Flexibility and symmetry of prokaryotic genome rearrangement reveal lineage-associated core-gene-defined genome organizational frameworks.
The prokaryotic pangenome partitions genes into core and dispensable genes. The order of core genes, albeit assumed to be stable under selection in general, is frequently interrupted by horizontal gene transfer and rearrangement, but how a core-gene-defined genome maintains its stability or flexibility remains to be investigated. Based on data from 30 species, including 425 genomes from six phyla, we grouped core genes into syntenic blocks in the context of a pangenome according to their stability across multiple isolates. A subset of the core genes, often species specific and lineage associated, formed a core-gene-defined genome organizational framework (cGOF). Such cGOFs are either single segmental (one-third of the species analyzed) or multisegmental (the rest). Multisegment cGOFs were further classified into symmetric or asymmetric according to segment orientations toward the origin-terminus axis. The cGOFs in Gram-positive species are exclusively symmetric and often reversible in orientation, as opposed to those of the Gram-negative bacteria, which are all asymmetric and irreversible. Meanwhile, all species showing strong strand-biased gene distribution contain symmetric cGOFs and often specific DnaE (α subunit of DNA polymerase III) isoforms. Furthermore, functional evaluations revealed that cGOF genes are hub associated with regard to cellular activities, and the stability of cGOF provides efficient indexes for scaffold orientation as demonstrated by assembling virtual and empirical genome drafts. cGOFs show species specificity, and the symmetry of multisegmental cGOFs is conserved among taxa and constrained by DNA polymerase-centric strand-biased gene distribution. The definition of species-specific cGOFs provides powerful guidance for genome assembly and other structure-based analysis. Prokaryotic genomes are frequently interrupted by horizontal gene transfer (HGT) and rearrangement. To know whether there is a set of genes not only conserved in position among isolates but also functionally essential for a given species and to further evaluate the stability or flexibility of such genome structures across lineages are of importance. Based on a large number of multi-isolate pangenomic data, our analysis reveals that a subset of core genes is organized into a core-gene-defined genome organizational framework, or cGOF. Furthermore, the lineage-associated cGOFs among Gram-positive and Gram-negative bacteria behave differently: the former, composed of 2 to 4 segments, have their fragments symmetrically rearranged around the origin-terminus axis, whereas the latter show more complex segmentation and are partitioned asymmetrically into chromosomal structures. The definition of cGOFs provides new insights into prokaryotic genome organization and efficient guidance for genome assembly and analysis.


A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.
Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.


GENETIC AND GEOGRAPHIC VARIATION IN REJECTION BEHAVIOR OF CUCKOO EGGS BY EUROPEAN MAGPIE POPULATIONS: AN EXPERIMENTAL TEST OF REJECTER-GENE FLOW.
Host responses toward brood parasitism have been shown to differ among populations depending on the duration of sympatry between host and parasite, although populations not currently parasitized show rejection behavior against parasitic eggs. The persistence of rejection behavior in unparasitized host populations and rapid increases of rejection rate in parasitized ones have sometimes been explained as the result of gene flow of rejecter genes from sympatry to allopatry (rejecter-gene flow hypothesis). We present data on the rejection behavior of magpies (Pica pica) the main European host of the great spotted cuckoo (Clamator glandarius), in 15 populations (nine sympatric six allopatric) across their distribution range in Europe. Rejection rates of mimetic and nonmimetic model eggs were significantly higher in sympatric than in allopatric magpie populations, although differences in rejection rate of both mimetic and nonmimetic model eggs between magpie populations were significantly correlated even after controlling tor phylogenetic effects, with differences between sympatric and allopatric magpie populations being larger for mimetic than for nonmimetic model eggs. Differences in rejection of mimetic model eggs were related to both genetic and geographic distances between populations, but differences in rejection rate of nonmimetic model eggs were unrelated to these distances. However, when comparing only sympatric populations, differences in rejection rate of both mimetic and nonmimetic model eggs were related to geographic distances. A multiple autocorrelation analysis revealed that differences among populations in rejection rates of mimetic model eggs had a strong geographic component whereas the main component of rejection rate of nonmimetic model eggs was genetic rather than geographic. These results support the rejecter-gene flow hypothesis. We discuss differences in rejection rates of mimetic and nonmimetic model eggs that suggest the egg-recognition ability of the host is genetically based, but is affected by a learning process for fine tuning of recognition.


Simulator-based driving test prescreening as a complement to driver testing - Toward safer and more risk-aware drivers.
Young people represent a high-risk group of drivers and the prevalence of road traffic crashes among young drivers is high. Thus, to increase traffic safety, it is essential to ensure that new drivers are both sufficiently educated in and assessed for risk awareness. The aim of this study was to examine the possibility and potential benefit of using a driving simulator screening test as a complement to the existing on-road driving test. The main idea is to detect drivers who are not ready to proceed to the driving test. A comparative study was performed with participants who passed and failed a simulator test and an on-road driving test, respectively. A comparison between subjective and objective measures of performance and risk was also included. A driving simulator was placed at a traffic school and customers were recruited as participants. In total, 70 participants took part in the study and the simulated drive consisted of rural roads, urban traffic, and motorways with 16 different scenarios, constructed from the second level of the GDE matrix, to examine driving behavior, attention, and risk perception. The results show that with a screening test in a driving simulator, it is possible to detect drivers who consider themselves ready to take a driving test, but who have not yet reached the level of risk awareness required to be a safe driver. Test scenarios should be suited to detect deficiencies in risk awareness, test different levels of the GDE matrix and, to complement the driving test, be difficult to assess in an on-road driving test. Deficiencies in self-evaluation that are well-known among young drivers are again confirmed. To practice self-evaluation, the driving simulator is suggested as a pedagogical tool, linked to the GDE matrix.


Primary health care resources for rehabilitation and secondary prevention after myocardial infarction - a questionnaire survey.
During the first year after a cardiac event, many patients are offered participation in a cardiac rehabilitation programme, after which the patients are often not given the opportunity to continue to attend rehabilitation and secondary prevention programmes. This study describes the primary health care centres' (PHCC) resources regarding cardiac rehabilitation/secondary prevention programmes for coronary heart disease (CHD) patients in a southern Swedish region. A questionnaire containing 26 dichotomous or multiple choice questions was sent to the responsible manager of all 137 public and private PHCCs in Region Skåne. Questionnaires from 91 (66%) of the PHCCs were completed and returned. Few nurses at the PHCCs had special training regarding CHD (10%), cardiac rehabilitation (8%) or heart failure (32%). Twenty-one per cent of the physicians had special training regarding CHD. One third of the PHCCs did not offer long-term secondary prevention programmes, and few (6%) had any routines for offering socio-economic support to CHD patients. Comparison of private and public PHCCs showed that the private centres could not offer a physiotherapist (61 vs. 84%) or dietician (32 vs. 73%; p = 0.03) to the same extension as the public ones. Furthermore, the majority (91%) of PHCCs had no cooperation with patient organizations. The PHCCs need to improve the strategies and long-term rehabilitation programmes. Furthermore, they need to focus on education programme for the staff. The result revealed that the PHCCs lack resources, strategies and long-term care programmes for CHD patients.


Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury.
To identify early predictive markers of poor outcomes in patients with acute liver injury from wild mushroom intoxication. This observational, retrospective record review involved adults aged ≥ 18 years admitted to emergency department with mushroom intoxication from January 2005 to December 2015. The diagnosis of mushroom intoxication was based on the following: (1) a positive history of recent wild mushroom intake (either raw or cooked); (2) the onset of gastrointestinal symptoms, such as watery diarrhea, vomiting, and/or abdominal pain, after ingestion; and (3) the exclusion of other possible causes of acute liver injury. Acute liver injury was defined by a > 5-fold elevation of liver enzymes or moderate coagulopathy [international normalized ratio (INR) > 2.0]. Clinical and laboratory findings were compared in survivors and non-survivors. Of 93 patients with mushroom intoxication, 23, 11 men (47.8%) and 12 women (52.2%), of median age 61 years, developed acute liver injury. The overall in-hospital mortality rate was 43.5% (10/23). Among the laboratory variables, mean serum alkaline phosphatase (73.38 ± 10.89 mg/dL vs 180.40 ± 65.39 mg/dL, P < 0.01), total bilirubin (2.312 ± 1.16 mg/dL vs 7.16 ± 2.94 mg/dL, P < 0.01) concentrations and indirect/direct bilirubin (2.45 ± 1.39 mg/dL vs 0.99 ± 0.45 mg/dL, P < 0.01) ratio as well as prothrombin time (1.88 ± 0.83 mg/dL vs 10.43 ± 4.81 mg/dL, P < 0.01), and activated partial thromboplastin time (aPTT; 32.48 ± 7.64 s vs 72.58 ± 41.29 s, P = 0.01), were significantly higher in non-survivors than in survivors. Logistic regression analysis showed that total bilirubin concentration (OR = 3.58, 95%CI: 1.25-10.22), indirect/direct bilirubin ratio (OR = 0.14, 95%CI: 0.02-0.94) and aPTT (OR = 1.30, 95%CI: 1.04-1.63) were significantly associated with mortality. All patients with total bilirubin > 5 mg/dL or aPTT > 50 s on day 3 died. Monitoring of bilirubin concentrations and aPTT may help in predicting clinical outcomes in patients with acute liver injury from wild mushroom intoxication.


Mycobacterium chelonae Eye Infections Associated with Humidifier Use in an Outpatient LASIK Clinic--Ohio, 2015.
Laser-assisted in situ keratomileusis (LASIK) eye surgery is increasingly common, with approximately 600,000 procedures performed each year in the United States. LASIK eye surgery is typically performed in an outpatient setting and involves the use of a machine-guided laser to reshape the lens of the eye to correct vision irregularities. Clinic A is an ambulatory surgery center that performs this procedure on 1 day each month. On February 5, 2015, the Toledo-Lucas County Health Department (TLCHD) in Ohio was notified of eye infections in two of the six patients who had undergone LASIK procedures at clinic A on January 9, 2015. The two patients experienced eye pain after the procedures and received diagnoses of infection with Mycobacterium chelonae, an environmental organism found in soil and water.


