[Omitted spinal X-ray examination after a fall from a height of 3 m].
A 59-year-old patient with right-sided chest pains after a fall from a height of 3 m was referred to hospital by an emergency physician. The chest x-rays showed fractures of the third and seventh ribs on the right side. Inpatient analgesic therapy was initiated and after 3 days the patient was discharged from hospital for further outpatient treatment. As the pain persisted the patient consulted a surgeon 5 weeks later and the first X-ray examination of the spine was carried out which revealed the formation of several wedge-shaped thoracolumbar vertebral bodies. Further magnetic resonance imaging (MRI) diagnostics also revealed alterations to T10, T12, L1 and L3 as well as radiological signs of Scheuermann's disease; however, a definite statement differentiating these findings from older spinal fractures as a result of the accident was no longer possible. The patient claimed that the hospital failed to perform spinal X-ray investigations leading to prolonged pain and limitations in the quality of life. An external expert stated that the distracting injury of the ribs and the pain medication might have veiled the additional vertebral fractures. Thus, an earlier diagnosis of the apparently stable vertebral fractures would not have changed the conservative therapy approach. The decision of the arbitration board differed from the expert opinion as additional imaging techniques of the spine should have been initially performed due to the mechanism of injury. Although no irreversible damage to health resulted an earlier targeted treatment could have reduced the overall length of therapy.


Consequences of Obstructive Sleep Apnea in Children.
Obstructive sleep apnea syndrome (OSAS) has various negative health and behavioral consequences in the pediatric population. As shown in adults, there are metabolic derangements such as obesity, insulin sensitivity, dyslipidemia, and metabolic syndrome, as well as cardiovascular derangements like hypertension, chronic inflammation, endothelial dysfunction, ventricular size/function abnormalities, and even elevated pulmonary arterial pressures, that can be seen in children with OSAS. The first two sections will discuss the metabolic and cardiovascular consequences on OSAS in children. The last section summarizes selected studies and reviews on the behavioral, neurocognitive and academic consequences of OSAS in children.


Appetitive traits and food groups consumption in school-aged children: prospective associations from the Generation XXI birth cohort.
Appetite can influence children's dietary choices; however, this relationship in school-aged children is still unclear. We aimed to explore the prospective associations between child appetitive traits at age 7 and food consumption at 10 years of age. The study included 3860 children from the Generation XXI birth cohort, recruited in 2005/2006 in Porto, Portugal. The Children's Eating Behaviour Questionnaire was used to evaluate children's appetitive traits at 7 years. Food consumption was measured at 10 years through a validated Food Frequency Questionnaire. Logistic regression models were performed and adjusted for possible confounders. Children with greater Enjoyment of Food at 7 years were 36% more likely to eat fruits ≥ 2 times/day and 54% more likely to eat vegetables > 2.5 times/day at 10 years compared to those with less frequent consumption. Children who ate more in response to negative emotions had higher odds of consuming energy-dense foods (OR = 1.33; 99% CI 1.13-1.58) and salty snacks (OR = 1.28; 99% CI 1.08-1.51) 3 years later. Those with less ability to adjust intake (higher Satiety Responsiveness) and more selective about foods (higher Food Fussiness) at 7 years were less likely to consume vegetables frequently, and were more likely to consume energy-dense foods and sugar-sweetened beverages. Children's appetitive traits at 7 years were associated with the consumption of several food groups at 10 years of age. Eating more in response to negative emotions (Emotional Eating), with less ability to adjust intake (Satiety Responsiveness) and more food selectivity (Food Fussiness) were associated with worse dietary choices (in general, lower fruit and vegetables, and higher energy-dense foods and sugar-sweetened beverages consumption). Level III: Evidence obtained from well-designed cohort or case-control analytic studies.


Effect of vasopressin on the expression of genes for key enzymes of hyaluronan turnover in Wistar Albino Glaxo and Brattleboro rat kidneys.
Hyaluronan (HA), the major glycosaminoglycan of the interstitial matrix, is heterogeneously distributed within the kidney. Using real-time RT-PCR, we tested the assumption that renal HA may be involved in the long-term effect of vasopressin on water reabsorption. The expression of the genes encoding hyaluronan synthase-2 (Has2), hyaluronidase-1 and hyaluronidase-2 (Hyal1 and Hyal2) was studied in the kidneys of Wistar Albino Glaxo (WAG) and homozygous vasopressin-deficient Brattleboro rats treated with the V2 receptor-selective vasopressin analogue dDAVP (100 μg (kg body wt)(-1), i.p., twice a day for 2 days). The Has2 mRNA content was the highest in the kidney papilla of the hydrated WAG and control Brattleboro rats, devoid of vasopressin. In WAG rats, dDAVP induced a considerable decrease in Has2 mRNA content in the papilla, with less pronounced changes in the cortex. The changes elicited by dDAVP in Brattleboro rats tended to be the same as in WAG rats, but weaker. In contrast to Has2, dDAVP treatment caused a significant increase in the Hyal1 and Hyal2 mRNA content in the renal papilla of WAG and Brattleboro rats. In rats of both strains, there was a good fit between Hyal1 and Hyal2 transcriptional levels and changes in hyaluronidase activity in the renal tissue. It is suggested that vasopressin is able to inhibit the synthesis of HA and concomitantly promote its degradation in the interstitium of the renal papilla, thereby facilitating water flow between elements of the renal countercurrent system. The implications for this effect are discussed in the context of the data in the literature.


Cooperation between Rho-GEF Gef2 and its binding partner Nod1 in the regulation of fission yeast cytokinesis.
Cytokinesis is the last step of the cell-division cycle, which requires precise spatial and temporal regulation to ensure genetic stability. Rho guanine nucleotide exchange factors (Rho GEFs) and Rho GTPases are among the key regulators of cytokinesis. We previously found that putative Rho-GEF Gef2 coordinates with Polo kinase Plo1 to control the medial cortical localization of anillin-like protein Mid1 in fission yeast. Here we show that an adaptor protein, Nod1, colocalizes with Gef2 in the contractile ring and its precursor cortical nodes. Like gef2, nod1 has strong genetic interactions with various cytokinesis mutants involved in division-site positioning, suggesting a role of Nod1 in early cytokinesis. We find that Nod1 and Gef2 interact through the C-termini, which is important for their localization. The contractile-ring localization of Nod1 and Gef2 also depends on the interaction between Nod1 and the F-BAR protein Cdc15, where the Nod1/Gef2 complex plays a role in contractile-ring maintenance and affects the septation initiation network. Moreover, Gef2 binds to purified GTPases Rho1, Rho4, and Rho5 in vitro. Taken together, our data indicate that Nod1 and Gef2 function cooperatively in a protein complex to regulate fission yeast cytokinesis.


Ischemic myopathy revealing systemic calciphylaxis.
Patients with renal failure who are being treated with dialysis frequently develop neuromuscular manifestations. Renal failure-associated calciphylaxis, also termed calcific uremic arteriolopathy (CUA), is a life-threatening condition usually observed in patients with end-stage renal disease on chronic dialysis or after renal transplantation. We describe a hemodialyzed patient who presented with rapidly progressive unexplained systemic vasculopathy, muscle atrophy, and proximal weakness, that unexpectedly proved to be caused by calciphylaxis. Quadriceps muscle biopsy disclosed diffuse vascular calcific deposits on medium- and small-sized vessels, characteristic of CUA. Other changes included ischemic myopathy, focal intracellular calcium accumulation within myofibers, and calcium deposits in endomysial capillaries associated with marked complement activation and C5b9 formation. There are only a few descriptions of muscle involvement in the context of CUA, a condition with a prognosis that depends on early diagnosis and treatment. This report underscores the usefulness of muscle biopsy in the diagnosis of systemic calciphylaxis. Muscle Nerve 56: 529-533, 2017.


Regional emphysema score is associated with tumor location and poor prognosis in completely resected NSCLC patients.
Lung cancer is a frequent comorbidity of chronic obstructive pulmonary disease (COPD). However, the local risk of developing lung cancer related to regional emphysema distribution and clinical outcome has not been investigated. Our aim was to evaluate the impact of regional emphysema score (RES) on tumor location and prognosis in non-small cell lung cancer (NSCLC) patients. We enrolled 457 patients who underwent curative surgery for NSCLC at seven hospitals at The Catholic University of Korea from 2014 to 2018. Emphysema was visually assessed for each lobe, with the lingula as a separate lobe. Semi-quantitative emphysema scoring was classified as follows: 0 = none, 0.5 = 1 to 10%, 1 = 11 to 25%, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. An RES was given to each of the six lung zone: the upper, middle, and lower lobes in the right and left lungs. There were 145 patients in the high RES (≥ 3) group and 312 in the low RES (< 3) group. The mean RES in each lobe with cancer was significantly higher than that in other lobes without cancer (0.51 vs. 0.37, P < 0.001). This group showed significantly shorter disease-free survival (P < 0.001), in addition, presence of COPD, low diffusing capacity of the lung for carbon monoxide (< 80), smoking status, and poor differentiation were more frequent in this group. Also, cancer in a lobe with a higher RES (odds ratio (OR) = 1.56; 95% confidence interval (CI:1.01-2.42; P = 0.04), pathologic stage ≥ III (OR = 2.23; 95% CI: 1.28-3.89; P < 0.001), and poor differentiation (OR = 1.99; 95% CI: 1.22-3.21; P < 0.001) were independent factors for tumor recurrence. The regional severity of emphysema by visual qualification was associated with the location of lung cancer, and was an independently poor prognostic factor for tumor recurrence in completely resected NSCLC patients.


