Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysis.
Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan-Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were -4.26 ± 8.54 (3rd month), -4.72 ± 11.83 (6th month), -6.16 ± 15.41 (9th month), -6.07 ± 15.71 (12th month), and -7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project.


Behavioral auditory function after transection of crossed olivo-cochlear bundle in the cat. III. Further study of ambient light intensity discrimination under intense noise.
This report describes the results in cats of a visual-auditory dual modal experiment after translateral olivo-cochlear bundle ablation at the floor of fourth ventricle. Subjects were behaviorally conditioned (avoidance) to respond in a shuttle box to show that they detected changes in ambient light intensity during the existence of intense background noise. With the given experimental paradigm, no noticeable difference was found between the response of the experimental animals and those of animals that underwent sham operation.


The TRP family of cation channels: probing and advancing the concepts on receptor-activated calcium entry.
Stimulation of membrane receptors linked to a phospholipase C and the subsequent production of the second messengers diacylglycerol and inositol-1,4,5-trisphosphate (InsP(3)) is a signaling pathway of fundamental importance in eukaryotic cells. Signaling downstream of these initial steps involves mobilization of Ca(2+) from intracellular stores and Ca(2+) influx through the plasma membrane. For this influx, several contrasting mechanisms may be responsible but particular relevance is attributed to the induction of Ca(2+) influx as consequence of depletion of intracellular calcium stores. This phenomenon (frequently named store-operated calcium entry, SOCE), in turn, may be brought about by various signals, including soluble cytosolic factors, interaction of proteins of the endoplasmic reticulum with ion channels in the plasma membrane, and a secretion-like coupling involving translocation of channels to the plasma membrane. Experimental approaches to analyze these mechanisms have been considerably advanced by the discovery of mammalian homologs of the Drosophila cation channel transient receptor potential (TRP). Some members of the TRP family can be expressed to Ca(2+)-permeable channels that enable SOCE; other members form channels activated independently of stores. TRP proteins may be an essential part of endogenous Ca(2+) entry channels but so far expression of most TRP cDNAs has not resulted in restitution of channels found in any mammalian cells, suggesting the requirement for further unknown subunits. A major exception is CaT1, a TRP channel demonstrated to provide Ca(2+)-selective, store-operated currents identical to those characterized in several cell types. Ongoing and future research on TRP channels will be crucial to understand the molecular basis of receptor-mediated Ca(2+) entry, with respect to the structure of the entry channels as well as to the mechanisms of its activation and regulation.


Monoclonal antibody to SV40 T-antigen blocks lysis of cloned cytotoxic T-cell line specific for SV40 TASA.
The lysis of SV40-transformed target cells by a cloned cytotoxic T cell line (CTB6) that is SV40 TASA-specific and H-2Kb-restricted is blocked by a monoclonal antibody reactive with the SV40 T-antigen. The blocking is maximized at high antibody concentrations and low effector-to-target cell ratios. These data indicate that at least one antigenic determinant of the SV40 T-antigen molecule is expressed at the cell surface and is either recognized by this cytotoxic T lymphocyte or is proximate to that determinant recognized by this cytotoxic T lymphocyte.


IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci.
Murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ) signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO) and vice versa (IFNγRperiKO). Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1. Alterations in distribution and composition of CNS inflammatory foci are not sufficient for the onset of atypical EAE. IFNγ dictates the course of neuroinflammatory disorders mainly through actions exerted within the CNS. This study provides strong evidence that link microglial STAT1 inactivation to vestibular dysfunction.


Validation of two-dimensional video-based inference of finger kinematics with pose estimation.
Accurate capture finger of movements for biomechanical assessments has typically been achieved within laboratory environments through the use of physical markers attached to a participant's hands. However, such requirements can narrow the broader adoption of movement tracking for kinematic assessment outside these laboratory settings, such as in the home. Thus, there is the need for markerless hand motion capture techniques that are easy to use and accurate enough to evaluate the complex movements of the human hand. Several recent studies have validated lower-limb kinematics obtained with a marker-free technique, OpenPose. This investigation examines the accuracy of OpenPose, when applied to images from single RGB cameras, against a 'gold standard' marker-based optical motion capture system that is commonly used for hand kinematics estimation. Participants completed four single-handed activities with right and left hands, including hand abduction and adduction, radial walking, metacarpophalangeal (MCP) joint flexion, and thumb opposition. The accuracy of finger kinematics was assessed using the root mean square error. Mean total active flexion was compared using the Bland-Altman approach, and the coefficient of determination of linear regression. Results showed good agreement for abduction and adduction and thumb opposition activities. Lower agreement between the two methods was observed for radial walking (mean difference between the methods of 5.03°) and MCP flexion (mean difference of 6.82°) activities, due to occlusion. This investigation demonstrated that OpenPose, applied to videos captured with monocular cameras, can be used for markerless motion capture for finger tracking with an error below 11° and on the order of that which is accepted clinically.


[Oral respiration. Diagnosis and physiopathology].
The oral breathing can change the functional connections during the development of the facial bones of the children. All this causes an abnormal growth of the facial bones and of the dental structures. This work developed a new discipline to remove this problem.


Non-Planar Structures of Sterically Overcrowded Trialkylamines.
Several amines with three bulky alkyl groups at the nitrogen atom, which exceed the steric crowding of triisopropylamine significantly, were synthesized, mainly by treating N-chlorodialkylamines with Grignard reagents. In six cases, namely tert-butyldiisopropylamine, 1-adamantyl-tert-butylisopropylamine, di-1-adamantylamines with an additional N-cyclohexyl or N-exo-2-norbonyl substituent, as well as 2,2,6,6-tetramethylpiperidine derivatives with N-cyclohexyl or N-neopentyl groups, appropriate single crystals were generated that enabled X-ray diffraction studies and analysis of the molecular structures. The four noncyclic amines adopt triskele-like conformations, and the sum of the three C-N-C angles is always in the range of 351.1° to 352.4°. Consequently, these amines proved to be structurally significantly flatter than trialkylamines without steric congestion, which is also signalized by the smaller heights of the NC3 pyramids (0.241-0.259 Å). There is no clear correlation between the heights of these pyramids and the degree of the steric crowding in the new amines, presumably because steric repulsion is partly compensated by dispersion interaction. In the cases of the two heterocyclic amines, the steric stress is smaller, and the molecular structures include quite different conformations. Quantum chemical calculations led to precise gas-phase structures of the sterically overcrowded trialkylamines exhibiting heights of the NC3 pyramids and preferred molecular conformers which are similar to those resulting from the X-ray studies.


Computed Tomography-Based Interstitial Brachytherapy for Recurrent Cervical Carcinoma in the Vaginal Apex.
To determine the factors influencing the outcomes of patients with recurrences post-hysterectomy for cervical cancers treated with external beam radiotherapy (EBRT) and interstitial brachytherapy. This prospective study accrued 90 patients between October 2008 and May 2014. All patients had had a prior hysterectomy and were diagnosed with recurrent vaginal apex cancers with squamous cell carcinomas. All underwent EBRT of 50 Gy (2 Gy/fraction) using tomotherapy-based image-guided intensity-modulated radiotherapy with concurrent chemotherapy of weekly cisplatin (40 mg/m2) followed by high dose rate interstitial brachytherapy boost of 20 Gy (4 Gy/fraction twice a day). Local relapse, disease-free and overall survival were determined. At a median follow-up of 74 months (4-123 months), 10/90 (11%) patients had local failure as the first site of relapse and 12/90 (13.3%) had first distant relapse. Only one patient had synchronous local and distant relapse. The 7-year local relapse-free, disease-free and overall survival were 87.6, 68.3 and 68.3%, respectively. Grade 2 and 3 rectal toxicity were seen in 5.6 and 3.1% of patients, respectively. Among these, two (2.2%) patients underwent temporary diversion colostomy due to vaginal sigmoid and rectovaginal fistula. Grade 2 and 3 bladder toxicity were seen in 5.6 and 1.1% of patients, respectively. In summary, the lateral disease extent (P = 0.048) and the presence of nodal disease at diagnosis (P = 0.08) had a statistically significant or borderline impact on local relapse without any impact on disease-free survival. Tumour size in itself did not affect overall survival. With the integration of EBRT and interstitial brachytherapy, most vaginal apex recurrences can be salvaged. An excellent local control and survival is achievable using intensity-modulated radiotherapy with image guidance and concurrent chemotherapy followed by high dose rate interstitial brachytherapy.


Functionalisation of vitamin B12 derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria.
This study describes the syntheses of four singly- and two doubly-modified vitamin B12 derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Coβ-phenyl-cobalamin-c,8-lactam and a 10-bromo-Coβ-phenylcobalamin combine a c-lactam or 10-bromo modification at the "eastern" site of the corrin ring with an artificial organometallic phenyl group instead of a cyano ligand at the β-site of the cobalt center. These two doubly-modified B12 antagonists (10 nM) inhibit fully B12-dependent (0.1 nM) growth of L. delbrueckii. In contrast to potent 10-bromo-Coβ-phenylcobalamin, single modified 10-bromo-Coβ-cyanocobalamin lacking the artificial organometallic phenyl ligand does not show any inhibitory effect. These results suggest, that the organometallic β-phenyl ligand at the Co center ultimately steers the metabolic effect of the 10-bromo-analogue.


