Imidazole-substituted oxoverdazyl radical as a mediator of intramolecular and intermolecular exchange interaction.
The 3-(2'-imidazolyl)-1,5-dimethyl-6-oxoverdazyl radical (imvd(*)) and the corresponding tetrazane H3imvd were prepared and structurally characterized, the former as two different hydrates. Reaction of imvd(*) with [M(hfac)2] led to the formation of monometallic complexes [M(hfac)2(imvd(*))] (M = Ni and Mn). They were characterized by single-crystal X-ray diffraction. In the solid state, all four radical-containing compounds exhibit imidazole-oxoverdazyl pi stacking. Following the structural analysis, imvd(*) behaves as an antiferromagnetic (AF) coupled chain with J = -100 cm(-1) (H = -J summation operator SiS(i+1)). The magnetic behavior of [M(hfac)2(imvd(*))] complexes is interpreted with a four-coupled spin model with a metal ion radical intramolecular interaction (JMn = -62.5 cm(-1) and JNi = 193 cm(-1); H = -JSMSimvd) and an AF intermolecular interaction (JMn' = -12.6 cm(-1) and JNi' = -4.3 cm(-1)) related to imidazole-oxoverdazyl pi stacking.


Behavioral characteristics of freemartins administered estradiol, estrone, testosterone, and dihydrotestosterone.
Eighteen genetic females born co-twin with males and diagnosed as being sterile intersexes (freemartins) were studied from birth to 79 weeks of age. Testosterone (T) and estrone (EI) were administered in Silastic capsules of two groups from birth to 50 weeks of age and other animals were left untreated. At 50 weeks the two treated groups had larger implants installed and the untreated animals were assigned to a new estrone (EII) and estradiol (E2) treatment. Later a dihydrotestosterone (DHT) group was formed in comparison with new E2 and testosterone propionate-enanthate (TP-TE) groups, plus untreated controls. Vulvar interest, Flehmen lip curl, mounting, and agonistic behavior were recorded daily for 30 min while animals were allowed social interaction. Agonistic behavior, interest in the genital area, and mounting were induced or stimulated by T, TP-TE, and E2, but not by DHT or estrone (EI or EII). Also, only animals in the T, TP-TE, and E2 groups induced to mount displayed the standing type of behavioral estrus. Flehmen lip curl was stimulated only by T or TP-TE. The evidence is interpreted to indicate that T, per se, evokes the lip curl, but it probably stimulates other responses at the neural level by conversion to E2. Also, the freemartin response, the response of castrates to steroid hormones, and current knowledge of circulating steroid hormones in male and female cattle could be interpreted to indicate that the neural tissue responsible for sexual behavior in both sexes of this species may respond similarly in several respects.


Recurrent circuits within medial entorhinal cortex superficial layers support grid cell firing.
Specialized cells in the medial entorhinal cortex (mEC), such as speed cells, head direction (HD) cells, and grid cells, are thought to support spatial navigation. To determine whether these computations are dependent on local circuits, we record neuronal activity in mEC layers II and III and optogenetically perturb locally projecting layer II pyramidal cells. We find that sharply tuned HD cells are only weakly responsive while speed, broadly tuned HD cells, and grid cells show pronounced transient excitatory and inhibitory responses. During the brief period of feedback inhibition, there is a reduction in specifically grid accuracy, which is corrected as firing rates return to baseline. These results suggest that sharp HD cells are embedded in a separate mEC sub-network from broad HD cells, speed cells, and grid cells. Furthermore, grid tuning is not only dependent on local processing but also rapidly updated by HD, speed, or other afferent inputs to mEC.


Evaluation of toxicities induced by chemotherapy in breast cancer patients.
The study includes the breast cancer female patients who had received chemotherapy (CMF, tamoxifen) and the newly diagnosed breast cancer patients, who had not received any chemotherapy. The patients who had received six cycles of CMF had shown low RBC, WBC and platelet count, elevated levels of SGPT, alkaline phosphatase and lactate dehydrogenase as compared to newly diagnosed breast cancer patients. The RBC count is increased in patients who had received CMF and tamoxifen as compared to the patients received only CMF, the alkaline phosphatase level is also declined in patients who had received CMF and tamoxifen as compared to the patients received CMF only.


[Functional role of proteins containing ankyrin repeats].
This review describes and discusses new data about the structure and function of proteins which contain ankyrin-like repeats in their structure. These proteins have been found in cells of different organisms but they are not belonging to the cytoskeletal proteins. Many important functions of such proteins are provided by ankyrin repeats which maintain protein-protein interactions involved in the formation of transcription complexes, initiation of immuno-responses, biogenesis and assembly of cation channels in the membranes, regulation of some cell cycle stages, symbiotic interactions and many other processes. Mutations in genes encoding ankyrin-like proteins can cause defects in gene expression leading to diseases onset and progression in animals and humans. Therefore, the structure, dynamics and function of these proteins is an area of extensive research in modern biology.


Effect of neuroleptics and other drugs on monoamine uptake by membranes of adrenal chromaffin granules.
1 The effects have been investigated of various reserpine-like, neuroleptic, antidepressant and other compounds on the adenosine-5'-triphosphate (ATP)-dependent uptake of noradrenaline (NA) (reserpine-sensitive) and tryptamine (reserpine-resistant) by membranes of isolated chromaffin granules of bovine adrenal medulla. 2 Reserpine and Ro 4-1284 (2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-hexahydro-11bH-benzo(a)quinolizine) as well as neuroleptics (e.g. chlorpromazine and haloperidol) inhibited the NA uptake, but the reserpine-like drugs were more potent. In contrast, Ro 4-1284 showed a considerably weaker effect thatn the neuroleptics in interfering with tryptamine uptake. Chlorpromazine had about the same potency in inhibiting NA and tryptamine uptake, whereas the action of haloperidol was more pronounced on the uptake of NA than of tryptamine. 3 The relative potencies of neuroleptic drugs in inhibiting NA uptake by granule membranes in vitro corresponded only partly to their relative potencies in enhancing dopamine turnover in vivo. 4 The inhibition of NA uptake by chloropromazine and Ro 4-1284 appeared to be of the noncompetitive type. 5 Chlorpromazine did not influence the decrease in ATP induced by granule membranes in the incubation medium. 6 Other basic, but not acidic compounds also inhibited NA uptake by granule membranes; their potency was of the order of that of chlorpromazine (antidepressants) or weaker (e.g. benzodiazepines). 7 In conclusion, the mechanism of action of neuroleptics probably differs from that of reserpine-like drugs in the inhibition of monoamine uptake by membranes of catecholamine storage organelles. While interference with the granular storage of dopamine at the granule membrane level may contribute to the in vivo action of neuroleptics (e.g. in enhancing dopamine turnover), additional effects of these drugs must be involved in vivo, e.g. blockade of pre- and postsynaptic dopamine receptors.


Cataract surgery with femtosecond lasers.
Cataract surgery with femtosecond lasers is approaching its practical application in ophthalmology. These lasers, working in the near infrared wavelength (1030 nm) can penetrate the transparent and even opaque tissues of the anterior segment of the eye, with limitations related to vessels and mineral opacities. Femtosecond lasers, guided by image systems can precisely outline the anatomy of the anterior segment of the eye, acting in a very precise way, performing corneal incisions, capsulorhexis, softening and breaking of the nucleus, which are essential steps in cataract surgery. In this article we summarize the four technologies available and approaching commercial application in the coming future. The main differences between the systems are based on the diagnostic imaging techniques, which might either be based on optical coherence tomography or the Scheimpflug principles. One model (the Technolas Femtec 520 F custom lens, 20/10 Perfect Vision), offers the possibility of combined use in corneal and intraocular surgery. While clinical studies are being performed with all of them, and most probably becoming available on the market during 2011 and 2012, the main problem of this emerging technology is its practical application as the increase in costs will affect their availability in the market of cataract surgery. Research is needed to confirm the practicality and the advantages of femtosecond laser cataract surgery over conventional surgery. Meanwhile, a new path for the future of cataract surgery is opening.


Nasal Elongation with Septal Half Extension Graft: Modification of Conventional Septal Extension Graft Using Minimal Septal Cartilage.
In Asian rhinoplasty, a septal extension graft can be used for both tip projection and derotation of the alar cartilage. However, patients often do not have enough harvestable septal cartilage to create the septal extension graft. We therefore devised a method with which to fix the derotated alar cartilage with a small amount of septal cartilage. From January 2012 to December 2016, 23 patients underwent short nose correction with a septal half extension graft made of septal cartilage and were postoperatively monitored for at least 6 months. The alar cartilage was completely separated from the adjacent structures, especially the scroll area and hinge complex, for caudal derotation. The septal half extension graft was then harvested from the septal cartilage and secured to the caudal septum and the lateral crura of the alar cartilage. Photographs of the patients were compared immediately before surgery and 1 year after surgery. Of the 23 patients, 21 (91%) had satisfactory results without short nose recurrence. Two (9%) patients developed recurrence: undercorrection and poor tip projection in one patient each. Aesthetic assessment of short nose correction was performed by comparing the columellar labial angle before and after surgery. Our method reduced the columellar labial angle by 6.2% (paired t test, p < 0.05, t = 31.698). In patients who cannot undergo conventional septal extension graft due to insufficient amounts of septal cartilage, the septal half extension graft could be a promising alternative technique for short nose correction with minimal septal cartilage harvesting. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis.
Stem cell based transplants effectively regenerate tissues; however, limitations such as immune rejection and teratoma formation prevent their application. Extracellular vesicles (EVs)-mediated acellular tissue regeneration is a promising alternative to stem cell based transplants. Although neural EGFL-like 1 (Nell1) is known to contribute to the osteogenic differentiation of bone marrow stem cells (BMSCs), it remains unknown whether EVs are involved in this process. Here, we present that EVs derived from Nell1-modified BMSCs (Nell1/EVs) have a stronger ability to promote BMSC osteogenesis owing to miR-25-5p downregulation. MiR-25-5p inhibits osteogenesis by targeting Smad2 and suppressing the SMAD and extracellular signal-related kinase 1 and 2 (ERK1/2) pathway activation. In addition, we demonstrate that the 3D-Nell1/EV-hydrogel system is beneficial for bone regeneration in vivo, probably stemming from a slow, continuous release and high concentration of EVs in the bone defect area. Thus, our results have shown the potential of Nell1/EVs as a novel acellular bone regeneration strategy. Mechanistically, the identification of miR-25-5p-SMAD2 signaling axis expands the knowledge of Nell1/EVs induced osteogenesis.


