence of lactate had little impact on the results. Removal of a filtration step increased antimony mobilization but this was attributed to artefacts associated with release from microfibres during extract storage and analysis. In general, antimony mobilization was sufficiently repeatable using either EN 1811 or ISO 105-E04 but the latter is recommended for an assessment of antimony mobilization and potential exposure because its pH is closer to that of human sweat. Since the first fraction of either extractions mobilized the greatest quantity of antimony, exposure can be minimized by washing articles before use.


Extensive investigation of the sap flow of maize plants in an oasis farmland in the middle reach of the Heihe River, Northwest China.
A better understanding of the sap flow characteristics of maize plants is critical for improving irrigation water-use efficiency, especially for regions facing water resource shortages. In this study, sap flow rates, related soil-physics and plant-growth parameters, and meteorological factors, were simultaneously monitored in a maize field in two consecutive years, 2011 and 2012, and the sap flow rates of the maize plants were extensively analyzed based on the monitored data. Seasonal and daily variational characteristics were identified at different growth stages and under different weather conditions, respectively. The analyses on the relationships between sap flow rate and reference evapotranspiration (ET0), as well as several plant-growth parameters, indicate that the irrigation schedule can exert an influence on sap flow, and can consequently affect crop yield. The ranking of the main meteorological factors affecting the sap flow rate was: net radiation > air temperature > vapor pressure deficit > wind speed. For a quick estimation of sap flow rates, an empirical formula based on the two top influencing factors was put forward and verified to be reliable. The sap flow rate appeared to show little response to irrigation when the water content was relatively high, implying that some of the irrigation in recent years may have been wasted. These results may help to reveal the bio-physical processes of maize plants related to plant transpiration, which could be beneficial for establishing an efficient irrigation management system in this region and also for providing a reference for other maize-planting regions.


Synthesis of hydantoins via N,N'-ureas derived from polymer-bound amino acids.
Starting from carboxy-linked amino acids on trityl functionalized polystyrene resin a highly efficient solid-phase synthesis of hydantoins via N,N'-ureas was elaborated. The polymer-bound hydantoins can be used as a scaffolds for further combinatorial transformations, such as alkylation. Cleavage from the resins yielded the corresponding hydantoins in good yields and purities as shown by ESI-MS and HPLC.