Neonatal clinical outcome after elective cesarean section before the onset of labor at the 37th and 38th week of gestation.
Although elective cesarean sections are often performed after the 37th week of gestation without any complicating factor that may influence the timing of delivery,there is a possibility that infants born in the 37th week of gestation,especially early in the 37th week of gestation, do not obtain a satisfactory clinical outcome due to premature birth. The authors analyzed the clinical course during the neonatal period in 96 infants born in the 37th (n = 81)and 38th (n = 15) week of gestation by an elective cesarean section. Subjects were retrospectively divided into two groups: infants born in the first half of the 37th week of gestation (37+0-37+3)(n = 48), and infants born from the latter half of the 37th week of gestation (37+4-37+6)through the 38th week of gestation (n = 48). Twin pregnancies, pregnancy with placenta previa, and pregnancy of women who had a diversity of medical complications were excluded from the present study, because of the possibility that these conditions may have affected the infants' status. The incidence of infants who showed clinical symptoms during the neonatal period and who needed medical care was compared between the two groups. Of the 96 subjects, 25 infants(26.0%) had significant clinical symptoms. The incidence of breathing difficulty was significantly higher in the infant group born in the first half of the 37th week of gestation than in the latter group. An elective cesarean section before the onset of labor early in the 37th week of gestation should not be routinely undertaken.


Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial dysfunction.
Regorafenib, a multiple kinase inhibitor, is recently approved for treatment of patients with advanced hepatocellular carcinoma (HCC). Previous studies demonstrated that regorafenib was a mitochondrial toxicant, which associated with the impairment of mitochondria. Sirt3 is involved in the regulation of mitochondrial function in cancers. This study aimed to investigate the mechanism of Sirt3 involved in the mitochondrial dysfunction which associated with regorafenib treatment in liver cancer cells. We found regorafenib inhibited Sirt3 and p-ERK expression in HCC cells in a dose-dependent manner. Bioinformatics analysis showed that Sirt3 expression was down-regulated in liver cancer tissues and its low expression was correlated with worse overall survival (OS) in liver cancer patients. After transfected with Sirt3 overexpression plasmid, we found that Sirt3 sensitized liver cancer cells to regorafenib and resulted in much more apoptosis with a significant increase of ROS level. However, exogenous antioxidant could not weaken the apoptosis. Mitochondrial membrane potential assay indicated that Sirt3 overexpression accelerated the mitochondrial depolarization process induced by regorafenib and aggravated mitochondrial injury. Cellular oxygen consumption assay showed that mitochondrial dysfunction was caused by the damage of the electron transport chain. The results demonstrated that Sirt3 overexpression promoted the increase of ROS and apoptosis induced by regorafenib through the acceleration of mitochondrial dysfunction by impairing function of the electron transport chain in liver cancer cells. Our studies verified the functional role of Sirt3 in regorafenib treatment and suggested that regorafenib accompanied with Sirt3 activator as a novel treatment strategy for HCC.


The genetic effects of the cytostatic drug TS160 on Chinese hamster fibroblasts in vitro.
The cytostatic agent TS160 inhibited DNA synthesis in V79 cells while the course of RNA synthesis and protein synthesis were not changed significantly. DNA inhibition was in direct correlation with the inhibition of growth and reduction of colony-forming ability in the treated cells. The study of the mutagenic consequences of single or repeated TS160 treatments showed that TS160 had a significant mutagenic activity on Chinese hamster V79 cells. In the study of mutagenic effects of TS160, we used the method of repeated treatment of surviving cell fractions with this compound. This method is suitable for those mutagens (e.g. weak mutagens) whose mutagenic activity on mammalian cells in vitro might escape attention after application of a single dose. The possible causes of mutagenic effects of TS160 are discussed.


The value of percentage of CD8+ T lymphocyte levels in distinguishing polymyalgia rheumatica from early rheumatoid arthritis.
To determine whether the low absolute numbers and percentages of CD8 positive T cells in the circulation of patients with polymyalgia rheumatica (PMR) could be used as a new diagnostic criterion for the disease. The % CD4 and CD8 positive T lymphocyte sub-populations were measured in 37 patients with PRM before treatment and during steroid treatment over the subsequent 2 years, in 21 patients with rheumatoid arthritis (RA), and in 27 normal (N) control subjects. During the study, 10 patients, who were initially diagnosed as PMR, were reclassified as having had a myalgic onset of RA (PMR-RA), according to the American College of Rheumatology criteria for the diagnosis of RA. No decreased %CD8+ T lymphocyte subset had been observed in these patients at presentation, before steroid therapy, or during treatment with steroids when compared with the RA and N groups. The measurement of %CD8+ T cell subset may provide a simple method for determining whether patients presenting with myalgia are "true" PMR or are destined to develop RA.


Outcomes of isolated glenoid labral injuries in professional baseball pitchers.
Major League Baseball (MLB) pitchers who return to competition after labral surgery show a decline in their pitching performance. Retrospective cohort. Tertiary institution. MLB starting or relief pitchers with isolated glenoid labral injuries. Open or arthroscopic surgical repair of isolated glenoid labral injuries. Individual statistics were reviewed for 42 MLB pitchers who underwent surgical repair of isolated glenoid labral injuries of their throwing shoulder between 1998 and 2003. Pertinent statistical data, including earned run average (ERA), innings pitched (IP), and walks plus hits per inning pitched (WHIP), were obtained for all players and compared before and after surgery. These statistics were evaluated for an association with demographic factors, pitching role, and rehabilitation time. A total of 42 MLB pitchers (26 starters, 16 relievers) were included in the study with an average age of 27.5 years for starters and 29.9 years for relievers at injury time. There were 30 right-handed pitchers and 12 left-handed pitchers. In all, 69% of pitchers returned postoperatively to MLB for at least one season; 29% pitched for three seasons or more. For both relievers and starters, there was no statistically significant postoperative change in ERA or WHIP at 1 and 3 years. Starters had significantly decreased IP at 1 year, but not at 3 years. Relievers had no significant change in IP at 1 year postoperatively, but IP were significantly decreased at 3 years. Relievers missed less time after surgery than did starters (11.4 vs. 18.4 months). Most pitchers who were able to return to competition after surgery showed insignificant changes in ERA and WHIP and significant decreases in IP. Age, MLB experience, and pitching role as a reliever were the most significant factors related to a successful return after surgery.


Rapid estimation of 2D relative B 1 + -maps from localizers in the human heart at 7T using deep learning.
Subject-tailored parallel transmission pulses for ultra-high fields body applications are typically calculated based on subject-specific B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps of all transmit channels, which require lengthy adjustment times. This study investigates the feasibility of using deep learning to estimate complex, channel-wise, relative 2D B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps from a single gradient echo localizer to overcome long calibration times. 126 channel-wise, complex, relative 2D B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps of the human heart from 44 subjects were acquired at 7T using a Cartesian, cardiac gradient-echo sequence obtained under breath-hold to create a library for network training and cross-validation. The deep learning predicted maps were qualitatively compared to the ground truth. Phase-only B 1 + $$ {\mathrm{B}}_1^{+} $$ -shimming was subsequently performed on the estimated B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps for a region of interest covering the heart. The proposed network was applied at 7T to 3 unseen test subjects. The deep learning-based B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps, derived in approximately 0.2 seconds, match the ground truth for the magnitude and phase. The static, phase-only pulse design performs best when maximizing the mean transmission efficiency. In-vivo application of the proposed network to unseen subjects demonstrates the feasibility of this approach: the network yields predicted B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps comparable to the acquired ground truth and anatomical scans reflect the resulting B 1 + $$ {\mathrm{B}}_1^{+} $$ -pattern using the deep learning-based maps. The feasibility of estimating 2D relative B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps from initial localizer scans of the human heart at 7T using deep learning is successfully demonstrated. Because the technique requires only sub-seconds to derive channel-wise B 1 + $$ {\mathrm{B}}_1^{+} $$ -maps, it offers high potential for advancing clinical body imaging at ultra-high fields.


Little imaginal discs, a Trithorax group member, is a constituent of nuclear matrix of Drosophila melanogaster embryos.
Nuclear Matrix (NuMat) is the structural and functional framework of the nucleus. It has been shown that attachment of chromatin to NuMat brings significant regulation of the transcriptional activity of particular genes; however, key components of NuMat involved in this process remain elusive. We have identified Lid (Little imaginal discs) as one of the components of NuMat. It belongs to the TrxG group of proteins involved in activation of important developmental genes. However, unlike other activator proteins of TrxG, Lid is a Jumonji protein involved in H3K4me3 demethylation. Here, we report the association of Lid and its various domains with NuMat which implicates its structural role in chromatin organization and epigenetic basis of cellular memory. We have found that both N and C terminal regions of this protein are capable of associating with NuMat. We have further mapped the association of individual domains and found that, PHD, ARID and JmjC domains can associate with NuMat individually. Moreover, deletion of N-terminal PHD finger does not alter Lid's NuMat association implying that although it is sufficient, yet, it is not necessary for Lid's structural role in NuMat. Based on our findings, we hypothesize that C terminal region of Lid which contains PHD fingers might be responsible for its NuMat association via protein-DNA interactions. However, for the N terminal region harboring both a PHD and an ARID finger, Lid anchors to the NuMat via both protein-protein and protein-DNA interactions. The association of JmjC domain with NuMat is the first report of the association of a demethylase domain with NuMat suggesting that Lid, a demethylase, being part of NuMat might be involved in regulating the chromatin dynamics via its NuMat association.


Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.
The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.


Increase in the flock prevalence of lameness in ewes is associated with a reduction in farmers using evidence-based management of prompt treatment: A longitudinal observational study of 154 English sheep flocks 2013-2015.
Since 2006, farmers in England have received new recommendations on best practice to manage lameness in sheep through a range of knowledge exchange activities. The adoption of each recommendation varied, but in 2013 approximately 50% of farmers reported treating all lame sheep within 3 days of onset of lameness (prompt treatment), 41% did not practice routine foot trimming, 50% culled sheep that had been lame and 14% vaccinated against footrot; all recommended best practices. The aim of this study was to investigate the prevalence of lameness in ewes in England from 2013 to 2015 and to identify changes in practice to manage lameness between 2013 and 2015 and the population attributable fraction for these managements. A longitudinal study with a cohort of 154 English sheep farmers was run for three years, farmers completed questionnaires on lameness in their flock for the previous 12 months in 2013, 2014 and 2015. The geometric mean prevalence of lameness in ewes was 4.1% in 2015, significantly higher than 3.3% and 3.2% for the same 128 farmers who provided data in both 2013 and 2014. Between 2013 and 2015 there was a significant reduction in farmers practising prompt treatment (50.6%-28.6%) but an increase in not practising routine foot trimming (40.9%-79.2%), culling sheep that had been lame (49.4%-81.8%), and vaccinating against footrot (14.3%-29.2%). Not practising prompt treatment, ≥5% of sheep feet bleeding during routine foot trimming, vaccinating ewes for <6 years or not vaccinating at all, and other flocks mixing with the flock, were associated with a significantly higher flock prevalence of lameness. Culling sheep that had been lame was not associated with prevalence of lameness. The population attributable fractions (PAFs) for not vaccinating for>5 years, not treating lame sheep promptly, ≥5% of sheep feet bleeding during routine foot trimming, and mixing of flocks were 34.5%, 25.3%, 2.9% and 2.4%. In 2013, when 50% of farmers used prompt treatment, the PAF for not using prompt treatment was only 13.3%. We conclude that the change in practice by these farmers towards flock-level managements and a reduction in individual prompt treatment of lame sheep negatively impacted the prevalence of lameness in sheep. This change occurred despite the evidence that prompt treatment of lame sheep is highly effective at reducing the prevalence of lameness in sheep flocks and is an example of cognitive dissonance.


Association between binge eating and physical violence perpetration among U.S. college students.
To date, no known research has explored the link between binge eating and physical violence perpetration despite overlapping psychological constructs that underpin these behaviors (i.e., emotion regulation difficulties, impulsivity). Therefore, this study aimed to determine the association between binge eating and self-reported physical violence perpetration. Cross-sectional data from four survey years (2016-2020) of the national (U.S.) Healthy Minds Study (N = 6210) were analyzed. Unadjusted (Independent samples t test) and adjusted (logistic regression) analyses were conducted to determine the associations between binge eating in the past four weeks and violence perpetration in the past 12 months, while adjusting for potential confounders. The unadjusted mean number of days of binge eating was significantly higher among participants who reported physical violence perpetration (M = 2.6, SD = 5.2) compared to those who did not (M = 1.8, SD = 3.7). Logistic regression analysis demonstrated that each additional day of binge eating was associated with 5% higher odds (95% confidence interval 1.02-1.09) of self-reported physical violence perpetration, while adjusting for potential confounders. Results from this study are the first known to identify an association between binge eating and physical violence perpetration among U.S. college students. Findings are supported by the potential mechanistic overlap of emotion regulation and impulsivity associated with both binge eating and violence perpetration, underscoring the need for more research.


Interaction between Cr(VI) and Tubificidae in sludge reduction system: effect, reduction, and redistribution of Cr(VI).
The treatment of heavy metals in sewage treatment systems has gained more attention with the increase in heavy metal hazards. Tubificidae in sludge reduction have been widely studied; however, little is known about the effect of Tubificidae in the treatment of Cr-containing wastewater. In this study, the mechanism of Tubificidae in the sludge reduction system with Cr stress was studied. Predation experiments by Tubificidae in a Cr-containing sludge reduction system were conducted to investigate the changes in enzyme activities in the Tubificidae under different concentrations of Cr, and the distribution of Cr in the sludge reduction reactor was analyzed. The kinetic model of uptake and elimination of Cr in Tubificidae was established. The results showed that the maximum activation multiplier factor of superoxide dismutase (SOD) activity was 1.95 under the low concentration of Cr(VI), which indicated that Tubificidae had a certain detoxification. After the effect of Tubificidae on Cr(VI) experiments, the Cr concentrations in Tubificidae, sludge, and feces increased first and then decreased with exposure time, and the proportion of total Cr and Cr(VI) in the sludge decreased from 71.98% and 42.7% to 29.18% and 6.82%, respectively. The detoxification mechanism of the Tubificidae could be activated with Cr stress, and 63.22% of the Cr(VI) was converted to Cr(III). The bioconcentration factor (BCF) for theoretical equilibrium was 446, the maximum bioaccumulation factor (BAF) reached 0.97 on the 15th day. It can be seen that Tubificidae could be considered a good scavenger of environmental Cr(VI). The hyperbolic model fits the process of Cr uptake and elimination well and can be used as a predictive tool for Tubificidae accumulation.


Comparison of different intravascular thread occlusion models for experimental stroke in rats.
For the induction of ischemic strokes of varying sizes in rats, different types of threads were used to occlude the middle cerebral artery (MCA) in combination with or without the posterior communicating artery (PCOM) and the common carotid artery (CCA). During vessel occlusion brain tissue partial oxygen pressure (ptiO2) and regional cerebral blood flow (rCBF) were monitored using a combined ptiO2/laser Doppler flow probe. Following neurological assessment animals were sacrificed at 3, 8 and 24 h and the necrotic volume was measured on serial coronary slices. In another experimental group, rCBF was measured 1h post-insult with the iodo[14C]antipyrine method. Animals with selective MCA occlusion showed less reduction of ptiO2 and rCBF and smaller infarcts when compared with animals with combined occlusion of the MCA, CCA and PCOM. Both groups, selective MCA occlusion and combined occlusion of the MCA, CCA and PCOM, demonstrated a high reproducibility and low variability of stroke size. Relative growth of stroke size within 24 h was higher in animals with selective MCA occlusion. Therefore, the selective MCAO model may be advantageous for studies of neuroprotective strategies.


Tasks and interfaces in primary and specialized palliative care for Duchenne muscular dystrophy - A patients' perspective.
In spite of the improvements in care and the emergence of disease-modifying treatments, Duchenne muscular dystrophy (DMD) remains a life-limiting disease of adolescence and (young) adulthood. Palliative care approaches and principles should be integrated from the point of diagnosis and implemented throughout the lifespan. A nationwide cross-sectional survey based on a mixed-method-design of qualitative and quantitative research approaches evaluated the structural implementation and perception of palliative care for DMD in Germany. Data analyses revealed that palliative care was predominantly provided at the primary care level by pediatricians, general practitioners and specialized multi-professional outpatient structures. The majority of patients did not utilize the scopes of specialized palliative structures. Simultaneously, insufficiently treated complex symptoms, emergent and elective hospitalizations and barriers in transitioning into adult care presented a considerable burden. A collaborative integrated model with a close cooperation of patients, families and care providers is proposed involving task areas and interfaces complementing primary and specialized palliative care (1) management of complex symptoms, (2) crisis support, (3) intermittent relief of the strain for caregivers, (4) coordination of care, (5) advance care planning and (6) end-of-life care. Specialized palliative care should be used as an "add-on" approach in time of need rather than as a prognosis or disease stage.


Similar simulation of overburden movement characteristics under paste filling mining conditions.
The method of filling mining can solve the problem of surface subsidence caused by coal mining. Among them, it is crucial to study the mechanism of filler strength improvement timeliness and filler mining to control rock movement for filler mining. In this paper, by combining theoretical analysis and similar simulation experiments, compressive strength is used as the research parameter to conduct proportioning test research on paste filling similar materials such as coal gangue, fly ash, and cement. The results prove that the strengths of the test ratios can meet the strength design criteria and lay the foundation for the requirements of similar simulation experiments. In order to study the characteristics of overburden failure, stress and displacement in the process of filling mining, the key technical parameters of overburden movement are determined. Similar simulation experiments were conducted to study the movement and deformation of overburden rock and the displacement and stress distribution law of overburden rock in the coal mine under different filling rates and filling steps conditions. The results show that the filling rate and filling step are the keys to preventing the overlying rock from rupture and collapse, and the larger the filling rate is, the smaller the stress and displacement of the overburden; the larger the filling step is, the larger the displacement and stress change of the overburden, and vice versa. In addition, the displacement curve along the strike is basically an "arch" type distribution, and the stress variation trend is "large-small-large" with a "Z" type distribution. The research results are of great significance to guide the practice of filling mining and can provide the theoretical basis for its further promotion.