Impacts of repeated coastal flooding on soil and groundwater following managed dike realignment.
Coastal defense structures (e.g., dikes, seawalls) protect vulnerable communities along marine coastlines and estuaries from the physical and chemical influences of adjacent water bodies. These structures are susceptible to overtopping or breaching by tides and waves, with risks amplified by climate change-induced sea-level rise. Repeated inundation by saline water can contaminate freshwater resources and salinize soil, impacting land-use activities, including agricultural productivity. Managed ecosystem-based dike realignment and salt marsh restoration can provide alternatives to traditional coastal adaptation approaches. We assess the changes to soil salinity at a managed dike realignment project prior to the transformation from a diked terrestrial environment to an estuarine environment. Baseline data are compared to conditions following 8-10 months of intermittent flooding at spring tides. Results show that an increase in salinity occurred over the entire site in the shallow subsurface, with the most significant contamination occurring in low-lying areas. Bulk soil electrical conductivity (salinity proxy) measured from geophysical surveys increased from the previous freshwater condition of ∼300 μS/cm to over 6000 μS/cm following <20 flood events, while successive flooding resulted in increased soil moisture as infiltrated floodwater propagated to greater depths. Sediment deposition occurred at high rates, with up to 4 cm of sediment deposited per flood, converting much of the previously cultivated land into tidal mudflats. Deeper sediments and groundwater (i.e., >1.8 m depth) were not impacted over the time scale of this research. This study demonstrates that intermittent shallow flooding can rapidly increase moisture content and soil salinity in surficial sediments and, in turn, adversely impact conditions suitable for agricultural crop production. The realignment zone serves as an engineered analog of coastal flooding, presenting an opportunity to investigate how low-lying coastal environments may experience regular flooding in the future due to sea-level rise and intensifying coastal storms.


Phosphotransfer circuitry of the putative multi-signal transducer, ArcB, of Escherichia coli: in vitro studies with mutants.
Recently we demonstrated the occurrence of a novel device of signal transducers in Escherichia coli. This class of bacterial sensory kinases, typified by ArcB and BarA, possesses two phospho-donor (His) sites, together with a phospho-accepting (Asp) site. These multi-phosphorylation sites were suggested to make a phosphotransfer circuit. To clarify this complex circuitry, we carried out a series of in vitro assays involving a set of ArcB mutant proteins which have an amino acid substitution at each putative phosphorylation site (His-292, Asp-576 and His-717). By these in vitro phosphorylation and/or phosphotransfer assays, the followings were assessed: (i) ArcB autophosphorylation; (ii) ArcB-mediated phosphorylation of the cognate response regulator, ArcA; (iii) ArcB-mediated phosphorylation of its truncated form (ArcBc) encompassing only the C-terminal phosphorylation site (His-717); (iv) phosphotransfer from ArcBc to ArcA; and (v) phosphotransfer from ArcBc to ArcB. On the basis of these in vitro results, a complex circuitry was revealed for the signal transducer ArcB. This evidence obtained in vitro supports the view that ArcB can serve as a powerful device for not only propagating multi-signals, but also making up signalling networks, in ways more sophisticated than previously thought.


Improved telemetric EEG monitoring in epileptic patients.
A 20-channel EEG telemetry system provides EEG monitoring with standard EEG recording performance for use in epileptic patients. The EEG activities of 20 electrodes are separately amplified and transmitted employing PCM cable telemetry. A standard EEG apparatus is used, allowing montages to be freely selected and changed during recording.


In vitro and intrathecal siRNA mediated K(V)1.1 knock-down in primary sensory neurons.
K(V)1.1 is a Shaker homologue K(+) channel that contributes to the juxta-paranodal membrane conductance in myelinated axons, and is blocked by fampridine (4-aminopyridine), used to treat the symptoms of multiple sclerosis. The present experiments investigate K(V)1.1 function in primary sensory neurons and A-fibres, and help define its characteristics as a drug-target using sequence specific small-interfering RNAs (siRNAs). siRNA (71nM) was used to knock-down functional expression of K(V)1.1 in sensory neurons (>25μm in apparent diameter) in culture, and was also delivered intrathecally in vivo (9.3μg). K(+) channel knock-down in sensory neurons was found to make the voltage-threshold for action potential generation significantly more negative than in control (p=0.02), led to the breakdown of accommodation and promoted spontaneous action potential firing. Exposure to dendrotoxin-K (DTX-K, 10-100nM) also selectively abolished K(+) currents at negative potentials and made voltage-threshold more negative, consistent with K(V)1.1 controlling excitability close to the nominal resting potential of the neuron cell body, near -60mV. Introduction of one working siRNA sequence into the intrathecal space in vivo was associated with a small increase in the amplitude of the depolarising after-potential in sacral spinal roots (p<0.02), suggesting a reduction in the number of working K(+) channels in internodal axon membrane. Our study provides evidence that K(V)1.1 contributes to the control of peripheral sensory nerve excitability, and suggests that its characteristics as a putative drug target can be assessed by siRNA transfection in primary sensory neurons in vitro and in vivo.


Design and characterization of new β-glucuronidase active site variants with altered substrate specificity.
To isolate and characterize the kinetics of variants of E. coli β-glucuronidase (GUS) having altered substrate specificity. Two small combinatorial libraries of E. coli GUS variants were constructed and screened for improved activities towards the substrate p-nitrophenyl-β-D-galactoside (pNP-gal). Nine of the most active variants were purified and their kinetic parameters were determined. These variants show up to 134-fold improved kcat/KM value towards pNP-gal compared to wild-type GUS, up to 9 × 108-fold shift in specificity from p-nitrophenyl-β-D-glucuronide (pNP-glu) to pNP-gal compared to wild-type, and 103-fold increase in specificity shift compared to a previously evolved GUS variant. The kinetic data collected for nine new GUS variants is invaluable for training computational protein design models that better predict amino acid substitutions which improve activity of enzyme variants having altered substrate specificity.


Risk-of-bias assessment of the randomized clinical trials and systematic reviews on surgical treatments for breast cancer-related lymphedema: A mapping review.
Breast cancer treatment is the principal cause of lymphedema in the upper extremities. Breast cancer-related lymphedema (BCRL) treatments were previously based on conservative therapy; surgical treatments are alternative options that could be highly beneficial, especially for patients who are not responsive to conservative therapy. The main aim of this study was to describe and critically assess the risk of bias of randomized clinical trials (RCTs) and systematic reviews (SRs) on surgical treatment for BCRL. We conducted an evidence mapping review according to the methodology proposed by Global Evidence Mapping (GEM). An update was done for our previous systematic search in MEDLINE, EMBASE, CENTRAL (Cochrane), and Epistemonikos from the year 2000 onward. We assessed the risk of bias for the RCTs and SRs using the RoB-2 and ROBIS tools, respectively. Two surgical RCTs and eight SRs were found among the 47 surgical studies that met the eligibility criteria. The overall risk-of-bias assessments of these studies were rated as some concerns (six outcomes) and high risk (three outcomes) for the measured outcomes among the RCTs and as a high risk of bias (five studies) and low risk (three studies) for the included SRs. The overall evidence in the literature on surgical treatment for BCRL is low, as there are few published RCTs and SRs, and the risk-of-bias assessment for the majority was rated as high risk of bias or with some concerns. High-quality studies are needed to improve evidence-based decision-making by surgeons and patients.


Bromodomain protein 4 mediates the roles of TGFβ1-induced Stat3 signaling in mouse liver fibrogenesis.
Epigenetic reader Bromodomain protein 4 (BrD4) functions as a global genomic regulator to direct hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. The pivotal pro-fibrotic cytokine transforming growth factor-β1 (TGFβ1) signals through both Smad and Stat3 to elicit a wide array of biological effects. Stat3 is widely acknowledged as a regulator of gene transcription and is involved in fibrosis of multiple tissues. The present study focused on BrD4 function implication in the roles of TGFβ1-induced Stat3 signaling in HSC activation and liver fibrosis by using heterozygous TGFβ1 knockout mice and HSC culture. Results showed that Stat3 was required for TGFβ1-induced BrD4 expression in HSCs. BrD4 expression paralleled Stat3 activation in activated HSCs in human cirrhotic livers. BrD4 was involved in the roles of TGFβ1-induced Stat3 in HSC activation and liver fibrogenesis. Smad3 bound to phosphorylated-Stat3 and contributed to TGFβ1-induced Stat3 signaling. BrD4 expression induced by Stat3 signaling required the early-immediate gene Egr1. Egr1 had a positive feedback on Stat3 activation. In conclusion, a network consisting of Stat3 signaling, Smad3 signaling, Egr1, and BrD4 was involved in the effects of TGFβ1 on liver fibrosis, providing new toxicological mechanisms for TGFβ1 in liver fibrogenesis.


Histochemical demonstration of mercury induced changes in rat neurons.
A histochemical method modified for ultrastructural studies of mercury induced changes is described. Rat neurons from areas known to be influenced by mercury are used as examples. The histochemical reaction, suggested to be caused by polymercury sulphide complexes, is localized to "dense bodies" where it is visible 14 days after initiation of peroral mercury treatment (20 mg HgCl2/l drinking water).


Hospital admission risk stratification of patients with gout presenting to the emergency department.
To characterise gout patients at high risk of hospitalisation and to develop a web-based prognostic model to predict the likelihood of gout-related hospital admissions. This was a retrospective single-centre study of 1417 patients presenting to the emergency department (ED) with a gout flare between 2015 and 2017 with a 1-year look-back period. The dataset was randomly divided, with 80% forming the derivation and the remaining forming the validation cohort. A multivariable logistic regression model was used to determine the likelihood of hospitalisation from a gout flare in the derivation cohort. The coefficients for the variables with statistically significant adjusted odds ratios were used for the development of a web-based hospitalisation risk estimator. The performance of this risk estimator model was assessed via the area under the receiver operating characteristic curve (AUROC), calibration plot, and brier score. Patients who were hospitalised with gout tended to be older, less likely male, more likely to have had a previous hospital stay with an inpatient primary diagnosis of gout, or a previous ED visit for gout, less likely to have been prescribed standby acute gout therapy, and had a significant burden of comorbidities. In the multivariable-adjusted analyses, previous hospitalisation for gout was associated with the highest odds of gout-related admission. Early identification of patients with a high likelihood of gout-related hospitalisation using our web-based validated risk estimator model may assist to target resources to the highest risk individuals, reducing the frequency of gout-related admissions and improving the overall health-related quality of life in the long term. KEY POINTS : • We reported the characteristics of gout patients visiting a tertiary hospital in Singapore. • We developed a web-based prognostic model with non-invasive variables to predict the likelihood of gout-relatedhospital admissions.