[The importance of inhibition of adhesion molecules in allergic inflammation].
Inflammation is a defensive reaction of an organism in response to injuring factors and is characterised by effector cells infiltration. Adhesion molecules are involved in their ordered influx. These molecules are glycoprotein particles present on cell surface and on intracellular matrix proteins. Cytokines, chemokines and other inflammatory process mediators modulate the expression of adhesion molecules. Anti-adhesion therapy involves many techniques. Most frequently monoclonal antibodies are used. Other forms of therapy contribute to blocking the synthesis of molecules at transcription level or to inhibition of their transfer from cell interior to its surface. Soluble molecule forms or their receptors are also applied.


The biological activity of bovine and human thyrotropin is differently affected by trypsin treatment of human thyroid cells: thyroid-stimulating antibody is related to human thyrotropin.
Pretreatment of cultured human thyroid cells with trypsin decreased the cAMP response to bovine TSH (bTSH) (by 50-60%). In striking contrast, in trypsin treated cells the cAMP stimulation by both human TSH (hTSH) and thyroid-stimulating antibodies (TSab) was unimpaired, indicating a similar behavior for these two stimulators. The effect of trypsin on inhibiting cAMP stimulation by bTSH was: 1) dose dependent; 2) present at a trypsin concentration as low as 3.3 mg/L; 3) fully reversible within 24 h after removal of the enzyme. In accordance with the altered biological activity in human thyroid cells exposed to trypsin the binding of labeled bTSH was reduced (about 40%). On the contrary, in the same cells, the binding of labeled human TSH was enhanced (about 3-fold). The cAMP response to cholera toxin and forskolin was unaffected in trypsin treated cells, indicating that the tryptic treatment did not alter any other component of the adenylate cyclase complex. The medium obtained from trypsin-treated human thyroid cells was able to neutralize the biological activity of bTSH but not that of hTSH or TSab. Our study demonstrates that in human thyroid cells: 1) trypsin impaires bovine, but not human TSH or TSab biological activity; 2) bovine and human TSH may bind to different components of the TSH receptor.


Duration of imipramine therapy and relapse in panic disorder with agoraphobia.
It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse. This study further explores the relationship between relapse and duration of imipramine treatment in this population.Fifty-one patients, all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and randomized to double-blind maintenance or placebo substitution, discontinued imipramine treatment eventually and were followed over a 12-month risk period: 27 during first year placebo substitution, 7 after 12 months of imipramine maintenance in placebo substitution, and 17 after variable durations of imipramine maintenance in open discontinuation. There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation. Duration of imipramine treatment, the method of discontinuation (open versus placebo substitution), or any of the 9 variables from the demographic, clinical, and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse. The rate of relapse after only 6 months of treatment (10 out of 27, 37%) was identical to the rate of relapse after 12 to 30 months of treatment (9 out of 24, 37.5%). The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients. Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction.


Local entropy in quasi-one-dimensional heat transport.
We study the nonequilibrium entropy of the heat transport problem by performing molecular dynamics simulations of a quasi-one-dimensional gas of hard disks in the steady state. The entropy density, flux, and production rate, associated with the entropy balance of the system, are obtained from the numerically measured velocity distributions, based on the kinetic theory analysis of the Boltzmann entropy. We obtain an equilibriumlike Clausius relation from the computer experiments which, in turn, fulfills the generalized Gibbs relation for spatially inhomogeneous states.


Schizosaccharomyces pombe Pak-related protein, Pak1p/Orb2p, phosphorylates myosin regulatory light chain to inhibit cytokinesis.
p21-activated kinases (Paks) have been identified in a variety of eukaryotic cells as key effectors of the Cdc42 family of guanosine triphosphatases. Pak kinases play important roles in regulating the filamentous actin cytoskeleton. In this study, we describe a function for the Schizosaccharomyces pombe Pak-related protein Pak1p/Orb2p in cytokinesis. Pak1p localizes to the actomyosin ring during mitosis and cytokinesis. Loss of Pak1p function leads to accelerated cytokinesis. Pak1p mediates phosphorylation of myosin II regulatory light chain Rlc1p at serine residues 35 and 36 in vivo. Interestingly, loss of Pak1p function or substitution of serine 35 and serine 36 of Rlc1p with alanines, thereby mimicking a dephosphorylated state of Rlc1p, leads to defective coordination of mitosis and cytokinesis. This study reveals a new mechanism involving Pak1p kinase that helps ensure the fidelity of cytokinesis.


A Dorsal Approach for Ulnar Shortening Osteotomy.
Aim This study aims to evaluate the long-term complications, results, and patient satisfaction rates of a dorsally approached ulnar shortening osteotomy for ulnar impaction syndrome. Methods A retrospective chart review of 20 patients was performed. Primary outcomes of interest were subjective, measured using the Patient-Rated Wrist Evaluation (PRWE) score, Disability of the Arm, Shoulder, and Hand (DASH) score, and the third questionnaire about patient satisfaction, composed by the authors. Secondary outcomes included hardware removal due to irritation and other complications. Results Mean postoperative functional score of PRWE was 28 (standard deviation [SD], 30) and DASH 20 (SD, 26), respectively. Fifteen patients were satisfied with the operation. Removal of hardware was noted in six patients. In one patient plate breakage occurred. Conclusion Similar postoperative functional scores and complications were seen in patients undergoing an ulnar shortening osteotomy with a dorsally placed plate for ulnar impaction syndrome, compared with other plate placement localizations. The incidence of plate removal is also comparable to previously described results. As the dorsally placed plate and freehand technique, are relatively easy, we feel that it has a place in the treatment of ulnar impaction syndrome. Level of Evidence Level IV, retrospective cohort study.


Total IgE, eosinophils, and interleukins 16, 17A, and 23 correlations in severe bullous pemphigoid and treatment implications.
Bullous pemphigoid (BP) patients are predominantly above 70 years of age, with limited tolerance to the side effects of the immunosuppressive drugs. Advancements in our understanding of the pathophysiology of BP have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. Patients with BP Disease Area Index above 60 and less than 100 were split into two groups-one with high and the other with normal levels of IgE. The tested parameters included eosinophils' count, total IgE serum level, and interleukins (IL) 16, 17A, and 23 counts in the peripheral blood and skin bulla serum, before any therapeutic intervention. Thirty individuals fulfilled the criteria for enrollment. Patients with high IgE blood serum levels had significantly higher levels of IL17A and normal IL23 levels in blood and bulla serum. Patients with normal serum IgE levels had slightly higher IL23 levels in blood and bulla serum. The eosinophil count was positively related to IL17 blood serum level and negatively related to IL23. IL16 did not differ in the two groups. BP patients may represent a group of patients benefiting most substantially from the introduction of nonimmunosuppressive therapeutics into the treatment regimens for their disease. Clinical criteria and immune biomarkers are needed for making the best therapeutic choice.


Outcome of LASIK in fleck corneal dystrophy.
To report the outcome of laser in situ keratomileusis (LASIK) in a patient with Fleck corneal dystrophy. Case report and literature review. A 48-year-old Taiwanese man presented in November 2005, 6 years after bilateral myopic LASIK. He complained of loss of uncorrected distance visual acuity that was worse in the left eye. The patient did not report glare, halos, or other visual aberrations. Preoperative best spectacle-corrected visual acuity (BSCVA) was 20/25 OU, with a manifest refraction of -14 D OU. In November 2005, uncorrected visual acuity (UCVA) was 20/40 OD and 20/50 OS, and BSCVA was 20/25 in each eye with a manifest refraction of -1.00 sphere OD and -1.75 -1.25 x 115 OS. Slit-lamp examination was remarkable for several subtle, small, gray corneal opacities present throughout the corneal stroma. Confocal microscopy revealed refractile bodies within swollen keratocytes and normal surrounding stromal mileu. The clinical and confocal appearance was consistent with Fleck corneal dystrophy. In this patient with Fleck corneal dystrophy, corneal clarity and BSCVA were maintained 6 years after bilateral myopic LASIK, suggesting that LASIK does not stimulate visually significant exacerbation of Fleck corneal dystrophy.


Comparison of pain levels of traditional radial, distal radial, and transfemoral coronary catheterization.
The aim of our study was to compare the traditional radial artery, distal radial artery, and transfemoral artery, which are vascular access sites for coronary angiography, in terms of pain level using the visual analog scale. Between April 2021 and May 2022, consecutive patients from three centers were included in our study. A total of 540 patients, 180 from each of the traditional radial artery, distal radial artery , and transfemoral artery groups, were included. The visual analog scale was applied to the patients as soon as they were taken to bed. When the visual analog scale was compared between the groups, it was found to be significantly different (transfemoral artery: 2.7±1.6, traditional radial artery: 3.9±1.9, and distal radial artery: 4.9±2.1, respectively, p<0.001). When the patients were classified as mild, moderate, and severe based on the visual analog scale score, a significant difference was found between the groups in terms of body mass index, process time, access time, and number of punctures (p<0.001). Based on the receiver operating characteristic analysis, body mass index>29.8 kg/m2 predicted severe pain with 72.5% sensitivity and 73.2% specificity [(area under the curve: 0.770, 95%CI: 0.724-0.815, p<0.0001)]. In our study, we found that the femoral approach caused less access site pain and a high body mass index predicts severe pain.