The "CONNECT" Protocol: Delivering Bad News by Phone or Video Call.
The COVID-19 pandemic has changed the principles of communication within the health-care setting. Communication skills as developed for use in the context of a direct and personal encounter have become insufficient. As a result, numerous health professionals came to believe they were not sufficiently prepared to deliver bad news in relation to medical care. The CONNECT protocol is a tool designed to help health-care professionals in the delivery of such messages. The name of the protocol is an acronym derived from C - context, O - organization, NN - near and niceties, E - emotions, C - counseling, T - taking care. The objective of the protocol is to improve the effectiveness of the delivery of bad news in relation to medical care by ensuring proper organization of the key elements of the encounter with the patient and/or their family.


[Daptomycin in the treatment of Gram-positive infections in patients with chronic renal failure].
Daptomycin is a cyclic lipopeptide that is effective in the treatment of Gram-positive infections, including those caused by multiresistant pathogens. This drug has rapid bactericidal action and low nephrotoxicity. Patients with severe renal failure show a dicrease in its renal clearance and an increase in the elimination half-life. The recommended dose in patients with creatinine clearance (CrCl) < 30 ml/min is 4 mg/kg/48 h in skin and soft tissue infections and is 6 mg/kg/48 h in bacteremia and right endocarditis. Pharmacokinetic studies and data from the CORE Registry have allowed improved the dosing regimen in patients under hemodialysis, peritoneal dialysis and other extrarenal depuration techniques. Patients with a CrCl < 30 ml/ min have rates of efficacy ranging between 69.2% and 96%, these rates being similar to or lower than those observed in patients with a CrCl > 30 ml/min. Patients under hemodialysis may have higher rates of clinical failure. This article presents the preliminary results of the EUCORE in Spain. The presence of renal failure at the start of daptomycin therapy is not associated with an increase in the rates of severe adverse effects. Daptomycin has a good safety and efficacy profile for the treatment of infections in patients with chronic renal insufficiency. The consensus documents of distinct societies have incorporated the use of daptomycin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus in patients with renal insufficiency.


Microbial composition, potential functional roles and genetic novelty in gypsum-rich and hypersaline soils of Monegros and Gallocanta (Spain).
Soil microbial communities (both Bacteria and Archaea) were studied after 16S rRNA genes massive sequencing in two hypersaline and gypsum-rich contrasted sites located in NE Spain. Soil microbial communities were also locally analysed according to environmental variables, including geological, physico-chemical, biogeochemically, and climatic data. Typical soil characteristics, climate data, and plant composition clearly split the two sites and major differences among the microbial communities for the areas were initially expected. Overall, high values of microbial species richness (up to 2300 taxa) and ecological diversity was detected in both sites. High genetic novelty levels were found mostly to environmental sequences, highlighting the high potential for microbiological studies. In contrast to the initial expectations, a substantial overlapping between Monegros and Gallocanta microbes was observed, indicating a high similarity despite of the geographical, botanical and environmental distances between sites, in agreement with both high dispersal and local selection inherent to the microbial world. The potential biogeochemical cycling showed small differences between sites, with presence of photosynthetic green and purple sulfur bacteria, cyanobacteria and aerobic and anaerobic chemolitotrophs. Potential for aerobic methane oxidation and anaerobic methanogenesis was observed in both sites, with predominance of potential nitrification mostly by ammonia-oxidizing archaea, nitrite oxidation and denitrification, and minor contribution for nitrate reduction and nitrate ammonification. The predicted functions based on the taxonomic composition showed high overlapping between the two studied regions, despite their difference in gypsum richness.


Immune asynchrony in COVID-19 pathogenesis and potential immunotherapies.
The outbreak of coronavirus disease 2019 (COVID-19) is an unprecedented global health crisis. Tissue and peripheral blood analysis indicate profound, aberrant myeloid cell activation, cytokine storm, and lymphopenia, with unknown immunopathological mechanisms. Spatiotemporal control of the quality and quantity of the antiviral immune responses involves synchronized cellular and molecular cascades and cross-talk between innate and adaptive immunity. Dysregulated responses in immunity, such as at the stages of immune sensing, alarming, polarization, and resolution, may contribute to disease pathology. Herein, we approach SARS-CoV-2 through an immunomodulatory lens, discussing possible mechanisms of the asynchronized antiviral immune response and proposing potential therapeutic strategies to correct the dysregulation.


Immobilization versus immediate mobilization after intrauterine insemination: A systematic review and meta-analysis.
The objective of this systematic review and meta-analysis was to investigate a possible association between immobilization and pregnancy rate in patients undergoing intrauterine insemination. To ensure the quality of the methodology, the PRISMA criteria were met at all stages of the development of this meta-analysis. We searched the Cochrane Library, EMBASE, PubMed MEDLINE, ScienceDirect and reference lists of eligible studies from inception to March 2017, without any restriction. We also interviewed the ClinicalTrials.gov database for unpublished articles. Finally, we sought potentially eligible studies in meeting abstracts. Two reviewers independently extracted study characteristics and outcome data. Estimates were pooled using random effects models and sensitivity analyses. We selected studies that compared bed rest to immediate mobilization after intrauterine insemination. The primary outcome was the ongoing pregnancy rate per couple. Of 176 identified abstracts, four primary studies, all of them randomized controlled trials, met the inclusion criteria, including 1361 couples. The overall relative risk of ongoing pregnancy rate in bed rest versus immediate immobilization was 1.67 95% CI [0.86; 3.22]. The overall relative risk of the live birth rate was 1.11 95% CI [0.56; 2.20]. This systematic review and meta-analysis was not able to demonstrate that bed rest after intrauterine insemination effectively increases in pregnancy rate. For everyday practice, no specific strategy, bed rest or immediate mobilization, can be recommended at this time.


An experimental study of the treatment of liver injury with InLine RFA.
The liver is the most frequently injured abdominal organ after blunt injury; sometimes it may be very difficult to achieve haemostasis. In this study we examined the use of InLine radiofrequency ablation (RFA) for the coagulation and haemostasis of simulated liver injury. Six pigs were tested in this study. We created two types of grade III to IV liver injury: peripheral and central. Then treatment with InLine RFA was compared to conventional diathermy and suture. A total of 32 surgeries were performed: peripheral injury (12 InLine versus 6 diathermy + suture); central injury (8 InLine versus 6 diathermy + suture). The reduction of blood loss was 63.88% in peripheral injury and 53.57% in central injury, respectively. There were significant differences in both types of injuries as regards blood loss (p<0.05) and blood loss per cm(2) (p<0.05). InLine RFA is efficacious in treating liver injuries in pigs and may have a significant potential for some human liver injuries.


Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).
Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.


Pentalogy of Cantrell: embryofetoscopic diagnosis.
Embryofetoscopy is an endoscopic technique that permits a direct visualization and morphologic study of embryos during the first and early second trimester. We report the early prenatal diagnosis of a case of Pentalogy of Cantrell combining data obtained by 2-dimensional and 3-dimensional ultrasonography and embryofetoscopy. Morphologic examination focused on a large omphalocele protruding from the anterior abdominal wall as an oval pulsating mass, measuring approximately 3 cm. The visualization of an omphalocele with ectopia cordis without other malformations confirmed the diagnosis of Pentalogy of Cantrell (class III). Currently, embryofetoscopy allows direct visualization of the embryo in vivo, enabling accurate diagnosis of developmental defects and yielding additional insights into developmental disorders in the embryo.


Model-based evaluation of the COVID-19 epidemiological impact on international visitors during Expo 2020.
The impact of the COVID-19 pandemic on large events has been substantial. In this work, an evaluation of the potential impact of international arrivals due to Expo 2020 in terms of potential COVID-19 infections from October 1st, 2021, until the end of April 2022 in the United Arab Emirates is presented. Our simulation results indicate that: (i) the vaccination status of the visitors appears to have a small impact on cases, this is expected as the small numbers of temporary visitors with respect to the total population contribute little to the herd immunity status; and (ii) the number of infected arrivals is the major factor of impact potentially causing a surge in cases countrywide with the subsequent hospitalisations and fatalities. These results indicate that the prevention of infected arrivals should take all precedence priority to mitigate the impact of international visitors with their vaccination status being of less relevance.


The cytotoxicity of endogenous CdS and Cd2+ ions during CdS NPs biosynthesis.
In the present study, cadmium-based nanoparticles (NPs) were biosynthesized by incubating their precursor salts with E. coli CD-2. Transmission electron microscopy (TEM) revealed the morphology of the NPs and confirmed that the NPs were formed via an intracellular growth. Energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD) determined the elemental composition of the NPs and identified the NPs as CdS. The contents of extracellular Cd2+, intracellular Cd2+ and intracellular CdS NPs were determined during the whole CdS biosynthetic process. The results demonstrated that the contents of Cd2+ and CdS NPs changed during the biosynthetic process. The colony-forming capability test showed that strain CD-2 could maintain its growth during CdS biosynthesis. Protein oxidation levels confirmed that the E. coli cells faced oxidative stress induced both by Cd2+ and CdS. Both Cd2+ and CdS NPs affected the cellular antioxidative system by upregulating related gene expression. However, different pathways might be involved to eliminate ROS induced by Cd2+ ions or CdS NPs, respectively. The expression levels of ef-tu, ftsZ, mutS and dnaK were enhanced together with CdS accumulation, indicating that the cells had to overexpress certain related genes to respond to the NPs-induced stress.