Structural characterization using 2D NMR spectroscopy and TMAH-GC × GC-MS: Application to humic acids from soils of an integrated agricultural system and an Atlantic native forest.
Understanding the chemical make-up of soils and their structure is critical for constraining the role of soil organic matter (SOM) into the global biogeochemical cycles, as well as to understand the capability of SOM to sequester carbon and mitigate greenhouse gas emissions. Here, we use two-dimensional 1H-13C heteronuclear single quantum coherence nuclear magnetic resonance (2D 1H-13C HSQC NMR) spectroscopy to structurally characterize the most refractory component of SOM, the humic acid (HA). The observations from 2D 1H-13C HSQC NMR were coupled with lignin phenol and fatty acid measurements using tetramethylammonium hydroxide (TMAH) thermochemolysis - two-dimensional gas chromatography - mass spectrometry (TMAH-GC × GC-MS). We studied humic acids extracted from an integrated Crop - Livestock - Forest System (CLFS) agricultural area and an undisturbed Atlantic Native Forest (NF) area. We evaluated soils from two different depths: the topsoil (0-20 cm) and subsoil (60-100 cm) layers, and reveal the presence of oxidized ligninaceous phenols as we had previously hypothesized. Collectively, our results indicate that there are significant oxidative processes with increasing soil depth which are more pronounced in the CLFS relative to the NF area. Degradation of stearic acid with increasing depth in the CLFS soils indicated that the CLFS is more microbiologically active than NF. Therefore, CLFS is less biochemically stable than we originally perceived. The enhanced bio-reactivity of CLFS is likely driving the enhanced carbon sequestration in the CLFS soils. This is perhaps due to the diversity of biomass remnants available at the CLFS soil rhizosphere which allows for more different types of biomass to be sequestered as oxidized ligninaceous phenols. Our results employing structural characterization with 2D 1H-13C HSQC NMR and TMAH-GC × GC-MS provide a new layer of knowledge about the practice of integrated agricultural systems and allow us to understand the structure and fate of sequestered carbon in soils from different soil environments.


Antiviral activity of a D-glucosamine derivative against herpetic ulcers (HSV type 2) in rabbit cornea.
Although most herpetic ocular infections in adults are caused by herpesvirus hominis type 1, several cases of culture proved HSV-2 ocular infection in adults have been described, with more severe and prolonged disease. In a screening for new antiherpetic compounds, we investigated the efficacy in vivo of a new compound, nitroderivative of D-glucosaminhydrochloride (GN-11) in comparison with D-glucosaminhydrochloride (GN), Acyclovir (ACV) and placebo against herpetic keratitis of herpes simplex type 2 in 4 x 4 eyes from 4 x 4 rabbits, respectively. ACV and GN-11 showed similar results. The treatment with GN-11 retarded the appearance of herpetic lesions, which were small and diffuse in comparison with the placebo group. A total recovery was obtained on the 12th day of the treatment. In the ACV treated group, a minimal number of small lesions appeared, but the eyes recovered normality on the 7th day of treatment. The appearance of acute herpetic keratitis was prevented by GN-11. Placebo and GN treated groups showed similar evolution, with lost vision and neurological involvement on the 7th day of infection.


A Structural Theory of Pitch(1,2,3).
Musical notes can be ordered from low to high along a perceptual dimension called "pitch". A characteristic property of these sounds is their periodic waveform, and periodicity generally correlates with pitch. Thus, pitch is often described as the perceptual correlate of the periodicity of the sound's waveform. However, the existence and salience of pitch also depends in a complex way on other factors, in particular harmonic content. For example, periodic sounds made of high-order harmonics tend to have a weaker pitch than those made of low-order harmonics. Here we examine the theoretical proposition that pitch is the perceptual correlate of the regularity structure of the vibration pattern of the basilar membrane, across place and time-a generalization of the traditional view on pitch. While this proposition also attributes pitch to periodic sounds, we show that it predicts differences between resolved and unresolved harmonic complexes and a complex domain of existence of pitch, in agreement with psychophysical experiments. We also present a possible neural mechanism for pitch estimation based on coincidence detection, which does not require long delays, in contrast with standard temporal models of pitch.


Physical exercise in myasthenia gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study.
Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients. In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes, and immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period. Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period. We propose that general recommendations regarding physical exercise can be applied safely to well-regulated MG patients. Muscle Nerve 56: 207-214, 2017.


Genetic and Phenotypic Analyses of Carpel Development in Arabidopsis.
Carpels are the female reproductive organs of the flower, organized in a gynoecium, which is likely the most complex organ of the plant. The gynoecium provides protection for the ovules, helps to discriminate between male gametophytes, and facilitates successful pollination. After fertilization, it develops into a fruit, a specialized organ for seed protection and dispersal. To carry out all these functions, coordinated patterning and tissue specification within the developing gynoecium has to be achieved. In this chapter, we provide different methods to characterize defects in carpel morphogenesis and patterning associated with developmental mutations, as well as a list of reporter lines that can be used to facilitate genetic analyses.


The protective effect of chemical and natural compounds against vincristine-induced peripheral neuropathy (VIPN).
Vincristine, an alkaloid extracted from Catharanthus rosea, is a class of chemotherapy drugs that act by altering the function of the microtubules and by inhibiting mitosis. Despite its widespread application, a major adverse effect of vincristine that limits treatment duration is the occurrence of peripheral neuropathy (PN). PN presents with several symptoms including numbness, painful sensation, tingling, and muscle weakness. Vincristine-induced PN involves impaired calcium homeostasis, an increase of reactive oxygen species (ROS), and the upregulation of tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) expression. Several potential approaches to attenuate the vincristine-induced PN including the concomitant administration of chemicals with vincristine have been reported. These chemicals have a variety of pharmaceutical properties including anti-inflammation, antioxidant, and inhibition of calcium channels and calcineurin signaling pathways and increased expression of nerve growth factor (NGF). This review summarized several of these compounds and the mechanisms of action that could lead to effective options in improving vincristine-induced peripheral neuropathy (VIPN).


Just My Imagination: Beauty premium and the evolved mental model.
Imagination, an important feature of the human mind, may be at the root of the beauty premium. The evolved human capacity for simulating the real world, developed as an adaptation to a complex social environment, may offer the key to understanding this and many other aspects of human behavior.


CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism.
Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum.


The influence of glutathione on redox regulation by antioxidant proteins and apoptosis in macrophages exposed to 2-hydroxyethyl methacrylate (HEMA).
Resin monomers like 2-hydroxyethyl methacrylate (HEMA) disturb cell functions including responses of the innate immune system, mineralization and differentiation, or induce cell death via apoptosis. These phenomena are associated with oxidative stress and a reduction in the concentration of the antioxidant glutathione (GSH), resulting in imbalanced redox homeostasis. Thus far, the precise mechanism of how resin monomers interfere with cellular redox regulation is unknown. The present study provides insight into the induction of apoptosis and the differential expression of antioxidant enzymes depending on the availability of GSH. Buthionine sulfoximine (BSO) was used to inhibit GSH synthesis, while 2-oxothiazolidine-4-carboxylate (OTC), and N-acetylcysteine (NAC) as prodrugs supported GSH synthesis in RAW264.7 mouse macrophages exposed to HEMA (0-8 mm) for 24 h. The level of GSH was significantly decreased after cells were preincubated with BSO, and the formation of reactive oxygen species (ROS) increased in cultures subsequently exposed to HEMA. Apoptosis was drastically increased by BSO in HEMA-exposed cell cultures as well, but OTC and NAC retracted HEMA-induced cell death. These results show that dental monomer-induced apoptosis is causally related to the availability of GSH. The hydrogen peroxide decomposing enzymes glutathione peroxidase (GPx1/2) and catalase were differentially regulated in HEMA-exposed cultures. Expression of GPx1/2 was inhibited by HEMA and further reduced in the presence of BSO. SOD1 (superoxide dismutase) expression was inhibited in the presence of HEMA, and was decreased to an even greater extent by BSO, possibly due to H(2)O(2)-feedback inhibition. The expression of catalase was considerably up-regulated in HEMA-exposed cultures, implying that H(2)O(2) is the type of ROS that is significantly increased in monomer-exposed cells. OTC and NAC counteracted the effect of HEMA on GPx1/2, SOD1, and catalase expression. HO-1 (heme oxygenase) expression was strongly enhanced by HEMA, suggesting the need for further antioxidants like bilirubin to support enzyme activities that directly regulate H(2)O(2) equilibrium. Expression of the oxidoreductase thioredoxin (TRX1), the second major thiol-dependent antioxidant system in eukaryotic cells, was slightly reduced, while the oxygen-sensing protein HIF-1α was downregulated in HEMA-exposed cell cultures. These results indicate that cells and tissues actively respond to monomer-induced oxidative stress by the differential expression of enzymatic antioxidants.


Corrigendum: The mediating role of psychological inflexibility in the relationship between anxiety, depression, and emotional eating in adult individuals with obesity.
[This corrects the article DOI: 10.3389/fpsyg.2022.861341.].


