Removal of hexavalent chromium in dual-chamber microbial fuel cells separated by different ion exchange membranes.
An ion exchange membrane (IEM) is an important component in dual-chamber microbial fuel cells (MFCs) to separate cathodic chromium from anode bacteria to avoid toxicity. Common used IEMs (e.g., BPM, CEM, PEM, AEM) have different ionic transfer abilities which could influence MFC performance and chromium removal. Additionally, to distinguish chromium "removal" or "reduction" by MFCs, the chromium removal in this study was further analyzed into cathodic reduction, adsorption on the membrane and permeation through membrane to the anode chamber. It was found that BPM achieved the best performance in removing hexavalent chromium (99.4 ± 0.2 %) and balancing pH and conductivity in both chambers, followed by AEM (97.9 ± 0.8 %) and CEM (95.6 ± 0.8 %), while PEM can not well maintain pH and conductivity leading to the worst anode performance and lowest chromium removal efficiency. However, the adsorption of chromium on the AEM accounts for 91.1 ± 0.7 %, which was much higher than the other three membranes. The permeation of chromium through the membrane were all lower than 0.2% which can be ignored. SEM and EDS results showed that chromium deposits and bacteria were detected on the membrane facing cahtode and anode, respectively, indicating that membrane scaling and fouling were inevitable and happened within 24 h operation.


Urethral caruncle in an unusual location occurring in prepubertal girl.
Urethral caruncles are the most frequent benign tumors of the female urethra; the great majority occur after the menopause. Caruncles in prepubertal girls are quite rare and location other than the posterior lip of the urethra is quite rare too. In this paper we report a case with these rare properties.


Plant cell polarity: sterols enter into action after cytokinesis.
In yeast and animal cells, the sterol composition of membranes is a key factor that controls the polarity of membrane proteins by regulating their intracellular trafficking or lateral diffusion. A recent study in Nature Cell Biology demonstrates that plant sterols play a major role in the acquisition of cell polarity by modulating endocytosis after cell division.


Carotid-Anterior Cerebral Artery Anastomosis Associated with Paraclinoid Aneurysm and Ophthalmic Artery Originating From Middle Meningeal Artery: Case Report and Consideration of Terminology.
We summarized 63 cases of anterior cerebral artery (ACA) anomaly with an infraoptic course reported in the literature including abstracts written in English. All cases were reported individually, with a maximum of 3 cases. This report describes our findings in another case and opinions regarding the terminology. A 78-year-old woman presented with subarachnoid hemorrhage. A carotid angiogram showed a right paraclinoid aneurysm with an anomaly of the ACA. The right ACA originated from the internal carotid artery at the level of the ophthalmic segment intradurally with an infraoptic course. The right ophthalmic artery originated from the ipsilateral middle meningeal artery. We performed an emergent endovascular coil embolization with balloon assistance, and the patient recovered well. Use of the terminology "infraoptic course of the ACA" versus "carotid-ACA anastomosis" was discussed. Based on the literature reports, at least one third of the cases have a normal-positioned ACA rather than the infraoptic ACA. Also, based on embryogenesis, it is thought that the infraoptic ACA is not a misplaced A1 segment, but rather persistence of an embryologic vessel. Therefore, based on the literature and embryology, we prefer the term "carotid-ACA anastomosis" rather than "infraoptic ACA." However, as a morphologic and positional description, the term "infraoptic ACA" has value. To the best of our knowledge, the present case of a carotid-ACA anastomosis associated with a paraclinoid aneurysm and ophthalmic artery originating from the middle meningeal artery is the first to appear in the literature.


Development of a liquid chromatography-tandem mass spectrometry method for the analysis of docetaxel-loaded Poly(lactic-co-glycolic acid) nanoparticles.
Docetaxel is among the most effective chemotherapeutic agents used for the treatment of solid tumors, such as breast cancer. Targeting docetaxel to the tumor site would increase the safety and efficacy of the treatment. The focus of this work was to develop an efficient liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify docetaxel entrapped in optimized poly lactic-co-glycolic acid (PLGA) nanoparticles. Several nanoparticle formulations were prepared to optimize the nanoparticles based on their size and yield percentage using a modified solvent evaporation technique. The MS/MS fingerprints of docetaxel and paclitaxel (as internal standard) were used to identify diagnostic product ion for developing a multiple reaction monitoring (MRM) LC-MS/MS method for the quantification of docetaxel in the PLGA nanoparticles. A triple quadrupole linear ion trap instrument (AB Sciex 4000 QTRAP) equipped with electrospray ionization was used. The optimized nanoparticles had a zeta potential of -23.2 ± 1.4 mV and mean particle sizes of 202.2 ± 4.7 nm and 251.7 ± 8.2 nm before and after freeze-drying, respectively. Polydispersity index values of the nanoparticles confirmed their uniform size distribution. The developed LC-MS/MS method could quantify docetaxel in the PLGA matrix with accuracy and precision covering a broad linear range of 15.6-4000 ng/mL. Method validation was conducted using the regulatory guidelines of the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and showed acceptable values for all the tested criteria. The developed LC-MS/MS method with the novelty of using a phenyl column will be beneficial for future analysis of docetaxel loaded polymeric nano-delivery systems.


Designing and validating a research questionnaire - Part 1.
Questionnaires are often used as part of research studies to collect data from participants. However, the information obtained through a questionnaire is dependent on how it has been designed, used, and validated. In this article, we look at the types of research questionnaires, their applications and limitations, and how a new questionnaire is developed.


Edge-to-Center Propagation of Photochemical Reaction during Single-Crystal-to-Single-Crystal Photomechanical Transformation of 2,5-Distyrylpyrazine Crystals.
Photomechanical molecular crystals are promising materials for photon-powered artificial actuators. To interpret the photomechanical responses, the spatiotemporal distribution of photoproducts in crystals could be an important role in addition to molecular structures, molecular packings, illumination conditions, crystal morphology, crystal size, and so on. In this study, we have found that single crystals of 2,5-distyrylpyrazine show a smooth single-crystal-to-single-crystal photomechanical expansion, and the photochemical reaction propagates from the edge to the center of the single crystal. We revealed that the surface effect (special reactivity at the crystal surface) in addition to the cooperative effect (the reaction is facilitated by neighboring molecules) is essential for the edge-to-center propagation of the photochemical reaction. Our results would provide a foundation for future studies of the photochemical reaction dynamics in photomechanical molecular crystals.


Sulforaphane response on aluminum-induced oxidative stress, alterations in sperm characterization and testicular histomorphometry in Wistar rats.
The exposure of male individual to environmental toxicant is regarded as a channel that results in reduced sperm counts and infertility. This study investigated the ameliorative response of Sulforaphane (SFN) on Aluminum trichloride (AlCl 3 ) induced testicular toxicity in adult male Wistar rats. A total of 32 adult male Wistar rats (180-200 gm between 8-10 wk) were divided into four groups (n = 8/each). Group A) received distilled water orally as placebo; Group B) received 100 mg/kgbw AlCl 3 only orally; Group C) received 100 mg/kgbw AlCl 3 and 100 mg/kgbw SFN orally; and Group D) received 100 mg/kgbw SFN only orally. After 28 days of experiment, animals underwent cervical dislocation, blood serum was obtained for analysis, and testes were harvested for biochemical assays, histology, hormonal profile, and sperm characterization. The sperm parameters showed a significant difference within the AlCl 3 only group compared with the control and SFN only groups (p = 0.02). However, AlCl 3 and SFN co-treatment showed improvement in the motility, viability, and sperm count compared with the AlCl 3 only group (p = 0.02). Furthermore, there was a significant decline in the levels of hormones profile and antioxidant status in AlCl 3 only group compared to the control and SFN only (p = 0.02). The testicular histoarchitecture of the AlCl 3 only group showed shrinkage of seminiferous tubules, spermatogenesis disruption, and empty lumen compared to the control and SFN only groups. The present study revealed the ameliorative response of SFN on AlCl 3 -induced testicular toxicity on serum hormone profiles, antioxidant status, lipid peroxidation, and histomorphometric analysis through oxidative stress.


Characterization of the complete mitochondrial genomes of Diplodiscus japonicus and Diplodiscus mehari (Trematoda: Diplodiscidae): Comparison with the members of the superfamily Paramphistomoidea and phylogenetic implication.
Diplodiscus japonicus and Diplodiscus mehari (Trematoda: Diplodiscidae) are two important parasites in wood frogs, which have large infection rates and essential importance of ecology, economy and society. In this study, the complete mitochondrial (mt) genomes of D. japonicus and D. mehari were sequenced, then compared with other related trematodes in the superfamily Paramphistomoidea. The complete circular mt sequence of D. japonicus and D. mehari were 14,210 bp and 14,179 bp in length, respectively. Both mt genomes comprised 36 functional subunits, consisting of 12 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one non-coding region. The mt genes of D. japonicus and D. mehari were transcribed in the same direction, and the gene arrangements were identical to those of Paramphistomoidea trematodes. In the 12 PCGs, GTG was the most common initiation codon, whereas TAG was the most common termination codon. All tRNAs had a typical cloverleaf structure except tRNA Ser1. A comparison with related Paramphistomoidea trematode mt genomes suggested that the cox1 gene of D. mehari was the longest in these trematodes. Phylogenetic analyses revealed that Paramphistomoidea trematodes formed a monophyletic branch, Paramphistomidae and Gastrothylacidae were more closely related than Diplodiscidae. And the further analysis with Pronocephalata branch found that the flukes parasitic in amphibians (frogs) formed one group, and the flukes from ruminants (cattle, sheep, ect) formed another group. Our study demonstrated the importance of sequencing mt genomes of D. japonicus and D. mehari, which will provide significant molecular resources for further studies of Paramphistomoidea taxonomy, population genetics and systematics.


