Urodynamics in children. Part I. Methodology.
We evaluated 237 children for various disorders in the urodynamic laboratory. A total of 334 studies was done, using a 6-channel recorder combined with a portable fluoroscopic unit. Simultaneous recordings of intravesical pressure, intra-abdominal pressure, urine flow rate, external urethral electromyography and cystourethrography were obtained during bladder filling and voiding. These objective tests have provided us with an insight into the nature of a variety of voiding dysfunctions in children. Details of the methods used for urodynamic testing in these children are outlined and compared to other methods that have been proposed.


Effects of the Isomerized Thiophene-Fused Ending Groups on the Performances of Twisted Non-Fullerene Acceptor-Based Polymer Solar Cells.
Recently, benefiting from the merits of small-molecule acceptors (NFAs), polymer solar cells (PSCs) have achieved tremendous advances. From the perspective of the structural characteristics of the π-conjugated acceptor-donor-acceptor (A-D-A) type of organic molecules, the backbone's planarity and the terminal groups and their substituents have strong influences on the performances of the constructed NFAs. Through enlarging the dihedral angle of the conjugated main chain of NFAs, a certain degree of enhancement of photovoltaic parameters has been achieved. To further probe the influences of ending groups on the performances of nonplanar NFAs, we synthesized two new NFAs i-cc23 and i-cc34 with isomerized thiophene-fused ending groups and a twisted π-conjugated main chain. Compared to i-cc23 containing the 2-(6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophen-4-ylidene)malononitrile ending group, the acceptor i-cc34 containing 2-(6-oxo-5,6-dihydro-4H-cyclopenta[c]thiophen-4-ylidene)malononitrile has a relatively higher molar extinction coefficient, bathochromic-shifted absorption spectrum, and deepened energy levels. When mixed with PBDB-T in solar cells, the i-cc23-based device achieved an excellent open-circuit voltage (VOC) of 1.10 V and a moderate power conversion efficiency of 7.34%. Although the VOC of the i-cc34-related device was decreased to 0.96 V, the short-circuit current density and fill factor were improved, giving rise to an enhanced efficiency of 9.51%. Apart from the distinct photovoltaic performances, the two isomer-based devices exhibit a high radiative efficiency of 8 × 10-4, leading to a very small nonradiative loss of 0.19 V. Our results emphasize the importance of the isomerized thiophene-fused ending groups on the performances of nonplanar NFA-based PSCs.


Comparison of outcomes of primary anterior chamber versus secondary scleral-fixated intraocular lens implantation in complicated cataract surgeries.
To compare the outcome of primary anterior chamber vs secondary scleral-fixated intraocular lens (IOL) implantation in complicated cataract surgeries. Retrospective, comparative study. A consecutive series of complicated cataract surgeries with primary anterior chamber (ACIOL) or secondary scleral-fixated IOL implantation from January 1, 2004 to December 31, 2009 was analyzed. Main outcome measures included the postoperative best-corrected visual acuity (BCVA) and postoperative complications. There were 89 eyes in the primary ACIOL group and 74 eyes in the secondary scleral-fixated IOL group. The mean follow-up duration was 64.1 ± 36.7 months. The mean postoperative logarithm of minimal angle of resolution (logMAR) BCVA at 1 year was 0.32 ± 0.54 and 0.34 ± 0.21 in the primary ACIOL group and the secondary scleral-fixated IOL group, respectively (P = .734). The mean latest logMAR BCVA was 0.68 ± 0.54 and 0.61 ± 0.47 in the primary ACIOL group and the secondary scleral-fixated IOL group, respectively (P = .336). The primary ACIOL group had more early postoperative complications (P < .001). No difference in late postoperative complications was observed between the 2 groups (P = .100). Regression analysis showed that primary ACIOL and secondary scleral-fixated IOL implantation had similar latest postoperative logMAR BCVA (P = .927), while the presence of late complications was associated with a worse final visual outcome (P = .000). This study shows that there are no long-term differences in the visual outcomes and complication profiles after primary ACIOL or secondary scleral-fixated IOL implantation in a complicated cataract operation when capsular support is inadequate.


Comparison of chemometric assisted targeted and untargeted approaches for the prediction of radical scavenging activity of ylang-ylang essential oils.
Essential oils have been used for centuries for their preservative properties. An example is ylang-ylang Cananga odorata [Lam.] Hook. f. & Thomson essential oil, which exists in four different distillation grades, where the fraction with the longest distillation time has the highest radical scavenging activity (RSA). Gas chromatography mass spectrometry (GC-MS) followed by multivariate statistical analysis is a powerful approach for determination of RSA. Herein the performance of such multivariate statistical analysis using three data sets derived from gas chromatography mass spectrometry (GC-MS) analysis, is compared to that achieved using two direct and fast spectroscopic techniques, for the prediction of RSA using partial least squares (PLS) regression analysis. The three GC-MS data sets were, 'full chemical composition', 'total chromatogram average mass spectra (TCAMS)' and 'segment average mass spectra (SAMS)', whilst two spectroscopic techniques, namely attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy, provided the spectroscopic data sets for comparison. PLS models created using ATR-FTIR and 'full chemical composition' data sets provided the lowest relative error of prediction (REP) and mean error of prediction (MEP) in validation, whilst in independent test sets, the PLS models created using ATR-FTIR and SAMS data sets delivered the lowest REP and MEP. The three GC-MS derived data sets were further compared for value in determination of compounds contributing to the RSA. PLS regression analysis of the full chemical composition data set revealed that germacrene D and (E,E)-α-farnesene were the major contributors to the RSA, whilst average mass spectrum based data sets, TCAMS and SAMS, also highlighted eugenol as another contributor to the RSA.


One-year analysis of the iStent trabecular microbypass in secondary glaucoma.
To evaluate the midterm efficacy and safety of the iStent(®) glaucoma device in patients with secondary open-angle glaucoma. A prospective, nonrandomized, interventional case series involving 10 patients with secondary open-angle glaucoma (traumatic, steroid, pseudoexfoliative, and pigmentary glaucoma) of recent onset who underwent ab interno implantation iStent. Patients were assessed following the procedure on days 1, 7, and 15 and months 1, 3, 6, and 12, and examinations included visual acuity, intraocular pressure (IOP) measurement using Goldmann tonometry, number of glaucoma medications, and complications. Wilcoxon rank-test for data with abnormal distribution was used for the analysis of IOP and glaucoma medications at baseline versus 3, 6, and 12 months following the procedure. The mean baseline IOP was 26.5 ± 7.9 (range 18-40) mmHg, and significantly decreased in 10.4 ± 9.2 mmHg at three months (P < 0.05), in 7.4 ± 4.9 mmHg at six months (P < 0.05), and in 6.6 ± 5.4 mmHg at 12 months (P < 0.05) following iStent implantation. The mean number of hypotensive medications at baseline was 2.9 ± 0.7 (range 2-4). Statistically significant reductions in the number of medications of 1.1 ± 1.1 were observed at three months (P < 0.05), 1.0 ± 0.7 at six months (P < 0.05), and 1.1 ± 0.6 at 12 months (P < 0.05). No significant changes in visual acuity were noted. The most common complications comprised mild hyphema in seven eyes and transient IOP ≥30 mmHg in three eyes on postoperative day 1. Obstruction of the lumen of the stent with a blood clot was seen in three eyes, and all instances resolved spontaneously. The iStent is a safe and effective treatment option in patients with secondary open-angle glaucoma, and reduces the topical treatment burden in one hypotensive medication.


Isopropyl 1-benzoyl-4-benzo-yloxy-2,6-di-phenyl-1,2,3,6-tetrahydropyridine-3-carboxyl-ate.
In the title compound, C35H31NO5, the piperidine ring has an envelope conformation, with the phenyl-substituted C atom adjacent to the methyl-ene C atom as the flap. This flap atom deviates by 0.633 (2) Å from the mean plane of the other five essentially coplanar atoms in the ring (r.m.s. deviation = 0.044 Å). Intra-molecular C-H⋯O hydrogen bonds form S(7) and S(9) ring motifs. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with R (2) 2(16) loops.


Transcription of the speC (ornithine decarboxylase) gene of Escherichia coli is repressed by cyclic AMP and its receptor protein.
The speC gene encoding ornithine decarboxylase (ODC) in Escherichia coli is negatively regulated by cAMP and the cAMP receptor protein (CRP). In minicells transformed with the plasmid pODC bearing speC, cAMP supplementation repressed ODC synthesis. In a cell-free protein synthesizing system directed by pODC, cAMP at 10(-5) M repressed ODC synthesis by 90%. This repression required a functional CRP as cAMP failed to repress ODC synthesis in vitro in an extract prepared from a crp- strain; the addition of purified CRP to the crp- extract restored the ability of cAMP to repress ODC synthesis. In a prototroph transformed with the plasmid pCOD bearing a speC::tet chimeric gene, cAMP supplementation decreased tetracycline (Tc) resistance. In contrast, in crp- strains transformed with pCOD or pTET (TcR), cAMP supplementation did not change their Tc resistance. When a cya- strain was supplemented with 2 mM cAMP, steady state levels of ODC mRNA were repressed by 80%. However, when a isogenic crp- strain was supplemented with 2 mM cAMP, no repression of ODC mRNA was observed. These results indicate that the cAMP-CRP complex exerts negative transcriptional control of ODC synthesis as a function of the speC promoter.


