Acute esophageal variceal bleeding: Current strategies and new perspectives.
Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary team plays a major role in the final outcome of this complication. It is currently recommended to combine pharmacological and endoscopic therapies for the initial treatment of the acute bleeding. Vasoactive drugs (preferable somatostatin or terlipressin) should be started as soon as a variceal bleeding is suspected (ideally during transfer to hospital) and maintained afterwards for 2-5 d. After stabilizing the patient with cautious fluid and blood support, an emergency diagnostic endoscopy should be done and, as soon as a skilled endoscopist is available, an endoscopic variceal treatment (ligation as first choice, sclerotherapy if endoscopic variceal ligation not feasible) should be performed. Antibiotic prophylaxis must be regarded as an integral part of the treatment of acute variceal bleeding and should be started at admission and maintained for at least 7 d. In case of failure to control the acute bleeding, rescue therapies should be immediately started. Shunt therapies (especially transjugular intrahepatic portosystemic shunt) are very effective at controlling treatment failures after an acute variceal bleeding. Therapeutic developments and increasing knowledge in the prognosis of this complication may allow optimization of the management strategy by adapting the different treatments to the expected risk of complications for each patient in the near future. Theoretically, this approach would allow the initiation of early aggressive treatments in high-risk patients and spare low-risk individuals unnecessary procedures. Current research efforts will hopefully clarify this hypothesis and help to further improve the outcomes of the severe complication of cirrhosis.


NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators.
Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and peripheral tissues. Surprisingly, however, using luminometry and single-cell bioluminescence imaging of PER2 expression, we now find that CLOCK-deficient dispersed SCN neurons and peripheral cells exhibit similarly stable, autonomous circadian rhythms in vitro. In CLOCK-deficient fibroblasts, knockdown of Npas2 leads to arrhythmicity, suggesting that NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in SCN. Our data overturn the notion of an SCN-specific role for NPAS2 in the molecular circadian clock, and instead indicate that, at the cellular level, the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar.


Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells.
Progressive growth of metastatic Lewis lung carcinoma (LLC) tumors results in a concurrent stimulation of myelopoiesis and the appearance of immune-suppressive bone marrow cells. The present study has shown that normal bone marrow cells could be induced to become immune-suppressive by 3 days of culture with supernatants of cloned metastatic LLC-LN7 variant cells. The capacity of the LLC-LN7 supernatants to stimulate the appearance of suppressor cells was directly proportional to the concentration of supernatant used in the bone marrow culture. When adoptively transferred with a LLC-LN7 tumor inoculum, the supernatant-induced suppressor bone marrow cells increased the rate of appearance of palpable tumors and the frequency of tumor establishment. The LLC-LN7 supernatants containing suppressor-cell-inducing activity also had colony-stimulating factor (CSF) activity. The CSF activity produced by the LLC-LN7 cells could be diminished with neutralizing antibodies to either granulocyte/monocyte(GM-) CSF or to interleukin-3 (IL-3). Likewise, the suppressor-inducing activity in the LLC-LN7 supernatants was diminished by pretreatment with anti-GM-CSF or anti-IL-3. The combination of anti-GM-CSF and anti-IL-3 completely neutralized all suppressor-inducing activity produced by the LLC-LN7 cells. These results suggest that the secretion of IL-3 and GM-CSF by LLC-LN7 tumor cells is a mechanism by which the tumors stimulate myelopoiesis and induce normal bone marrow cells to become immune-suppressive. Bone marrow cells that are induced to become immune-suppressive by culture with LLC-LN7 supernatants can, in turn, facilitate the establishment of tumor in vivo.


Behind the Wheel: Unraveling the Impact of Experience Over Age Over the First 18 Months of Licensure.
This study examined how driving attention develops with age and driving. In this observational longitudinal study, 190 adolescents (53% female, 73% Black) were enrolled across four groups: 16- and 18-year olds with and without driving experience. They underwent driving simulation with eye-tracking technology seven times over 18 months. By using a combination of factorial and longitudinal designs, the study examined the individual and combined effects of age and driving experience on driving attention over time. Licensed participants had higher odds of glancing at safety-critical events initially (OR = 15.01, 95% CI: 1.36-165.53), but these odds decreased at higher driving speeds (b = -0.17, p<.01). Average glance length decreased over time (b = -0.26, p=.01), but less so in licensed participants (b=0.14, p=.01). Several visual behaviors were influenced by environmental and driving factors. Motor vehicle crashes (MVCs) are burdensome and costly to society. This study focused on the role of inattention in MVCs, particularly during the risky period of adolescence. Findings indicated that driving experience, as determined by licensure, had a considerable impact on visual behavior in both the short term (within two weeks of obtaining a license) and over the first 18 months of independent driving. Overall, these findings suggest that licensed adolescents are more likely to identify potential hazards on the road and navigate safely. To ensure effective guidance, pediatric psychologists and other professionals should consider the unique circumstances, needs, and concerns of individual patients.


The Family as an Actor in High School Students' Eating Habits: A Qualitative Research Study.
In order to discover family conceptions and their difficulties with regard to healthy eating habits during the school day, a qualitative study framed in the phenomenological, exploratory, and explanatory perspective has been carried out to detect and describe the aspects and interrelationships that shape the study phenomenon. The researchers performed triangulation techniques and information analysis support with the Atlas-ti programme. As participants, the students' parents belonging to public secondary education high schools in Huelva, and the capital and its province were included. The participants were intentionally chosen based on established selection and segmentation criteria. Four main categories were obtained from the triangulated analysis. Healthy breakfast, school snack, school cafeteria, and promotion of healthy food measures. Other subcategories were established within them. Families are well aware of the composition of a healthy breakfast, although this is often not translated into practice. Lack of time, comfort and market influence are the main challenges they encounter for their children to acquire healthy habits. The maintenance of healthy habits, their responsibility and control on behalf of the family, and promoting fruit consumption and healthy products from the part of the centre and its cafeteria were highlighted as improvement proposals.


Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers.
The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technologytrade mark was used to determine the genotype at the MDM2 SNP309 locus. The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80). We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.


Imperceptible bonded composite resin Class III restoration using labial access.
Proper use of modern composite resin materials precludes the need to mask Class III restorations behind residual labial enamel. With the use of micromechanical enamel bonding, chemical adhesion to dentin, and traditional mechanical interlocking, visible Class III composite resin restorations that exactly simulate the color and texture of natural enamel surfaces can be placed. Such imperceptible restorations, when performed properly, can last for many years. This paper details a step-by-step procedure for restoring a Class III carious lesion with composite resin, using labial access and a recently introduced dentinal and enamel bonding agent.


Surgical tray reduction for cost saving in pediatric surgical cases: A qualitative systematic review.
Standardization of surgical instrument trays and doctor preference cards (DPC) are known to reduce the cost of adult surgical cases. The practice in pediatric surgery may be more complex owing to a wide range of patient age, leading to difficulty with practice implementation and loss of potential financial savings, which underscore the importance of the review of this topic. A systematic review of pediatric surgical tray standardization and cost-effectiveness was performed. Original and review articles from 2000 to 2018 were extracted from MEDLINE (via PubMed), Embase, Cinahl, Cochrane, and an electronic search through Scopus. After screening by inclusion and exclusion criteria, articles were selected and reviewed. Five articles were included. On average, discontinuation of disposable instruments and standardization of equipment resulted in a removal of 40%-70% of surgical instruments per set. This yielded a cost savings of 20% (an average US $200), with no intraoperative complications or perceived safety issues. Standardization of operating room (OR) doctor preference cards (DPC) and surgical instrument trays in pediatric surgical cases result in lower operative supply costs without impacting OR time or safety. Level 3.


Comparison of lower body specific resistance training on the hamstring to quadriceps strength ratios in men and women.
In this study, we compared hamstring (H) and quadriceps (Q) strength changes in men and women, as well as changes in conventional and functional H:Q ratios following an identical 12-week resistance training program. An isokinetic dynamometer was used to assess 14 male and 14 female participants before and after the intervention, and conventional and functional H:Q ratios were calculated. Hamstring strength improved similarly in men and women, but improvement in quadriceps strength was significantly greater in men, while women showed only modest improvements. For the conventional and functional H:Q ratios, women showed significantly greater improvements than men. Both men and women were able to exceed the commonly recommended 0.6 conventional and 1.0 functional H:Q ratios after the 12-week lower-body resistance training program.


Chronic resistance training in women potentiates growth hormone in vivo bioactivity: characterization of molecular mass variants.
This investigation determined the influence of acute and chronic resistance exercise on responses of growth hormone (GH) molecular variants in women. Seventy-four healthy young women (23 +/- 3 yr, 167 +/- 7 cm, 63.8 +/- 9.3 kg, 26.3 +/- 4.0% body fat) performed an acute bout of resistance exercise (6 sets of 10 repetition maximum squat). Blood samples were obtained pre- and postexercise. Resulting plasma was fractionated by molecular mass (fraction A, >60 kDa; fraction B, 30-60 kDa; and fraction C, <30 kDa) using chromatography. Fractionated and unfractionated (UF) plasma was then assayed for GH using three different detection systems (monoclonal immunoassay, polyclonal immunoassay, and rat tibial line in vivo bioassay). Subjects were then matched and randomly placed into one of four resistance exercise training groups or a control group for 24 wk. All experimental procedures were repeated on completion of the 24-wk resistance training programs. After acute exercise, immunoassays showed consistent increases in UF GH samples and fractions B and C; increases in fraction A using immunoassay were seen only in the monoclonal assay. No consistent changes in bioactive GH were found following acute exercise. Conversely, chronic exercise induced no consistent changes in immunoassayable GH of various molecular masses, whereas, in general, bioassayable GH increased. In summary, although acute exercise increased only immunoactive GH, chronic physical training increased the biological activity of circulating GH molecular variants. Increased bioactive GH was observed across all fractions and training regimens, suggesting that chronic resistance exercise increased a spectrum of GH molecules that may be necessary for the multitude of somatogenic and metabolic actions of GH.


