In Silico Screening for Anti-inflammatory Bioactive Molecules from Ayurvedic Decoction, Balaguluchyadi kashayam.
Balaguluchyadi kashayam, a polyherbal Ayurvedic decoction prepared from Sidacordifolia L., Tinospora cordifolia (Willd.) Miers, and Cedrusdeodara (Roxb. ex D.Don) G.Don, is used in Ayurveda for the treatment of chronic inflammatory conditions. Although this herbal decoction has been used for a long period for treating chronic inflammatory conditions, the mechanism of action of the decoction in reducing inflammatory conditions associated with chronic inflammation has not been clearly understood. Mass spectroscopy-based identification of bioactive molecules present in the decoction and its interaction with enzymes/proteins involved in the pathogenesis of chronic inflammation has been carried and reported in this study. Polyherbalism is one of the major principles of Ayurveda. Various phytoconstituents with different activities in the polyherbal decoction act on multi targets of a wide range of diseases. Balaguluchyadi kashayam is a polyherbal decoction prescribed for chronic inflammatory etiologies and the present study aims to evaluate the binding potential of the compounds, identified from Balaguluchyadi kashayam to enzymes/proteins involved in the development and progression of chronic inflammation. The bioactive compounds present in the Balaguluchyadi Kashayam fractions were extracted by preparative HPLC and identified using UPLC MS Q-TOF. The physicochemical characteristics and ADMET properties of the compounds were calculated using Mol soft, Swiss ADME and OSIRIS data warrior software. Then the binding interactions between the molecules and the proinflammatory mediators such as 5 Lipoxygenase, Cyclooxygenase 2, Tumor necrosis factoralpha convertase enzyme (TACE) and Caspase 1 were determined using molecular docking software Auto Dock 4.0 (http://autodock.scripps.edu/downloads). The identified bioactive molecules in the decoction showed a good binding affinity towards the enzymes/proteins involved in the development and progression of chronic inflammation compared to the binding affinity of known inhibitors/drugs to the respective enzymes/proteins. The bioactive molecules identified in Balaguluchyadi Kashayam could be developed as potential therapeutic molecules against enzymes/proteins involved in the development and progression of chronic inflammation.


Bright light alone or combined with caffeine improves sleepiness in chronically sleep-restricted young drivers.
Young drivers are over-involved in sleepiness-related crashes. The alerting effects of bright light offer a potential countermeasure for driver sleepiness, either replacing or in conjunction with current countermeasures such as the use of caffeine. Thirty young (18-25) chronically sleep-restricted drivers drove in a simulator under randomized conditions of continuous bright light ('Light,' 500 nm, 230μw/cm2), caffeine ('Caffeine,' 100 mg caffeinated gum), or light and caffeine together ('Light + Caffeine'), after driving under a placebo condition ('Placebo,' decaffeinated gum, 555 nm light, 0.3 μW/cm2) on three consecutive days. Using mixed-effects linear models, the associations between these conditions and physiological outcomes (EEG alpha and theta power, heart rate, and beat-to-beat intervals), driving performance (lateral lane and steering-related outcomes and lateral acceleration), and subjective sleepiness was assessed. Relative to Placebo, all conditions improved driving performance outcomes (P < 0.0001), with effects of Light + Caffeine equal to Light but greater than Caffeine. Light + Caffeine reduced EEG alpha power more than Light or Caffeine (P < 0.0006), but ECG outcomes were generally worse under all conditions relative to Placebo. Subjective sleepiness improved under the Light + Caffeine condition only (P < 0.0001). Combining bright light and caffeine enhances their alerting effects on lateral lane variability and subjective sleepiness. A bright light could be a practical alternative to caffeine for sleepy drivers who avoid caffeine. The alerting effects of bright light could alleviate chronic community-level mild sleep restriction and provide on-road benefits to reduce severe injuries and fatal sleepiness-related crashes.


Association of serum uric acid and fasting plasma glucose with cognitive function: a cross-sectional study.
The combined effect of serum uric acid (SUA) and blood glucose on cognition has not been explored. This study aimed to examine the separate and combined association of SUA and fasting plasma glucose (FPG) or diabetes mellitus (DM) with cognition in a sample of Chinese middle-aged and elderly population. A total of 6,509 participants aged 45 years or older who participated in the China Health and Retirement Longitudinal Study (CHARLS, 2011) were included. The three cognitive domains assessed were episodic memory, mental status, and global cognition (the sum of the first two terms). Higher scores indicated better cognition. SUA and FPG were measured. The participants were grouped based on SUA and FPG quartiles to evaluate their combined associations of cognition with SUA Q1-Q3 only (Low SUA), with FPG Q4 only (High FPG), without low SUA and high FPG levels (Non), and with low SUA and high FPG levels (Both), multivariate linear regression models were used to analyze their association. Lower SUA quartiles were associated with poorer performance in global cognition and episodic memory compared with the highest quartile. Although no association was found between FPG or DM and cognition, high FPG or DM combined with low SUA levels in women (βFPG = -0.983, 95% CI: -1.563--0.402; βDM = -0.800, 95% CI: -1.369--0.232) had poorer cognition than those with low SUA level only (βFPG = -0.469, 95% CI: -0.926--0.013; βDM = -0.667, 95% CI: -1.060--0.275). Maintaining an appropriate level of SUA may be important to prevent cognitive impairment in women with high FPG.


New Challenges in Drug Discovery - July 8-11, 2019, Vitoria-Gasteiz, Spain.
The 2019 edition "New Challenges in Drug Discovery", one of the biennial meetings under the patronage of the SEQT and EFMC, was held at the Faculty of Pharmacy of the University of the Basque Country in Vitoria-Gasteiz from July 8 to 11, 2019. On this occasion, attendees from Spain as well as from five EU countries and three non-EU countries were spectators of many scientific highlights related with the main research areas for different diseases and with protein-protein interactions, analytical tools and methods in discovery and development of drugs and computer-assisted methods in medicinal chemistry. The interesting scientific program was also complemented by an entertaining social program: a gastronomic opening ceremony held at the Museum of Fine Arts of Alava, visits to the Medieval Old City of Gasteiz and a gala dinner in a typical restaurant nestled in a building from the XVth Century.


Does "forced abstinence" from gaming lead to pornography use? Insight from the April 2018 crash of Fortnite's servers.
In April 2018, the servers of the popular video game "Fortnite" crashed for 24 hr. During this period, Pornhub (a popular pornographic website) analyzed trends in pornography access, finding that: (a) the percentage of gamers accessing Pornhub increased by 10% and (b) the searches of pornographic videos using the key term "Fortnite" increased by 60%. In this letter, we discuss these observations in the context of ongoing debate regarding the validity of "withdrawal" when applied to problematic involvement in video gaming and the potential use of pornography as a "compensation behavior" during the periods of "forced abstinence" from gaming.


Development of Refractive Parameters in 3- to 6-Year-Old Children and Its Application in Myopia Prediction and Intervention Guidance.
To investigate refractive development and prevalence of myopia in children aged 3-6 years in Hebei Province, China, and to explore the developmental law of refraction, so as to clinically guide the prediction and intervention of myopia. In May 2019, a total of 6120 people were inspected in 68 kindergartens in 11 cities in Hebei Province. Child refractive refraction was checked under noncycloplegia using a handheld binocular vision screener (SW-800, SUOER, Tianjin, China). Axial length (AL) and corneal radius of curvature (CR) were measured using an ocular biometry (IOLMaster 500, Carl Zeiss, Germany). Myopia was defined as spherical equivalent (SE) ≤ -0.75 D. A total of 5506 children aged 3-6 years met the criteria and were included in the statistical analysis. The prevalence of myopia was 3.49% (1.93% at age 3, 2.90% at age 4, 3.78% at age 5, and 3.88% at age 6). Overall, the mean SE was +0.67 ± 1.05 D (+0.81 ± 1.00 D at age 3, +0.79 ± 1.05 D at age 4, +0.67 ± 1.08 D at age 5, and +0.13 ± 1.01 D at age 6); the mean CR was 7.76 ± 0.26 mm (7.78 ± 0.26 mm at age3, 7.75 ± 0.25 mm at age 4, 7.77 ± 0.26 mm at age 5, and 7.76 ± 0.25 mm at age 6); the mean AL was 22.31 ± 0.73 mm (21.98 ± 0.63 mm at age 3, 22.12 ± 0.69 mm at age 4, 22.34 ± 0.73 mm at age 5, and 22.49 ± 0.73 mm at age 6). Prevalence of myopia increases with age in children aged 3-6 years in Hebei, China. With the increase of age, CR is basically stable, and AL increases gradually. AL/CR, which is closely related to SE, can be used as an indicator to predict myopia and guide clinical work.


Insight into silicate-glass corrosion mechanisms.
The remarkable chemical durability of silicate glass makes it suitable for a wide range of applications. The slowdown of the aqueous glass corrosion kinetics that is frequently observed at long time is generally attributed to chemical affinity effects (saturation of the solution with respect to silica). Here, we demonstrate a new mechanism and highlight the impact of morphological transformations in the alteration layer on the leaching kinetics. A direct correlation between structure and reactivity is revealed by coupling the results of several structure-sensitive experiments with numerical simulations at mesoscopic scale. The sharp drop in the corrosion rate is shown to arise from densification of the outer layers of the alteration film, leading to pore closure. The presence of insoluble elements in the glass can inhibit the film restructuring responsible for this effect. This mechanism may be more broadly applicable to silicate minerals.