Botulinum toxin for treatment of parkinsonian sialorrhea.
Sialorrhea is one of the main problems of patients with Parkinson's disease (PD). Most of the medications used for the treatment of it are ineffective. We decided to try in such patients local injections of botulinum toxin, type A, into both parotid glands. 11 patients with clinical diagnosis of idiopathic PD and drooling assessed as at least 2 point on the UPDRS part II and 14 control subjects. Salivation was measured by weighting dental rolls before and 2 minutes after insertion at 6 places of highest secretion of saliva in mouth (buccal vestibule, and sublingual area). PD patients were assessed before and one week after injections of 5 units of BOTOX into each parotid salivary gland and the results were compared to the salivation of controls. Average excretion of saliva in PD patients was significantly higher than in controls -0.39 +/- 0.4 g/2 min. (range: 0.02-1.82) vs. 0.19 +/- 0.16 g/2 min. (range: 0.02-0.98) (p = 0.03). After the treatment the average excretion of saliva in PD patients decreased to 0.25 +/- 0.26 g/2 min. (range: 0.004-0.99) and did not differ significantly from controls. All patients improved also according to UPDRS. No side-effects were observed in any of the patients injected. Botulinum toxin may be an effective and safe treatment of parkinsonian sialorrhea.


Low-loss microwave photonic switching for satellite communication.
For traditional switching architecture, packet switching performs fine granularity data packet forwarding, but its digital signal processing (DSP) has high power consumption (PC). All-optical switching provides rapid exchange of wavelength resources, which has coarse granularity. In scenarios where the PC is limited, such as broadband satcom, a switching architecture with lower PC and finer granularity than optical switching would be useful. In this paper, we propose a novel, to the best of our knowledge, low-loss microwave photonic switching architecture that can exchange subband signals across beams and frequency bands. The switching process is realized by exchanging optical carriers instead of payload signals, which does not degrade the signal power, guaranteeing the signal-to-noise ratio (SNR). We conducted a proof-of-concept experiment of 2 × 2 switching with two 1.2-GBaud quadrature phase-shift keying (QPSK) signals; an error vector magnitude (EVM) of or less than 13.87% is realized after forwarding. The proposed system has the advantages of low PC, high SNR, and fine granularity, and is very promising for flexible forwarding in future satcom systems.


High-Performance Inverted Organic Photovoltaics Without Hole-Selective Contact.
A detailed investigation of the functionality of inverted organic photovoltaics (OPVs) using bare Ag contacts as the top electrode is presented. The inverted OPVs without a hole-transporting layer (HTL) exhibit a significant gain in hole-carrier selectivity and power-conversion efficiency (PCE) after exposure in ambient conditions. Inverted OPVs comprised of ITO-ZnO-poly(3-hexylthiophene-2,5-diyl)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM)-Ag demonstrate over 3.5% power conversion efficiency only if the devices are exposed in air for over 4 days. As concluded through a series of measurements, the oxygen presence is essential to obtaining fully operational solar cell devices without HTL. Moreover, accelerated stability tests under damp heat conditions (RH = 85% and T = 65 °C) performed to nonencapsulated OPVs demonstrate that HTL-free inverted OPVs exhibit comparable stability to the reference inverted OPVs. Importantly, it is shown that bare Ag top electrodes can be efficiently used in inverted OPVs using various high-performance polymer-fullerene bulk heterojunction material systems demonstrating 6.5% power-conversion efficiencies.


Pain in the ear resulting from misplaced subclavian dialysis catheter into ipsilateral internal jugular vein.
This case describes pain in the ear resulting from inadvertent placement of a subclavian dialysis catheter into the ipsilateral internal jugular vein. The pain subsided when the catheter was withdrawn.


Shifting our thinking about uncommon disease trials: the case of methotrexate in scleroderma.
Randomized trials for uncommon diseases suffer from methodological challenges: difficulty in recruiting sufficient numbers of patients and low power to detect important treatment effects. Using traditional (frequentist) analysis, p values > 0.05 mean investigators are unable to reject the null hypothesis (of no treatment effect). The medical community often labels trials with p values > 0.05 as "negative." Our study demonstrates how Bayesian analysis conveys more relevant information to clinicians - using the example of methotrexate (MTX) in systemic sclerosis (SSc). Data from 71 patients with diffuse SSc (n = 35 MTX, n = 36 placebo) in the trial were reanalyzed using Bayesian models. We examined 3 primary outcomes: modified Rodnan skin score (MRSS), University of California Los Angeles (UCLA) skin score, and physician global assessment of overall disease activity. Using noninformative prior probability distributions, the probability of beneficial treatment effects for each outcome and the probability of simultaneous benefit in outcomes were computed. The probability that treatment with MTX results in better mean outcomes than placebo was 94% for MRSS, 96% for UCLA skin score, and 88% for physician global assessment. There was 96% probability that at least 2 of 3 primary outcomes were better on treatment. Bayesian analysis of uncommon disease trials allows for more flexible and clinically relevant interpretations of the data. From the trial data, clinicians can infer that MTX has a high probability of beneficial effects on skin score and global assessment.


The Impact of Elexacaftor/Ivacaftor/Tezacaftor on Cystic Fibrosis Patients Who Acquire COVID-19 Infection.
The combination of medication containing elexacaftor, ivacaftor, and tezacaftor (EIT) has dramatically impacted the treatment and prognosis for patients with cystic fibrosis (CF). Lung function, weight, and self-reported quality of life have improved for many of these patients, but little is known about whether this treatment will have a beneficial effect in preventing morbidity and/or mortality from respiratory infections such as COVID-19. EIT received Food and Drug Administration (FDA) approval shortly before the first cases of COVID-19 appeared in the United States. We performed an analysis using the TriNetX (Cambridge, MA, USA) research database to determine if patients being treated with EIT who became infected with COVID-19 experienced significantly different outcomes compared to patients who were not receiving it.


Effects of inhaled hexachlorobenzene aerosols on rat pulmonary host defenses.
Pulmonary bactericidal activity, macrophage phagocytic activity, alveolar macrophage (AM) enzyme activity, and T- and B-cell mitogenesis of lymphocytes from lung associated lymph nodes (LALN) or mesenteric lymph nodes (MESLN) were assessed in Sprague-Dawley rats exposed 4 hr/d, 4 days/wk for 1, 4, or 16 days to hexachlorobenzene (HCB) aerosols. Pulmonary bactericidal activity was depressed after 1 or 4 but not 16 exposures to 35 mg/m3 of HCB. AM phagocytosis of 51Cr-RBC in vitro was increased after 4 but not 1 or 16 exposures to HCB, and no effect was observed in peritoneal macrophages. HCB significantly enhanced mitogenesis in MESLN to the B-cell mitogen Salmonella typhimurium lipopolysaccharide (STM) after 4 exposures; LALN STM mitogenesis and LALN and MESLN mitogenesis to phytohemagglutinin (PHA) were not affected. After 16 exposures, however, the PHA responses in LALN and MESLN were significantly increased and decreased, respectively.


Autonomic innervation of immune organs and neuroimmune modulation.
1. Increasing evidence indicates the occurrence of functional interconnections between immune and nervous systems, although data available on the mechanisms of this bi-directional cross-talking are frequently incomplete and not always focussed on their relevance for neuroimmune modulation. 2. Primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid organs are supplied with an autonomic (mainly sympathetic) efferent innervation and with an afferent sensory innervation. Anatomical studies have revealed origin, pattern of distribution and targets of nerve fibre populations supplying lymphoid organs. 3. Classic (catecholamines and acetylcholine) and peptide transmitters of neural and non-neural origin are released in the lymphoid microenvironment and contribute to neuroimmune modulation. Neuropeptide Y, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide represent the neuropeptides most involved in neuroimmune modulation. 4. Immune cells and immune organs express specific receptors for (neuro)transmitters. These receptors have been shown to respond in vivo and/or in vitro to the neural substances and their manipulation can alter immune responses. Changes in immune function can also influence the distribution of nerves and the expression of neural receptors in lymphoid organs. 5. Data on different populations of nerve fibres supplying immune organs and their role in providing a link between nervous and immune systems are reviewed. Anatomical connections between nervous and immune systems represent the structural support of the complex network of immune responses. A detailed knowledge of interactions between nervous and immune systems may represent an important basis for the development of strategies for treating pathologies in which altered neuroimmune cross-talking may be involved.


Versatile Reactivity of Scorpionate-Anchored Yttrium-Dialkyl Complexes towards Unsaturated Substrates.
A series of unusual chemical-bond transformations were observed in the reactions of high active yttrium-dialkyl complexes with unsaturated small molecules. The reaction of scorpionate-anchored yttrium-dibenzyl complex [Tp(Me2)Y(CH2Ph)2(thf)] (1, Tp(Me2)=tri(3,5-dimethylpyrazolyl)borate) with phenyl isothiocyanate led to C=S bond cleavage to give a cubane-type yttrium-sulfur cluster, {Tp(Me2)Y(μ3-S)}4 (2), accompanied by the elimination of PhN-C(CH2Ph)2. However, compound 1 reacted with phenyl isocyanate to afford a C(sp(3)) H activation product, [Tp(Me2)Y(thf){μ-η(1):η(3)-OC(CHPh)NPh}{μ-η(3):η(2)-OC(CHPh)NPh}YTp(Me2)] (3). Moreover, compound 1 reacted with phenylacetonitrile at room temperature to produce γ-deprotonation product [(Tp(Me2))2Y](+)[Tp(Me2)Y(N=C=CHPh)3](-) (6), in which the newly formed N=C=CHPh ligands bound to the metal through the terminal nitrogen atoms. When this reaction was carried out in toluene at 120 °C, it gave a tandem γ-deprotonation/insertion/partial-Tp(Me2)-degradation product, [(Tp(Me2)Y)2(μ-Pz)2{μ-η(1):η(3)-NC(CH2Ph)CHPh}] (7, Pz=3,5-dimethylpyrazolyl).


