Dataset on researcher's mobility by utilising bibliometric data: Case of Finland-based scholars for the duration of 2008-2018.
Scientific discoveries are the result of global collaboration and often the multidisciplinary nature of collaborations. A core element of these successful collaborations will materialise through a researcher's mobility in location and disciplinary focus. Researchers experience numerous opportunities to practice locational mobility throughout their careers as well as by conducting multidisciplinary research. Both changes have short- and long-term impacts on individual researchers and science, technology, and innovation systems that have an immediate interest for the public and private research and development funding mechanisms. With the advancement in data science tools and increasing computational capacities, we can use bibliometric data for calculating a researcher's mobility on location and a disciplinary focus over time. We looked at Finland as a case, and by incorporating analytical procedures, the processed data is capable of delivering insights on researcher mobility between cities over time as well as disciplinary change over time. This dataset can reveal hidden dynamics in the scholar's career progress. If combined with funding information and mission-oriented policies, the dataset can evaluate the long-lasting effect of instruments in mobilising researchers, steering research agendas, and consequently the resulting impacts.


Growth changes of general and dental health status in Taiwanese children from mixed to early permanent dentition.
For this study, the general and dental health status of 463 Taiwanese children aged 9 to 12 years was evaluated. There were statistically significant increases in all measurements from Hellman's dental developmental stages IIIA to IVA except for the maximum mandibular protrusive, right lateral, and left lateral movements. Maximum bite forces had diminished in stage IIIB. Boys had larger maximum bite forces and hand-grip forces than did girls after stage IIIC. The proportion of subjects with TMD signs or symptoms increased to 60% by stage IVA.


First do no harm: routine use of aminoglycosides in the operating room.
For decades aminoglycosides have been used routinely in intraocular surgery to prevent and treat endophthalmitis. However, as more and more studies are conducted, the reality is that these drugs are causing more harm than they are preventing. Summarized herein are the most recent studies concluding that even low-dose aminoglycosides can cause toxic retinal damage. The conclusion, with pertinent recommendations from the Johns Hopkins Hospital, Wilmer Eye Institute Infection Control Committee, is that the questionable benefit of use of aminoglycosides intraoperatively is not justified by the risk of injury.


C-low threshold mechanoafferent targeted dynamic touch modulates stress resilience in rats exposed to chronic mild stress.
Affiliative tactile interactions buffer social mammals against neurobiological and behavioral effects of stress. The aim of this study was to investigate the cutaneous mechanisms underlying such beneficial consequences of touch by determining whether daily stroking, specifically targeted to activate a velocity/force tuned class of low-threshold c-fiber mechanoreceptor (CLTM), confers resilience against established markers of chronic unpredictable mild stress (CMS). Adult male Sprague Dawley rats were exposed to 2 weeks of CMS. Throughout the CMS protocol, some rats were stroked daily, either at CLTM optimal velocity (5 cm/s) or outside the CLTM optimal range (30 cm/s). A third CMS exposed group did not receive any tactile stimulation. The effect of CMS on serum corticosterone levels, anxiety- and depressive-like behaviors in these three groups was assessed in comparison to a control group of non-CMS exposed rats. While stroking did not mitigate the effects of CMS on body weight gain, CLTM optimal velocity stroking did significantly reduce CMS-induced elevations in corticosterone following an acute forced-swim. Rats receiving CLTM optimal stroking also showed significantly fewer anxiety-like behaviors (elevated plus-maze) than the other CMS exposed rats. In terms of depressive-like behavior, whereas the same velocity-specific resilience was observed in a forced-swim test and social interaction test both groups of stroked rats spent significantly less time interacting than control rats, though they also spent significantly less time in the corner than non-stroked CMS rats. Together, these findings support the theory CLTMs play a functional role in regulating the physiological condition of the body.


Early mouse endoderm is patterned by soluble factors from adjacent germ layers.
Endoderm that forms the respiratory and digestive tracts is a sheet of approximately 500-1000 cells around the distal cup of an E7.5 mouse embryo. Within 2 days, endoderm folds into a primitive gut tube from which numerous organs will bud. To characterize the signals involved in the developmental specification of this early endoderm, we have employed an in vitro assay using germ layer explants and show that adjacent germ layers provide soluble, temporally specific signals that induce organ-specific gene expression in endoderm. Furthermore, we show that FGF4 expressed in primitive streak-mesoderm can induce the differentiation of endoderm in a concentration-dependent manner. We conclude that the differentiation of gastrulation-stage endoderm is directed by adjacent mesoderm and ectoderm, one of the earliest reported patterning events in formation of the vertebrate gut tube.


Targeted disruption of mouse fibroblast activation protein.
Human fibroblast activation protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein selectively expressed by fibroblastic cells in areas of active tissue remodeling, such as the embryonic mesenchyme, areas of wound healing, the gravid uterus, and the reactive stroma of epithelial cancers. Homologues of FAP have been identified in the mouse and Xenopus laevis. FAP is a dual-specificity enzyme that acts as a dipeptidyl peptidase and collagenase in vitro. To explore the role of FAP in vivo, Fap(-/-) mice were generated by homologous recombination. RNase protection analysis and reverse transcription-PCR confirmed the absence of full-length Fap transcripts in mouse embryonic tissues. No FAP protein was detected in Fap(-/-) animals by immunohistochemistry, and no FAP-specific dipeptidyl peptidase activity was found. We report that Fap(-/-) mice are fertile, show no overt developmental defects, and have no general change in cancer susceptibility.


Multiple-beam lateral-shear interferometer.
A Ronchi ruling is photographed through a phase object that deforms the grating lines. The object is displaced longitudinally, and a second exposure is made. After developing, the photographic plate is observed with a frequency-plane mask that cuts off all but one of the diffracted orders. A lateral-shear interferogram of the phase object is obtained in this way. The experiment may be carried out by making multiple exposures and by displacing the object through equal distances after each exposure. This will produce a multiple-beam lateral-shear interferogram, and the fringes become very sharp.


[The vectorcardiogram pattern of the athlete's heart (author's transl)].
In order to assess the vectorcardiographic pattern of the athlete's heart, we evaluated the vectorcardiograms of 17 professional footballers; the signs of ventricular hypertrophy were particularly studied. 9 athletes had left ventricular hypertrophy, 3 showed VCgraphic signs of combined ventricular hypertrophy and 5 had normal vectorcardiograms. In all athletes with left ventricular hypertrophy the initial forces had normal spatial orientation (I A left ventricular hypertrophy). Likely, the combined right ventricular hypertrophy explains these VCgraphic patterns. The QRS loop did not show abnormal morphology, only the high magnitude of the spatial maximum QRS vectors was significant for diagnosis of left ventricular hypertrophy. The increase of the cardiac volumes induced by training might explain the high magnitude of the QRS loop.


Impaired gustatory neophobia following traumatic brain injury in rats.
To investigate the function of the amygdala following traumatic brain injury (TBI), rats were tested on a gustatory neophobia task that is sensitive to amygdala and hippocampal damage. Rats were either injured at a moderate level of fluid percussion injury (2.1 atm) or surgically prepared but not injured (sham-injury). Seven days after injury (n = 8) or sham injury (n = 9), rats were habituated to the testing chamber without food items present for 30 min. All rats were then food deprived. Twenty-four hours later, rats were placed in the testing chamber for 30 min and allowed to eat freely from four dishes of different foods: rat chow, raisins, potatoes, and cookies. Results showed that injured and sham-injured rats did not differ in their ability to find hidden food, suggesting that TBI does not produce an enduring impairment of olfaction. There was also no difference in the total amount of food eaten between injured and sham groups (p > 0.05). The percentage of each type of food consumed did differ between the two groups with sham controls consuming more familiar food (rat chow) compared to the unfamiliar foods (p < 0.01). The injured animals distributed their eating evenly among the four foods with no particular preference for any one food (p < 0.05). This pattern of eating behavior in injured animals is similar to animals that have lesions to both the hippocampus and amygdala (Sutherland and McDonald, 1990). Therefore, the results of this experiment suggest that, in addition to the hippocampus, the amygdala may also contribute to the behavioral changes observed following TBI.


Efficacy, Safety, and Role of Antiplatelet Drugs in the Management of Acute Coronary Syndrome: A Comprehensive Review of Literature.
Acute coronary syndrome (ACS) is a complex condition characterized by myocardial ischemia or infarction which can lead to significant morbidity and death. Antiplatelet drugs play a crucial role in the management of ACS and have been shown to minimize the incidence of significant adverse cardiovascular events and recurrent myocardial infarction (MI). This comprehensive literature review is intended to summarize current information on the effectiveness, safety, and function of frequently used antiplatelet medications in treating ACS. Aspirin, clopidogrel, prasugrel, ticagrelor, abciximab, tirofiban, dipyridamole, cilostazol, and novel antiplatelets are included in the review. Aspirin's effectiveness as a first-line antiplatelet medication in ACS is well established. It has significantly lowered the risk of serious adverse cardiovascular events. Clopidogrel, prasugrel, and ticagrelor are P2Y12 receptor inhibitors found to lower the incidence of recurrent ischemia episodes in ACS patients. Using glycoprotein IIb/IIIa inhibitors such as abciximab, tirofiban, and eptifibatide is effective in managing ACS, especially in high-risk patients. Dipyridamole effectively reduces the risk of recurrent ischemic events in patients with ACS, particularly when used with aspirin. Cilostazol, a phosphodiesterase III inhibitor, has also been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with ACS. Antiplatelet drugs' safety in managing ACS has also been well established. Aspirin is generally well-tolerated with a low risk of adverse effects, although the risk of bleeding events, particularly gastrointestinal bleeding, cannot be eliminated. The P2Y12 receptor inhibitors have been associated with a small increase in the risk of bleeding events, particularly in patients with a high risk of bleeding. The glycoprotein IIb/IIIa inhibitors are associated with a higher risk of bleeding than other antiplatelet drugs, especially in high-risk patients. To summarize, antiplatelet drugs play a crucial role in the management of ACS, and the efficacy and safety of these drugs have been well-established in the literature. The choice of antiplatelet drugs will depend on the patient's risk factors, including age, comorbidities, and bleeding risk. The novel antiplatelets may offer new therapeutic options for managing ACS, and further studies are needed to determine their role in managing this complex condition.