Enhanced Antibacterial Activity of Highly Biocompatible Polymeric Core-Shell Levofloxacin Gold Nanocomposite Formulation Against Pseudomonas aeruginosa.
Using natural and synthetic polymers as the components for the core-shell nanocomposite preparation has received recent attention in biomedicine due to their high biocompatibility, high efficacy, and biodegradability. In this present investigation, chitosan-polyvinyl alcohol core-shell gold nanocomposite was synthesised adopting green science principles followed by fabrication with fluoroquinolone antibiotic levofloxacin (LE-CS-PVA-AuNC). Core-shell nanocomposite was prepared from biogenic gold nanoparticles, chitosan, polyvinyl alcohol polymer mixture, and levofloxacin under optimum conditions, and the synthesised nanocomposite exhibited a highly stable nanoarchitecture. Enhancement of antibacterial activity of the nanocomposite was evaluated against the clinical strain of Pseudomonas aeruginosa by determination of growth inhibition, survival rate parameters, and biofilm inhibition rate. Levofloxacin-fabricated core-shell nanocomposite brought about higher growth inhibition than the free levofloxacin, which was confirmed by a notable zone of inhibition, growth inhibition at a lower concentration, rapid biofilm inhibitory rate, and changes in survival growth parameters. In vitro drug release pattern was studied by continuous dialysis, which reveals that the nanocomposite exhibited controlled, sustained release pattern and cumulative release reached almost 98.0% at 72 h. Biocompatibility was studied with human keratinocytes (HaCaT cell line), which was studied by measuring cell viability, oxidative stress marker protein, and genotoxicity. The tested nanocomposite was not inducing any sign of toxicity which was confirmed by no marked impact on cell viability, intracellular reduced glutathione, lipid peroxidase, and lactate dehydrogenase activity. In addition, the nanocomposite has not shown any toxic effect on DNA, and all findings indicate that the synthesised nanocomposite was compatible with human keratinocytes. LE-CS-PVA-AuNC synthesised in the present system adopting green science principles can be used in modern biomedicine as an effective and safe antimicrobial agent due to its high antimicrobial action against wound infection pathogens and its best compatibility with human keratinocytes.


A case of cerebello-pontine angle infarction found by vertebral angiography.
A patient was admitted complaining of sudden vertigo. Otoneurological examinations, electronystagmography (ENG), and vertebral angiography (VAG) showed constriction of vertebral artery and anterior inferior cerebellar artery, and basilar artery obstruction. Based on these findings, we diagnosed the case as posterior cranial fossa infarction. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were negative. The authors conclude that VAG should be performed in certain cases of vertigo thought to be of central nervous origin when CT and MRI findings are both negative.


A quantitative analysis of blood-brain barrier ultrastructure in the aging human.
The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.


Common bile duct and Oddi sphincter pressure before and after endoscopic papillotomy in patients with common bile duct stones.
Pressures in the Oddi sphincter and common bile duct were determined before, immediately after and several weeks after endoscopic papillotomy. Fifteen patients were included in the study. Significant decreases in Oddi sphincter and common bile duct pressures were found and the decrease in Oddi sphincter pressure was to some extent dependent upon the length of the papillotomy.


Hybridization-displaced charges for amino-acids: a new model using two point charges per atom along with bond-center charges.
A new charge distribution is proposed for the amino acids where each atom is associated with two point charges while each bond center is associated with one point charge. Centroids of charges arising due to atomic orbital hybridization called hybridization-displaced charges (HDC) and those located at the atomic sites and bond centers obtained by a modified form of the Mulliken scheme were combined. The density matrix calculations required for this analysis were performed at the B3LYP/6-31G** level of density functional theory. The combination of HDC centroids with the modified Mulliken charges was found to yield dipole moments and surface molecular electrostatic potentials (MEP) of the amino acids in good agreement with those obtained by rigorous DFT calculations or those obtained using the MEP-fitted CHelpG charges. This study shows that the combination of HDC centroids with the modified Mulliken charges is significantly superior to the conventional Mulliken charges.


Aerosol-induced intensification of cooling effect of clouds during Indian summer monsoon.
Measurements and models show that enhanced aerosol concentrations can modify macro- and micro-physical properties of clouds. Here, we examine the effect of aerosols on continental mesoscale convective cloud systems during the Indian summer monsoon and find that these aerosol-cloud interactions have a net cooling effect at the surface and the top-of-atmosphere. Long-term (2002-2016) satellite data provide evidence of aerosol-induced cloud invigoration effect (AIvE) during the Indian summer monsoon. The AIvE leads to enhanced formation of thicker stratiform anvil clouds at higher altitudes. These AIvE-induced stratiform anvil clouds are also relatively brighter because of the presence of smaller sized ice particles. As a result, AIvE-induced increase in shortwave cloud radiative forcing is much larger than longwave cloud radiative forcing leading to the intensified net cooling effect of clouds over the Indian summer monsoon region. Such aerosol-induced cooling could subsequently decrease the surface diurnal temperature range and have significant feedbacks on lower tropospheric turbulence in a warmer and polluted future scenario.


Evaluation of the separation characteristics of application-specific (pesticides and dioxins) open-tubular columns for gas chromatography.
The solvation parameter model is used to characterize the retention properties of four application-specific open-tubular columns (Rtx-CLPesticides, Rtx-OPPesticides, Rtx-Dioxin and Rtx-Dioxin2) at five equally spaced temperatures over the range 60-140 degrees C. Cluster analysis is used to compare the system constants to a database of forty open-tubular columns characterized according to the same method. System constants differences and retention factor correlation plots are then used to determine selectivity differences between the application-specific columns and their nearest neighbors identified by cluster analysis. The Rtx-CLPesticides and Rtx-OPPesticides columns are shown to belong to the selectivity group containing poly(dimethylmethyltrifluoroprpylsiloxane) stationary phases with Rtx-OPPesticides having a similar selectivity to a poly(dimethylmethyltrifluoropropylsiloxane) stationary phase containing 20% methyltrifluoropropylsiloxane monomer (DB-200) and Rtx-CLPesticides separation properties for a stationary phase containing less than 20% methyltrifluoropropylsiloxane monomer. The Rtx-Dioxin and Rtx-Dioxin2 columns are located in the selectivity group dominated by the poly(dimethyldiphenylsiloxane) stationary phases containing less than 20% diphenylsiloxane monomer. The Rtx-Dioxin and Rtx-Dioxin2 columns are shown to be selectivity equivalent to a (5% phenyl) carborane-siloxane copolymer stationary phase (Stx-500) and a second generation silarylene-siloxane copolymer stationary phase containing dimethylsiloxane and diphenylsiloxane monomers (DB-XLB), respectively.


Uncommon radiologic observations in renal milk-of-calcium stone.
Milk-of-calcium stone is a rare finding in the kidney. It is diagnosed radiologically based on the fact that the opacity takes a semilunar shape and layers according to the position of the patient. An unusual observations is that layering may require some time to take place and that the semilunar configuration may be found incidentally in the supine position as well.


Deficiency of plasminogen activator inhibitor-2 impairs nutritionally induced murine adipose tissue development.
A functional role for several components of the fibrinolytic (plasminogen/plasmin) system in development of adipose tissue has been demonstrated. No information is available, however, on a potential role of plasminogen activator inhibitor-2 (PAI-2) in obesity. In vitro, 3T3-F442A murine pre-adipocytes were differentiated into mature adipocytes. In vivo, 5-week-old male PAI-2-deficient (PAI-2(-/-)) mice and wild-type (WT) controls of the same genetic background (C57Bl/6) were kept on a high fat diet (HFD, caloric value of 20.1 kJ g(-1)) for 15 weeks. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of PAI-2 mRNA during in vitro differentiation of pre-adipocytes and in vivo in s.c. and gonadal (GON) adipose tissues of WT mice, where it was localized both in the stromal/vascular cell fraction and in adipocytes. During HFD feeding, food intake and body weight gain were comparable for WT and PAI-2(-/-) mice. Subcutaneous plus GON fat mass was, however, significantly lower in PAI-2(-/-) mice (3.15 +/- 0.21 vs. 3.91 +/- 0.18 g; P < 0.05). Immunohistochemical analysis of adipose tissues revealed significant adipocyte hypotrophy in s.c. fat of PAI-2(-/-) mice (about 25% reduction in size; P < 0.01). Blood vessel density, normalized to adipocyte number, was comparable in s.c. fat, but was lower (P < 0.05) in GON fat of PAI-2(-/-) mice. Adipose tissue-associated fibrinolytic activity was not affected by PAI-2 deficiency. PAI-2 promotes adipose tissue development in mice via a mechanism independent of its antifibrinolytic effect.


Improved broad learning system for machinery intelligent fault diagnosis with increasing fault samples, fault modes, and running conditions.
Intelligent fault diagnosis (IFD) plays an indispensable role in protecting machinery from catastrophic accidents. Existing IFD methods are mainly developed in the framework of one-time learning. Therefore, they work under the hypothesis of complete dataset. Nevertheless, it is unrealistic to gain the complete dataset of machinery faults at once. More practically, new data will be progressively acquired over time. Therefore, it is urgently required to develop the incremental learning (IL) capabilities for IFD models to learn new knowledge continually from new data. For this purpose, this study proposes an improved broad learning system (IBLS) for lifelong learning IFD. Firstly, the initial IBLS is constructed based on the original broad learning system (BLS). Then, the IL capabilities of the IBLS are developed for three scenarios: increasing fault samples, increasing fault modes, and increasing running conditions. Based on these IL capabilities, the IBLS can be progressively updated to learn more and more diagnosis functions. Finally, the effectiveness of the proposed IBLS is verified using three experiments of high-speed train bearing, disc component, and Case Western Reserve University bearing. The results show that the IBLS is capable of learning continually new knowledge from new data. Besides, the diagnosis accuracy of the IBLS is 12.45%, 7.84%, and 5.10% higher than that of the original BLS in the three case studies. The satisfying results prove that the proposed IBLS is a useful method to solve the lifelong learning IFD problem.


Safety and outcomes of new generation hormone-therapy in elderly chemotherapy-naive metastatic castration-resistant prostate cancer patients in the real world.
Abiraterone acetate and enzalutamide are standard treatments for chemotherapy-naive metastatic castration-resistant prostate cancer (CN-mCRPC). The purpose of this study was to evaluate the effectiveness and safety of these medications in elderly (≥ 75 years old) compared with young CN-mCRPC patients in a real-world clinical setting. Secondarily, we explored the survival prognostic value of different anatomo-clinical factors in elderly group. In this retrospective observational multicentre study, we included 134 consecutive CN-mCRPC patients, 64 young and 70 elderly men, who had received AA or Enz. We did not find significant differences in treatment duration [16.6 months, (95% CI 9-24.2 months) vs. 16.8 months (95% CI: 6.3-27.2 months); p = 0.926] and overall survival [median not reached vs. 23.3 months (95% CI 10.2-36.3 months); p = 0.131] between the young and elderly groups. In elderly group, the only predictors of overall survival with AA or Enz were good ECOG performance status and high G8 score. Adverse events of grade ≥3 was similar in elderly group (12.9%) and in the young group (15.6%). Treatment was discontinued due to AEs in 6.3% of young group and 18.6% of elderly group. Effectiveness and safety of treatment of CN-mRCPC with Abiraterone acetate and enzalutamide were similar in older and younger patients, although treatment discontinuation due to AEs was more frequent in the older age group. In addition to ECOG PS, assessment using specific geriatric scales as G8 screening tool could help to identify patients aged ≥75 who would most benefit from treatment with new-generation hormone therapy.