[X-linked adult onset adrenoleukodystrophy. A case report].
The authors report a case of an X-linked-adrenoleukodystrophy (ALD) in a young adult presenting with hemianopsia. Adult onset cerebral ALD is rare and represents only 3% of cases of ALD. The observation describes clinical data, as well as conventional and spectroscopic MR imaging and related value in prognosis evaluation.


Laparoscopic uterine anastomosis for traumatic separation of the cervix from the uterine corpus caused by closed pelvic fracture: case report and literature review.
Primary amenorrhea caused by separation of the cervix from the uterine body resulting from pelvic trauma is exceptionally rare. This case report describes the diagnosis and successful laparoscopic approximation of traumatic separation of the cervix from the uterine corpus. A 16-year-old girl who was involved in a car accident at age 2 years had primary amenorrhea and cyclic abdominal pain. A closed pelvic fracture was managed nonsurgically, with an uneventful recovery. Since age 13 years, the patient has been experiencing cyclic abdominal pain. Ultrasonography suggested a 5-cm left adnexal mass. Diagnostic laparoscopy revealed complete separation of the uterine corpus from the cervix, and an endometrioma in the left ovary. The uterine corpus was approximated to the cervix with circumferentially placed sutures under direct laparoscopic guidance. The endometrioma was resected concomitantly. Normal cyclic menstruation resumed 2 months postoperatively, without cyclic abdominal pain. This case report demonstrates successful laparoscopic approximation of traumatic separation of the uterine corpus from the cervix, manifested as primary amenorrhea.


Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8- to 9-year-old children: A prospective observational study.
Glucocorticoid (GC) -induced fetal programming of the activity of the hypothalamus-pituitary-adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood. Prospective observational study in 31 children whose mothers received single (n = 19) or multiple (n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+6 weeks of gestation) compared with 38 non-exposed, age-matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention-deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG). There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM-exposed children had lower IQ scores than the unexposed group. BM-exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose-response relation between BM exposure and activity of the ANS and IQ was estimated in post-hoc analyses. Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life-saving therapy, but its prescription may warrant a well-balanced risk-benefit assessment.


The roles of RNA N6-methyladenosine in esophageal cancer.
Esophageal cancer is a malignant tumour with a high degree of malignancy and high mortality. Its pathogenesis and treatment strategy remain unclear. N6-methyladenosine (m6A) is important for various biological functions in RNA modification and is currently being investigated extensively. It plays an essential role in RNA modification. m6A modification is a dynamic process that reversibly regulates the target RNA through its regulatory factors and plays an important role in several diseases, especially cancer. However, the role of m6A in esophageal cancer remains elusive. RNA modification and splicing are regulated by RNA methylation regulators called 'writers' (methyltransferases), 'erasers' (demethylases) and 'readers' (modified RNA-binding proteins). These regulatory factors recognise and bind to RNA methylation sites, regulate biological functions such as RNA splicing and translation and influence the occurrence, development, invasion and metastasis of tumours. Considering the importance of m6A modification, we reviewed the regulatory mechanisms, biological functions and therapeutic prospects of m6A RNA methylation regulators in esophageal cancer.


Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats.
Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo-2'-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the significant increase in the number of BrdU-positive cells in DG. However, acupuncture at acupoint ST36, near the knee joint, produced no increase in the number of BrdU-positive cells. These findings indicate that acupuncture at acupoint HT7 appears to stimulate cell proliferation, and we suggested that acupuncture may be useful in the treatment of diseases related to maternal separation.


Maternal-fetal medicine specialist density is inversely associated with maternal mortality ratios.
Our study's objective was to determine the relationship between state-specific maternal mortality ratios and the density of maternal-fetal medicine specialists. State maternal mortality ratios from 1994 to 2001 were calculated from the Centers for Disease Control and Prevention WONDER database. Practitioner distribution data were obtained from professional associations. Demographic information regarding states was gathered from the 2000 US census data. Bivariable and multivariable analyses were conducted with the use of Spearman correlations and Poisson regression, respectively. The median state maternal-mortality ratio was 7.5/100,000 live births. Our study showed that an increase of 5 maternal-fetal specialists per 10,000 live births results in a 27% reduction in the risk of maternal death (relative risk [RR] = 0.73, 95% CI = 0.58-0.93, P = 0.012). This risk reduction was based on a multivariable Poisson regression model that included the following variables and their significant interactions: state-specific percentages of mothers in poverty, mothers without a high school diploma, minority mothers, and teenage mothers. The density of maternal-fetal medicine specialists is significantly and inversely associated with maternal mortality ratios, even after controlling for state-level measures of maternal poverty, education, race, age, and their significant interactions.


Posterior tibial slope changes after opening- and closing-wedge high tibial osteotomy: a comparative prospective multicenter study.
Valgus high tibial osteotomy is considered to be an effective treatment for unicompartmental medial osteoarthritis. It is generally admitted that tibial slope increases after open-wedge high tibial osteotomy and decreases after closing-wedge high tibial osteotomy. However, the effects on posterior tibial slope of closing- or opening-wedge osteotomies remain controversial. We analyzed the modifications of tibial slope after opening- and closing-wedge high tibial osteotomies and compared the results of these two procedures. We hypothesized that there was no difference in postoperative tibial slope between opening and closing-wedge osteotomies. This prospective consecutive nonrandomized multicenter study was conducted between January 2008 and March 2009 and included 321 patients: 205 men and 116 women. A total of 224 patients underwent an opening-wedge high tibial osteotomy and 97 a closing-wedge osteotomy. The mean age was 52 years ± 9 and the mean body mass index was 28kg/m(2) ± 5. The main etiology was primary arthritis. Posterior tibial slope was measured preoperatively and at the last follow-up on a lateral radiograph in relation to the posterior tibial cortex. In the opening-wedge group, a definite 0.6° increase in tibial slope (P=0.016) was observed. In the closing-wedge group, a definite 0.7° decrease in tibial slope (P=0.02) was found. Fourteen percent of the opening-wedge osteotomies increased tibial slope by 5° or more versus only 2% of the closed-wedge osteotomies (P<0.001). Twelve percent of the closing-wedge high tibial osteotomies led to a decrease of 5° or more of the tibial slope versus 7% of the opening-wedge osteotomies (P<0.02). These results confirm what is generally reported in the literature, i.e., an increase in tibial slope in opening-wedge high tibial osteotomy and a decrease in the slope in closing-wedge osteotomies. These tibial slope changes appear to be very limited in this series, less than 1° on average. However, there was a bias since the open-wedge technique was preferred in cases with substantial varus deformity. We emphasize the importance of surgical technique to avoid alteration of the tibial slope, particularly in opening-wedge high tibial osteotomy for which we recommend a release of posterior soft tissue and a complete osteotomy of the posterior cortex of the tibia. III. Prospective consecutive nonrandomized multicenter study.


Modification of radiosensitivity and recovery from X ray damage in vitro by retinoic acid.
We studied the effects of all-trans retinoic acid (RA) combined with X-irradiation on confluent cultures of human breast cancer (MCF-7) and melanoma (C-143) cell lines, as well as in a normal human diploid fibroblast strain (AG 1522). RA in non-cytotoxic concentrations was a potent inhibitor of confluent holding recovery of potentially lethal damage (PLD repair) for all three cell types. A complete inhibition of recovery was observed at lower RA concentrations in the tumor lines than in the fibroblast strain. Exposure to RA prior to and during irradiation resulted in a radiosensitizing effect that was similar in MCF-7 and AG 1522 cells. The implications of these findings are discussed in terms of the potential value of retinoids as biological response modifiers for the clinical radiotherapy of cancer.


ATG4B (Autophagin-1) phosphorylation modulates autophagy.
Autophagy is a catabolic cellular mechanism for entrapping cellular macromolecules and organelles in intracellular vesicles and degrading their contents by fusion with lysosomes. Important roles for autophagy have been elucidated for cell survival during nutrient insufficiency, eradication of intracellular pathogens, and counteracting aging through clearance of senescent proteins and mitochondria. Autophagic vesicles become decorated with LC3, a protein that mediates their fusion with lysosomes. LC3 is a substrate of the cysteine protease ATG4B (Autophagin-1), where cleavage generates a C-terminal glycine required for LC3 conjugation to lipids in autophagosomes. ATG4B both cleaves pro-LC3 and also hydrolyzes lipids from cleaved LC3. We show here that phosphorylation of ATG4B at Ser-383 and Ser-392 increases its hydrolyase activity as measured using LC3 as a substrate. Reconstituting atg4b(-/-) cells with phosphorylation-deficient ATG4B showed a role of ATG4B phosphorylation in LC3 delipidation and autophagic flux, thus demonstrating that the cellular activity of ATG4B is modulated by phosphorylation. Proteolytic conversion of pro-LC3 to LC3-I was not significantly impacted by ATG4B phosphorylation in cells. Phosphorylation-deficient ATG4B also showed reduced interactions with the lipid-conjugated LC3 but not unconjugated LC3. Taken together, these findings demonstrate a role for Ser-383 and Ser-392 phosphorylation of ATG4B in control of autophagy.


Protective immune response to Mycoplasma gallisepticum demonstrated in respiratory-tract washings from M. gallisepticum-infected chickens.
Chickens inoculated with Mycoplasma gallisepticum (MG) produced IgA, IgM, and IgG detectable in washings from the upper respiratory tract (URTW; nasal sinuses and turbinates) and lower respiratory tract (LRTW; trachea, lungs, and air sacs). URTW and LRTW from infected chickens had significant protective effects in a MG-inoculated tracheal-ring-organ-culture system. Protective effects in vitro correlated positively with total MG-specific immunoglobulin titer, but not IgA titer, as determined by enzyme-linked immunosorbent assay. URTW and LRTW from infected chickens inhibited attachment of MG to tracheal-ring-organ cultures in a dose-dependent manner. This suggests that chickens produce a protective immune response to MG that locates in the respiratory tract and that attachment inhibition may be responsible for this protective effect.