Kinetic characterization and inhibition of the rat MAB elastase-2, an angiotensin I-converting serine protease.
An elastase-2 has been recently described as the major angiotensin (Ang) II-forming enzyme of the rat mesenteric arterial bed (MAB) perfusate. Here, we have investigated the interaction of affinity-purified rat MAB elastase-2 with some substrates and inhibitors of both pancreatic elastases-2 and Ang II-forming chymases. The Ang II precursor [Pro 11 -D-Ala 12]-Ang I was converted into Ang II by the rat MAB elastase-2 with catalytic efficiency of 8.6 min-1 microM-1, and the chromogenic substrates N-succinyl-Ala-Ala-Pro-Leu-p-nitroanilide and N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide were hydrolyzed by the enzyme with catalytic efficiencies of 10.6 min-1 microM-1 and 7.6 min-1 microM-1, respectively. The non-cleavable peptide inhibitor CH-5450 inhibited the rat MAB elastase-2 activities toward the substrates Ang I (IC50 = 49 microM) and N-succinly-Ala-Ala-Pro-Phe-p-nitroanilide (IC 50 = 4.8 microM), whereas N-acetyl-Ala-Ala-Pro-Leu-chloromethylketone, an effective active site-directed inhibitor of pancreatic elastase-2, efficiently blocked the Ang II-generating activity of the rat MAB enzyme (IC 50 = 4.5 microM). Altogether, the data presented here confirm and extend the enzymological similarities between pancreatic elastase-2 and its rat MAB counterpart. Moreover, the thus far unrealized interaction of elastase-2 with [Pro 11-D-Ala 12]-Ang I and CH-5450, both regarded as selective for chymases, suggests that evidence for the in vivo formation of Ang II by chymases may have been overestimated in previous investigations of Ang II-forming pathways.


Metal-Organic Pt(II) Hexagonal-Prism Macrocycles and Their Photophysical Properties.
In this work, we present the formation of two open-ended hexagonal-prism tubular macrocycles by the [6 + 12] self-assembly of the symmetric ∼120° organic ligand donor with ∼90° Pt(II) acceptor in a 1:2 ratio. The assembled structures were characterized by multinuclear NMR (1H NMR, 31P{1H} NMR, and 1H-1H COSY NMR), electrospray ionization mass spectrometry (ESI-TOF-MS), traveling wave ion mobility-mass spectrometry (TWIM-MS), and transmission electron microscopy. Molecular modeling was further conducted to get insight into their structured characteristics. We also examined their photophysical properties.


Overview of General and Discriminating Markers of Differential Microglia Phenotypes.
Inflammatory processes and microglia activation accompany most of the pathophysiological diseases in the central nervous system. It is proven that glial pathology precedes and even drives the development of multiple neurodegenerative conditions. A growing number of studies point out the importance of microglia in brain development as well as in physiological functioning. These resident brain immune cells are divergent from the peripherally infiltrated macrophages, but their precise in situ discrimination is surprisingly difficult. Microglial heterogeneity in the brain is especially visible in their morphology and cell density in particular brain structures but also in the expression of cellular markers. This often determines their role in physiology or pathology of brain functioning. The species differences between rodent and human markers add complexity to the whole picture. Furthermore, due to activation, microglia show a broad spectrum of phenotypes ranging from the pro-inflammatory, potentially cytotoxic M1 to the anti-inflammatory, scavenging, and regenerative M2. A precise distinction of specific phenotypes is nowadays essential to study microglial functions and tissue state in such a quickly changing environment. Due to the overwhelming amount of data on multiple sets of markers that is available for such studies, the choice of appropriate markers is a scientific challenge. This review gathers, classifies, and describes known and recently discovered protein markers expressed by microglial cells in their different phenotypes. The presented microglia markers include qualitative and semi-quantitative, general and specific, surface and intracellular proteins, as well as secreted molecules. The information provided here creates a comprehensive and practical guide through the current knowledge and will facilitate the choosing of proper, more specific markers for detailed studies on microglia and neuroinflammatory mechanisms in various physiological as well as pathological conditions. Both basic research and clinical medicine need clearly described and validated molecular markers of microglia phenotype, which are essential in diagnostics, treatment, and prevention of diseases engaging glia activation.


Multiphoton pi pulses.
Multiphoton excitation in a two-level system is exceedingly weak because of small multiphoton coupling strengths, large ac Stark shifts, and ionization. I will discuss a three-level system in which the ac Stark shift is greatly reduced and the multiphoton coupling strength is greatly enhanced over a two-level system, to such an extent that multiphoton pi pulses can be produced. I will also present two-electron calculations in a model potential, including ionization that shows a 12-photon pi pulse driven with 800-nm photons. This three-level configuration may provide the basis for an amplifying medium in the vacuum ultraviolet, as well as multiphoton adiabatic passage and innershell ionization.


Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: critical update and emerging trends.
Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors.


EEG-directed connectivity from posterior brain regions is decreased in dementia with Lewy bodies: a comparison with Alzheimer's disease and controls.
Directed information flow between brain regions might be disrupted in dementia with Lewy bodies (DLB) and relate to the clinical syndrome of DLB. To investigate this hypothesis, resting-state electroencephalography recordings were obtained in patients with probable DLB and Alzheimer's disease (AD), and controls (N = 66 per group, matched for age and gender). Phase transfer entropy was used to measure directed connectivity in the groups for the theta, alpha, and beta frequency band. A posterior-to-anterior phase transfer entropy gradient, with occipital channels driving the frontal channels, was found in controls in all frequency bands. This posterior-to-anterior gradient was largely lost in DLB in the alpha band (p < 0.05). In the beta band, posterior brain regions were less driving in information flow in AD than in DLB and controls. In conclusion, the common posterior-to-anterior pattern of directed connectivity in controls is disturbed in DLB patients in the alpha band, and in AD patients in the beta band. Disrupted alpha band-directed connectivity may underlie the clinical syndrome of DLB and differentiate between DLB and AD.


Neuro-Behçet's disease--rapidly reversible with early diagnosis and treatment.
Behçet's disease is an idiopathic multi-systemic, inflammatory disorder that may affect major organs, including the central nervous system. It is a clinical diagnosis, and a history of recurrent oral and genital ulcers should be elicited, especially in cases of unexplained uveitis with atypical neurological symptoms. We describe the rapid neurological recovery and neuroimaging changes following high-dose systemic corticosteroids in a 44-year-old man with recurrent oral ulcers, panuveitis, and acute neuro-Behçet's, presenting with meningoencephalitis. Early diagnosis with the aid of appropriate neuroimaging and immunosuppressive therapy prevented long-term neurological complications. Appropriate neuroimaging can facilitate early diagnosis and treatment, and provide prognostic information on neuro-Behçet's.


PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core.
In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV) replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc) protein and dimethylates arginine residues within the arginine-rich domain (ARD) of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI) and R156 (outside ARDs) were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs), arginine methylation and ubiquitination.


Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase.
CSBP p38 is a mitogen-activated protein kinase that is activated in response to stress, endotoxin, interleukin 1, and tumor necrosis factor. Using a catalytically inactive mutant (D168A) of human CSBP2 as the bait in a yeast two-hybrid screen, we have identified and cloned a novel kinase which shares approximately 70% amino acid identity to mitogen-activated protein kinase-activated protein kinase (MAPKAP kinase)-2, and thus was designated MAPKAP kinase-3. The binding of CSBP to MAPKAP kinase-3 was confirmed in vitro by the precipitation of epitope-tagged CSBP1, CSBP2, and CSBP2(D168A) and endogenous CSBP from mammalian cells by a bacterially expressed GST-MAPKAP kinase-3 fusion protein and in vivo by co-precipitation of the epitope-tagged proteins co-expressed in HeLa cells. MAPKAP kinase-3 was phosphorylated by both CSBP1 and CSBP2 and was then able to phosphorylate HSP27 in vitro. Treatment of HeLa cells with sorbitol or TNF resulted in activation of CSBP and MAPKAP kinase-3 and activation of MAPKAP kinase-3 could be blocked by preincubation of cells with SB203580, a specific inhibitor of CSBP kinase activity. These data suggest that MAPKAP kinase-3 is activated by stress and cytokines and is a novel substrate of CSBP both in vitro and in vivo.


Effects of anticonvulsants on K+-induced excitation and on penicillin-induced seizures.
Excitation induced in mice by intracerebral injection of KCl was antagonized by prior i.p. injection of phenytoin, chlordiazepoxide or phenobarbital, but was not significantly affected by muscimol, valproate, ethosuximide or trimethadione. In contrast, seizures induced by intracerebral injection of benzyl penicillin were antagonised by chlordiazepoxide, phenobarbital, valproate, ethosuximide and trimethadione, but not by phenytoin or muscimol. Implications with regard to mechanisms of action of the anticonvulsants and of penicillin are discussed.