The safety of flucloxacillin in HIV-infected patients with positive HLA-B*5701 genotype.
Positive HLA-B*5701 genotype has recently been identified as the main genetic risk factor for flucloxacillin drug-induced liver injury (DILI). Testing for HLA-B*5701 is routine in many HIV clinics to identify those at risk of hypersensitivity reaction (HSR) to abacavir. Considering the high prevalence of soft-tissue infections in HIV patients, we conducted a retrospective study to investigate whether flucloxacillin use was associated with adverse events in HIV patients known to be HLA-B*5701 positive.


Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients.
Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow-up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment-emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty-eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug-unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis-dependent patients with genotype 1b AHC.


Mutagenic activity and structure-activity relationships of short-chain dialkyl N-nitrosamines in a hamster hepatocyte V79 cell-mediated system.
A series of 19 short chain dialkyl N-nitrosamines was studied for mutagenic activity in an uninduced hamster hepatocyte V79 cell-mediated mutagenesis system. Ouabain was used as the selective agent to quantitatively analyze for chemically induced mutants. None of the nitrosamines was mutagenic in the absence of hamster hepatocyte activation. The relative mutagenic activities of the nitrosamines at an equimolar dose are presented. The results of the study indicated that: increasing alkyl chain length decreased mutagenic activity; oxidation of the 2-carbon position to a carbonyl group increased the mutagenic activity of symmetrical and asymmetrical nitrosamines, whereas oxidation to a hydroxyl group only increased the mutagenic activity of the asymmetrical nitrosamines tested; and the carbon position at which oxidation occurred was important in determining mutagenic activity. The relationships between structure, metabolic activation, and mechanisms of mutagenic activity are discussed.


[Characteristics of the reaction of the macrophage lysosomal apparatus in guinea pigs immunized with a live and a killed Br. abortus culture].
Accumulation of fluorescent antigen-antibody complex in the cytoplasmic granules at various time intervals after the phagocytosis of brucellae treated with brucella fluorescent serum was studied in the peritoneal macrophage culture of guinea pigs immunized with live and killed brucella culture. The activity of the lysosomic system was also studied. Immunization with live brucellae led to an increase in the acid phosphatase activity, to an increased rate of destruction of phagocytosed spheroplasts with fluorescent antibodies fixed on their surface, to a more rapid accumulation of fluorescent antigen-antibody complex in secondary lysosomes and to a more marked humoral response than the immunization with the killed culture. Changes in macrophages correlated with positive skin allergic reactions, and were apparently associated with increased sensitivity of a delayed type.


Flavan-3-ol esters: new agents for exploring modulatory sites on GABA(A) receptors.
Enhancement of GABAergic function is the primary mechanism of important therapeutic agents such as benzodiazepines, barbiturates, neurosteroids, general anaesthetics and some anticonvulsants. Despite their chemical diversity, many studies have postulated that these agents may bind at a common or overlapping binding site, or share an activation domain. Similarly, we found that flavan-3-ol esters act as positive modulators of GABA(A) receptors, and noted that this action resembled the in vitro profile of general anaesthetics. In this study we further investigated the interactions between these agents. Using two-electrode voltage clamp electrophysiological recordings on receptors of known subunit composition expressed in Xenopus oocytes, we evaluated positive modulation by etomidate, loreclezole, diazepam, thiopentone, 5α-pregnan-3α-ol-20-one (THP) and the flavan-3-ol ester 2S,3R-trans 3-acetoxy-4'-methoxyflavan (Fa131) on wild-type and mutated GABA(A) receptors. The newly identified flavan, 2S,3S-cis 3-acetoxy-3',4'-dimethoxyflavan (Fa173), antagonized the potentiating actions of Fa131, etomidate and loreclezole at α1β2 and α1β2γ2L GABA(A) receptors. Furthermore, Fa173 blocked the potentiation of GABA responses by high, but not low, concentrations of diazepam, but did not block the potentiation induced by propofol, the neurosteroid THP or the barbiturate thiopental. Mutational studies on 'anaesthetic-influencing' residues showed that, compared with wild-type GABA(A) receptors, α1M236Wβ2γ2L and α1β2N265Sγ2L receptors are resistant to potentiation by etomidate, loreclezole and Fa131. Fa173 is a selective antagonist that can be used for allosteric modulation of GABA(A) receptors. Flavan-3-ol derivatives are potential ligands for etomidate/loreclezole-related binding sites at GABA(A) receptors and the low-affinity effects of diazepam are mediated via the same site.


Dynamic regulation of fatty acid pools for improved production of fatty alcohols in Saccharomyces cerevisiae.
In vivo production of fatty acid-derived chemicals in Saccharomyces cerevisiae requires strategies to increase the intracellular supply of either acyl-CoA or free fatty acids (FFAs), since their cytosolic concentrations are quite low in a natural state for this organism. Deletion of the fatty acyl-CoA synthetase genes FAA1 and FAA4 is an effective and straightforward way to disable re-activation of fatty acids and drastically increase FFA levels. However, this strategy causes FFA over-accumulation and consequential release to the extracellular medium, which results in a significant loss of precursors that compromises the process yield. In the present study, we aimed for dynamic expression of the fatty acyl-CoA synthetase gene FAA1 to regulate FFA and acyl-CoA pools in order to improve fatty alcohol production yields. We analyzed the metabolite dynamics of a faa1Δ faa4Δ strain constitutively expressing a carboxylic acid reductase from Mycobacterium marinum (MmCAR) and an endogenous alcohol dehydrogenase (Adh5) for in vivo production of fatty alcohols from FFAs. We observed production of fatty acids and fatty alcohols with different rates leading to high levels of FFAs not being converted to the final product. To address the issue, we expressed the MmCAR + Adh5 pathway together with a fatty acyl-CoA reductase from Marinobacter aquaeolei to enable fatty alcohol production simultaneously from FFA and acyl-CoA, respectively. Then, we expressed FAA1 under the control of different promoters in order to balance FFA and acyl-CoA interconversion rates and to achieve optimal levels for conversion to fatty alcohols. Expressing FAA1 under control of the HXT1 promoter led to an increased accumulation of fatty alcohols per OD600 up to 41% while FFA levels were decreased by 63% compared with the control strain. Fine-tuning and dynamic regulation of key metabolic steps can be used to improve cell factories when the rates of downstream reactions are limiting. This avoids loss of precursors to the extracellular medium or to competing reactions, hereby potentially improving the process yield. The study also provides knowledge of a key point of fatty acid regulation and homeostasis, which can be used for future design of cells factories for fatty acid-derived chemicals.


Eye-hand decoupling decreases visually guided reaching independently of posture but reduces sway while standing: Evidence for supra-postural control.
We investigated whether visually guided reaching differs for sitting and standing postures while the eyes and hand are coupled to move in the same direction or decoupled to move in opposite directions. We also investigated how coupled and decoupled reaching tasks influenced standing postural control. Eighteen healthy young adults (M = 21 years) moved a cursor using finger movements along a vertical touchscreen while sitting or standing. In an eye-hand coupling (EH) task, participants moved their finger/cursor from a central target to a peripheral target located either up, down, left, or right. In an eye-hand decoupling (EHD) task, participant's finger movement moved the cursor in the opposite direction. Sway measures during the standing condition and kinematic variables for the cursor offered insight into whole-body control. Performances in EH revealed smaller errors and faster movements than EHD regardless of postural condition. Similar hand movements existed between sitting and standing when accounting for task, while greater variability in absolute endpoint errors existed for standing than sitting when task was ignored. Less postural sway existed for EHD than EH when standing. These data provide evidence that when participants decoupled the eyes and hand movement direction while standing, they attenuated sway to support control of this complex, cognitively demanding, visuomotor task.


High body mass index is associated with impaired cognitive control.
The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and cognitive deficits concerning mental flexibility and inhibitory control efficiency. The present study aims at replicating and extending these observations. We compared cognitive control performance of normal weight (BMI < 25) and overweight (BMI ≥ 25) university students on a task tapping either inhibitory control (Experiment 1) or interference control (Experiment 2). Experiment 1 replicated previous findings that found less efficient inhibitory control in overweight individuals. Experiment 2 complemented these findings by showing that cognitive control impairments associated with high BMI also extend to the ability to resolve stimulus-induced response conflict and to engage in conflict-driven control adaptation. The present results are consistent with and extend previous literature showing that high BMI in young, otherwise healthy individuals is associated with less efficient cognitive control functioning.


CRISPR/Cas9 RNP-Mediated Gene Fusion to Assess Protein Quantification and Subcellular Localization in Fusarium oxysporum.
F. oxysporum is a notorious filamentous pathogenic fungus that causes serious problems in agriculture and animal/human health. Knowing how the fungus interacts throughout the course of an infection is necessary to propose an effective control strategy, and consequently the manipulation of the F. oxysporum genome is essential to investigate the molecular interplay between the host and fungus. To facilitate assessing protein quantification and subcellular localization, we developed a simple, economical CRISPR/Cas9-mediated endogenous gene tagging (EGT) system based on two different strategies, homology-independent targeted integration (HITI) and homology-dependent recombination integration (HDRI). Reporter genes, including GFP and LacZ, can be inserted at the N- or C-terminus of an endogenous gene of interest at the original chromosomal locus, allowing partial characterization of the gene function.