Determination of DC-SIGN and DC-SIGNR repeat region variations.
DC-SIGN and DC-SIGNR efficiently bind HIV-1 and other viral as well as nonviral pathogens and assist either cis or trans infection. Both are type II transmembrane proteins that consist of an N-terminal cytoplasmic domain, a repeat region consisting of seven 23-amino-acid tandem repeats, and a C-terminal C-type carbohydrate recognition domain that binds mannose-enriched carbohydrate modifications of host and pathogen proteins. The normal functions of DC-SIGN and DC-SIGNR include binding to ICAM-2 and ICAM-3. Binding of DC-SIGN to ICAM-2 on endothelial cells facilitates chemokine-induced dendritic cell extravasation; binding to ICAM-3 on T lymphocytes provides the initial step for establishing cell-mediated immunity. Based on the number of tandem repeats, DC-SIGNR is highly polymorphic in the repeat region, while variations in DC-SIGN repeat region are rare. A change in the number of DC-SIGN and DC-SIGNR repeats may influence their normal functions as well as their binding capacity to viral and nonviral pathogens. This chapter describes the methods for detection of DC-SIGN and DC-SIGNR repeat region variations by polymerase chain reaction.


The 3D structure of the defense-related rice protein Pir7b predicted by homology modeling and ligand binding studies.
To better understand the ligand-binding mechanism of protein Pir7b, important part in detoxification of a pathogen-derived compound against Pyricularia oryzae, a 3D structure model of protein Pir7b was constructed based on the structure of the template SABP2. Three substrates were docking to this protein, two of them were proved to be active, and some critical residues are identified, which had not been confirmed by the experiments. His87 and Leu17 considered as 'oxyanion hole' contribute to initiating the Ser86 nucleophilic attack. Gln187 and Asp139 can form hydrogen bonds with the anilid group to maintain the active binding orientation with the substrates. The docking model can well interpret the specificity of protein Pir7b towards the anilid moiety of the substrates and provide valuable structure information about the ligand binding to protein Pir7b.


Genetic origin of IgG antibodies cloned by phage display and anti-idiotypic panning from three patients with autoimmune thrombocytopenia.
The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of patients with autoimmune thrombocytopenic purpura (AITP) has been proven. AITP is a severe disease in children with a still unknown etiology. It is not clear how IVIG functions in this and other autoimmune diseases. To analyze and compare patient-derived monoclonal IgG antibodies that are bound by IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients with AITP, a large number of clones specifically reacting with IVIG molecules were enriched. The heavy and light chain variable regions were sequenced and compared with each other and with databases. Many variable regions showed extensive replacement mutations within the complementarity-determining regions, while two were identical to germ-line genes. Our data show that the most frequently used germ-line gene loci of these IVIG binders are identical to those observed for many other autoantibodies. This implicates a specific interaction of IVIG particularly with autoantibodies and B cell receptors derived from germ-line genes that are often used for the generation of autoantibodies.


The GLIM criteria for defining malnutrition can predict physical function and prognosis in patients with cardiovascular disease.
The Global Leadership Initiative on Malnutrition (GLIM) published a new international standard for defining malnutrition in 2018. The GLIM criteria were compared with the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria in relation to physical function and mortality risk in patients with cardiovascular disease (CVD). A total of 921 CVD patients ≥ 20 years old (67.8 ± 13.4 years, 631 men) hospitalised for heart failure, acute coronary syndrome and other conditions were stratified according to the presence or absence of malnutrition according to the GLIM and ESPEN criteria. Physical function was assessed by measuring grip strength, 6-minute walking distance and quadriceps isometric strength before hospital discharge, and the endpoint was all-cause mortality. During the median follow-up period of 2.3 years (interquartile range, 0.9-3.5 years), 194 deaths occurred in the study population. Malnutrition defined by the GLIM criteria was significantly associated with low physical function. Malnutrition defined by both the GLIM and ESPEN criteria was significantly related to all-cause mortality (P < 0.05). Malnutrition defined according to the GLIM criteria was a predictor of both low physical function and mortality in patients with CVD.


Association between time to revascularization and limb loss in military femoropopliteal arterial injuries.
Expeditious revascularization is key to limb salvage after arterial injuries, but the relationship between time to revascularization and amputation risk is not well-defined. We aimed to explore amputation risk based on time to revascularization in a cohort of military femoropopliteal arterial injuries. A database of vascular injuries from Iraq and Afghanistan casualties (2004-2012) was queried for femoral (common, superficial, or deep) and/or popliteal arterial injuries that underwent revascularization. Time from injury to initial revascularization (via shunt or reconstruction) was divided into groups of <3 hours, 3 to 6 hours, 6 to 9 hours, and >9 hours, and bivariate comparisons were performed. Revascularization times were available for 120 cases. Injury and treatment characteristics by time group were generally similar between time groups. Shunting and vein injuries were more common in limbs revascularized earlier, whereas blast mechanism and fasciotomy were more common with later revascularization. Ten cases (8%) underwent revascularization in less than 3 hours, 63 (53%) were revascularized in 3 to 6 hours, 33 (28%) in 6 to 9 hours, and 14 (12%) after 9 hours. Amputation rates within the cohorts were 10%, 21%, 24%, and 50%, respectively (P = .085, χ2 of amputation rates across time groups). The mean ± standard deviation revascularization time for amputated limbs was 442 ± 348 minutes vs 347 ± 183 minutes for salvaged limbs (P = .057). Amputation was performed in 19% of limbs revascularized in <6 hours and in 32% revascularized >6 hours from injury (P = .112). The >9-hour group, however, had a 50% amputation rate vs 21% for those with revascularization in <9 hours (P = .016). Fractures were more common in >9-hour limbs than <9-hour limbs (79% vs 44%; P = .016), but other limb injury characteristics were similar, with no difference in limb injury severity scores. Among 91 salvaged limbs, neither vascular nor other complications were predicted by time to revascularization. All seven >9-hour limbs had a limb complication, most commonly infection (71%), and three (42%) required a skin graft to close their fasciotomies. Increasing time from injury to initial revascularization was associated with increasing rates of limb loss. Revascularization within 3 hours of injury resulted in a low amputation rate, whereas one-half of limbs treated after 9 hours were amputated. Arterial shunting was associated with earlier revascularization and should be considered a mainstay of combat casualty vascular care. Forward-deployed surgical assets play a pivotal role in providing early revascularization and reducing rates of limb loss in modern combat casualty care.


Plant competition for light analyzed with a multispecies canopy model : II. Influence of photosynthetic characteristics on mixtures of wheat and wild oat.
The importance of photosynthetic characteristics such as quantum efficiency or carboxylation efficiency for carbon gain of plants competing for light in dense stands is dependent on several environmental factors and structural features of the canopy. A quantitative analysis of photosynthesis of competing plants in mixed stands of wheat and wild oat (Avena fatua L.), a common weed of wheat, involved measuring photosynthetic parameters of individual leaves at different heights in the canopy throughout the growing season. This information combined with detailed assessments of canopy structure was used with a multispecies canopy model to evaluate the importance of different photosynthetic characteristics for carbon gain in this canopy environment. Independent photosynthesis data sets were used to validate predictions of the model. Carboxylation efficiency (CE) and CO2-and light-saturated photosynthetic capacity (AML) were highly correlated and decreased with depth in the canopy for both species. Quantum efficiency (α) did not tend to decrease with depth in the canopy. Sensitivity analyses with the model for whole-plant carbon gain of each species over entire day periods were conducted. These showed that changes in CE and AML had an influence similar to that of changes in α on carbon gain for both species. This was not necessarily expected from single-leaf photosynthetic behavior in response to changes in CE, AML and α. The influence of α is more pronounced in the lower, more shaded portions of the canopy than are changes in CE and AML. Appreciable differences between the species were apparent for carbon gain under different weather conditions. The differences between the species in carbon gain when in competition for light were associated more with structural features rather than with photosynthetic characteristics.


Stereoselective synthesis of a novel 2-aza-7-oxabicyclo[3.3.0]octane as neurokinin-1 receptor antagonist.
A novel neurokinin-1 receptor antagonist, (+/-)-(1R( *),3S( *),4S( *),5S( *))-4-[(N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-3-phenyl-2-aza-7-oxabicyclo[3.3.0]octane (1), was synthesized stereoselectively using Padwa's intramolecular 1,3-dipolar cycloaddition methodology as the key step. Compound (+/-)-1 showed high affinity for the NK-1 receptors in human IM-9 cells with an IC(50) value of 0.22 nM. This new structural scaffold demonstrated significant in vivo antagonistic activity in the guinea pig ureter capsaicin-induced plasma extravasation model with an ED(50) value of 1-10mg/kg, po.


Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis.
To compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). Endpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates. At 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: -0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was -0.22 (95% CI -0.38 to -0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: -1.9% versus 1.6% (adjusted difference for etanercept minus control: -4.7%,95% CI -9.9 to 0.5, p=0.07) for change in mNY criteria; -1.9% versus 7.8% (adjusted difference: -18.2%,95% CI -30.9 to -5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and -0.6% versus 6.7% (adjusted difference: -16.4%,95% CI -27.9 to -5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change. Despite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy. NCT01258738, NCT01648907; Post-results.