Evolution of gene regulatory network of C4 photosynthesis in the genus Flaveria reveals the evolutionary status of C3-C4 intermediate species.
C4 photosynthesis evolved from ancestral C3 photosynthesis by recruiting pre-existing genes to fulfill new functions. The enzymes and transporters required for the C4 metabolic pathway have been intensively studied and well documented; however, the transcription factors (TFs) that regulate these C4 metabolic genes are not yet well understood. In particular, how the TF regulatory network of C4 metabolic genes was rewired during the evolutionary process is unclear. Here, we constructed gene regulatory networks (GRNs) for four closely evolutionarily related species from the genus Flaveria, which represent four different evolutionary stages of C4 photosynthesis: C3 (F. robusta), type I C3-C4 (F. sonorensis), type II C3-C4 (F. ramosissima), and C4 (F. trinervia). Our results show that more than half of the co-regulatory relationships between TFs and core C4 metabolic genes are species specific. The counterparts of the C4 genes in C3 species were already co-regulated with photosynthesis-related genes, whereas the required TFs for C4 photosynthesis were recruited later. The TFs involved in C4 photosynthesis were widely recruited in the type I C3-C4 species; nevertheless, type II C3-C4 species showed a divergent GRN from C4 species. In line with these findings, a 13CO2 pulse-labeling experiment showed that the CO2 initially fixed into C4 acid was not directly released to the Calvin-Benson-Bassham cycle in the type II C3-C4 species. Therefore, our study uncovered dynamic changes in C4 genes and TF co-regulation during the evolutionary process; furthermore, we showed that the metabolic pathway of the type II C3-C4 species F. ramosissima represents an alternative evolutionary solution to the ammonia imbalance in C3-C4 intermediate species.


Preliminary Results of Utrasound-Guided Percutaneous Radiofrequency Ablation in the Treatment of Refractory Non-nodular Hyperthyroidism.
To assess the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of refractory non-nodular hyperthyroidism. This was a single-center retrospective study in 9 patients with refractory non-nodular hyperthyroidism (2 males, 7 females; median age, range, 36 years, 14-55 years) who underwent RFA between August 2018 and September 2020. The incidence of post-procedural complications, changes in thyroid volume, thyroid function and the use and dosages of anti-thyroid drugs, were compared pre- and post-RFA. All patients completed the procedure successfully, and no serious complications occurred. Three months after ablation, thyroid volumes were significantly decreased with the mean volumes of the right and left lobes reduced to 45.6% (10.9 ± 2.2 ml/23.9 ± 7.2 ml, p < 0.001) and 50.2% (10.8 ± 7.4 ml/21.5 ± 11.4 ml, p = 0.001) of the volumes within 1 week after ablation. The thyroid function was gradually improved in all patients. At 3 months post-ablation, the levels of FT3 and FT4 were returned to the normal range (FT3, 4.9 ± 1.6 pmol/L vs. 8.7 ± 4.2 pmol/L, p = 0.009; FT4, 13.1 ± 7.2 pmol/L vs. 25.9 ± 12.6 pmol/L, p = 0.038), the TR-Ab level was significantly lower (4.8 ± 3.9 vs. 16.5 ± 16.4 IU/L, p = 0.027), and the TSH level was significantly higher (0.76 ± 0.88 vs. 0.03 ± 0.06, p = 0.031) than that before-ablation. Additionally, three months after RFA, the anti-thyroid medication dosages were reduced to 31.25% compared to baseline (p < 0.01). Ultrasound-guided RFA in the treatment of refractory non-nodular hyperthyroidism was safe and effective in this small group of patients with limited follow-up. Further studies with larger cohorts and longer follow-up are needed to validate this potential new application of thyroid thermal ablation.


Genome-wide comprehensive characterization and expression analysis of TLP gene family revealed its responses to hormonal and abiotic stresses in watermelon (Citrullus lanatus).
Thaumatin-like protein (TLP) is the well-known sweetest protein which plays a crucial role in diverse developmental processes and different stress conditions in plants, fungi and animals. The TLP gene family is extensively studied in different plant species including crop plants. Watermelon (Citrullus lanatus) is an important cucurbit crop cultivated worldwide; however, the comprehensive information about the TLP gene family is not available in watermelon. In the present study, we identified the 29 TLP genes as gene family members in watermelon using various computational methods to understand its role in different developmental processes and stress conditions. ClaTLP gene family members were not uniformly distributed on 22 chromosomes. Phylogenetic analysis revealed that the ClaTLP gene family members were grouped into 10 sub-groups. Further, gene duplication analysis showed thirteen gene duplication events which included one tandem and twelve segmental duplications. Amino acid sequence alignment has shown that ClaTLP proteins shared 16 conserved cysteine residues in their THN domain. Furthermore, cis-acting regulatory elements analysis also displayed that ClaTLP gene family members contain diverse phytohormone, various defense, and stress-responsive elements in their promoter region. The expression profile of the ClaTLP gene family revealed the differential expression of gene family members in different tissues and abiotic stresses conditions. Moreover, the expression profile of ClaTLP genes was further validated by semi-quantitative reverse transcriptase PCR. Taken together, these results indicate that ClaTLP genes might play an important role in developmental processes and diverse stress conditions. Therefore, the outcome of this study brings forth the valuable information for further interpret the precise role of ClaTLP gene family members in watermelon.


Differential regulation of neutrophil CD18 integrin function by di- and tri-valent cations: manganese vs. gadolinium.
Affinity regulation of integrin function plays an important role during both leukocyte-endothelial and leukocyte-leukocyte interactions. We compared the roles of Mn(2+) (Manganese) and Gd(3+) (Gadolinium) in regulating leukocyte CD18-integrin function. We observed that: (i) Both cations prolonged neutrophil homotypic aggregation following chemoattractant IL-8 stimulation, with Gd(3+) being effective at doses two orders of magnitude (10 microM range) lower that Mn(2+). (ii) While both Gd(3+) and Mn(2+) mediate homotypic cell aggregation via L: -selectin and CD18 integrins, their effects on the integrin subunits, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), was different. Gd(3+) altered both LFA-1 and Mac-1 function, while the dominant effect of Mn(2+) was on Mac-1. This effect of Gd(3+) on LFA-1 function was confirmed in cell-free studies that measured the binding of recombinant ICAM-1 to LFA-1 immobilized on beads. (iii) Both ions augmented the binding of 327C, an antibody that recognizes active CD18 on human neutrophils, both in the presence and absence of exogenous IL-8. The effects of Mn(2+) was more pronounced since it caused 3-4-fold increase in mAb 327C binding to neutrophils compared to Gd(3+) which increased antibody binding by only approximately 80%. 327C binding was partially reduced by Ca(2+). Further, 327C binding induced by Mn(2+) did not correlate tightly with cell adhesion function. (iv) In studies that monitored intracellular Ca(2+) ([Ca(2+)](i)), the addition of Mn(2+) but not Gd(3+) to neutrophils altered [Ca(2+)](i) levels. Overall, while both Gd(3+) and Mn(2+) stabilize high affinity CD18 mediated cell adhesion, Gd(3+) affects integrin conformation while Mn(2+) may also trigger other effects.


Simultaneous determination of 12 β-agonists in feeds by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry.
A new analysis method using ultra-performance liquid chromatography (UPLC)-quadrupole-time-of-flight mass spectrometry (Q/TOF MS) was developed for screening and confirmation of 12 β-agonists in feeds. Under the optimized gradient elution conditions, it takes only 6 min to separate all 12 β-agonists, and the critical pair of Ractopamine and Isoxsuprine isomers was almost completely separated. Based on the over 10,000 full-width at half maximum (FWHM) mass resolution and high mass accuracy features of TOF MS with 20 mDa mass window, accurate mass chromatograms were reconstructed for individual compounds. The fragmentation pathways of 12 β-agonists were also studied using Q-TOF MS. The potential of UPLC-Q/TOF MS for confirmatory analysis was shown by determining the accurate mass of all compounds and fragment ions upon collision-induced-dissociation (CID) at different energies. The extra mass measurement errors for all β-agonists were found to be within 5 ppm. The limits of detection (LODs) and limits of quantitation (LOQs) were determined for all β-agonists in feeds and found to be 1-5 ng/mL and 5-50 μg/kg, respectively. The method of UPLC-Q/TOF MS developed in this study was initially applied to the research of feeds for analysis of 12 β-agonists and proved to be accurate, sensitive, convenient and practical.