Determination of heavy metals in muscle tissue of six fish species with different feeding habits from the Danube River, Belgrade-public health and environmental risk assessment.
The aim of this study was to investigate the presence of heavy metals/metalloids (Pb, Cd, Hg, Cu, Fe, Zn, As) in the muscle tissue of fish from the Danube River (two locations: Zemun and Grocka). For the purpose of heavy metal determination in fish muscle, 120 samples of six different fish species, Prussian carp, barbel, bream, carp, pike perch, and catfish were collected. For determining heavy metals, we used microwave oven digestion and atomic absorption spectrometer methods. The highest average content of Pb (0.084 ± 0.004 mg kg-1), Cd (0.082 ± 0.003 mg kg-1), Hg (0.466 ± 0.006 mg kg-1), and As (0.333 ± 0.007 mg kg-1) was found in the muscle of carp (an omnivorous fish) from Grocka, while the highest average level of Fe (13.60 ± 0.03 mg kg-1) was deposited in bream (also omnivorous) from Zemun. Also, the average Cu level (1.62 ± 0.13 mg kg-1) was the highest in catfish muscle (a carnivorous fish) from Grocka, while the highest Zn content (11.16 ± 0.17 mg kg-1) was determined in muscle of Prussian carp (an omnivorous fish) from Zemun. The highest content of heavy metals (Cu, Fe, and Zn, respectively) in muscle of the six different types of fish from both locations was symmetrically arranged by species (catfish, barbel, and Prussian carp, respectively). Concentrations of Pb, Hg, and As in the Danube River fish muscle were under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia. On the other hand, in all fish muscle from both locations (Zemun and Grocka), higher concentrations of Cd than prescribed (MAC) were found, with the exception of bream and pike perch.


Stereoselective synthesis of myo-inositol via ring-closing metathesis: a building block for glycosylphosphatidylinositol (GPI) anchor synthesis.
Here we report a concise stereoselective synthesis of myo-inositol via ring-closing metathesis. A readily available bis-Weinreb amide of D-tartrate served as a key intermediate. [reaction: see text]


Expanding the applicability domain of QSPRs for predicting water solubility and vapor pressure of PFAS.
This work aimed to verify whether it is possible to extend the applicability domain (AD) of existing QSPR (Quantitative Structure-Property Relationship) models by employing a strategy involving additional quantum-chemical calculations. We selected two published QSPR models: for water solubility, logSW, and vapor pressure, logVP of PFAS as case studies. We aimed to enlarge set of compounds used to build the model by applying factorial planning to plan the augmentation of the set of these compounds based on their structural features (descriptors). Next, we used the COSMO-RS model to calculate the logSW and logVP for selected chemicals. This allowed filling gaps in the experimental data for further training QSPR models. We improved the published models by significantly extending number of compounds for which theoretical predictions are reliable (i.e., extending the AD). Additionally, we performed external validation that had not been carried out in original models. To test effectiveness of the AD extension, we screened 4519 PFAS from NORMAN Database. The number of compounds outside the domain was reduced comparing the original model for both properties. Our work shows that combining physics-based methods with data-driven models can significantly improve the performance of predictions of phys-chem properties relevant for the chemical risk assessment.


De Quervain tendinopathy: survivorship and prognostic indicators of recurrence following a single corticosteroid injection.
To determine short- and long-term success rates of a single corticosteroid injection for de Quervain tendinopathy while identifying prognostic indicators for symptom recurrence and repeat intervention. Fifty consecutive patients with de Quervain tendinopathy treated with corticosteroid injections (lidocaine plus triamcinolone acetonide or dexamethasone) were prospectively enrolled. Patients with inflammatory arthritis, carpometacarpal osteoarthritis, or a previous distal radius fracture affecting the symptomatic wrist were excluded. Demographic data and information on existing comorbidities were recorded. Patients were seen in clinic at 6 weeks after injection and contacted at 3, 6, 9, and 12 months following injection to determine symptom recurrence and further intervention. Medical records were also reviewed for this purpose. Kaplan-Meier survival analysis and Cox regression modeling were used to estimate recurrence rates and identify predictors of symptom recurrence and repeat intervention. Fifty wrists in 50 patients (average age, 49 y) were included. One patient was lost to follow-up. Eighty-two percent of patients had resolved symptoms 6 weeks after a steroid injection. Twenty-four patients had a recurrence of symptoms at a median of 84 days after the injection. Eleven patients underwent additional intervention (7 surgical releases and 4 repeat injections) at a median of 129 days (range, 42-365) after the injection. Estimated freedom from symptom recurrence was 52% at 6 and 12 months. Estimated freedom from repeat intervention was 81% at 6 months and 77% at 12 months. Two of 3 patients with a history of trigger finger required subsequent de Quervain surgery. We demonstrated that a single cortisone injection was effective in alleviating symptoms of de Quervain tendinopathy in 82% of patients and that over half remained symptom-free for at least 12 months. All patients with recurring symptoms developed them within the first 6 months. Prognostic IV.


Polysaccharide based transdermal patches for chronic wound healing: Recent advances and clinical perspective.
Polysaccharides form a major class of natural polymers with diverse applications in biomedical science and tissue engineering. One of the key thrust areas for polysaccharide materials is skin tissue engineering and regeneration, whose market is estimated to reach around 31 billion USD globally by 2030, with a compounded annual growth rate of 10.46 %. Out of this, chronic wound healing and management is a major concern, especially for underdeveloped and developing nations, mainly due to poor access to medical interventions for such societies. Polysaccharide materials have shown promising results and clinical potential in recent decades with regard to chronic wound healing. Their low cost, ease of fabrication, biodegradability, and ability to form hydrogels make them ideal candidates for managing and healing such difficult-to-heal wounds. The present review presents a summary of the recently explored polysaccharide-based transdermal patches for managing and healing chronic wounds. Their efficacy and potency of healing both as active and passive wound dressings are evaluated in several in-vitro and in-vivo models. Finally, their clinical performances and future challenges are summarized to draw a road map towards their role in advanced wound care.


miR-122-5p Mediates Fluoride-Induced Osteoblast Activation by Targeting CDK4.
Chronic intake of fluoride, existing in the environment, may cause endemic fluorosis, which is characterized by the occurrence of skeletal and dental fluorosis. However, the pathogenesis of fluorosis has not yet been elucidated. Abnormal osteoblast proliferation and activation have a pivotal role in bone turnover disorders which are linked to skeletal fluorosis. MicroRNAs are involved in fundamental cellular processes, including cell proliferation. Based on our previous study, population study and in vitro experiments were designed to understand the effect of miR-122-5p on osteoblast activation in skeletal fluorosis through targeting cyclin-dependent kinase 4 (CDK4). In human populations with coal-burning type fluoride exposure, the results showed that miR-122-5p was downregulated but CDK4 expression was upregulated and miR-122-5p was negatively correlated with CDK4 expression. Furthermore, in human osteoblasts treated with sodium fluoride, we demonstrated that miR-122-5p mediated osteoblast activation of skeletal fluorosis via upregulation of the CDK4 protein. In support of this, dual-luciferase reporter assay showed that miR-122-5p modulated CDK4 protein levels by targeting its 3'-untranslated region. These findings show, for the first time, that miR-122-5p may be involved in the cause and development of skeletal fluorosis by targeting CDK4.


[Oligo-amnios].
The amniotic fluid shares closely in the well-being of the future child and volume abnormalities represent a valuable factor in the screening of fetal pathology. Many publications have recently reminded of the importance of oligo-amnios as a prognosis factor in prenatal monitoring. Through an incomplete review of the literature, the author reminds of the physiology of amniotic fluid, diagnosis methods of oligo-amnios (essentially sonography), its causes and consequences, and finally its practical use as a monitoring parameter. A few possibilities of treatment are also discussed.


Hereditary, socio-behavioural, and immuno-hormonal predictors of incident rheumatoid arthritis and therapy response influences on survival versus matched control subjects using a generalised structural equation model.
Incident onset and survival outcomes involve multiple risk factors and complex interactions preferably investigated in a single study. A generalized structural equation model (GSEM) was used to build an integrative framework to analyse multiple risk factors for incident rheumatoid arthritis (RA) and factors affecting long-term survival outcome. Incident RA cases (n=54) had onsets between 1977 and 1994, after cohort entry in 1974. Four cohort control (CN) subjects (n=216) were matched on entry to each case in the community-based CLUE cohort and 270 subjects were followed from 1995 through 2017. Baseline variables included demographic, RA family history, behavioural factors and z-score levels of serum immunological, cytokine, isotype rheumatoid factors (RFs), adrenal steroids, luteinising hormone, prolactin and sex steroids. Four numerical integration methods of GSEM were performed in Stata 15. Cohort entry factors predicting RA onset included family history of RA, cigarette smoking and IgM RF. Total survival time from cohort entry was associated with incident RA and baseline variables of age, years of completed education, cigarette smoking, immunoreactive proteins and androgenic-anabolic steroids. Mortality of RA was significantly greater than CN subjects for cases having less than good therapy responses in 1995 and only for RA onset before age 60 years. Androgenic-anabolic steroid z-scores significantly correlated with improved survival only in CN subjects with assigned onset before the age of 60. Successful use of GSEM is feasible in analyses of prospective incident and subsequent survival data and promises to advance understanding of risk factors, survival, and casual pathways.


Effect of contrast-enhanced ultrasound (CEUS) on liver stiffness measurements obtained by transient and shear-wave elastography.
Since liver fibrosis is one of the most accurate predictors of prognosis in hepatopatic patients, its accurate assessment and staging is a major public health issue. Transient elastography (TE) (Fibroscan, Echosens, Paris, France) and shear wave elastography (SWE) represent the gold standard techniques among non-invasive methods to assess liver fibrosis. Contrast-enhanced ultrasound (CEUS) is increasingly used to diagnose the nature of liver lesions and is often performed together with TE and SWE. In this study we evaluated the effect of CEUS on liver stiffness measurements obtained by TE and SWE. A retrospective analysis of ultrasound (US) exams performed by an expert operator was carried out. TE and SWE were performed 30 seconds before and after the execution of CEUS. Statistical analysis was carried out using the statistical software R. Kolmogorov-Smirnov analysis was performed to test the normality of continuous variables. The pre- and post-CEUS liver stiffness values were compared using the Wilcoxon's Test. Ninety-six patients were enrolled. While the measurements were comparable when performed with TE, those obtained by SWE decreased by 6% after administration of the contrast agent (P=0.0005). Fibrosis stage deviated between pre- and post-CEUS in 16 (17%) patients with Fibroscan and 22 (23%) patients with SWE. Among the latter, in 9 cases (10%) a deviation from absent-low (F0-F2) to high-fibrosis (F3, F4), or vice versa, occurred. Our study, the first to assess the effects of CEUS on US elastography, shows that the contrast agent (Sonovue, Bracco Suisse SA, Cadempino, Switzerland) does not significantly affect liver stiffness measurements obtained by TE, whereas the accuracy decreases when performed by SWE.