Development and Validation of the Design Organization Test (DOT): a rapid screening instrument for assessing visuospatial ability.
A brief paper-and-pencil instrument was developed to rapidly assess visuospatial ability and serve as an alterative to the WAIS Block Design subtests during screening or when assessment time is limited. The Design Organization Test (DOT) consists of square black-and-white grids with visual patterns similar to those of the Block Design subtests. Administration is straightforward and requires examinees to reproduce as many designs as possible in 2 minutes using a numerical code key. For 411 college students, alternate forms of the DOT yielded reliability estimates comparable to that of the test-retest reliability of WAIS-III Block Design subtest. In a clinical sample, the DOT was significantly correlated (r = .92) with WAIS-III Block Design scores and was successfully substituted in place of Block Design raw scores without significant change in Performance IQ or Full Scale IQ. The results suggest that the DOT provides a useful and rapid screening measure of visuospatial ability.


Healthcare costs and utilization associated with muscle weakness diagnosis codes in patients with chronic obstructive pulmonary disease: a United States claims analysis.
Muscle weakness (MW)-attributable healthcare resource utilization (HCRU) and costs in patients with chronic obstructive pulmonary disease (COPD) have not been well-characterized in US insurance claims databases. The primary objective of this study was to estimate HCRU in patients with evidence of COPD with and without MW diagnosis codes. This retrospective analysis used the MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Between January 2007 and March 2016, we identified patients aged ≥40 years with diagnosis codes for COPD (≥1 emergency department or inpatient claim or ≥2 outpatient claims within 1 year). The cohort was divided into patients with and without ≥1 MW diagnosis code. Propensity score matching was used to generate pairs of patients with and without MW (1:1). Multivariable regression analyses were used to estimate adjusted incremental costs and utilization attributable to the presence of MW diagnosis codes among patients with COPD. Of 427,131 patients who met the study inclusion criteria, 14% had evidence of MW. After matching, 107,420 unique patients remained equally distributed across MW status. Patients with MW diagnosis codes had greater predicted annual HCRU, $2,465 greater total predicted annual COPD-related costs, and $15,179 greater total all-cause costs than those without MW diagnosis codes. Overall, <1% of patients received COPD-related pulmonary rehabilitation services. Study limitations include the potential for undercoding of MW and lack of information on severity of MW in claims data. The presence of MW diagnosis codes yielded higher HCRU in this COPD population and suggests that the burden of MW affects both all-cause and COPD-related care. However, utilization of pulmonary rehabilitation, a known effective treatment for MW, remains low. Future research should expand on our results by assessing data sources that allow for clinical confirmation of MW among patients with COPD.


A comparison of alternative assays to measure DNA damage in stallion spermatozoa: TUNEL test versus 'Nicoletti assay'.
The aberrations of sperm DNA may cause various problems and have negative consequences on fertility. These influence embryonic development or might lead to early embryo loss. Sperm Chromatin Structure Assay (SCSA) is the flow cytometric method most often used for the detection of DNA lesions; however, some studies using that method reached confusing conclusions. The aim of this pilot study was to adjust and compare two alternative tests, namely the TUNEL test and the Nicoletti assay. The above-mentioned two flow cytometric methods capable of detecting the fragmented DNA of sperm were tested on 12 frozen-thawed stallion semen samples. The TUNEL test demonstrated much higher DNA fragmentation ratio than the Nicoletti assay (mean ± SD: 30.77 ± 13.03% vs. 1.93 ± 0.89%, respectively). A fluorescent microscopic check of the samples showed that TUNEL labelled the plasma membrane and the mitochondria in a nonspecific way, rather than detecting only the fragmented DNA, thus eventually resulting in a false positive sign. The Nicoletti assay is simpler, quicker and does not detect nonspecific binding; however, further analyses are required to determine its diagnostic value.


UP446, analgesic and anti-inflammatory botanical composition.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease. Long-term use of currently available therapies for RA produces adverse effects that limit dosage and duration; hence there is a need for safe and effective alternatives suitable for long term chronic use. UP446, a composition consisting primarily of baicalin from Scutellaria baicalensis Georgi (Family: Lamiaceae) and (+)-catechin from the heartwoods of Acacia catechu (Family: Mimosaceae), has been previously shown to reduce production of eicosanoids and leukotrienes through dual inhibition of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes and to decreased mRNA and protein levels of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. To evaluate the likelihood of UP446 in moderating arthritis and its associated symptoms in an experimental animal model of RA. A RA rat model was induced by injecting Freund's complete adjuvant into left and right hind paw and base of the tail. Animals were administered UP446 (50 mg/kg), ibuprofen (150 mg/kg mg/kg) or vehicle by oral gavage 30 min prior to arthritis induction and each day thereafter for 14 days. Animals treated with UP446 showed 23.7, 31.9, 33.4, 29.3, and 33.1% reduction in pain sensitivity; 46.0, 36.7, 33.7, 34.8, and 33.4% reduction in ankle diameter on days 3, 5, 7, 9, and 13; respectively; compared to vehicle. Similarly paw edema was significantly reduced with an average of 30% for the first inflammatory reaction period (day 1-8) followed by 37.1 and 33.6% reduction on day 9 and 13. These data indicate potential benefit of UP446 in alleviating symptoms of RA and support human clinical evaluation of this botanical composition in patients with RA.


Novel cooperation experimentally evolved between species.
Cooperation violates the view of "nature red in tooth and claw" that prevails in our understanding of evolution, yet examples of cooperation abound. Most work has focused on maintenance of cooperation within a single species through mechanisms such as kin selection. The factors necessary for the evolutionary origin of aiding unrelated individuals such as members of another species have not been experimentally tested. Here, I demonstrate that cooperation between species can be evolved in the laboratory if (1) there is preexisting reciprocation or feedback for cooperation, and (2) reciprocation is preferentially received by cooperative genotypes. I used a two species system involving Salmonella enterica ser. Typhimurium and an Escherichia coli mutant unable to synthesize an essential amino acid. In lactose media Salmonella consumes metabolic waste from E. coli, thus creating a mechanism of reciprocation for cooperation. Growth in a spatially structured environment assured that the benefits of cooperation were preferentially received by cooperative genotypes. Salmonella evolved to aid E. coli by excreting a costly amino acid, however this novel cooperation disappeared if the waste consumption or spatial structure were removed. This study builds on previous work to demonstrate an experimental origin of interspecific cooperation, and to test the factors necessary for such interactions to arise.


Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute to the disclosure of the A1006E mutation.
Since the identification of the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene in 1989, many genetic mutations have been found in cystic fibrosis (CF) patients. Dysfunctions of the CFTR gene are responsible for the highly variable clinical presentation ranging from severe CF, disseminated bronchiectasis, idiopathic chronic pancreatitis and congenital bilateral absence of vas deferens (CBAVD). Linkage disequilibrium studies have shown that some mutations are stringently coupled with polymorphisms in a genetic complex called haplotype. From a familial study of a patient with CBAVD, carrier of the A1006E mutation, we have observed its strict association with the polymorphism 5T-TG11. In order to speed up the genetic diagnosis and to correlate the clinical setting to this genetic feature, we have directly investigated the exon 17a, where the A1006E mutation is located, of five cystic fibrosis patients belonging to two unrelated families. All patients had the 5T-TG11 tract, F508del and one unknown mutation. One more family with two affected individuals carrying the Q220X/A1006E mutations was investigated for the poly-T polymorphism. All the members were found to have the A1006E mutation and the 5T-TG11 in the same DNA strand, demonstrating that this strategy is a reliable and inexpensive method for genotyping the CFTR gene. A detailed description of the clinical presentation and follow-up are provided in order to highlight common phenotypic features useful to improve the management of cystic fibrosis patients.


Physiological and pathological roles of LRRK2 in the nuclear envelope integrity.
Mutations in LRRK2 cause autosomal dominant and sporadic Parkinson's disease, but the mechanisms involved in LRRK2 toxicity in PD are yet to be fully understood. We found that LRRK2 translocates to the nucleus by binding to seven in absentia homolog (SIAH-1), and in the nucleus it directly interacts with lamin A/C, independent of its kinase activity. LRRK2 knockdown caused nuclear lamina abnormalities and nuclear disruption. LRRK2 disease mutations mostly abolish the interaction with lamin A/C and, similar to LRRK2 knockdown, cause disorganization of lamin A/C and leakage of nuclear proteins. Dopaminergic neurons of LRRK2 G2019S transgenic and LRRK2 -/- mice display decreased circularity of the nuclear lamina and leakage of the nuclear protein 53BP1 to the cytosol. Dopaminergic nigral and cortical neurons of both LRRK2 G2019S and idiopathic PD patients exhibit abnormalities of the nuclear lamina. Our data indicate that LRRK2 plays an essential role in maintaining nuclear envelope integrity. Disruption of this function by disease mutations suggests a novel phosphorylation-independent loss-of-function mechanism that may synergize with other neurotoxic effects caused by LRRK2 mutations.


Rapid start-up strategy and microbial population evolution of anaerobic ammonia oxidation biofilm process for low-strength wastewater treatment.
The implementation of the anaerobic ammonium oxidation (anammox) process in treating low-strength wastewater is limited by the difficulty in enriching anammox bacteria (AnAOB). Here, the first enrichment of AnAOB at a high nitrogen (N) loading rate (NLR) as a strategy was proposed to achieve the rapid start-up of the anammox biofilm process treating low-strength wastewater. The long-term stability of the anammox biofilm process after start-up operating at a low NLR of 0.2-0.4 kg N/(m3⋅d) was evaluated. Results showed that the N removal efficiency was up to 75 % under a low NLR of 0.2 kg N/(m3⋅d) condition. Low-strength organic matter promoted the metabolic coupling between partial denitrifying bacteria (PDB) and AnAOB. The genus Candidatus Brocadia as AnAOB (18 %-27 %) can coexist with Limnobacter (PDB, 9 %-12 %) for efficient N removal. This study offers a rapid start-up strategy of anammox biofilm process in treating low-strength wastewater.