Head-up tilt and hyperventilation produce similar changes in cerebral oxygenation and blood volume: an observational comparison study using frequency-domain near-infrared spectroscopy.
During anesthesia, maneuvers which cause the least disturbance of cerebral oxygenation with the greatest decrease in intracranial pressure would be most beneficial to patients with intracranial hypertension. Both head-up tilt (HUT) and hyperventilation are used to decrease brain bulk, and both may be associated with decreases in cerebral oxygenation. In this observational study, our null hypothesis was that the impact of HUT and hyperventilation on cerebral tissue oxygen saturation (SctO2) and cerebral blood volume (CBV) are comparable. Surgical patients without neurological disease were anesthetized with propofol-remifentanil. Before the start of surgery, frequency-domain near-infrared spectroscopy was used to measure SctO2 and CBV at the supine position, at the 30° head-up and head-down positions, as well as during hypoventilation and hyperventilation. Thirty-three patients were studied. Both HUT and hyperventilation induced small decreases in SctO2 [3.5 (2.6)%; P < 0.001 and 3.0 (1.8)%; P < 0.001, respectively] and in CBV [0.05 (0.07) mL x 100 g(-1); P < 0.001 and 0.06 (0.05) mL x 100 g(-1); P < 0.001, respectively]. There were no differences between HUT to 30° and hyperventilation to an end-tidal carbon dioxide (ETCO2) of 25 mmHg (from 45 mmHg) in both SctO2 (P = 0.3) and CBV (P = 0.4). The small but statistically significant decreases in both SctO2 and CBV caused by HUT and hyperventilation are comparable. There was no correlation between the decreases in SctO2 and CBV and the decreases in blood pressure and cardiac output during head-up and head-down tilts. However, the decreases in both SctO2 and CBV correlate with the decreases in ETCO2 during ventilation adjustment.


Storm deposition layer on the Fujian coast generated by Typhoon Saola (2012).
Typhoons have a significant effect on the marine depositional environment and depositional process. In this paper, we used the high-resolution Chirp sonar sub-bottom profiler and radioisotope detection techniques to examine the storm-deposited layer formed in the seawater near the path of Typhoon Saola along the coast of Fujian, China. The thickness of the typhoon-deposited layer acquired using these two methods was 10-25 cm. The thickness, sediment grain size, and δ(13)C values of the deposited sedimentary layer indicated that it was mainly matter from the re-suspension and redistribution of seafloor sediments. The particle sizes of the sediments in the storm-deposited layer became coarser, indicating that the fine-grade compositions spread over a wider range out of the coastal zone.


The adipokine SAA3 is induced by interleukin-1beta in mouse adipocytes.
Serum amyloid A (SAA) 3 has been characterized as an inflammatory adipocyte-secreted acute-phase reactant. In the current study, regulation of SAA3 by the proinflammatory and insulin resistance-inducing cytokine interleukin (IL)-1beta was determined in 3T3-L1 and brown adipocytes. Interestingly, SAA3 mRNA and protein synthesis were dramatically increased by IL-1beta in a time-dependent fashion with maximal induction after 24 h. Furthermore, IL-1beta significantly induced SAA3 mRNA expression dose-dependently with maximal 36.4-fold upregulation seen at 2 ng/ml effector. Moreover, IL-1beta-induced SAA3 expression was mediated by nuclear factor-kappaB and janus kinase 2. Taken together, our data show a potent upregulation of SAA3 by IL-1beta.


Utility of intraoperative parathyroid hormone measurement in predicting postparathyroidectomy hypocalcemia.
To evaluate the role of a standardized intraoperative parathyroid hormone (PTH) assay in predicting postoperative hypocalcemia following parathyroidectomy for primary hyperparathyroidism. Prospective series of 66 patients undergoing unilateral or bilateral parathyroidectomy between January 2004 and June 2005. Tertiary care centre in Vancouver, British Columbia. Preoperatively, ionized calcium and PTH levels were recorded. A standardized intraoperative PTH assay was used to measure PTH levels on all patients at the following times: just prior to initial incision (Ti), just prior to adenoma excision (T0), and 5 and 10 minutes after excision (T5 and T10, respectively). Calcium levels were drawn at 8 and 16 hours postoperatively. Clinically significant hypocalcemia was defined as a symptomatic patient or a serum ionized calcium < or = 1.1 mmol/L. Postoperative hypocalcemia following parathyroidectomy. The incidence of postoperative hypocalcemia was 12% (8 of 66). There was no significant correlation between postoperative hypocalcemia and any of the evaluated factors, including intraoperative values of PTH (all p > .05). The percentage change between ioPTH at Ti and at T10 was, however, significantly associated with the development of postoperative hypocalcemia (odds ratio = 3.47 for a 10% decline, p = .03). Percentage change in intraoperative PTH levels between the initial incision and at 10 minutes post-parathyroid adenoma excision is a significant predictor of postoperative hypocalcemia following parathyroidectomy for primary hyperparathyroidism.


Stimulation of mu opioid, but not GABAergic, receptors of the lateral habenula alters free feeding in rats.
Overconsumption, or eating beyond the point of homeostasis, is a key feature in the development of obesity. Although people are consuming beyond the point of homeostasis, they are not consuming constantly or indefinitely. Thus, there is likely a mechanism that acts to terminate periods of food intake at some point beyond satiation and prior to aversion, or the negative effects of extreme excess (nausea, bloating, etc.). The purpose of the present study was to assess the lateral habenula as a candidate region for such a mechanism, due to its connectivity to midbrain reward circuitry, sensitivity to metabolic signaling, and pronounced role in drug-related motivated behaviors. Two groups of male Sprague-Dawley rats were surgically implanted with bilateral guide cannula targeting the LHb. Rats were then habituated to feeding chambers, wherein locomotion and food intake were monitored throughout a two-hour session. One experimental group was tested in the presence of rat chow; the second group was instead given access to a sweetened fat diet. Each subject separately received a 0.2 μL vehicle (0.9% saline solution) and baclofen-muscimol (50 ng/0.2 μL of each drug dissolved in 0.9% saline) injection. Additionally, on a third injection day, each rat received an injection of mu-opioid agonist DAMGO (0.1 μg/0.2 μL) prior to placement in the chamber. LHb inactivation did not result in significant alterations in feeding behavior, but produced a consistent increase in locomotor activity in both experimental groups. Mu-opioid receptor stimulation increased feeding on standard chow, but decreased intake of the sweetened-fat diet. Although LHb inactivation did not increase feeding as predicted, the novel finding that mu opioid receptor stimulation decreased feeding on a highly palatable diet, but increased intake of rat chow, highlights a differential role for the LHb in regulating hedonic consummatory behavior.


Anatomy for endoscopic sinus surgery.
An understanding of the anatomy of the paranasal sinuses is essential for successful endoscopic sinus surgery. The anatomy of the sinuses is carefully described and illustrated.


Complexation of okadaic acid: a preliminary study.
A complexation study was carried out with okadaic acid (OA) and the univalent metal ions Li+, Na+ and K+, and the divalent metal ions Ca2+ and Mg2+. K+ binding was observed identical with a complex obtained from the natural source (OAC). The pharmacological trials demonstrated that this cation has a very important influence on the pharmacological activity of okadaic acid.


Human T cell development and HIV infection in human hemato-lymphoid system mice.
Advances in generation of mice that on human hematopoietic stem and progenitor cell transplantation develop and maintain human hemato-lymphoid cells have fueled an already thriving field of research. We focus here on human T cell development and HIV infection in Rag2 -/- gamma(c) -/- mice transplanted as newborns with human CD34+ cord blood hematopoietic stem and progenitor cells.


Effect of topotecan as second-line chemotherapy for small cell lung cancer patients with interstitial lung disease.
Small cell lung cancer with interstitial lung disease (ILD-SCLC) is difficult to treat because of the risk of fatal pneumonitis. Our study aims to evaluate the validity of topotecan (TOP) as chemotherapy for patients with relapsed ILD-SCLC. Overall survival was compared between TOP and other drugs as second-line treatments for ILD-SCLC patients. Forty-seven patients began chemotherapy and second-line treatment was administered in 48.5% of relapsed cases. The response rate of TOP for second-line therapy was 16.7%. Hematologic toxicities were grade 4 anemia, grade 3 neutropenia and grade 3 thrombocytopenia. Mild pulmonary toxicity was observed in 1 case. Patients receiving TOP as second-line treatment showed no significant difference in survival when compared to patients who underwent other regimens (median survival time 179 vs. 76 days; p =0.76). TOP is a well tolerated drug and is a viable candidate for second-line treatment of ILD-SCLC patients.


Does Relationship Matter during a Health Crisis: Examining the Role of Local Government- Public Relationship in the Public Acceptance of COVID-19 Vaccines.
Viewing government-public relationships as important antecedents of individuals' health protection behaviors, this study uses a relationship management approach to examine COVID-19 vaccine promotion among local government agencies. The study hypothesizes that the quality of local government-public relationships is positively associated with pro-vaccine outcomes, including more frequent risk information seeking, pro-vaccine attitudes, and greater vaccination intention. In addition, an important pathway through which the government-public relationship promotes vaccination acceptance is by enhancing the public's risk perceptions. Using a representative community sample, findings support the positive roles of certain but not all relationship quality variables in predicting vaccine acceptance. Meanwhile, risk perceptions consistently predict risk information seeking, pro-vaccine attitudes, and vaccination intention.


Appearance of a proteoglycan in developing sea urchin embryos.
It was shown that a proteoglycan is synthesised by embryos of a Japanese sea urchin, Hemicentrotus pulcherrimus. This proteoglycan appears as a single peak on sucrose density gradient ultracentrifugation throughout the development. About half of the mucopolysaccharide moiety in this proteoglycan was found to be dermatan sulphate and the rest to be chondroitinase-resistant mucopolysaccharides. Evidence is presented to show that both types of mucopolysaccharide do not exist in a free form but reside as an integral part of the proteoglycan. The linkage between mucopolysaccharide and protein moieties of the proteoglycan appeared not to be an O-glycosidic bond, which is common among other proteoglycans such as proteochondroitin sulphate and proteodermatan sulphate.