[The relevance of the sagittal profile in cervical artificial discs].
We report on the results of 246 Bryan cervical discs, which were implanted between June 2002 and September 2010 in 146 patients. Of the patients 74 (128 prostheses) could be followed up for more than 1 year and the average follow-up period was 2.6 years. Of the patients 18 were operated on at one level (group 1), 77 prostheses were multilevel surgery (group 2) and with 33 patients arthroplasty was combined with fusion (hybrid, group 3). The global lordosis remained unchanged during follow-up and a recurrence of kyphosis was evident in group 3. The overall mobility improved in all 3 subgroups and 2 cases (group 3) fused. With 5 patients the prosthesis had to be removed and the segment had to be fused in the postoperative course. As a conclusion a meticulous preoperative planning as well as a subtle surgical technique is the main prerequisite for long-lasting mobility of the Bryan prosthesis.


Within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry.
Three auditory and three visual tests of PA were administered to 45 healthy dextrals in order to evaluate within-modal and cross-modal consistency in the direction and magnitude of perceptual asymmetry (PA). Thirty-three subjects were retested after a 4-8 week interval to determine reliability of individual measures and stability of inter-test relationships. Pairs of visual and auditory tests consisted of exactly the same stimuli. Within-modal and cross-modal concordance in the direction of PA was high, providing additional empirical support for existing models of the neural basis of PA. Cross-modal correlations in the magnitude of PA were near zero despite highly significant within-modal correlations. Meaningfulness of the stimuli did not affect the magnitude of PA, although the presence of an orienting expression prior to each dichotic pair did. These three observations provide new information about the neural processes that determine the magnitude of PA.


Protective effect of ellagic acid on healing alveolar bone after tooth extraction in rat--a histological and immunohistochemical study.
This study has attempted to evaluate the effects of ellagic acid (EA) on alveolar bone healing after tooth extraction in rats. Twenty-four Sprague Dawley (SD) male rats (200-250g) were selected and were anaesthetised for the extraction of upper left incisor. Then, the rats were divided into two groups, comprising 12 rats each; the first group has been considered as a control group and was given only normal saline, whereas, the second group (treated group) was intragastrically administrated with EA daily once, for 28 days. Then three rats from each group had been selected on 7th, 14th, 21st, and 28th days to dissect their maxilla tissue either for histological observation and homogenisation purposes. The tissues fixed, decalcified and embedded in paraffin. Serial sections of 5μm thickness were prepared and stained with haematoxylin and eosin (H&E) for the histological study. Similar sections were taken for immunohistochemical analysis to assess osteocalcin (OSC) and osteopontin (OPN). Furthermore, Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in homogenated gingival maxilla tissue of rat by commercial kit. Based on the histological analysis we have identified that, EA treatment has induced earlier trabecular bone deposition in the treated group, resulting in more organised bone matrix on the 14th, 21st, and 28th days after tooth extraction, as against the control group. In comparison to control group, the positive labelling of OSC and OPN of the treated group have been highly expressed in the alveolar socket on 14th, and 21st days, which has indicated a the possibility of formation of new bone trabeculae at the beginning of the mineralisation process, after tooth extraction. In the EA treatment group, lipid per-oxidation (MDA) was significantly decreased (P<0.05), as opposed to the control group. However, the antioxidant defense enzyme (SOD) was significantly increased in the maxilla tissue treated with EA (P<0.05), compared to control group, which suggests that, after tooth extraction, EA plays an important role in the protection against the induction of lipid per-oxidation, particularly after 28 days of treatment with EA. This study has concluded that, EA may accelerated the healing process in teeth socket of rats. Furthermore, the EA treated group showed a stronger positive immunolabelling for OSC and OPN, when compared with the control group.


Electron-transfer capacity of catechin derivatives and influence on the cell cycle and apoptosis in HT29 cells.
Galloylated and nongalloylated catechin conjugates with cysteine derivatives have been synthesized and evaluated for their capacity to scavenge free radicals and to influence crucial functions (cell cycle, apoptosis) in HT29 colon carcinoma cells. We show that the nonphenolic part of the molecule modified the capacity of catechins to donate hydrogen atoms and to transfer electrons to free radicals. Nongalloylated derivatives did not significantly influence either the cell cycle or apoptosis. Among the galloylated species, 4beta-[S-(O-ethyl-cysteinyl)]epicatechin 3-O-gallate, which showed a high electron-transfer capacity (5 e- per molecule), arrested the cell cycle and induced apoptosis as expected for galloylated catechins such as tea (-)-epigallocatechin 3-O-gallate. 4beta-[S-(N-Acetyl-O-methyl-cysteinyl)]epicatechin 3-O-gallate, which showed the highest hydrogen-donating capacity (10 H per molecule) while keeping the electron-transfer capacity low (2.9 e- per molecule), did not trigger any significant apoptosis. The gallate moiety did not appear to be sufficient for the pro-apoptotic effect of the catechin derivatives in HT29 cells. Instead, a high electron-transfer capacity is more likely to be behind this effect. The use of stable radicals sensitive exclusively to electron transfer may help to design molecules with either preventive scavenging action (high hydrogen donation, low electron transfer) or therapeutic pro-apoptotic activity (high electron transfer).


Role of active and inactive cytotoxic immune response in human immunodeficiency virus dynamics.
Mathematical models can be helpful to understand the complex dynamics of human immunodeficiency virus infection within a host. Most of work has studied the interactions of host responses and virus in the presence of active cytotoxic immune cells, which decay to zero when there is no virus. However, recent research highlights that cytotoxic immune cells can be inactive but never be depleted. We propose a mathematical model to investigate the human immunodeficiency virus dynamics in the presence of both active and inactive cytotoxic immune cells within a host. We explore the impact of the immune responses on the dynamics of human immunodeficiency virus infection under different disease stages. Standard mathematical and numerical analyses are presented for this new model. Specifically, the basic reproduction number is computed and local and global stability analyses are discussed. Our results can give helpful insights when designing more effective drug schedules in the presence of active and inactive immune responses.


Water, Sanitation, and Hygiene (WASH) Factors Influencing the Effectiveness of Mass Drug Administration to Eliminate Trachoma as a Public Health Problem in Malawi.
Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1-9 years following MDA. A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1-9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. Among 16,142 children aged 1-9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p = .034, or more than 1 h away aOR: 0.31, p = .018) compared with water in the yard. The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma.


Development of the VIIIth nerve compound action potential evoked by low-intensity tone pips in the Mongolian gerbil.
Maturation of the cochlea and afferent auditory units is reflected by changes in VIIIth nerve compound action potential (CAP) parameters. We studied auditory nerve CAPs evoked by low-intensity stimuli in Mongolian gerbils (Meriones unguiculatus) ranging in age from 22 to 92 days after birth. The gerbil CAP development is characterized by marked changes in latency, threshold, and amplitude during the first few weeks of life. CAP latency and CAP threshold reach adult-like values at about 1 month of age. In contrast, the CAP amplitude continues to grow in size even after 2 months. This dichotomy suggests that the development of afferent auditory nerve function in the gerbil is preceded by maturation of the mechanical processes of the middle ear and cochlea.


Characterization, toxicity and therapeutic efficacy of adriamycin encapsulated in liposomes.
The inherent toxicities of drug-free liposomes were compared. Positively charged liposomes were more toxic in vitro (chick heart cells) and in vivo (5-fold reduction in LD50 in mice) than neutral or negatively charged liposomes. Based on these findings, adriamycin was encapsulated in negatively charged liposomes (PG: PC: Chol--1:4:5), sequentially extruded through polycarbonate membranes (to 0.2 micrometer pore size) and purified by exhaustive dialysis. This preparation had a mean vesicle diameter of 0.24 micrometer and was stable in serum (24 hr drug retention of 85%). As compared with free drug, liposome-encapsulated adriamycin was less toxic in vitro to chick heart cells. In mice, adriamycin displayed short- (4-14 day) and long- (45-70 day) term toxicity. Encapsulating adriamycin increased both short- (20-50 mg/kg) and long- (10-15 mg/kg to 25-30 mg/kg) term LD50 levels. As compared with free drug, administering encapsulated adriamycin in vivo reduced the incidence of cardiac histopathologic lesions at 20 and 40 mg/kg. Compared in vivo, plasma levels of liposome-encapsulated adriamycin were 2/3-fold higher than free drug up to 24 hr post drug administration. Cardiac uptake of adriamycin was reduced 2-fold (conc x time value for 48 h) following encapsulated drug administration. Encapsulating adriamycin in liposomes did not alter its therapeutic effect against L1210 leukemic cells in vivo.


[New view points on the pathogenesis and treatment of strabismus. 2nd part: Management of strabismus (author's transl)].
A new method of surgical treatment of strabismus is presented. The desagittalisation of the oblique muscles is the main part of surgery; it is associated to surgery of the horizontal recti muscles and sometimes to surgery of the vertical recti muscles. The surgical procedures are described; the indications are set up for the primary surgery as well as for the secondary surgery which aims at the treatment of under and over corrections.