Growth failure in bronchopulmonary dysplasia: elevated metabolic rates and pulmonary mechanics.
Growth failure is a major problem in infants with bronchopulmonary dysplasia (BPD), but the cause is unknown. We studied 13 infants with BPD but without other medical problems that could contribute to growth failure at 6 months' corrected age. We measured resting oxygen consumption (Vo2), Pao2, airway resistance, specific airway conductance, and dynamic pulmonary compliance (Cdyn) by body plethysmography and growth. Growth failure was defined as height and weight less than the tenth percentile of the Babson growth curves. Vo2 in infants with growth failure and BPD was markedly elevated compared with that in control infants and infants with BPD and normal growth. Vo2 showed an inverse correlation with body weight in infants with BPD but not in control infants. Although Vo2 was inversely related to Cdyn, the total work of breathing only partially explained the increased metabolic demands of the growth failure group. We speculate that growth failure in infants with BPD is partially the result of increased metabolic demands from increased work of breathing but that other mechanisms may act to elevate the metabolic expenditure of these infants.


Effects of father-daughter contact on use of pregnancy services by Mexican, Mexican-American, and Anglo adolescents.
This study describes whether frequency and quality of father-daughter contact during adolescent pregnancy differ by ethnicity, whether this contact affects health behavior, and how ethnicity conditions the relationship between contact and behavior. Health behavior is defined as timing of pregnancy test and first prenatal visit. Data were gathered from a sample of 105 Anglo, Mexican-American, and Mexican adolescents interviewed at mid-pregnancy. Almost twice as many Mexicans (64%) as Mexican-Americans never saw their fathers (p less than 0.03). Girls living with their fathers obtained pregnancy tests significantly later (p less than 0.01) than those living independently. This relationship was maintained when ethnicity was held constant (p less than 0.01). When quality of contact was included, the relationship between residency with father and timing of pregnancy test became even stronger (p less than 0.003).


Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells.
IL-13 has been shown to play a pivotal role in mucous cell metaplasia, which is an important feature of the pathogenesis of asthma. However, the signalling pathways evoked by IL-13 in airway epithelial cells remain unclear. This study investigated the signalling mechanism of IL-13-induced mucous cell metaplasia in primary cultures of mouse tracheal epithelial cells (mTEC). mTEC were cultured in an air-liquid interface system in the presence or absence of IL-13. Goblet cell hyperplasia was evaluated quantitatively by immunofluorescent staining for MUC5AC, which is a major component of airway mucins. Western blotting was used to assess activation of the signalling molecules, signal transducer and activator of transcription 6 (STAT6), p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2. MUC5AC gene expression was measured by RT-PCR. IL-13 induced mucous cell metaplasia for 7-14 days in mTEC. IL-13 phosphorylated STAT6 within 20 min, whereas it induced delayed phosphorylation of p38 MAPK 36-48 h after stimulation. In contrast, ERK1/2 was constantly activated and was not enhanced by IL-13. An inhibitor of p38 MAPK (SB202190) suppressed mucous cell differentiation in a concentration-dependent manner. In STAT6 knockout mice, IL-13 failed to induce mucous cell metaplasia and activate p38 MAPK. Cycloheximide also diminished activation of p38 MAPK and induction of MUC5AC mRNA expression by IL-13. The p38 MAPK pathway is involved in IL-13-induced mucous cell metaplasia and MUC5AC mRNA regulation in mTEC. In addition, p38 MAPK phosphorylation may require STAT6-dependent de novo protein synthesis induced by IL-13.


Antigen presentation by endothelial cells: what role in the pathophysiology of malaria?
Disruption of the endothelial cell (EC) barrier leads to pathology via edema and inflammation. During infections, pathogens are known to invade the EC barrier and modulate vascular permeability. However, ECs are semi-professional antigen-presenting cells, triggering T-cell costimulation and specific immune-cell activation. This in turn leads to the release of inflammatory mediators and the destruction of infected cells by effectors such as CD8(+) T-cells. During malaria, transfer of parasite antigens to the EC surface is now established. At the same time, CD8 activation seems to play a major role in cerebral malaria. We summarize here some of the pathways leading to antigen presentation by ECs and address the involvement of these mechanisms in the pathophysiology of cerebral malaria.


Progress with stem cell therapies for tendon tissue regeneration.
Chronic musculoskeletal pain is very prevalent, and accounts for major health-care expenses. Many of the present therapeutic modalities are only partially effective, and great interest is now posed on regenerative medicine. The authors discuss the role of a variety of regenerative medicine options to induce and favor regeneration and healing of tendon tissue, focusing on the role of mesenchymal stem cell therapy and their derivatives. Stem cells, tissue engineering, and growth factors are new strategies for tendon repair and regeneration. MSCs not only can differentiate in tendon cells, but also secrete several cytokines that modulate inflammation and tissue healing. Future studies should be undertaken to overcome current obstacles to clinical translation. Further investigation of cell source, isolation, expansion, and differentiation methods, characterization of the tenogenic differentiation pathways, and clarifications of tendon-specific molecular markers are required. The role of donor variability, tendon type, and anatomic location also requires further understanding and research.


Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro.
Calcipotriol (MC903) is a novel vitamin D analogue which effects cellular differentiation and proliferation in vitro and has reduced effects on calcium metabolism in vivo. In the present study its in vitro activity was evaluated using the MCF-7 breast cancer cell line, and its effects on calcium metabolism and mammary tumour growth were measured in vivo in adult female rats. Calcipotriol was compared to the natural metabolite of vitamin D3, 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] and its synthetic analogue 1 alpha hydroxycholecalciferol [1 alpha(OH)D3]. Both calcipotriol and 1,25(OH)2D3 produced significant inhibition of MCF-7 cell proliferation at a concentration of 5 x 10(-11) M. Intraperitoneal administration of calcipotriol to normal female rats showed that the analogue was 100-200 times less active than 1,25(OH)2D3 in raising serum calcium concentration and urinary calcium excretion. Anti-tumour activity of the vitamin D analogues was investigated in vivo using the nitrosomethylurea-induced rat mammary tumor model. Rats, maintained on a low calcium diet, were treated with 1 alpha(OH)D3 (0.25 and 1.25 micrograms/kg). Both doses produced a response rate of 25% but hypercalcaemia developed. Treatment with calcipotriol (50 micrograms/kg) of rats maintained on a normal laboratory diet caused inhibition of tumour progression (response rate 17%) without the development of severe hypercalcaemia. This study supports the concept that vitamin D derivatives may inhibit breast cancer cell proliferation in vivo.


Data on genome resequencing of pigmented and non-pigmented Malaysian rice varieties.
The genomics and genetic data of pigmented and non-pigmented Malaysian rice varieties are still limited. Hence, we performed the genome resequencing of two black rice varieties (Bali, Pulut Hitam 9), two red rice varieties (MRM16, MRQ100) and two white rice varieties (MR297 and MRQ76) using Illumina HiSeq 4000 platform with 30x sequencing coverage. We aimed to identify and annotate single nucleotide polymorphisms (SNPs) from the genome of these four pigmented and two non-pigmented rice varieties. The potential SNPs will be used in developing the functional SNP markers related to nutritional (i.e. antioxidant, folate, amylose) and quality (i.e. aromatic) traits. Raw data of the pigmented and non-pigmented rice varieties have been deposited into the European Nucleotide Archive (ENA) database with accession number PRJEB29070 and PRJEB32344, respectively.


Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF: Warfarin Versus NOACs Versus LAA Closure.
Left atrial appendage closure (LAAC) and nonwarfarin oral anticoagulants (NOACs) have emerged as safe and effective alternatives to warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF). This analysis assessed the cost-effectiveness of warfarin, NOACs, and LAAC with the Watchman device (Boston Scientific, Marlborough, Massachusetts) for stroke risk reduction in patients with nonvalvular AF at multiple time points over a lifetime horizon. A Markov model was developed to assess the cost-effectiveness of LAAC, NOACs, and warfarin from the perspective of the Centers for Medicare & Medicaid Services over a lifetime (20-year) horizon. Patients were 70 years of age and at moderate risk for stroke and bleeding. Clinical event rates, stroke outcomes, and quality of life information were drawn predominantly from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) 4-year data and meta-analyses of warfarin and NOACs. Costs for stroke risk reduction therapies, treatment of associated acute events, and long-term care following disabling stroke were presented in 2015 U.S. dollars. Relative to warfarin, LAAC was cost-effective at 7 years ($42,994/quality-adjusted life-years [QALY]), and NOACs were cost-effective at 16 years ($48,446/QALY). LAAC was dominant over NOACs by year 5 and warfarin by year 10. At 10 years, LAAC provided more QALYs than warfarin and NOACs (5.855 vs. 5.601 vs. 5.751, respectively). In sensitivity analyses, LAAC remained cost-effective relative to warfarin ($41,470/QALY at 11 years) and NOACs ($21,964/QALY at 10 years), even if procedure costs were doubled. Both NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs. The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF.


Synopsis of the Japanese species of Aleocharinae (Coleoptera: Staphylinidae), with review of the type specimens II. Genus Myllaena Erichson of tribe Myllaenini,<br>with redescription of four Japanese species.
Four Japanese species the rove beetle genus Myllaena are redescribed based on the type material. They are: M. japonica Sharp, 1888, M. lewisi Cameron, 1933, M. rufotestacea Cameron, 1933, and M. torrentum Cameron, 1933. Myllaena chinoculata Pace, 1998 described from China is synonymized with M. lewisi. All of these species are illustrated and mapped.