Laparoscopic sleeve gastrectomy with staple line buttress reinforcement in 116 consecutive morbidly obese patients.
Obesity rates have reached epidemic levels with over 300 million obese individuals worldwide. Laparoscopic sleeve gastrectomy (LSG) as a primarily restrictive bariatric surgical procedure has been shown to be effective in producing marked weight loss. However, LSG-associated gastric leakage and hemorrhages remain the most important challenges postoperatively. Staple line buttress reinforcement has been suggested to reduce these postoperative complications. Our objective was to assess staple line buttress reinforcement via the Duet™ tissue reinforcement stapler system in morbidly obese patients undergoing LSG as part of a comprehensive weight management strategy, focusing on postoperative complications. Between January 2008 and April 2011, we retrospectively reviewed the medical records of 116 consecutive patients that underwent LSG with staple line buttress reinforcement at an academic teaching hospital with advanced bariatric fellowship. The mean age of patients was 44.3 ± 9.5 years, with mean preoperative BMI of 44 ± 7 kg/m2. The mean operative time to perform LSG was 96 ± 25 min. Postoperative weight was significantly lower following LSG at 1-year follow-up compared to baseline (104 ± 25 vs. 125 ± 27 kg, P < 0.05). There were no postoperative gastric leaks observed. Postoperative bleeding from the gastric staple line occurred in one patient (0.9%) and was treated with conservative management. In LSG, staple line buttress reinforcement limits postoperative gastric leakage and bleeding in morbidly obese patients.


Low intake of β carotene and dietary fiber from vegetables and fruits in patients with chronic kidney disease.
Patients with chronic kidney disease (CKD) occasionally need to restrict their consumption of vegetables and fruits. However, recent evidence suggests that plant-based diets have beneficial effects in patients with CKD. We aimed to determine the sufficiency of β carotene and dietary fiber intake in patients with CKD. We conducted a cross-sectional study among 4476 patients registered in the Fukuoka Kidney Disease Registry (FKR) study, a Japanese prospective cohort study of patients with CKD. Data from 3545 patients were analyzed after excluding cases with insufficient information. We evaluated the relationship between CKD stages and the intake of vegetables and fruits. The intake of β carotene and dietary fiber in CKD stages was evaluated using analysis of covariance. As the CKD stage advanced, the intake of vegetables, green leafy vegetables, and fruits significantly decreased (P-value for all trends < 0.01). The intake of vegetables significantly decreased as the CKD stage advanced (P for trend < 0.01). After adjusting for confounding factors, the intake of β carotene and dietary fiber also decreased (both P < 0.01) as the CKD stage advanced. Patients with CKD had insufficient vegetable and fruit intake and a lack of β carotene and dietary fiber from vegetables and fruits.


In-situ hydrogen peroxide formation and persulfate activation over banana peel-derived biochar cathode for electrochemical water treatment in a flow reactor.
Electrochemical advanced oxidation processes (EAOPs) are effective for the removal of organic contaminants from groundwater. The choice of an affordable cathode material that can generate reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and hydroxyl radicals (•OH) will increase practicality and cost effectiveness of EAOPs. Carbon enriched biochar (BC), which is derived from pyrolysis of biomass, has emerged as an inexpensive and environmentally-friendly electrocatalyst for removing contaminants from groundwater. In this study, a banana peel-derived biochar (BP-BC) cathode packed in a stainless steel (SS) mesh was used in a continuous flow reactor to degrade the ibuprofen (IBP), as a model contaminant. The BP-BC cathodes generate H2O2 via a 2-electron oxygen reduction reaction, initiate the H2O2 decomposition to generate •OH, adsorb IBP from contaminated water, and oxidize IBP by formed •OH. Various reaction parameters such as pyrolysis temperature and time, BP mass, current, and flow rate, were optimized to maximize IBP removal. Initial experiments showed that H2O2 generation was limited (∼3.4 mg mL-1), resulting in only ∼ 40% IBP degradation, due to insufficient surface functionalities on the BP-BC surface. The addition of persulfate (PS) into the continuous flow system significantly improves the IBP removal efficiency via PS activation. The in-situ H2O2 formation and PS activation over BP-BC cathode results in concurrent generation of •OH and sulfate anion radicals (SO4•-, a reactive oxidant), respectively, which collectively achieve ∼ 100% IBP degradation. Further experiments with methanol and tertiary butanol as potential scavengers for •OH and SO4•- confirm their combined role in complete IBP degradation.


Evaluation of Health-Related Quality of Life among Patients with Cervical Cancer in Indonesia.
Evaluation of health-related quality of life (HRQOL) in cervical cancer patients is important in order to design the interventions for improving patient outcomes. Reports of HRQOL among cervical cancer patients in Indonesia are limited. Moreover, measurement using EQ-5D-3L is to our best knowledge has hitherto not been performed. This study aimed to examine the HRQOL of cervical cancer patients in Indonesia using EQ- 5D-3L. A cross-sectional study was conducted by interviewing cervical cancer patients using the EQ-5D-3L questionnaire. Percentages of patients who reported having problems in each dimension of EQ-5D as well as EQ-5D index score (utility) were calculated. Our findings indicated that the most frequent reported problems were pain/discomfort (67.8%) followed by anxiety/depression (57.5%). The mean of EQ-5D VAS was 75.8 (SD=17.0). The mean (SD) utility scores were 0.85 (0.19), 0.76 (0.20), 0.71 (0.21), and 0.77 (0.13) for cervical cancer patients in stage I, II, III, and IV, respectively. Cervical cancer significantly affects patient HRQOL. Efforts should be made to improve the quality of life of cervical cancer patients especially in terms of pain /discomfort and anxiety/depression reduction.


Time course of effect of capsaicin on ultrastructure and histochemistry of substance P-immunoreactive nerves associated with the cardiovascular system of the guinea-pig.
Capsaicin, a neurotoxin which depletes substance P from primary afferent nerve fibres, was injected systematically into adult guinea pigs. The effects of capsaicin were studied by immunohistochemistry, electron microscopy and radioimmunoassay at times from 5 min to 1 year. Within 5 min after a single injection of capsaicin (50 mg/kg) substance P immunofluorescence appeared less intense and less homogeneous than normal (i.e. it appeared granular). Large nerve trunks remained evident, but there were fewer fine single nerve fibres. With increasing time there was a progressive decrease in the number of immunoreactive fibres; by 4 h there was a marked reduction in the number of fibres and by 24 h only an occasional fibre was evident. In animals sacrificed 2 or more hours after treatment large brightly fluorescent swellings were seen in many nerves. Depletion of substance P-immunoreactivity persisted for as long as 365 days after treatment. Electron microscopy revealed alterations in capsaicin-sensitive nerve fibres within 5 min after treatment. Many fibres appeared swollen and there was disruption of their internal morphology, e.g. loss of microtubules and filaments and presence of an amorphous flocculent material in the axons. With increasing time after treatment, electron-dense profiles, indicative of degenerating nerve fibres, were commonly seen associated with Schwann cells. These findings demonstrate that the effects of systemic administration of capsaicin to adult guinea pigs occur rapidly in capsaicin-sensitive nerve fibres. The long lasting depletion of substance P-containing fibres is due to their degeneration.


Isolation of amide proton transfer effect and relayed nuclear Overhauser enhancement effect at -3.5ppm using CEST with double saturation powers.
Quantifications of amide proton transfer (APT) and nuclear Overhauser enhancement (rNOE(-3.5)) mediated saturation transfer with high specificity are challenging because their signals measured in a Z-spectrum are overlapped with confounding signals from direct water saturation (DS), semi-solid magnetization transfer (MT), and CEST of fast-exchange pools. In this study, based on two canonical CEST acquisitions with double saturation powers (DSP), a new data-postprocessing method is proposed to specifically quantify the effects of APT and rNOE. For CEST imaging with relatively low saturation powers ( ω 1 2 $$ {\upomega}_1^2 $$ ), both the fast-exchange CEST effect and the semi-solid MT effect roughly depend on ω 1 2 $$ {\upomega}_1^2 $$ , whereas the slow-exchange APT/rNOE(-3.5) effect do not, which is exploited to isolate a part of the APT and rNOE effects from the confounding signals in this study. After a mathematical derivation for the establishment of the proposed method, numerical simulations based on Bloch equations are then performed to demonstrate its specificity to detections of the APT and rNOE effects. Finally, an in vivo validation of the proposed method is conducted using an animal tumor model at a 4.7 T MRI scanner. The simulations show that DSP-CEST can quantify the effects of APT and rNOE and substantially eliminate the confounding signals. The in vivo experiments demonstrate that the proposed DSP-CEST method is feasible for the imaging of tumors. The data-postprocessing method proposed in this study can quantify the APT and rNOE effects with considerably increased specificities and a reduced cost of imaging time.