New Insights in the Genetics and Genomics of Adrenocortical Tumors and Pheochromocytomas.
This article collection includes 16 scientific papers that present the current state of the art of genetics and genomics research in the fascinating field of adrenal tumors [...].


Functional characterization of bovine von Willebrand factor gene promoter in bovine endothelial cells demonstrates species-specific properties.
Von Willebrand factor (vWF), a protein necessary for platelet adhesion and thrombus formation, is specifically synthesized in endothelial cells and in platelet precursors (megakaryocytes). We previously demonstrated that the sequences localized either in the 5'-flanking region or in the first exon of human (hu) vWF gene (vWF), which regulate the cell-specific transcription, are not conserved in the bovine counterpart. In order to look for cis-acting elements involved in the endothelial expression of bovine (bo) vWF, fragments including 113 base pairs (bp) of a sequence 5'-flanking the transcription start point (tsp, +1) and various deletions of the first 233 bp exon were linked in plasmids to the bacterial chloramphenicol (Cm) acetyltransferase gene (cat). These constructs were analyzed by transient transfection in calf pulmonary artery endothelial (CPAE), human epithelial (HeLa) from cervix and green monkey fibroblasts from kidney (COS) cells. The longest fragment, containing 229 bp of the first exon, was the most active, with identical cat expression in the three cell types. The CAT activity was equivalent to that measured by transfection of the same cells with the basal promoter (from bp -89 to +19) of hu vWF. Addition of upstream bo vWF sequences from bp -113 to -1362 resulted in progressive reduction of the activity of the -113/+229 fragment. The upstream negative regulatory domains between -1362 and -278 also repressed the heterologous thymidine kinase (tk) promoter in CPAE and HeLa cells. Comparison of results with those previously obtained by transfection of hu vWF promoter in bovine endothelial cells demonstrates that the cis-acting elements do not behave identically in bo vWF promoter. In particular, positive tissue-specific elements able to overcome the negative regulation in endothelial cells could not be found in bo vWF between bp -1362 and +229.


Menopause and diabetes: EMAS clinical guide.
Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. Literature review and consensus of experts' opinions. Metabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17β-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient's specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.


Family history of asthma influences outpatient respiratory outcomes in children with BPD.
Preterm children with bronchopulmonary dysplasia (BPD) are at increased risk for intermittent and chronic respiratory symptoms during childhood and adult life. Identifying children at higher risk for respiratory morbidities in the outpatient setting could help improve long-term outcomes. In this study, we hypothesized that a family history of asthma (FHA) is a risk factor for higher acute care usage and respiratory symptoms in preterm infants/children with BPD, following initial discharge home. Subjects were recruited from the Johns Hopkins Bronchopulmonary Dysplasia outpatient clinic between January 2008 and February 2020 (n = 827). Surveys were administered to caregivers and demographics and clinical characteristics were obtained through chart review. Demographic features associated with FHA included public health insurance, lower median household income, and nonwhite race. Children with FHA had higher odds of emergency department (ED) visits, systemic steroid use, nighttime respiratory symptoms, and activity limitations. There was no association between FHA and BPD severity. This study found that children with BPD and FHA were more likely to have respiratory symptoms and acute care usage during the first 3 years of life and that FHA was associated with lower socioeconomic status. Although there was no association between FHA and BPD severity, FHA could predict an increased likelihood of both ED visits and need for systemic steroids in infants/children with BPD followed in the outpatient setting.


The clinical characteristics of pancreatic colloid carcinoma and the development and validation of its cancer-specific survival prediction nomogram.
Pancreatic colloid carcinoma (CC) is a subtype of pancreatic ductal adenocarcinoma (DAC) with low incidence but high malignancy. Unfortunately, there is no consensus regarding the clinical features and prognostic factors associated with CC, and the prognosis is unpredictable. We aimed to assess the clinicopathological characteristics of this rare disease and develop a nomogram for predicting cancer-specific survival (CSS) in CC. We gathered comprehensive clinicopathological data from the Surveillance, Epidemiology, and End Results (SEER) database on 17,617 patients with DAC and 561 individuals with CC. Kaplan-Meier was used to plot each survival curve. Subsequently, we split the 561 patients with CC in a 7:3 split ratio between an internal training cohort (n=393) and an external validation cohort (n=168). The independent prognostic factors for CC patients in the training cohort were discovered using univariate and multivariate Cox regression analyses, and a nomogram was created. We assessed the nomogram's performance by using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). The median for follow-up of CC patients was 15 months (range: 1-163 months), and the 1-, 3-, and 5-year CSS were 58.4%, 30.2% and 22.6%. For CC patients in the training cohort, age [hazard ratio (HR) =1.29; 95% confidence interval (CI): 1.00-1.65], sex (HR =0.64; 95% CI: 0.51-0.81), T3 stage (HR =2.21; 95% CI: 1.26-3.88), T4 stage (HR =2.76; 95% CI: 1.47-5.18), N1 stage (HR =1.29; 95% CI: 1.02-1.63), M1 stage (HR =1.60; 95% CI: 1.17-2.18), surgery (HR =0.30; 95% CI: 0.22-0.42), and radiotherapy (HR =0.76; 95% CI: 0.58-1.01) were the main predictors of the nomogram. The C-indexes of the training cohort and the validation cohort were 0.734 and 0.732, respectively. The 1-, 3-, and 5-year AUC values of the nomogram were predicted to be 0.827, 0.816, and 0.831 in the training cohort, 0.801, 0.841, and 0.835 in the validation cohort, respectively. Based on several clinical features, we established the first predictive model of CC. This nomogram could be used to guide treatment decisions in patients with CC.


Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.
An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.


Safflower (Carthamus tinctorius) Biochemical Properties, Yield, and Oil Content Affected by 24-Epibrassinosteroid and Genotype under Drought Stress.
The steroid hormones, including brassinosteroids, regulate plant growth under stress. It is hypothesized that 24-epibrassinosteroids (24-EBR) can affect safflower (Carthamus tinctorius) biochemical properties, crop yield, and oil content under drought stress. The objective of our study was to determine the response of three safflower genotypes (Goldasht, Faraman, and Sina) to exogenous 24-EBR (0 and 10-7 M) under drought stress, including 85, 65, and 45% of field capacity in 2015. Stress decreased chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, relative water content (RWC), seed yield, and oil percentage. The activities of superoxide dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO), and proline contents increased in response to either drought stress or 24-EBR. Genotypes behaved significantly different under stress. 24-EBR significantly increased plant chlorophyll contents and oil percentage, and it significantly reduced the malondialdehyde (MDA) content via increasing the proline and carotenoid contents under stress. 24-EBR can increase safflower oil and seed yield under drought stress.


The effect of clenbuterol on lung function parameters in calves suffering from bronchopneumonia.
Pulmonary function testing was performed in calves affected with bronchopneumonia. In these calves respiratory rate, viscous work per litre air and per minute, intrapleural pressure difference, mean inspiratory and expiratory flow rate and ventilation per minute were significantly increased. Total resistance of the lung was just not significantly increased. Dynamic compliance and tidal volume were significantly reduced. The main effect of clenbuterol was a significant increase in dynamic compliance. The reduction in the total resistance of the lung was just not significant. These results indicate that clenbuterol can antagonise, at least partly, the alterations caused by bronchopneumonia.


The effects of TETs on DNA methylation and hydroxymethylation of mouse oocytes after vitrification and warming.
Oocyte vitrification has extensively been applied in the field of embryo engineering and in the preservation of genetic resources of fine livestock. Following our previous work in oocyte vitrification and the level change of DNA methylation, here we further explored the dynamic change of three active demethylation proteins: Ten-Eleven-Translocation 1/2/3(TET1/2/3), 5-methylcytosine (5 mC) and 5-hydroxymethycytosine (5hmC) after vitrification and warming. In order to observe the active demethylation in vitrified oocytes, two small molecular regulators, i.e. Vitamin C (VC) and dimethyloxaloylglycine (DMOG) were used to adjust activity and level of the TET 3 protein. The results showed that the levels of 5 mC and 5hmC were significantly decreased after 2 h of vitrification (P < 0.01). Moreover, the level of TET3 protein was significantly increased after 2 h warming (P < 0.01). And the relative gene expression of TET2/3 did not change in the first 2 h, but significantly increased after 2 h (P < 0.01). When VC was added to vitrification and recovery medium, it could not significantly improve the level of TET3 gene expression, and affect 5 mC and 5hmC expression (P > 0.05). When the DMOG was added to the solutions of vitrification, the level of 5hmC showed significantly increase (P < 0.01). In conclusion, the oocyte vitrification procedure reduced DNA methylation and hydroxymethylation in MII oocytes, but adding VC and DMOG to vitrification medium can prevent the reduction of DNA hydroxymethylation by increasing activity of TET3 methylation protein after vitrification and warming.


Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.
Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.