Uptake route and resulting toxicity of silver nanoparticles in Eisenia fetida earthworm exposed through Standard OECD Tests.
Despite the increasing interest in silver nanoparticles toxicity still few works dealt with the hazards of nanosized Ag in soils (either dissolved in pore water or coupled to colloids) although disposal of biosolids in landfills has been reported as the major source of silver nanoparticles in terrestrial environments. Presently, Eisenia fetida was used to assess the toxicity of 5 nm sized PVP-PEI coated silver nanoparticles in soil through the implementation of different exposure media Standard Toxicity Tests (Paper Contact and Artificial Soil -OECD-207- and Reproduction -OECD-222- Tests) together with cellular biomarkers measured in extruded coelomocytes. In order to decipher the mode of action of silver nanoparticles in soil and the uptake routes in earthworms, special attention was given to the Ag accumulation and distribution in tissues. High Ag accumulation rates, weight loss, and mortality due to the disruption of the tegument could be the result of a dermal absorption of Ag ions released from silver nanoparticles (Paper Contact Test). However, autometallography showed metals mainly localized in the digestive tract after Artificial Soil Test, suggesting that Ag uptake occurred mostly through soil ingestion. That is, silver nanoparticles attached to soil colloids seemed to be internalized in earthworms after ingestion of soil and transferred to the digestive gut epithelium where at high doses they have triggered severe effects at different levels of biological complexity.


Sabotaging one's own medical care. Prevalence in a primary care setting.
This study determines the prevalence of medically self-sabotaging behaviors reported by patients in a primary care setting. A 19-item self-report survey was completed by patients on-site at the Family Medicine Clinic, University of Oklahoma College of Medicine-Tulsa. Four hundred eleven consecutive male and female patients were seen for nonemergent care. Each of the 19 items was endorsed by at least 1 respondent. The most commonly endorsed self-sabotaging behaviors were not seeking medical care when needed (37.2%) and not taking a prescribed medication (25.1%). Significantly more women (26.4%) than men (17.5%) reported not taking a prescribed medication (P < .05). After excluding these 2 commonly endorsed items, 27 (6.6%) of the respondents reported at least 1 other self-sabotaging behavior, with most indicating 1 (63.0%) or 2 (22.2%); the remaining 4 individuals reported 4 to 12 behaviors. Significantly more men (4.8%) than women (0.6%) reported not following instructions from a physician or nurse to prolong illness (P < .05). A few patients (6.6%) seen in a primary care university outpatient clinic acknowledged the active and intentional sabotage of their medical care, beyond not taking a prescribed medication or seeking medical care when needed. This is probably a conservative estimate and indicates that medical care is actively compromised by a few patients.


Aging and work: how do SOC strategies contribute to job performance across adulthood?
The authors examined the impacts of selection, optimization, and compensation (SOC) strategies-elective selection, loss-based selection, optimization, and compensation-on job performance across adulthood. A cross-sectional survey (Study 1, N=355) and a 5-day experience sampling study (Study 2, N=87) were conducted to assess Chinese insurance sales workers' global and momentary employment of SOC strategies at work and compare the effectiveness of these strategies in predicting their job performance. Study 1 revealed that the use of compensation predicted higher performance maintenance among older workers, whereas the use of elective selection contributed positively to sales productivity for both age groups, with stronger association for younger workers. Study 2 demonstrated that the positive impact of SOC strategies on global and momentary measures of job performance differed across tasks with various difficulty levels. When the task was perceived as highly difficult, older workers' greater use of elective selection predicted higher self-rated task performance; however, the positive association was weaker among younger workers. Older workers' greater use of the 4 SOC strategies was positively associated with sales increases when the task was not difficult or moderately difficult, yet the relationship was negative when the task was highly difficult. A reverse pattern was observed among younger workers. This article contributes to the understanding of working adults' psychological adaptation to the process of aging and reveals the moderating role of task difficulty on the association between SOC strategies and performance outcomes.


Joint Hypermobility as a Potential Indicator of Marfan Syndrome and Ehlers-Danlos Syndrome.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder associated with the mutation of the FBN1 gene. Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders with similar clinical features to MFS that often requires genetic testing to confirm a diagnosis of an EDS subtype. MFS is diagnosed using the Ghent Nosology criteria, which screens for cardiovascular, musculoskeletal, integumentary, ocular, and pulmonary abnormalities. Though genetic testing has recently been increasingly emphasized in diagnosing MFS, it is not currently a mandatory component of the Ghent Nosology. We present the case of a nine-year-old male who presented with joint hypermobility of the shoulders, knees, and thumbs, and a family history of joint hypermobility in his 15-year-old brother. Genetic testing ruled out MFS, and the patient subsequently underwent testing for EDS, which further ruled out classical and hypermobile EDS. This case highlights the importance of supplementing the Ghent Nosology criteria with genetic testing in diagnosing MFS because it can aid in generating a differential diagnosis and optimizing diagnostic accuracy.


Reversion of tumor hepatocytes to normal hepatocytes during liver tumor regression in an oncogene-expressing transgenic zebrafish model.
Tumors are frequently dependent on primary oncogenes to maintain their malignant properties (known as 'oncogene addiction'). We have previously established several inducible hepatocellular carcinoma (HCC) models in zebrafish by transgenic expression of an oncogene. These tumor models are strongly oncogene addicted, as the induced and histologically proven liver tumors regress after suppression of oncogene expression by removal of a chemical inducer. However, the question of whether the liver tumor cells are eliminated or revert to normal cells remains unanswered. In the present study, we generated a novel Cre/loxP transgenic zebrafish line, Tg(fabp10: loxP-EGFP-stop-loxP-DsRed; TRE: CreERT2) (abbreviated to CreER), in order to trace tumor cell lineage during tumor regression after crossing with the xmrk (activated EGFR homolog) oncogene transgenic line, Tg(fabp10: rtTA; TRE: xmrk; krt4: EGFP) We found that, during HCC regression, restored normal liver contained both reverted tumor hepatocytes (RFP+) and newly differentiated hepatocytes (GFP+). RNA sequencing (RNA-seq) analyses of the RFP+ and GFP+ hepatocyte populations after tumor regression confirmed the conversion of tumor cells to normal hepatocytes, as most of the genes and pathways that were deregulated in the tumor stages were found to have normal regulation in the tumor-reverted hepatocytes. Thus, our lineage-tracing studies demonstrated the potential for transformed tumor cells to revert to normal cells after suppression of expression of a primary oncogene. This observation may provide a basis for the development of a therapeutic approach targeting addicted oncogenes or oncogenic pathways.


Two-photon induced photopolymerization using photoinitiator with an intramolecular radical quenching moiety for nanolithography.
We have investigated the photoinitiating properties of the photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-(4-methoxy-benzyl)-carbazole (BNMBC), which has an intramolecular radical quenching group "p-methoxybenzyl," in the substrate lines fabrication of two-photon induced photopolymerization (TPIP). Another photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-benzyl-carbazole (BNBC) with similar chemical structure but not radical quenching group was studied for comparison. Their photopolymerization properties were studied with resins in which BNBC and BNMBC were used as photoinitiators with a molar ratio of 0.02%, respectively. The linewidth of polymer lines fabricated by TPIP of the photoresist that contained BNMBC could be decreased to 65% of those using BNBC. Besides, we introduced a radical quencher, phenyl methyl ether (PhOCH3), to BNBC and further studied the photopolymerization properties by using BNBC, BNBC/PhOCH3 and BNMBC as photoinitiators with a molar ratio of 0.1%. The results further indicated that BNMBC was effective to confine the radical diffusion in polymerization due to the radical quenching effect of moiety. This intramolecular radical quenching moiety exhibited more effective confining effect of radical diffusion compared to the intermolecular radical quencher PhOCH3. Furthermore, arbitrary complex three-dimensional (3D) microstructure was achieved using the photoresist with photoinitiator BNMBC. The approach could open up broad prospect for improving the resolution in TPIP.


Capillary-Force-Pattern Formation of Indium-Zinc-Oxide Thin-Film Transistor.
Studies of the pattern-formation technique used with solution-processed oxide thin-film transistors (TFTs) continue to explore its uses as an efficient manufacturing method. However, research remains to be completed to achieve high performance and to apply the refined technique to various current industrial technologies. We studied the patterning technique of solution-processed indiumzinc-oxide (IZO) by using the capillary-force phenomenon, the method of controlling the pattern of the IZO semiconductor layer, and approaches to reducing problems such as the cracking that occurs during patterning. The device we fabricated was filled uniformly with droplets in the capillary-force pattern. It showed a high current-on/current-off ratio, high mobility, low threshold voltage, and low subthreshold slope. Consequently, this paper demonstrates a strategy that uses the capillary-forcepattern technique to exceed the performance of traditional fabrication techniques in managing the electrical properties of solution-processed oxide TFTs.


Gender differences in the temporal organization of proclactin (PRL) secretion: evidence for a sleep-independent circadian rhythm of circulating PRL levels- a clinical research center study.
Although a nocturnal rise in PRL secretion is well known, it has long been presumed to be evoked by sleep. To determine whether PRL secretion was driven by a sleep-independent circadian rhythm, we studied 12 men and 10 women using a constant routine protocol. Under the constant routine conditions of continuous semirecumbent wakefulness in constant indoor room light with hourly meals distributed throughout the day and night, a persistent circadian rhythm of PRL secretion was present in men and in women at the follicular and luteal phases of the menstrual cycle. Furthermore, the amplitude of this rhythm in women was significantly greater than that in men. The present data demonstrate the presence of a robust sleep-independent endogenous circadian rhythm of PRL secretion in humans. We hypothesize that this endogenous component of the circadian rhythm of PRL secretion together with those of body temperature, urine production, and cortisol, TSH, and melatonin secretion are driven by the central circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus.