Organoactinides in catalytic transformations: scope, mechanisms and Quo Vadis.
The last decade has witnessed wonderful and remarkable advances in the chemistry of early actinides, providing information on not only the reactivity of these types of compounds in stoichiometric reactions but also their utilization in challenging catalytic processes. This canvas of knowledge allows the design of chemical reactivities to reach a high level of sophistication. As compared to early/late transition metal and lanthanide complexes, the actinides display complementary and in some cases real unique performances for similar organic transformations. The study of organoactinides allows us to design new chemical transformations due to their distinctive electronic structures, which feature a large coordination number exhibiting steric interactions. This review highlights the latest results obtained since 2008 on the catalytic activities of organoactinides. This review presents a brief introduction, and two main parts: (i) organoactinide mediated catalytic transformations of small molecules, including hydroelementation, coupling reactions, etc.; (ii) organoactinide catalysed polymerization and oligomerization reactions, including olefin, diene, cyclic ester and epoxide substrates. At the end, we present our Quo Vadis opinion and pose some challenging questions and our personal opinion regarding where this field should continue to develop.


Different pain responses to distinct levels of physical activity in women with patellofemoral pain.
Physical activity levels seem to play a role in patellofemoral pain (PFP); however, few studies have been conducted to confirm this hypothesis. To determine the reported pain levels of women with and without PFP who maintain different levels of physical activity; to determine the capability of these levels to predict pain; and to test the capability of two stair-negotiation protocols, with and without external load, to equalize pain between groups. Four groups were divided based on the women's physical activity levels: moderate activity PFP group (28), moderate activity control group (23), intense activity PFP group (22), and intense activity control group (22). All participants were asked to perform 15 repetitions of stair negotiation with and without external load on a seven-step staircase on two separate days. Pain levels were reported using a visual analog scale at five distinct moments: previous month, before stair negotiation, after stair negotiation, before patellofemoral joint (PFJ) loading protocol, and after PFJ loading protocol. The intense activity PFP group showed higher levels of pain than the moderate activity PFP group (F(8,158)=11.714, p=0.000, η2=0.30). The PFJ loading protocol was able to equalize and exacerbate pain in the PFP groups. Intense physical activity seems to have a higher association with knee pain than moderate physical activity. A PFJ loading protocol may be an alternative to equalize pain in women with PFP during clinical assessments.


[Effect of negative pressure and occluding cuffs on the intravascular pressure in the lower extremity of the healthy human being].
The effect of local negative pressure on the leg (with a bladder sealed above the knee) and occlusion cuffs (located as close as possible to Poupart's ligament) on the leg intravascular pressure was investigated in recumbency. In two experimental runs 8 healthy volunteers participated. Each of the two exposures was used at two levels: local negative pressure at -50 and -100 mm Hg and occlusion cuffs at +40 and +60 mm Hg with the exposure time averaging 5-7 min. Catheters were inserted into the femoral artery and vein, and arteries and veins of the back of the foot. The arterial pressure remained unchanged during both exposures: local negative pressure and occlusion cuffs. Upon exposure to local negative pressure the venous pressure in the back of the foot (with respect to the atmospheric pressure) did not change and in the femoral vein decreased. Upon exposure to occlusion cuffs the venous pressure in the back of the foot increased noticeably and in the femoral vein decreased slightly. It is concluded that none of the exposures can reproduce the major gravitational effect on leg vessels, i.e. characteristic changes in gradients of the intravascular (transmural) pressure.


Customized guidance/training improved the psychometric properties of methodologically rigorous risk of bias instruments for non-randomized studies.
To evaluate the impact of guidance and training on the inter-rater reliability (IRR), inter-consensus reliability (ICR) and evaluator burden of the Risk of Bias (RoB) in Non-randomized Studies (NRS) of Interventions (ROBINS-I) tool, and the RoB instrument for NRS of Exposures (ROB-NRSE). In a before-and-after study, seven reviewers appraised the RoB using ROBINS-I (n = 44) and ROB-NRSE (n = 44), before and after guidance and training. We used Gwet's AC1 statistic to calculate IRR and ICR. After guidance and training, the IRR and ICR of the overall bias domain of ROBINS-I and ROB-NRSE improved significantly; with many individual domains showing either a significant (IRR and ICR of ROB-NRSE; ICR of ROBINS-I), or nonsignificant improvement (IRR of ROBINS-I). Evaluator burden significantly decreased after guidance and training for ROBINS-I, whereas for ROB-NRSE there was a slight nonsignificant increase. Overall, there was benefit for guidance and training for both tools. We highly recommend guidance and training to reviewers prior to RoB assessments and that future research investigate aspects of guidance and training that are most effective.


Paracreptotrema blancoi n. gen., n. sp. (Digenea: Plagiorchiformes: Allocreadiidae) in the Olomina, Priapichthys annectens (Osteichthyes: poeciliidae), from the Area de Conservación Guanacaste, Costa Rica.
A new species of allocreadiid digenean is described from Priapichthys annectens (Regan) (Osteichthyes: Poeciliidae) in the Area de Conservación Guanacaste, Costa Rica. A new genus, Paracreptotrema, is proposed to accommodate this species as well as Fellodistomum mendezi Songandares-Bernal, 1955, which was previously described from another poeciliid, Brachyrhaphis episcopi, in Panama. Paracreptotrema differs from all other nominal genera of Allocreadiidae by a combination of its symmetrical testes, restricted vitellaria, and the lack of oral lappets (muscular 'papillae') or other such appendages. Paracreptotrema blancoi n. sp. resembles Creptotrema creptotrema Travassos, Artigas and Pereira, 1928, but differs in lacking ventral oral lappets and in having vitellaria extending posteriorly only to the level of the testes. It can be distinguished from P. mendezi n. comb. in having a relatively larger and more posteriorly placed acetabulum, vitellaria that are more restricted anteriorly, smaller testes, and a uterus that does not extend to the posterior end of the body. The genus seems to be restricted to poeciliids in Central America.


[Oxidative-reductive processes in diabetes mellitus].
Altogether 70 patients with diabetes mellitus of medium severity were examined to determine sulfhydryl (SH) groups, total glutathione (tG) and its individual forms, reduced (rG) and oxidized (oG), cytochrome oxidase activity (CCO), blood and urine V-O, and underoxidation coefficient of the urine with respect to the degree of hyperglycemia and glucosuria. Effect of sugar-reducing therapy on these parameters was studied in 26 subjects. A statistically significant reduction in SH groups balance, in oG content at the expense of rG, increase in CCO activity, in the blood and urine V-O, and in underoxidation coefficient of the urine were detected. The observed changes depend on the sugar content in the blood and urine, and do not disappear even when normoglycemia and aglycosuria are achieved after the use of sugar-reducing drugs.


Metal-free photocatalysts for hydrogen evolution.
This review focuses on the discussion of the latest progress and remaining challenges in selected metal-free photocatalysts for hydrogen production. The scope of this review is limited to the metal-free elemental photocatalysts (i.e. B, C, P, S, Si, Se etc.), binary photocatalysts (i.e. BC3, B4C, CxNy, h-BN etc.) and their heterojunction, ternary photocatalysts (i.e. BCN) and their heterojunction, and different types of organic photocatalysts (i.e. linear, covalent organic frameworks, microporous polymer, covalent triazine frameworks etc.) and their heterostructures. Following a succinct depiction of the latest progress in hydrogen evolution on these photocatalysts, discussion has been extended to the potential strategies that are deemed necessary to attain high quantum efficiency and high solar-to-hydrogen (STH) conversion efficiency. Issues with reproducibility and the disputes in reporting the hydrogen evolution rate have been also discussed with recommendations to overcome them. A few key factors are highlighted that may facilitate the scalability of the photocatalyst from microscale to macroscale production in meeting the targeted 10% STH. This review is concluded with additional perspectives regarding future research in fundamental materials aspects of high efficiency photocatalysts followed by six open questions that may need to be resolved by forming a global hydrogen taskforce in order to translate bench-top research into large-scale production of hydrogen.


How CEOs respond to mortality salience during the COVID-19 pandemic: Integrating terror management theory with regulatory focus theory.
The COVID-19 pandemic has caused hundreds of thousands of deaths in the U.S. As chief strategists of their respective firms, how do Chief Executive Officers (CEOs) react to mortality salience associated with the number of new daily COVID deaths in the U.S.? To answer this question, we integrate terror management theory (TMT) with regulatory focus theory to examine how CEOs respond to mortality salience. Based on a sample of CEOs of S&P 500 firms, we found that mortality salience was associated with CEOs' increased other-orientation, and this association was more pronounced among those with high prevention focus. Mortality salience also was associated with CEOs' decreased self-orientation, particularly among those with high promotion focus. We also found that CEOs' self-orientation was negatively related to the likelihood of their firms' making community donations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Nutrient intake in aging infants and toddlers: 3-year follow-up of the Nutrintake study.
We performed a 3-year follow-up of the children enrolled into the Nutrintake Study to evaluate the changes of anthropometry and nutrient intake in aging infants and toddlers. Nutrient intake was assessed using a 7-day weighted food-diary. Of the 390 Nutrintake children, 164 (42%) participated in the present study. Their median (IQR) age was 54 (48; 66) months and their anthropometrical status, expressed as standard deviation scores, remained stable during the follow-up. During the same period, there was no biologically relevant change in the intake of macronutrients expressed as percentage of energy while median increases of 757 mg/day, 0.7 mg/day and 3.1 g/1000 kcal per day were detected for sodium, iron and fibre, respectively. As compared to the Italian reference standards, the Nutrintake children continued to show at the 3-year follow-up an excessive intake of simple carbohydrates, proteins, sodium, and a low intake of iron and fibre.


Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI).
The pathogenesis of ST-elevation myocardial infarction (STEMI) involves plaque disruption, platelet aggregation and intracoronary artery thrombus formation. Aspirin is the cornerstone of antiplatelet therapy in patients with STEMI, reducing the risk of recurrent myocardial infarction or death during the acute phase and long term by about one-quarter. Recent large randomized trials have demonstrated that the addition of clopidogrel to aspirin reduces the risk of major ischemic events by up to a further one-third in patients with STEMI treated with fibrinolytic therapy and undergoing percutaneous coronary intervention, with no significant increase in bleeding. Thus, dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with STEMI.


[Near surface CO2 concentration and its quantitative relationship with character of underlying surface in Shanghai City, China].
Land use change and fossil fuel combustion due to urbanization have a significant effect on global carbon cycle and climate change. It's important to have an explicit understanding of the spatial distribution of CO2 to recognize and control GHG emission, which is helpful to reduce human-induced contribution to global climate change. The study area of this project was set in the city of Shanghai with intensive human activity and rapid urbanization. The monitoring of near surface CO2 concentration along 3 transects was conducted across an urban-rural gradient by means of near infrared gas analyzer Li-840A in spring, 2014. Remote sensing data were also used to derive underlying surface information. Further quantitative analysis of the mechanism of CO2 concentration's response to the characteristics of underlying surface was presented in this paper. The results showed that the average near surface CO2 concentration was (443.4±22.0) µmol . mol-1. CO2 concentration in city center was in average 12.5% (52.5 µLmol . mol-1) higher than that in the suburban area. Also, CO2 concentration showed a significant spatial differentiation, with the highest CO2 concentration in the northwest, the second highest in the southwest, and the lowest in the southeast, which was in accordance with the urbanization level of the underlying surface. The results revealed that the vegetation coverage rate (CVeg) was an important indicator to describe near surface CO2 concentration with a negative correlation, and the impervious surface area coverage rate (CISA) had lower explanatory power with a positive correlation. The study also found that the determination coefficient (R2) between CO2 concentration (CCO2) and CISA or CVeg achieved its highest value when the buffer distance was 5 km, and their quantitative relationships be described by a stepwise regression equation: CCO2=0.32CISA-0.89CVeg+445.13 (R2 =0.66, P<0.01).


Between-method differences in prostate-specific antigen assays affect prostate cancer risk prediction by nomograms.
To date, no published nomogram for prostate cancer (PCa) risk prediction has considered the between-method differences associated with estimating concentrations of prostate-specific antigen (PSA). Total PSA (tPSA) and free PSA were measured in 780 biopsy-referred men with 5 different assays. These data, together with other clinical parameters, were applied to 5 published nomograms that are used for PCa detection. Discrimination and calibration criteria were used to characterize the accuracy of the nomogram models under these conditions. PCa was found in 455 men (58.3%), and 325 men had no evidence of malignancy. Median tPSA concentrations ranged from 5.5 μg/L to 7.04 μg/L, whereas the median percentage of free PSA ranged from 10.6% to 16.4%. Both the calibration and discrimination of the nomograms varied significantly across different types of PSA assays. Median PCa probabilities, which indicate PCa risk, ranged from 0.59 to 0.76 when different PSA assays were used within the same nomogram. On the other hand, various nomograms produced different PCa probabilities when the same PSA assay was used. Although the ROC curves had comparable areas under the ROC curve, considerable differences were observed among the 5 assays when the sensitivities and specificities at various PCa probability cutoffs were analyzed. The accuracy of the PCa probabilities predicted according to different nomograms is limited by the lack of agreement between the different PSA assays. This difference between methods may lead to unacceptable variation in PCa risk prediction. A more cautious application of nomograms is recommended.


Association between proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhotic patients with ascites.
There are data suggesting a link between proton pump inhibitor (PPI) use and the development of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites; however, these data are controversial. To assess whether the use of PPIs in cirrhotic patients with ascites is associated with an increased risk for SBP. A retrospective case-control study (June 2004 to June 2010) was conducted at the Centre Hospitalier de l'Université de Montréal in Montreal, Quebec. Fifty-one cirrhotic patients admitted with paracentesis-proven SBP (≥250 neutrophils/mm3), occurring within seven days of hospital admission, met the inclusion criteria. These patients were matched 1:2 (for age, Child-Pugh class and year of admission) with 102 comparable cirrhotic patients with ascites who were admitted for conditions other than SBP. Patients with SBP had a significantly higher rate of pre-hospital PPI use (60.8%) compared with cirrhotic patients without SBP (42.2%; P=0.03). On multivariate analysis, PPI use was the only factor independently associated with SBP (OR 2.09 [95% CI 1.04 to 4.23]; P=0.04). Thirty-five (35%) patients in both groups had no documented indication for PPI use in their charts. Forty-five percent of the remaining cirrhotic patients with SBP had an inappropriate indication, as defined in the protocol, for PPI use compared with 25% of controls. Cirrhotic patients with SBP were twice as likely to have taken PPIs than patients without SBP. These findings reinforce the association between PPI use and SBP observed in other studies. A high percentage of cirrhotic patients were taking a PPI without any documented indication.


Linear Combination of Hamiltonian Simulation for Nonunitary Dynamics with Optimal State Preparation Cost.
We propose a simple method for simulating a general class of nonunitary dynamics as a linear combination of Hamiltonian simulation (LCHS) problems. LCHS does not rely on converting the problem into a dilated linear system problem or on the spectral mapping theorem. The latter is the mathematical foundation of many quantum algorithms for solving a wide variety of tasks involving nonunitary processes, such as the quantum singular value transformation. The LCHS method can achieve optimal cost in terms of state preparation. We also demonstrate an application for open quantum dynamics simulation using the complex absorbing potential method with near-optimal dependence on all parameters.


Short-Term Effectiveness of Precut Kinesiology Tape Versus an NSAID as Adjuvant Treatment to Exercise for Subacromial Impingement: A Randomized Controlled Trial.
To compare the short-term effectiveness of precut kinesiology tape (PCT) to a nonsteroidal anti-inflammatory drug (NSAID) as adjuvant treatment to exercise physiotherapy in improving pain and function in patients with shoulder impingement. Randomized, controlled assessor-blind parallel-design trial with 3 groups. Academic-community hospital. One hundred patients (mean age: 48 ± 12.3, 61 men, 39 women) with a diagnosis of subacromial impingement (SAI) syndrome were randomized to a treatment group from October 2009 to June 2012. Eighty-one patients completed the study. Patients were randomized to one of the 3 treatment groups: PCT and Exercise (n = 33), NSAID and Exercise (n = 29), or Exercise only (n = 38) for a 4 session 2-week intervention with a registered physiotherapist. Numeric pain rating scales for pain at rest and pain with arm elevation, the Simple Shoulder Test (SST), and the Constant Score were assessed pretreatment and post-treatment. A statistically significant reduction in pain at rest and pain with arm elevation, as well as improvement in SST and Constant Score were observed in all 3 treatment groups, with minimal clinically important differences shown on pain with elevation and SST scores. Between-group differences on all outcome measures were not statistically significant or clinically meaningful. The improvements in pain and function observed with an NSAID or PCT as adjuvant treatments were no greater than with rehabilitation exercise alone. If adjuvant treatment is desired, PCT seems to be better tolerated than an NSAID, although the difference did not reach significance. The routine addition of adjuvant treatment is not supported by the results of this study. As adjuvant therapy, PCT seems to be better tolerated than an NSAID. If desired, clinicians may consider incorporating PCT along with an exercise component in the conservative treatment of SAI syndrome.


Modulating the polarization phenotype of microglia - a valuable strategy for central nervous system diseases.
Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.


Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy.
Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicited mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production resulted in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis was inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibited mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reversed sesamol-induced apoptosis and mitochondrial respiration disorders. Moreover, it was also shown that sesamol has potent anti-hepatoma activity in a xenograft nude mice model. These data suggest that mitochondria play an essential role in sesamol-induced HepG2 cells death, and further research targeting mitochondria will provide more chemotherapeutic opportunities.


The Association between Tooth Loss and Insulin Resistance Mediated by Diet Quality and Systemic Immunoinflammatory Index.
(1) Background: Both tooth loss and diabetes have high global prevalence, and both have a significant influence on patients' general health and quality of life. Previous research has indicated a possible connection between tooth loss and diabetes, but it has been unclear whether tooth loss has an effect on the development of diabetes and how it affects it. We aim to investigate the relationship between insulin resistance (IR) and tooth loss and examine how the systemic immune-inflammation index (SII) level and diet quality mediate it. (2) Methods: The cross-sectional study data were obtained from the National Health and Nutrition Examination Survey (NHANES). After describing and comparing baseline data, we used regression models to evaluate the relationship between IR and tooth loss, diet quality and tooth loss and IR, SII and tooth loss and IR. Furthermore, we applied bootstrapping to test the mediation effect of diet quality and SII between tooth loss and IR. Diet quality is reflected by the HEI (Healthy Eating Index)-2015 score. (3) Results: The total number of subjects included was 8197, with 3861 individuals belonging to the IR group (HOMA-IR ≥ 2.5) and 4336 in the non-IR group (HOMA-IR < 2.5). In the model with all covariates adjusted, tooth loss in the fourth quartile was found to be positively correlated with an increase in HOMA-IR (OR = 1.301; 95% confidence interval (CI) = [1.102, 1.537]; p < 0.001) compared to the first quartile; tooth loss in the fourth quartile correlated with the HEI-2015 score compared to the first quantile (β = -0.121, 95% CI = [-4.839, -2.974], p < 0.001); and the highest number of tooth loss was found to have a significant effect on SII (β = 0.032; 95%CI = [1.777, 47.448]; p < 0.05). Compared to average diet quality, best diet quality acts as a safeguard against elevated HOMA-IR (OR = 0.776; 95% CI = [0.641, 0.939]; p < 0.01); inadequate diet quality is a risk factor (OR = 1.267; 95%CI = [1.138, 1.411]; p < 0.001) conversely. Meanwhile, it can be seen that compared with the first quantile of SII, the highest score is significantly correlated with the higher incidence of IR (OR = 1.363; 95%CI = [1.179, 1.575]; p < 0.001). Diet quality and SII played a partial mediating role in the relationship between HOMA-IR and tooth loss, and the mediating effect ratio for the total effect value was 4.731% and 4.576%, respectively. The mediating effect of SII and diet quality in the association of the relationship between HOMA-IR and tooth loss both was 0.003 (95%CI = [0.001, 0.004]). (4) Conclusions: Our study revealed the relationship between IR and tooth loss, and further explored the mediating role of SII and diet quality between the number of missing teeth and IR, emphasizing that improving diet quality and reducing SII can effectively prevent and treat IR and related diseases. It provides new theoretical support for the study of IR mechanisms and new ideas and approaches to deal with related diseases.