Characterisation of Crandell-Rees Feline Kidney (CRFK) cells as mesenchymal in phenotype.
The Crandell-Rees Feline Kidney Cell (CRFK) is an immortalised cell line derived from the feline kidney that is utilised for the growth of certain vaccinal viruses. Confusion exists as to whether CRFK are epithelial or mesenchymal in phenotype. The aim of this study was to characterise CRFK cells via immunofluorescence, enzyme cytochemistry, western blotting, RT-qPCR for S100A4 and comparison to primary feline proximal tubular epithelial cells (FPTEC) and feline cortical fibroblasts (FCF). CRFK cells were of fusiform morphology and appeared similar to FCF. CRFK expressed the mesenchymal intermediate filament (IF) protein vimentin together with two cell adhesion molecules associated with feline fibroblasts (CD29 and CD44), and lacked expression of the epithelial IF cytokeratin, myogenic IF desmin and endothelial marker von Willebrand factor (vWF). In addition, CRFK did not demonstrate brush border enzyme activity typical of FPTEC. S100A4 gene expression, implicated in both neoplastic transformation and epithelial to mesenchymal transition, was highly upregulated in CRFK in comparison to the primary feline renal cells. CRFK appear phenotypically similar to fibroblasts, rather than tubular epithelial cells, and may have undergone neoplastic transformation or epithelial-to-mesenchymal transition after extensive passaging. This finding may have potential implications for future research utilising this cell line.


Adaptation of gut microbiome and host metabolic systems to lignocellulosic degradation in bamboo rats.
Bamboo rats (Rhizomys pruinosus) are among the few mammals that lives on a bamboo-based diet which is mainly composed of lignocellulose. However, the mechanisms of adaptation of their gut microbiome and metabolic systems in the degradation of lignocellulose are largely unknown. Here, we conducted a multi-omics analysis on bamboo rats to investigate the interaction between their gut microbiomes and metabolic systems in the pre- and post-weaning periods, and observed significant relationships between dietary types, gut microbiome, serum metabolome and host gene expression. For comparison, published gut microbial data from the famous bamboo-eating giant panda (Ailuropoda melanoleuca) were also used for analysis. We found that the adaptation of the gut microbiome of the bamboo rat to a lignocellulose diet is related to a member switch in the order Bacteroidales from family Bacteroidaceae to family Muribaculaceae, while for the famous bamboo-eating giant panda, several aerobes and facultative anaerobes increase after weaning. The conversion of bacteria with an increased relative abundance in bamboo rats after weaning enriched diverse carbohydrate-active enzymes (CAZymes) associated with lignocellulose degradation and functionally enhanced the biosynthesis of amino acids and B vitamins. Meanwhile, the circulating concentration of short-chain fatty acids (SCFAs) derived metabolites and the metabolic capacity of linoleic acid in the host were significantly elevated. Our findings suggest that fatty acid metabolism, including linoleic acid and SCFAs, are the main energy sources for bamboo rats in response to the low-nutrient bamboo diet.


How to investigate oxygen supply, uptake, and utilization simultaneously by interleaved NMR imaging and spectroscopy of the skeletal muscle.
Human skeletal muscle perfusion, oxygenation, and high-energy phosphate distribution were measured simultaneously by interleaved (1)H and (31)P NMR spectroscopy and (1)H NMR imaging in vivo. From these parameters, arterial oxygen supply (DO(2)), muscle reoxygenation rate, mitochondrial ATP production, and O(2) consumption (VO(2)) were deduced at the recovery phase of a short ischemic exercise bout. In addition, by using a reformulation of the mass conservation law, muscle maximum O(2) extraction was calculated from these parameters.


All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction.
Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined. Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP). ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment. ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.


A case of tri-segmental cranial nerve V herpes zoster.
Varicella-zoster is the causative virus underlying varicella or "chickenpox" and herpes zoster or "shingles." Cases of disseminated disease have been widely reported in immunocompromised patients. We describe an interesting case of tri-segmental cranial nerve V herpes zoster here with discussion of the salient clinical features as well as brief discussion about ongoing trials for herpes zoster ophthalmicus prophylaxis. This case also highlights the importance of timely treatment and diagnosis, as the patient presented 6 days prior to hospitalization with a mild vesicular facial rash but was lost to follow up without filling a prescription for acyclovir, returning with severe facial involvement.


Immature alveolar/blood barrier and low disaturated phosphatidylcholine in fetal lung after intrauterine exposure to O,O,S-trimethylphosphorothioate.
Intrauterine exposure to the potent lung toxicant OOS-TMP was found to result in neonatal lethality attributed to immature lungs (Koizumi et al. 1988). The present study was initiated to investigate biological/pathological profiles of such pulmonary immaturity. OOS-TMP was given p.o. to five pregnant female Sprague-Dawley rats on gestation day (G) 19 at 2.5, 7 or 20 mg/kg. Control (N = 6) or pair-fed dams (N = 5: pair-fed to 20 mg/kg dams) received 2 ml/kg corn oil. On G 22, fetuses were delivered by Cesarean section. The biochemical maturity of lungs was assessed by glycogen content and production of disaturated phosphatidylcholine (DSPC), a major component of pulmonary surfactant. Mean DSPC content was significantly lower in fetuses from dams dosed at 7 or 20 mg/kg while mean glycogen concentration, in contrast, was 3- to 6-fold higher in those fetuses than fetuses from control or pair-fed dams. Pathological examination revealed that in fetuses delivered from dams dosed at 7 mg/kg or 20 mg/kg, glycogen-rich cuboidal epithelial cells completely covered the terminal air space and alveolar/blood barriers stayed at the poorly developed stage. The stage of the pulmonary development in those fetuses was similar to those in fetuses on G19. Therefore it was concluded that intrauterine exposure to OOS-TMP delayed pulmonary development, thereby causing respiratory failure after birth.


Gene Fusion Discovery with INTEGRATE.
Next-generation sequencing (NGS) has become the primary technology for discovering gene fusions. Decreasing NGS costs have resulted in a growing quantity of patients with whole transcriptome sequencing (RNA-seq) and whole genome sequencing (WGS) data. We developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read alignment. INTEGRATE has become widely adopted by the larger cancer research community to discover biologically and clinically relevant gene fusions. Here we explain the rationale driving the development of the INTEGRATE tool and describe the detailed practical procedures for applying INTEGRATE to discover gene fusions using NGS data. INTEGRATE can be applied to both combined data and RNA-seq only data.


Purification of adenovirus hexon by high performance liquid chromatography.
Hexon is the major structural protein of adenovirus, and has significance in studies of virus structure and function, vaccine development, and immunodiagnosis. We describe a simple, single-step, anion-exchange high performance liquid chromatography (HPLC) method for the high yield purification of hexon. Purity of the isolated hexon was assessed by SDS-PAGE and HPLC methods. The isolated hexon was immunologically reactive with anti-hexon monoclonal antibody in a dot-blot assay. It also retained immunogenicity, as polyclonal antisera from rabbits immunized with hexon showed the desired antigen specificity. The enhanced speed of this purification method allows for the efficient isolation of hexon from various serotypes, and thus may facilitate comparative studies of hexon immunobiology.


First report of parasitism by Hexametra boddaertii (Nematoda: Ascaridae) in Oxyrhopus guibei (Serpentes: Colubridae).
The current study summarizes the postmortem examination of a specimen of Oxyrhopus guibei (Serpentes, Colubridae) collected in Iguazu National Park (Argentina), and found deceased a week following arrival to the serpentarium of the National Institute of Tropical Medicine (Argentina). Although the snake appeared to be in good health, a necropsy performed following its death identified the presence of a large number of roundworms in the coelomic cavity, with indications of peritonitis and serosal adherence. Additional observations from the necropsy revealed small calcifications in the mesothelium of the coelomic cavity; solid and expressive content in the gallbladder; massive gastrointestinal obstruction due to nematodes; and lung edema and congestion. Histopathological analyses of lung sections also showed proliferative heterophilic and histiocytic pneumonia. Parasites isolated from both the intestine and coelomic cavity were identified as Hexametra boddaertii by a combination of light and scanning electron microscopic examination. Results from this necropsy identify O. guibei as a new host for H. boddaertii, and is the first report of a natural infection by Hexametra in Argentina. Since Hexametra parasites may contribute to several pathological conditions in humans, and with the recent availability of O. guibei specimens through the illegal pet trade, it is necessary to consider the possibility of zoonotic helminth transmission of Hexametra from snake to human.


DNA modifying enzymes of Agrobacterium tumefaciens: effect of DNA topoisomerase, restriction endonuclease, and unique DNA endonuclease on plasmid and plant DNA.
Extracts from Agrobacterium tumefaciens strain ID135 contain three enzymes that have been characterized and partially purified. The first enzyme, a DNA topoisomerase, appeared to relax only negatively twisted DNA. The second enzyme, Atu I, a type II restriction endonuclease, generated the identical DNA digestion pattern as EcoRII when several DNAs were used. The third enzyme, endonuclease A, showed a preference for superhelical DNAs as substrates. When plasmid pCK135DNA, obtained from the virulent strain IDI135 of A. tumefaciens, or plant DNA was exposed to the three enzymes, changes in DNA patterns were observed due to either conformational changes or digestion of the DNAs. These enzymes may function in vivo in the processing and incorporation of bacterial DNA in plant cells.


Stoichiometry of Receptors at the Plasma Membrane During Their Endocytosis Using Total Internal Reflection Fluorescent (TIRF) Microscopy Live Imaging and Single-Molecule Tracking.
Determination of protein stoichiometry in living cells is key to understanding basic biological processes. This is particularly important for receptor-mediated endocytosis, a highly regulated mechanism that requires the sequential assembly of numerous factors. Here, we describe a quantitative approach to analyze receptor clustering dynamics at the plasma membrane. Our workflow combines TIRF live imaging of a CRISPR-Cas9-edited cell line expressing a GFP-tagged receptor in a physiological relevant environment, a calibration technique for single-molecule analysis of GFP, and detection and tracking with an open-source software. This method allows to determine the number of receptor molecules at the plasma membrane in real time.