Reducing Wait Times for Radiology Exams Around Holiday Periods: A Monte Carlo Simulation.
Reducing patient wait times is a key operational goal and impacts patient outcomes. The purpose of this study is to explore the effects of different radiology scheduling strategies on exam wait times before and after holiday periods at an outpatient imaging facility using computer simulation. An idealized Monte Carlo simulation of exam scheduling at an outpatient imaging facility was developed based on the actual distribution of scheduled exams at outpatient radiology sites at a tertiary care medical center. Using this simulation, we examined three scheduling strategies: (1) no scheduling modifications, (2) increase imaging capacity before or after the holiday (i.e. increase facility hours), and (3) use a novel rolling release scheduling paradigm. In the third scenario, a fraction of exam slots are blocked to long-term follow-up exams and made available only closer to the exam date, thereby preventing long-term follow-up exams from filling the schedule and ensuring slots are available for non-follow-up exams. We examined the effect of these three scenarios on utilization and wait times, which we defined as the time from order placement to exam completion, during and after the holiday period. The baseline mean wait time for non-follow-up exams was 5.4 days in our simulation. When no scheduling modifications were made, there was a significant increase in wait times in the week preceding the holiday when compared to baseline (10.0 days vs 5.4 days, p < 0.01). Wait times remained elevated for 4 weeks following the holiday. Increasing imaging capacity during the holiday and post-holiday period by 20% reduced wait times by only 6.2% (9.38 days vs 10.0 days, p < 0.01). Increasing capacity by 50% resulted in a 7.1% reduction in wait times (9.28 days, p < 0.01), and increasing capacity by 100% resulted in a 13% reduction in wait times (8.75 days, p < 0.01). In comparison, using a rolling release model produced a reduction in peak wait times equivalent to doubling capacity (8.76 days, p < 0.01) when 45% of slots were reserved. Improvements in wait times persisted even when rolling release was limited to the 3 weeks preceding or 1 week following the holiday period. Releasing slots on a rolling basis did not significantly decrease utilization or increase wait times for long-term follow-up exams except in extreme scenarios where 80% or more of slots were reserved for non-follow-up exams. A rolling release scheduling paradigm can significantly reduce wait time fluctuations around holiday periods without requiring additional capacity or impacting utilization.


Effect of supercooling and freezing on photosynthesis in freezing tolerant leaves of Afroalpine 'giant rosette' plants.
The effect of supercooling and freezing on the photosynthetic capability of representatives of the permanent frost hardy giant rosette plants Dendrosenecio keniodendron, D. brassica and Lobelia telekii, of the tropical alpine regions was investigated with the non-invasive chlorophyll a fluorescence technique. While supercooling, normal chlorophyll a fluorescence kinetics exhibiting the sequence 0, I, (D), P, S, M, were recorded, however with some retardation of both, the fast and the slow characteristics as compared to those obtained at day-time temperature. As long as the leaves remained unfrozen, the rise of the variable fluorescence F ν from the level 0 to P was inversely related to a drop of the temperature from about 0°C to-8°C. The increase of F ν with lower temperature is understood to result from a decrease of the velocity of the quenching reactions while photoreduction of the primary electron acceptor appeared to be unimpeded. The second fluorescence maximum (M), usually interpreted to indicate the commencement of the biochemical reactions of photosynthesis was consistenly to be observed during supercooling. Fluoescence induction kinetics of frozen leaves showed only fast rise to presumably F max which was not followed by a significant decay for as long as 4 min. The lack of substantial quenching indicates that in the freeze-dehydrated state neither reoxidation of the primary acceptor nor energetization of the thylakoid membrane was accomplished. This effect however was immediately and fully reserved upon thawing of the leaves when the usual fluorescence induction kinetics as well as normal rates of CO2-uptake were observed. Thus the permanent frost-hardy afroalpine plants do not exhibit any even short-term memory effect of the nocturnal frost on such a delicate process as is photosynthesis.


Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.
The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.


Long lasting inhibition of horseradish peroxidase (HRP) transport in sensory nerves induced by capsaicin pretreatment of the receptive field.
Capsaicin, when injected into the scrotal skin of adult rats was seen to produce a long-lasting desensitization. To investigate the possible effect of this treatment on the sensory neurones of the pudendal nerve, rats were injected with horseradish peroxidase (HRP) at different time intervals following pretreatment with capsaicin. The HRP was applied in two different ways. In one group of rats HRP was injected into both sides of the scrotal skin between 2 and 12 days after capsaicin pretreatment of one side of the scrotal skin. More HRP labelled neurones were seen in the S1 and L6 dorsal root ganglia (DRG) on the non-treated side than on the pretreated side. Similar results were obtained when the HRP was injected directly into the pudendal nerve. A marked decrease in the number of HRP labelled neurones on the pretreated side was observed even when HRP was injected into the nerve up to 1 year after the capsaicin pretreatment. It appears therefore that at least part of the effect of capsaicin on peripheral sensory neurones is due to an effect of capsaicin on the axoplasmic transport processes, and that this effect is long lasting.


Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.
Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.


Cytotoxicity responses to selected ESAT-6 and CFP-10 peptides in tuberculosis.
Cytotoxicity responses were studied for the ESAT-6 peptides Esp1, Esp6, Esp7, Esp8, and CFP-10 peptides, Cfp6, Cfp7, Cfp8, Cfp9 (synthetic 20-mer peptides) and the recombinant ESAT-6, CFP-10 proteins. Cytolytic molecules perforin, granzymes A and B, granulysin responses in healthy household contacts (HHC) and pulmonary tuberculosis patients (PTB), were studied by intracellular flow cytometry. Functional cytotoxicity was studied in both the groups for the peptides Esp6 and Cfp8 by an enzyme (lactate dehydrogenase) based assay. The results revealed that cytolytic molecule positive CD4+ and CD8+ T cells were increased in HHC in response to Esp1, Esp6, Cfp8 and Cfp9 immunogenic peptides compared to PTB. Functional cytotoxicity results showed higher cytotoxicity (not statistically significant) to be exhibited by the peptide Esp6 than Cfp8 in the HHC.


Advances in forecasting harmful algal blooms using machine learning models: A case study with Planktothrix rubescens in Lake Geneva.
The development of anthropic activities during the 20th century increased the nutrient fluxes in freshwater ecosystems, leading to the eutrophication phenomenon that most often promotes harmful algal blooms (HABs). Recent years have witnessed the regular and massive development of some filamentous algae or cyanobacteria in Lake Geneva. Consequently, important blooms could result in detrimental impacts on economic issues and human health. In this study, we tried to lay the foundation of an HAB forecast model to help scientists and local stakeholders with the present and future management of this peri-alpine lake. Our forecast strategy was based on pairing two machine learning models with a long-term database built over the past 34 years. We created HAB groups via a K-means model. Then, we introduced different lag times in the input of a random forest (RF) model, using a sliding window. Finally, we used a high-frequency dataset to compare the natural mechanisms with numerical interaction using individual conditional expectation plots. We demonstrate that some HAB events can be forecasted over a year scale. The information contained in the concentration data of the cyanobacteria was synthesized in the form of four intensity groups that directly depend on the P. rubescens concentration. The categorical transformation of these data allowed us to obtain a forecast with correlation coefficients that stayed above a threshold of 0.5 until one year for the counting cells and two years for the biovolume data. Moreover, we found that the RF model predicted the best P. rubescens abundance for water temperatures around 14°C. This result is consistent with the biological processes of the toxic cyanobacterium. In this study, we found that the coupling between K-means and RF models could help in forecasting the development of the bloom-forming P. rubescens in Lake Geneva. This methodology could create a numerical decision support tool, which should be a significant advantage for lake managers.


On A New Reptilian Cestode Oochoristica Pauriensis N.Sp. From Hemidactylus Brooki (Gray) And Hemidactylus Flaviviridis (Ruppell) From Garhwal Hills, U.P., India.
Oochoristica pauriensis n.sp. has been described and figured from Hemidactylus brooki(Gray) and H. flaviviridis(Ruppell) on size of strobila, scolex, suckers, testes, ovary, eggs and oncosphere, and number of testes. The new species has been compared with close species.


Recovery of high-purity metallic Pd from Pd(II)-sorbed biosorbents by incineration.
This work reports a direct way to recover metallic palladium with high purity from Pd(II)-sorbed polyethylenimine-modified Corynebacterium glutamicum biosorbent using a combined method of biosorption and incineration. This study is focused on the incineration part which affects the purity of recovered Pd. The incineration temperature and the amount of Pd loaded on the biosorbent were considered as major factors in the incineration process, and their effects were examined. The results showed that both factors significantly affected the enhancement of the recovery efficiency and purity of the recovered Pd. SEM-EDX and XRD analyses were used to confirm that Pd phase existed in the ash. As a result, the recovered Pd was changed from PdO to zero-valent Pd as the incineration temperature was increased from 600 to 900°C. Almost 100% pure metallic Pd was recovered with recovery efficiency above 99.0% under the conditions of 900°C and 136.9 mg/g.


Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway.
The blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats. BTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues. QJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB. These results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.


First clinical case series of frosted branch angiitis: A diagnostic algorithm is suggested.
FBA is a clinical diagnosis of a diverse spectrum, which needs a high index of suspicion to identify the possible specific etiologies. The zones of retinal involvement can help in predicting the final visual outcome. The proposed diagnostic algorithm facilitates meticulous evaluation and targeted treatment to improve the final visual outcome. Frosted branch angiitis is a clinical diagnosis of a diverse spectrum, which needs a high index of suspicion to identify the possible specific etiologies. We present a series of three cases of FBA with an attempt to formulate a diagnostic algorithm and refine the definition of FBA.


Tandem reassembly of split luciferase-DNA chimeras for bioluminescent detection of attomolar circulating microRNAs using a smartphone.
Detection of dysregulated circulating microRNAs (miRNAs) in human biofluids is a fundamental ability to determine tumor occurrence and metastasis in a minimally invasive fashion. However, the requirements for sophisticated instruments and professional personnel impede the translation of miRNA tests into routine clinical diagnostics, especially for resource-limited regions. Herein, we developed a DNA-guided bioluminescence strategy for the detection of circulating miRNAs. In this strategy, a pair of split luciferase-DNA chimeras was constructed and integrated into the miRNA-triggered rolling circle amplification (RCA) process. The tandem reassembly of split luciferase-DNA chimeras on the RCA products elicited a turn-on bioluminescence response with ultrahigh signal-to-background (S/B) ratio. This strategy enabled smartphone-based assays for different miRNAs with attomolar sensitivity and single-base specificity, as demonstrated here for miR-21. miR-148b, and cel-miR-39. Further application of our approach to the clinical serum samples realized identification of dysregulated miR-21 and miR-148b in the lung cancer patients, showing a satisfactory agreement with the control assays performed with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Therefore, the developed method possesses the benefits of high performance and reliability, offering a potential tool for implementing miRNA-based diagnosis in point-of-care (POC) settings.