Strategic assessment of COVID-19 pandemic in Bangladesh: comparative lockdown scenario analysis, public perception, and management for sustainability.
Community transmission of COVID-19 is happening in Bangladesh-the country which did not have a noteworthy health policy and legislative structures to combat a pandemic like COVID-19. Early strategic planning and groundwork for evolving and established challenges are crucial to assemble resources and react in an appropriate timely manner. This article, therefore, focuses on the public perception of comparative lockdown scenario analysis and how they may affect the sustainable development goals (SDGs) and the strategic management regime of COVID-19 pandemic in Bangladesh socio-economically as well as the implications of the withdrawal of partial lockdown plan. Scenario-based public perceptions were collected via a purposive sampling survey method through a questionnaire. Datasets were analysed through a set of statistical techniques including classical test theory, principal component analysis, hierarchical cluster analysis, Pearson's correlation matrix and linear regression analysis. There were good associations among the lockdown scenarios and response strategies to be formulated. Scenario 1 describes how the death and infection rate will increase if the Bangladesh Government withdraws the existing partial lockdown. Scenario 2 outlines that limited people's movement will enable low-level community transmission of COVID-19 with the infection and death rate will increase slowly (r = 0.540, p < 0.01). Moreover, there will be less supply of necessities of daily use with a price hike (r = 0.680, p < 0.01). In scenario 3, full lockdown will reduce community transmission and death from COVID-19 (r = 0.545, p < 0.01). However, along with the other problems gender discrimination and gender-based violence will increase rapidly (r = 0.661, p < 0.01). Due to full lockdown, the formal and informal business, economy, and education sector will be hampered severely (R = 0.695). Subsequently, there was a strong association between the loss of livelihood and the unemployment rate which will increase due to business shutdown (p < 0.01). This will lead to the severe sufferings of poor and vulnerable communities in both urban and rural areas (p < 0.01). All these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed which will undoubtedly affect the Bangladesh targets to achieve the SDGs of 2030 and other development plans that need to be adjusted. From our analysis, it was apparent that maintaining partial lockdown with business and economic activities with social distancing and public health guidelines is the best strategy to maintain. However, as the government withdrew the partial lockdown, inclusive and transparent risk communication towards the public should be followed. Recovery and strengthening of the health sector, economy, industry, agriculture, and food security should be focused on under the "new normal standard of life" following health guidelines and social distancing. Proper response plans and strategic management are necessary for the sustainability of the nation.


Distinct Metabolites in Osteopenia and Osteoporosis: A Systematic Review and Meta-Analysis.
Multiple studies have indicated that distinct metabolites are involved in the occurrence and development of osteopenia (ON) and osteoporosis (OP); however, these metabolites in OP and ON have not yet been classified and standardized. This systematic review and meta-analysis included 21 articles aiming to investigate the distinct metabolites in patients with ON and OP. The quality of the included articles was generally high; seventeen studies had >7 stars, and the remaining four received 6 stars. This systematic review showed that three metabolites (phosphatidylcholine (PC) (lipid metabolites), galactose (carbohydrate metabolites), and succinic acid (other metabolites)) increased, four (glycylglycine (gly-gly), cystine (amino acids), sphingomyelin (SM) (lipid metabolites) and glucose (carbohydrate metabolites)) decreased, and five (glutamine, hydroxyproline, taurine (amino acids), lysophosphatidylcholine (LPC) (lipid metabolites), and lactate (other metabolites)) had conflicting directions in OP/ON. The results of the meta-analysis show that gly-gly (MD = -0.77, 95%CI -1.43 to -0.11, p = 0.02) and cystine (MD = -5.52, 95%CI -7.35 to -3.68, p < 0.00001) decreased in the OP group compared with the healthy control group. Moreover, LPC (MD = 1.48, 95%CI 0.11 to 2.86, p = 0.03) increased in the OP group compared with the healthy control group. These results indicate that distinct metabolites were associated with ON and OP, which could be considered a predictor for OP.


Size dependent behavior of Fe3O4 crystals during electrochemical (de)lithiation: an in situ X-ray diffraction, ex situ X-ray absorption spectroscopy, transmission electron microscopy and theoretical investigation.
The iron oxide magnetite, Fe3O4, is a promising conversion type lithium ion battery anode material due to its high natural abundance, low cost and high theoretical capacity. While the close packing of ions in the inverse spinel structure of Fe3O4 enables high energy density, it also limits the kinetics of lithium ion diffusion in the material. Nanosizing of Fe3O4 to reduce the diffusion path length is an effective strategy for overcoming this issue and results in improved rate capability. However, the impact of nanosizing on the multiple structural transformations that occur during the electrochemical (de)lithiation reaction in Fe3O4 is poorly understood. In this study, the influence of crystallite size on the lithiation-conversion mechanisms in Fe3O4 is investigated using complementary X-ray techniques along with transmission electron microscopy (TEM) and continuum level simulations on electrodes of two different Fe3O4 crystallite sizes. In situ X-ray diffraction (XRD) measurements were utilized to track the changes to the crystalline phases during (de)lithiation. X-ray absorption spectroscopy (XAS) measurements at multiple points during the (de)lithiation processes provided local electronic and atomic structural information. Tracking the crystalline and nanocrystalline phases during the first (de)lithiation provides experimental evidence that (1) the lithiation mechanism is non-uniform and dependent on crystallite size, where increased Li+ diffusion length in larger crystals results in conversion to Fe0 metal while insertion of Li+ into spinel-Fe3O4 is still occurring, and (2) the disorder and size of the Fe metal domains formed when either material is fully lithiated impacts the homogeneity of the FeO phase formed during the subsequent delithiation.


Carbohydrate-binding module 74 is a novel starch-binding domain associated with large and multidomain α-amylase enzymes.
Microbacterium aurum B8.A is a bacterium that originates from a potato starch-processing plant and employs a GH13 α-amylase (MaAmyA) enzyme that forms pores in potato starch granules. MaAmyA is a large and multi-modular protein that contains a novel domain at its C terminus (Domain 2). Deletion of Domain 2 from MaAmyA did not affect its ability to degrade starch granules but resulted in a strong reduction in granular pore size. Here, we separately expressed and purified this Domain 2 in Escherichia coli and determined its likely function in starch pore formation. Domain 2 independently binds amylose, amylopectin, and granular starch but does not have any detectable catalytic (hydrolytic or oxidizing) activity on α-glucan substrates. Therefore, we propose that this novel starch-binding domain is a new carbohydrate-binding module (CBM), the first representative of family CBM74 that assists MaAmyA in efficient pore formation in starch granules. Protein sequence-based BLAST searches revealed that CBM74 occurs widespread, but in bacteria only, and is often associated with large and multi-domain α-amylases containing family CBM25 or CBM26 domains. CBM74 may specifically function in binding to granular starches to enhance the capability of α-amylase enzymes to degrade resistant starches (RSs). Interestingly, the majority of family CBM74 representatives are found in α-amylases originating from human gut-associated Bifidobacteria, where they may assist in resistant starch degradation. The CBM74 domain thus may have a strong impact on the efficiency of RS digestion in the mammalian gastrointestinal tract.


Behavior of the lysosomal system during organ perfusion. An inquiry into the mechanism of hepatic proteolysis.
In this chapter we have attempted to provide some insight into a mechanism(s) of protein degradation in liver which we believe is implicated in the physiological regulation of free amino acid pools. The association we have observed between regulatory effects of insulin and amino acids in the perfused rat liver and physical alterations of the lysosomal system in similarly treated livers suggests that the final stage of the process is localized within the lysosomal-vacuolar system. The present studies show that perfusion of the isolated rat liver is in itself a potent stimulus to general proteolysis, an effect which is associated with increases in lysosomal size, density and sensitivity to osmotic shock. Since the osmotic and density alterations can be prevented or reversed by the provision of insulin or amino acid mixtures, we believe these agents normally act to restrain some inherent proteolytic process. Although the attendant lysosomal alterations are similar in many respects to those induced by glucagon, they differ sharply from the latter in having no sequestered organelles or evident membrane structures and the fact that they rise in the absence of any increase in the tissue level of cyclic AMP. Aside from the obvious problem of evaluating the quantitative importance of the lysosomal system in hepatic proteolysis, three interesting problems remain to be solved: (1) the nature of the proteins involved, (2) their mode of acquisition by the lysosome, and (3) the relationship of this inherent proteolytic process to glucagon or cyclic AMP-induced cellular autophagy. With regard to the former it seems reasonably clear from our studies and those of others that protein substrate does not gain access to lysosomal proteases by the direct penetration of lysosomal membranes, but more likely by fusion of a preexisting lysosome with some, as yet undefined, membrane-bound element. Whether such an element is formed in a manner analogous to that of the precursor vacuoles in autophagy (Ericsson 1969) or by some other process is not known. Closely related to this is the question of the nature of the substrate and the factors determining its uptake by the lysosome. Space does not permit us to review evidence from a number of laboratories which suggests that the turnover of intracellular protein may be a function of size (Dehlinger and Schimke 1971; Dice et al. 1973), charge (Dice and Goldberg 1975), or conformational stability (Li and Knox 1972; Ballard et al. 1974). We have no idea at the moment whether the mechanism we have outlined will eventually be shown to encompass a wide range of turnover of intracellular proteins or, alternatively, whether it will be limited to a certain class of proteins that turnover as a unit. While there is undoubtedly far more specificity in the regulation of intracellular proteins than our present data indicate, we do not view this as an incompatibility, but rather as another aspect of a complex problem we are only beginning to understand.