Obesity-related promotion of aberrant crypt foci in DMH-treated obese Zucker rats correlates with dyslipidemia rather than hyperinsulinemia.
Obesity and energy restriction modulate the development of precancerous aberrant crypt foci (ACF) in animal models of colon cancer. Investigation of the major obesity-associated determinants for ACF-development and underlying mechanisms leading to ACF-modulation, such as changes in DNA damage or colonocytes hyperproliferation. Lean and obese Zucker rats fed ad libitum (a.l.) or obese pair fed (p.f.) were induced with 1,2-dimethylhydrazine (DMH) for colon cancer. Multiple regression analyses were performed to identify major metabolic factors correlated with ACF number and size (aberrant crypts/ACF). DNA damage is analyzed by the comet-assay, epithelial proliferation by immunohistochemistry. Aberrant crypt foci number was significantly elevated in Zucker obese a.l. (205.7+/-65.4 vs. lean 9.5+/-6.3, P<0.05) and is reduced by pair feeding in Zucker obese rats (81.4+/-28.5 vs. obese a.l., P<0.05). Compared to lean the ACF size was higher in Zucker obese a.l. (2.1+/-0.3 vs. lean 1.3+/-0.2., P<0.05) but is not reduced by pair feeding (1.7+/-0.2; P>0.05). While ACF number and size were modulated by genotype and/or pair feeding the DMH-induced DNA damage and hyperproliferation in colonocytes did not differ significantly between groups. Regression analysis showed that plasma parameters associated with lipid-metabolism (triglycerides, cholesterol, malondialdehyde) significantly correlated with the ACF number and size while parameters linked to carbohydrate-metabolism (glucose, insulin) were weaker determinants. Obesity or pair feeding-associated modulation of ACF correlate with parameters related to lipid-metabolism but is not accompanied by changes in DNA damage and proliferation.


Are we overtreating patients with malignant colorectal polyps? A 5-year review of the ACPGBI position statement.
In 2013, The Association of Coloproctology of Great Britain and Ireland (ACPGBI) issued a position statement regarding management of malignant polyps. We reviewed the management of endoscopically resected malignant colorectal polyps in a district general hospital to evaluate whether patients were being overtreated as per these guidelines. All patients who underwent a complete, non-piecemeal endoscopic removal of a malignant polyp between October 2013 and September 2018 were studied. Polyps were risk stratified for residual disease and followed up as per the ACPGBI. Patients were divided into two groups based on management after polypectomy. Primary outcome measured was the presence of residual tumour or involved lymph nodes in the resection specimen. Secondary outcomes included complications and recurrence. Thirty-three patients were included: 21 in the non-operative group (NOG) and 12 in the operative group (OG). The ACPGBI risk score in the NOG varied between 1 and over 4 compared with the OG who all scored over 4. Two patients in the OG (16%) demonstrated residual disease. Five patients suffered a postoperative complication. No recurrences were noted in the OG and one in the NOG. Our findings against a backdrop of the available literature suggest that the risk of residual disease after malignant polypectomy may not be as high as stated by the ACPGBI. As a result, there is a risk of overtreating patients and exposing them to the significant complications of surgery if careful consideration is not exercised.


Locations of moose in northwestern Canada with hair loss probably caused by the winter tick, Dermacentor albipictus (Acari: Ixodidae).
Five hundred two trappers representing 389 registered traplines in northern Alberta, northern British Columbia, Northwest Territories and Yukon Territory (Canada) responded to a questionnaire on the occurrence of hair loss and the winter tick (Dermacentor albipictus) on moose (Alces alces). Results suggested that winter ticks may occur as far as 62 degrees N. Several sightings of moose with presumed tick-induced hair loss near Kluane Lake, Yukon Territory, suggest the possibility of introduction of this serious pest into the moose population in Alaska.


Combined effect of Photorhabdus luminescens and Bacillus thuringiensis subsp. aizawai on Plutella xylostella.
In this study, we evaluated a new biopesticide containing different combinations of Photorhabdus luminescens (ATCC 29,999; Pl) and Bacillus thuringiensis subsp. aizawai (Bt) to leverage their insecticidal activity against Plutella xylostella. Mixtures containing proteins of various sizes were assayed to determine which combination of the two bacteria would yield the maximum insecticidal activity. A histopathologic slide revealed vacuole formations and rifts near the apical membrane (a symptom of Bt) and severe thinning of the intestinal wall (a symptom of Pl). When the two bacteria were cultured separately and then mixed, the insecticidal activity of the treatment reached 83.33% ± 8.82%. The insecticidal activity was elevated and significantly accelerated when Bt was mixed with both the Pl supernatant and the isolated protein with a molecular mass [Formula: see text] 100 kDa of Pl. These results highlight the potential of Pl as a potent bioinsecticide to economically and sustainably control Pl. xylostella and other lepidopteran pests. KEY POINTS: • Growth inhibition by Bacillus thuringiensis exerted a significant effect on insecticidal activity. • Large Photorhabdus luminescens proteins can accelerate the synergistic insecticidal effect on Plutella xylostella.


Host H-2 genotype regulates the metastatic ability of H-2-associated variants of B16 melanoma: defense systems screening for absence of self H-2 components by natural killer cells and host-associated homing barrier.
The mechanisms of host H-2-associated resistance against metastasis of tumor cells were evaluated in relation to the H-2 phenotype of tumor cells. We used H-2 heterozygous H-2a/b and H-2d/b, and H-2 homozygous H-2b/b hosts, and H-2-associated variant lines of B16 cells (H-2b+, H-2b-). In H-2b/b hosts, H-2+ cells were highly metastatic in vivo, and were resistant to host NK effectors in vitro. Therefore, H-2a/b and H-2d/b hosts showed resistance to metastasis of H-2+ cells and their effectors showed killing activity to these cells in vitro. Though the host resistance was reduced by anti-asialo GM1 serum treatment, these hosts continued to demonstrate a considerable resistance against early survival and metastasis of the B16 cells. To evaluate this natural resistance, aside from the NK system, radiation bone marrow chimeras of F1-parental combinations were used. The data suggest that host MHC-associated resistance involves not only the NK defense system but also the host environmental resistance. Both exert resistance by recognizing the H-2 mismatch in relation to the host.


Assessment of psychological and physical stressors among nurses in different functional areas before and during the COVID-19 pandemic: a cross-sectional study.
The COVID-19 (coronavirus disease) pandemic placed a great burden on all health-care resources, especially nurses. The prevalence and underlying risk factors of affective symptoms related to the COVID-19 pandemic have been studied primarily among nurses in intensive care units (ICU) and emergency departments. The aim of this study was to identify at-risk nursing areas by examining the psychological and physical stress values of nurses in different functional areas. A questionnaire with standardized items was developed to assess psychological and physical stress values. At least 50 nurses with a minimum work experience of 3 years were recruited from the ward, outpatient clinic (OC), intermediate care (IMC) unit, and operating room (OR) of the University Hospital RWTH Aachen. The participants answered the questionnaire by referring to their perceptions before and during the COVID-19 pandemic. Absolute differences and relative trends in psychological and physical stress values were compared within and across functional areas. The ward and OR nurses experienced significant increases in workload (p < 0.001 and p = 0.004, respectively) and time stressors (p < 0.001 and p = 0.043, respectively) during the COVID-19 pandemic. Regardless of functional area, the nurses showed strong tendencies toward increases in subclinical affective symptoms. After adjustments for age, sex, working in a shift system, the treatment of patients with COVID-19, and the impact of the COVID-19 pandemic on personal life, the values for working with pleasure decreased significantly among the ward (p = 0.001) and OR nurses (p = 0.009) compared with the OC nurses. In addition, the ward (p < 0.001) and OR nurses (p = 0.024) were significantly more likely to express intent to leave their profession than OC nurses. The IMC nurses showed good adaptation to the exacerbated situation caused by the COVID-19 pandemic. The ward nurses, followed by the OR nurses, were the most vulnerable to mental and physical exhaustion, which threatened the nurses' resilience and retention in the wake of the COVID-19 pandemic. Therefore, intervention programs must specifically address the professional and emotional needs of ward and OR nurses to prepare the health-care system for future crises.


Characterization of an Amylolytic Enzyme from Massilia timonae of the GH13_19 Subfamily with Mixed Maltogenic and CGTase Activity.
This work reports the characterization of an amylolytic enzyme from the bacteria Massilia timonae CTI-57. A gene encoding this protein was expressed from the pTrcHis2B plasmid in Escherichia coli BL21 Star™ (DE3). The purified protein had 64 kDa, and its modeled structure showed a monomer with the conserved α-amylases structure composed of the domain A with the characteristic (β/α)8-barrel, the small domain B, and the domain C with an antiparallel beta-sheet. Phylogenetic analysis demonstrated that the expressed protein belongs to the GH13_19 subfamily of glycoside hydrolases. The ions Ca2+, Mn2+, Na+, Mg2+, Mo6+, and K+ did activate the purified enzyme, while EDTA and the ions Fe2+, Hg2+, Zn2+, and Cu2+ were strong inhibitors. SDS was also a strong inhibitor. The enzyme's optimal pH and temperature were 7.0 and 45 °C, respectively, and its Tm was 62.2 °C. The KM of the purified enzyme for starch was 13 mg/mL, and the Vmax was 0.24 μmol of reducing sugars released per min. The characterized enzyme presented higher specificity for maltodextrin and starch and produced maltose as the main starch hydrolysis product. This is the first characterized maltose-forming amylolytic enzyme from the GH13_19 subfamily. The purified enzyme produced β-cyclodextrin from starch and maltodextrin and could be considered a cyclodextrin glucanotransferase (CGTase). This is the first report of a GH13_19 subfamily enzyme with CGTase activity.


Epidemiology and risk factors for progression in Chinese patients with IgA nephropathy.
IgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN. In this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients' data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR<60ml/min). At the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P<0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P<0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P<0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001). Male, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.