Immunohistochemical characterization and quantitative analysis of neurons in the myenteric plexus of the equine intestine.
The present study was performed on whole-mount preparations to investigate the chemical neuroanatomy of the equine myenteric plexus throughout its distribution in the intestinal wall. The objective was to quantify neurons of the myenteric plexus, especially the predominant cholinergic and nitrergic subpopulations. Furthermore, we investigated the distribution of vasoactive intestinal polypeptide and the calcium-binding protein calretinin. Samples from different defined areas of the small intestine and the flexura pelvina were taken from 15 adult horses. After fixation and preparation of the tissue, immunofluorescence labeling was performed on free floating whole-mounts. Additionally, samples used for neuropeptide staining were incubated with colchicine to reveal the neuropeptide distribution within the neuronal soma. The evaluation was routinely accomplished using confocal laser-scanning microscopy. For quantitative and qualitative analysis, the pan-neuronal marker anti-HuC/D was applied in combination with the detection of the marker enzymes for cholinergic neurons and nitrergic nerve cells. Quantitative data revealed that the cholinergic subpopulation is larger than the nitrergic one in several different locations of the small intestine. On the contrary, the nitrergic neurons outnumber the cholinergic neurons in the flexura pelvina of the large colon. Furthermore, ganglia are more numerous in the small intestine compared with the large colon, but ganglion sizes are bigger in the large colon. However, comparison of the entire population of neurons in the different locations of the gut showed no difference. The present study adds further data on the chemoarchitecture of the myenteric plexus which might facilitate the understanding of several gastrointestinal disorders in the horse.


Anatomy and Pathology of the Skull Base: Malignant and Nonmalignant Lesions.
The skull base (SB) is the osseous foundation of the cranial vault. It contains many openings that allow communication between the extracranial and intracranial structures. This communication is crucial in normal physiologic processes yet may also arrow spread of disease. This article provides a comprehensive review of SB anatomy including important landmarks and anatomic variants relevant to SB surgery. We also illustrate the diverse pathologies affecting the SB.


Positive impact of a therapeutic drug-monitoring program on total aminoglycoside dose and cost of hospitalization.
A prospective evaluation was undertaken to assess the impact of an aminoglycoside therapeutic drug-monitoring (TDM) program on the total dose of aminoglycoside antibiotics, the duration of therapy, the number of serum concentrations determined, the length of hospital stay, and the potential cost reduction in 221 patients with proven or suspected gram-negative infections. The patients were allocated to a group that received individualized aminoglycoside doses (study) or to a group that did not (control). The mean total dose of gentamicin or tobramycin per patient course of therapy was 1,258 mg in the study group and 1,981 mg in the control group (p less than 0.0001). The mean duration of therapy was 5.9 and 10.3 days per patient in the study and control group, respectively (p less than 0.0001). The mean length of hospital stay was 8.4 days in the study group and 11.8 days for the control (p less than 0.005). The type and site of infection, number of serum concentration determinations, and mortality were not statistically different for the groups. These data indicate that a TDM program can markedly reduce the total dose of aminoglycoside, which can potentially reduce tissue accumulation and toxicity. In addition, the hospital costs were $725 less per patient in the study group, which would produce a savings of approximately $640,000 per year at our institution.


High-definition colonoscopy increases adenoma detection rate.
The adenoma detection rate (ADR) is a quality indicator for colonoscopy. High-definition (HD) imaging has been reported to increase polyp detection rates. The primary objective of this study was to compare polyp detection rate (PDR) and adenoma detection rate (ADR) before and after the implementation of HD colonoscopy. A retrospective chart review was performed on patients aged 48-55 years old, who underwent first-time screening colonoscopy. The first group underwent standard-definition (SD) colonoscopy in the first 6 months of 2011. The second group underwent screening with HD colonoscopy during the first 6 months of 2012. We compared age, gender, PDR, ADR, and average sizes of adenomatous polyps between gastroenterologist and colorectal surgeon and among physicians themselves. Statistical analysis was performed with Fischer's exact test and Pearson Chi-square. A total of 1268 patients were involved in the study (634 in each group). PDR (35.6 vs. 48.2 %, p < 0.001) and ADR (22.2 vs. 30.4 %, p = 0.02) were higher in the HD group. The average size of an adenomatous polyp was the same in the two groups (0.58 vs. 0.57, p = 0.69). However, this difference was not seen among colorectal surgeons PDR (35.7 vs. 37 %, p = 0.789), ADR (22.9 vs. 24.5 % p = 0.513), but clearly seen among gastroenterologist, PDR (35.6 vs. 53.1 % p < 0.001) and ADR (21.9 vs. 32.9 % p < 0.001). When polyps were categorized into size groups, there was no difference in ADR between the two timeframes (<5 mm in size (41.5 vs. 35.4 %), 5-10 mm (49.3 vs. 60.1 %) and >10 mm (9.2 vs. 4.5 %), p = 0.07). Polyps were most commonly seen in the sigmoid colon (26.1 vs. 24.7 %). There was no difference in the rate of synchronous polyp detection between modalities (25.6 vs. 29 %, p = 0.51). Withdrawal time was the same in both procedure (9.2 vs. 8.5 min, p = 0.10). Screening colonoscopy with high-definition technology significantly improved both PDR and ADR. In addition, high-definition colonoscopy may be particularly useful and advantageous among less experienced endoscopists in various community settings. However, there needs to be application to specific patient populations in future studies to assess for any statistical differences between standard- and high-definition modalities to determine clinical utility.


Comparison of MR imaging findings in paediatric and adult patients with acute mastoiditis and incidental intramastoid bright signal on T2-weighted images.
To compare MR imaging features in patients with incidental mastoid T2-hyperintensity with those of clinical acute mastoiditis, to ascertain characteristic differences between them. MR images of 35 adult and paediatric patients with clinical acute mastoiditis and 34 consecutive age-matched controls without relevant middle ear pathology and with incidental T2-hyperintensity that covered ≥ 50 % of the mastoid were retrospectively analysed with regard to signal, diffusion, and enhancement characteristics, and presence of complications. Incidental mastoid T2-hyperintensity that covered ≥ 50 % of the mastoid volume was found in 4.6 % of reviewed MR scans (n = 2341), and associated significantly (p < 0.05) less with the involvement of the tympanic cavity (38 % vs. 74 %) and mastoid antrum (56 % vs. 80 %), hypointense-to-CSF signal intensity on T2 FSE (6 % vs. 86 %), intramastoid diffusion restriction (0 % vs. 62 %), intense intramastoid enhancement (0 % vs. 51 %), periosteal enhancement (3 % vs. 69 %), perimastoid dural enhancement 3 % vs. 43 %), bone destruction (0 % vs 49 %), intratemporal abscess or cholesteatoma (0 % vs. 24 %), labyrinth involvement (0 % vs. 14 %), and extracranial abscesses (0 % vs. 20 %). Hypointense-to-CSF signal intensity on T2WI, restricted diffusion, intense intramastoid enhancement among other MR imaging characteristics favoured an acute mastoiditis diagnosis over clinically non-relevant incidental mastoid pathology. • Intramastoid T2-hyperintensity alone is not a reliable sign for acute mastoiditis. • In acute mastoiditis, intramastoid T2-weighted signal intensity is usually hypointense to CSF. • Diffusion restriction and intense intramastoid enhancement are absent in incidental mastoid effusion. • An ADC value ≥ 1.72 × 10 (-3) mm (2) /s contradicts the AM diagnosis.


Prepregnancy Body Mass Index and Infant Mortality in 38 U.S. States, 2012-2013.
To estimate whether prepregnancy body mass index (BMI) is related to infant mortality and whether adherence to weight gain recommendations mitigates the relationship between BMI and infant mortality. This was a cohort study using 2012-2013 U.S. national linked birth certificate and infant death files for 38 states and the District of Columbia with the BMI measure, including 6,419,836 singleton births and 36,691 infant deaths (infant mortality rate 5.72/1,000). Prenatal weight gain in three categories was based on adherence to Institute of Medicine recommendations. The outcome measure was infant deaths in the first year of life subdivided into two time periods: neonatal (less than 28 days) and postneonatal (28 days to 1 year). With normal prepregnancy weight as a reference, after adjustment, the odds ratio (OR) for an infant death rose from 1.32 (95% confidence interval [CI] 1.27-1.37) for mothers in the obese I category to 1.73 (95% CI 1.64-1.83) for obese III. Higher BMI was related to higher rates of both neonatal and postneonatal mortality. The adjusted OR for the risk of an infant death among singleton, term, vertex births for those gaining less than the recommended weight was 1.07 (95% CI 1.01-1.12) and 1.04 (95% CI 0.99-1.09) for those gaining more than recommended. Even after controlling for multiple risks, prepregnancy BMI was strongly related to infant mortality. Efforts to lower the infant mortality rate may benefit from a focus on reducing obesity among women of reproductive age.