Congenital partial absence of the left pericardium.
A 38 year old woman with congenital partial absence of the left pericardium is presented. The condition is fairly rare, usually diagnosed incidentally during intrathoracic operations or at autopsy. Eleven operatively corrected cases are reported in the literature. The present case was admitted because of transient attacks of chest pain, palpitation and dyspnoea. These attacks were brought on when she lay on her left side and were promptly relieved by a change of position. The chest radiograph revealed a prominence of the superior aspect of the left heart border and a slight laevo-position of the heart. A diagnostic pneumothorax on the left side confirmed the diagnosis of a pericardial defect. The defect was repaired by pericardioplasty. Operative correction of a partial left pericardial defect is indicated because of the danger of luxation of the heart out of the pericardium and sudden death. This has been reported, as well as a death caused by spreading of infection from the pleural cavity into the pericardium and heart.


Treatment of mandibular angle fractures with a malleable noncompression miniplate.
This study evaluated the results in patients treated for fractures of the mandibular angle with a single, thin, malleable miniplate designed for use in the midface. Forty-six patients with 51 fractures of the mandibular angle were treated by open reduction and internal fixation using one noncompression, thin, malleable miniplate and 1.3-mm self-threading screws placed through a transoral incision. No patient was placed into postsurgical maxillomandibular fixation. They were prospectively studied for complications. Seven patients (15.2%) experienced complications. All were considered minor and did not require hospitalization. Three had asymptomatic fracture of the bone plate, but at the time of diagnosis the fracture had already healed and it required no treatment. Two patients had fracture of the bone plate with continued fracture mobility requiring maxillomandibular fixation. Three minor infections occurred requiring intraoral incision and drainage. The use of this small bone plate for fractures of the angle of the mandible provided adequate fixation in most cases but was associated with an unacceptable incidence of plate fracture. However, the results also indicate that the fixation requirements for angle fractures is less than previously thought.


Evaluation of an enzyme immunoassay kit for estrogen receptor measurements.
Using an enzyme immunoassay (EIA) procedure, we evaluated the ability of the glass beads in the ER-EIA kit of Abbott Laboratories, which were coated with monoclonal anti-estrogen receptor (ER) antibodies, to bind hormone-free and hormone-filled Type I ER in cytosols, buffer washes, and 0.4 mol/L KCI extracts of ultracentrifugal pellets of breast cancer tissue homogenates. The unmodified ER-EIA technique yields higher values than does the dextran-coated charcoal (DCC) method for Type I ER. However, the antibody-coated beads fail to bind hormone-free ER and react with only a certain proportion of ER-[3H]estradiol complexes. The antigen saturation limit of the beads could not be determined because the quantity of antigen bound by the beads was disproportionate and unrelated to the total amount of the antigen available in the cytosols. In buffer extracts of tissue pellets that were ER-negative by the DCC assay, the EIA method detected high quantities of ER. We recommend checking the ability of the monoclonal antibodies to recognize proteins other than Type I ER in the extra-nuclear and nuclear compartments of target cells before using them for immunohistochemical detection of ER.


The Pat Jasan drug eradication social movement in Northern Myanmar, part three: Legal pluralism & the challenge of everyday justice.
This paper provides an overview of the activities of a large drug eradication movement called Pat Jasan in northern Myanmar. It will outline the different everyday justice systems available in the Myanmar borderlands to communities who are seeking to push forward a 'solutions focused' agenda to manage drug-related social problems. They have at their disposal a range of statutory, customary, and quasi-statutory-customary legal processes and instruments. However, a close analysis of everyday justice highlights the complex challenges posed in this contested borderland concerning how to address these issues through multiple, overlapping authorities. The paper shows how notions of legitimacy for drug related legal processes are constructed and the key role of brokers in this environment, who are vital in managing the dilemmas of governance and legal administration. It also touches upon emerging intergenerational and gendered tensions that serve to orientate ideological and political perspectives towards different outcomes as these systems are navigated. The complexity and sensitivity of the local everyday justice social field contrasts sharply with the debates conducted about Pat Jasan at a national and drugs policy reform level, in which these local actors are marginalized as disruptive and reactionary forces that work entirely outside the rule of law. The paper invites consideration of how national and international drug policy actors engage with such social movements, as well as how concerns about illicit drug use and supply within local communities provides a helpful tool of analysis for understanding other critical issues for sustainable development and peacebuilding.


Global miRNA expression of bone marrow mesenchymal stem/stromal cells derived from Fanconi anemia patients.
Fanconi anemia (FA) is a rare genetic disorder characterized by genomic instability, developmental defects, and bone marrow (BM) failure. Hematopoietic stem cells (HSCs) in BM interact with the mesenchymal stem/stromal cells (MSCs); and this partly sustains the tissue homeostasis. MicroRNAs (miRNAs) can play a critical role during these interactions possibly via paracrine mechanisms. This is the first study addressing the miRNA profile of FA BM-MSCs obtained before and after BM transplantation (preBMT and postBMT, respectively). Non-coding RNA expression profiling and quality control analyses were performed in Donors (n = 13), FA preBMT (n = 11), and FA postBMT (n = 6) BM-MSCs using GeneChip miRNA 2.0 Array. Six Donor-FA preBMT pairs were used to identify a differentially expressed miRNA expression signature containing 50 miRNAs, which exhibited a strong correlation with the signature obtained from unpaired samples. Five miRNAs (hsa-miR-146a-5p, hsa-miR-148b-3p, hsa-miR-187-3p, hsa-miR-196b-5p, and hsa-miR-25-3p) significantly downregulated in both the paired and unpaired analyses were used to generate the BM-MSCs' miRNA-BM mononuclear mRNA networks upon integration of a public dataset (GSE16334; studying Donor versus FA samples). Functionally enriched KEGG pathways included cellular senescence, miRNAs, and pathways in cancer. Here, we showed that hsa-miR-146a-5p and hsa-miR-874-3p were rescued upon BMT (n = 3 triplets). The decrease in miR-146a-5p was also validated using RT-qPCR and emerged as a strong candidate as a modulator of BM mRNAs in FA patients.


Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings.
Formal telestroke training for neurovascular fellows (NVFs) is necessary because of growing use of telestroke technologies in the management of acute ischemic stroke; yet, educational approaches and training benchmarks are not formalized. Time between telestroke consultant page and tissue-type plasminogen activator administration (page-to-needle time, PTNT) can provide an objective measure of proficiency. We compared PTNT between NVFs and neurovascular attendings (NVAs) and evaluated changes in PTNT with experience. We identified suspected acute ischemic stroke patients in our telestroke registry from July 2013 to December 2015 who received tissue-type plasminogen activator. Using multivariable quantile regression, we estimated the difference and 95% confidence interval in median PTNT between NVFs and NVAs. We also report the coefficient of change in PTNT over increasing number of telestroke consults. NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7). This difference persisted when adjusted for relative tissue-type plasminogen activator contraindications. For each additional telestroke consult, PTNT decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively). PTNT improves by ≈1 minute for every 14 consults for both NVFs and NVAs. Our findings support the importance of integrating telestroke training into supervised neurovascular fellowships to increase proficiency prior to independent practice and suggest that PTNT can be a benchmark for tracking proficiency.


Inflammatory pathways in liver homeostasis and liver injury.
The liver is a unique organ with respect to its anatomical location, allowing continuous blood flow from the gastrointestinal tract through the sinusoids, and its cellular composition, comprising metabolically active hepatocytes, nonhepatocytic parenchymal cells, and various immune cell populations. Cytokines are key mediators within the complex interplay of intrahepatic immune cells and hepatocytes, as they can activate effector functions of immune cells, as well as hepatocytic intracellular signaling pathways controlling cellular homeostasis. Kupffer cells and liver-infiltrating monocyte-derived macrophages are primary sources of cytokines such as tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6. The liver is also enriched in natural killer (NK) and NK T cells, which fulfill functions in pathogen defense, T cell recruitment, and modulation of liver injury. TNF-alpha can activate specific intracellular pathways in hepatocytes that influence cell fate in different manners, e.g., proapoptotic signals via the caspase cascade, but also survival pathways, namely the nuclear factor (NF)-kappaB pathway. NF-kappaB regulates important functions in liver physiology and pathology. Recent experiments with genetically modified mice demonstrated important and partly controversial functions of this pathway, e.g., in cytokine-mediated hepatocyte apoptosis or ischemia-reperfusion injury. The exact dissection of the contribution of recruited and resident immune cells, their soluble cytokine and chemokine mediators, and the intracellular hepatocytic response in liver homeostasis and injury could potentially identify novel targets for the treatment of acute and chronic liver disease, liver fibrosis, or cirrhosis.