Effects of robot viscous forces on arm movements in chronic stroke survivors: a randomized crossover study.
Our previous work showed that speed is linked to the ability to recover in chronic stroke survivors. Participants moving faster on the first day of a 3-week study had greater improvements on the Wolf Motor Function Test. We examined the effects of three candidate speed-modifying fields in a crossover design: negative viscosity, positive viscosity, and a "breakthrough" force that vanishes after speed exceeds an individualized threshold. Negative viscosity resulted in a significant speed increase when it was on. No lasting after effects on movement speed were observed from any of these treatments, however, training with negative viscosity led to significant improvements in movement accuracy and smoothness. Our results suggest that negative viscosity could be used as a treatment to augment the training process while still allowing participants to make their own volitional motions in practice. This study was approved by the Institutional Review Boards at Northwestern University (STU00206579) and the University of Illinois at Chicago (2018-1251).


[A new paeoniflorin derivative isolated from the root bark ethanol extract of Paeonia suffruticosa].
To study the chemical constituents of paeoniflorins from root cortex of the Paeonia suffruticosa. Paeoniflorins were isolated by partition, silica gel column chromatography, medium-pressure RP chromatography and HPLC. Their structures were elucidated by spectroscopic methods including IR, MS and NMR techniques. Nine paeoniflorins were isolated and identified from the root bark ethanol extract of P. suffruticosa. The new compound was identified as paeoniflorin-4-ethyl ether, which may be an artifact produced during extraction proved by simulate experiment.


Whole fruit staining with aniline blue at harvest is associated with superficial pathogenesis of "Fuji" apples after storage.
Whole "Fuji" apples (Malus domestica Borkh cv. Fuji) were treated with 0.2% aniline blue before storage in 2006, 2007 and 2008 to determine whether cuticular microcracking was associated with post-storage disorders. After storage for 7 months at 0° C and 90% relative humidity followed by 3 days at 20° C, a higher aniline blue staining scale value was associated with a higher peel browning and decay index. These results indicate that superficial disorders or diseases of apples may be related to cuticular microcracking that can be seen by aniline blue staining. Scanning electron microscopy was used to analyze the ultrastructure of stained portions of the cuticular complex. Disorders or diseases of the cuticle of epidermal tissue was associated with cracked lenticels, unhealed microcracks around the edge of the lenticel, and collapsed epicuticular wax; these areas stained more intensely. Our results indicated the potential of using an aniline blue staining prior to storing the fruit to predict the ultimate quality.


Comparison of planned versus achieved central corneal stromal thickness reduction in SMILE versus FS-LASIK: a retrospective study.
Accuracy of planned corneal stromal thickness (CST) reduction is essential to the safety of laser vision correction. This study was to compare the accuracy of the planned central CST reduction in small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). A total of 77 patients (43 for SMILE, 34 for FS-LASIK using Custom-Q algorithm) were included in this retrospective study. At postoperative 6-18 months, the central CST reduction was overestimated by 18.49 ± 6.42 μm in the SMILE group (P < 0.001) and underestimated by 2.56 ± 7.79 μm in the FS-LASIK group (P = 0.064). The planned-achieved difference (PAD) of central CST reduction was positively correlated with preoperative manifest refraction spherical equivalent (MRSE) and with planned central CST reduction in both groups. When calculated by manifest refraction (MR) without nomogram adjustment, the central CST reduction was overestimated by 11.14 ± 6.53 μm in the SMILE group and underestimated by 2.83 ± 7.39 μm in the FS-LASIK group. The PAD of central CST reduction without nomogram was significantly narrowed in SMILE and maintained in FS-LASIK, suggesting estimation using MR without nomogram adjustment may be feasible for SMILE and FS-LASIK in clinical practice.


The utility of optical coherence tomography for diagnosis of basal cell carcinoma: a quantitative review.
Optical coherence tomography (OCT) is a noninvasive near-infrared light imaging technology that can be utilized to diagnose basal cell carcinomas (BCCs) based on specific morphological features. To conduct a quantitative review using tumour-level data from published studies to assess: (i) the in vivo diagnostic accuracy of different OCT systems; (ii) correlation between OCT features and histopathological diagnosis; and (iii) factors that impact the accuracy of tumour depth estimation. Primary tumour-level data were extracted from published studies on the use of time-domain (TD-OCT), frequency-domain (FD-OCT) and high-definition (HD-OCT) systems for diagnosis of BCCs. Quality assessment was performed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool. Sensitivity and specificity for diagnosis of BCC, prevalence of morphological features and correlation of tumour depth between OCT and histopathology were analysed. In total, 901 BCCs from 31 studies were included. The sensitivity and specificity were 89·3% and 60·3% overall, and were highest for FD-OCT (93·7% and 61·4%, respectively). The most prevalent morphological features were lobular pattern (80·2%, 315 of 393 tumours) and hyper-reflective peritumoral stroma (51·7%, 203 of 393). Concordance between OCT and histopathological tumour depth categories was moderate (Pearson coefficient 0·48); it was highest for tumours < 1 mm and those on the extremities. The overall bias was 0·075 mm with an agreement range from -0·88 to 1·03 mm. HD-OCT and FD-OCT were superior to TD-OCT at identifying morphological features, but not at tumour depth estimation. OCT is a viable tool for in vivo diagnosis of BCCs. FD-OCT and HD-OCT outperformed TD-OCT in diagnostic accuracy and detection of morphological features, but not tumour depth estimation.


The adjuvant effect of tuberculin in experimental sensitization to merthiolate.
When guinea pigs were sensitized to tuberculin by exposure to complete Freund's adjuvant the size of the intradermal PPD test was positively correlated to the body weight of the animal. Old Tuberculin showed stimulating effect in a subsequent sensitization to merthiolate (thimerosal). The high frequency of delayed cutaneous allergy to merthiolate in Swedish population is probably explained by sensitization through intradermal testing with tuberculin containing merthiolate as a preservative.


Amyloidosis of the breast mimicking recurrence in a previously treated early breast cancer.
Amyloid involvement of the breast is infrequently reported and may have clinical and radiological features suspicious for a primary breast malignancy. We describe a case of amyloid of the breast in which asymptomatic mammographic findings were suspicious for locally recurrent disease in a patient with previously treated breast cancer.


Virtual colonography: identification and differentiation of colorectal lesions using multi-detector computed tomography.
Early detection of precancerous or malignant lesions may be decisive for prognosis of patients with colorectal cancer. In this prospective feasibility study, multi-detector spiral computed tomography (CT) colonography was compared with conventional colonoscopy for the detection of colorectal polyps. Seventy-eight patients underwent CT colonography (standard colonoscopy preparation, distension with room air, prone and supine position) immediately before colonoscopy. Sixty-five (83%) were asymptomatic screening subjects, while the rest had symptoms suggestive of colorectal disease. Presence, location, and size of lesions were prospectively assessed. Sensitivity, specificity, and positive and negative predictive values of CT colonography were calculated using conventional colonoscopy as the reference standard. Conventional colonoscopy was normal in 52 patients. In 26 patients a total of 49 polyps and 3 carcinomas were identified. All three carcinomas and 39 polyps (80%) were identified by CT colonography. Seven of 7 polyps > or = 10 mm (100%), 13 of 16 polyps of 6 to 9 mm (81%), and 19 of 26 polyps < or = 5 mm (73%) in diameter were identified. Fourteen false-positive findings (10 of which were < or = 5 mm in diameter) were related to 8 patients (specificity at the patient level was 86%). In 10 patients, a total of 10 polyps were missed by CT colonography, 7 of which were < or = 5 mm in diameter. In this feasibility study, multi-detector spiral CT colonography allows accurate detection of polyps > 5 mm in diameter, but at the expense of low specificity in the small size range.


First safety outcomes for rigicon conticlassic® artificial urinary sphincter.
The Rigicon ContiClassic® is a new sphincteric device designed to treat male stress urinary incontinence. This study evaluates the surgical outcomes and safety profile of the first 116 patients who received the implant between September 2021 and April 2022. Data were collected from patient information forms completed at the time of the implant and submitted by implanting surgeons, nursing staff in the Operating Room or company representatives present during the surgery. The study analyzed patient demographics, surgical details, and etiology of incontinence. The mean age of patients was 68.3 years +/- 9.65 yrs. Minimum age was 23 and maximum age was 83. The most common reason for implantation was urinary incontinence (58.6%) after radical prostatectomy. The results showed a revision rate of 6.90%, with three cases of fluid loss, four cases of iatrogenic mistaken sizing, and one case of patient dissatisfaction. There were no reported infections. Kaplan-Meier calculation showed survival rate of 93.2% at 12 months. This study shows the early safety outcomes for the Rigicon ContiClassic® sphincter device to be comparable to others presently on the market.


Interaction of antitumor flavonoids with dsDNA in the absence and presence of Cu(II).
The binding of antitumor flavonoids, namely 3-hydroxyflavone (3HF) and hesperidin (Hesp) with dsDNA was investigated in the absence and presence of Cu(II) using cyclic voltammetry and square wave voltammetry at the hanging mercury drop electrode. The reduction currents of 3HF, 3HF-Cu complex, and the 3HF-β-cyclodextrin inclusion complex decreased after intercalation into dsDNA. The intercalation of Hesp into dsDNA is weak. dsDNA is reduced at a potential of -1.48 V overlaying the reduction of Hesp. In contrast, in the presence of Cu(II), the interaction of Hesp with dsDNA leads to a much stronger intercalation. The binding constants of the flavonoid-Cu complex with dsDNA were evaluated and calibration graphs for the determination of dsDNA were obtained from the decrease in the peak current in the cyclic voltammograms of 3HF in the presence of dsDNA. The proposed method exhibited good recovery and reproducibility for indirect determination of dsDNA.


Multiple channel exposure therapy for women with PTSD and comorbid panic attacks.
Multiple channel exposure therapy (M-CET; Falsetti & Resnick, 2000) was developed to treat posttraumatic stress disorder (PTSD) with comorbid panic attacks and can be administered in a group format. In addition to being a cost-effective way to provide treatment, group treatment for those with PTSD has been proposed as potentially very beneficial for addressing feelings of shame related to the traumatic event as well as social isolation in general (Foy et al., 2000). Previous studies of M-CET indicate that it may be effective for the treatment of PTSD with comorbid panic attacks (Falsetti et al., 2001, 2003, 2005). The authors examine the relationship of PTSD and panic symptoms pre- and posttreatment and present 6-month follow-up data on the long-term effectiveness of M-CET.