Evaluating the psychometric properties of the Immunotherapy module of the MD Anderson Symptom Inventory.
Immunotherapies have revolutionized the treatment of various cancers, but little is known about their symptomatic toxicity. Assessing these symptoms is best accomplished by asking the patients themselves. However, such reports are subjective and may face challenges as bonafide scientific data. Demonstrating the validity of symptom assessment tools, mainly through the reduction of measurement errors, has the potential to improve patient care if these tools are widely adopted. To that end, we present herein the psychometric properties of the Immunotherapy for Early-Phase Trials module of the MD Anderson Symptom Inventory (MDASI-Immunotherapy EPT) in patients receiving various immunotherapies in early phase trials at a major cancer center. One hundred forty-five patients completed the inventory at baseline, with 85 of them also doing so after 9 weeks of treatment. The mean (±SD) age of the patients was 57.0±12.9 years. Also, 56% of the patients were women, 79% identified as white, and 49% had at least some college education. The internal consistency reliability of the MDASI-Immunotherapy EPT was excellent, as the Cronbach's alphas for all of its subscales were at least 0.88 (range 0.88-0.95). Known-group validity based on Eastern Cooperative Oncology Group performance status groupings was excellent at 9 weeks after the start of an immunotherapy trial for the MDASI-Immunotherapy EPT severity (effect size, 0.96) and interference (effect size, 0.82) subscales. We found substantial changes in the symptom items difficulty remembering (effect size, -0.85), fever and/or chills (effect size, -0.63), disturbed sleep (effect size, -0.52), diarrhea (effect size, -0.42), and swelling of hands, legs, or feet (effect size, -0.39). In conclusion, the MDASI-Immunotherapy EPT is a valid, reliable, and sensitive tool for measuring symptomatic toxicity.


Flexible Polymer-Organic Solar Cells Based on P3HT:PCBM Bulk Heterojunction Active Layer Constructed under Environmental Conditions.
In this study, some crucial parameters were determined of flexible polymer-organic solar cells prepared from an active layer blend of poly(3-hexylthiophene) (P3HT) and the fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) mixed in 1:1 mass ratio and deposited from chlorobenzene solution by spin-coating on poly(ethylene terephthalate) (PET)/ITO substrates. Additionally, the positive effect of an electron transport layer (ETL) prepared from zinc oxide nanoparticles (ZnO np) on flexible photovoltaic elements' performance and stability was investigated. Test devices with above normal architecture and silver back electrodes deposed by magnetron sputtering were constructed under environmental conditions. They were characterized by current-voltage (I-V) measurements, quantum efficiency, impedance spectroscopy, surface morphology, and time-degradation experiments. The control over morphology of active layer thin film was achieved by post-deposition thermal treatment at temperatures of 110-120 °C, which led to optimization of device morphology and electrical parameters. The impedance spectroscopy results of flexible photovoltaic elements were fitted using two R||CPE circuits in series. Polymer-organic solar cells prepared on plastic substrates showed comparable current-voltage characteristics and structural properties but need further device stability improvement according to traditionally constructed cells on glass substrates.


[Spanish translation and validation of the Neuromuscular Module of the Pediatric Quality of Life Inventory (PedsQL): evaluation of the quality of life perceived by 8-18 years old children with neuromuscular diseases and by their parents].
The quality of life related to health of children with pediatric neuromuscular diseases is studied from the perspective of self-perception and parent-perception. It is therefore essential to dispose valid scales such as Pediatric Quality of Life inventory (PedsQL) Neuromuscular Module for its correct assessment. To assess the validity and reliability of the Spanish version of PedsQL Neuromuscular Module for self-perceived and parent-perceived quality of life of children aged 8-18 with neuromuscular disorders. The cognitive validity of the Spanish version of PedsQL was carried out with Mapi Research Trust permission. Subsequently, a test-retest was performed with 90 children volunteers with neuromuscular diseases, 50 aged 8-12 and 40 aged 13-18, and 85 of those children's parents. This allowed an evaluation of PedsQL intra-observer concordance and internal consistency. Finally, construct validity was evaluated through factor analysis. The Cronbach alpha and all correlation intra-observer coefficients were higher than 0.8, indicating excellent validity and reliability and a higher internal consistency. The construct validity analysis suggested that a new construct with more might be a better fit than three and it will be able to explain a higher percentage of variability. The Spanish version of PedsQL Neuromuscular Module for self-perceived and parent-perceived quality of life of children aged 8-18 presented excellent validity and reliability.


Off-pump coronary artery grafting in patients with left main coronary artery disease.
Left main coronary artery disease (LMCD) is considered a relative contraindication to off-pump coronary artery bypass (OPCAB) grafting. This study evaluates the safety and feasibility of OPCAB in these patients compared to an on-pump group (cardiopulmonary bypass, CPB) with LMCD. Between January 2000 and July 2002, 95 patients with left main coronary artery stenosis >50% underwent coronary revascularization. Seventy-three unselected patients underwent OPCAB and 22 underwent revascularization using CPB. The techniques used for OPCAB included the use of deep traction sutures in the posterior pericardium and stabilizers to expose the distal coronary targets. Intraluminal coronary shunts were routinely used during construction of the anastomoses. Variables were analyzed using a Student's paired t-test with statistical significance defined as p < 0.05. The mean age in the OPCAB group was 59.9 years and the CPB group 61.8 years (p = 0.54). There were 56 males (77%) in the OPCAB and 18 (82%) in the CPB groups. Mean preoperative left ventricular ejection fraction (LVEF) was 40.3% in OPCAB and 47.3% in CPB (p = 0.015). Average number of grafts was 3.1 in OPCAB and 4.1 in CPB (p = 0.0038). There were no conversions to CPB in those patients initially chosen to undergo OPCAB. There were no early deaths in OPCAB. There was one death in CPB. Mean hospital length of stay was 6.9 days for OPCAB and 9.1 for CPB (p = 0.0159). Patients with LMCD can undergo OPCAB grafting safely and effectively despite reduced LVEF. LMCD should no longer be seen as a contraindication to perform OPCAB grafting.


Physiotherapist as an alternative to a GP for musculoskeletal conditions: a 2-year service evaluation of UK primary care data.
Physiotherapists are currently working in primary care as first contact practitioners (FCP), assessing and managing patients with musculoskeletal conditions instead of GPs. There are no published data on these types of services. To evaluate a new service presenting the first 2 years of data. Analysis of 2 years' data of patient outcomes and a patient experience questionnaire from two GP practices in Forth Valley NHS, UK. The service was launched in November 2015 in response to GP shortages. Data were collected from every patient contact in the first 2 years. This included outcomes of appointments, GP support, capacity of the service, referral rates to physiotherapy and orthopaedics, numbers of steroid injections, and outcomes from orthopaedic referrals. A patient experience questionnaire was also conducted. A total of 8417 patient contacts were made, with the majority managed within primary care (n = 7348; 87.3%) and 60.4% (n = 5083) requiring self-management alone. Referrals to orthopaedics were substantially reduced in both practices. Practice A from 1.1 to 0.7 per 1000 patients; practice B from 2.4 to 0.8 per 1000 patients. Of referrals to orthopaedics, 86% were considered 'appropriate'. Extended scope physiotherapists (ESPs) asked for a GP review in 1% of patients. The results suggest that patients with musculoskeletal conditions may be assessed and managed independently and effectively by physiotherapists instead of GPs. This has the potential to significantly reduce workload for GPs as the service requires minimal GP support. The majority of patients were managed within primary care, with low referral rates and highly appropriate referrals to orthopaedics. Patients reported positive views regarding the service.


miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance.
The ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumulating evidences indicate that miR-205-5p is significantly downregulated in breast tumors compared with normal breast tissue and acts as a tumor suppressor directly targeting oncogenes such as Zeb1 and ErbB3. In this study, we report that miR-205-5p is highly expressed in BCSCs and represses directly ERBB2 and indirectly EGFR leading to resistance to targeted therapy. Furthermore, we show that miR-205-5p directly regulates the expression of p63 which is in turn involved in the EGFR expression suggesting a miR-205/p63/EGFR regulation.


A Study of Association between H. Pylori Genotype and Chronic Gastritis.
The prevalence of Helicobacter pylori (HP) infection is very high in Bangladesh. Chronic gastritis due to H. pylori is commonly associated with important gastric diseases such as peptic ulcer diseases or gastric carcinoma and MALT-oma. The natural course of chronic gastritis is HP-associated antral gastritis or pangastritis or rarely atrophies. This study was done to see the association of H. pylori genotypes with chronic gastritis. This observational cross sectional study was carried out at Bangabandhu Sheikh Mujib Medical University from July 2012 to April 2013 to find out the association of H. pylori genotypes with chronic gastritis in dyspeptic patients of Bangladesh. A total of 50 dyspeptic subjects were involved in the study whose upper GI endoscopies were carried out in presence of an experienced endoscopist. During the procedure four biopsies were taken, two from the antrum and two from body of the stomach. Endoscopic diagnosis was categorized into normal and erosive gastritis. Two (one from antrum and one from body) biopsy samples were collected in phosphate buffer saline and PCR analysis carried out by Multiplex PCR assay. Another two were collected in 10% formalin and histopathological examination was done according to updated Sydney system of classification. Among 50 patents only 34 were PCR positive. So, only 34 subjects were included in the study. Among them 21 patients (61.8%) were male and 13 patients (38.2%) were female, with the mean age of 29.91 years. Endoscopy revealed erosive gastritis in 5(14.7%) patients and normal findings in 29(86.3%) patients. Amongst the strains, cagA gene was detected in 58.8% and was not significantly associated with severity of any parameter of chronic gastritis such as H. pylori density, inflammation (mononuclear infiltration), activity (neutrophilic infiltration), atrophy and intestinal metaplasia. All the strains were positive for vacA allele. s1m1 (55.9%) genotype was most predominant. No vacA allele (s1m1, s1m2, s2m1 and s2m2) were significantly associated with severity of chronic gastritis. In this study, H. pylori genotype -cagA, vacA-s1, s2, m1, m2 allele and histological grading of chronic gastritis according to updated Sydney system of classification is identified. This study will identify the genotypes associated with severe gastritis in our country and thereby help us to take appropriate preventive measure. Further study with larger sample size may be carried out to establish proper association between different genotypes and parameters of chronic gastritis.