Detecting critical slowing down in high-dimensional epidemiological systems.
Despite medical advances, the emergence and re-emergence of infectious diseases continue to pose a public health threat. Low-dimensional epidemiological models predict that epidemic transitions are preceded by the phenomenon of critical slowing down (CSD). This has raised the possibility of anticipating disease (re-)emergence using CSD-based early-warning signals (EWS), which are statistical moments estimated from time series data. For EWS to be useful at detecting future (re-)emergence, CSD needs to be a generic (model-independent) feature of epidemiological dynamics irrespective of system complexity. Currently, it is unclear whether the predictions of CSD-derived from simple, low-dimensional systems-pertain to real systems, which are high-dimensional. To assess the generality of CSD, we carried out a simulation study of a hierarchy of models, with increasing structural complexity and dimensionality, for a measles-like infectious disease. Our five models included: i) a nonseasonal homogeneous Susceptible-Exposed-Infectious-Recovered (SEIR) model, ii) a homogeneous SEIR model with seasonality in transmission, iii) an age-structured SEIR model, iv) a multiplex network-based model (Mplex) and v) an agent-based simulator (FRED). All models were parameterised to have a herd-immunity immunization threshold of around 90% coverage, and underwent a linear decrease in vaccine uptake, from 92% to 70% over 15 years. We found evidence of CSD prior to disease re-emergence in all models. We also evaluated the performance of seven EWS: the autocorrelation, coefficient of variation, index of dispersion, kurtosis, mean, skewness, variance. Performance was scored using the Area Under the ROC Curve (AUC) statistic. The best performing EWS were the mean and variance, with AUC > 0.75 one year before the estimated transition time. These two, along with the autocorrelation and index of dispersion, are promising candidate EWS for detecting disease emergence.


Excitable properties and voltage-sensitive ion conductances of horizontal cells isolated from catfish (Ictalurus punctatus) retina.
External horizontal cells were enzymatically dissociated from intact catfish (Ictalurus punctatus) retina and pipetted onto a small chamber attached to the stage of an inverted phase-contrast microscope. Individual horizontal cells were recognized by their large size and restricted dendritic arborization. Low-resistance (3-12 M omega) patch-type electrodes were used to record intracellular potentials and to pass current across the cell membrane under either current or voltage-clamp conditions. The average resting potential of isolated horizontal cells was -67 V + 6.9 mV (mean +/- SD, n = 40). At the resting potential, the cell membrane appears to be mainly permeable to K. A depolarizing current step evoked an action potential in the cell. The maximum rate of rise of the action potential (dV/dt) in normal physiological solution was 6.5 +/- 1.8 V/s (means +/- SD, n = 24) and was reduced to 1.2 +/- 0.39 V/s (means +/- SD, n = 9) in 1-10 micron tetrodotoxin (TTX) and 3.2 +/- 1.4 V/s (means +/- SD, n = 6) in Ca-free solution. The maximum dV/dt was reduced in 10 mM extracellular K concentration [K]o to about half of that seen in standard saline, and values in 30 or 80 mM [K]o were similar to that measured in TTX. Following an action potential, the membrane potential reached a plateau potential of + 17.4 +/- 8.1 mV (means +/- SD, n = 17) and remained depolarized for variable periods of time lasting from less than a second to a few minutes. When the plateau potential was long lasting, the cell repolarized slowly and upon reaching zero rapidly repolarized to the original resting potential. The duration of the plateau potential decreased or was absent in saline containing one of the following calcium channel antagonists: La, Cd, Co, or Ni. The voltage-clamp technique was used to identify the membrane currents responsible for the membrane potential changes seen under current clamp. Experiments were carried out using either a single or two individual electrodes. Fast and steady-state inward currents were recorded from isolated horizontal cells in the voltage range between -20 and +20 mV. These currents were a result of increased membrane conductance to both Na and Ca ions. The Na channels are inactivated at depolarized potentials and are TTX sensitive. Ca channels are partially inactivated at depolarized potentials. The Ca conductance is decreased by Cd, Co, Ni, and La. Ba can substitute for Ca in the channel.(ABSTRACT TRUNCATED AT 400 WORDS)


Influence of Topography and Composition of Commercial Titanium Dental Implants on Cell Adhesion of Human Gingiva-Derived Mesenchymal Stem Cells: An In Vitro Study.
The topography and composition of dental implant surfaces directly impact mesenchymal cell adhesion, proliferation, and differentiation, crucial aspects of achieving osseointegration. However, cell adhesion to biomaterials is considered a key step that drives cell proliferation and differentiation. The aim of this study was to characterize characterize the topography and composition of commercial titanium dental implants manufactured with different surface treatments (two sandblasted/acid-etched (SLA) (INNO Implants, Busan, Republic of Korea; BioHorizonsTM, Oceanside, CA, USA) and two calcium phosphate (CaP) treated (Biounite®, Berazategui, Argentina; Zimmer Biomet, Inc., Warsaw, IN, USA)) and to investigate their influence on the process of cell adhesion in vitro. A smooth surface implant (Zimmer Biomet, Inc.) was used as a control. For that, high-resolution methodologies such as scanning electron microscopy (SEM), X-ray dispersive spectroscopy (EDX), laser scanning confocal microscopy (LSCM), and atomic force microscopy (AFM) were employed. Protein adsorption and retromolar gingival mesenchymal stem cells (GMSCs) adhesion to the implant surfaces were evaluated after 48 h. The adherent cells were examined by SEM and LSCM for morphologic and quantitative analyses. ANOVA and Tukey tests (α = 0.05) were employed to determine statistical significance. SEM revealed that INNO, BioHorizonsTM, and Zimmer implants have an irregular surface, whereas Biounite® has a regular topography consisting of an ordered pattern. EDX confirmed a calcium and phosphate layer on the Biounite® and Zimmer surfaces, and AFM exhibited different roughness parameters. Protein adsorption and cell adhesion were detected on all the implant surfaces studied. However, the Biounite® implant with CaP and regular topography showed the highest protein adsorption capacity and density of adherent GMSCs. Although the Zimmer implant also had a CaP treatment, protein and cell adhesion levels were lower than those observed with Biounite®. Our findings indicated that the surface regularity of the implants is a more determinant factor in the cell adhesion process than the CaP treatment. A regular, nanostructured, hydrophilic, and moderately rough topography generates a higher protein adsorption capacity and thus promotes more efficient cell adhesion.


A model for using community-based participatory research to address the diabetes epidemic in East Harlem.
Diabetes prevalence and mortality are increasing, with minority populations disproportionately affected. Despite evidence that weight loss due to improved nutrition and increased physical activity can prevent or control diabetes, there is often a disconnect between this evidence and individuals' lifestyles. East Harlem is a predominantly African-American and Latino neighborhood that has the highest rates of diabetes prevalence and mortality in New York City. The East Harlem Diabetes Center of Excellence is a community-centered coalition. To help direct their work, the coalition used their experiences, research, outreach, and literature review to build a conceptual model describing how local factors affect health behaviors and health outcomes such as obesity and diabetes. This model describes the relationship between the physical environment, the social/medical environment and individual factors including demographic data, food and exercise beliefs and behaviors, and health outcomes. The coalition inserted local data from surveys and focus groups into the model to identify targets for future interventions, research, and activism. This type of collaboration and the model may be useful tools to help communities identify and address the deficits that prevent their residents from enjoying the health benefits of improved nutrition and increased physical activity, and that also lead to racial and ethnic disparities in health.


Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM).
First-line treatment for metastatic colorectal cancer (mCRC) typically entails a biologic such as bevacizumab (BEV) with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI). STEAM (NCT01765582) assessed the efficacy of BEV plus FOLFOX/FOLFIRI (FOLFOXIRI), administered concurrently (cFOLFOXIRI-BEV) or sequentially (sFOLFOXIRI-BEV, FOLFOX-BEV alternating with FOLFIRI-BEV), versus FOLFOX-BEV for mCRC. Patients with previously untreated mCRC (n = 280) were randomized 1:1:1 to cFOLFOXIRI-BEV, sFOLFOXIRI-BEV, or FOLFOX-BEV and treated with 4-6-month induction followed by maintenance. Coprimary objectives were overall response rate (ORR; first-line cFOLFOXIRI-BEV vs. FOLFOX-BEV) and progression-free survival (PFS; pooled first-line cFOLFOXIRI-BEV and sFOLFOXIRI-BEV vs. FOLFOX-BEV). Secondary/exploratory objectives included overall survival (OS), liver resection rates, biomarker analyses, and safety. ORR was 72.0%, 72.8%, and 62.1% and median PFS was 11.9, 11.4, and 9.5 months with cFOLFOXIRI-BEV, sFOLFOXIRI-BEV, and FOLFOX-BEV, respectively. OS was similar between arms. ORR between cFOLFOXIRI-BEV and FOLFOX-BEV did not significantly differ (p = .132); thus, the primary ORR endpoint was not met. cFOLFOXIRI-BEV and sFOLFOXIRI-BEV numerically improved ORR and PFS, regardless of RAS status. Median PFS was higher with pooled concurrent and sequential FOLFOXIRI-BEV versus FOLFOX-BEV (11.7 vs. 9.5 months; hazard ratio, 0.7; 90% confidence interval, 0.5-0.9; p < .01). Liver resection rates were 17.2% (cFOLFOXIRI-BEV), 9.8% (sFOLFOXIRI-BEV), and 8.4% (FOLFOX-BEV). Grade ≥ 3 treatment-emergent adverse events (TEAEs) were observed in 91.2% (cFOLFOXIRI-BEV), 86.7% (sFOLFOXIRI-BEV), and 85.6% (FOLFOX-BEV) of patients, with no increase in serious chemotherapy-associated TEAEs. cFOLFOXIRI-BEV and sFOLFOXIRI-BEV were well tolerated with numerically improved ORR, PFS, and liver resection rates versus FOLFOX-BEV, supporting triplet chemotherapy plus BEV as a first-line treatment option for mCRC. IMPLICATIONS FOR PRACTICE: The combination of first-line FOLFIRI with FOLFOX and bevacizumab (concurrent FOLFOXIRI-BEV) improves clinical outcomes in patients with metastatic colorectal cancer (mCRC) relative to FOLFIRI-BEV or FOLFOX-BEV, but it is thought to be associated with increased toxicity. Alternating treatment of FOLFOX and FOLFIRI (sequential FOLFOXIRI-BEV) could improve tolerability. In the phase II STEAM trial, which is the largest study of FOLFOXIRI-BEV in patients in the U.S., it was found that both concurrent and sequential FOLFOXIRI-BEV are active and well tolerated in patients with previously untreated mCRC, supporting the use of these regimens as potential first-line treatment options for this population.