A new set of electronic modules (NIM standard) for a coincidence system using the pulse mixing method.
The three electronic modules presented here, connected to two MTR2 modules of extended dead-time discriminators, allow setting-up a complete coincidence system according to the principle of the pulse-mixing method. Results produced by such a system including these modules were compared with those of an older system working in a completely different mode (IMPECC).


Evaluation of a real-time impedance analysis platform on fungal infection.
End-point assays of in vitro cell proliferation and death have been employed to study the mechanisms of fungal pathogenesis and have shown the responses of host cells at individual time points. A new cell analysis technology has been developed that allows for the continuous measurement and quantification of cell activities, thus enabling the dynamic assessment of electrical impedance when various pathogens are cultured in vitro. In this study, this system was evaluated to determine the response of the cell line RAW264.7 to infection by several clinically relevant fungi in vitro, including Aspergillus fumigatus, Candida albicans, and melanized and albino mutant strains of Fonsecaea monophora. The results showed that infection resulted in rounding of the host cells with a loss of contact between individual cells and a decline in the electrical impedance of all test groups. However, changes in the electrical impedance were variable. Aspergillus fumigatus caused initial increases and later significant decreases in the electrical impedance, while for C. albicans and F. monophora, the effect was reduced. The melanized strain of F. monophora caused a faster change in the electrical impedance than the albino strain. Our data proved that this system can be used as an efficient tool for monitoring cellular responses to fungal infection.


Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a prospective study in adult and elderly patients with newly diagnosed partial epilepsy.
The aim of the study described here was to investigate the efficacy, tolerability, and side effects of oxcarbazepine (OXC) monotherapy in newly diagnosed, previously untreated adult and elderly patients with partial epilepsy. We prospectively analyzed and recorded the efficacy, tolerability, and side effects of OXC monotherapy. The results were analyzed on the basis of etiologic classifications and age distributions. Remission was defined as seizure freedom for at least 1 year. A total of 147 patients were evaluated in a single center for a median of 18 months (range: 14-36 months). Overall, 92 patients (62.6%) were seizure free for at least 12 months and 55 of them (37.4%) were unresponsive despite treatment with the maximum tolerable dose of OXC. There was a significant difference in the outcomes of patients with cryptogenic (75% remission) and symptomatic (51.9% remission) epilepsy (P=0.004). Patients with cerebral tumors did worse than the remainder of the patients in the symptomatic group (36.7% remission) (P=0.03). Results were favorable for the elderly; 14 patients (73.6%) in the elderly subgroup became seizure free for at least 1 year, and the remission was achieved with low to moderate doses (approximately 900 mg/day). Overall, 13 patients (8.8%) discontinued OXC due to intolerable side effects. Side effects leading to discontinuation were: Stevens-Johnson syndrome (n=2, 1.4%); fatigue and drowsiness (n=2, 1.4%); dizziness, nausea, and vomiting with normal laboratory tests (n=2, 1.4%); dizziness, nausea, and vomiting with serum Na levels <130 mEq/L (n=5, 3.4%); and elevated serum gamma-glutamyl transferase levels (GGT>200mg/dL) (n=1, 0.7%). OXC proved to be a tolerable drug for the elderly; only one patient experienced symptomatic hyponatremia with mild symptoms and responded well to fluid restriction, which did not lead to discontinuation of OXC. Although the limitations of our study include its open-label design, the results suggest that OXC monotherapy may be regarded as an effective first-line monotherapy option for adult and elderly patients with partial epilepsy, but has low efficacy in patients with cerebral tumors.


Beaten but not down! Exploring resilience among female sex workers (FSWs) in Nairobi, Kenya.
In Kenya sex work is illegal and those engaged in the trade are stigmatized and marginalized. We explored how female sex workers in Nairobi, Kenya, utilize different resources to navigate the negative consequences of the work they do. Qualitative data were collected in October 2019 from 40 FSWs who were randomly sampled from 1003 women enrolled in the Maisha Fiti study, a 3-year longitudinal mixed-methods study exploring the relationship between HIV risk and violence and mental health. All interviews were audio-recorded, transcribed and translated. Data were thematically coded and analyzed using Nvivo 12. Participants' age range was 18-45 years. Before entry into sex work, all but one had at least one child. Providing for the children was expressed as the main reason the women joined sex work. All the women grew up in adverse circumstances such as poor financial backgrounds and some reported sexual and physical abuse as children. They also continued to experience adversity in their adulthood including intimate partner violence as well as violence at the workplace. All the participants were noted to have utilised the resources they have to build resilience and cope with these adversities while remaining hopeful for the future. Motherhood was mentioned by most as the reason they have remained resilient. Coming together in groups and engaging with HIV prevention and treatment services were noted as important factors too in building resilience. Despite the adverse experiences throughout the lives of FSWs, resilience was a key theme that emerged from this study. A holistic approach is needed in addressing the health needs of female sex workers. Encouraging FSWs to come together and advocating together for their needs is a key resource from which resilience and forbearance can grow. Upstream prevention through strengthening of education systems and supporting girls to stay in school and complete their secondary and/or tertiary education would help them gain training and skills, providing them with options for income generation during their adult lives.


The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial.
Peripheral vasodilatation is central to the pathogenesis of the accompanying hyperkinetic circulatory state and portal hypertension in cirrhotic patients. Selective intestinal decontamination with norfloxacin has been demonstrated to partially correct nitric oxide production in the forearm vasculature of cirrhotic patients. To examine the effects of selective intestinal decontamination on regional and systemic hemodynamics in cirrhotic patients. Randomized, double-blind, placebo-controlled, crossover study. Alfred Hospital, Melbourne, Australia. 14 patients with alcohol-related cirrhosis and 14 matched healthy controls. Norfloxacin, 400 mg twice daily, for 4 weeks. Venous occlusion plethysmography was used to determine forearm blood flow. Cardiac output and the hepatic venous pressure gradient were determined after cardiac catheterization. Glomerular filtration rate was assessed by measuring inulin clearance. Serum levels of endotoxin were determined by chromogenic Limulus amebocytelysate assay. Norfloxacin significantly diminished serum endotoxin levels (average change, -2.14 EU/mL [95% CI, -3.6 to -0.68 EU/mL]). Derived systemic vascular resistance increased significantly with norfloxacin (2.94 units [CI, 0.74 to 5.11 units]) and was accompanied by an increase in mean arterial pressure (8.70 mm Hg [CI, 2.65 to 14.73]), a trend toward decreased cardiac output (-1.207 L/min [range, 0.05 to -2.37 L/min]), a decrease in forearm blood flow (-0.99 mL/100 mL per min [CI, -1.80 to -0.17 mL/100 mL per min]), and a trend toward reduced hepatic venous pressure gradient (-2.43 mm Hg [CI, -5.2 to 0.34 mm Hg]). Norfloxacin did not significantly alter glomerular filtration rate. Selective intestinal decontamination with norfloxacin partially reverses the hyperdynamic circulatory state in cirrhotic patients without harming splanchnic or renal hemodynamics.


The cold pressor pain paradigm in children: feasibility of an intervention model (Part II).
The purpose of this study was to examine the feasibility of testing a psychological approach (hypnosis) to pain reduction in children using the cold pressor paradigm. Children's pain ratings at 10 sec intervals and duration of arm immersion (40 sec maximum) in 15 degrees C (n = 37) and 12 degrees C water (n = 29) were assessed in 6-12-year-old children during 2 baseline trials (alternating arms), followed by 2 more trials after randomization to a control or hypnosis treatment condition. Hypnosis was found to reduce pain significantly more than the control condition in both 15 degrees C and 12 degrees C water. Hypnotic susceptibility was not strongly related to hypnotic pain reduction. However, age was significant, with younger children showing higher pain ratings and early arm withdrawal rates and less response to hypnosis than older children. In 15 degrees C water, females had higher pain ratings and early withdrawal rates than males, but this sex discrepancy disappeared in 12 degrees C water. This study demonstrated the feasibility of the cold pressor paradigm for testing intervention strategies and its potential for enhancing our understanding of pain in children.


Differential control of vesicle priming and short-term plasticity by Munc13 isoforms.
Presynaptic short-term plasticity is an important adaptive mechanism regulating synaptic transmitter release at varying action potential frequencies. However, the underlying molecular mechanisms are unknown. We examined genetically defined and functionally unique axonal subpopulations of synapses in excitatory hippocampal neurons that utilize either Munc13-1 or Munc13-2 as synaptic vesicle priming factor. In contrast to Munc13-1-dependent synapses, Munc13-2-driven synapses show pronounced and transient augmentation of synaptic amplitudes following high-frequency stimulation. This augmentation is caused by a Ca(2+)-dependent increase in release probability and releasable vesicle pool size, and requires phospholipase C activity. Thus, differential expression of Munc13 isoforms at individual synapses represents a general mechanism that controls short-term plasticity and contributes to the heterogeneity of synaptic information coding.


Evaluation of microvascular permeability with dynamic contrast-enhanced MRI for the differentiation of primary CNS lymphoma and glioblastoma: radiologic-pathologic correlation.
Dynamic contrast-enhanced MR imaging can provide in vivo assessment of the microvasculature in intracranial tumors. The aim of the present study was to evaluate the diagnostic performance of dynamic contrast-enhanced MR imaging derived vascular permeability parameters, including the volume transfer constant, the volume of extravascular extracellular space, and the flux rate constant between the extravascular extracellular space and plasma, for the differentiation of primary CNS lymphoma and glioblastoma. Sixty glioblastomas and 11 primary central nervous system lymphomas were included. Pretreatment T1-weighted dynamic contrast-enhanced MR imaging with a 3D T1-weighted spoiled gradient-echo sequence was performed on a 3T MR imaging scanner. Perfusion parameters (volume transfer constant, the volume of extravascular extracellular space, and the flux rate constant) were measured on the basis of the Tofts-Kernmode model. The Mann-Whitney U test and receiver operating characteristic analysis were used to compare those parameters between primary central nervous system lymphoma and glioblastoma. Histopathologic correlation of dynamic contrast-enhanced MR imaging findings was performed by using reticulin staining and CD31 immunohistochemistry. Median volume transfer constant and flux rate constant values were significantly higher in primary central nervous system lymphoma (0.145 ± 0.057 and 0.396 ± 0.088) than in glioblastoma (0.064 ± 0.021 and 0.230 ± 0.058) (P < .001, respectively). Median volume of extravascular extracellular space values did not differ significantly between primary central nervous system lymphoma (0.434 ± 0.165) and glioblastoma (0.319 ± 0.107). On receiver operating characteristic analysis, volume transfer constant had the best discriminative value for differentiating primary central nervous system lymphoma and glioblastoma (threshold, 0.093; sensitivity, 90.9%; specificity, 95.0%). Histopathologic evaluation revealed intact vascular integrity in glioblastoma despite endothelial proliferation, whereas primary central nervous system lymphoma demonstrated destroyed vessel architecture, thereby promoting vascular disintegrity. Primary central nervous system lymphoma demonstrated significantly higher volume transfer constant and flux rate constant values compared with glioblastoma, implying a higher vascular permeability in primary central nervous system lymphoma. These findings confirm initial observations from perfusion CT and dynamic contrast-enhanced MR imaging studies, correlating with underlying histopathologic features, and may be useful in distinguishing primary central nervous system lymphoma from glioblastoma.