Mechanism of Mepiquat Chloride Regulating Soybean Response to Drought Stress Revealed by Proteomics.
Soybeans are the main sources of oil and protein for most of the global population. As the population grows, so does the demand for soybeans. However, drought is a major factor that limits soybean production. Regulating soybean response to drought stress using mepiquat chloride (MC) is a feasible method; however, its mechanism is still unclear. This study used PEG-6000 to simulate drought stress and quantitative proteomic techniques to reveal changes in Heinong44 (HN44) and Heinong65 (HN65) subjected to drought following the application of 100 mg/L of MC. The results showed that SOD in HN44 did not change significantly but decreased by 22.61% in HN65 after MC pretreatment, and MDA content decreased by 22.75% and 21.54% in HN44 and HN65, respectively. Furthermore, MC improved the GSH-ASA cycle and simultaneously promoted the Calvin cycle process to enable the plant to maintain a certain carbon assimilation rate under osmotic stress. In addition, MC upregulated some proteins during gluconeogenesis and starch metabolism and increased soluble sugar content by 8.41% in HN44. MC also reduced ribosomal protein abundance, affecting translation and amino acid metabolism. In summary, MC improved GSH-ASA cycle and Calvin cycle under stress to alleviate oxidative damage and maintain crop growth. Our study is the first to report the mechanism of MC regulation in soybean under osmotic stress, providing new insights for the rational application of MC in soybean.


Value of high-resolution computerized tomography in localizing diseased parathyroid glands.
Eighteen patients with hyperparathyroidism underwent high-resolution computerized tomography of the neck and superior mediastinum to assess the accuracy of the method in localizing diseased parathyroid glands preoperatively. The tomograms were correlated with surgical and pathological findings. Four scans were technically unsatisfactory. Of the remaining 14 scans, 8 showed an enlarged parathyroid gland; in 7 cases, the scan correctly identified the location of the diseased gland while in 1 case, the side of the lesion was incorrect. The other six scans did not show an abnormal parathyroid. These glands varied in size from 0.05 to 5.0 cm3 at the time of pathological examination. Three patients were undergoing re-exploration for persistent disease; technically acceptable scans were obtained in two and, in both, the location of the adenoma was correctly identified. Excluding patients with technically unsatisfactory scans, this technique has a sensitivity of 50% (7/14) and a false-negative rate of 43% (6/14) independent of gland size. However, in the eight scans interpreted as positive, the correct side of the lesion was localized in 7 (88%). This technique is not recommended for routine preoperative localization but may be of value in re-exploration for persistent disease.


The University of Minnesota's Clinical Research Support Center Feasibility Review: An objective protocol assessment carving a pathway to study success.
To successfully and efficiently initiate clinical research studies, it is critical to develop a strong, feasible, and well-written study protocol early in the start-up phase. The University of Minnesota's Clinical Research Support Center designed and implemented a structured Feasibility Review process in 2018 that addresses common start-up challenges such as poor study design, inappropriate outcomes, and limited resources. This process has been shown to turn an unfeasible study into a well-designed protocol that is IRB-approved with few protocol-related stipulations and well prepared for execution. It has also educated study teams on how to write better quality and more robust protocols for subsequent studies. Once a draft protocol is available, the entire process takes just six working days and is free of charge to investigators, study teams, and departments. From 2018-2021, one hundred sixteen Feasibility Reviews (n=116) have been completed across eight schools or colleges. Mean satisfaction scores for study team members who responded were high (N=126, M=4.71 ± 0.5) on a 5-point Likert-type scale. Most respondents (96%) indicated that they planned to modify their protocol based on reviewer feedback. Open ended/qualitative feedback was highly positive with most responses centered around the helpfulness of feasibility review, the high level of expertise, and fast turnaround time. The Feasibility Review is a valuable and multifunctional program providing timely expert guidance to study teams to efficiently and successfully launch and execute clinical research studies. It can be easily replicated, adapted, and implemented at other institutions to increase the quality and efficacy of academic research.


VEGF Expression to Support Targeted Therapy in Ovarian Surface Epithelial Neoplasms.
Vascular Endothelial Growth Factor (VEGF), a promoter of angiogenesis, is a promising target for anti-angiogenic therapy in ovarian cancer. In our study, we examined the expression of VEGF in the spectrum of epithelial ovarian neoplasms (benign, borderline and malignant) by Immunohistochemistry (IHC). Diagnosing ovarian epithelial neoplasms, examining the expression of VEGF in benign, borderline and malignant neoplasms and correlating it with histological grade and stage of malignant cases. This is a cross-sectional, observational study where, total of 50 cases of surface epithelial ovarian neoplasms were examined for expression of VEGF by IHC. Scoring for VEGF expression was done for each case. A total of 42 of the 50 cases (84%) showed VEGF expression. Out of the 42 positive cases, 19 were high VEGF expressors and 23 were low VEGF expressors. VEGF expression was significantly higher in carcinomas as compared to benign and borderline neoplasms (p=<0.001). All neoplasms of serous morphology were positive for VEGF. High VEGF expression was significantly associated with high grade (p=0.003) and stage (p=0.001) of disease. Ovarian surface epithelial neoplasms significantly express VEGF. Though, some VEGF expression was noted in benign and some borderline neoplasms, high VEGF expression was noted only in carcinomas and one case of borderline serous papillary tumour. Thus, these results suggest that epithelial ovarian tumours are candidates for VEGF targeting therapy as most of them are dependent on VEGF for progression.


Association of Long-Term Adherence to the MIND Diet with Cognitive Function and Cognitive Decline in American Women.
There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet. Population-based prospective cohort study. A total of 16,058 older women aged 70 and over from the Nurses' Health Study. Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively. Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.


Prospective randomized clinical trial on suction elastic band ligator versus forceps ligator in the treatment of haemorrhoids.
This prospective randomized clinical trial was undertaken to compare the use of a single-operator vacuum suction ligator and the traditional forceps ligator in terms of pain perception following the procedure, intra-procedure bleeding and other complications. One hundred consecutive patients with second- and third-degree haemorrhoids presenting between July 2002 and September 2003 were randomized into suction and forceps groups for rubber band ligations. They were equally distributed in both groups, with a mean age of 48.7 years (range, 15-83 years). The immediate, 24-hour, 7-day and 14-day pain scores after the procedure were evaluated using a visual analogue scale. Intra-procedure bleeding and other complications at follow-up were evaluated. Pain perception was worse in the forceps group immediately after ligation, with a mean score of 6.08 compared with 3.08 in the suction group (p < 0.001). Pain score remained high among the forceps patients at 24 hours post-banding, with a mean score of 4.00 compared with 1.92 in the suction group (p < 0.001). There was no significant difference in terms of immediate and 24-hour pain perceptions whether two or three haemorrhoids were banded per session (p = 0.904 and p = 0.058). The amount of analgesia consumed after banding correlated well with the severity of pain reported, being higher among the forceps group with a mean of 4.48 tablets (p = 0.003). Intra-procedure bleeding occurred in 25 patients in the forceps group compared with five in the suction group (p < 0.001). There were no severe complications such as perianal sepsis, urinary retention, sphincter dysfunction or bleeding during the trial. Suction band ligation is superior to forceps ligation for the treatment of second- and third-degree haemorrhoids in terms of pain tolerance, amount of analgesia consumed and intra-procedure bleeding.


Protective effect of pulp oil extracted from Canarium odontophyllum Miq. Fruit on blood lipids, lipid peroxidation, and antioxidant status in healthy rabbits.
The aim of this paper was to compare the effects of pulp and kernel oils of Canarium odontophyllum Miq. (CO) on lipid profile, lipid peroxidation, and oxidative stress of healthy rabbits. The oils are rich in SFAs and MUFAs (mainly palmitic and oleic acids). The pulp oil is rich in polyphenols. Male New Zealand white (NZW) rabbits were fed for 4 weeks on a normal diet containing pulp (NP) or kernel oil (NK) of CO while corn oil was used as control (NC). Total cholesterol (TC), HDL-C, LDL-c and triglycerides (TG) levels were measured in this paper. Antioxidant enzymes (superoxide dismutase and glutathione peroxidise), thiobarbiturate reactive substances (TBARSs), and plasma total antioxidant status (TAS) were also evaluated. Supplementation of CO pulp oil resulted in favorable changes in blood lipid and lipid peroxidation (increased HDL-C, reduced LDL-C, TG, TBARS levels) with enhancement of SOD, GPx, and plasma TAS levels. Meanwhile, supplementation of kernel oil caused lowering of plasma TC and LDL-C as well as enhancement of SOD and TAS levels. These changes showed that oils of CO could be beneficial in improving lipid profile and antioxidant status as when using part of normal diet. The oils can be used as alternative to present vegetable oil.


Mitigation of BMP-induced Inflammation in Craniofacial Bone Regeneration and Improvement of Bone Parameters by Dietary Hesperidin.
Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n=10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 μg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE+BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 caused cystic-like regeneration with incomplete defect closure. HE+BMP2 showed virtually complete bone fusion. Red collagen fibrils were significantly higher in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p<0.05) indicating high organization. Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p<0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in locally delivered high-dose BMP2-induced bone possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE has a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.


Hunter-Prey Discourse: A Critical Discourse Analysis of the Online Posts of Men Who Buy Sex.
The Internet has emerged as a major expediter of the commercial sex (CS) industry. While use of web-based CS industry sites is brisk, the full extent of their impact remains unclear particularly how they influence users' views of the CS industry. This research study sought to uncover the nuances of buyers' interactions on an online CS website. Six hundred sixty-six online posts from 363 unique members were collected and analyzed using critical discourse analysis. Via the use of language and dialogue, particular ways of thinking about and talking about buying sex are normalized and reinforced. Evident within these discursive patterns are mechanisms by which assumptions are forwarded, perceptions shaped, and authority established. Information about how CS industry websites establish beliefs, relationships, and practices among its users may increase understanding of how the CS industry seeks to gain acceptance in the American culture and normalize its activities.


BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal.
Mutations in genes encoding the dystrophin-associated glycoprotein complex (DGC) can cause muscular dystrophy and disturb synaptic transmission in the photoreceptor ribbon synapse. However, the molecular composition and specific functions of the photoreceptor DGC remain unknown. Brefeldin A-resistant Arf-GEF 2 (BRAG2), also known as IQSEC1, is a guanine nucleotide exchange factor for ADP-ribosylation factor 6 (Arf6), a critical GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. In the present study, we characterized the expression of BRAG2a, an alternative splicing isoform of BRAG2, in the adult mouse photoreceptor. Immunofluorescence and immunoelectron microscopic analyses of adult mouse retinas were performed using a novel anti-BRAG2a antibody. Pull-down, immunoprecipitation, and in situ proximity ligation assays were performed to examine the interaction between BRAG2a and the DGC in vivo. Immunofluorescence demonstrated punctate colocalization of BRAG2a with β-dystroglycan in the outer plexiform layer. Immunoelectron microscopy revealed the localization of BRAG2a at the plasma membrane of lateral walls and processes of photoreceptor terminals within the synaptic cavity. Pull-down and immunoprecipitation assays using retinal lysates demonstrated the protein complex formation between BRAG2a with the DGC. In situ proximity ligation assays further detected a close spatial relationship between BRAG2a and β-dystroglycan in the outer plexiform layer. The present study provided evidence that BRAG2a is a novel component of the photoreceptor DGC, suggesting functional involvement of the BRAG2a-Arf6 pathway downstream of the DGC.


Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy.
Incontinentia pigmenti (IP) is a rare hereditary disorder that has recently been classified as a chromosomal instability syndrome. As in Fanconi anemia and ataxia telangiectasia, spontaneous and inducible chromosomal aberrations primarily of the chromatid type are increased in patients with IP. Both Fanconi anemia and ataxia telangiectasia are genetic diseases that predispose to cancer. A case report of an infant with IP and malignancy (rhabdoid tumor of the kidney) is presented, and five previously reported cases of this association are reviewed. The malignancies in all of these cases occurred before age three, whereas malignancy associated with Fanconi anemia and ataxia telangiectasia tends to appear in late childhood or in adulthood. The chromosomal instability seen with IP may increase the risk for malignancy in young children.


Congenital heart defects in offspring of women with Type 2 diabetes - a systematic review.
The risk of congenital heart defects in the offspring of women with Type 2 diabetes is only sparsely described. The aim of this review was to estimate the prevalence of congenital heart defects in offspring of women with Type 2 diabetes in comparison to offspring of women with Type 1 diabetes and to offspring of the background population. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed in the PubMed, Embase and Cochrane databases. Studies were included if they were published from 2007 to 2018, comprised a minimum of 200 offspring of women with Type 2 diabetes and examined the prevalence of congenital heart defects. Five cohort studies with a total of 23,845 offspring of women with Type 2 diabetes were included. The studies were heterogeneous with respect to method of diagnosis and whether terminated pregnancies were included, and a meta-analysis could not be performed. The mean prevalence of congenital heart defects was 44 (range: 26-65) per 1,000 offspring. The mean relative risk was 0.82 (range: 0.53-1.01) compared with offspring of women with Type 1 diabetes, and 3.83 (range: 2.53-5.49) compared with the background population. A positive association was described between the prevalence of congenital heart defects and the maternal glycated haemoglobin level, but not with medical treatment. The risk of congenital heart defects among offspring of women with Type 2 diabetes was comparable to that of offspring of women with Type 1 diabetes and almost four times higher than in the background population.


A new ultraviolet transparent hydra-cyanurate K2(C3N3O3H) with strong optical anisotropy from delocalized π-bonds.
A new metal hydra-cyanurate, K2(C3N3O3H), was synthesized by a slow evaporation method in aqueous solution. It possesses a short ultraviolet cutoff wavelength at 240 nm. First-principles calculations reveal that its birefringence (∼0.35@800nm) is two times larger than that of commercial calcite crystals. Therefore, K2(C3N3O3H) and metal cyanurates, are very promising ultraviolet birefringent materials in future optical devices.


Permeability of gastric capillaries to small and large molecules.
The permeability of capillaries in the stomach to small and large solutes was studied with the double-indicator diffusion technique in the dog stomach and by analysis of steady-state lymph and plasma samples in the cat stomach. The effective pore radius in gastric capillaries determined by indicator diffusion was 53 A, whereas steady-state lymph samples predicted a small-pore radius of 47 A. At the highest plasma flow rates studied (achieved by intra-arterial infusion of isoproterenol), indicator diffusion estimates of the permeability-surface area product for raffinose, inulin, and beta-lactoglobulin A were 140, 70, and 8 ml . min-1 . 100 g-1, respectively. The lymph studies indicate that gastric capillaries are more permeable than capillaries in the intestine and colon to albumin and larger molecules. The calculated effective large-pore radius of gastric capillaries was 250 A. The osmotic reflection coefficients (sigma d) ranged from 0.73 +/- 0.03 for albumin to 0.91 +/- 0.02 for beta-lipoprotein (120-A radius). The sigma d for total plasma protein was 0.78 +/- 0.03, indicating a substantial transcapillary oncotic pressure gradient, despite the greater permeability of these capillaries for macromolecules.


Familiarity speeds up visual short-term memory consolidation.
Existing long-term memory (LTM) can boost the number of retained representations over a short delay in visual short-term memory (VSTM). However, it is unclear whether and how prior LTM affects the initial process of transforming fragile sensory inputs into durable VSTM representations (i.e., VSTM consolidation). The consolidation speed hypothesis predicts faster consolidation for familiar relative to unfamiliar stimuli. Alternatively, the perceptual boost hypothesis predicts that the advantage in perceptual processing of familiar stimuli should add a constant boost for familiar stimuli during VSTM consolidation. To test these competing hypotheses, the present study examined how the large variance in participants' prior multimedia experience with Pokémon affected VSTM for Pokémon. In Experiment 1, the amount of time allowed for VSTM consolidation was manipulated by presenting consolidation masks at different intervals after the onset of to-be-remembered Pokémon characters. First-generation Pokémon characters that participants were more familiar with were consolidated faster into VSTM as compared with recent-generation Pokémon characters that participants were less familiar with. These effects were absent in participants who were unfamiliar with both generations of Pokémon. Although familiarity also increased the number of retained Pokémon characters when consolidation was uninterrupted but still incomplete due to insufficient encoding time in Experiment 1, this capacity effect was absent in Experiment 2 when consolidation was allowed to complete with sufficient encoding time. Together, these results support the consolidation speed hypothesis over the perceptual boost hypothesis and highlight the importance of assessing experimental effects on both processing and representation aspects of VSTM. (PsycINFO Database Record


Sex, Gender, and Sexual Orientation in Psychological Research: Exploring Data Trends & Researcher Opinions.
Psychology researchers have historically neglected variables related to sex, gender, and sexual orientation, leading to the erasure of sex, gender, and sexual orientation in research, which limits the generalizability of psychological findings. We argue that these important variables need to be considered more consistently by researchers across psychology subdisciplines. In Study 1 we found that 15.1% of a large MTurk sample (i.e., 8500+) identified as a sexual or gender minority (SGM; e.g., lesbian, gay, bisexual, transgender, queer [LGBTQ+]). In addition, data from Study 1 showed that our youngest cohort (i.e., aged 18-25 years) reported significantly higher rates of LGBTQ+ identification (22.7%) than our oldest cohort (i.e., 65-84 years; 1.3%), suggesting that endorsement of these idnetities is increasing. Next, in Study 2 we found that psychology researchers (N = 135) tended to rate expansive sex, gender, and sexual orientation demographic variables as important in general, but were much less likely to report actually using these variables in their own studies. Moreover, younger faculty and faculty who identified as women rated these variables as more important than their colleagues. Based on our findings, we conclude that psychology researchers should use expansive sex, gender, and sexual orientation items in their studies, report these demographic variables consistently, and analyze their data by these important variables when possible. Because a substantial and growing proportion of individuals identify as LGBTQ+, and because SGM identity is related to additional life stressors, it is imperative to better understand these individuals. Various resources are offered and challenges are discussed.


Reversible, metal-free hydrogen activation by frustrated Lewis pairs.
The Lewis acid cyclohexylbis(pentafluorophenyl)boron 1, which exhibits about 15% lower Lewis acidity in comparison with B(C(6)F(5))(3), activates H(2) in the presence of the bulky Lewis bases 2,2,6,6-tetramethylpiperidine (TMP), 1,2,2,6,6-pentamethylpiperidine (PMP), tri-tert-butylphosphine (t-Bu(3)P) leading in facile reactions at room temperature to heterolytic splitting of dihydrogen and formation of the salts [TMPH][CyBH(C(6)F(5))(2)] 2, [PMPH][CyBH(C(6)F(5))(2)] 3 and [t-Bu(3)PH][CyBH(C(6)F(5))(2)] 4, which could be dehydrogenated at higher temperatures. The related Lewis acid 1-phenyl-2-[bis(pentafluorophenyl)boryl]ethane 5 exhibiting about 10% lower Lewis acidity than B(C(6)F(5))(3) is also capable of splitting H(2) in a heterolytic fashion in the presence of TMP, PMP and t-Bu(3)P yielding [TMPH][PhC(2)H(4)BH(C(6)F(5))(2)] 6, [PMPH][PhC(2)H(4)BH(C(6)F(5))(2)] 7 and [t-Bu(3)PH][PhC(2)H(4)BH(C(6)F(5))(2)] 8. Under comparable conditions as for 2-4, the dehydrogenations of 6-8 were much slower. 4b and 6 were characterized by single crystal X-ray diffraction studies.