[Effect of thrombopenia on bone marrow CFU-S level and its capability to modify the circulating thrombocyte number].
Thrombocytopenia (rise of the thrombopoietin level) was induced by an antithrombocyte serum in mice. After 6 hours of existence of thrombocytopenia, the CFU-S and megakaryocyte-commmitted stem cell content of the bone marrow and spleen was determined by transplantation into mice pretreated with 800 cGy-rtg irradiation. Thrombocytopenia did not influence the CFU-S content. Thrombocytopoiesis of the recipient mice was better restored by bone marrow and spleen cells of thrombocytopenic animals than by cells transplanted from animals with a normal thrombocyte count.


New Insights Into Cellular Stress Responses to Environmental Metal Toxicants.
Exposures to metal toxicants in the environment disrupt normal physiological functions and have been linked to the development of a myriad of human diseases. While the molecular and cellular mechanisms underlying metal toxicities remain to be fully understood, it is well appreciated that metal toxicants induce cellular stresses and that how cells respond to the stresses plays an important role in metal toxicity. In this review, we focus on how metal exposures induce stresses in the endoplasmic reticulum (ER) to elicit the unfolded protein response (UPR). We document the emerging evidence that induction of ER stress and UPR in the development of human diseases is associated with metal exposures. We also discuss the role of the interplay between ER stress and oxidative stress in metal toxicity. Finally, we review recent advances in functional genomics approaches and discuss how applications of these new tools could help elucidate the molecular mechanisms underlying cellular stresses induced by environmental metal toxicants.


Effectiveness of progressive moderate-vigorous intensity elastic resistance training on quality of life and perceived functional abilities in people with hemophilia: Secondary analysis of a randomized controlled trial.
Strength exercise training is advised for people with hemophilia (PWH); however, few studies have been published and have methodological limitations. The purpose of this study was to evaluate the effectiveness of progressive elastic resistance training on quality of life and perceived functional abilities in PWH. Participants were randomly allocated to the intervention (n = 10) or control (n = 10) group. The intervention group performed progressive moderate-vigorous elastic resistance training (2 days/week, a total of 8 weeks), focusing on the muscles of the knee, elbow, and ankle joints. The control group continued its usual daily activities for 8 weeks. Quality of life (A36 Hemofilia-QoL®) and perceived functional abilities (Haemophilia Activities List) were assessed at baseline and an 8-week follow-up. The intervention group improved the quality-of-life dimension of joint damage perception in comparison to the control group (p = .015, large effect size). Regarding perceived functional abilities, the intervention group improved lying, sitting, kneeling, and standing (p = .006, small effect size), and complex lower extremities activities (i.e., walking short and long-distance, and up-down stairs) (p = .006, small effect size) compared to the control group. No other significant differences were observed. Eight weeks of progressive moderate-vigorous elastic resistance training in PWH improve the quality-of-life dimension of joint damage perception and perceived functional abilities (lying/sitting/kneeling/standing, and complex lower extremities activities). Our results suggest a limited effect of the program on the other items of quality of life measured by the questionnaire as emotional functioning, mental health, and social relationships. Importantly, no serious adverse effects occurred.


Catechol-substituted phenoxypropanolamines: adrenoceptor activity in the anaesthetized cat.
1 The pharmacological actions of racemic noradrenaline, adrenaline, isoprenaline and N-t-butylnoradrenaline have been compared with those of their corresponding derivatives containing an oxymethylene (OXY) link between the ring and ethanolamine side chain. 2 The compounds were tested in the anaesthetized cat for their ability to produce positive chronotropic effects, bronchodilator actions, changes in perfusion pressure in the perfused hind limb and decreases in soleus muscle contractions. 3 All the OXY-derivatives were potent beta-adrenoceptor agonists. The inclusion of the oxymethylene link promotes selectivity for beta1-as opposed to beta2-adrenoceptor activity. 4 In comparison with the parent compounds, the OXY-derivatives of adrenaline and noradrenaline had very weak alpha-adrenoceptor stimulant effects.


Integration of magnetic resonance imaging into radiation therapy treatment planning: I. Technical considerations.
This paper presents the results of a feasibility study specifically addressing the technical and operational difficulties in making quantitative use of Magnetic Resonance Imaging (MRI) in radiation therapy treatment planning (RTTP). Selected radiotherapy patients have been studied with both CT and MRI as part of the treatment planning process. Both sets of images, along with mechanically-obtained external contour and simulator film data, are entered into the treatment planning system. All of the capabilities of the fully three dimensional planning system U-MPlan are available to both the CT and MRI images, in which any image can be used as the backdrop for interactive beam positioning, beam portal simulation, and dose distribution displays for external beam and brachytherapy applications in both 2- and 3-dimensionally-oriented displays. The study has shown that to use MRI data for RTTP, one must (a) use careful patient positioning and marking, (b) transfer information from CT to MRI and vice versa, (c) determine the geometrical consistency between the CT and MR data sets, (d) investigate the unwarping of distorted MR images, and (e) have the ability to use non-axial images for determination of beam treatment technique, dose calculations, and plan evaluation.


A kinetic re-interpretation of the regulation of rabbit skeletal-muscle phosphorylase kinase activity by Ca2+ and phosphorylation.
The regulation of phosphorylase kinase has been proposed to occur physiologically under conditions of zero-order ultrasensitivity [Meinke & Edstrom (1991) J. Biol. Chem. 266, 2259-2266]. This is also one of the conditions that recent theoretical approaches have indicated to be essential in order for an interconvertible enzyme cascade to generate a sensitive response to an effector [Cardenas & Cornish-Bowden (1989) Biochem. J. 257, 339-345]. In contrast, all published kinetic data to date have strongly suggested that activation of phosphorylase kinase by Ca2+ or phosphorylation is attributable solely to a change in affinity for phosphorylase, with no effect on the Vmax. of the reaction. In this study an attempt is made to resolve this conflict. Findings suggest that changes in Vmax. can fully account for the activation of phosphorylase kinase by the physiological mechanisms of cyclic AMP-dependent phosphorylation and increase in Ca2+ concentration.


Use of solvent suppression technique to enhance changes due to susceptibility variations in magnetic resonance imaging.
This communication describes the use of a binomial pulse sequence designed from solvent suppression in proton spectroscopy to convert the small frequency changes associated with field variations into significant amplitude changes in magnetic resonance images. This technique can be used to demonstrate tissue susceptibility change.


Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-beta1 in synovial fibroblasts from rheumatoid arthritis and normal individuals.
Transforming growth factor (TGF)-beta1 is expressed abundantly in the rheumatoid synovium. In this study, the inflammatory effect of TGF-beta1 in rheumatoid arthritis (RA) was investigated using cultured fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients, as well as non-arthritic individuals. mRNA expressions of IL-1beta, tumour necrosis factor (TNF)-alpha, IL-8, macrophage inflammatory protein (MIP)-1alpha and metalloproteinase (MMP)-1 were increased in RA and OA FLS by TGF-beta1 treatment, but not in non-arthritic FLS. Enhanced protein expression of IL-1beta, IL-8 and MMP-1 was also observed in RA FLS. Moreover, TGF-beta1 showed a synergistic effect in increasing protein expression of IL-1beta and matrix metalloproteinase (MMP)-1 with TNFalpha and IL-1beta, respectively. Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-beta1 in the culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were shown to increase by TGF-beta1 as well. These results suggest that TGF-beta1 contributes for the progression of inflammation and joint destruction in RA, and this effect is specific for the arthritic synovial fibroblasts.


Infrared and Raman spectra of phosphatidyl-ethanolamine and related compounds.
Infrared and Raman spectra of phosphatidylethanolamine from Escherichia coli, L-alpha-glycero-phosphorylethanolamine and 0-phosphorylethanolamine were obtained. Most of the bands were assigned to each vibrational mode based on the N deuteration effect, comparison of the intensity in the infrared and Raman spectra and the depolarization degree measurement in the Raman spectra. The spectra of phosphatidylethanolamine can be interpreted by assuming that the molecule takes the dipolar ionic structure both in non-polar solvent and in solid.


Structures and single-molecule analysis of bacterial motor nuclease AdnAB illuminate the mechanism of DNA double-strand break resection.
Mycobacterial AdnAB is a heterodimeric helicase-nuclease that initiates homologous recombination by resecting DNA double-strand breaks (DSBs). The AdnA and AdnB subunits are each composed of an N-terminal motor domain and a C-terminal nuclease domain. Here we report cryoelectron microscopy (cryo-EM) structures of AdnAB in three functional states: in the absence of DNA and in complex with forked duplex DNAs before and after cleavage of the 5' single-strand DNA (ssDNA) tail by the AdnA nuclease. The structures reveal the path of the 5' ssDNA through the AdnA nuclease domain and the mechanism of 5' strand cleavage; the path of the 3' tracking strand through the AdnB motor and the DNA contacts that couple ATP hydrolysis to mechanical work; the position of the AdnA iron-sulfur cluster subdomain at the Y junction and its likely role in maintaining the split trajectories of the unwound 5' and 3' strands. Single-molecule DNA curtain analysis of DSB resection reveals that AdnAB is highly processive but prone to spontaneous pausing at random sites on duplex DNA. A striking property of AdnAB is that the velocity of DSB resection slows after the enzyme experiences a spontaneous pause. Our results highlight shared as well as distinctive properties of AdnAB vis-à-vis the RecBCD and AddAB clades of bacterial DSB-resecting motor nucleases.