Experience with polymicrobial sepsis in a regional burn unit.
A 2-year review of 795 patients admitted to a regional burn unit was carried out to determine the incidence of polymicrobial sepsis. Of 38 bacteraemic patients, 21 (55 per cent) had polymicrobial sepsis in 1990. Of 38 cases in 1991, 12 patients (31.6 per cent) had polymicrobic infections. Of 36 deaths in 1990, 13 were attributed to sepsis, 12 of 29 (31.6 per cent) in 1991. Of the patients who died in 1990, eight (21 per cent) were polymicrobic septic deaths and six (15.8 per cent) in 1991. The problem has been reported in immunocompromised patients, especially those with terminal malignancies, but has rarely been noted in burn patients. Recognition of the seriousness of the problem and the aggressive antibiotic therapy appropriate to the organisms in question is advised.


[An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study].
Our aim was to investigate: a) the average cost per patient with osteoarthritis treated with chondroitin sulfate compared with NSAIDs for 6 months and b) the possible impact that the reduction NSAID use due to monotherapy with or combined administration of chondroitin sulfate treatment may have on the budget of the Spanish National Health System. A cost-minimization model compared both treatments (efficacy equivalence assumption), used at the recommended doses and regimens during a 6-month period. Data used in the model was obtained from the VECTRA study, a retrospective study of 530 patients with osteoarthritis treated with chondroitin sulfate or NSAIDs that was conducted to determine the consumption of health care resources. The efficacy and incidence of adverse events was estimated from meta-analysis based on randomized clinical trials. Univariate sensitivity analysis was performed for the base case scenario. The overall 6-month cost per patient given chondroitin sulfate was 141 € compared with 182 € when treated with NSAIDs. If during the forthcoming 3 years, 5%, 10%, and 15% of patients currently treated with NSAIDs would gradually be replaced by treatment with chondroitin sulfate, the expected savings for the Spanish National Health System during these 3 years would be over 38,700,000 €. In addition, 2,666 cases of gastrointestinal adverse events (including 90 serious adverse events) will have been avoided for every 10,000 patients treated with chondroitin sulfate instead of NSAID. Sensitivity analysis confirmed the strength of base-case in all scenarios. On the basis of these findings, chondroitin sulfate is a treatment for osteoarthritis with a lesser cost and better gastrointestinal tolerability compared with NSAIDs.


A review of tumours of the deep lobe of the parotid salivary gland.
Tumours of the deep lobe of the parotid gland may present as a swelling in the oropharynx. They are uncommon when compared with those of the superficial lobe, are frequently misdiagnosed and subjected to per-oral biopsy which is hazardous and predisposes to seeding of the tumour. Investigation and diagnosis are discussed with particular reference to the role of computed tomography. The surgical approach to these inaccessible tumours is illustrated by reference to patients treated. Modifications to the technique of Cooke and Ranger (1969) for excision of parapharyngeal tumours are suggested, which are applicable to tumours of the deep lobe extending medial to the mandible and presenting in the side wall of the pharynx.


Evaluation of hemodynamics and hepatic mitochondrial function on extrahepatic portal obstruction in the rat.
An animal model resembling clinical cases with extrahepatic portal vein obstruction was developed. The changes in hepatic mitochondrial function and the hepatic hemodynamics including hepatic regional blood flow, portal venous pressure, and portogram were evaluated to assess the effect of portal vein obstruction in the model. Portal vein ligation in this model was a simple and easy maneuver and could produce collateral veins to the liver--cavernomatous transformation--which were obviously seen in clinical patients with extrahepatic portal obstruction. Hepatic blood flow was significantly decreased until 5 days after portal vein ligation; however, hepatic blood flow was gradually increased and reached the normal value at 3 weeks after portal vein ligation due to the formation of the collateral veins to the liver. Respiratory parameters of mitochondria were gradually decreased and reached the lowest levels at 5 days after portal vein ligation, while they recovered to normal values in accordance with increasing hepatic blood flow at 3 weeks after portal vein ligation. In extrahepatic portal obstruction, although the liver is temporarily deteriorated by portal vein obstruction such as portal vein thrombosis, hepatic blood flow and the liver functions are to be normally improved with the formation of collateral veins to the liver.


Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial).
Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.


Effect of age on the activity of rat testicular arginine-aminopeptidase.
Effects of age on arginine-aminopeptidase activity were investigated in the rat testis. A marked rise of the enzyme activity in 6-week-old rats corresponded to the appearance of spermatids in the later stages of their development.


Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity.
Signaling microclusters are a common feature of lymphocyte activation. However, the mechanisms controlling the size and organization of these discrete structures are poorly understood. The Ezrin-Radixin-Moesin (ERM) proteins, which link plasma membrane proteins with the actin cytoskeleton and regulate the steady-state diffusion dynamics of the B cell receptor (BCR), are transiently dephosphorylated upon antigen receptor stimulation. In this study, we show that the ERM proteins ezrin and moesin influence the organization and integrity of BCR microclusters. BCR-driven inactivation of ERM proteins is accompanied by a temporary increase in BCR diffusion, followed by BCR immobilization. Disruption of ERM protein function using dominant-negative or constitutively active ezrin constructs or knockdown of ezrin and moesin expression quantitatively and qualitatively alters BCR microcluster formation, antigen aggregation, and downstream BCR signal transduction. Chemical inhibition of actin polymerization also altered the structure and integrity of BCR microclusters. Together, these findings highlight a crucial role for the cortical actin cytoskeleton during B cell spreading and microcluster formation and function.


Preferred viewing distance of liquid crystal high-definition television.
This study explored the effect of TV size, illumination, and viewing angle on preferred viewing distance in high-definition liquid crystal display televisions (HDTV). Results showed that the mean preferred viewing distance was 2856 mm. TV size and illumination significantly affected preferred viewing distance. The larger the screen size, the greater the preferred viewing distance, at around 3-4 times the width of the screen (W). The greater the illumination, the greater the preferred viewing distance. Viewing angle also correlated significantly with preferred viewing distance. The more deflected from direct frontal view, the shorter the preferred viewing distance seemed to be.


The moderating role of spirituality and gender in Canadian and Iranian emerging adolescents' theory of mind and prosocial behavior.
While research has found a link between ToM and prosociality in terms of caring and helping others which may also vary across cultures, the moderating role of spirituality and culture of this association in emerging adolescence has received little attention. The current study empirically "examined" the role of spirituality and gender in relation to ToM and prosocial behavior in Canadian and Iranian emerging adolescents. A total of 300 (153 girls) emerging adolescents (M = 11.502, SD = 2.228) were recruited from Montreal, Canada and Karaj, Iran. A series of double moderation analysis and ANOVA was conducted. Results indicated the difference between direct and indirect influences of ToM and its interactions with culture, gender, and spirituality on prosocial behavior. This implies an emerging complex framework which suggests the dynamic nonlinear interactions between these factors. Implications for youth's social-emotional understanding will be discussed.


Epidemiology of cancer among Hispanic males. The experience in Florida.
To assess cancer incidence among Hispanic males in Dade County, Florida, data were analyzed from the statewide tumor registry. For all cancer sites (combined), the age standardized rate among Hispanic males was 308.75 cases per 100,000 person-years, compared with 349.55 among non-Hispanics (standardized rate ratio [SRR] = 0.88; 95% confidence interval [CI] = 0.84-0.93). Hispanics experienced significantly greater rates of cancers of the larynx (SRR = 1.58; 1.19-2.09), thyroid (SRR = 3.12; 1.18-8.26), and gallbladder (SRR = 5.45; 1.55-19.15), compared with non-Hispanics, but significantly lower rates of testicular cancer (SRR = 0.17; 0.09-0.37), melanoma (SRR = 0.20; 0.12-0.34), esophagus (SRR = 0.52; 0.49-0.55), stomach (SRR = 0.61; 0.43-0.87), pancreas (SRR = 0.65; 0.45-0.94), kidney and renal pelvis (SRR = 0.68; 0.48-0.97), colon (SRR = 0.79; 0.67-0.94), lung (SRR = 0.82; 0.73-0.94), and Kaposi's sarcoma (SRR = 0.03; 0.00-0.25). These data suggest that Dade Hispanic males have not experienced the cancers traditionally elevated among US Latinos, or those common among non-Hispanics.


Ultrasonic-Assisted Extraction of Flavonoids from Juglans mandshurica Maxim.: Artificial Intelligence-Based Optimization, Kinetics Estimation, and Antioxidant Potential.
Ultrasonic-assisted extraction (UAE) of flavonoids (JMBF) from Juglans mandshurica Maxim., an important industrial crop in China, was investigated in the present study. To improve the extraction efficiency of JMBF, suitable UAE was proposed after optimization using a hybrid response surface methodology-artificial neural network-genetic algorithm approach (RSM-ANN-GA). The maximum extraction yield (6.28 mg·g-1) of JMBF was achieved using the following optimum UAE conditions: ethanol concentration, 62%; solid-liquid ratio, 1:20 g·mL-1; ultrasonic power, 228 W; extraction temperature, 60 °C; extraction time, 40 min; total number of extractions, 1. Through the investigation of extraction kinetics, UAE offered a higher saturated concentration (Cs) for JMBF in comparison to traditional solvent extraction (TSE). Scanning electron microscopy (SEM) images showed that deeper holes were generated in J. mandshurica powder under the action of ultrasound, indicating that ultrasound significantly changed the structure of the plant materials to facilitate the dissolution of active substances. Extracts obtained using UAE and TSE were compared by Fourier-transform infrared spectroscopy analysis, the results of which revealed that the functional group of bioactive compounds in the extract was unaffected by the ultrasonication process. Moreover, JMBF was further shown to exhibit significant antioxidant properties in vitro. This study provides a basis for the application of JMBF as a natural antioxidant.