Distinct neurotrophic factors from skeletal muscle and the central nervous system interact synergistically to support the survival of cultured embryonic spinal motor neurons.
Motor neurons isolated from 6-day-old embryonic chick spinal cords require muscle extract for survival in culture; however, it was found, that some motor neurons, identified by retrograde labeling with rhodamine, will survive in mixed spinal cell cultures in the absence of the extract. The motor neuron survival-promoting activity produced by spinal cells is soluble and differs from the factor present in muscle extract, the two activities acting in a synergistic manner: the spinal cell activity potentiated that of muscle to decrease its ED50 by an order of magnitude, the motor neuronal survival (30%) seen in the presence of both factors being more than the sum of their individual activities. This synergism was shown to be restricted to the action of the spinal cell factor on motor neurons, no effect of the factor being noted with sympathetic neurons. As a series of defined growth and survival factors present in the central nervous system (nerve growth factor, brain-derived neurotrophic factor, acidic and basic fibroblast growth factors) had no effect on motor neuron survival, we conclude that the molecule responsible for the motor neuron survival-promoting activity of the spinal cells is a previously undefined factor.


The Impact of COVID-19 on Radiation Oncology Residency Applicant Away Rotations, Interviews, and Rank Lists: A Comparison Between the 2020 Match and 2021 Match.
The COVID-19 pandemic modified the Residency Match process for fourth-year medical students. In-person away rotations were discouraged, interviews were virtual, and traditional factors used to rank programs were absent. Here, we compare survey results administered to both the 2020 and 2021 Match applicants to assess the influence of the pandemic on the radiation oncology (RO) Match process. An institutional review board-approved prospective cross-sectional study was conducted. The 2020 and 2021 RO Match applicants at a large RO program were invited to participate. Descriptive summary statistics were assessed. The 2020 and 2021 Matches each had 76 applicants complete the survey with response rates of 54% and 57%, respectively. The 2 groups were predominantly white, cisgender male, single, and without children. Whereas 11% of 2020 applicants did not complete away rotations, 45% of 2021 applicants did not. For 2021 Match applicants, 65% of away rotations were performed virtually, whereas 51% were not for medical school credit. Of the applicants, 84% were satisfied with virtual interviews and 72% felt cost savings were worth not having in-person interviews. Whereas 49% of Match 2020 applicants spent >$5000 in interview costs, 0% of the Match 2021 applicants did so, with 45% spending <$100. Postinterview communications from programs increased during the pandemic from 36% to 42% in 2020 Match and 2021 Match, respectively. Although program culture was the most common factor influencing 2021 Match applicants program rankings, half of applicants did not gain a sense of program culture during virtual interviews. We found 2021 Match applicants completed fewer away rotations, were satisfied with virtual interviews/reduced costs, and did not gain a sense of program culture through virtual rotations/interviews despite it being the most important ranking factor reported. This study supports further exploration of virtual away rotations and virtual interviews moving forward beyond the pandemic.


Quantification of dystrophin immunofluorescence in dystrophinopathy muscle specimens.
Duchenne muscular dystrophy (DMD) is usually associated with absent or nearly absent dystrophin expression at the sarcolemmal membrane. Quantification of very low levels of dystrophin signal in immunofluorescent studies of muscle biopsy sections presents a technical challenge. This is particularly true in the setting of proof-of-principle drug trials, in which the detection and quantification of what may be significant changes in levels of expression is important, even if absolute dystrophin levels remain low. We have developed a method of image analysis that allows reliable and semi-automated immunofluorescent quantification of low-level dystrophin expression in sections co-stained for spectrin. Using a custom Metamorph script to create a contiguous region spectrin mask, we quantify dystrophin signal intensity only at pixels within the spectrin mask that presumably represent the sarcolemmal membrane. Using this method, we analysed muscle biopsy tissue from a series of patients with DMD, Becker muscular dystrophy, intermediate muscular dystrophy and normal control tissue. Analysis of serial sections on multiple days confirms reproducibility, and normalized dystrophin:spectrin intensity ratios (expressed as a percentage of normal control tissue) correlate well with the dystrophin expression levels as determined by Western blot analysis. This method offers a robust and reliable method of biomarker detection for trials of DMD therapies.


[When is cytoreductive nephrectomy not beneficial for patients with metastatic renal cell carcinoma?]
Primary tumor resection in patients with synchronous metastatic renal cell carcinoma and a good performance status corresponds to a guideline recommendation which, however, is based on weak data from the era of cytokine therapy. This article presents arguments that weigh heavily against cytoreductive nephrectomy. From a molecular genetic viewpoint, the intervention eliminates only the easiest adversary but cannot prevent cancer-related death. Therefore, benefits and risks must be carefully and critically considered. Cytoreductive nephrectomy is not beneficial if treatment-induced morbidity will substantially affect the patient's quality of life and/or life expectancy or if the size and topography of the primary tumor renders it less dangerous than the metastases.


Characterization study of heavy metal-bearing phases in MSW slag.
Slag products derived from the pyrolysis/melting and plasma/melting treatment of municipal solid waste (MSW) in Japan were examined for the characterization study of heavy metal-bearing phases using petrographic techniques. Detailed microscopic observations revealed that the shapes of heavy metal-rich inclusions are generally spherical to semi-spherical and their sizes range from submicron to scarcely large size spheres (over 100 microm). The experiments (both optical microscopy and electron probe microanalysis) indicated that Fe and Cu participate in mutual substitution and different proportions, and form mainly two-phase Fe-Cu alloys that bound in the silicate glass. This alloy characterizes the composition of more than 80% of the metal-rich inclusions. Other metals and non-metals (such as Pb, Ni, Sb, Sn, P, Si, Al and S) with variable amounts and uneven distributions are also incorporated in the Fe-Cu alloy. In average, the bulk concentration of heavy metals in samples from pyrolysis/melting type is almost six times greater than samples treated under plasma/arc processing. The observations also confirmed that slag from pyrolysis origin contains remarkably higher concentration of metallic inclusions than slag from plasma treatment. In the latter, the metallic compounds are separately tapped from molten slag during the melting treatment that might lead to the generation of safer slag product for end users from environmental viewpoint.


Patterns of Care and RTOG studies in prostate cancer: long-term survival, hazard rate observations, and possibilities of cure.
This study was undertaken to show the long-term survival and probability of cure of prostate cancer patients treated with external beam radiation in USA national surveys and in the prospective clinical trials of the RTOG. Two national patterns of care surveys of patients treated in 1973 and 1978 are reported along with two RTOG prospective trials (7506 and 7706). Hazard rates represent the risk of death and are compared to the rate expected for a normal population. For patients with Stage A cancers, the survival is not different from the expected survival for any of the reported surveys. The hazard rate for death does not significantly exceed the expected hazard rate out to 15 years. For patients with Stage B cancer, there is a decrease in survival below expected and hazard rates show a continuing excess mortality as long as 15 years after treatment. For patients with Stage C cancers, there is a more rapid decrease in survival that then becomes parallel to the expected survival. Hazard rates indicate there has been a return to expected mortality at 15 years. These data make a strong argument for the long-term cure of prostate cancer by external beam radiation, and support the continued use and study of radiation therapy as a curative modality in prostate cancer. No similar national data is available for any other method of management.


Eight-Year Trends in the Effect of the Great East Japan Earthquake on Obstetrics Outcomes: A Study from the Fukushima Health Management Survey.
Information regarding the longitudinal effects of natural/environmental disasters on obstetrics outcomes is limited. This study aimed to analyze the longitudinal changes in obstetrics outcomes over 8 years after the Great East Japan Earthquake and the Fukushima power plant accident. We used data from the first 8 years of the Pregnancy and Birth Survey by the Fukushima prefectural government, launched in 2011. We compared data on obstetrics outcomes by year and divided Fukushima Prefecture into six districts based on administrative districts. Longitudinal changes in the occurrence of preterm birth before 37 gestational weeks, low birth weight, and anomalies in newborns were accessed using the Mantel-Haenszel test for trends in all six districts. Overall, 57,537 participants were included. In 8 years, maternal age, conception rate after sterility treatment, and cesarean section delivery incidence increased. Although significant differences were observed in preterm birth and low birth weight occurrence among districts, there was no significant trend in the occurrence of preterm birth, low birth weight, and anomalies in newborns in all six districts of Fukushima Prefecture. The Great East Japan Earthquake and Fukushima power plant accident were associated with increased cesarean section delivery incidence but had no significant adverse effects on obstetrics outcomes.


Nighttime media use in adolescents with ADHD: links to sleep problems and internalizing symptoms.
This study examined nighttime media use in relation to sleep problems and anxiety/depression symptoms in adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were 81 adolescents (69% male) ages 13-17 with ADHD. Adolescents completed measures assessing pubertal development, nighttime media use, circadian preference, and daytime sleepiness. Both adolescents and parents completed measures of sleep duration, sleep problems, and internalizing symptoms. When summing across media uses (eg, social networking, playing video games, watching television), the average nighttime media use (after 9:00PM) was 5.31 h. Overall, 63% of adolescents reported obtaining less than 8 h of sleep on school nights, and this percentage rose to 77% for parent-reported sleep duration. Moreover, adolescents obtaining less sleep than recommended had more nighttime media use than those obtaining ≥8 h of nightly sleep. Controlling for age, sex, pubertal development, stimulant medication use, and ADHD symptom severity; nighttime media use was associated with shorter sleep duration and increased sleep problems across both adolescent and parent report. Media use was also associated with greater adolescent-reported anxiety and depression, and marginally associated with eveningness circadian preference and greater daytime sleepiness. In considering specific anxiety dimensions, media use was associated with greater adolescent-reported panic symptoms and parent-reported generalized anxiety disorder symptoms. Our findings suggest that nighttime media use may contribute to sleep problems and comorbid internalizing symptoms in adolescents with ADHD, although additional studies are needed to determine causality, potential bidirectional associations, and underlying mechanisms such as using media to (mis)manage negative emotions. Media use is important to assess and monitor and may be a significant intervention target when addressing sleep and internalizing problems, and possible underlying cognitive-emotional processes in adolescents with ADHD.