Cosmopolitical obstetrics: some insights from the training of traditional midwives.
In most countries of the third world, strategies for development in the health sector include efforts to upgrade the skills of village level health care workers, including traditional birth attendants (TBAs). In spite of several decades of experience, training programs for TBAs have not been particularly successful. Drawing on data from several years of ethnographic fieldwork with Maya midwives in Yucatan and on participation in government-sponsored training courses for indigenous midwives, this paper examines some of the reasons underlying this failure. Paramount among these are differences in world view and the misapplication of didactic modes of teaching in situations where learning in the apprenticeship mode is more appropriate and culturally customary.


Will people in conflict affected zones in Africa have access to COVID-19 vaccine? A case of Nigeria.
Vaccination is an important and cost-effective disease prevention and control strategy. Over the years, milestone discoveries in vaccine research and development as well as vaccine delivery systems, have contributed to expanded immunisation coverage and reduction in morbidity and mortality associated with vaccine-preventable diseases. While this outstanding development in vaccine delivery continues, there are considerable gaps in access to vaccines among populations living in fragile and conflict-affected zones which appeared to be the fault line of limited vaccine coverage. Despite progress in coronavirus disease 2019 (COVID-19) vaccine development, there are concerns about the feasibility of African countries affected by armed conflict and violence to effectively deliver COVID-19 vaccines at the unprecedented level required to fight against the virus. In this article we discuss the feasibility of access to COVID-19 vaccine among populations in conflict affected areas in Nigeria including methods that can be applied to reach and vaccinate populations in these settings.


Fluorotelomer alcohols induce hepatic vitellogenin through activation of the estrogen receptor in male medaka (Oryzias latipes).
Here we report on the in vivo estrogenic effects of two fluorotelomer alcohols, such as 1H,1H,2H,2H-perfluorooctan-1-ol (6:2 FTOH) and 1H,1H,2H,2H-perfluorodecan-1-ol (8:2 FTOH), in male medaka (Oryzias latipes). An in vitro yeast two-hybrid assay indicated a significant, dose-dependent interaction between medaka estrogen receptor alpha (ERalpha) and coactivator TIF2 upon treatment with 6:2 FTOH, 8:2 FTOH or 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-nonadecafluoro-1-decanol (NFDH). The relative ranks of tested chemicals on the estrogenic effects for medaka ERalpha descended in the order of estradiol-17beta (100)>>6:2 FTOH (0.16)>NFDH (0.016)>8:2 FTOH (0.0044). In contrast, no interaction with the ERalpha was observed upon treatment with perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDA) or perfluoroundecanoic acid (PFUnDA). Expression analysis of hepatic vitellogenin (VTG) protein showed estrogenic potentials with, 6:2 FTOH and 8:2 FTOH, indicative of the induction of VTG synthesis in the livers of male medaka. We also investigated mRNA expression levels of two ER subtypes (ERalpha and beta) and two VTGs (VTG I and VTG II) in the livers of male medaka following exposure to FTOHs. Quantitative real-time polymerase chain reaction analyses revealed that hepatic ERalpha, VTG I, and VTG II mRNA responded rapidly to FTOHs such as 6:2 FTOH and 8:2 FTOH after 8-h exposure, whereas no effects of these compounds on ERbeta mRNA transcription were observed. These results from both in vitro and in vivo assays strongly suggest that certain FTOHs, such as 6:2 FTOH and 8:2 FTOH, induce hepatic VTG through activation of ERalpha in male medaka.


Innate Lymphoid Cells: Role in Immune Regulation and Cancer.
Immune regulation is composed of a complex network of cellular and molecular pathways that regulate the immune system and prevent tissue damage. It is increasingly clear that innate lymphoid cells (ILCs) are also armed with immunosuppressive capacities similar to well-known immune regulatory cells (i.e., regulatory T cells). In cancer, immunoregulatory ILCs have been shown to inhibit anti-tumour immune response through various mechanisms including: (a) direct suppression of anti-tumour T cells or NK cells, (b) inhibiting T-cell priming, and (c) promoting other immunoregulatory cells. To provide a framework of understanding the role of immunosuppressive ILCs in the context of cancer, we first outline a brief history and challenges related to defining immunosuppressive ILCs. Furthermore, we focus on the mechanisms of ILCs in suppressing anti-tumour immunity and consequentially promoting tumour progression.


The role of sodium and potassium in insulin secretion from rabbit pancreas.
1. Insulin secretion from pieces of rabbit pancreas incubated in vitro was studied in media of different ionic composition and in response to different substances added to the media.2. Experiments were performed which demonstrated that a sodium pump played a role in insulin secretion and that inhibition of the pump by ouabain, or by the omission of extracellular potassium, stimulated insulin secretion.3. A rise in extracellular potassium concentration stimulated insulin secretion independently of changes in the osmolarity or sodium or chloride concentration of the incubation medium.4. The role of extracellular sodium in insulin secretion was investigated. Extracellular sodium was a pre-requisite for insulin secretion stimulated by glucose, glucagon, L-leucine, tolbutamide, potassium or ouabain.5. The presence of 3.3 mM glucose in the incubation medium was not essential for the stimulation of insulin secretion by L-leucine, tolbutamide or ouabain. Glucagon did not stimulate insulin secretion in the presence of 3.3 mM glucose but did so in the presence of 16.5 mM glucose.6. The results obtained in these experiments suggested that a transmembrane sodium flux probably in the beta cell was a fundamental event in the stimulation of insulin secretion by diverse stimuli.


Ecological restoration is not sufficient for reconciling the trade-off between soil retention and water yield: A contrasting study from catchment governance perspective.
Ecological restoration program (ERP) is widely recognized as an effective measure to combat land degradation and improve environmental quality. However, inappropriate ERPs lead to trade-offs between soil retention and water yield as well as conflicts of soil and water resources between the midstream and the downstream of catchment. This study aims to assess the efficiency of ERPs in soil erosion control and identify the trade-offs between soil retention and water yield through the lens of runoff and sediment regimes in contrasting catchments of the Loess Plateau (LP) and the Karst Plateau (KP). Although favorable climate and rapid vegetation restoration substantially reduced water erosion in both these areas, the hydrological responses were not the same because of climate differences. In the arid LP, water and energy variables correlated closely with vegetation cover. Excessive afforestation programs in drylands increased vegetation transpiration and soil evaporation, further exhausting soil water resources, and eventually causing water yield reduction. However, soil and water conservation programs (SWCPs) in the humid KP reduced sediment yield substantially, and the runoff remained stable. Significant runoff reduction in the midstream of the Yellow River aggravated water scarcity and threatened the downstream water demand. Meanwhile, sediment load decline in the LP and the KP impacted sediment deposition in the downstream and estuary formation. From the perspective of integrated catchment governance, human interventions including ERP and SWCP should be more sustainable and consider not only the target process at the local scale (intracoupling effect), but also unprecedented non-target process at the regional scale (telecoupling effect). In addition, it should allow for the supply-demand balance of competing soil and water resources to achieve the coordinated development of resources, environment, and production.


Re-evaluating the relevance of ancestral shared synteny as a tool for crop improvement.
In addition to the Arabidopsis and rice genomic sequences, numerous expressed sequence tags (ESTs) and sequenced tag sites are now available for many species. These tools have made it possible to re-evaluate the extent of synteny and collinearity not only between Arabidopsis and related crops or between rice and other cereals but also between Arabidopsis and rice, between Arabidopsis and other dicots, and between cereals other than rice. Major progress in describing synteny relies on statistical tests. Overall, the data point to the occurrence of ancestral genome fragments in which a framework of common markers can be recognised. Micro-synteny studies reveal numerous rearrangements, which are likely to complicate map-based cloning strategies that use information from a model genome.


α-Hydroxylation of α,α-Disubstituted N-tert-Butanesulfinyl Ketimines with Molecular Oxygen: Stereoselective Synthesis of α-Tertiary Hydroxyimines.
α-Tertiary hydroxyimines were stereoselectively synthesized from enantioenriched N-tert-butanesulfinyl ketimines using potassium tert-butoxide, molecular oxygen, and trimethyl phosphite. The stereoselective hydroxylation of acyclic ketimines bearing two sterically similar α-substituents was achieved by controlling the geometry of the metalloenamine intermediates and the facial selectivity of hydroxylation. The synthetic utility of the resulting α-tertiary hydroxyimines was demonstrated through the successful diastereoselective synthesis of highly substituted β-amino alcohols.


Improvement of chemical analysis of antibiotics. XII. Simultaneous analysis of seven tetracyclines in honey.
An analytical system for the simultaneous determination of residual oxytetracycline, tetracycline, chlortetracycline, doxycycline, methacycline, demethylchlortetracycline and minocycline in honey has been established by a combination of simple thin-layer chromatographic (TLC) and precise high-performance liquid chromatographic (HPLC) methods. In this system, screening by TLC can detect tetracyclines (TCs) at a level of 0.1 ppm in honey without the need for special equipment, and the quantitative method by HPLC can determine TCs with good recovery (83.7-99.6%) and coefficient variation (0.9-4.3%).