The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence.
To determine whether oestrogen replacement will produce an improvement in the quantity, or quality, of pelvic collagen in postmenopausal women. A prospective double-blind placebo controlled trial of oestrogen therapy. Southmead Hospital, Bristol, UK. Fifty-five postmenopausal women with a urodynamic diagnosis of genuine urinary stress incontinence. Randomisation to a six-month, double-blind, placebo-controlled, trial of oestradiol valerate 2mg once daily. A 10mg-30mg periurethral biopsy was taken from the vaginal epithelium before and after treatment. Tissue was analysed for total collagen content, intermolecular cross-links, advanced glycation end-products, collagen type ratios and matrix metalloproteinase (MMP) activity. Forty-nine women completed the trial of whom 26 received oestrogen and 23 received placebo. When compared with placebo, oestrogen treatment resulted in significant decreases in total collagen (P = 0.0054), the mature cross-link HHL (P = 0.0009) and the advanced glycation end-product NFC-1 (P = 0.0009). There was a significant rise in the immature cross-link HLKNL (P = 0.0191). Oestrogen produced a significant increase in MMP-2 expression (Pro MMP-2, P = 0.0017). Six months treatment with oestrogen has profound effects upon pelvic collagen metabolism, stimulating collagen degradation via increased proteinase activity. While aged collagen is being lost, new collagen is synthesised as witnessed by the increase in the immature cross-links and the decrease in both mature cross-links and advanced glycation end-products. Collagen loss contradicts previous reports; perhaps aged collagen degradation is merely an early response to oestrogen stimulation. We have evidence of new collagen synthesis, and it may be that a longer treatment interval would show total collagen content increasing. Further studies within this field are warranted.


Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells.
Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases.


A study on long-term prognosis of epilepsy.
Of 631 epileptic patients examined in our seizure clinic in the period between January 1961 and December 1966, 97 (15.4%) have been treated until September 1976, when the long-term prognosis was evaluated. The "good prognosis (completely controlled)" were found in 59% of grand mal, in 55% of focal motor seizure, in 42% of psychomotor and in 33% of the mixed seizure in which more than two types of seizures were combined; in 49% (48 cases) on the average. Seventy-nine percent of the cases of the mixed seizure were combined with psychomotor seizures. In the psychomotor and the mixed seizure groups, the presence of personality disorders tended to lead them to "poor prognosis" which meant that the seizures were not well controlled. Twelve cases manifested psychotic (paranoid) state: a schizophrenic, a case with chronic paranoid-hallucinatory state, and 10 patients with episodic paranoid state, whose episodes may be identified with the paranoid reactions. Out of the 49 "poor prognosis" cases, 17 (35%) had had seizure-free periods for more than three years in the past course of their treatment.


Epidemiology and clinical relevance of microbial resistance determinants versus anti-Gram-positive agents.
Gram-positive pathogens are a major cause of community-acquired and hospital-acquired infections, and exhibit a remarkable ability to develop antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci (GRE) and multidrug-resistant pneumococci are currently the major resistance challenges among Gram-positives, due to their global dissemination and overall clinical impact. The mechanisms of evolution of these resistance phenotypes are based on a diverse array of mutational events and gene transfer phenomena carried out by several types of mobile genetic elements, followed by the dissemination of successful resistant clones. Resistance to glycopeptides in staphylococci remains uncommon, likely due to fitness issues. Resistance to the new anti-Gram-positive agents (linezolid, daptomycin and tigecycline) overall remains very rare. However, a transferable resistance mechanism to linezolid, mediated by ribosomal target modification by the Cfr protein, has recently emerged among S. aureus, being a matter of raising concern. Linezolid resistance among enterococci and coagulase-negative staphylococci is also increasingly reported. Moreover, a role for antibiotic resistance has been advocated in the recent increase of Clostridium difficile infection (CDI) associated with the emergence of hypervirulent strains.


Multistep evolution of B-cell-derived tumors in humans and rodents.
At least three genetic changes are known to contribute to the genesis of Burkitt's lymphoma (BL): the Ig/myc translocation, the presence of Epstein-Barr virus (EBV) in the vast majority of the endemic and a minority of sporadic tumors, and a p53 mutation, present in approximately 60% of the BL-derived lines. Activation of c-myc by juxtaposition to Ig sequences is a universal common denominator in endemic and sporadic EBV positive and negative BLs. It acts by preventing the cell from leaving the cycling compartment and by facilitating immune escape. EBV probably acts by expanding the target cell population at risk and prolonging its life span. This, together with the malaria co-factor, would increase the risk of the translocation accident. The p53 mutation may be essential for the continued growth of the tumors where it occurs, since introduction of wild-type p53 leads to their apoptotic death.


Studies on vitamin D metabolism: catabolism of 1 alpha, 25-dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 to a metabolite inactive on bone mineral mobilization.
A heretofore unknown metabolite of vitamin D3 was isolated from the 1 alpha, 24, 25-trihydroxyvitamin D3 fraction of lipid extracts obtained from plasma of rats which were given intravenous or oral doses of 100 pmol/100 g of either 1 alpha-hydroxyvitamin D3 or 1 alpha, 23-dihydroxyvitamin D3. Doses of 25-250 pmoles of the new metabolite when given to a vitamin D deficient rat were completely inactive in terms of stimulating the classic vitamin D response of bone calcium mobilization. The nature of the metabolism of 1 alpha-hydroxyvitamin D3 or 1 alpha, 25-dihydroxyvitamin D3 to the metabolite is not clear at the present time, but it is probable that neither of these steroids undergo side-chain cleavage to yield the new metabolite.


LONG-TERM THYROID DISORDERS IN CHILDREN RECEIVING ONCOLOGIC TREATMENT AND RADIOTHERAPY.
Childhood cancer survival has increased substantially over the past few decades. However, long-term side effects associated with cancer treatment have also risen. Especially thyroid gland disorders are common. The present retrospective cross-sectional study aimed to investigate risk factors of long-term TD in survivors of leukemia-lymphoma. The study included 44 acute lymphoblastic leukemia (ALL) and 26 Hodgkin lymphoma survivors (HL). Abnormal laboratory and pathological ultrasonographic findings of the thyroid gland were accepted as a thyroid disorder. The possible causes of thyroid disorders were investigated. Long-term thyroid disorder was found in 40% of the patients. This rate was higher in HL patients than in ALL (65% vs. 25%). Thyroid disorder was significantly more common in patients who received radiotherapy to the neck (57% vs. 17%). Radiotherapy to the neck area was the only significant determinant for thyroid disorders in the regression models [OR 33.17, 95% CI (2.76-398.9) p = 0.006]. However, HL remained significantly associated with TD in the logistic model performed using cancer type [OR 19.25, 95% CI (2.39-155.3) p = 0.006]. The study showed that radiotherapy applied to the neck was an essential risk factor for long-term TD in the average 6-year follow-up of cancer survivors. However, we recommend that childhood cancer survivors should be followed closely for a long time since long-term endocrine side effects were reported during longer than six years follow-up periods.


Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers.
Hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) is a feature of many solid tumours and is a key pathogenic driver in the inherited condition Tuberous Sclerosis Complex (TSC). Modulation of the tumour microenvironment by extracellular vesicles (EVs) is known to facilitate the development of various cancers. The role of EVs in modulating the tumour microenvironment and their impact on the development of TSC tumours, however, remains unclear. This study, therefore, focuses on the poorly defined contribution of EVs to tumour growth in TSC. We characterised EVs secreted from TSC2-deficient and TSC2-expressing cells and identified a distinct protein cargo in TSC2-deficient EVs, containing an enrichment of proteins thought to be involved in tumour-supporting signalling pathways. We show EVs from TSC2-deficient cells promote cell viability, proliferation and growth factor secretion from recipient fibroblasts within the tumour microenvironment. Rapalogs (mTORC1 inhibitors) are the current therapy for TSC tumours. Here, we demonstrate a previously unknown intercellular therapeutic effect of rapamycin in altering EV cargo and reducing capacity to promote cell proliferation in the tumour microenvironment. Furthermore, EV cargo proteins have the potential for clinical applications as TSC biomarkers, and we reveal three EV-associated proteins that are elevated in plasma from TSC patients compared to healthy donor plasma.


Influence of supports on photocatalytic degradation of phenol and 4-chlorophenol in aqueous suspensions of titanium dioxide.
The photocatalytic degradation of phenol and 4-chlorophenol (4-CP) in aqueous suspensions with the use of titanium dioxide (TiO2) under UV irradiation was examined. The effects of different supporting materials mixed physically with TiO2 were studied to achieve maximum degradation efficiency. Among the three supports, namely activated carbon (AC), silica (SiO2) and zeolite (ZSM-5), all exhibited paramount efficiency for degradation of phenol and 4-CP and was better than TiO2 alone. The optimum concentration was found to be 50 mg for all supporting materials. The efficiency order of the three supports was as follows: AC > ZSM-5 > SiO2, respectively. Whilst, the degradation of phenol and 4-CP was improved from 70.6% to 87.6% and 80.6% to 89.7%, respectively, within 120 min photocatalysis in the presence of optimal amount of AC. The degradation was also comparatively enhanced in the presence of cheaper rice husk and the activity was closed to ZSM-5 and lower than AC.


Construction of an inexpensive, hand-held fundus camera through modification of a consumer "point-and-shoot" camera.
To construct a low-cost, easy-to-use, high-image-quality mydriatic fundus camera with "point-and-shoot" operation, and to evaluate the efficacy of this camera to accurately document retinal disease. A prototype portable fundus camera was designed by interfacing a novel optical module with a Panasonic Lumix G2 consumer camera. Low-cost, commercially available optics were used to create even illumination of the fundus, providing a 50° retinal field of view. A comparative study assessing the image quality of the prototype camera against a traditional tabletop fundus camera was conducted under an Institutional Review Board (IRB)-approved study. A stand-alone, mydriatic camera prototype was successfully developed at a parts cost of less than $1000. The prototype camera was capable of operating in a point-and-shoot manner with automated image focusing and exposure, and the image quality of fundus photos was comparable to that of existing commercial cameras. Pathology related to both nonproliferative and proliferative diabetic retinopathy and age-related macular degeneration was easily identified from fundus images obtained from the low-cost camera. Early prototype development and clinical testing have shown that a consumer digital camera can be inexpensively modified to image the fundus with professional diagnostic quality. The combination of low cost, portability, point-and-shoot operation, and high image quality provides a foundational platform on which one can design an accessible fundus camera to screen for eye disease.