Erythema Multiforme-Like Presentation in an Asymptomatic COVID-19 Patient.
In clinical practice, there are a lot of variations in disease manifestations. Diseases are constantly evolving, and one negative test cannot completely rule out a disease. Erythema multiforme (EM) is a common mucocutaneous disease that can be linked to a lot of etiologies, with the most common being herpes simplex virus (HSV) types 1 and 2, Mycoplasma pneumoniae, and the use of various drugs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus, and traditionally it is not the first differential for EM eruptions. We report the case of a 52-year-old female patient with a history of multiple drug use, pneumonia-like symptoms, an initial negative viral panel for SARS-CoV-2, followed by a positive polymerase chain reaction (PCR) test, asymptomatic coronavirus disease 2019 (COVID-19) clinical course, and break-out of typical targetoid lesions of EM. Throughout her hospital stay, the patient maintained her oxygenation levels and improved clinically with steroids and symptomatic treatment. She regained her health and was counseled to quit smoking, alcohol, and opioid usage at the time of discharge from the hospital, and a regular follow-up with her primary care practitioner (PCP) was advised.


Effects of sodium bicarbonate ingestion on swim performance in youth athletes.
The purpose of this study was to evaluate the effect of oral administration of sodium bicarbonate (300 mg·kg(-1) b.w.) on swim performance in competitive, (training experience of 6.6 ± 0.6 years) youth, (15.1 ± 0.6 years) male swimmers. The subjects completed a test trial, in a double blind fashion, on separate days, consisting of 4 x 50m front crawl swims with a 1(st) minute passive rest interval twice, on two occasions: after ingestion of bicarbonate or placebo, 72 hours apart, at the same time of the day. Blood samples were drawn from the finger tip three times during each trial; upon arrival to the laboratory, 60 min after ingestion of placebo or the sodium bicarbonate solution and after the 4 x 50m test, during the 1st min of recovery. Plasma lactate concentration, blood pH, standard bicarbonate and base excess were evaluated. The total time of the 4 x 50 m test trial improved from 1.54.28 to 1.52.85s, while statistically significant changes in swimming speed were recorded only during the first 50m sprint (1.92 vs. 1.97 m·s(-1), p < 0.05). Resting blood concentration of HCO(-) 3 increased following the ingestion of sodium bicarbonate from 25.13 to 28.49 mM (p < 0.05). Sodium bicarbonate intake had a statistically significant effect on resting blood pH (7.33 vs. 7.41, p < .05) as well as on post exercise plasma lactate concentration (11.27 vs. 13.06 mM, p < 0.05)). Collectively, these data demonstrate that the ingestion of sodium bicarbonate in youth athletes is an effective buffer during high intensity interval swimming and suggest that such a procedure can be used in youth athletes to increase training intensity as well as swimming performance in competition at distances from 50 to 200 m. Key pointsSodium bicarbonate is an effective ergogenic aid, also in youth athletes.Sodium bicarbonate intake improves swimming sprint performance.Sodium bicarbonate intake increases resting blood pH and bicarbonate level.


De Novo Whole-Genome Sequence of Xylella fastidiosa subsp. multiplex Strain BB01 Isolated from a Blueberry in Georgia, USA.
This study reports a de novo-assembled draft genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 causing blueberry bacterial leaf scorch in Georgia, USA. The BB01 genome is 2,517,579 bp, with a G+C content of 51.8%, 2,943 open reading frames (ORFs), and 48 RNA genes.


Contrast-enhanced ultrasound improves hepatic vessel visualization after orthotopic liver transplantation.
We investigated whether color-coded Doppler sonography combined with an ultrasound contrast medium would improve the assessment of liver-supplying vessels after orthotopic liver transplantation. Forty-seven patients after orthotopic liver transplantation participated. Examinations were done without and then with the ultrasound contrast medium Levovist. Visualization of the liver-supplying vessels was assessed with a scoring system. Visualization of the portal vein was similar without and with contrast medium. Hepatic arteries were visualized in 39 patients without contrast medium and 46 patients with contrast medium. The remaining patient showed hepatic artery thrombosis, which was confirmed angiographically. With the use of Levovist, the examination took 3.7 min rather than the usual 6.4 min. Imaging of hepatic arteries after liver transplantation improved significantly with the use of ultrasound contrast medium. These findings are important because the early detection of blood flow through the liver after transplantation affects prognosis.


Synthesis and biological evaluation of 4-(hydroxyalkyl)estradiols and related compounds.
A series of synthetic estrogens containing hydroxyalkyl side chains at the C-4 position of the A ring were designed as metabolically stable analogs of 4-hydroxyestradiol, a catechol estrogen. These synthetic steroids would facilitate investigations on the potential biological role of catechol estrogens and also enable further examination of the structural and electronic constraints on the A ring in the interaction of estrogens with the estrogen receptor. Catechol estrogens are implicated as possible causative agents in estrogen-induced tumorigenesis. 4-Hydroxyestradiol has weaker affinity for the estrogen receptor and exhibits lower estrogenic activity in vivo; on the other hand, the catechol estrogens are prone to further oxidative metabolism and can form reactive intermediates. This report describes the synthesis and initial biochemical evaluation of 4-(hydroxyalkyl)estrogens and 4-(aminoalkyl)estradiols. The 4-(hydroxyalkyl)estrogens were prepared by oxidative hydroboration of 4-alkenylestradiols. The alkenylestradiols were obtained via a Stille cross-coupling between a MOM-protected 4-bromoestradiol and an alkenylstannane. The (4-aminoalkyl)estrogens were prepared from the hydroxyalkyl derivatives with phthalimide under Mitsunobu conditions. The substituted estradiols were evaluated for estrogen receptor binding activity in MCF-7 human mammary carcinoma cells, and 4-(hydroxymethyl)estradiol 1 exhibited the highest affinity with an apparent EC50 value of 364 nM. The relative activities for mRNA induction of the pS2 gene in MCF-7 cell cultures by the 4-(hydroxyalkyl)estrogens closely parallel the relative binding affinities. 4-(Hydroxymethyl)estradiol 1 did not stimulate the growth of MCF-7 cells at concentrations up to 1 microM. Thus, 4-(hydroxymethyl)estradiol 1 exhibited similar estrogen receptor affinity as the catechol estrogen, 4-hydroxyestradiol, and may prove useful in the examination of the biological effects of 4-hydroxyestrogens.


Dentin surface treatments for the removal of the smear layer: an SEM study.
Previous studies have shown that the bond strength of glass ionomer to dentin can be increased by the removal of the smear layer. Seven materials readily available were evaluated for smear layer removal. Clinical conditions were simulated as closely as possible.


Accreditation of postgraduate speciality training programmes in Endodontology. Minimum criteria for training Specialists in Endodontology within Europe.
This consensus statement from the European Society of Endodontology (ESE) sets out the minimum criteria for training Specialists in Endodontology within Europe. The case is made for recognizing Endodontology as a distinctive dental discipline throughout Europe. Guidelines are presented on the requirements of a specialist and of a specialist training programme in Endodontology. The aims, objectives and curriculum content of a specialist training pathway are outlined, with guidelines on trainee appraisal, and the expectations of faculty and institutional commitment. In publishing these guidelines, the ESE is responding to a public and professional need for consistently high standards of training and specialist clinical service within Europe.


Clinical management of electrical burns in the developing world: a case of electrical burn injury left untreated leading to amputation.
We discuss the case of a 26-year-old male patient from Northern Samar, the Philippines who was left without essential health services after the amputation of all four limbs following a high voltage (20 000 volts) injury in Metro Manila in 2011. Local health services in the developing world are faced with enormous challenges in providing first-line care for burn patients. The cost of maintaining a burn unit, finding suitable qualified staff, and appropriate referral mechanisms are only some of the challenges faced. Once a patient is discharged from hospital they face more obstacles in obtaining artificial limbs, physiotherapy and access to mental health services. Disability pensions are non-existent thus patients place a considerable lifelong burden on their families.


[Effect of ultraviolet-B irradiation pretreatment on a second-set rejection model of orthotopic corneal grafts].
To investigate the effect of ultraviolet-B irradiation (UV-B) on the donor cornea in a second-set rejection model of rat orthotopic corneal transplantation. Three patterns of fully mismatched allogeneic bilateral orthotopic corneal transplantations (DA to AO) after 10-week interval were studied: Untreated primary corneal grafts into the right eyes followed by untreated secondary grafts into the left eyes, UV-B treated primary corneal grafts into the right eyes followed by untreated secondary grafts into the left eyes, and untreated primary corneal grafts into the right eyes followed by UV-B treated secondary grafts into the left eyes. The rejection of untreated secondary grafts was hastened in recipients who had previously rejected untreated primary grafts (p = 0.00507). Recipients bearing long-surviving UV-B pretreated corneal grafts rejected secondary untreated corneal grafts at the first-set tempo. Recipients who had previously rejected untreated primary grafts rejected UV-B pretreated secondary grafts at the first-set tempo. The UV-B pretreatment to donor corneas may induce dysfunction of antigen presentation so that the recipients' immune system fails to be sensitized in second-set phenomena.