Osteoblasts subjected to mechanical strain inhibit osteoclastic differentiation and bone resorption in a co-culture system.
Bone remodeling is strictly mediated by the coupled activities of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively. Although many papers have been published on the mechanical responses of osteoblasts and osteoclasts, little is known about their communication during mechanical loading. In this study, a novel co-culture system was first established using Transwell culture inserts; MC3T3-E1 cells were embedded in the lower compartment of the inserts, and RAW264.7 cells were co-cultured in the upper compartment. The MC3T3-E1 cells were subjected to a mechanical strain of 2500 με at 0.5 Hz to investigate the effect of strain-loaded osteoblasts on co-cultured osteoclasts. The results showed that osteoblast-like cells were activated with an increase of alkaline phosphatase (ALP) activities. The strain-conditioned medium caused decreased activity of tartrate-resistant acid phosphatase and reduced the number of mature multinucleated osteoclasts, which subsequently resulted in the suppressed formation of resorption pits. The expression levels of cathepsin-K and matrix metalloproteinase-9 were also depressed by the strain-conditioned medium. In addition, we found that the expression ratio between osteoprotegerin (OPG) and receptor activator of NF-kB ligand in osteoblasts was significantly up-regulated due to the enhanced levels of OPG. In summary, we conclude that the strain-stimulated osteoblasts inhibited the differentiation and bone resorption of osteoclasts and that the mechanism was associated with the increased secretion of OPG in osteoblasts.


Diurnal changes in proline content of desert plants.
The diurnal changes in proline and water contents of Zygophyllum quatarense and Francoeuria crispa were investigated under desert conditions. In both plants, the proline content was low before sunrise amounting to 10.42 μmoles/g fresh weight in Zygophyllum and 6.3 μmoles/g fresh weight in Francoeuria. By the progress of the day and the intensification of the evaporative power of the atmosphere, the proline content increased considerably in the two plants. The proline content reached maximal values at 5 p.m., reaching 23.36 μmoles/g in Zygophyllum and 11.16 μmoles/g in Francoeuria. The proline content of the artificially watered plants was kept at a low level throughout the day. The conditions and role of proline accumulation were discussed.


Artificial kernels and food bands for raising Sitophilus oryzar (L.) on microscopic concave slides.
Artificial kernels and food bands (1 mm thick) stretched on concave microscopic slides proved inviting and very suitable for oviposition and for completing the life cycle of Sitophilus oryzae (L.). This artificial medium contains jelly, wheat flour and corn oil, its moisture content is 18.1%. This is the first time it was possible to breed an insect on artificial media on glass slides.


In situ ruminal disappearance of crude protein and phytate from differently processed rapeseed meals in dairy cows.
The influence of different processing conditions of rapeseed meal on ruminal degradation of crude protein and phytate in dairy cows was investigated. Following oil extraction from the rapeseed, five residence times in the desolventizer/toaster were chosen to remove the solvent from the meal. Rapeseed cake and rapeseed meals were incubated in situ in the rumen of three fistulated dairy cows to determine ruminal degradation parameters. With increasing residence time in the desolventizer/toaster the ruminal degradation of crude protein decreased significantly for every treatment step. Ruminal phytate degradation and crude protein degradation were affected almost identically. The processing conditions of rapeseed meal have a major impact on the ruminal degradation of crude protein and phytate, indicating a potential conflict of interest regarding the production process. Large amounts of undegradable rumen protein are often intended for high-yielding dairy cows whereas a high level of ruminal degradation is preferred for phytate to increase absorption of phosphorus in the small intestine. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Four weeks of repetitive acute hypoxic preconditioning did not alleviate allergen-induced airway dysfunction in rats.
Clinical case series suggest beneficial effects of low-dose intermittent hypoxia in asthma. We tested cardiopulmonary effects of repetitive acute hypoxic preconditioning (RAHP) during allergic inflammation. Brown Norway rats were sensitized to house dust mites (HDM) and exposed to 4-week RAHP or normoxia (SHAM), concurrent with weekly HDM or saline (SAL) challenges. We assessed methacholine responses and lung HIF-1α expression at endpoint, and weekly blood pressure (BP). RAHP relative to SHAM: 1) in HDM-challenged rats, showed no protection against HDM-induced airway dysfunction and did not significantly impact BP (week 4 mean BP difference = 10.51 mmHg, p = 0.09) or HIF-1α expression; 2) in SAL-challenged rats, attenuated airway responses to methacholine, reduced BP (week 4 mean BP average difference = -8.72 mmHg, p = 0.04) and amplified HIF-1α expression (p = 0.0086). Four weeks of RAHP did not mitigate the allergen-induced lower airway dysfunction and may detrimentally affect BP. However, it elicited beneficial cardiopulmonary responses in SAL-challenged rats, concurrent with increased HIF-1α expression.


Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae.
Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for on a minimal medium.


Expression of Angiogenic Proteins in Tumor and Stroma Affects Survival in Patients With Gastric Cancer.
Gastric cancer is one of the most frequent malignancies worldwide. Angiogenic growth factors play a crucial role in mediating the crosstalk between cancer cells and the surrounding microenvironment. In this exploratory study, we investigate the impact of angiogenic proteins within the tumor cell or stroma compartment on survival of patients with gastric cancer. In 29 patients, tumor and stromal compartments were separated using laser capture microdissection. Angiogenic protein expression was measured using a bead-based immunoassay and correlated with tumor stage and overall survival. Overall survival was significantly shorter in patients with a high stroma concentration of vascular endothelial growth factor (VEGF)-A (23.5 (±17.6) versus 33.6 (±21.0) mo; P = 0.009) and stem cell factor (22.2 (±18.5) versus 33.6 (±21.8) mo; P = 0.01) compared with patients with a low stroma concentration. High stromal VEGF-D showed a trend toward worse survival (26.8 (±22.0) versus 37.2 (±19.0) mo; P = 0.09). We did not observe any significant correlation between tumor-specific expression of angiogenic cytokines and survival. This translational study highlights the difference in clinical impact between tumor and stromal expression of angiogenic proteins. Compartment-specific concentrations of VEGF-A and stem cell factor affect the clinical prognosis and help to identify the best therapy for patients with gastric cancer.


Determination of B cell epitopes and evaluation of antigen capture ELISA for the earlier diagnosis of CHIK virus using anti-rCHIK E1 rabbit antibodies.
Chikungunya fever caused by an alpha virus has been generally considered as self limiting and non fatal. Recent reports on Chikungunya infection indicate high mortality rates due to the severity of the viral infection. For the early diagnosis of CHIK virus, the incubation period required for the development of antibodies in the serum of patients was a constraint for antigen based ELISA. The results of the present study demonstrates the development and evaluation of the antigen capture ELISA using recombinant anti-CHIK rabbit antibodies and anti-CHIK human antibody for more specific and rapid detection of CHIK viral antigen. A comprehensive bioinformatics analysis of the amino acid sequence of CHIK E1 protein was done for determining the antigenic residues, predominant B cell epitopes and their properties. Rabbit antibodies against recombinant CHIK E1 antigen was developed and purified. Antigen capture ELISA was done in 104 CHIK patient serum samples using anti-rCHIK E1 rabbit antibodies and anti-CHIK human antibodies. The highest rate of sensitivity (96%) and specificity (100%) was observed in the assay data and it highlights the accuracy of the test as a clinical diagnostic tool. No cross reactivity was observed with samples of dengue patients. Apart from the development and evaluation of the ELISA test, the dominant epitopes identified in the recombinant CHIK E1 protein sequence can be exploited for the development of a subunit Chikungunya vaccine.


Serotyping and genotyping of hepatitis C virus in Taiwanese patients with type C chronic liver disease and uraemic patients on maintenance haemodialysis.
To evaluate a recombinant immunoblot hepatitis C virus (HCV) serotyping assay, which determines HCV serotypes 1, 2, and 3 by detecting type-specific antibodies to core-and NS-4-derived peptides. Immunoreactivity of type-specific antibodies among 173 chronic hepatitis C patients and 43 haemodialysis patients in Taiwan was examined and the serotyping results were compared with genotyping by Okamoto's method. Serial specimens from 29 patients undergoing interferon-alpha therapy were also evaluated. Of the 205 specimens for which genotyping data were available, 51.2% were of serotype 1, 31.7% of serotype 2, 1.0% of serotype 3, 2.4% of either serotype 1 or 3, and the remaining 13.7% were untypable. The serotypable rate was significantly lower in haemodialysis patients than in chronic hepatitis C patients (70.0% vs 94.9%; P < 0.001). Serotyping of genotype 2b specimens was significantly more dependent on core peptide bands than other genotypes. Using genotyping as the reference, the overall sensitivity, specificity and concordance of the recombinant immunoblot HCV serotyping assay were 86.3%, 97.2% and 83.9%, respectively. However, the serotyping assay had significantly lower sensitivity (69.2%), specificity (77.8%) and concordance (53.8%) for genotype 2b specimens. Of nine HCV complete responders, one lost type-specific antibodies 6 months after the cessation of interferon-alpha treatment. These results suggest that, except for less than optimal performance with immunocompromised or genotype 2b patients, the HCV serotyping assay is a practical and useful method for HCV typing in the clinical setting in Taiwan.