Development and initial validation of the Miranda vocabulary scale.
Miranda vocabulary forms the essential foundation for Miranda comprehension and subsequent decisions to exercise or waive Miranda rights. The purpose of the current study is the development of the Miranda Vocabulary Scale (MVS), designed to evaluate key vocabulary words found in Miranda warnings and waivers across American jurisdictions. A preliminary list of MVS words was refined by expert ratings and by each word's discriminability between failed and good Miranda comprehension. Miranda and other measures were collected at multiple sites on 376 pretrial defendants. With further refinements, the MVS is composed of 36 words with excellent scale homogeneity and interrater reliability (r = .99). It also demonstrated good convergent and discriminant validity for cognitive abilities and psychological impairment.


Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: A cost-effectiveness analysis.
Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I.


Multi-residue method for determination of selected neonicotinoid insecticides in honey using optimized dispersive liquid-liquid microextraction combined with liquid chromatography-tandem mass spectrometry.
The objective of this study was to develop analytical method based on optimized dispersive liquid-liquid microextraction (DLLME) as a pretreatment procedure combined with reversed phase liquid chromatographic separation on C18 column and isocratic elution for simultaneous MS/MS determination of selected neonicotinoid insecticides in honey. The LC-MS/MS parameters were optimized to unequivocally provide good chromatographic separation, low detection (LOD, 0.5-1.0 μg kg(-1)) and quantification (LOQ, 1.5-2.5 μg kg(-1)) limits for acetamiprid, clothianidin, thiamethoxam, imidacloprid, dinotefuran, thiacloprid and nitenpyram in honey samples. Using different types (chloroform, dichloromethane) and volumes of extraction (0.5-3.0 mL) and dispersive (acetonitrile; 0.0-1.0 mL) solvent and by mathematical modeling it was possible to establish the optimal sample preparation procedure. Matrix-matched calibration and blank honey sample spiked in the concentration range of LOQ-100.0 μg kg(-1) were used to compensate the matrix effect and to fulfill the requirements of SANCO/12495/2011 for the accuracy (R 74.3-113.9%) and precision (expressed in terms of repeatability (RSD 2.74-11.8%) and within-laboratory reproducibility (RSDs 6.64-16.2%)) of the proposed method. The rapid (retention times 1.5-9.9 min), sensitive and low solvent consumption procedure described in this work provides reliable, simultaneous, and quantitative method applicable for the routine laboratory analysis of seven neonicotinoid residues in real honey samples.


Revealing the production process of Joaquín Albarrán's Les Tumeurs de la Vessie 125 years after its writing.
Investigate how in 1891 Joaquín Albarrán organised and wrote his Les Tumeurs de la Vessie, a manuscript printed by Georges Steinheil in 1892. An analysis was conducted of the manuscript that compiles the casuistry set forth in the work, which helps us understand his production process. The contents of the text are analysed, revealing the originality and value of the text in the manuscript. The book describes the author's personal histopathology findings from surgical and autopsied cases in Necker Hospital between 1868 and 1891: 28 numbered autopsy specimens and 67 identified by the patient's name (or, in lieu thereof, the physician's name, bed, ward and date of surgery). The notebook also contains the preliminary design of a number of photomicrographs printed in the book. Histopathology data are provided on the classification of bladder cancer, the pathway of lymphocytic spread, the genesis of cancer, tumoural heterogeneity and a number of original descriptions (squamous cell carcinoma, Von Brunn nests). Other notable clinical concepts include diagnostic symptomatology, prognosis assessment, extirpation by vesical height (with primary closure of the bladder and abdominal wall), the role of nascent endoscopic tumour extirpation and the experimental development of radical cystectomy with urinary diversion. Joaquín Albarrán analysed his experience and that of professors Reverdin, Guyon and Horteloup. He reviewed autopsies and surgical specimens from patients and performed the histopathology study in each case. The main original observations from the work are discussed.


Printable ion-gel gate dielectrics for low-voltage polymer thin-film transistors on plastic.
An important strategy for realizing flexible electronics is to use solution-processable materials that can be directly printed and integrated into high-performance electronic components on plastic. Although examples of functional inks based on metallic, semiconducting and insulating materials have been developed, enhanced printability and performance is still a challenge. Printable high-capacitance dielectrics that serve as gate insulators in organic thin-film transistors are a particular priority. Solid polymer electrolytes (a salt dissolved in a polymer matrix) have been investigated for this purpose, but they suffer from slow polarization response, limiting transistor speed to less than 100 Hz. Here, we demonstrate that an emerging class of polymer electrolytes known as ion gels can serve as printable, high-capacitance gate insulators in organic thin-film transistors. The specific capacitance exceeds that of conventional ceramic or polymeric gate dielectrics, enabling transistor operation at low voltages with kilohertz switching frequencies.


Splenic injury--a prospective multicentre diagnostic study.
One hundred and forty-seven patients with splenic injury were entered in a prospective multicentre study including 18 hospitals. The diagnosis was made by scintigraphy in 55 patients, ultrasonography in 51 and computed axial tomography in 31. Exploratory laparotomy was performed in 52 patients, in 23 of these after a positive peritoneal lavage. Splenic injury was found in 33 per cent of the ultrasound examinations, indicated in another 20 per cent and not indicated in 16 per cent. In 31 per cent increased intraperitoneal effusion was the only finding. There was a tendency towards an underestimation of the injury by ultrasonography. Peritoneal lavage was positive in all examinations.


Evolutionary conservation and association of SPARC with the basal lamina in Drosophila.
SPARC (secreted protein, acidic, rich in cysteine, also called BM40 and osteonectin) is a multifunctional calcium-binding glycoprotein whose modular organization has been highly conserved between invertebrates and vertebrates, indicating a conservation of function during metazoan evolution. Genome analysis has revealed a single copy of the DrosophilaSPARC ( dSPARC) gene. As a first step towards investigating the function of SPARC in Drosophila, we examined its spatiotemporal distribution during development. During embryogenesis, dSPARC mRNA transcripts are restricted to mesoderm derivatives, hemocytes, and the fat body. Immunostaining with anti- DrosophilaSPARC antibodies indicates that dSPARC secreted by the hemocytes and fat body cells is concentrated in basal laminae surrounding internal organs. During oogenesis, dSPARC transcripts are restricted to the somatic cells of the germarium and follicles. Consistent with embryonic development, the resultant protein is concentrated in basal laminae. Mutations in type IV collagen are associated with a dramatic decrease in dSPARC protein immunostaining in hemocytes. The data suggest that the production and assembly of dSPARC in the basal lamina is dependent on type IV collagen, and raise the possibility that dSPARC and type IV collagen interactions are a prerequisite to the assembly and structural integrity of basal laminae in Drosophila.


Longitudinal myocardial function is more compromised in cardiac syndrome X compared to insignificant CAD: Role of stress echocardiography and calcium scoring.
The aim of this study was to assess the nature of myocardial dysfunction in the cardiac syndrome X (CSX) and insignificant coronary artery disease (ICAD) using dobutamine stress echocardiography (DSE) and coronary calcium scoring (CAC). We prospectively studied 35 consecutive patients who complained of exertional angina, had ≥1 mm ST shift on exercise stress test but normal or no obstructive CAD (<50%) on angiography. Patients were divided into CSX (n = 27) with normal arteries and ICAD (n = 8) with insignificant stenosis. CSX patients had more females, lower calcium score and less prevalent cardiac risk factors compared to ICAD (p < 0.05 for all). At peak stress, MAPSE and TAPSE failed to increase in both groups. LV septal and lateral s' increased in the two groups but the increment increase was less in CSX than ICAD (p < 0.05) while other diastolic indices did not differ between groups (p > 0.05 for all). CAC correlated modestly with LV and RV systolic velocities: septal s' (r = -0.65, p < 0.001) lateral s' (r = -0.35, p = 0.04) and right s' (r = -0.53, p = 0.005) in CSX, while in ICAD patients only with RV s' (r = -0.58, p = 0.02). On multivariate model, only septal s' OR 1.816 (1.1090-3.820, p = 0.04) proved the most powerful independent predictor of CAC. Compromised LV longitudinal systolic velocities were more pronounced and calcium score as a surrogate for atherosclerosis was lower in CSX than ICAD. These findings strengthen the evidence for different pathogenesis of CSX compared to ICAD, with microvascular disease in the former and calcification in the latter.


Diagnostic and therapeutic evaluation of multiple choroidal granulomas in a patient with confirmed sarcoidosis using enhanced depth imaging optical coherence tomography.
Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.


Is there any relation between umbilical artery and vein diameter and estimated fetal weight in healthy pregnant women?
The aim of this study was to investigate the relation between umbilical vessel diameter and estimated fetal weight (EFW) and other fetal biometric parameters, and to assess the role of umbilical vessel diameter in prediction of EFW. Umbilical vein/umbilical artery (UV/UA) ratio and its relation to EFW were also examined. A prospective study was designed to assess the sonographic diameter of UA and UV in 720 low-risk pregnant women at 20-40 weeks' gestation. Fetal biometry, EFW, and umbilical vessel measurements were performed. There were strong correlations between umbilical vessel diameter versus gestational age and EFW. Umbilical vessel diameters increased linearly up to 34 weeks, after which they plateaued. No relation was found between EFW versus UV/UA ratio and gestational age versus UV/UA. Based on these findings, it is not possible at present to recommend the use of umbilical vessel diameters for prediction of EFW after 34 weeks, but it may be helpful under 34 weeks. UV/UA ratio is not useful for prediction and management of complicated pregnancies.