Phospholipase A2 and antioxidant enzyme activities in normal and PSE pork.
In order to reveal the relationship between phospholipase A(2) and antioxidant enzymes and drip loss in pork, the study was designed to examine the effects of phospholipase A(2) and antioxidant enzymes on the water-holding capacity of pork during postmortem chilling. Six PSE and RFN samples (longissimus muscle) were used to determine the activities of phospholipase A(2) (tPLA(2,) cPLA(2)+sPLA(2) and iPLA(2)), superoxide dismutase (SOD) and GSH-Px, and acid phospholipase. The results showed that pH(1 h) and pH(24 h) from PSE pork were lower (p<0.01) than for normal pork (RFN), but the L* value at 1h and 24h postmortem, TBARS content, drip loss at 48 h and 96 h, cooking loss, tPLA(2) activity and iPLA(2) were higher (p<0.01) than of normal pork. Correlation analysis indicated that drip loss at 48 h was negatively related to pH(1 h) (p<0.01) and pH(24 h) (p<0.01) but positively to T(1 h) (p<0.01) and the activities of total phospholipase A(2) (p<0.05) and calcium-independent phospholipases A(2) (p<0.01). The tPLA(2) and GSH-Px play important roles in drip loss.


Disulfiram causes sustained behavioral and biochemical effects in rats.
The present experiment examined effects of disulfiram (Antabuse) administration on behavioral measures of nociception (hot plate and tail flick), peripheral muscular performance (grip strength), motivated performance, balance, and coordination (rotorod) in 24 male Sprague-Dawley rats during and 2 wk after an eight-day administration of disulfiram. In addition, peptidylglycine 5(-hydroxylating monooxygenase (PHM) activity in several tissues and levels of alpha-amidated alpha-melanocyte stimulating hormone (alpha-MSH) in the neurointermediate lobe of the pituitary were assayed to evaluate biochemical effects of disulfiram. These particular assays were included because it has been reported that disulfiram affects alpha-amidated peptides via alteration of PHM activity. Decrements in all behavioral measures, except tail flick, occurred after one week of disulfiram administration. Decrements in grip strength continued for the 2 wk after cessation of disulfiram. Dose-related reductions in changes in PHM activity and levels of alpha-MSH were found 2 wk after cessation of disulfiram administration. The time course of the results suggest that changes in PHM activity may underlie decrements in grip strength. The present experiment provides a paradigm for further investigations of effects of alpha-amidated peptides on behavior.


[French validation of the Multiple Sclerosis International Quality of Life Questionnaire].
Health-related quality of life (HRQL) measurements have become an important outcome both for population health assessment and for evaluating treatments and care management. HRQL indicators require completion of a well-validated questionnaire. Few specific questionnaires are available for French multiple sclerosis (MS) patients. The Multiple Sclerosis International Quality of Life questionnaire (MusiQoL), a self-administered and multidimensional questionnaire, was co-developed and validated in 17 countries, including France. We report the main results of the French clinical validity of this instrument. The French patients were recruited between January 2004 and February 2005. The main inclusion criteria were: diagnosis of MS according to McDonald criteria, age over 18 years, having given informed consent. The self-administered survey materials that were completed by the patients included the MusiQoL, the generic HRQL questionnaire SF36, and one checklist of 14 MS-specific symptoms reported by the patients. MusiQoL comprises 31 items describing nine dimensions: activity of daily living (eight items), psychological well-being (four), symptoms (three), friends relationships (four), family relationships (three), satisfaction with health care (three), sentimental and sexual life (two), coping (two), and rejection (two). A global index score is computed. Patients were evaluated at inclusion (T0), and retested 21±7 days later (T1). At T0, an experienced neurologist collected sociodemographic data, clinical history related or unrelated to the MS condition, treatments. At T1, change in the patient's health status from T0 was reported. The analyses were performed with data from 179 subjects. The mean patient age was 44.1 years (SD: 11.5); there were 120 women and 59 men, 58.1% were unemployed, 13.6% had a tertiary educational level. MS clinical forms were 69 relapsing-remitting, 47 secondary-progressive, 37 primary-progressive, and nine clinically isolated syndrome. The EDSS median was 4.5 (25-75(th) percentiles: 2.5-6.0). The final French version showed satisfactory psychometric properties (external validity, internal consistency, reliability, reproducibility, and acceptability). The availability of a reliable and valid French version of MusiQoL, a self-administered and multidimensional questionnaire, co-developed in different countries, enables evaluation of QoL in French MS patients that are eligible for international multicenter studies.


Identification and Validation of MicroRNA Profiles in Fecal Samples for Detection of Colorectal Cancer.
Screening for colorectal cancer (CRC) is effective in the population at average risk. The most extended strategy in organized programs involves the fecal immunochemical test, which is limited by low sensitivity for the detection of advanced adenomas (AAs). We aimed to identify microRNA (miRNA) signatures in fecal samples that identify patients with AAs or CRC and might be used in noninvasive screening. Our study comprised 4 stages. In the discovery phase, we performed genome-wide miRNA expression profiling of 124 fresh, paired colorectal tumor and nontumor samples (30 CRC; 32 AAs) from patients in Spain. In the technical validation stage, miRNAs with altered expression levels in tumor vs nontumor tissues were quantified by reverse-transcription polymerase chain reaction in fecal samples from a subset of patients included in the discovery phase (n = 39) and individuals without colorectal neoplasms (controls, n = 39). In the clinical validation stage, the miRNAs found to be most significantly up-regulated by quantitative reverse transcription polymerase chain reaction analysis were measured in an independent set of fecal samples (n = 767) from patients with positive results from fecal immunochemical tests in a CRC screening program. Finally, we developed a model to identify patients with advanced neoplasms (CRCs or AAs) based on their miRNA profiles, using findings from colonoscopy as the reference standard. Among 200 and 324 miRNAs significantly deregulated in CRC and AA tissues, respectively, 7 and 5 of these miRNAs were also found to be deregulated in feces (technical validation). Of them, MIR421, MIR130b-3p, and MIR27a-3p were confirmed to be upregulated in fecal samples from patients with advanced neoplasms. In our model, the combination of fecal level of MIR421, MIR27a-3p, and hemoglobin identified patients with CRC with an area under the curve (AUC) of 0.93, compared with an AUC of 0.67 for fecal hemoglobin concentration alone. We found that increased levels of 2 miRNAs and hemoglobin in feces can identify patients with AAs or CRC more accurately than fecal hemoglobin concentration alone. Assays for these miRNAs might be added to fecal tests for the detection of CRC or AAs.


Genome Sequence of Australian Indigenous Wine Yeast Torulaspora delbrueckii COFT1 Using Nanopore Sequencing.
Here, we report the first sequenced genome of an indigenous Australian wine isolate of Torulaspora delbrueckii using the Oxford Nanopore MinION and Illumina HiSeq sequencing platforms. The genome size is 9.4 Mb and contains 4,831 genes.


Influence of apolipoprotein E genotype on cerebral amyloid angiopathy in the elderly.
The inheritance of the epsilon 4 allele of the apolipoprotein E gene (APOE) is associated with increased risk of developing dementia of the Alzheimer type (DAT). We have investigated whether the APOE genotype influences the severity of cerebral amyloid angiopathy (CAA) in elderly individuals with or without DAT. From a consecutive autopsy series, we studied 88 patients (85.2 +/- 8.1 years) without degenerative disorders other than DAT. The percentages of amyloid-laden vessels in the occipital lobes were calculated and compared between APOE genotypes. For epsilon 3/3 and epsilon 3/4 genotypes, there was a trend toward increased CAA in epsilon 3/4 individuals for non-DAT and conversely in epsilon 3/3 individuals for DAT patients, but these did not achieve significance. The present study suggests that the epsilon 4 allele is not a strong risk factor for CAA in elderly people.


Oocyte ultrastructure in bovine primordial to early tertiary follicles.
The aim of the present study was to describe in detail the changes occurring in the cytoplasmic ultrastructure of the bovine oocyte from the onset of growth in the primordial follicle until the completion of growth in the tertiary follicle. Bovine oocytes from primordial, primary, secondary and early to mid-antral follicles were processed and analysed by light and transmission electron microscopy. The primordial follicular oocyte was characterized by numerous coated pits on the oolemma and the accumulation of free and organelle-related smooth (SER) and rough (RER) endoplasmic reticulum, round mitochondria and Golgi complexes around the nucleus, which was located slightly off centre. Up to the secondary follicular stage the oocyte displayed an increase in the number of microvilli, elongated mitochondria and Golgi complexes. During the secondary follicular stage, formation of the zona pellucida, development of gap junctions between the oocyte and the granulosa cells, formation of the cortical granules in the oocyte and reduction in the number of coated pits on the oolemma were seen. In the tertiary follicular oocyte up to 100 microm in diameter, the number of Golgi complexes and lipid droplets increased and the organelles were dislocated to the deep cortical region. During the final growth of the oocyte up to >120 microm, the organelles were dislocated further to the peripheral region, the extent of the free SER and RER compartments were reduced, the number of individual cortical granules increased, hooded mitochondria became abundant and the perivitelline space developed. In conclusion, the growth of the bovine oocyte is associated with the relocation and modulation of a number of cytoplasmic organelles as well as the development of oocyte specific structures such as the zona pellucida and cortical granules.