The controllable and efficient synthesis of two-dimensional metal-organic framework nanosheets for heterogeneous catalysis.
Two-dimensional (2D) MOFs exhibit unique periodicity in surface structures and thus have attracted much interest in the fields of catalysis, energy, and sensors. However, the expanded production scale of 2D MOFs had remained a great challenge in most previous studies. Herein, a controllable and efficient crystallization method for synthesizing 2D MOF nanosheets using high-gravity reactive precipitation is proposed, significantly improving heterogeneous catalysis efficiency. The two-dimensional ZIF-L nanosheets prepared in a rotating packed bed (RPB) reactor show a smaller lateral and lamellar thickness and a higher BET surface area compared to ZIF-L nanosheets prepared in a conventional stirred tank reactor (STR), with a greatly shortened reaction time. Applying the ZIF-L-RPB nanosheets as a catalyst, the catalytic Knoevenagel condensation as a probe reaction displays a high conversion rate of benzaldehyde (99.3%) within 2 h at room temperature, greatly exceeding that displayed by ZIF-L-STR and other reported catalysts. Furthermore, ZIL-L-RPB nanosheets of only 0.2 wt% enhanced the catalytic activity for the glycolysis of poly(ethylene terephthalate) (PET) with a PET conversion and a monomer yield of 90% in a short period of 15 min at 195 °C and almost completely depolymerized PET with a monomer yield of 94% in 30 min, which was far above that achieved by ZIL-L-STR. These results indicate the promising prospects of a high-gravity reactive precipitation strategy with precise size control in an economical way to prepare high-activity 2D MOF nanosheets for a wide range of heterogeneous catalysis.


Three-dimensional high-definition neuroendoscopic surgery: a controlled comparative laboratory study with two-dimensional endoscopy and clinical application.
The purpose of this research was to investigate the usefulness of three-dimensional (3D) endoscopy compared with two-dimensional (2D) endoscopy in neuroendoscopic surgeries in a comparative study and to test the clinical applications. Forty-three examinees were divided into three groups according to their endoscopic experience: novice, beginner, or expert. Examinees performed three separate tasks using 3D and 2D endoscopy. A recently developed 3D high-definition (HD) neuroendoscope, 4.7 mm in diameter (Shinko Optical Co., Ltd., Tokyo, Japan) was used. In one of the three tasks, we developed a full-sized skull model of acrylic-based plastic using a 3D printer and a patient's thin slice computed tomography data, and evaluated the execution time and total path length of the tip of the pointer using an optical tracking system. Sixteen patients underwent endoscopic transnasal transsphenoidal pituitary surgery using both 3D and 2D endoscopy. Horizontal motion was evaluated using task 1, and anteroposterior motion was evaluated with task 3. Execution time and total path length in task 3 using the 3D system in both novice and beginner groups were significantly shorter than with the 2D system (p < 0.05), although no significant difference between 2D and 3D systems in task 1 was seen. In both the novice and beginner groups, the 3D system was better for depth perception than horizontal motion. No difference was seen in the expert group in this regard. The 3D HD endoscope was used for the pituitary surgery and was found very useful to identify the spatial relationship of carotid arteries and bony structures. The use of a 3D neuroendoscope improved depth perception and task performance. Our results suggest that 3D endoscopes could shorten the learning curve of young neurosurgeons and play an important role in both general surgery and neurosurgery.


High volume local infiltration analgesia compared to peripheral nerve block for hip and knee arthroplasty-what is the evidence?
Since being reported in 2008, high volume local infiltration analgesia (HVLIA) has rapidly gained popularity for patients undergoing hip and knee replacement. We undertook this review to investigate whether there was evidence for equivalence of HVLIA compared to peripheral nerve block techniques with respect to early postoperative analgesia and functional recovery, or for other outcomes such as cost and process efficiency, persistent postsurgical pain and arthroplasty revision rate. We found that despite the popularity of HVLIA, supporting evidence for its use is currently limited. HVLIA certainly provides postoperative analgesia, but it is not clear whether it is equivalent to contemporary peripheral nerve block techniques in terms of either analgesia or early or later functional outcome in the context of a modern, comprehensive enhanced recovery program. Nor is it possible to state whether HVLIA provides benefits in terms of persistent postsurgical pain or cost and process efficiency. Well designed trials directly comparing peripheral nerve block with a standardised HVLIA technique are urgently required.


Analysis and management of renal failure in fourth MRC myelomatosis trial. MRC working party on leukaemia in adults.
During March 1980 to February 1982, 73 out of 80 patients in renal failure admitted to the fourth MRC myelomatosis trial were managed by a planned policy of high fluid intake (greater than or equal to 3 1/24 h) in addition to receiving one of the two chemotherapeutic regimens being tested in the main trial. Patients were also randomised to receive either sodium bicarbonate to render their urine neutral or no supplement. Follow up continued till death or to April 1983. Of 49 patients who survived more than 100 days, 39 achieved reversal of their renal failure (18 complete, 21 partial). Recovery of renal function, as assessed by a fall in the serum creatinine concentration, was achieved even when light chain proteinuria persisted. Partial recovery of renal function was associated with prolonged useful life in several patients. In only 14 of the 80 patients studied was death directly attributable to renal failure. Survival of patients in the study was appreciably better than in equivalent groups of patients in other MRC trials in which less stringent policies of fluid intake were used. Patients randomised to receive alkali fared marginally better than the others, but the difference was not significant. These results show that in many cases patients with myelomatosis who develop renal failure may have this complication reversed by taking a high fluid intake. Furthermore, though light chain is an essential component of renal disease in these patients, other factors are also important and are accessible to treatment.


Signatures of contamination in invasive round gobies (Neogobius melanostomus): a double strike for ecosystem health?
The invasive round goby has a recognised role in transferring contaminants through foodwebs, but little work has been done on contaminant impacts on round gobies themselves. Here we present the first case study of contaminant biomarkers and subpopulation structure variation in round gobies, in relation to habitat contamination, within a Canadian Area of Concern, Hamilton Harbour. Copper and cadmium were elevated in livers of fish from contaminated habitats. Although catch abundances were similar across sites, fish were smaller, a greater proportion of fish were female and more males were in reproductive condition in contaminated sites. Fish from contaminated areas showed more fin loss. Males from contaminated sites showed intersex gonads and genitalia. Ethoxyresorufin-o-deethylase (EROD) activity was higher in fish collected near polycyclic aromatic hydrocarbon (PAH)-rich sediments. The results indicate that contaminants impact the characteristics of round goby populations, which could affect ecosystems beyond toxicant biomagnification. This study also confirms that round gobies can be abundant in polluted habitats, which may draw predators-facilitating mobilisation of contaminants in foodwebs.


Magnetic Resonance-guided Procedures: Consensus on Rationale, Techniques, and Outcomes.
Magnetic resonance (MR) image guidance has demonstrated significant potential in the field of interventional radiology in several applications. This article covers the main points of MR-guided hepatic tumor ablation as a representative of MR-guided procedures. Patient selection and appropriate equipment utilization are essential for successful MR-guided tumor ablation. Intra-procedural planning imaging enables the visualization of the tumor and surrounding anatomical structures in most cases without the application of a contrast agent, ensuring optimal planning of the applicator tract. MRI enables real-time, multiplanar imaging, thus simultaneous observation of the applicator and target tumor is possible during targeting with adaptable slice angulations in case of challenging tumor positions. Typical ablation zone appearance during therapy monitoring with MRI enables safe assessment of the therapy result, resulting in a high primary efficacy rate. Recent advancements in ablation probes have shortened treatment times, while technical strategies address applicator visibility issues. MR-imaging immediately after the procedure is used to rule out complications and to assess technical success. Especially in smaller neoplasms, MRI-guided liver ablation demonstrates positive outcomes in terms of technical success rates, as well as promising survival and recurrence rates. Additionally, percutaneous biopsy under MR guidance offers an alternative to classic guidance modalities, providing high soft tissue contrast and thereby increasing the reliability of lesion detection, particularly in cases involving smaller lesions. Despite these advantages, the use of MR guidance in clinical routine is still limited to few indications and centers, due to by high costs, extended duration, and the need for specialized expertise. In conclusion, MRI-guided interventions could benefit from ongoing advancements in hardware, software, and devices. Such progress has the potential to expand diagnostic and treatment options in the field of interventional radiology.


Challenges for the Periodic Systems of Elements: Chemical, Historical and Mathematical Perspectives.
We celebrate 150 years of periodic systems that reached their maturity in the 1860s. They began as pedagogical efforts to project corpuses of substances on the similarity and order relationships of the chemical elements. However, these elements are not the canned substances wrongly displayed in many periodic tables, but rather the abstract preserved entities in compound transformations. We celebrate the systems, rather than their tables or ultimate table. The periodic law, we argue, is not an all-encompassing achievement, as it does not apply to every property of all elements and compounds. Periodic systems have been generalised as ordered hypergraphs, which solves the long-lasting question on the mathematical structure of the systems. In this essay, it is shown that these hypergraphs may solve current issues such as order reversals in super-heavy elements and lack of system predictive power. We discuss research in extending the limits of the systems in the super-heavy-atom region and draw attention to other limits: the antimatter region and the limit arising from compounds under extreme conditions. As systems depend on the known chemical substances (chemical space) and such a space grows exponentially, we wonder whether systems still aim at projecting knowledge of compounds on the relationships among the elements. We claim that systems are not based on compounds anymore, rather on 20th century projections of the 1860s systems of elements on systems of atoms. These projections bring about oversimplifications based on entities far from being related to compounds. A linked oversimplification is the myth of vertical group similarity, which raises questions on the approaches to locate new elements in the system. Finally, we propose bringing back chemistry to the systems by exploring similarity and order relationships of elements using the current information of the chemical space. We ponder whether 19th century periodic systems are still there or whether they have faded away, leaving us with an empty 150th celebration.