Increased fraction of exhaled nitric oxide predicts new-onset wheeze in a general population.
Fraction of exhaled nitric oxide (Fe(NO)) is regarded as a marker of airway inflammation. It is unknown whether increased Fe(NO) in respiratorily healthy subjects increases the risk of developing wheeze. To examine if increased levels of Fe(NO) predicts later onset of wheeze. We followed up 2,200 men and women from a general population-based study. At baseline, the subjects were investigated with questionnaires, blood samples, pulmonary function tests, and Fe(NO). At follow-up 4 years later, all subjects were mailed a respiratory questionnaire. The association between incident wheeze and baseline levels of Fe(NO) over the 90th percentile were evaluated calculating hazard ratios using Cox regression models adjusted for smoking habits, age, height, sex, and atopy. The follow-up questionnaire was completed by 1,896 subjects (86.2%). All subjects reporting wheeze, asthma, or asthma symptoms at baseline were excluded resulting in a study population of 1,506 subjects. Of these, 49 subjects reported new-onset wheeze. The median concentration of Fe(NO) at baseline was significantly higher among those with new-onset wheeze (18.8 ppb vs. 15.8 ppb, P = 0.03). In a Cox regression model including all subjects, Fe(NO) over the 90th percentile predicted onset of wheeze (hazard ratio 2.7; 95% confidence interval, 1.4-5.4). In stratified models, this was most apparent among never-smokers and in atopic subjects, for whom the odds ratios were higher. Our results indicate that increased Fe(NO) is associated with an increased risk of developing wheeze. The results also support the hypothesis that increased level of Fe(NO) among subjects without respiratory symptoms is a sign of subclinical airways inflammation.


Curative effect of pelvic floor muscle exercise on urinary incontinence after radical prostatectomy-Comparisons of different approaches at different time point.
Pelvic floor muscle exercise (PFME) is widely applied for urinary incontinence (UI) after radical prostatectomy (RP). This research aimed to explore the relationship between PFME and UI after RP. We searched databases for studies that met our requirements until 17/4/2021. The UI symptoms of the PFME group and the control group were compared at 1, 3, 6 and 12 months after the operation. Subgroup analysis based on surgical approach (open radical prostatectomy vs laparoscopy & robotics radical prostatectomy) and UI definition (questionnaire vs. pad weight) were also conducted. The UI rate in PFME group is significantly lower when compared with control group at each time point. According to subgroup analysis, PFME is more effective to alleviate UI after laparoscopy & robotics radical prostatectomy when compared with open RP at mid-term (3s and 6 months) whereas no significant difference was detected between two groups at short (1 month) or long (12 months) term. According to this meta-analysis, post-operation PFME treatment can effectively alleviate the symptoms of UI after RP at any time point; pre-operation PFME alone was not sufficient to relieve UI. Compared with open prostatectomy, PFME is more effective for the UI after laparoscopy & robotics radical prostatectomy.


Non-ocular primary malignancies in patients with uveal melanoma: the Liverpool experience.
To identify the prevalence of self-reported non-ocular primary malignancies in patients at the time of diagnosis with uveal melanoma (UM) and to describe the cohort's characteristics. A data query for cases of UM seen at the Liverpool Ocular Oncology Centre between January 1993 and May 2014 was performed. Only patients who had UM with other non-ocular primary malignancies were included. Demographic and clinical data were analysed. A total of 5042 (2563 males, 50.8%) patients with UM were found in the database; of whom, 216 (4.3%) had at least one other primary non-ocular malignancy. Of these 216 patients, 119 were males (55.1%). Forty five males (37.8%) had been diagnosed with prostate cancer, 30 (25.2%) with unspecified skin cancers, 15 (12.6%) with colon and bowel carcinoma, eight (6.7%) with systemic lymphoma and the remaining patients with less common tumours. Of the 97 females, 45 (46.4%) had been diagnosed with breast carcinoma, 19 (19.6%) had unspecified skin cancers, seven (7.2%) renal cell carcinoma, six (6.2%) colon and bowel carcinoma, and the remaining patients had other less common tumour types. In this cohort, the frequency of the most common additional malignancy in male and female patients with UM was comparable with their prevalence in the general UK population. Additional primary malignancies can occur in association with UM; therefore, medical history taking in patients with UM should always include this aspect. Apart from providing demographic and clinical data in such cases, future collaborative studies, which would include germline mutational testing, may reveal relevant common patterns.


Synthesis of classes of ternary metal oxide nanostructures.
Nanoscale structures, such as nanoparticles, nanorods, nanowires, nanocubes, and nanotubes, have attracted extensive synthetic attention as a result of their novel size-dependent properties. Ideally, the net result of nanoscale synthesis is the production of structures that achieve monodispersity, stability, and crystallinity with a predictable morphology. Many of the synthetic methods used to attain these goals have been based on principles derived from semiconductor technology, solid state chemistry, and molecular inorganic cluster chemistry. We describe a number of advances that have been made in the reproducible synthesis of various ternary oxide nanomaterials, including alkaline earth metal titanates, alkali metal titanates, bismuth ferrites, ABO(4)-type oxides, as well as miscellaneous classes of ternary metal oxides.


Medical Care Expenditures for Individuals with Prediabetes: The Potential Cost Savings in Reducing the Risk of Developing Diabetes.
The United States has 86 million adults with prediabetes. Individuals with prediabetes can prevent or delay the development of type 2 diabetes through lifestyle modifications such as participation in the National Diabetes Prevention Program (DPP), thereby mitigating the medical and economic burdens associated with diabetes. A cohort analysis of a commercially insured population was conducted using individual-level claims data from Truven Health MarketScan® Lab Database to identify adults with prediabetes, track whether they develop diabetes, and compare medical expenditures for those who are newly diagnosed with diabetes to those who are not. This study then illustrates how reducing the risk of developing diabetes by participation in an evidence-based lifestyle change program could yield both positive net savings on medical care expenditures and return on investment (ROI). Annual expenditures are found to be nearly one third higher for those who develop diabetes in subsequent years relative to those who do not transition from prediabetes to diabetes, with an average difference of $2671 per year. At that cost differential, the 3-year ROI for a National DPP is estimated to be as high as 42%. The results show the importance and economic benefits of participation in lifestyle intervention programs to prevent or delay the onset of type 2 diabetes.


[Primary hydatid cyst of the psoas muscle: description of 9 cases in Tunisia and review of the literature].
The psoas muscle is an uncommon location for hydatid cyst accounting for only 1 to 3% of cases. The purpose of this report is to describe the epidemiologic, clinical, paraclinical, and therapeutic features of primary hydatid cyst of the psoas muscle. A retrospective study conducted in Surgery Department A at the Rabta Hospital in Tunisia compiled a total of 9 cases of primary hydatid cyst of the psoas muscle treated between 1980 and 2006. There were 6 men and 3 women with a mean age of 42.8 years. Symptomatology was nonspecific with pain in 6 cases. Discovery was coincidental in two cases. Clinical examination detected a mass in the presents of an abdominal mass in 7 cases. Radiologic findings (ultrasound and/or CT scan) confirmed diagnosis in 8 cases. In one case a mistaken diagnosis of psoas muscle abscess was made in a patient with an infected hydatid cyst. Serological tests were performed in 4 cases and were positive in 3. All patients underwent surgical treatment. The extraperitoneal approach (Leriche) was used in 7 cases and the transperitoneal approach via median laparotomy in 2. In all cases the surgical procedure consisted of partial cystectomy leaving a part of the pericystic against neurovascular structures. There was no operative mortality. The only postoperative complication was urinary infection in one patient. Mean follow-up was 2.5 years. One local recurrence was observed 4 years after surgical treatment and required reoperation.


MHCBN 4.0: A database of MHC/TAP binding peptides and T-cell epitopes.
Many databases housing the information about MHC binders and non-binders have been developed in the past to help the scientific community working in the field of immunology, immune-informatics or vaccine design. As the information about these MHC binding and non-binding peptides continues to grow with the time and there is a need to keep the databases updated. So, in order to provide the immunological fraternity with the most recent information we need to maintain and update our database regularly. In this paper, we describe the updated version of 4.0 of the database MHCBN. MHCBN is a comprehensive database comprising over 25,857 peptide sequences (1053 TAP binding peptides), whose binding affinity with either MHC or TAP molecules has been assayed experimentally. It is a manually curated database where entries are collected & compiled from published literature and existing immunological public databases. MHCBN has a number of web-based tools for the analysis and retrieval of information like mapping of antigenic regions, creation of allele specific dataset, BLAST search, various diseases associated with MHC alleles etc. Further, all entries are hyper linked to major databases like SWISS-PROT, PDB etc. to provide the information beyond the scope of MHCBN. The latest version 4.0 of MHCBN has 6080 more entries than previously published version 1.1. MHCBN database updating is meant to facilitate immunologist in understanding the immune system and provide them the latest information. We feel that our database will complement the existing databases in serving scientific community.