Alterations in Cortical Thickness in Young Male Patients With Childhood-Onset Adult Growth Hormone Deficiency: A Morphometric MRI Study.
The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in brain structure and maintenance of brain function. There is a close correlation between serum GH and IGF1 levels and age-related cognitive function. The effects of childhood-onset growth hormone deficiency (GHD)on brain morphology are underestimated so far. In this cross-sectional study, T1-weighted magnetic resonance imaging was assessed in 17 adult males with childhood-onset GHD and 17 age and gender-matched healthy controls. The cortical thickness was analyzed and compared between the two groups of subjects. Effects of disease status and hormone levels on cortical thickness were also evaluated. Although there was no difference in whole brain volume or gray matter volume between the two groups, there was decreased cortical thickness in the parahippocampal gyrus, posterior cingulate gyrus and occipital visual syncortex in the adult growth hormone deficiency (AGHD) group, and increased cortical thickness in a partial area of the frontal lobe, parietal lobe and occipital visual syncortex in AGHD group. Cortical thickness of the posterior cingulum gyrus was prominently associated with FT3 serum levels only in control group after adjusting of IGF-1 levels. These results suggest that young adult male patients with childhood-onset GHD have alterations in cortical thickness in different brain lobes/regions.


Systolic and diastolic septal and posterior wall echocardiographic measurements in normal subjects.
M-mode echocardiographic measurement of septal and left ventricular excursions and velocities was attempted in 109 subjects. Seventy subjects had adequate echocardiograms enabling detailed measurement. Two groups of subjects were studied: a group of normal adults aged nineteen to seventy-eight years and a group of normal juveniles aged nine to eighteen years. The posterior wall excursion (PWE), systolic septal excursion (SSE), diastolic septal excursion (DSE), and diastolic septal velocity (DSV) did not differ in these groups. There were significant differences in the posterior wall excursion during isovolumetric contraction (B-Ce, p less than 0.002), mean posterior wall velocity (PWV mean, p less than 0.002), and systolic septal velocity (SSV, p = 0.05) between the two groups. The measurements were obtained by using the recently published method of the specific points for labeling and description of the wall motion.


Clinical application of thermal isoeffect dose.
Clinically, there is strong rationale for developing a method which will provide a scientific basis for comparing the efficacy of one hyperthermia treatment with another. In order to accomplish this goal, methods must first be developed which will allow the clinician to know the three-dimensional temperature distribution in heated tissue. In this paper, examples of how this goal can be achieved are presented. Techniques for compensating for various modifiers of hyperthermia effectiveness are proposed. The limitations and advantages of these approaches are described and directions for future research are discussed.


Tier 3 specialist weight management service and pre-bariatric multicomponent weight management programmes for adults with obesity living in the UK: A systematic review.
NHS England has recommended a multidisciplinary weight management services (MWMS-Tier 3 services) for patients requiring specialized management of obesity, including bariatric surgery, but clinical and measurable health-related outcomes from these services remains fragmented. We therefore undertook a systematic review to explore the evidence base of effect on body weight loss and comorbidities outcomes of Tier 3 or UK pre-bariatric MWMPs. AMED, CINAHL, EMBASE, HMIC, MEDLINE, PsycINFO, PubMed, HDAS search and Google Scholar were searched from January 2000 to September 2017 in a free-text fashion and crossed-references of included studies to identify potential illegibility. Inclusion criteria were as follows: (a) published Tier 3 original study abstracts/articles; (b) intervention studies with before and after data; (c) studies that included any sort of MWMPs conducted on British residents with obesity; and (d) studies included T2DM measurements in a MWMPs. In total, 19 studies met the inclusion criteria. The total number of participants analysed was N = 11,735. Baseline accumulative average BMI was calculated at 42.54 kg/m2, weight 117.88 kg and waist circumference 126.9 cm. And at 6 months, 40.73 kg/m2, 112.17 kg and 120.3 cm, respectively. Secondary outcome variables were as improved with reduction in HbA1c, fasting blood sugars, insulin usage and blood pressure. Physical activity increased at 3 months then declined after 6 months with no significant changes in cholesterol levels. Tier 3 and MWMPs have a short to mid-ranged positive effect on obese patients (BMI ≥30 kg/m2) living in the UK regarding accumulated reduction in weight, glycaemic control, blood pressure and with subtle improvements in physical activity.


Metabolism of monoterpenes: oxidation of isopiperitenol to isopiperitenone, and subsequent isomerization to piperitenone by soluble enzyme preparations from peppermint (Mentha piperita) leaves.
Soluble enzyme extracts from peppermint leaves, when treated with polystyrene resin to remove endogenous monoterpenes and assayed with unlabeled substrates coupled with capillary gas-liquid chromatographic/mass spectrometric detection methods, were shown to oxidize isopiperitenol to isopiperitenone, and to isomerize isopiperitenone to piperitenone. The enzymes responsible for the monoterpenol dehydrogenation and the subsequent allylic isomerization were separated and partially purified by chromatography on Sephadex G-150, and were shown to have molecular weights of approximately 66,000 and 54,000, respectively. The general properties of the NAD-dependent dehydrogenase were examined, and specificity studies indicated that a double bond adjacent to the carbinol carbon was a required structural feature of the monoterpenol substrate. General properties of the isomerase were also determined, and it was demonstrated that the double bond migration catalyzed by this enzyme involved an intramolecular 1,3-hydrogen transfer. These enzymatic transformations represent two key steps in the metabolic pathway for the conversion of the initially formed cyclic olefin, (+/-)-limonene, to (-)-menthol and related monoterpenes characteristic of peppermint. Some stereochemical features of these reactions, and of the overall biogenetic scheme, are described.


Ultrastructural study of amelogenesis imperfecta.
An ultrastructural study of teeth with amelogenesis imperfecta revealed various aspects of microcavities in the enamel surface, which ranged from isolated imprints of ameloblasts corresponding to the mildest lesions at the end of amelogenesis, to pits caused by the death of 20 to 30 ameloblasts at the beginning of amelogenesis. Abnormalities in the shape of the prisms can be observed. Further, crystals are distributed randomly within a prism or at the junction of 2 contiguous prisms while intercrystalline spaces are widened, indicating in various places the lack of a preferred orientation of the crystals. In amelogenesis imperfecta, two different crystalline periods are found: 1 of about 250 A, the other of about 500 A and over. The fact that amorphous areas are found among the crystals of enamel may be related to different stages of crystallization. However, it was not possible to find any lattice defect.


Investigations into factors affecting the cascade developer used in ESDA--a review.
The Electrostatic Detection Apparatus (ESDA) is a technique most commonly used for the visualisation of indented impressions on questioned documents. This work investigates some of the variables which are known to affect the results of ESDA and some variables which have, as yet, not been addressed. The investigation of variables included: examining the effects of different levels of indentation on different qualities of paper, chronological aging of cascade developer and the effects of repeated use of cascade developer on both the quality of results and the glass beads themselves, the effects of storage of cascade developer in a humidified environment and finally the effects of variation on the image development time. Results indicate that chronological aging of cascade developer does not have a negative effect on the quality of results and a 200 g portion of cascade developer will give good quality results for up to 30 traces before the quality will begin to deteriorate. Humidification of the cascade developer appears to have no advantages over storage in a normal environment and, in fact, the toner is lost sooner with humidification. The surface of the glass beads are affected through repeated use of cascade developer and appear to become visually smoother which may lead to a loss of attraction between them and the toner particles.


Photosynthesis and respiration in Alocasia macrorrhiza following transfers to high and low light.
Photosynthetic capacities and respiration rates of Alocasia macrorrhiza leaves were measured for 4 weeks following reciprocal transfers between high (20% of full sun) and low (1% of full sun) light environments. Photosynthetic capacities and respiration rates of mature, high-light leaves were 1.7 and 4.5 times those of low-light leaves, respectively. Following transfer, respiration rates adjusted within 1 week to those characteristic of plants grown in the new environment. By contrast, photosynthetic capacities either did not adjust or changed only slowly following transfer. Most of the difference in respiration between high- and low-light leaves was related to the carbohydrate status as determined by the daily PFD and little was directly related to the maintenance costs of the photosynthetic apparatus. Leaf construction cost was directly proportional to maximum photosynthetic capacity. Consequently, although daily carbon gain per unit leaf area was the same for low-light and high to low-light transferred plants within a week after transfer, the carbon return per unit of carbon investment in the leaves remained lower in the high to low transfer plants throughout the 4 week measurement period. Conversely, in high-light, the low leaf construction cost of the low to high-light transferred plants resulted in carbon gain per unit investment just as high as that of the high-light plants.


Genetic selection for dissociative inhibitors of designated protein-protein interactions.
Many biological processes rely on protein-protein interactions. These processes include signal transduction, cell cycle regulation, gene regulation, and viral assembly and replication. Moreover, many proteins and enzymes manifest their function as oligomers. We describe here an efficient means to sift through large combinatorial libraries and identify molecules that block the interaction of target proteins in vivo. The power of this approach is demonstrated by the identification of nine-residue peptides from a combinatorial library that inhibit the intracellular dimerization of HIV-1 protease. Fewer than 1 in 106 peptides do so. In vitro biochemical analyses of one such peptide demonstrate that it acts by dissociating HIV-1 protease into monomers, which are inactive catalysts. Inhibition is enhanced further by dimerizing the peptide. This approach enables the facile identification of new molecules that control cellular processes.