[Electrophoretic evaluation of blood serum proteins during corticosteroid treatment of women with chronic adnexitis].
In the period 1980-1986 in the II Department of Surgical Gynaecology, Medical Academy in Lublin 61 patients were treated with corticosteroids for chronic adnexitis. They were given prednisone (Encorton POLFA) 10 mg twice daily for 10 days. The clinical effect of regression of infiltrations was achieved in over half the cases. In the analysis of the clinical state, ESR value, leucocytosis and electrophoretic separation of serum proteins it was found that the effectiveness of the treatment was highest in the group of patients with initial ESR values greater than 10 mm after one hour. The mean values of white blood cell count before and after the treatment were without essential prognostic importance. The best results were found in patients without clinical evidence of acute inflammation but with alpha 2globulin proportion in electrophorogram typical for acute phase of inflammation.


[Toxicity of dibutyl phthalate in primary cultured rat hippocampal neurons and the toxicological mechanism].
To investigate the neurotoxicity and toxicological mechanism of dibutyl phthalate (DBP) in primary cultured rat hippocampal neurons. Primary rat hippocampal neurons cultured for 4 days were exposed to 1 g/L DBP for 24, 48, or 96 h. Immunofluorescence assay and transmission electron microscopy (TEM) were used to observe the morphological changes of the axons and the ultrastructure of DBP-treated neurons. The action potential (AP) of the hippocampal neurons was measured with patch-clamp electrophysiology. CCK-8 assay was used to detect the viability of the hippocampal neurons, and Western blotting was performed to determine the mRNA and protein expressions of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY) and estrogen receptor β (ERβ). High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was employed to detect the release of the neurotransmitter GABA. After exposure to DBP for 96 h, the cellular network of the hippocampal neurons became sparse, and the neurons showed significantly decreased axonal length (P < 0.01) and presented with round cell nuclei, chromatin aggregation and cytoplasmic vacuolization. Patch-clamp electrophysiology revealed depolarization drift and increased frequency of discharge in the exposed neurons (P < 0.01). The neurons with DBP exposure for 24, 48 and 96 h all showed significantly decreased cell viability (P < 0.01). DBP exposure for 48 and 96 h significantly lowered the protein expressions of ERβ, BDNF and NPY, and a 96-h exposure significantly reduced the release of the neurotransmitter GABA in the neurons (P < 0.05). DBP exposure causes morphological and functional damages of primary cultured rat hippocampal neurons. DBP-induced neurotoxicity is probably associated with GABA-mediated blockage of the ERβ-BDNF-NPY signaling communication.


Morbidity of breast cancer and cervico-uterine cancer in women from the occidental region of Mexico.
The incidences of breast cancer (BC) and cervico-uterine cancer (CC) vary widely from country to country. In Mexico, BC mortality has doubled in the last 20 years to become the second leading cause of death for women aged 30 to 54 years. CC is the most common cause of death from neoplasia in women over 25 years old. In 2006, the state of Nayarit had one of the highest mortality rates for these types of cancers in Mexico. To analyze and characterize the current demographics and morbidities associated with BC and CC in the state of Nayarit. In this retrospective study, the clinical histories of patients who were diagnosed with BC or CC at the State Cancer Center from January 2006 to December 2010 were analyzed. A total of 406 patients with BC and 328 patients with CC were registered. The most common clinical stage for both cancer types was IIB. The municipalities of San Pedro Lagunillas and El Nayar presented the highest prevalences of BC and CC, respectively. Our results suggest that women living in poorer and more marginalized regions have a higher possibility of developing BC and CC. Because BC and CC are preventable and treatable in their early stages, demographic information from population records for these cancers is helpful in determining the incidence rates and patterns and improving decision-making processes.


Conformational changes in the cytoplasmic domain of human anion exchanger 1 revealed by luminescence resonance energy transfer.
The cytoplasmic domain of the human erythrocyte anion exchanger 1 (cdAE1) serves as a center of organization for the red blood cell cytoskeleton as well as several metabolic enzymes and hemoglobin. The protein is known to undergo a reversible pH-dependent conformational change characterized by a 2-fold change in the intrinsic fluorescence and an 11 A change in the Stokes radius. While the exact changes in the molecular structure are unknown, on the basis of the crystal structure of the protein at pH 4.8 and site-directed mutagenesis studies, Zhou and Low (19) have proposed that the peripheral protein binding (PPB) domain of cdAE1 moves away from the dimerization domain in response to increasing alkalinity. To test this hypothesis, we have applied luminescence resonance energy transfer (LRET) to measure the intermonomer distance between donor and acceptor probes at the Cys201 site (located in the PPB domain) within the cdAE1 dimer. This distance was found to increase as the pH is increased from 5 to 10, in recombinant forms of both the wild type and a mutant (C317S) of cdAE1. Furthermore, LRET measurements in red blood cell inside-out vesicles indicate that when cdAE1 is linked to the membrane, the intermonomer distance is larger at pH 5, compared to that of the purified cdAE1 segments, and exhibits a different pH-dependent behavior. An increase in the distance was also observed on binding of a metabolic enzyme, glyceraldehyde-3-phosphate dehydrogenase, to cdAE1. These data provide the first demonstration of a defined change in the molecular structure of cdAE1, and also indicate that the structure under physiological conditions is different from the crystal structure determined at low pH.


Current Status of CTCs as Liquid Biopsy in Lung Cancer and Future Directions.
Circulating tumor cells (CTCs) have garnered a lot of attention in the past few decades. Isolation of these rare cells from the billions of blood cells has been a challenge until recent times. With the advent of new sensitive technologies that permit live cell isolation and downstream genomic analysis, the existing paradigm of CTC research has evolved to explore clinical utility of these cells. CTCs have been identified as prognostic and pharmacodynamic biomarkers in many solid tumors, including lung cancer. As a means of liquid biopsy, CTCs could play a major role in the development of personalized medicine and targeted therapies. This review discusses the state of various isolation strategies, cell separation techniques and key studies that illustrate the application of liquid biopsy to lung cancer.


The relationship between serum homocysteine and highly sensitive C- reactive protein levels in children on regular hemodialysis.
Hyperhomocysteinemia has attracted a lot of attention in renal patients, not only because of its close relationship with renal function but also because it has been implicated as an independent cardiovascular risk factor in these patients. An increased level of C-reactive protein (CRP) has been reported to be a strong predictor of cardiovascular mortality in hemodialysis (HD) patients. The aim of this study was to assess the association between homocysteine (Hcy) and highly sensitive CRP (hsCRP) in cardiovascular risk prediction in children with chronic kidney disease (CKD) on HD. This case-control study was conducted on 40 children with CKD on regular HD and 20 age- and sex-matched healthy children as controls. Their ages ranged from 4 to 18 years, and they were selected from the pediatric nephrology and HD unit at Al-Azhar University Hospital, during the period from May 2015 to April 2016. Complete blood count, serum ferritin, cholesterol, triglycerides, calcium, phosphorus, parathormone (PTH), Hcy, and hsCRP levels were measured in both groups. Measurements of anthropometry and blood pressure (BP) were performed. There was a significant increase in serum Hcy levels in cases than controls; it was 17.22 ± 9.66 pmol/L and 6.32 ± 1.47 pmol/L, respectively (P <0.01). Furthermore, there was a significant increase in hsCRP in patients than controls; 2.73 ± 2.65 and 0.9 ± 0.85, respectively (P <0.01). There was a significant positive correlation between hsCRP and Hcy with BP, cholesterol, triglyceride, PTH, and ferritin levels. Our data highlighted the important correlation between serum Hcy and hsCRP to detect high-risk patients for subsequent cardiovascular disease and utility of preventive strategies that attenuate inflammatory risk.


External rotation as a result of suprascapular nerve neurotization in obstetric brachial plexus lesions.
Obstetric brachial plexus lesions may cause lifelong limitations of upper limb function. Nerve repair is widely advocated in infants who do not show spontaneous recovery. Typically, the suprascapular nerve (SSN) is involved in the lesion. Neurotization of the SSN routinely is performed, aiming at reinnervation of the infraspinatus muscle to restore external rotation. The results after SSN neurotization have not, as yet, been studied in detail; therefore, this study was undertaken. Of special interest was the comparison of two commonly applied SSN neurotization procedures: nerve grafting from C5 versus nerve transfer of the accessory nerve. Infants with obstetric brachial plexus lesions after nerve grafting of C5 to the SSN (n = 65) or nerve transfer of the accessory nerve to the SSN (n = 21) were selected for retrospective analysis after a mean follow-up period of 3 years. Outcome was expressed in degrees of true glenohumeral external rotation. This was defined as the angle between the position of the 90 degrees (actively or passively) flexed elbow resting against the abdomen and the position of the flexed elbow after external rotation with the upper arm held in adduction by the investigator. This movement can be executed only by infraspinatus muscle contraction. In addition, functional external rotation was evaluated by testing the ability to reach the mouth and the back of the head. Only 17 (20%) of the 86 patients reached more than 20 degrees of external rotation, whereas 35 (41%) were unable to perform true external rotation. There was no statistically significant difference between nerve grafting from C5 and extraplexal nerve transfer using the accessory nerve. Functional scores showed that 88% can reach the mouth and that 75% can reach the head. The restoration of a fair range of true glenohumeral external rotation after neurotization of the SSN in infants with obstetric brachial plexus lesions, whether by grafting from C5 or by nerve transfer of the accessory nerve, is disappointingly low. However, it seems that compensatory techniques contribute to effectuate a considerable range of movement.