Paternal Communication and Sexual Health Clinic Visits Among Latino and Black Adolescent Males With Resident and Nonresident Fathers.
Latino and Black adolescent males experience sexual health inequities, and their engagement in sexual health services remains low. Parents shape adolescent sexual health behavior and other youth outcomes. However, the role of Latino and Black fathers in promoting male adolescent sexual health is understudied, in part because about one in four fathers resides apart from their children and nonresident fathers are presumed to be less influential. We examined associations of paternal communication with sexual health service use and perceived paternal role modeling among Latino and Black adolescent males with resident and nonresident fathers. We recruited 191 Latino and Black adolescent males aged 15-19 years and their fathers in the South Bronx, New York City, using area sampling methods; dyads completed surveys. We estimated bivariate and adjusted associations of paternal communication with adolescent male sexual health service use and perceived paternal role modeling using logistic and linear regressions. Effect measure modification by paternal residence was assessed. A unit increase on a five-point paternal communication scale was associated with approximately twice and 1.7 times the likelihood of clinical sexual health service use during adolescent males' lifetime and in the past 3 months, respectively; there was no significant effect measure modification by paternal residence. Paternal communication was associated with increased levels of perceived paternal role modeling and usefulness of paternal advice, with stronger associations for nonresident fathers. Both resident and nonresident Latino and Black fathers warrant greater consideration as partners in promoting male adolescent sexual health service use.


Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study.
Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients' long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia. . A total of 100 patients, aged 35-60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10) in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS) scores, hemodynamics, and side effects were recorded. . Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p<0.050) was earlier than the D5 group. Sensory and motor block duration and time to first analgesic use were significantly longer and the need for rescue analgesics was lower in the D10 group than the D5 group. The 24-hour VAS score was significantly lower in the D10 group (p<0.050). Intergroup hemodynamics were comparable (p>0.050) without any appreciable side effects. . Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner.


Ischaemia modified albumin in patients with acute coronary syndrome and negative cardiac troponin I.
Approximately 40-60% of patients with acute coronary syndrome (ACS) have normal cardiac troponin I (cTnI) concentrations on admission. Ischaemia modified albumin (IMA) has been suggested as a new biomarker of myocardial ischaemia. A total of 43 patients presenting with symptoms suggestive of ACS but with normal (< 0.1 μg/L) cTnI concentrations and 45 healthy subjects were studied. The patients from the study group were divided into two groups: STEMI (n = 28) and NSTEMI (n = 15). All these patients were undergoing percutaneous coronary intervention (PCI) with stenting. The concentrations of cTnI, myoglobin and IMA were determined on admission and 4 h after PCI. Mean (SD) IMA concentrations were higher in patients with ACS (114.39 ± 25.18 U/ml) as compared to the control group (96.24 ± 6.28 U/ml, p < 0.005). IMA concentrations ≥ 104.0 U/ml demonstrated 72.1% sensitivity and 75.6% specificity for the diagnosis of ACS. The area under the receiver operator characteristic curve was 0.766 (95% CI 0.664-0.868) for ACS patients (NSTEMI + STEMI). In both groups increased median (IQR) cTnI concentration after PCI was observed (STEMI patients to 65.4 (10.9-106.9) μg/L and NSTEMI to 17.6 (0.77-84.0) μg/L). In contrast, no increase in IMA concentration was observed. IMA may be a useful biomarker for the identification of ACS patients presenting with typical acute chest pain and/or abnormal electrocardiograms but negative cTnI.


Scalable Contour Tree Computation by Data Parallel Peak Pruning.
As data sets grow to exascale, automated data analysis and visualization are increasingly important, to intermediate human understanding and to reduce demands on disk storage via in situ analysis. Trends in architecture of high performance computing systems necessitate analysis algorithms to make effective use of combinations of massively multicore and distributed systems. One of the principal analytic tools is the contour tree, which analyses relationships between contours to identify features of more than local importance. Unfortunately, the predominant algorithms for computing the contour tree are explicitly serial, and founded on serial metaphors, which has limited the scalability of this form of analysis. While there is some work on distributed contour tree computation, and separately on hybrid GPU-CPU computation, there is no efficient algorithm with strong formal guarantees on performance allied with fast practical performance. We report the first shared SMP algorithm for fully parallel contour tree computation, with formal guarantees of O(lg V lg t) parallel steps and O(V lg V) work for data with V samples and t contour tree supernodes, and implementations with more than 30× parallel speed up on both CPU using TBB and GPU using Thrust and up 70× speed up compared to the serial sweep and merge algorithm.


Well-preserved liver function enhances the clinical impact of curative-intent subsequent treatment during lenvatinib treatment for unresectable hepatocellular carcinoma.
The aims of this study were to evaluate the clinical impact of curative-intent subsequent treatment on overall prognosis in lenvatinib-treated hepatocellular carcinoma (HCC) patients. Eighty-three consecutive patients with intrahepatic target nodules who received lenvatinib were reviewed. The clinical impact of curative-intent subsequent treatments was investigated through analysis of overall survival (OS) according to pathological deterioration stratified by mALBI grade. In patients with mALBI grade 1 and 2a liver function, R0 resection and lenvatinib-transarterial chemoembolization (lenvatinib-TACE) sequential therapy resulted in significantly better OS compared with other, non-curative-intent subsequent therapy and lack of additional treatment (median OS, 37.6 vs 29.0 months and 17.1 vs 8.9 months, respectively; P < 0.001). Multivariate analysis confirmed that use of R0 resection and lenvatinib-TACE sequential therapy were associated with better OS (hazard ratio [HR], 0.021; P < 0.001 and 0.108; P < 0.001) compared with other, non-curative-intent subsequent treatment (HR 0.256; P = 0.010). In contrast, in patients with mALBI grade 2b liver function, multivariate analysis confirmed higher treatment efficacy for non-curative-intent subsequent treatment with respect to OS (HR 0.041; P < 0.001) compared with R0 resection and lenvatinib-TACE sequential therapy (HR 0.057; P = 0.027 and 0.063; P = 0.001). Curative-intent subsequent treatment is more useful for HCC patients with better liver function (mALBI grade 1 and 2a) and intrahepatic target nodules who have received lenvatini b-based treatment.


Stroke of the substance nigra and parkinsonism as first manifestation of systemic lupus erythematosus.
The authors report one case of parkinsonism associated with systemic lupus erythematosus (SLE): a 45-year-old woman, who presented with a strategic infarct of the right substance nigra secondary to vasculitis, and contralateral symptoms. Other causes of parkinsonism were excluded. She had a partial response to therapy with levodopa. Parkinsonism as the first manifestation of lupus is extremely rare. This is the first reported case with strategic infarction in the substance nigra secondary to vasculitis in a patient with SLE.


Rhodococcus equi: an emerging opportunistic pathogen.
Rhodococcus equi is emerging as a cause of pneumonia in immunocompromised people, especially those with AIDS. Like mycobacteria, R. equi is phagocytosed by alveolar macrophages and replicates within them. Recent work is beginning to elucidate the cell and molecular biology of this opportunistic pathogen and the host immune response to it.


Balanced biochemical reactions: a new approach to unify chemical and biochemical thermodynamics.
A novel procedure is presented which, by balancing elements and electric charge of biochemical reactions which occur at constant pH and pMg, allows assessing the thermodynamics properties of reaction Δ(r)G'⁰, Δ(r)H'⁰, Δ(r)S'⁰ and the change in binding of hydrogen and magnesium ions of these reactions. This procedure of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties of formation Δ(f)G'⁰, Δ(f)H'⁰ and Δ(f)S'⁰ hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions. As a consequence, the term "conditional" is proposed in substitution of "Legendre transformed" to indicate these thermodynamics properties. It is also shown that the thermodynamic potential G is fully adequate to give a criterion of spontaneous chemical change for all biochemical reactions and then that the use of the Legendre transformed G' is unnecessary. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately.


Novel azalides derived from sixteen-membered macrolides.
The design and synthesis of novel 15-membered 11-azalides and 16-membered 11,12-diazalide starting from 16-membered macrolides are reported. A mobile linear dialdehyde was isolated via a cyclic tetraol which was prepared by osmium oxidation of a conjugated diene. One-pot macrocyclization of this dialdehyde with an amine or a diamine afforded corresponding 15-membered azalides or 11,12-diazalide. Fundamental SAR studies of 15-membered 11-azalides disclosed their potentiality as a lead molecule for further chemical modifications. For environmental preservation, sustainable chemistry for synthesis of these azalides is also discussed.


The 100K-chaperone protein from adenovirus serotype 2 (Subgroup C) assists in trimerization and nuclear localization of hexons from subgroups C and B adenoviruses.
Recombinant hexons from subgroup C adenoviruses (Ad2 and Ad5) and from a member of subgroup B (Ad3) adenoviruses have been expressed in insect cells. When expressed alone, all three hexons were found to be insoluble and accumulated as inclusion bodies in the cytoplasm. However, co-expression of recombinant Ad2, Ad5 or Ad3 hexon with Ad2 L4-100K protein resulted in the formation of soluble trimeric hexons. EM analysis of hexons revealed that they were indistinguishable from native hexon capsomers isolated from Ad2-infected human cells, or released from partially disrupted adenovirions. This suggests that 100K acts as a chaperone for hexon folding and self-assembly into capsomer in insect cells. Since 100K protein assists in the trimerization of subgroup C hexon, and of subgroup B hexon protein, it implies that it functions in a manner that is both homo- and heterotypic. During the course of recombinant protein expression, the 100K protein was found in association with hexon monomers and trimers within the cytoplasm. In the nucleus, however, 100K was found in complexes with hexon trimers exclusively. EM observation of purified 100K protein samples showed a dumb-bell-shaped molecule compatible with a monomeric protein. EM analysis of hexon-100K protein complexes showed that interaction of hexon with the 100K protein occurred via one of the globular domains of the 100K protein molecule. Our data confirm the role of the 100K protein as a scaffold protein for hexon, and provide evidence suggesting its function in hexon nuclear import in insect cells.