Managing interorganizational dependencies in the new health care marketplace.
To survive, let alone thrive, in an increasingly competitive and threatening environment, health care organizations must skillfully manage their dependencies. Such dependencies traditionally have been managed through marketplace exchanges (buying and selling) and ownership relationships (acquisition, merger, and business development). An alternative strategy for designing and managing interorganizational relationships, the quasi-firm, is introduced. The quasi-firm is a hybrid market/ownership arrangement that allows participating organizations to pursue strategically important purposes while simultaneously preserving a high degree of functional and legal autonomy. We suggest that this distinctive interorganizational form is particularly well suited to the features of the new health care marketplace.


Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms.
The wild-type protein p53 plays a key role in preventing the formation of neoplasms by controlling cell growth. However, in more than a half of all cancers, the TP53 gene has missense mutations that appear during tumorigenesis. In most cases, the mutated gene encodes a full-length protein with the substitution of a single amino acid, resulting in structural and functional changes and acquiring an oncogenic role. This dual role of the wild-type protein and the mutated isoforms is also evident in the regulation of the redox state of the cell, with antioxidant and prooxidant functions, respectively. In this review, we introduce a new concept of the p53 protein by discussing its sensitivity to the cellular redox state. In particular, we focus on the discussion of structural and functional changes following post-translational modifications of redox-sensitive cysteine residues, which are also responsible for interacting with zinc ions for proper structural folding. We will also discuss therapeutic opportunities using small molecules targeting cysteines capable of modifying the structure and function of the p53 mutant isoforms in view of possible anticancer therapies for patients possessing the mutation in the TP53 gene.


Tailoring of Electron-Collecting Oxide Nanoparticulate Layer for Flexible Perovskite Solar Cells.
Low-temperature-processed perovskite solar cells (PSCs), especially those fabricated on flexible substrates, exhibit device performance that is worse than that of high-temperature-processed PSCs. One of the main reasons for the inferior performance of low-temperature-processed PSCs is the loss of photogenerated electrons in the electron collection layer (ECL) or related interfaces, i.e., indium tin oxide/ECL and ECL/perovskite. Here, we report that tailoring of the energy level and electron transporting ability in oxide ECLs using Zn2SnO4 nanoparticles and quantum dots notably minimizes the loss of photogenerated electrons in the low-temperature-fabricated flexible PSC. The proposed ECL with methylammonium lead halide [MAPb(I0.9Br0.1)3] leads to fabrication of significantly improved flexible PSCs with steady-state power conversion efficiency of 16.0% under AM 1.5G illumination of 100 mW cm(-2) intensity. These results provide an effective method for fabricating high-performance, low-temperature solution-processed flexible PSCs.


Bert-Enhanced Text Graph Neural Network for Classification.
Text classification is a fundamental research direction, aims to assign tags to text units. Recently, graph neural networks (GNN) have exhibited some excellent properties in textual information processing. Furthermore, the pre-trained language model also realized promising effects in many tasks. However, many text processing methods cannot model a single text unit's structure or ignore the semantic features. To solve these problems and comprehensively utilize the text's structure information and semantic information, we propose a Bert-Enhanced text Graph Neural Network model (BEGNN). For each text, we construct a text graph separately according to the co-occurrence relationship of words and use GNN to extract text features. Moreover, we employ Bert to extract semantic features. The former part can take into account the structural information, and the latter can focus on modeling the semantic information. Finally, we interact and aggregate these two features of different granularity to get a more effective representation. Experiments on standard datasets demonstrate the effectiveness of BEGNN.


Discrete dislocation plasticity analysis of loading rate-dependent static friction.
From a microscopic point of view, the frictional force associated with the relative sliding of rough surfaces originates from deformation of the material in contact, by adhesion in the contact interface or both. We know that plastic deformation at the size scale of micrometres is not only dependent on the size of the contact, but also on the rate of deformation. Moreover, depending on its physical origin, adhesion can also be size and rate dependent, albeit different from plasticity. We present a two-dimensional model that incorporates both discrete dislocation plasticity inside a face-centred cubic crystal and adhesion in the interface to understand the rate dependence of friction caused by micrometre-size asperities. The friction strength is the outcome of the competition between adhesion and discrete dislocation plasticity. As a function of contact size, the friction strength contains two plateaus: at small contact length [Formula: see text], the onset of sliding is fully controlled by adhesion while for large contact length [Formula: see text], the friction strength approaches the size-independent plastic shear yield strength. The transition regime at intermediate contact size is a result of partial de-cohesion and size-dependent dislocation plasticity, and is determined by dislocation properties, interfacial properties as well as by the loading rate.


Update on Current Technologies for Deep Brain Stimulation in Parkinson's Disease.
Deep brain stimulation (DBS) is becoming increasingly central in the treatment of patients with Parkinson's disease and other movement disorders. Recent developments in DBS lead and implantable pulse generator design provide increased flexibility for programming, potentially improving the therapeutic benefit of stimulation. Directional DBS leads may increase the therapeutic window of stimulation by providing a means of avoiding current spread to structures that might give rise to stimulation-related side effects. Similarly, control of current to individual contacts on a DBS lead allows for shaping of the electric field produced between multiple active contacts. The following review aims to describe the recent developments in DBS system technology and the features of each commercially available DBS system. The advantages of each system are reviewed, and general considerations for choosing the most appropriate system are discussed.


Suicide Among American Indian and Alaska Native Veterans Who Use Veterans Health Administration Care: 2004-2018.
American Indian and Alaska Natives (AI/ANs) veterans may be at elevated risk for suicide, but little is known about suicide among this population. We conducted a retrospective cohort analysis of AI/AN veterans who received health care services provided or paid for by the Veterans Health Administration (VHA) between October 1, 2002, and September 30, 2014, and who were alive as of September 30, 2003. Age-specific and age-adjusted suicide rates through 2018, per 100,000 person-years (PY) at risk and 95% confidence intervals were computed. Age-adjusted suicide rates among AI/AN veterans in this cohort more than doubled (19.1-47.0/100,000 PY) over the 15-year observation period. In the most recent observation period (2014-2018), the age-adjusted suicide rate was 47.0 per 100,000 PY, with the youngest age group (18-39) exhibiting the highest suicide rate (66.0/100,000 PY). The most frequently used lethal means was firearms (58.8%), followed by suffocation (19.3%), poisoning (17.2%), and other (4.7%). Results suggest that: (1) suicide is an increasing problem among AI/AN VHA veterans; and (2) younger AI/AN VHA veterans are at particularly high risk and warrant focused prevention efforts. Findings are similar to those observed in general AI/AN population. There is a compelling need to review and strengthen VHA suicide prevention efforts directed towards AI/AN veterans.


Epidemiology of Rett syndrome: a population-based registry.
The Texas Rett Syndrome Registry maintains the largest population-based registry of cases and potential cases of Rett syndrome in the world. The most precise estimate of the prevalence of Rett syndrome of 1 per 22800 (0.44/10000) females aged 2 through 18 years of age was generated from this Registry. In addition, the first prevalence figures for black and Hispanic female cases were estimated. Registry cases are actively ascertained from multiple sources. Registry staff identify presumptive cases from review of information provided to the Registry by the parent or guardian. Preliminary diagnostic evaluation includes standardized review of medical records and videotape of key behaviors. Diagnosis is confirmed at clinical evaluation. The active surveillance system is monitored with the two-source capture-recapture methodology and case ascertainment is projected. The 1990 prevalence estimate of Rett syndrome indicates that the syndrome occurs less frequently than previously estimated. Until a biologic marker for Rett syndrome is identified or a standard definition for an incident case of Rett syndrome is designated, the prevalence of Rett syndrome will remain a major investigative issue of its epidemiology, and the Registry will be an important, systematic mean to gather case material for clinical and laboratory studies providing the foundation for the development of preventive interventions.


Nedocromil sodium inhibits substance P-induced potentiation of cholinergic neural responses in the isolated innervated rabbit trachea.
1. Sensory neuropeptides such as substance P may be implicated in the pathophysiology of asthma. 2. It has been proposed that nedocromil sodium may inhibit the effects of neuropeptides. 3. In this study, using an isolated innervated preparation of rabbit trachea, substance P, 10(-6) M, potentiated contractions induced by parasympathetic stimulation. The effect of substance P at the preganglionic site (307 +/- 38% of control, n = 5), was similar to that at the postganglionic site (307 +/- 61% of control, n = 5). 4. Nedocromil sodium, 10(-7) M, significantly inhibited the substance P-induced potentiation preganglionically (199 +/- 44%, n = 4, P less than 0.05) but not postganglionically (356 +/- 118%, n = 4). 5. These results suggest that nedocromil sodium may modify neuropeptide action selectively at a preganglionic site and that this may contribute to its therapeutic efficacy.


Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection.
HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified. Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load. Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.


Sarcocystis bovifelis in Raw Hamburgers Marketed in Hamadan City, Western Iran.
We aimed to evaluate Sarcocystis contamination in conventional and industrial raw beef burger samples from butcheries and retail stores in Hamadan, western Iran. Overall, 80 samples including 30 conventional and 50 industrial hamburgers were randomly obtained from different butcheries and supermarkets. All specimens were studied by digestion method following microscopic examination. Samples' genomic ribosomal DNA were amplified and nucleotide sequences were analyzed by BLAST for comparison with the sequences in the gene bank of the NCBI. Sarcocystis bradyzoites were detected in 46 of 80 (57.6%) samples. Positive specimens were included as 46 (57.6%) and 30 (37.5%) by digestion and molecular method, respectively. Differences between two studied (digestion and molecular) methods was statistically significant (P=0.00). Twenty-six (86.5 %) of 30 conventional beef burgers and 20 (40%) of 50 industrial burgers were positive for Sarcocystis sp. by digestion method. There was a significant difference between Sarcocystis infested conventional and industrial beef burgers (P=0.01). The parasitic contamination of beef burgers implied a high level of infection in cattle. Felids as the definitive hosts for S. bovifelis urged on the improvement of the hygienic conditions of keeping and feeding livestock in order to reduce the infection. Molecular techniques confirm species in meat products with high sensitivity and distinguish it from human species.