Selection of the optimal dose of sertraline for depression: A dose-response meta-analysis of randomized controlled trials.
Sertraline has been shown to be effective in the treatment of depression. However, the relationship between the dosage of sertraline and its efficacy and safety are unclear. We identified RCTs that compared sertraline with placebo for the treatment of depression, conducted conventional meta-analyses on the efficacy and safety of sertraline, and assessed the nonlinear dose-response relationship between sertraline dosage and the changes in HAM-D and CGI-S scores, dropout from care for any reason or due to adverse effects, and the rate of adverse effects, using a 1-stage restricted cubic spline regression model. Twenty-one RCTs involving 4,235 patients were included. The pooled mean differences (MD) in the change in HAM-D total score [MD=-2.34, 95% confidence interval (CI) -2.93, -1.76], CGI-S score and MADRS score, but also the dropout rate for adverse effects, and rate of adverse effects were higher in sertraline group. The therapeutic response of sertraline for treating depression increased with the dosage. Meanwhile, the risk of total adverse reactions slightly decreased between 50 and 150 mg, and increased at doses above 150 mg. The dose-dependence of both efficacy and safety need to be considered when choosing the optimal dosage of sertraline.


Characteristics and removal of antibiotics and antibiotic resistance genes in a constructed wetland from a drinking water source in the Yangtze River Delta.
Safe drinking water is crucial to public health. However, approximately one-third of the world's population lacks access to clean drinking water. The presence of antibiotics and antibiotic resistance genes (ARGs) in drinking water sources has become a severe problem worldwide due to its potential threat to human health. We monitored the occurrence and variations of 23 antibiotics and 9 ARGs in different treatment processes in a constructed wetland serving as drinking water source in the Yangtze River Delta, China. The studied wetland is consisted of four treatment processes: pretreatment area, pump station lifting, root-channel ecological purification area and deep purification area. Except for sulfapyridine and roxithromycin, 21 antibiotics were detected at concentrations ranging from 0.15 to 59.52 ng/L. The concentration of macrolides was the highest in this wetland, especially tylosin (42.86-59.52 ng/L). TetG, tetX and sul2 were the dominant ARGs in both water (2.41 × 10-4-1.87 × 10-2) and sediment (6.65 × 10-5-4.92 × 10-3). In addition, a strong correlation between ARGs in water and ARGs in sediment (Pearson, R2 > 0.9, p < 0.05) indicated an exchange between the two phases. Moreover, the significantly positive correlation of ARGs between the inlet and outlet of each subsystem illustrated that upstream pollution was the primary source for downstream processes. In general, the wetland system could efficiently eliminate antibiotics (9.0-53.8%) and ARGs (14.5-94.1%), with the deep purification area having the highest removal efficiency. Overall, our results provide important insights into the occurrence, abundance and removal of antibiotics and ARGs in the constructed wetland serving as drinking water sources.


Evolution of brains, cognition, and consciousness.
Most current hypotheses about the neural basis for consciousness, including higher-level consciousness, are based on mammalian neural features, particularly focusing on thalamocortical circuitry. It is postulated here that since higher-level consciousness is correlated with higher-level cognitive abilities in humans and other mammals, this correlation also holds for nonmammalian taxa; that the level of cognitive ability may be proportional to the level of consciousness; and that the neural basis for both is either the same or highly overlapping. Recent studies, ingeniously designed to be species-sensitive, have revealed a host of highly cognitive abilities in birds, including manifestations of working memory (delayed match-to-sample, episodic memory, transitive inference, and multistability) and category formation, language and numerical comprehension, tool manufacture and cultural transmission of tool design, theory of mind, and Piagetian object permanence to a high level. Comparisons of the neural circuitry reveal extensive similarity in thalamic nuclei and ascending systems to the pallium. However, the avian pallium lacks the laminar architecture and therefore cortical columns of mammals, and avian pallial projection neurons are multipolar rather than specifically pyramidal as in mammals. Neural features common to both mammals and birds, which thus may be crucially involved in the generation of both higher-level cognitive abilities and higher-level consciousness, include large, multipolar, glutamatergic neurons with extensive and densely spiny dendrites, with extensive interconnectedness as well as inter-regional connections, GABAergic inputs from local interneurons, and connections with thalamic nuclei that are regulated by the thalamic reticular nucleus as well as basal ganglia loops.


Function of blood monocytes among patients with orofacial infections.
Few data are available on the significance of the integrity of the innate immune system among patients with orofacial infections. This was assessed in the present study. Peripheral blood mononuclear cells (PBMCs) were isolated from 23 patients with orofacial infections before surgical debridement and from 12 healthy volunteers. PBMCs were stimulated with bacterial endotoxin (LPS) and with Pam3Cys. Concentrations of interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNFα) were estimated in supernatants by an enzyme immunoassay. Concentrations of estimated cytokines released from PBMCs of healthy volunteers and of patients did not differ. Intensity of cytokine release after stimulation was related with the time until complete resolution of the infection (p: 0.046). It is concluded that adequate functions of blood monocytes are associated with favorable outcome after surgery for orofacial abscesses. It seems, however, that impairment of monocyte function predisposes to infection persistence.


BIK1 protein homeostasis is maintained by the interplay of different ubiquitin ligases in immune signaling.
Pathogen-associated molecular patterns (PAMPs) trigger plant innate immunity that acts as the first line of inducible defense against pathogen infection. A receptor-like cytoplasmic kinase BOTRYTIS-INDUCED KINASE 1 (BIK1) functions as a signaling hub immediately downstream of multiple pattern recognition receptors (PRRs). It is known that PLANT U-BOX PROTEIN 25 (PUB25) and PUB26 ubiquitinate BIK1 and mediate BIK1 degradation. However, how BIK1 homeostasis is maintained is not fully understood. Here, we show that two closely related ubiquitin ligases, RING DOMAIN LIGASE 1 (RGLG1) and RGLG2, preferentially associate with the hypo-phosphorylated BIK1 and promote the association of BIK1 with the co-receptor for several PRRs, BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1). PUB25 interacts with RGLG2 and mediates its degradation. In turn, RGLG2 represses the ubiquitin ligase activity of PUB25. RGLG1/2 suppress PUB25-mediated BIK1 degradation, promote BIK1 protein accumulation, and positively regulate immune signaling in a ubiquitin ligase activity-dependent manner. Our work reveals how BIK1 homeostasis is maintained by the interplay of different ubiquitin ligases.


Plasma dopamine-beta-hydroxylase activity and thyroid suppressibility in Graves' disease.
Plasma dopamine-beta-hydroxylase (DBH) activity, serum T4, T3, T3U, and the 24-hr thyroid uptake before triiodothyronine suppression testing were studied in 34 patients with treated Graves' disease. Although all of them were in the euthyroid state, there was a statistically significant difference in presuppression plasma DBH activity between those patients who showed suppression of their RAI uptake with triidothyronine and those who did not. This suggests a relationship between plasma DBH activity and thyroid suppressibility.


Traumatic hemipelvectomy--the tenth survivor: a case report and a review of the literature.
This tenth survivor of traumatic hemipelvectomy was a young male involved in a collision between a car and his bicycle. As in previous cases, he sustained severe associated injuries to the genitourinary tract and rectum. Atypically he required secondary closure with autogenous skin taken from the severed lower limb, and in addition, he developed a compartment syndrome in the opposite leg.


An arginine specific protease from Spirulina platensis.
An arginine specific protease, Sp-protease, was purified by column chromatography from freeze-dried Spirulina platensis using a five-step process. Purified Sp-protease has a molecular weight of 80 kDa. It hydrolyzed the synthetic substrates containing arginine residue in the P1 position but did not hydrolyze synthetic substrates containing other amino acid residues, including lysine residue in the P1 position. Among the synthetic substrates tested, a substrate of plasminogen activator (Pyr-Gly-Arg-MCA) was hydrolyzed most effectively with the enzyme (Km = 5.5 x 10(-6) M), and fibrin gel was solubilized via activation of intrinsic plasminogen to plasmin with the enzyme. Activity was inhibited completely with camostat mesilate (Ki = 1.1 x 10(-8) M) and leupeptin (Ki = 3.9 x 10(-8) M) but was not inhibited with Nalpha-tosyl-L-lysine chloromethyl ketone (TLCK). The optimum pH of the enzyme has a range of pH 9.0 to pH 11.0. The optimum temperature was 50 degrees C; the enzyme was stable at 0-50 degrees C.


The genetic architecture of the corpus callosum and its genetic overlap with common neuropsychiatric diseases.
The corpus callosum (CC) is the main structure transferring information between the cerebral hemispheres. Although previous large-scale genome-wide association study (GWAS) has illustrated the genetic architecture of white matter integrity of CC, CC volume is less stressed. Using MRI data from 33,861 individuals in UK Biobank, we conducted univariate and multivariate GWAS for CC fractional anisotropy (FA) and volume with PLINK 2.0 and MOSTest. All discovered SNPs in the multivariate framework were functionally annotated in FUMA v1.3.8. In the meanwhile, a series of gene property analyses was conducted simultaneously. In addition, we estimated genetic relationship between CC metrics and other neuropsychiatric traits and diseases. We identified a total of 36 and 82 significant genomic loci for CC FA and volume (P < 5 × 10-8). And 53 and 27 genes were respectively mapped by four mapping strategies. For CC volume, gene-set analysis revealed pathways mainly relating to cell migration; cell-type analysis found the top enrichment in neuroglia while for CC FA in GABAergic neurons. Furthermore, we found a lot of genetic overlap and shared loci between CC FA and volume and common neuropsychiatric diseases. Collectively, this study helps to better understand the genetic architecture of whole CC and CC subregions. However, the way to divide CC FA and volume in our study restricts the interpretations of our results. Future work will be needed to pay attention to the genetic structure of white matter volume, and an appropriate division of CC may help to better understand CC structure.


Chemical Composition and Antipathogenic Activity of Artemisia annua Essential Oil from Romania.
The essential oil extracted by hydrodistillation from Romanian Artemisia annua aerial parts was characterized by GC/MS analysis, which allowed the identification of 94.64% of the total oil composition. The main components were camphor (17.74%), α-pinene (9.66%), germacrene D (7.55%), 1,8-cineole (7.24%), trans-β-caryophyllene (7.02%), and artemisia ketone (6.26%). The antimicrobial activity of this essential oil was evaluated by determining the following parameters: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), minimal fungicidal concentration (MFC), and minimal biofilm eradication concentration (MBEC). Moreover, the soluble virulence factors were quantified with different biochemical substrates incorporated in the culture media. The reference and resistant, clinical strains proved to be susceptible to the A. annua oil, with MICs ranging from 0.51 to 16.33 mg/ml. The tested essential oil also showed good antibiofilm activity, inhibiting both the initial stage of the microbial cell adhesion to the inert substratum and the preformed mature biofilm. When used at subinhibitory concentrations, the essential oil proved to inhibit the phenotypic expression of five soluble virulence factors (hemolysins, gelatinase, DNase, lipases, and lecithinases). Briefly, the present results showed that the A. annua essential oil contained antimicrobial compounds with selective activity on Gram-positive and Gram-negative bacterial strains as well as on yeast strains and which also interfere with the expression of cell-associated and soluble virulence factors.