Degradation of polycyclic aromatic hydrocarbons by combined chemical pre-oxidation and bioremediation in creosote contaminated soil.
The ability of pre-oxidation to overcome polycyclic aromatic hydrocarbons (PAH) recalcitrance to biodegradation was investigated in creosote contaminated soil. Sand and peat artificially spiked with creosote (quality WEI C) were used as model systems. Ozonation and Fenton-like treatment were proved to be feasible technologies for PAH degradation in soil. The efficiency of ozonation was strongly dependent on the water content of treated soil samples. The removal of PAH by Fenton-like treatment depended on the applied H2O2/soil weight ratio and ferrous ions addition. It was determined that the application of chemical oxidation in sand resulted in a higher PAH removal and required lower oxidant (ozone, hydrogen peroxide) doses. The enhancement of PAH biodegradability by different pre-treatment technologies also depended on the soil matrix. It was ascertained that combined chemical and biological treatment was more efficient in PAH elimination in creosote contaminated soil than either one alone. Thus, the combination of Fenton-like and the subsequent biological treatment resulted in the highest removal of PAH in creosote contaminated sand, and biodegradation with pre-ozonation was found to be the most effective technology for PAH elimination in peat.


Effects of buprenorphine in heroin addicts.
Twelve heroin addicts on the 8th day after withdrawal, and 8 healthy volunteers were given a single i.m. injection of buprenorphine 0.6 mg and their subjective response rated on 10 psychological variables. Pre-injection rating differed significantly between addicts and controls on 7 variables out of 10. Following buprenorphine more subjective changes were noted in the control group which became more calm, depressed, more aware of the environment, sleepy, tired, intoxicated, dizzy and nauseated. The drug addicts reported changes only in 2 variables (less tense and dysphoric) but otherwise showed no significant changes. These findings support the notion that buprenorphine induces low or normalizing effects in heroin addicts. This drug might thus be suitable for maintenance therapy in opiate addiction.


Monodisperse porous polymer particles with polyionic ligands for ion exchange separation of proteins.
A new "grafting to" strategy was proposed for the preparation of polymer based ion exchange supports carrying polymeric ligands in the form of weak or strong ion exchangers. Monodisperse porous poly(glycidyl methacrylate-co-ethylene dimethacrylate), poly(GMA-co-EDM) particles 5.9 microm in size were synthesized by "modified seeded polymerization". Poly(2,3-dihydroxypropyl methacrylate-co-ethylene dimethacrylate), poly(DHPM-co-EDM) particles were then obtained by the acidic hydrolysis of poly(GMA-co-EDM) particles. The hydroxyl functionalized beads were treated with 3-(trimethoxysilyl)propyl methacrylate to have covalently linked methacrylate groups on the particle surface. The selected monomers carrying weak or strong ionizable groups (2-acrylamido-2-methyl-1-propane sulfonic acid, AMPS; 2-dimethylaminoethylmethacrylate, DMAEM and N-[3-(dimethylamino)propyl] methacrylamide, DMAPM) were subsequently grafted onto the particles via immobilized methacrylate groups. The final polymer based materials with polyionic ligands were tried as chromatographic packing in the separation of proteins by ion exchange chromatography. The proteins were successfully separated both in the anion and cation exchange mode with higher column yields with respect to the previously proposed materials. The plate heights obtained for poly(AMPS) and poly(DMAEM) grafted poly(DHPM-co-EDM) particles by using proteins as the analytes were 80 and 200 microm, respectively. Additionally, the plate height exhibited no significant increase with the increasing linear flow rate in the range of 1-20 cm/min. The most important property of the proposed strategy is to be applicable for the synthesis of any type of ion exchanger both in the strong and weak form.


In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance.
Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of cancer patients. To gain mechanistic insights, we developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. In two distinct PDX samples, tumors initially responded to treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly similar kinetics between replicate mice. Notably, replicate tumors developed different mutations in TP53 and individual sets of chromosomal alterations, suggesting independent parallel clonal evolution rather than selection, driven by a combination of stochastic and deterministic processes. Transcriptome and proteome showed shared dysregulations between replicate tumors providing putative targets to overcome resistance. In vivo CRISPR/Cas9 dropout screens in PDX revealed broad dependency on BCL2, BRIP1 and COPS2. Accordingly, venetoclax re-sensitized derivative tumors towards chemotherapy, despite genomic heterogeneity, demonstrating direct translatability of the approach. Hence, despite the presence of multiple resistance-associated genomic alterations, effective rescue treatment for polychemotherapy-resistant tumors can be identified using functional testing in preclinical models.


Positive COVID-19 Diagnosis Following Primary Elective Total Joint Arthroplasty: Increased Complication and Mortality Rates.
This study analyzed complication rates following primary elective total joint arthroplasty (TJA) in patients who subsequently contracted COVID-19. A large national database was queried for adult patients who underwent primary elective TJA in 2020. Patients who contracted COVID-19 after total knee arthroplasty (TKA) or total hip arthroplasty (THA) underwent 1:6 matching (age [±6 years], sex, month of surgery, COVID-19-related comorbidities) to patients who did not. Differences between groups were assessed using univariate and multivariate analyses. Overall, 712 COVID-19 patients were matched to 4,272 controls (average time to diagnosis: 128-117 days [range, 0-351]). Of patients diagnosed <90 days postoperatively, 32.5%-33.6% required COVID-19-driven readmission. Discharge to a skilled nursing facility (adjusted odds ratio [aOR] 1.72, P = .003) or acute rehabilitation unit (aOR 4.93, P < .001) and Black race (aOR 2.28, P < .001) were associated with readmission after TKA. Similar results were associated with THA. COVID-19 patients were at increased risk of pulmonary embolism (aOR 4.09, P = .001) after TKA and also periprosthetic joint infection (aOR 4.65, P < .001) and sepsis (aOR 11.11, P < .001) after THA. The mortality rate was 3.51% in COVID-19 patients and 7.94% in readmitted COVID-19 patients compared to 0.09% in controls, representing a 38.7 OR and 91.8 OR of death, respectively. Similar results were observed for TKA and THA separately. Patients who contracted COVID-19 following TJA were at greater risk of numerous complications, including death. These patients represent a high-risk cohort who may require more aggressive medical interventions. Given the potential limitations presently, prospectively collected data may be warranted to validate these findings.


Reliable and efficient scale to assess upper motor neuron disease burden in amyotrophic lateral sclerosis.
Validation of biomarkers of upper motor neuron (UMN) impairment in amyotrophic lateral sclerosis (ALS) requires a reliable clinical assessment of UMN findings. The Penn Upper Motor Neuron Score© (PUMNS) is a standardized measure of UMN signs in ALS. Our aims were to evaluate its intra- and inter-rater reliability, and to examine inter-item reliability as a proxy for item relatedness and scale efficiency. Study procedures were performed during routine clinic visits. We calculated intra and inter-rater reliability using Pearson's correlation coefficient and inter-item reliability using Cronbach's alpha. PUMNS had high intra and inter-rater reliability. Total and sub-score correlation coefficients were all ≥0.96. The inter-item reliability indicated appropriate item relatedness with reasonable efficiency and sub-score correlation coefficients between 0.68 and 0.85. PUMNS is a reliable measure of UMN signs in ALS and would be a useful tool in validating imaging and laboratory biomarkers of UMN injury in ALS.


[Psychometric Testing of a Generic Assessment Tool for the Identification of Biopsychosocial Impairments in Persons with an Approval for Medical Rehabilitation].
In Germany, different rehabilitation measures were developed for patients with problems due to their specific chronic disease. The aim of the study was to test a generic assessment tool for a valid identification of disability patterns. This tool can effectively display the demand of specific rehabilitation measures in the medical rehabilitation. The generic assessment tool was tested in a representative sample of individuals who have been granted a medical rehabilitation by the German Federal Pension Insurance. With this sample, we performed a cross-sectional study. Full data were available for 2 530 persons. Our analyses showed good psychometric properties of the integrated instruments concerning missing rate, ceiling and floor effects, reliability and factorial validity. We could identify a 3-dimensional structure of the assessment tool according to the biopsychosocial model. The presented assessment tool is suitable for the identification of biopsychosocial impairments and resources. This can help to allocate patients with chronic diseases in appropriate rehabilitation facilities and therapeutic modules.


Bright photon upconversion in LiYbF4:Tm3+@LiYF4 nanoparticles and their application for singlet oxygen generation and in immunoassay for SARS-CoV-2 nucleoprotein.
Photon upconversion is an intensively investigated phenomenon in the materials sciences due to its unique applications, mainly in biomedicine for disease prevention and treatment. This study reports the synthesis and properties of tetragonal LiYbF4:Tm3+@LiYF4 core@shell nanoparticles (NPs) and their applications. The NPs had sizes ranging from 18.5 to 23.7 nm. As a result of the energy transfer between Yb3+ and Tm3+ ions, the synthesized NPs show intense emission in the ultraviolet (UV) range up to 347 nm under 975 nm excitation. The bright emission in the UV range allows for singlet oxygen generation in the presence of hematoporphyrin on the surface of NPs. Our studies show that irradiation with a 975 nm laser of the functionalized NPs allows for the production of amounts of singlet oxygen easily detectable by Singlet Oxygen Sensor Green. The high emission intensity of NPs at 800 nm allowed the application of the synthesized NPs in an upconversion-linked immunosorbent assay (ULISA) for highly sensitive detection of the nucleoprotein from SARS-CoV-2, the causative agent of Covid-19. This article proves that LiYbF4:Tm3+@LiYF4 core@shell nanoparticles can be perfect alternatives for the most commonly studied upconverting NPs based on the NaYF4 host compound and are good candidates for biomedical applications.


Investigating a nickel-decorated fullerene for adsorbing tespa anticancer: drug delivery assessments.
A representative model of nickel-decorated fullerene (C19Ni) was investigated in this work for the adsorption of tespa (TESPA) anticancer towards approaching the drug delivery purposes. The singular and bimolecular models were stabilized by density functional theory (DFT) calculations to yield two complexes of TESPA@C19Ni models, TN and TS. The models were in a reasonable adsorption strength and their features showed benefits of such complex formations for approaching a carrier role fullerene. Frontier molecular orbitals were analyzed and atomic features were evaluated to reach a point of employing the investigated models in the drug delivery processes. One important observation of this complex model was movement of all frontier molecular orbitals to the fullerene side and the other point was the significant effects of adsorption process of those atoms of TESPA in a direct communication with the fullerene. Accordingly, the dominant role of fullerene was highlighted for the purpose of this work.