Improvement of left ventricular function after percutaneous coronary intervention in patients with stable coronary artery disease and preserved ejection fraction: Impact of diabetes mellitus.
Many patients with stable coronary artery disease (CAD) have no visual segmental wall motion abnormalities and a left ventricular (LV) ejection fraction (LVEF) ≥ 50% at rest despite significant coronary artery stenosis. Here, the aim was to determine the impact of percutaneous coronary intervention (PCI) on LV function assessed by enhanced echocardiography in patients with stable CAD with or without diabetes mellitus type 2 and a preserved LVEF. Sixty-six consecutive patients with CAD and LVEF ≥ 50%, admitted to the hospital for planned coronary angiography, were prospectively assessed. PCI was performed for coronary artery stenosis > 70%. CAD extent was assessed using SYNTAX and EXTENT scores. To assess LV function, LVEF, global longitudinal strain (GLS), and LV peak systolic myocardial velocity (S') were measured and Tei index was calculated before and 3 months after PCI. Before PCI, LVEF, GLS, and Tei index were significantly worse in diabetic patients. LV functional indices improved significantly after PCI in all patients (p < 0.001). Multivariate linear regression analyses were performed to evaluate the impact of selected factors on LV function after PCI expressed as changes (D) of LVEF, GLS, S', and Tei index. LV function improvement expressed as DGLS was associated only with SYNTAX score. Higher SYNTAX scores were related to greater GLS improvement (b = 0.003, 95% confidence interval: 0.0004-0.005; p = 0.02). Percutaneous coronary intervention significantly improved LV function in diabetic and non-diabetic CAD patients with preserved LVEF. Enhanced echocardiography allowed an assessment of subtle changes in LV function.


[Functional changes in the cardioesophageal region following laparoscopic fundoplication].
Functional changes of antireflux mechanisms after laparoscopic fundpolication. To examine manometry and pH-study in evaluation of the changes in measurable features of antireflux mechanisms after fundoplication for gastro-oesophageal reflux disease. Laparoscopic Nissen-Rossetti fundoplications with hiatorhaphy were performed in patients with gastroesophageal reflux disease. Preoperative and postoperative manometry and pH-study were compared in set of twenty satisfied orjerated without any complaints after surgery who agreed with preoperative and postoperative examinations. Higher length of lower esophageal sphincter following antireflux fundoplication (P = 0.0003), increased tone of lower esophageal sphincter with antireflux fundoplication (P = 0.0001) and lower value of pH-study after fundoplication (P = 0.0001) were observed. Postoperative manometry and pH-study effectively evaluated gastro-oesophageal reflux changes following fundoplication for gastro-oesophageal reflux disease.


Mobile pedunculated left ventricular masses in a man with recurrent emboli.
A 51-year-old man was found to have left ventricular masses by transthoracic echocardiography, one attached to the posterior wall of the left ventricle and another attached to the anterolateral wall of the left ventricle. He had several events of systemic embolization over the last few weeks. Surgical excision was recommended to avoid further embolization. The patient underwent successful resection of the left ventricular masses under cardiopulmonary bypass through the left atrial and transverse aortotomy approach. Histopathologic exam was diagnostic for organized thrombi.


Biomarkers and the prediction of atrial fibrillation: state of the art.
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, and it places a substantial burden on the health care system. Despite improvements in our understanding of AF pathophysiology, we have yet to develop targeted preventive therapies. Recently, numerous biological markers have been identified to aid in the prediction of future AF events. Subclinical markers of atrial stress, inflammation, endothelial dysfunction, kidney dysfunction, and atherosclerosis have been linked to AF. The connection between these markers and AF is the identification of subclinical states in which AF propagation is likely to occur, as these conditions are associated with abnormal atrial remodeling and fibrosis. Additionally, several risk scores have been developed to aid in the identification of at-risk patients. The practicing clinician should be aware of these subclinical markers, as several of these markers improve the predictive abilities of current AF risk scores. Knowledge of these subclinical markers also provides clinicians with a better understanding of AF risk factors, and the opportunity to reduce the occurrence of AF by incorporating well-known cardiovascular disease risk factor modification strategies. In this review, we highlight several novel biological markers that have improved our understanding of AF pathophysiology and appraise the utility of these markers to improve our ability to predict future AF events.


Identification of the adult resting progenitor cell by autoradiographic tracking of oligodendrocyte precursors in experimental CNS demyelination.
The new population of oligodendrocytes remyelinating an experimental demyelinating optic nerve lesion has been tracked backwards in time. Using autoradiography combined with electron microscopy and immunocytochemistry, serial sections of optic nerves from young adult cats were studied from 42 h (2 days) post-injection to 93 h (4 days) post-injection. The remyelinating oligodendrocyte lineage was found to commence with the single division of a resting progenitor cell residing in a central fascicular location outside the demyelinative lesion. The division of the founding progenitor cell occurs at 2 days post-lesion and results in two motile daughter cells. These cells, previously described by us as precursor cells, migrate to the lesion, closely appose demyelinated axons, produce axon wrapping processes and differentiate to become remyelinating oligodendrocytes. This study confirms that remyelinating oligodendrocytes originate from resting progenitor cells outside the lesion and not from mature oligodendrocytes, and implies that repeated demyelinative injury could exhaust the reparative capacity of such a region.


Extracellular vesicles in renal disease.
Extracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell-cell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information. We also describe their physiological functions in cellular interactions, such as in thrombosis, immune modulation, cell proliferation, tissue regeneration and matrix modulation, with an emphasis on renal processes. We discuss how the detection of extracellular vesicles could be utilized as biomarkers of renal disease and how they might contribute to disease processes in the kidney, such as in acute kidney injury, chronic kidney disease, renal transplantation, thrombotic microangiopathies, vasculitides, IgA nephropathy, nephrotic syndrome, urinary tract infection, cystic kidney disease and tubulopathies. Finally, we consider how the release or uptake of extracellular vesicles can be blocked, as well as the associated benefits and risks, and how extracellular vesicles might be used to treat renal diseases by delivering therapeutics to specific cells.


Ventricular unipolar potential in radiofrequency catheter ablation of idiopathic non-reentrant ventricular outflow tachycardia.
We conducted this study to verify the efficacy of ventricular unipolar potential (V-uni) for ablation of idiopathic non-reentrant ventricular tachycardia (idio-VT). The morphology of V-uni at the successful and unsuccessful sites was analyzed in 27 patients with idio-VT [20 with right ventricular outflow tachycardia (RVOVT) and 7 with left ventricular outflow tachycardia (LVOVT)]. The usefulness of V-uni was compared with a pacemapping method and the V-QRS interval. The incidence of QS-pattern V-uni at the successful and best unsuccessful sites were 100 versus 25% (P = 0.000005) in RVOVT and 86 versus 29% (P = 0.10) in LVOVT. The pacemapping scores at the successful and best unsuccessful sites were 11.5/12 versus 11.2/12; NS in RVOVT, and 11.2/12 versus 11.1/12; NS in LVOVT. The mean V-QRS interval at the successful and the best unsuccessful sites were 22.5 +/- 3.8 versus 21.6 +/- 3.4 msec; NS in RVOVT, 15.1 +/- 3.2 versus 12.5 +/- 3.3 msec; NS in LVOVT. The sensitivity (sen) and specificity (spe) of QS-pattern V-uni to determine the optimum target sites were 1.0 and 0.89 in RVOVT and 0.86 and 0.83 in LVOVT, respectively. In the ablation of idio-VT, QS-pattern V-uni is simply and visually identifiable, is very useful, and should be given a high priority when determining the optimum target site.


Reducing the distal profile of dual mobility liners can mitigate soft-tissue impingement and liner entrapment without affecting mechanical performance.
Soft-tissue impingement with dual mobility liners can cause anterior hip pain and intra-prosthetic dislocation. The hypothesis of this study was that reducing liner profile below the equator (contoured design) can mitigate soft-tissue impingement without compromising inner-head pull-out resistance and hip joint stability. The interaction of conventional and contoured liners with anterior soft tissues was evaluated in cadaver specimens via visual observation and fluoroscopic imaging. Resistance to inner-head pull-out was evaluated via finite element analyses, and hip joint stability was evaluated by rigid-body mechanics simulation of dislocation in two modes (A, B). Cadaveric experiments showed that distal portion of conventional liners impinge on anterior hip capsule and cause iliopsoas tenting at low flexion angles (≤30°). During hip extension, the rotation imparted to the liner from posterior engagement with femoral neck was impeded by anterior soft-tissue impingement. The iliopsoas tenting was significantly reduced with contoured liners (p ≤ 0.04). Additionally, the contoured and conventional liners had identical inner-head pull-out resistance (901 N vs. 909 N), jump distance (9.4 mm mode-A, 11.7 mm mode-B) and impingement-free range of motion (47° mode-A, 29° mode-B). Thus, soft-tissue impingement with conventional dual mobility liners may be mitigated by reducing liner profile below the equator, without affecting mechanical performance. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:889-897, 2016.


Predicting mixing via resonances: Application to spherical piecewise isometries.
We present an analytic method to find the areas of nonmixing regions in orientation-preserving spherical piecewise isometries (PWIs), and apply it to determine the mixing efficacy of a class of spherical PWIs derived from granular flow in a biaxial tumbler. We show that mixing efficacy has a complex distribution across the protocol space, with local minima in mixing efficacy, termed resonances, that can be determined analytically. These resonances are caused by the interaction of two mode-locking-like phenomena.


Therapeutic modalities for patients with lower-risk myelodysplastic syndromes: current options and future directions.
The treatment of myelodysplastic syndromes (MDS) involves a complex algorithm that depends on multiple factors, including symptoms, performance status, and severity of disease. Current therapies are aimed at promoting hematopoiesis, inhibiting apoptosis, and reducing the risk of transformation to acute myeloid leukemia. Although there is no cure for MDS outside of allogeneic stem cell transplantation, goals of treatment include improvement of peripheral blood cytopenias, reduction of transfusions, improvement of the quality of life, and prolongation of survival. Patients with lower-risk MDS are often asymptomatic and can be monitored for long periods without therapeutic intervention. Anemia, the most common symptomatic cytopenia, warrants treatment in an attempt to eliminate transfusion dependence. This article reviews current treatment strategies for lower-risk MDS and examines the data for selected novel agents that are available or are being developed for the treatment of this disease.