Detection of early cartilage degeneration in the tibiotalar joint using 3 T gagCEST imaging: a feasibility study.
To establish and optimize a stable 3 Tesla (T) glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging protocol for assessing the articular cartilage of the tibiotalar joint in healthy volunteers and patients after a sustained injury to the ankle. Using Bloch-McConnell simulations, we optimized the sequence protocol for a 3 T MRI scanner for maximum gagCEST effect size within a clinically feasible time frame of less than 07:30 min. This protocol was then used to analyze the gagCEST effect of the articular cartilage of the tibiotalar joint of 17 healthy volunteers and five patients with osteochondral lesions of the talus following ankle trauma. Reproducibility was tested with the intraclass correlation coefficient. The mean magnetization transfer ratio asymmetry (MTRasym), i.e., the gagCEST effect size, was significantly lower in patients than in healthy volunteers (0.34 ± 1.9% vs. 1.49 ± 0.11%; p < 0.001 [linear mixed model]). Intra- and inter-rater reproducibility was excellent with an average measure intraclass correlation coefficient (ICC) of 0.97 and a single measure ICC of 0.91 (p < 0.01). In this feasibility study, pre-morphological tibiotalar joint cartilage damage was quantitatively assessable on the basis of the optimized 3 T gagCEST imaging protocol that allowed stable quantification gagCEST effect sizes across a wide range of health and disease in clinically feasible acquisition times.


Child maltreatment rates assessed in a national household survey of caregivers and youth.
This paper reports on national estimates for past year child maltreatment from a national household survey conducted in 2011. It also discusses the validity of such estimates in light of other available epidemiology. The Second National Survey of Children Exposed to Violence obtained rates based on 4,503 children and youth from interviews with caregivers about the children ages 0-9 and with the youth themselves for ages 10-17. The past year rates for physical abuse by caregivers were 4.0% for all sample children, emotional abuse by caregivers 5.6%, sexual abuse by caregivers 0.1%, sexual abuse by caregivers and non-caregivers 2.2%, neglect 4.7% and custodial interference 1.2%. Overall, 12.1% of the sample experienced at least one of these forms of maltreatment. Twenty-three percent of the maltreated children or 2.8% of the full sample experienced 2 or more forms of maltreatment. Some authority (teacher, police, medical personnel or counselor) was aware of considerable portions of most maltreatment, which suggests the potential for intervention. Many of the study's estimates were reasonable in light of other child maltreatment epidemiological studies, but comparisons about emotional abuse and neglect were problematic because of ambiguity about definitions.


Community care coordination for stroke survivors: results of a complex intervention study.
Outpatient follow-up care for stroke survivors is often inadequate and mostly self-organized by the patients themselves. In the German health care system, there are no standard care programs for patients after they are discharged from the hospital to support them with their multifaceted and heterogeneous health care needs. The objective of this complex intervention study was to evaluate the effectiveness of a post-stroke care coordination program in comparison to standard care in the first year after a stroke. Patients aged 55 and older who had survived a stroke or a transient ischemic attack (TIA) within the last 6 months before enrollment were included. Participants received care coordination either by telephone or face-to-face for up to 1 year. Patients' health insurance claims data were used to measure outcomes. The control group consisted of stroke survivors receiving standard care and was constructed by exact matching based on six criteria. Outcome measures were health services utilization, rate of recurrent events, readmissions and accompanying costs, and mortality. Outcomes were tested using different multiple models. In total, N = 361 patients were included in the analyses. Intervention participants had seen an outpatient neurologist more often (OR = 4.75; 95% CI: 2.71-8.31) and were readmitted to a hospital less frequently (IRR = 0.42; 95% CI: 0.29-0.61), resulting in lower hospital costs (IQR = €0-1910 in the intervention group, IQR = €0-4375 in the control group). There were no substantial group differences in the rate of recurrent events and mortality. This study showed the beneficial potential of care coordination for a vulnerable patient population: the utilization rate of important health services was increased, and the rate of hospital readmissions decreased as a result. Future research should focus on the risk of recurrent strokes and the long-term effects of improved care. DRKS00017526 on DRKS - German Clinical Trials Register (retrospectively registered: 21 June 2019).


Virtual Interviews Improve Equity and Wellbeing: Results of a Survey of Applicants to Obstetrics and Gynecology Subspecialty Fellowships.
Nationwide restrictions and recommendations from the Association of American Medical Colleges mandated program directors to conduct all graduate medical education interviews virtually in the Spring of 2020 in response to the COVID-19 pandemic. This study was conducted to assess the impact of virtual interviews on a candidates' ability to effectively create a rank list. The primary objective of this study was to evaluate Obstetrics and Gynecology (ObGyn) subspecialty fellowship applicants' perspectives regarding the effectiveness of virtual interviews for creating a rank list. Secondary outcomes included perceived advantages and disadvantages of the process and costs of the process. This was a cross-sectional IRB-exempt study, using an electronic survey administered to a convenience sample of applicants to ObGyn subspecialty fellowship programs. The survey was administered via RedCap between the rank list submission deadline and the Match. Descriptive statistics were used. Response rate was 158/330 (48%). Overall, 129/158 (82%) percent of respondents felt confident in making their rank list based on the virtual interviews, and 146/158 (92%) were "very satisfied" or "somewhat satisfied" with the process. Of those who expressed an interview style preference, 65/149(44%) of respondents preferred virtual interviews; 49/149(33%) had no preference or were not sure. Nearly all 146/148(99%) applicants cited cost-savings as a distinct advantage of virtual interviews. Applicants to ObGyn subspecialty fellowships felt comfortable to create a rank list based on the virtual interview. This study indicates that the virtual format is effective, less stressful and less costly for ObGyn subspecialty interviews and should be considered beyond the pandemic to remove barriers and burdens for applicants.


Human Curvularia infections. Report of five cases and review of the literature.
Curvularia lunata is a saprobic dematiaceous mould that resides primarily in soil (Ellis, 1966). Reports of human disease caused by this organism are rare but include: endocarditis, brain abscess, skin infections, onychomycosis, keratitis, pneumonia, disseminated disease, mycetoma, allergic bronchopulmonary disease, and one case of sinusitis. Since 1983, we have encountered five cases of paranasal sinusitis due to C. lunata. None of the patients suffered from known immunologic disorders or underlying debilitating diseases. These five cases are presented and the literature of human phaeohyphomycosis caused by Curvularia spp. is reviewed.


Ultrasonic-assisted stewing enhances the aroma intensity of chicken broth: A perspective of the aroma-binding behavior of fat.
This experiment investigated the underlying mechanism of ultrasonic-assisted stewing to enhance the aroma intensity of chicken broth by measuring fat content, oil droplet sizes, zeta potential, viscosity, surface protein loading, lipid oxidation, and aroma compound concentrations. As the thermo-ultrasound time increased, the fat content increased from 0.3 % to 1.2 %, resulting in a milky white appearance. After 1 h of thermo-ultrasound, the broth had the smallest particle size and the highest surface protein load, viscosity, and emulsion stability, as well as the highest total amount of aroma-active compounds of 314.70 ng/mg. With the further extension of thermo-ultrasound time, lipid oxidation increased, but the stability of chicken broth decreased, lowering the content of aroma-active compounds. These outcomes suggested that thermo-ultrasound could enhance the aroma intensity of chicken broth by increasing the fat content and the emulsion stability of the broth.


Ploidy mosaicism in well-developed nuclear transplants produced by transfer of adult somatic cell nuclei to nonenucleated eggs of medaka (Oryzias latipes).
Chromosomal abnormalities such as ploidy mosaicism have constituted a major obstacle to the successful nuclear transfer of adult somatic cell nuclei in lower vertebrates to date. Euploid mosaicism has been reported previously in well-developed amphibian transplants. Here, we investigated ploidy mosaicisms in well-developed transplants of adult somatic cell nuclei in medaka fish (Oryzias latipes). Donor nuclei from primary cultured cells from the adult caudal fin of a transgenic strain carrying the green fluorescent protein gene (GFP) were transferred to recipient nonenucleated eggs of a wild-type strain to produce 662 transplants. While some of the transplants developed beyond the body formation stage and several hatched, all exhibited varying degrees of abnormal morphology, limited growth and subsequent death. Twenty-one transplants, 19 embryos and two larvae, were selected for chromosomal analysis; all were well-developed 6-day-old or later embryonic stages exhibiting slight morphological abnormalities and the same pattern of GFP expression as that of the donor strain. In addition, all exhibited various levels of euploid mosaicism with haploid-diploid, haploid-triploid or haploid-diploid-triploid chromosome sets. No visible chromosomal abnormalities were observed. Thus, euploid mosaicism similar to that observed in amphibians was confirmed in well-developed nuclear transplants of fish.