Enzymatic regioselective acylation of nucleosides in biomass-derived 2-methyltetrahydrofuran: kinetic study and enzyme substrate recognition.
Enzymatic regioselective acylation of pyrimidine nucleosides was mediated by immobilized lipase from Penicillium expansum in 2-methyltetrahydrofuran (MeTHF), a bio-solvent derived from biomass. Despite of the moderate dissolution ability of MeTHF toward nucleosides, the initial enzymatic reaction rate was much higher in this eco-friendly solvent than in other commonly used organic solvents. This could be explained by the lower apparent activation energy of the enzymatic reaction (24.5 vs. 43.3-57.1kJ/mol) and the higher catalytic efficiency of the enzyme (Vmax/Km, 5.8 vs. 1.1-2.9h(-1)) in MeTHF. The enzymatic acylation of a group of ribonucleosides afforded the desirable 5'-esters with the conversions of 96-99% and 5'-regioselectivities of 96 to >99%. In enzymatic acylation of 2'-deoxynucleosides, however, 5'-regioselectivities showed a clear dependence on the 5-substituents present in the base moiety although the substrate conversions reached >98% within 1-3h. In the cases of 2',3'-dideoxynucleoside analogs, the reaction rate decreased markedly due to the lack of 3'-hydroxyl.


The increasing incidence of initial steroid resistance in childhood nephrotic syndrome.
Recently, a number of reports have highlighted changes in the histopathology and response to corticosteroid treatment in childhood nephrotic syndrome; however, these involved ethnically mixed populations. For comparison, the purpose of our research was to search for changes in the characteristics of nephrotic syndrome in a homogeneous population of Caucasian children over two consecutive decades. Chart analysis was performed to identify children with new-onset nephrotic syndrome. The children were admitted to the Division of Pediatric Nephrology, Zabrze, during two periods: 1986-1995 (76 patients) and 1996-2005 (102 patients). Specifically, a comparison of clinical characteristics and morphology of nephrotic syndrome between the two groups was performed. Steroid resistance was defined as no remission within 8 weeks of corticosteroid treatment. Histopathology was available in 36.8% and 43.1% of patients respectively. There was a significant increase in primary steroid resistance in the latter decade: 15.8% vs 31.4% (P = 0.017). Changes in the histopathology did not reach the level of statistical significance: minimal change nephrotic syndrome 25% vs 9% (P = 0.095), mesangial proliferative glomerulonephritis 46.4% vs 61.3% (P = 0.21), focal segmental glomerulosclerosis 17.9% vs 20.4% (P = 0.78), membranoproliferative glomerulonephritis 7.1% vs 6.8% (P = 1.0), membranous glomerulonephritis 3.6% vs 0% (P = 0.39). Our results show the increasing incidence of primary steroid resistance in childhood nephrotic syndrome.


Freedom through constraint: Young women's embodiment, space and wellbeing during lockdown.
Following the emergence of the COVID-19 pandemic and the associated lockdown restrictions in March 2020, young people were suddenly faced with a reduction and reconfiguration of the spaces in which they could 'be'. This paper explores how in this lockdown context, young women (aged 10-20) experienced their bodies and wellbeing, where traditional social connections (particularly school and physical connections) were not possible. Based on qualitative responses (n = 511) from an online, open-ended survey on wellbeing, physical activity, body image and social media usage, we explore how a reduction and reconfiguration of space, understood relationally, contributes to an individual's wellbeing. Using abductive reasoning and taking a phenomenological approach, we concentrate on the embodied experience of wellbeing and how this links to the spaces in which the body is lived. We suggest that the removal of spaces during lockdown, which on the one hand can be seen as problematic for maintaining wellbeing, also enabled many young women to experience new connections - with their bodies, family, and the environment and nature, that supplemented previous connections and fostered positive relationships and wellbeing. The removal of specific performative modes of judgement associated with the school environment was a positive influence on many young women's relationships with their own bodies and their wider construction of wellbeing, but increased use of social media spaces were found to reconstitute these performative experiences. The benefits of the specific and newly delimited freedoms associated with the forced lockdown have implications for an understanding of embodied wellbeing that is not individual, instead embedded inextricably in relations of connectedness with others in space and the nature of these intersubjective experiences.


Complexation and biodistribution study of 111In and 90Y complexes of bifunctional phosphinic acid analogs of H4dota.
In this study, the complexation rates of two new phosphinate H(4)dota (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) analogs, H(5)do3ap(PrA) and H(4)do3ap(ABn), and H(4)dota itself were compared under identical conditions (H(5)do3ap(PrA)=10-{[(2-carboxyethyl)hydroxyphosphoryl]methyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; H(4)do3ap(ABn)=10-{[(4-aminophenyl)hydroxyphosphoryl]methyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). The biodistribution of their (111)In and (90)Y complexes in healthy rats was also studied. Unlike the observation obtained under "chemical" conditions where differences between the ligands were observed no such differences in complexation rates were found under radiochemical conditions. The ligands bind the radiometals similarly to H(4)dota. So, "chemical" formation kinetic data should be transferred into radiochemical conditions only with high care and "radiochemical" complexation experiments should be run as part of standard in vitro studies with new ligands considered as potential radiopharmaceuticals. Pharmacokinetic studies in rats showed similar distribution characteristics for both phosphinate H(4)dota analogs radiolabelled with (111)In and (90)Y when compared with that of the (111)In-H(4)dota complex. No specific uptake in any organ and tissue of rats was determined. The phosphinate complexes are not accumulated in calcified tissues.


Angiosarcoma of the spleen: a report of two cases and review of the literature.
Results of the ultrastructural study of one of two cases of splenic angiosarcoma established the blood vessel origin of this tumor. Fifty-three previously reported cases were reviewed. None of the 55 patients had a history of exposure to thorium dioxide, vinyl chloride, or arsenic, which are known to be associated with hepatic angiosarcoma and other tumors. A comparison of the splenic and hepatic angiosarcomas showed that tumors not associated with exogenous material frequently involve the spleen and liver simultaneously, and that tumors associated with thorium dioxide, vinyl chloride, or arsenic commonly involve the liver with sparing of the spleen.


Are prehospital treatment or conveyance decisions affected by an ambulance crew's ability to access a patient's health information?
A shift from a predominantly emergency service, towards one where a wide range of conditions are managed and treated on scene presents numerous challenges for ambulance services and clinicians. The effective management of a broad range of patients and conditions in the ambulance setting will have an impact on other parts of the health service including emergency departments and primary care. A two part online survey was distributed to operational staff working for a regional UK ambulance service. Clinicians were asked to report their experiences of accessing patient information and making decisions about patient management based on four hypothetical patient scenarios. A survey of clinical staff (n = 302) revealed that (i) the vast majority experienced difficulties in accessing patients' health information, (ii) this was particularly true in the out of hours period and (iii) They felt that better access would likely lead to more appropriate selection of care pathways. Decisions regarding the most appropriate care for patients presenting to the ambulance service are best informed by access to accurate and complete health information and records. An understanding of patients' pre-existing medical conditions, recent treatments and health information is needed for the selection of the most appropriate care; this information is often difficult to obtain in the ambulance service setting.


[Effects of Schistosoma 22.6 kDa/26 GST molecule mixed with Sepharose 4B beads on induction of CD4+CD25+ regulatory T cells].
To study the responses of regulatory T cells induced by Sepharose 4B beads mixed antigen. Mice were immunized with different dosages of antigens, and the proportions of regulatory T cells were examined by flow cytometry. The 3H-thymidin incorporation method was used to detect the inhibitory function of Tregs. In vitro, dendritic cells were pulsed with different antigens. The expressions of MHC II, CD40, CD80/86 molecules on dendritic cells and the proportions of regulatory T cells were examined by flow cytometry. The 3H-thymidin incorporation method was used for the determination of Tregs function. Compared with control groups, the proportion of regulatory T cells in mice immunized with Sepharose 4B beads mixed antigen was(11.48 +/- 4.12)%, and the difference was significant (P < 0.05). The inhibition of regulatory T cells in mice immunized with Sepharose 4B beads mixed antigen showed a stronger potential (cpm was 720 +/- 180.4). Meanwhile, the proportions of regulatory T cells were (17.0 +/- 80.57)% and (30.14 +/- 3.62)% when the CD4+ T cells were co-cultured with dendritic cells pulsed with Sepharose 4B beads mixed rSj22.6/26GST and OVA, respectively. Sepharose 4B beads mixed antigen could induce the regulatory T cells in vivo and in vitro.


Molecular characterization and distribution of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi from yaks in Tibet, China.
With worldwide distribution and importance for veterinary medicine, Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi have been found in a wide variety of vertebrate hosts. At present, few available molecular data can be used to understand the features of genetic diversity of these pathogens in areas without or less intensive farming. Dominated by grazing, Tibet is a separate geographic unit in China and yaks are in frequent contact with local herdsmen and necessary for their daily life. Therefore, to investigate the distribution of these pathogens in yaks of Tibet, 577 fecal specimens were screened using nested PCR for the presence and genotypes of the three intestinal pathogens. The overall prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 1.4% (8/577), 1.7% (10/577), and 5.0% (29/577), respectively. Cryptosporidium andersoni (n = 7) and Cryptosporidium bovis (n = 1) were detected by sequence analysis of the SSU rRNA gene. Genotyping at the SSU rRNA and triosephosphate isomerase genes suggested that all G. duodenalis positive specimens belonged to assemblage E. Sequence analysis of the internal transcribed spacer gene identified six known E. bieneusi genotypes: BEB4 (n = 11), I (n = 6), D (n = 5), J (n = 2), CHC8 (n = 1), and BEB6 (n = 1). One subtype (A5,A4,A2,A1) for C. andersoni and three multilocus genotypes for E. bieneusi were identified by multilocus sequence typing. We report for the first time the status of three enteric pathogens infection simultaneously for grazing yaks in Tibet. Yaks in our study are likely to impose a low zoonotic risk for humans. The molecular epidemiology data add to our knowledge of the characteristics of distribution and transmission for these pathogens in Tibet and their zoonotic potential and public health significance.