Power spectral density of free-standing viscoelastic films by adiabatic approximation.
In a previous study, we calculated the surface dynamics of noisy viscoelastic supported films by using an adiabatic approximation. An expression was derived for the time-dependent power spectral density (PSD), which was found to produce good agreement with experiment. In this study, we extend the treatment to viscoelastic free-standing films. Two sets of surface capillary normal modes, namely, the squeezing and bending modes, were found. The frequency dispersion relation of the former resembles that of supported films. The latter is distinctively different and diverges at long wavelengths. By incorporating the experimental conditions, we obtained satisfactory agreement between theory and experiment.


Genistein Suppressing the ROS-Induced Hypersensitivity of Rat Vagal Lung C-Fiber Afferents through an ERα-Mediated Mechanism.
Reactive oxygen species (ROS) may induce hypersensitivity of vagal lung C-fibers (VLCFs) through the interaction of transient receptor potential ankyirn 1 (TRPA1) and P2X receptors. Genistein is a soy-derived isoflavone that exerts antioxidant effects by binding to estrogen receptors (ERs), ERα and ERβ. We investigated whether ER activation by genistein can suppress H₂O₂-mediated VLCF hypersensitivity and identified the types of ERs involved. Results revealed that subcutaneous injection of genistein or 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, a selective ERα agonist) can attenuate H₂O₂-induced VLCF hypersensitivity. The suppressive effects of genistein and PPT were inhibited by an additional treatment with ICI182780 (a nonselective ER antagonist) or 1,3-bis(4- hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP, a selective ERα antagonist). Treatment with a combination of PPT, HC030031 (a TRPA1 receptor antagonist), and iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS, a P2X receptor antagonist) did not further inhibit H₂O₂-induced VLCF hypersensitivity as compared with combined HC030031 and iso-PPADS treatment. In conclusion, ERα activation by genistein can suppress H₂O₂- induced VLCF hypersensitivity through its functional interaction with TRPA1 and P2X receptors.


Extracting tag hierarchies.
Tagging items with descriptive annotations or keywords is a very natural way to compress and highlight information about the properties of the given entity. Over the years several methods have been proposed for extracting a hierarchy between the tags for systems with a "flat", egalitarian organization of the tags, which is very common when the tags correspond to free words given by numerous independent people. Here we present a complete framework for automated tag hierarchy extraction based on tag occurrence statistics. Along with proposing new algorithms, we are also introducing different quality measures enabling the detailed comparison of competing approaches from different aspects. Furthermore, we set up a synthetic, computer generated benchmark providing a versatile tool for testing, with a couple of tunable parameters capable of generating a wide range of test beds. Beside the computer generated input we also use real data in our studies, including a biological example with a pre-defined hierarchy between the tags. The encouraging similarity between the pre-defined and reconstructed hierarchy, as well as the seemingly meaningful hierarchies obtained for other real systems indicate that tag hierarchy extraction is a very promising direction for further research with a great potential for practical applications. Tags have become very prevalent nowadays in various online platforms ranging from blogs through scientific publications to protein databases. Furthermore, tagging systems dedicated for voluntary tagging of photos, films, books, etc. with free words are also becoming popular. The emerging large collections of tags associated with different objects are often referred to as folksonomies, highlighting their collaborative origin and the "flat" organization of the tags opposed to traditional hierarchical categorization. Adding a tag hierarchy corresponding to a given folksonomy can very effectively help narrowing or broadening the scope of search. Moreover, recommendation systems could also benefit from a tag hierarchy.


Framboidal Nanoparticles Containing a Curcumin-Phenylboronic Acid Complex with Antiangiogenic and Anticancer Activities.
Curcumin (Cur) has a wide range of bioactivities that show potential for the treatment of cancer as well as chronic diseases associated with inflammation and aging. However, the therapeutic efficacy of Cur has been hampered by its rapid degradation under physiological conditions and low aqueous solubility. To address these problems, we prepared Cur-loaded polymeric nanoparticles (CNPs), in which Cur was complexed with phenylboronic acid-containing framboidal nanoparticles (NPs), by simple mixing of Cur and NPs in an aqueous solution. CNPs showed improved chemical stability of Cur and released it in a sustained manner under physiological conditions. Furthermore, CNPs significantly enhanced the antiangiogenic and anticancer activities of Cur in chicken chorioallantoic membrane models.


Interventions for postoperative pain in children: An overview of systematic reviews.
The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti-inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non-Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.


Barodontalgia Among Aircrew and Divers.
BACKGROUND: Barodontalgia, barometric pressure-induced dental pain, may jeopardize diving/flight safety. The aim of this systematic review was to investigate the rate of barodontalgia among military and civilian divers and aircrews based on previous reports.METHODS: We analyzed the data of 4894 aircrew/divers reported in the literature. Barodontalgia rates (flight vs. diving, military vs. civilian, pressurized vs. non-pressurized aircrafts) were analyzed. The Chi-squared test was used to compare between groups.RESULTS: Of the 4894 individuals, 402 (8.2%) suffered from barodontalgia. Divers (9.8%) were more vulnerable than aircrews (5.8%). Barodontalgia experience rate was 5.4% and 6.5% in military and civilian aircrews, respectively, and 7.3% and 12.8% in military and civilian scuba divers, respectively. Barodontalgia was more common among aircrews of pressurized than non-pressurized aircrafts (7.3% vs. 3.2%, respectively).DISCUSSION: The greater amplitude of barometric pressure changes explains the higher rate of barodontalgia in divers than aircrew. The higher rate during pressurized flights is possibly because intracabin pressure in the pressurized cabin is still routinely higher than in nonpressurized aircrafts. Improved oral care and mandatory annual dental checkups may be the reason for the significantly lower rate of barodontalgia experienced among military aircrews and divers compared to their civilian counterparts. These results emphasize the essential role of atmospheric pressure change in the generation of pain during flight or diving and the importance of proper dental care.Nakdimon I, Zadik Y. Barodontalgia among aircrew and divers. Aerosp Med Hum Perform. 2019; 90(2):128-131.


Compact coupling scheme to achieve the synchronously dual self-mode-locked operation with a 35.2 THz optical beating.
A synchronously dual self-mode-locked (SML) operation at 946 and 1064 nm is experimentally accomplished by using a compact coupling scheme to obtain the optical beating frequency up to 35.2 THz. The SML emissions at 946 and 1064 nm are established by a monolithic Nd:YAG cavity and a Nd:YVO4 crystal in a flat-flat cavity, respectively. Two gain media are butt adjoined to be longitudinally pumped by a single laser diode. The monolithic Nd:YAG crystal is used not only as the 946 nm laser cavity, but also as the output coupler of the Nd:YVO4 1064 nm laser. More importantly, the output surface of the monolithic Nd:YAG laser is coated to generate the optical feedback for the synchronization of the dual SML operation. At a pump power of 10.7 W, the output powers at 1064 and 946 nm can simultaneously reach 1.5 W by controlling the focal position of the pump waist.


Nano-carrier mediated co-delivery of methyl prednisolone and minocycline for improved post-traumatic spinal cord injury conditions in rats.
The objective of this study is to investigate the fate of albumin coupled nanoparticulate system over non-targeted drug carrier in the treatment of hemisectioned spinal cord injury (SCI). Targeted delivery of methyl prednisolone (MP) and minocycline (MC) portrayed improved therapeutic efficacy as compared with non-targeted nanoparticles (NPS). Albumin coupled, chitosan stabilized, and cationic NPS (albumin-MP + MC - NPS) of poly-(lactide-co-glycolic acid) were prepared using the emulsion solvent evaporation method. Prepared NPS were characterized for drug entrapment efficiency, particle size, poly-dispersity index (PDI), zeta potential, and morphological characteristics. Their evaluation was done based on the pharmaceutical, toxicological, and pharmacological parameters. In vitro release of MP + MC from albumin-MP + MC - NPS and MP + MC - NPS was observed to be very controlled for the period of eight days. Cell viability study portrayed non-toxic nature of the developed NPS. Albumin-MP + MC - NPS showed prominent anti-inflammatory potential as compared with non-targeted NPS (MP + MC - NPS) when studied in LPS-induced inflamed astrocytes. Albumin-MP + MC - NPS reduced lesional volume and improved behavioral outcomes significantly in rats with SCI (hemisectioned injury model) when compared with that of MP + MC - NPS. Albumin-coupled NPS carrier offered an effective method of SCI treatment following safe co-administration of MP and MC. The in vitro and in vivo effectiveness of MP + MC was improved tremendously when compared with the effectiveness showed by MP + MC - NPS. That could be attributed to the site specific, controlled release of MP + MC to the inflammatory site.


Management of Severely Atrophic Mandibular Ridge using Hollow Denture with an Analytical Discussion: A Clinical Case Report.
A severely resorbed edentulous mandibular ridge, although fairly common in occurrence, its rehabilitation poses a challenging clinical situation for the prosthodontist. This has implored prosthodontists to seek for ingenious modifications in the conventional prosthetic forms so as to gratify patient's expectations who have difficulty in wearing the mandibular complete dentures. Opting for the most suitable treatment modality mandates equilibrating the retention, stability and support triad to the fullest. Extreme resorption of the denture bearing tissue bed may lead to problems with achieving adequate levels of prosthetic satisfaction for the patient. One such entrusted treatment option, that has proven its mettle over tides of time in such a scenario, the hollow denture by virtue of its reduced excessive acrylic resin weight, efficaciously replaces the lost voluminous alveolar ridge in the increased inter-ridge space of the denture wearer.