[Optimization of ostheogenesis with the use of vascularized periosteal-cortical autotransplants in patients with false joints of long bones].
The issue analyzes the use of free revascularizable or rotatable periosteal-cortical autotransplants as an additional source of ostheogenesis in patients with false joints of long tubular bones. The experience of treatment of 58 patients was summarized. The terms of fracture consolidation was similar to that after non-complicated fractures of the same localization.


Musa acuminata as electroporation model.
Electrochemotherapy (ECT) and Irreversible electroporation (IRE) are cancer treatments based on electric field distribution in tissues. Solanum tuberosum (potato tissue) phantom is known to mimic changes in the electrical conductivity that occur in animal tissues during electroporation (EP). Electric field distribution is assessed through enzymatic staining. However, the 24-h wait for this assessment could slow agile response scenarios. We developed and validated the Musa acuminata (cavendish banana) conductivity model, which quickly evaluates EP by tissue staining. We investigated the frequency response of the tissue using impedance spectroscopy analysis, conductivity changes, and enzymatic staining. We optimized three usual EP models: adapted Gompertz, smoothed Heaviside, and the sigmoid or logistic function. We found dielectric parameters in banana tissue similar to those in potato (electrical conductivity of 0.035 S/m and relative permittivity of 4.1×104). The coefficients of determination R2 were 99.94% (Gompertz), 99.85% (Heaviside), and 99.58% (sigmoid). The sigmoid and Heaviside functions described the calibration and validation electric currents with 95% confidence. We observed the electroporated areas in bananas 3h30m after EP. Staining was significant after 450 V/cm. The conductivity model of Musa acuminata suits treatment planning, hardware development, and training scenarios. Banana phantom supports the 3Rs practice and is a reliable alternative for potato in EP studies.


First interlaboratory test for the detection of Alaria spp. mesocercariae in meat samples using the Alaria spp. mesocercariae migration technique (AMT).
Emerging and re-emerging zoonotic diseases affect both public and animal health and require the development and contemporary implementation of suitable detection methods. A growing number of findings of the mesocercarial stage of the digenean trematode Alaria alata in game inhabiting wetlands have necessitated the development of a specific detection method. With the Alaria spp. mesocercariae migration technique (AMT), a specific and sensitive detection method is now available. To make the method accessible to the official controls, method validation is necessary. In this context, interlaboratory tests (IT) are a key factor to demonstrate both (1) the suitability of the respective method and (2) the reference materials. In the first IT performed on this issue, 15 laboratories from nine German federal states took part. Every lab received two negative and four positive standard samples each as well as a standardized examination device for AMT, and a standard operating procedure. All participating laboratories showed very good results in terms of qualitative analysis: 96.7 % of the samples were assessed correctly positive or negative. An analysis of the qualitative performance shows that 263 (58.4 %) of 450 mesocercariae that were inserted in the meatballs were identified by the participants, and 5 (33.3 %) out of 15 labs were able to count at least 70 % of the Alaria spp. mesocercariae. A direct comparison with the results of the German Trichinella IT, which were conducted since 2004, shows that the overall sensitivity of the AMT is even higher than that registered for the reference method for Trichinella detection (e.g. 93 % in 2010). Also, in terms of quantitative analysis, AMT stands up to the comparison with the results from the German Trichinella IT. The refinement of the implementation protocol of this innovative, easy-to-use and cost-effective method harbours great potential for further optimization and successful implementation in the official controls.


The catecholamine-containing tubero-infundibular system and the control of luteinizing hormone release in the rabbit.
As determined by fluorescence histochemistry, the distribution of catecholamine-containing neurons in the hypothalamus of the female rabbit is similar to that seen in the rat. The fluorescence appearance of the hypothalamus was not appreciably different from normal at 0.25, 1, 4 or 24 h after mating, but in animals in which the synthesis of catecholamines was inhibited by the administration of the tyrosine hydroxylase inhibitor, H44/68, the number of fluorescent neurons seen in the nucleus periventricularis arcuatus following copulation was markedly reduced. However, the concentrations of luteinizing hormone (LH) in serum and in the pituitary glands of mated and unmated animals treated with H44/68 were not significantly different from those found in the corresponding control animals. This, together with the fact that ovulation followed mating in drug-treated rabbits suggests that a normal level of catecholamines in the tubero-infundibular system is not essential for the secretion of the amount of LH necessary for ovulation.


The nature and way of root adaptation of juvenile woody plants Sorbus and Pyrus to drought.
The functional root traits of Pyrus pyraster (L.) Burgsd. and Sorbus domestica L. during early growth stages were evaluated. The aim of the study was to identify the functional traits of root systems that determine the adaptability of these woody species to drought conditions. The experiment was carried out under the controlled environment of a growth chamber. The root systems were analyzed using WinRhizo software. Several functional root traits were identified, including specific root length, root surface area, root length, root volume, root-to-shoot mass ratio (R:S), fine root (ϕ ˂ 2 mm) volume, coarse root (ϕ > 2 mm) volume, and fine-to-coarse root volume ratio (F/C). In drought, P. pyraster maintained the absorptive root surface unchanged, when increased the volume of the fine root fraction. The different strategy of adaptation to drought has been confirmed for S. domestica, which accumulated more dry mass in the root system in comparison to aboveground organs (significant increase of R:S ratio). The functional root traits analyzed here were species-dependent. The key functional traits that indicate the responses of studied tree taxa to drought conditions include root thickening, F/C, and R:S. Increased values of these parameters indicate the investment of the plant towards root extension. A higher proportion of fine roots increases the absorbing surface of the root system, thereby promoting water uptake from the soil.


Changes in cigarette consumption and drinking outcomes: findings from Project MATCH.
Individuals undergoing treatment for alcohol use disorders smoke at rates that exceed those reported in the general population, and most patients will continue to smoke after treatment completion. A growing body of research indicates that quitting smoking is associated with better alcoholism treatment outcomes. Studies that dichotomize participants into smokers and nonsmokers, however, may be overlooking the possibility that even decreases in cigarette consumption over time among continuing smokers may also be related to improved alcohol use outcomes. The purpose of this article was to examine the relationship between cigarette consumption and alcohol use outcomes using data from Project MATCH. Smokers were divided into three groups according to whether their cigarette consumption decreased, increased, or remained constant from baseline to the 15-month follow-up. Results showed that smokers whose cigarette consumption decreased were significantly less likely to relapse to alcohol use than those whose consumption increased or remained unchanged. These findings suggest that even reductions in tobacco use may be associated with better drinking outcomes in alcoholism treatment.


Mefloquine, a new type of compound against schistosomes and other helminthes in experimental studies.
Up to date, schistosomiasis is still prevalent worldwide. It is estimated that more than 200 million individuals are infected, and 120 million suffer from clinical morbidity. Facing such huge cases of schistosomiasis, only heavy reliance on a single praziquantel for schistosomiasis control does not adapt and may promote the selection and spread of drug-resistant parasites. Therefore, it is an urgent need to develop the new antischistosomal drug. In 2008-2009, the antimalarial drug mefloquine, an arylaminoalcohol compound, has been found to be effective against schistosomes. According to the experimental studies, the deepest impression on the antischistosomal properties of mefloquine can be summarized as following points: (1) single dose of mefloquine possesses potential effect against three major species of schistosomes (Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum) infecting humans; (2) the drug displays similar effects against developing stages of juvenile and adult schistosomes, which are superior to that of artemisinins and praziquantel; (3) in vitro mefloquine exerts direct killing effect on juvenile and adult schistosomes, while in vivo, the efficacy of the drug is independent to host immune response, (4) mefloquine causes extensive and severe morphological, histopathological, and ultrastructural damage to adult and juvenile schistosomes, particularly, the worm tegument, musculature, gut, and vitelline glands of female worms are the key sites attacked by the drug; (5) combined treatment with mefloquine and praziquantel, or artemisinins shows synergistic effect against schistosome in experimental therapy,while in initially clinical trial, mefloquine in combination with artesunate also exhibits higher cure rates against schistosomiasis hematobia and schistosomiasis mansoni, and (6) several mefloquine-related arylmethanols exhibit potential effect against schistosomes in vivo, which is a useful clue helpful for development of new antischistosomal compound. In the present review, we have summarized the major results published in recent years, and the significance as well as the prospect for the future study of mefloquine have been discussed briefly.


Cloning and sequencing of a 16 kDa outer membrane protein gene of Pasteurella multocida P52.
The outer membrane proteins (OMPs) of Pasteurella multocida are potential immunogens. The 16 kDa OMP of P. multocida P52, serotype B:2, was identified as one of the major immunodominant antigens. The gene omp16, encoding a 16 kDa outer membrane protein, was amplified, cloned into a pBluescript SK(-) vector and sequenced. Complete sequence homology was observed between the 16 kDa OMP gene of P. multocida P52 (serotypes B:2) and P. multocida T16 (somatic serotype 3,4). This gene was distributed among different serotypes of P. multocida and found to localize in a 6.0 kb HindII fragment of the P. multocida genome.