Reflective metalens with sub-diffraction-limited and multifunctional focusing.
We propose an ultra-thin planar reflective metalens with sub-diffraction-limited and multifunctional focusing. Based on the equal optical path principle, the specific phase distributions for multifunction focusing are derived. Following the formulas, on-center focusing with the characteristics of sub-diffraction-limited, high focusing efficiency (85%) and broadband focusing is investigated in detail. To demonstrate the flexibility of the reflective metalens, off-center and dual spots focusing (at the horizontal and longitudinal directions) are demonstrated. Note that all these focusings are sub-diffraction-limited due to the evanescent-filed enhancement mechanism in our elaborately designed structure. The designed reflective metalens will find important applications in super-resolution imaging, microscopes, and spectroscopic designs.


Gene stacking in plant cell using recombinases for gene integration and nucleases for marker gene deletion.
Practical approaches for multigene transformation and gene stacking are extremely important for engineering complex traits and adding new traits in transgenic crops. Trait deployment by gene stacking would greatly simplify downstream plant breeding and trait introgression into cultivars. Gene stacking into pre-determined genomic sites depends on mechanisms of targeted DNA integration and recycling of selectable marker genes. Targeted integrations into chromosomal breaks, created by nucleases, require large transformation efforts. Recombinases such as Cre-lox, on the other hand, efficiently drive site-specific integrations in plants. However, the reversibility of Cre-lox recombination, due to the incorporation of two cis-positioned lox sites, presents a major bottleneck in its application in gene stacking. Here, we describe a strategy of resolving this bottleneck through excision of one of the cis-positioned lox, embedded in the marker gene, by nuclease activity. All transgenic lines were developed by particle bombardment of rice callus with plasmid constructs. Standard molecular approach was used for building the constructs. Transgene loci were analyzed by PCR, Southern hybridization, and DNA sequencing. We developed a highly efficient gene stacking method by utilizing powerful recombinases such as Cre-lox and FLP-FRT, for site-specific gene integrations, and nucleases for marker gene excisions. We generated Cre-mediated site-specific integration locus in rice and showed excision of marker gene by I-SceI at ~20 % efficiency, seamlessly connecting genes in the locus. Next, we showed ZFN could be used for marker excision, and the locus can be targeted again by recombinases. Hence, we extended the power of recombinases to gene stacking application in plants. Finally, we show that heat-inducible I-SceI is also suitable for marker excision, and therefore could serve as an important tool in streamlining this gene stacking platform. A practical approach for gene stacking in plant cell was developed that allows targeted gene insertions through rounds of transformation, a method needed for introducing new traits into transgenic lines for their rapid deployment in the field. By using Cre-lox, a powerful site-specific recombination system, this method greatly improves gene stacking efficiency, and through the application of nucleases develops marker-free, seamless stack of genes at pre-determined chromosomal sites.


The PRISMA Symposium 4: how should Europe progress end-of-life and palliative clinical care research? Recommendations from the proceedings.
Within aging European populations, the need to progress end-of-life and palliative care policy is becoming increasingly important. PRISMA, a European Commission-funded project, aimed to identify and coordinate research priorities, measurement, and practice in end-of-life care for Europe. PRISMA conducted a three-year multidisciplinary program to advance science and policy and to enhance coordination of cross-national activity. The final PRISMA symposium was convened to disseminate our new knowledge and activities and was held for European Union-level and national-level policy makers, policy influencers, and funders. Nearly 100 international invited delegates participated in the symposium, with the understanding that European research is aided by international partnerships and the free exchange of ideas and resources across states. The series of invited speakers, roundtables, and floor discussions underlined the necessity for clinical and public priorities to inform holistic outcome measurement research supported by government action informed by policy. Sustainable leadership, clear terminology and pan-European collaborative networks, and protected research funding designated for end-of-life or palliative care were identified as essential to progress end-of-life and palliative care research and innovation in Europe. An agreed set of outcome measures for end-of-life and palliative care that builds on previous pan-European projects is fundamental to a cross-national program of development in order to advance research and innovation within Europe.


Cutting the encircling band.
To report the effect of cutting the encircling band on ocular blood flow. In an interventional case series of 27 eyes with an encircling band, the ocular pulse amplitude (OPA) was measured and pulsatile ocular blood flow (POBF) derived and compared with fellow eyes. The bands were cut in 11 eyes and the POBF measured at 1 month, 3 months, and 1 year. Changes in POBF, buckle height, and visual acuity were determined. The presence of the encircling band reduced the POBF to a mean of 43% (P < 0.001) of the fellow eye. Cutting the band resulted in a mean recovery to 85.6%. No retina detached after cutting, buckle height was only slightly diminished, and the visual acuity was unaffected. An encircling band diminishes the POBF. Cutting the band restores significant flow.


Impact of pandemic control over airport economics: Reconciling public health with airport business through a streamlined approach in pandemic control.
Rapid aviation commercialisation and upsurge in worldwide affluence created a new avenue for disease proliferation across countries at an unprecedented rate. Epidemic and pandemic occurrences over the last decade demonstrate airports' role in disease transmission; while also exhibiting their importance as containment nodes. Tremendous amount of resources and effort are necessary to achieve the latter but inevitably, disrupt normal operations. The contrasting objectives between public health authorities and airport authorities result in compromising measures for both parties. Broadly similar controlling measures were adopted by various airports during outbreaks in the last decade. Their effectiveness have been analysed in terms of disease control; economic impact to airports were, however, not quantified. This paper concludes that more efficient airport pandemic control plans cause less severe economic impact on airports during pandemic and recommends a streamlined approach that improves overall effect of pandemic control while minimising economic impacts to airport businesses.


Fibro-Osseous Pseudotumor of the Digits Mimicking Pyogenic Granuloma.
Fibro-osseous pseudotumor of the digits is a benign neoplasm that originates in the soft tissue adjacent to the short bones of the hands and feet. We present a case in a 13-year-old girl that was initially misdiagnosed as pyogenic granuloma. Familiarity with this entity and imaging and histologic studies are necessary to avoid incorrect diagnoses and aggressive surgical interventions.


Modeling fiber type grouping by a binary Markov random field.
A new approach to the quantification of fiber type grouping is presented, in which the distribution of histochemical type in a muscle cross section is regarded as a realization of a binary Markov random field (BMRF). Methods for the estimation of the parameters of this model are discussed. The first order BMRF, which is used in this article, contains 2 parameters: alpha and beta. The parameter beta is of prime importance, as it is an interaction parameter which governs the degree of type grouping. The value of this parameter is estimated for 9 muscle biopsies. The interpretation of the results is discussed.


Early and Mid-term Efficacy of Fenestrated Endograft in the Treatment of Juxta-Renal Aortic Aneurysms.
The aim of this study was to report early and mid-term outcomes of fenestrated endografting (FEVAR) for juxtarenal aneurysm (J-AAAs). Between 2008 and 2017, all consecutive J-AAAs treated by FEVAR were prospectively collected. Early endpoints were technical success, renal function worsening, and 30-day mortality. Follow-up endpoints were survival, freedom from reinterventions (FFRs), target visceral vessels (TVVs) patency, J-AAAs shrinkage, and renal function worsening. Among 181 cases who underwent FB-EVAR, 66 (36%) were J-AAAs. Endograft with 1, 2, 3, and 4 fenestrations were planned in 2 (3%), 22 (33%), 27 (41%) and 15 (23%) cases, respectively. Overall, 236 TVVs were treated by fenestrations and scallops. Technical success was achieved in 65 (99%) cases. The only failure occurred for a type III endoleak requiring renal artery relining. No TVVs were lost. Renal function worsening occurred in 7 (10%) cases: 4 returned to baseline within 30-day, 1 required hemodialysis and died within 30 days (1.5%). This was the only case of 30-day mortality. The mean follow-up was 46 ± 32 months. Aneurysm sac shrinkage or stability was observed in 42 (64%) and 22 (33%) cases, respectively. Two patients (3%) with persistent type II endoleak had sac enlargement and required reinterventions. Freedom from reinterventions at 5 years was 88%. An asymptomatic celiac trunk occlusion (accommodated by a scallop) occurred at 24 months in a case with a severe preoperative stenosis. No late renal arteries occlusions or type I-III endoleaks occurred. Overall, renal function worsening was reported in 5 (8%) patients during follow-up. Survival at 5 years was 67%, with no j-AAA-related mortality. COPD was the only independent predictor for mortality at the multivariate analysis (P: 0.021; OR: 5.3; 95% CI, 1.3-21.9). FEVAR for J-AAAs is safe and effective at early and mid-term follow-up. According to these results, it could be proposed as the first-line treatment in high-risk patients if anatomically fit. Long-term survival is reduced in the presence of preoperative COPD.


SUMO protease SENP6 protects the nucleus from hyperSUMOylation-induced laminopathy-like alterations.
The small ubiquitin-like modifier (SUMO) protease SENP6 disassembles SUMO chains from cellular substrate proteins. We use a proteomic method to identify putative SENP6 substrates based on increased apparent molecular weight after SENP6 depletion. Proteins of the lamin family of intermediate filaments show substantially increased SUMO modification after SENP6 depletion. This is accompanied by nuclear structural changes remarkably like those associated with laminopathies. Two SUMO attachment sites on lamin A/C are close to sites of mutations in Emery-Driefuss and limb girdle muscular dystrophy. To establish a direct link between lamin SUMOylation and the observed phenotype, we developed proximity-induced SUMO modification (PISM), which fuses a lamin A/C targeting DARPin to a SUMO E3 ligase domain. This directly targets lamin A/C for SUMO conjugation and demonstrates that enhanced lamin SUMO modification recapitulates the altered nuclear structure manifest after SENP6 depletion. This shows SENP6 activity protects the nucleus against hyperSUMOylation-induced laminopathy-like alterations.