Development of fetal rat lung during prolonged gestation.
Pregnancies were prolonged by daily subcutaneous injection of progesterone to the maternal rats from day 20 through 24 of gestation (Term is 22 days). The fetuses were harvested by cesarean section on gestation days (GD) 21 through 25. In spite of reduction in placental weight the fetal body weight increased during prolonged gestation. Both lung wet and dry weights decreased resulting in smaller lung per body weight. Compared to term fetuses, post term fetuses (GD 25) exhibited a 10% reduction in lung cell numbers, and a 90% reduction in lung glycogen. Lung disaturated phosphatidyl choline expressed per lung increased up to GD 23 and subsequently decreased by GD 25. Surface tension of lung extracts and pulmonary lavage fluids increased with prolongation of gestation. Histological studies revealed a decrease in the number of lamellar bodies in the Type II cells and a gradual reduction in the size of terminal sacs leading to areas of complete atelectasis at GD 25. It is suggested that lung hypocellularity, depletion of lung glycogen, reduction in intracellular reserve of phospholipids, loss of pulmonary fluid leading to atelectasis, and loss of surface activity of pulmonary fluid may be predisposing factors for the development of respiratory distress in postmaturity.


Effects of a barium-based additive on gaseous and particulate emissions of a diesel engine.
The addition of barium-based additives is one of the main methods used to suppress smoke emissions in non-road diesel engines. Herein, a commercial barium-based additive was added to diesel fuel at the manufacturer's recommended concentration and used in a non-road four-cylinder supercharged diesel engine, without an after-treatment system, in bench experiments. Regulated emissions of the diesel engine were measured, volatile organic compounds (VOCs) and particulate matter (PM) were sampled. The carbonaceous fraction, water-soluble ions and inorganic elements in the PM were analyzed. Results indicated that the additive effectively reduced carbon monoxide (CO), hydrocarbon (HC) and smoke emissions from the engine. A 71% reduction in smoke was observed at the rated working condition, which was the maximum reduction of the three tested conditions. The additive produced a 36% reduction of VOCs at the rated working condition. The proportion of high carbon number hydrocarbons in the VOCs increased while the atmospheric reactivity of the VOCs decreased. The additive suppressed the concentration of organic carbon (OC) and elemental carbon (EC) emissions with a maximum reduction (40%) of total carbon achieved under the rated working condition. After the application of the additive, the concentration of water-soluble ions (Cl-, SO42-, NO3-, Na+, K+, Ca2+, NH4+) and elements (Fe, Mn, S, Ca, Ba) in the PM increased. A trend of increasing Barium content in the PM matched a similar trend of decreasing smoke.


[Chronic fibular instability of the ankle-joint -- x-ray diagnostic and ligamentous graft (author's transl)].
It was tried to find out how many radiographs are necessary to show instabilities of the ankle-joint with ruptures of the ligamentum talofibulare anterius alone (which is the most common ligamentous lesion) and in combination with other fibular ligaments. Therefore stress views of anatomical speciems of ankle-joints with previous artifically coused lesions were done. It was found that one lateral view with the talus stressed in subluxation and one a.p. view with stressed pes equinus and supination with slight internal rotation of the foot are enough in comparison with the other side. The mostly used plastic reconstructions of old fibular ligament teares by Watson-Jones and Evans act as a tenodesis for the subtalar joint, because the natural anatomical position of the ligamentum calcaneofibulare, which should be replaced, is not respected. We looked for the best positioning of a graft as a replacement of the ligamentum calcaneofibulare by help of a string model in anatomical speciems. Only the straight graft of this ligament gives the best chance of free mobility in the subtalar joint. Other directions of this ligamentous graft lead either to a tenodesis or to an outwear of the graft without a stabilizing effect. Postoperative examinations of nine patients with ligamentous grafts stress this point.


Delayed diagnosis of cystic fibrosis in children with a rare genotype (delta F508/R117H).
In neonatal screening for cystic fibrosis (CF), infants recognised as delta F508 heterozygotes require a sweat test to confirm the diagnosis. However, compound heterozygotes with delta F508 and the R117H mutation are known to have non-diagnostic sweat chlorides (< 60 mmol/L) at an early age. As genotyping for rare mutations is not readily available in Australia, there is a need to determine whether quantitative pancreatic stimulation tests could facilitate the diagnosis of CF in three infants with the delta F508/R117H mutation. Formal sweat testing, genotyping and pancreatic stimulation tests were performed in three subjects heterozygous for delta F508 who initially had non-diagnostic sweat chloride results (40-60 mmol/L) but presented later with persisting chest symptoms and/or signs consistent with CF. All three patients were shown to have the delta F508/R117H genotype with initial sweat chloride results ranging from 40 to 58 mmol/L. Pancreatic stimulation tests demonstrated reduced enzyme secretion in two and decreased fluid, bicarbonate and chloride secretion in all three patients. In infants recognized as delta F508 heterozygotes by the newborn screening programme, the presence of an equivocal sweat chloride does not exclude the diagnosis of CF. If such patients with an initially equivocal sweat chloride subsequently develop symptoms suggestive of CF and have a persisting non-diagnostic sweat chloride then the diagnosis of CF can be confirmed by more extensive genotyping if available or by pancreatic stimulation testing.


En face view of Mansonella (Mansonella) akitensis (Uni, 1983) by scanning electron microscopy.
The en face view of the head of M. (M.) akitensis was examined by scanning electron microscopy (SEM). The cephalic extremity with major axis dorsoventral confirmed the taxonomical position of the species.


Microtubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport.
The lissencephaly-related protein LIS1 is a critical regulator of cytoplasmic dynein that governs motor function and intracellular localization (for example, to microtubule plus-ends). Although LIS1 binding is required for dynein activity, its unbinding prior to initiation of cargo transport is equally important, since preventing dissociation leads to dynein dysfunction. To understand whether and how dynein-LIS1 binding is modulated, we engineered dynein mutants locked in a microtubule-bound (MT-B) or microtubule-unbound (MT-U) state. Whereas the MT-B mutant exhibits low LIS1 affinity, the MT-U mutant binds LIS1 with high affinity, and as a consequence remains almost irreversibly associated with microtubule plus-ends. We find that a monomeric motor domain is sufficient to exhibit these opposing LIS1 affinities, and that this is evolutionarily conserved between yeast and humans. Three cryo-EM structures of human dynein with and without LIS1 reveal microtubule-binding induced conformational changes responsible for this regulation. Our work reveals key biochemical and structural insight into LIS1-mediated dynein activation.


Protective and destructive immunity in the periodontium: Part 1--innate and humoral immunity and the periodontium.
Based on the results of recent research in the field, the present paper will discuss the protective and destructive aspects of the innate vs. adaptive (humoral and cell-mediated) immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) the Toll-like receptors (TLR), the innate immune repertoire for recognizing the unique molecular patterns of microbial components that trigger innate and adaptive immunity for effective host defenses, in some general non-oral vs. periodontal microbial infections; (ii) T-cell-mediated immunity, Th-cytokines, and osteoclastogenesis in periodontal disease progression; and (iii) some molecular techniques developed and used to identify critical microbial virulence factors or antigens associated with host immunity (using Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species). Therefore, further understanding of the molecular interactions and mechanisms associated with the host's innate and adaptive immune responses will facilitate the development of new and innovative therapeutics for future periodontal treatments.


Obstetric management of a patient with Andersen-Tawil syndrome: A case report.
Andersen-Tawil syndrome (ATS) is a rare hereditary long QT syndrome type 7 caused by a missense mutation in the KCNJ2 gene. ATS is characterized by ventricular arrhythmia, periodic limb paralysis and minor external malformations. Although only three reports of pregnant women with Andersen-Tawil syndrome have been reported to date, no exacerbation of ventricular arrhythmia was observed from pre-partum to delivery in all cases compared to that before pregnancy, and it was suggested that the risk of arrhythmic events from pre-partum to delivery is not high. Unlike these previous reports, we herein present a case of Andersen-Tawil syndrome in which ventricular arrhythmias increased and sustained ventricular tachycardia was developed during labor progression. We also advise caution that pregnant patients with Andersen-Tawil syndrome may have varying times of exacerbation of the arrhythmia, and ventricular arrhythmias may be associated with painful uterine contractions.


Asymptomatic spontaneous rupture of craniopharyngioma cyst.
Spontaneous rupture of craniopharyngioma cyst is a rare phenomenon. Either chemical meningitis or neurological improvement is usually associated with spontaneous cyst rupture. We experienced two patients who underwent asymptomatic spontaneous cyst rupture. MRI revealed reductions in the sizes of cysts in the left cerebellopontine cistern and middle fossa in a 4-year-old girl and a cyst in the suprasellar region of a 47-year-old man. These patients did not develop chemical meningitis, nor was there any change in neurological symptoms related to the craniopharyngioma cysts. According to our review of the literature, spontaneous rupture of craniopharyngioma cysts can be divided into three subtypes: (i) cyst rupture associated with chemical meningitis; (ii) cyst rupture with improvement in symptoms related to the craniopharyngioma and not associated with chemical meningitis; and (iii) asymptomatic rupture. It is important to be aware of unexpected cyst rupture during observation of craniopharyngiomas.


A prospective study on the efficacy of sequential treatment of technology Lipido-Colloid Impregnated with Silver and Technology Lipido-Colloid Nano-Oligosaccharide Factor in the management of venous leg ulcers.
Venous leg ulcers (VLUs) are associated with significant morbidity and poor quality of life (QOL). Compression therapy and wound dressing are the mainstay treatment options. Technology Lipido-Colloid Impregnated with Silver (TLC-Ag) reduces bacterial load and Technology Lipido-Colloid Nano-Oligosaccharide Factor (TLC-NOSF) reduces elevated matrix metalloproteinases and improve wound healing. However, evidence is scarce on the role of sequential therapy. This study aims to evaluate if sequential treatment with TLC-Ag and TLC-NOSF improves VLU wound healing and QOL. This is a prospective cohort study from May 2020 to October 2021 on patients with VLUs who received sequential therapy, consisting of 2 weeks of TLC-Ag followed by two-layer compression bandage (2LB) with TLC-NOSF until complete wound healing. Participants were followed-up with weekly dressing changes. Our primary outcomes were wound area reduction (WAR) and Pressure Ulcer Scale of Healing (PUSH) score. Our secondary outcomes were QOL measures. There were 28 patients with 57.1% males (n = 16) with a mean age of 65.3 years. Mean duration of VLU was 13.9 ± 11.7 weeks before the initiation of sequential therapy. Mean baseline wound area was 8.44 cm2. Median time to wound healing was 10 weeks. 57.1% of patients achieved complete wound closure at 3 months. There was significant WAR after 1 month (mean area 8.44-5.81 cm2, 31.2% decrease) and after 3 months (mean area 8.44-2.53 cm2, 70.0% decrease). Mean monthly WAR was 28.9%. PUSH score also decreased at 1 month (16.5% decrease, p < 0.001) and 3 months (63.3% decrease, p < 0.001) marks following the sequential therapy. EuroQol Visual Analog Scale (EQ-VAS) improved following sequential therapy (baseline: 69.0 ± 15.0, week 13: 80.2 ± 13.2, p < 0.001). Sequential therapy with TLC-Ag followed by TLC-NOSF and 2LB is feasible, with good wound healing and improvement in QOL of patients with VLUs.