Comparison of Early Morbidity and Mortality Between Sleeve Gastrectomy and Gastric Bypass in High-Risk Patients for Liver Disease: Analysis of American College of Surgeons National Surgical Quality Improvement Program.
Chronic liver disease is prevalent in obese patients presenting for bariatric surgery and is associated with increased postoperative morbidity and mortality (M&M). There are no comparative studies on the safety of different types of bariatric operations in this subset of patients. The aim of this study is to compare the 30-day postoperative M&M between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-Y-gastric bypass (LRYGB) in the subset of patients with a model of end-stage liver disease (MELD) score ≥ 8. Data for LSG and LRYGB were extracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from years 2012 and 2013. MELD score was calculated using serum creatinine, bilirubin, INR, and sodium. Postoperative M&M were assessed in patients with a score ≥ 8 and compared for the type of operation. This was followed by analysis for MELD subcategories. Multiple logistic regression was performed to adjust for confounders. Out of 34,169, 9.8% of cases had MELD ≥ 8 and were included. Primary endpoint, 30-day M&M, was significantly lower post-LSG (9.5%) compared to LRYGB (14.7%); [AOR = 0.66(0.53, 0.83)]. Superficial wound infection, prolonged hospital stay, and unplanned readmission were more common in LRYGB. M&M post-LRYGB (30.6%) was significantly higher than LSG (15.7%) among MELD15-19 subgroup analysis. LRYGB is associated with a higher postoperative risk than LSG in patients with MELD ≥ 8. The difference in postoperative complications between procedures was magnified with higher MELD. This suggests that LSG might be a safer option in morbidly obese patients with higher MELD scores, especially above 15.


Ebolabase: Zaire ebolavirus-human protein interaction database for drug-repurposing.
Ebola Virus (EBOV) is one of the deadliest pathogenic virus which causes hemorrhagic fever. Though many Ebola-human interaction studies and databases are already reported, the unavailability of an adequate model and lack of publically accessible resources requires a comprehensive study to curate the Ebola-Human-Drug interactions. In total, 270 human proteins interacted with EBOV are collected from published experimental evidence. Then the protein-protein interaction networks are generated as EBOV-human and EBOV-Human-Drugs interaction. These results can help the researcher to find the effective repurposed drug for EBOV treatment. Further, the illustration of gene enrichment and pathway analysis would provide knowledge and insight of EBOV-human interaction describes the importance of the study. Investigating the networks may help to identify a suitable human-based drug target for ebola research community. The inclusion of an emerging concept, a human-based drug targeted therapy plays a very significant role in drug repurposing which reduces the time and effort is the highlight of the current research. An integrated database namely, Ebolabase has been developed and linked with other repositories such as Epitopes, Structures, Literature, Genomics and Proteomics. All generated networks are made to be viewed in a customized manner and the required data can be downloaded freely. The Ebolabase is available at http://ebola.bicpu.edu.in.


Evaluation of functional outcome of bilateral kidney tumors after sequential surgery.
There are limited data concerning patients treated with sequential bilateral kidney surgery. Current guidelines still lack an optimal surgical sequencing approach. We evaluated renal functional outcomes after sequential partial nephrectomy (PN) and radical nephrectomy (RN) in patients with bilateral renal cell carcinoma (RCC). A propensity score matched cohort of 267 patients (synchronous bilateral RCCs, N = 44 [88 lesions]; metachronous bilateral, N = 45 [90 lesions]; unilateral, N = 178) from two tertiary institutions were retrospectively analyzed. Synchronous bilateral RCCs were defined as diagnosis concomitantly or within 3 months of former tumor. Renal functional outcomes were defined as estimated glomerular filtration rate (eGFR) changes and de novo chronic kidney disease (CKD, stage ≥3) after surgery. Renal functional outcomes and clinical factors predicting de novo CKD were assessed using descriptive statistics and Cox regression analysis. In subgroup of bilateral RCCs, patients underwent sequential PN (N = 48), PN followed by RN (N = 8), or RN followed by PN (N = 25). Final postoperative estimated glomerular filtration rates (eGFRs) were 79.4, 41.4, and 61.2 ml/minute/1.73 m2, respectively (p = 0.003). There were significant differences in eGFR decline from baseline and de novo chronic kidney disease (CKD stage ≥ III) among groups, with PN followed by RN group showing the worst functional outcomes (all p < 0.05). Moreover, sequential PN subgroup in bilateral RCC showed significantly higher rate of de novo CKD than unilateral RCC group (13.8% vs. 6.9%, p = 0.016). On multivariate analysis, hypertension (p = 0.010) and surgery sequence (PN followed by RN, p < 0.001) were significant predictors of de novo CKD. The surgery sequence should be prudently determined in bilateral renal tumors. PN followed by RN showed a negative impact on renal functional preservation. Nephron-sparing surgery should be considered for all amenable bilateral RCCs.


PHYLOGEOGRAPHIC PATTERNS IN MITOCHONDRIAL DNA OF THE DESERT TORTOISE (XEROBATES AGASSIZI), AND EVOLUTIONARY RELATIONSHIPS AMONG THE NORTH AMERICAN GOPHER TORTOISES.
Restriction-fragment polymorphisms in mitochondrial DNA (mtDNA) were used to evaluate population-genetic structure in the desert tortoise Xerobates agassizi and to clarify evolutionary affinities among species of the gopher tortoise complex. Fourteen informative endonucleases were employed to assay mtDNAs from 56 X. agassizi representing 22 locations throughout the species' range. The mtDNA genotypes observed were readily partitioned into three major phylogenetic assemblages, each with striking geographic orientation. Overall, the X. agassizi mtDNA genotypes typify a common phylogeographic pattern, in which broad genetic uniformity of populations is interrupted by geographic features that presumably have functioned as dispersal barriers. The geologic history of the Colorado River area, which includes extensive marine incursions, may account for the marked mtDNA divergence between eastern and western X. agassizi assemblages. In mtDNA comparisons among the four species of the gopher tortoise complex, both UPGMA and Wagner parsimony analysis strongly support the recognition of two distinct species groups previously suggested by traditional systematic approaches. Furthermore, the mtDNA data identify the eastern X. agassizi assemblage as the probable inceptive lineage of X. berlandieri. Results from both intra- and interspecific comparisons illustrate how clues to historical events may be present in the geographic structure of mtDNA phylogenies.


Folic acid-functionalized graphene quantum dots: Synthesis, characterization, radiolabeling with radium-223 and antiviral effect against Zika virus infection.
The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha-particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors.


Generation and expression of a minimal hybrid Ig-receptor formed between single domains from proteins L and G.
The Ig-binding properties of protein L from Peptostreptococcus magnus and protein G from Streptococcus have been successfully combined through the construction of a novel hybrid protein, consisting of a single Ig-binding domain from each protein. The biophysical and biochemical properties of this construct have been characterized through equilibrium and pre-equilibrium fluorescence spectroscopy, circular dichroism, isothermal titration calorimetry, affinity chromatography, and conformational stability studies using a chemical denaturant in order to examine the structure and availability of ligand binding sites in each domain. These studies show that despite the small size of the protein (Mw=16.5 kDa) each domain behaves in an independent manner with respect to the binding characteristics of the same domain in isolation.


Screening for bipolar disorders using the Hypomanic Personality Scale.
The Hypomanic Personality Scale (Hyp; Eckblad and Chapman, 1986) might be an indicator for the risk for bipolar affective disorders. We investigated whether the results with American samples can be replicated in a different sample. The participants (N=224) completed a questionnaire package including the Hyp Scale and were independently interviewed with a psychiatric interview schedule. Compared to the control group, persons scoring high on the Hyp scale reported significantly more manic or hypomanic episodes but not episodes of major depression. Correspondingly, the risk group exceeded the control group only on the rate of bipolar affective disorders (20.8% vs. 1.3%) but not unipolar depression, anxiety disorders, or other psychiatric conditions. It seems that the Hyp scale assesses a similar concept in American and German samples, and that it might be a useful tool to study more closely the processes associated with the development of bipolar spectrum disorders.


PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors.
Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.


The effects of knee pain on knee contact force and external knee adduction moment in patients with knee osteoarthritis.
Knee osteoarthritis (OA) is a major cause of knee pain, leading to physical dysfunction. External knee adduction moment (KAM), a surrogate measure of knee contact force (KCF) in the medial compartment, is related to knee pain, but the association between KCF and pain severity remains unclear. This study aimed to reveal the differences in KCF due to pain severity. Twenty-eight patients with knee OA were evaluated knee symptoms including pain severity via the Knee Society Score. Based on the median symptom score, 17 points in this study, subjects were classified as having Mild symptomatic OA (n = 15) and Severe symptomatic OA (n = 13). Subjects walked three times at a comfortable speed along a six-meter walkway, and we calculated KAM during the stance phase. KCF magnitude and distribution were also computed using the subject-specific musculoskeletal model, considering physical characteristics such as the femorotibial angle measured by X-ray. No differences in physical characteristics such as femorotibial angle and gait speed were found by symptom severity, whereas KAM and medial KCF at minimum and second peak in Severe symptomatic OA patients were significantly greater than those in Mild symptomatic OA. A significant medial shift of KCF in Severe symptomatic OA was also seen at first peak and minimum. Severe symptomatic OA had a greater medial KCF and medial shift of KCF. Detailed evaluations of KCF magnitude and distribution in addition to KAM would provide crucial information on knee contact force in relation to symptom severity.