Identification of a calcitonin-like diuretic hormone that functions as an intrinsic modulator of the American lobster, Homarus americanus, cardiac neuromuscular system.
In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.


Patient-Centered Robot-Aided Passive Neurorehabilitation Exercise Based on Safety-Motion Decision-Making Mechanism.
Safety is one of the crucial issues for robot-aided neurorehabilitation exercise. When it comes to the passive rehabilitation training for stroke patients, the existing control strategies are usually just based on position control to carry out the training, and the patient is out of the controller. However, to some extent, the patient should be taken as a "cooperator" of the training activity, and the movement speed and range of the training movement should be dynamically regulated according to the internal or external state of the subject, just as what the therapist does in clinical therapy. This research presents a novel motion control strategy for patient-centered robot-aided passive neurorehabilitation exercise from the point of the safety. The safety-motion decision-making mechanism is developed to online observe and assess the physical state of training impaired-limb and motion performances and regulate the training parameters (motion speed and training rage), ensuring the safety of the supplied rehabilitation exercise. Meanwhile, position-based impedance control is employed to realize the trajectory tracking motion with interactive compliance. Functional experiments and clinical experiments are investigated with a healthy adult and four recruited stroke patients, respectively. The two types of experimental results demonstrate that the suggested control strategy not only serves with safety-motion training but also presents rehabilitation efficacy.


Uptake and phytotoxicity of the herbicide metsulfuron methyl in corn root tissue in the presence of the safener 1,8-naphthalic anhydride.
Growth of Zea mays L. cv Potro roots was inhibited by the herbicide metsulfuron methyl (MSM) at the lowest concentration tested: 5 nanomoles per liter. Pretreatment of corn seeds with commercial 1,8-naphthalic anhydride (NA) at 1% (w/w) partially reversed MSM-induced root growth inhibition. MSM at a concentration of 52 nanomoles per liter was taken up rapidly by roots and accumulated in the corn tissue to concentrations three times those in the external medium; the safener NA increased MSM uptake up to 48 hours. The protective effect of NA was related to the ability of the safener to increase the metabolism of MSM; tenfold increases in the metabolic rates of MSM were observed in NA-pretreated corn seedlings grown for 48 hours on 52 nanomolar [(14)C]MSM solution. DNA synthesis determined by measurement of [(3)H]thymidine incorporation into DNA was inhibited by root MSM applications; after a 6-hour application period, 13 nanomolar MSM solution reduced DNA synthesis by 64%, and the same reduction was also observed with NA-pretreated seedlings. Pretreatment of corn seeds with safener NA did not increase the acetolactate synthase activity in the roots and did not change, up to 13 micromoles per liter, the in vitro sensitivity of roots to MSM.


The effect of parity on the relation between maternal history of spontaneous pregnancy loss and the risk of sudden infant death syndrome in offspring.
We conducted a population-based case-control study, using the 1984-1989 linked Washington State birth and death certificate data, to determine whether maternal prior spontaneous pregnancy loss was associated with the risk of sudden infant death syndrome (SIDS). We identified 872 autopsied SIDS cases and 3,704 controls matched to cases on year of birth. To reduce the confounding from unmeasured socioeconomic and behavioral factors, we analyzed the data separately for infants with and without father's race provided on the birth certificate. Among infants whose father's race was known, those of multiparous women with a prior spontaneous pregnancy loss before 20 weeks gestational age were at reduced risk of SIDS, after adjustment for maternal age, prenatal smoking,a nd gravidity. An increased number of prior pregnancy losses was associated with a further reduction in the risk of SIDS: one prior pregnancy loss was associated with a 25% decrease [odds ratio (OR) = 0.75; 95% confidence interval (CI) = 0.52-1.08], and two or more prior pregnancy losses was associated with a 47% decrease (OR = 0.53; 95% CI = 0.30-0.94). There was no such association, however, among infants of women with no prior livebirth. Similar associations were observed between prior spontaneous pregnancy loss during the entire gestational period and the risk of SIDS in offspring. To explain the different associations between maternal prior pregnancy loss and the risk of SIDS observed among infants of women with and without a prior livebirth, we hypothesize an upward bias resulting from the presence of a larger proportion of infants of human leukocyte antigen-compatible couples among first liveborn infants.


NK cell-mediated lysis of autologous HCMV-infected skin fibroblasts is highly variable among NK cell clones and polyclonal NK cell lines.
Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which HLA class I was >70% downregulated. The clones ranged broadly in their ability to lyse AD169-infected fibroblasts, correlating neither with the expression of inhibitory KIR, leukocyte inhibitory receptor-1, or CD94:NKG2A receptors nor with the number of different inhibitory KIR expressed per clone. Some lines of polyclonal NK cells preferentially lysed AD169-infected cells and similarly lysed fibroblasts infected with mutant virus RV798, which lacks the genes for downregulating HLA class I. These results demonstrate that NK cell lysis of HCMV-infected autologous fibroblasts is more complex than a simple missing-self mechanism involving downregulation of HLA class I and failure to engage inhibitory self-specific KIR.


Transjugular intrahepatic portosystemic shunt for the prevention of rebleeding in patients with cirrhosis and portal vein thrombosis: Systematic review and meta-analysis.
Background: Transjugular intrahepatic portosystemic shunt (TIPS) has been performed on patients with cirrhosis and portal vein thrombosis (PVT) to prevent rebleeding; however, the associated evidence is scarce. Hence, the study aimed to evaluate the feasibility and efficacy of TIPS in patients with cirrhosis and PVT and promote personalized treatment in such patients. Methods: Literature was systematically obtained from PubMed, EMBASE, Cochrane Library, and Web of Science. Data from the included studies were extracted, and meta-analyses by the random effects model were used to pool data across studies. Heterogeneity was assessed using Cochran's Q and I2 statistics. The source of heterogeneity was explored using subgroup analyses and meta-regressions. Results: A total of 11 studies comprising 703 patients with cirrhosis and portal vein thrombosis (PVT: complete, 32.2%; chronic, 90.2%; superior mesenteric vein or splenic vein involvement, 55.2%; cavernous transformation, 26.8%) were included. TIPS showed feasibility in 95% of the cases (95% confidence interval [CI]: 89%-99%) with heterogeneity (I2 = 84%, p < 0.01) due to cavernous transformation. The pooled rebleeding rate was 13% (95% CI: 7%-20%) with heterogeneity (I2 = 75%, p < 0.01) explained by chronic PVT and anticoagulation (AC) therapy. Hepatic encephalopathy occurred in 32% of patients. The survival rate, portal vein recanalization rate, and shunt patency rate were 80%, 82%, and 77%, respectively. Conclusion: TIPS is feasible and effectively prevents rebleeding in patients with cirrhosis and PVT, regardless of cavernous transformation of the portal vein. Due to a potentially high risk of rebleeding and no apparent benefits of AC, post-TIPS AC must be employed cautiously. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258765], identifier [CRD42021258765].


Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells.
We have purified and determined the complete primary structure of human stromelysin, a secreted metalloprotease with a wide range of substrate specificities. Human stromelysin is synthesized in a preproenzyme form with a calculated size of 53,977 Da and a 17-amino acid long signal peptide. Prostromelysin is secreted in two forms, with apparent molecular masses on NaDodSO4/PAGE of 60 and 57 kDa. The minor 60-kDa polypeptide is a glycosylated form of the major 57-kDa protein containing N-linked complex oligosaccharides. Zymogen activation by trypsin results in the removal of 84 amino acids from the amino terminus of the enzyme generating a 45-kDa active enzyme species. Human stromelysin is capable of degrading proteoglycan, fibronectin, laminin, and type IV collagen but not interstitial type I collagen. The enzyme is not capable of activating purified human fibroblast procollagenase. Analysis of its primary structure shows that stromelysin is in all likelihood the human analog of rat transin, which is an oncogene transformation-induced protease. The pattern of enzyme expression in normal and tumorigenic cells revealed that human skin fibroblasts in vitro secrete stromelysin constitutively (1-2 micrograms per 10(6) cells per 24 hr). Human fetal lung fibroblasts transformed with simian virus 40, human bronchial epithelial cells transformed with the ras oncogene, fibrosarcoma cells (HT-1080), and a melanoma cell strain (A 2058), do not express this protease nor can the enzyme be induced in these cells by treatment with phorbol 12-myristate 13-acetate. Our data indicate that the expression and the possible involvement of secreted metalloproteases in tumorigenesis result from a specific interaction between the transforming factor and the target cell, which may vary in different species.


Spin Caloritronics in 3D Interconnected Nanowire Networks.
Recently, interconnected nanowire networks have been found suitable as flexible macroscopic spin caloritronic devices. The 3D nanowire networks are fabricated by direct electrodeposition in track-etched polymer templates with crossed nano-channels. This technique allows the fabrication of crossed nanowires consisting of both homogeneous ferromagnetic metals and multilayer stack with successive layers of ferromagnetic and non-magnetic metals, with controlled morphology and material composition. The networks exhibit extremely high, magnetically modulated thermoelectric power factors. Moreover, large spin-dependent Seebeck coefficients were directly extracted from experimental measurements on multilayer nanowire networks. This work provides a simple and cost-effective way to fabricate large-scale flexible and shapeable thermoelectric devices exploiting the spin degree of freedom.