Mechanistic study of the enantiomeric recognition of a basic compound with negatively charged single-isomer gamma-cyclodextrin derivatives using capillary electrophoresis, nuclear magnetic resonance spectroscopy, and infrared spectroscopy.
The possible mechanisms for the chiral recognition of 2-(R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide (RR-M3), and its enantiomer (SS-M3) with octakis(2,3-di-O-acetyl-6-sulfo)-gamma-cyclodextrin (ODAS-gamma-CD) and octakis(6-sulfo)-gamma-cycöpdextrom enantiomer; (OS-gamma-CD), were investigated using capillary electrophoresis (CE), proton ((1)H), fluorine ((19)F) and carbon ((13)C) nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) spectroscopy. Clear evidence for the formation of diastereomeric complexes between the enantiomers and the two CDs was observed. NMR spectra suggest that the phenyl and difluorocyclopentyl rings are involved in the complexation. The phenyl ring on the guest molecule is deeply penetrated into the cavity of OS-gamma-CD, but it is not included into the cavity of ODAS-gamma-CD. The continuous variation plots built based on the (1)H NMR and IR spectra indicate a 1:1 complex stoichiometric ratio of the M3 enantiomers for both CDs. The affinity of the enantiomers for the two CDs is opposite.


Accumulating candidate genes for broad-spectrum resistance to rice blast in a drought-tolerant rice cultivar.
Biotic stresses, including diseases, severely affect rice production, compromising producers' ability to meet increasing global consumption. Understanding quantitative responses for resistance to diverse pathogens can guide development of reliable molecular markers, which, combined with advanced backcross populations, can accelerate the production of more resistant varieties. A candidate gene (CG) approach was used to accumulate different disease QTL from Moroberekan, a blast-resistant rice variety, into Vandana, a drought-tolerant variety. The advanced backcross progeny were evaluated for resistance to blast and tolerance to drought at five sites in India and the Philippines. Gene-based markers were designed to determine introgression of Moroberekan alleles for 11 CGs into the progeny. Six CGs, coding for chitinase, HSP90, oxalate oxidase, germin-like proteins, peroxidase and thaumatin-like protein, and 21 SSR markers were significantly associated with resistance to blast across screening sites. Multiple lines with different combinations, classes and numbers of CGs were associated with significant levels of race non-specific resistance to rice blast and sheath blight. Overall, the level of resistance effective in multiple locations was proportional to the number of CG alleles accumulated in advanced breeding lines. These disease resistant lines maintained tolerance to drought stress at the reproductive stage under blast disease pressure.


Characterizing the penumbras of white matter hyperintensities in patients with cerebral small vessel disease.
The white matter hyperintensity penumbra (WMH-P) is the subtly changed normal-appearing white matter (NAWM) that surrounds white matter hyperintensities (WMHs). The goal of this study was to define WMH-P in cerebral small vessel disease (CSVD) by arterial spin labeling (ASL) and diffusion tensor imaging (DTI)/diffusion kurtosis imaging (DKI). We prospectively analyzed 42 patients with CSVD. To determine the range of cerebral blood flow (CBF) and DTI/DKI penumbras around white matter hyperintensities, we generated NAWM layer masks from periventricular WMHs (PVWMHs) and deep WMHs (DWMHs). Mean values of CBF, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis, and radial kurtosis within the WMHs and their corresponding NAWM layer masks were analyzed. Paired sample t tests were used for analysis, and differences were considered statistically significant if the associated p value was ≤ 0.05. For DWMHs, the CBF penumbras were 13 mm, and the DTI/DKI penumbras were 8 mm. For PVWMHs, the CBF penumbras were 14 mm, and the DTI/DKI penumbras were 14 mm. Our findings revealed that DTI/DKI and ASL can show structural and blood flow changes in brain tissue surrounding WMHs. In DWMHs, the blood flow penumbra was larger than the structural penumbra, while in PVWMHs, the blood flow penumbra was almost the same as the structural penumbra.


Water environmental degradation of the Heihe River Basin in arid northwestern China.
Water environmental degradation is a major issue in the Heihe River Basin belonging to the inland river basin of temperate arid zone in northwestern China. Mankind's activities, such as dense population and heavy dependence on irrigated agriculture, place immense pressure on available and limited water resources during the last century, especially the recent five decades. An investigation on the water environmental degradation in the Heihe River Basin and analysis of its causation were conducted. The results indicated that water environmental changes in the whole basin were tremendous mostly in the middle reaches, which reflected in surface water runoff change, decline of groundwater table and degeneration of surface water and groundwater quality. Some new forms of management based on traditional and scientific knowledge must be introduced to solve problems of water environmental degradation in the Heihe River Basin.


Theoretical components of smoking cessation interventions for persons with physical disabilities: A scoping review.
Rationale Persons with physical disabilities report higher cigarette smoking rates and a lower likelihood of accessing health services (e.g., smoking cessation services). Explicit and systematic application of behaviour change theory may be a promising approach to addressing these inequities and developing impactful smoking cessation interventions for persons with physical disabilities. This scoping review aimed to explore how behaviour change theory and intervention components have been used to design smoking cessation interventions for persons with physical disabilities. Electronic databases (Medline, Embase, PsycINFO, CINAHL, Web of Science) were systematically searched. Smoking cessation interventions for persons with physical disabilities were identified. Behaviour change theory and intervention components, including behaviour change techniques, intervention functions, mode of delivery, intervention source, and setting, were extracted from the included articles. Among the eleven included articles, there were nine unique smoking cessation interventions for persons with physical disabilities. Three interventions mentioned theory, but none of these articles explicitly applied or tested the theory. Intervention components were consistently combined to deliver pharmacotherapy and behavioural counselling-based interventions. The results of this review highlight the scarcity of theory-based smoking cessation interventions for persons with physical disabilities. While the interventions were not theory-based, they were evidence-based and aligned with recommendations for smoking cessation treatment (i.e., behavioural counselling plus pharmacotherapy). Future research should take a theory-based approach to intervention development to enhance the likelihood that smoking cessation interventions for persons with physical disabilities are effective, replicable, and equitable.


Placement of the Decompression Tube as a Bridge to Surgery for Acute Malignant Left-Sided Colonic Obstruction.
The aim of this study is to investigate the feasibility, safety, and effectiveness of placing the decompression tube as a bridge to surgery for acute malignant left-sided colonic obstruction. From January 2009 to August 2014, consecutive patients with acute malignant left-side colonic obstruction underwent placement of the decompression tube as a bridge to surgery in our center. The technical and clinical success of placing the decompression tube was evaluated. Clinical success was defined as relief of obstructive symptoms within 48 h after placing the decompression tube. Elective tumor resection was performed 7-9 days after colonic decompression. The types of surgery, primary anastomosis rate, and follow-up findings were analyzed. Twenty patients with acute malignant left-side colonic obstruction underwent placement of the decompression tube as a bridge to surgery. Placement of decompression tube was technically successful in all patients. No procedure-related complication occurred. Clinical success was achieved in 19 patients. Elective tumor resection and primary anastomosis were successfully performed in all 19 patients. The postoperative complications included wound infection (n = 2) and anastomotic stenosis (n = 1). Decompression tube can serve as an easy, safe, and effective bridge to subsequent surgery for patients with acute malignant left-sided colonic obstruction.


Aneurysms of the pancreaticoduodenal arteries in association with celiac axis occlusion.
Four patients with aneurysms of the inferior pancreaticoduodenal artery are described. All had occlusion of the celiac axis at its origin, with the inferior pancreaticoduodenal arcades serving as a collateral pathway. We propose that the association of the celiac axis occlusion and aneurysms in the collateral supply via the pancreatic arcades is more than coincidental. Awareness of this relationship may be of significance in planning therapeutic intervention.


Versatile microbial surface-display for environmental remediation and biofuels production.
Surface display is a powerful technique that uses natural microbial functional components to express proteins or peptides on the cell exterior. Since the reporting of the first surface-display system in the mid-1980s, a variety of new systems have been reported for yeast, Gram-positive and Gram-negative bacteria. Non-conventional display methods are emerging, eliminating the generation of genetically modified microorganisms. Cells with surface display are used as biocatalysts, biosorbents and biostimulants. Microbial cell-surface display has proven to be extremely important for numerous applications, ranging from combinatorial library screening and protein engineering to bioremediation and biofuels production.


Soil transport and plant uptake of radio-iodine from near-surface groundwater.
This paper describes a 12-month experiment designed to study the extent of upward migration of (125)I (as a surrogate for (129)I) from near-surface groundwater, through a 50-cm column of soil and into perennial ryegrass. The water table was established at a depth of 45 cm below the soil surface. By 3 months, (125)I had migrated about half way up the soil column. After this, it tended to accumulate just above this mid-point, with only very small amounts being transported to the upper 20 cm of soil. This behaviour seemed to be explained well by soil moisture and redox conditions. The experiment indicated that (125)I was mobile only within the saturated/low redox zone at the base of the soil column and accumulated in the zone of transition between anoxic and oxic soil conditions. Uptake of (125)I by the ryegrass was found to be low.


Effect of methyl cellulose on tear film break-up-time in health and disease.
Methyl cellulose instillation enhanced the values of BUT in healthy individuals, as well as in patients with trachoma stage III and chronic conjunctivitis, while no effect was observed in patients with squamous blepharitis.