Musculoskeletal Pitfalls on Fluorodeoxyglucose F 18 PET-Computed Tomography: Pictorial Review.
A wide range of musculoskeletal processes can demonstrate increased uptake on PET-computed tomography (CT) with fluorodeoxyglucose (FDG) F 18, including reactive, benign neoplastic, inflammatory, traumatic, posttreatment, and arthritic conditions that may mimic malignancy. In addition, physiologic causes of increased FDG uptake such as asymmetric muscle use and presence of brown fat can lead to increased FDG uptake and potential false-positive results. This article presents various case examples of non-malignant musculoskeletal hypermetabolism on 18F-FDG PET-CT and describes useful tools to avoid the potential pitfall of misinterpreting these as malignancy.


Effect of AcrySof versus silicone or polymethyl methacrylate intraocular lens on posterior capsule opacification.
To investigate the effect of AcrySof intraocular lenses (IOLs) on the development of posterior capsule opacification (PCO) compared with silicone or polymethyl methacrylate (PMMA) IOLs for patients with senile cataracts. Meta-analysis of randomized controlled trials (RCTs). Patient data from previously reported RCTs. A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify RCTs comparing AcrySof with silicone or PMMA IOLs in patients with senile cataract. A meta-analysis was performed on the results of RCTs. Posterior capsule opacification score, neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy rate, and best-corrected visual acuity (BCVA) of 0.5 or better after cataract surgery. In total, 10 RCTs involving 1202 eyes with senile cataract were included in this meta-analysis. The results suggested that AcrySof had lower PCO scores than round-edged silicone IOLs (standard mean difference [SMD], -0.25; 95% confidence interval [CI], -0.42 to -0.08; P = 0.003) and a somewhat higher PCO score than sharp-edged silicone IOLs (SMD, 0.48; 95% CI, 0.29-0.68; P<0.00001). AcrySof had a lower Nd:YAG capsulotomy rate than round-edged silicone IOLs (odds ratio [OR], 0.29; 95% CI, 0.14-0.62; P = 0.001) and did not differ from sharp-edged IOLs (OR, 1.72; 95% CI, 0.23-13.13; P = 0.60). AcrySof had a lower PCO score (SMD, -1.07; 95% CI, -1.29 to -0.85; P<0.00001) and a lower Nd:YAG capsulotomy rate (OR, 0.09; 95% CI, 0.04-0.20; P<0.00001) than round-edged PMMA IOLs. Furthermore, there was no significant difference in BCVA between AcrySof and round-edged silicone IOLs (OR, 2.28; 95% CI, 0.66-7.82; P = 0.19) or PMMA IOLs (OR, 3.20; 95% CI, 0.78-13.16; P = 0.11). AcrySof and sharp-edged silicone IOLs are similarly effective in inhibition of PCO after cataract surgery. In patients implanted with the AcrySof lens, significantly less PCO developed than in those who had round-edged silicone or PMMA IOLs. The results of this meta-analysis support the theory that a major factor in preventing PCO development is a sharp-edged IOL design.


Daily variations in the formation of gastric ulcers caused by cervical cord transection in the rat.
Cervical spinal cord transection is used as a model of mammalian stress ulcerogenesis. Circadian variations in gastric ulceration have been demonstrated in other animal models. We investigated whether gastric ulceration changed after cervical cord transection throughout a 24-h period by subjecting different groups of rats to cord transection. Ulcers were quantitated using an index described by Szabo and colleagues. Ulcer formation showed significant variation as a function of time of lesioning, with least severe ulceration at 8 AM. We found that cord transection, like other models of gastric ulceration, is also influenced by the circadian system.


Study of a new indirect method based on absolute norms of variation to detect autologous blood transfusion.
The aim of this study was to investigate an indirect method based on a determination of absolute norms of variation in biological markers that could be used to identify autologous blood transfusion within the framework of the fight against doping. The selection of markers was made from experimental variations obtained during different phases including an increase in training volume at sea level, high altitude training, blood withdrawal and autologous blood reinfusion. The global statistical method was then developed in order to fix absolute norms of variation for each selected marker. The markers selected were haematocrit (Hct), haemoglobin concentration ([Hb]), stimulation index (Off-hr) and the absolute norms of variation (normDelta) established for a maximal 15 days period were normDeltaHct(0-15) >6%, normDelta[Hb](0-15) >4% and normDeltaOff-hr(0-15) >20%. From analyses between two blood samples spaced at an interval of maximum 15 days, this method allows to show "abnormal" variation when a variation for one of the selected markers is strictly superior to the absolute norms of variation established. The legal framework for an immediate application of this method could be that of the internal regulations implemented by each international federation in accordance with the health policy in vigour.


Arthroscopic findings of the glenohumeral joint in symptomatic anterior instabilities: comparison between overhead throwing disorders and traumatic shoulder dislocation.
The term shoulder instability refers to a variety of mechanisms and clinical presentations. One of the common pathologies of throwing disorders is internal impingement with anterior instability. Most throwing athletes with symptomatic internal impingement with anterior instability exhibit positive apprehension and relocation test results, whereas those with recurrent anterior shoulder instability display positive apprehension test results. While the glenoid labrum-inferior glenohumeral ligament complex is a significant critical stabilizer for the prevention of anterior shoulder dislocation, the characteristics of the essential lesion in internal impingement with anterior instability have not been determined yet. This study aimed to compare the intra-articular lesion of athletes with internal impingement related to the overhead throwing motion in athletes with a traumatic shoulder dislocation. Sixty-one athletes (all men; mean age, 25.2 ± 12.6 yr) who underwent an arthroscopic procedure were divided into 2 groups: 25 in the throwing group and 36 in the dislocation group. All shoulders had subtle glenohumeral instability defined by a positive anterior apprehension test and a relocation test. Those with voluntary and multidirectional instability and large glenoid bone loss (more than 25%) were excluded from the current study. All shoulders were evaluated for the following evidence: rotator cuff injury, superior labrum tear anterior and posterior lesions, labral pathologies including Bankart lesions, osteochondral lesions to the humeral head, biceps tendon fraying or rupture, and inferior glenohumeral ligament and middle glenohumeral ligament (MGHL) conditions. Arthroscopic findings of the throwing group showed more supraspinatus injuries (92% and 25%, P < .001), type II superior labrum tear anterior and posterior lesions (60% and 3%, P < .001), posterosuperior labral lesions (92% and 39%, P < .001), and hypoplastic MGHLs (56% and 6%, P < .001) and lesser Bankart lesions (8% and 92%, P < .05) than those of the dislocation group. These results indicate that the characteristic lesions of internal impingement with anterior instability in throwing athletes include partial thickness rotator cuff tears, superior labrum tear anterior and posterior lesions, posterosuperior labral tears, and hypoplastic MGHLs. As expected, the physiopathology of internal impingement with anterior instability in throwing athletes may be related to the dysfunction of the anterosuperior glenohumeral capsular ligament, including the MGHL, rather than the inferior glenohumeral ligament as in traumatic anterior shoulder dislocations. These findings would be useful for defining treatment strategies for internal impingement with anterior instability in overhead throwing athletes.


Let the Sun shine.
There is more than enough power available from the Sun to satisfy the world's needs, so why are we not rushing to exploit it?


[Psychological care of patients with head and neck cancer].
Treatments for head and neck cancers are generally complex and debilitating. Surgery, often mutilating, profoundly affects the relationship between oneself and others and causes verbal communication, breathing and swallowing difficulties. The functional and aesthetic sequelae are a constant reminder to the patient of the disease and make them conscious of their appearance.


Deaf or hard of hearing children in Saudi Arabia: Status of early intervention services.
This study aims to determine the status of early intervention services provided to children who are deaf or hard of hearing and their parents/caregivers from birth to five years of age at two main state hospitals in Riyadh, Saudi Arabia, based on their parents' perceptions. A descriptive quantitative research design was used to determine the status of early intervention services for deaf or hard of hearing children in Saudi Arabia based on their parents' perceptions. Semistructured interviews based on a questionnaire were conducted with 60 research participants from two main state hospitals where early detection and intervention services are provided. A purposive sampling technique was employed. Descriptive and inferential statistical analyses were performed on the data collected. The participants' children were diagnosed at a substantially late age, resulting in delayed ages for initial hearing aid fitting and enrolment in early intervention services. A significant relationship was found between the residential area of the participants and timely access to intervention services. The results indicated that participants residing in Riyadh were fitted with hearing aids and enrolled into EI services earlier than those living outside of Riyadh. The delivery of information also emerged as a weakness in the EI system for the majority of participants. The findings of the study suggested that limited services of detection and intervention for deaf or hard of hearing children and residential area of participants are likely to be barriers to early access to intervention services. It is proposed that the benefits of UNHS accompanied by appropriate early intervention services should be made available in all regions throughout Saudi Arabia.


p34cdc2 in invasive breast cancer: relationship to DNA content, Ki67 index and c-erbB-2 expression.
One-hundred and eighty-eight cases of human mammary carcinoma were examined immunohistochemically for their expression of Ki67, p34cdc2 and c-erbB-2. DNA image cytometry was performed to evaluate DNA ploidy, Auer type, S-phase fraction (SPF), 5c exceeding rate (5cER) and 2c deviation index (2cDI). One-hundred and sixty-eight cases were invasive ductal carcinomas, 20 were of invasive lobular type. Routinely assessed oestrogen and progesterone receptor scores were available. The results were analysed statistically in comparison to tumour type, histopathological grade, lymph node status, menopausal status, patient age and overall survival. Ki67 (P < 0.002) and c-erbB-2 (P < 0.0001) correlated well with overall survival (P < 0.0008) and grade (P < 0.038) but not with lymph node status and tumour type. p34cdc2 showed a trend towards a positive correlation with Ki67 (P < 0.058) and a significant negative correlation with receptor status (P < 0.008) but with none of the other parameters examined. No association between the DNA measured parameters (Auer type, SPF, 5cER and 2cDI) and survival was found. Our results suggest that c-erbB-2 and Ki67 are parameters which might, in combination with receptor status, help to define subgroups with different outcomes.