Superdormant Spores as a Hurdle for Gentle Germination-Inactivation Based Spore Control Strategies.
Bacterial spore control strategies based on the germination-inactivation principle can lower the thermal load needed to inactivate bacterial spores and thus preserve food quality better. However, the success of this strategy highly depends on the germination of spores, and a subpopulation of spores that fail to germinate or germinate extremely slowly hinders the application of this strategy. This subpopulation of spores is termed 'superdormant (SD) spores.' Depending on the source of the germination stimulus, SD spores are categorized as nutrient-SD spores, Ca2+-dipicolinic acid SD spores, dodecylamine-SD spores, and high pressure SD spores. In recent decades, research has been done to isolate these different groups of SD spores and unravel the cause of their germination deficiency as well as their germination capacities. This review summarizes the challenges caused by SD spores, their isolation and characterization, the underlying mechanisms of their germination deficiency, and the future research directions needed to tackle this topic in further depth.


Synthesis of isoxazolidine-containing uridine derivatives as caprazamycin analogues.
Simplification of caprazamycins, which are promising antibacterial nucleoside natural products, was conducted by scaffold-hopping of the structurally complex diazepanone moiety to the isoxazolidine scaffold. The designed isoxazolidine-containing uridine derivatives were synthesized by an intramolecular 1,3-dipolar cycloaddition of alkenyl nitrone as a key step. The lactone-fused isoxazolidine intermediate was easily converted to the target compounds by sequential introduction of key substituents upon ring-opening the lactone moiety by nucleophilic substitution and electrophilic capping of the resulting primary alcohol. Several analogues exhibited good activity against H. influenzae ATCC 10211 (MIC 0.25-0.5 μg mL(-1)) and moderate activity against vancomycin-resistant E. faecalis SR7914 (MIC 4-8 μg mL(-1)).


Double-step repetitive stimulation in myasthenia gravis.
The double-step technique of repetitive nerve stimulation was compared with repetitive nerve stimulation to a distal and a proximal muscle and with single fiber needle electromyography in 10 patients with myasthenia gravis. We conclude that the double-step technique is slightly more sensitive than repetitive nerve stimulation to a proximal muscle but only 60% as sensitive as single fiber electromyography in demonstrating abnormal neuromuscular transmission in myasthenia gravis.


Comparison of in-hospital and out-of-hospital cardiac arrest patients receiving targeted temperature management: A matched case-control study.
Evidences that support the use of targeted temperature management (TTM) for in-hospital cardiac arrest (IHCA) are lacking. We aimed to investigate the hypothesis that TTM benefits for patients with IHCA are similar to those with out-of-hospital cardiac arrest (OHCA) and to determine the independent predictors of resuscitation outcomes in patients with cardiac arrest receiving subsequent TTM. This is a retrospective, matched, case-control study (ratio 1:1) including 93 patients with IHCA treated with TTM after the return of spontaneous circulation, who were admitted to Partners HealthCare system in Boston from January 2011 to December 2018. Controls were defined as the same number of patients with OHCA, matched for age, Charlson score, and sex. Survival and neurological outcomes upon discharge were the primary outcome measures. Patients with IHCA were more likely to have experienced a witnessed arrest and receive bystander cardiopulmonary resuscitation, a larger total dosage of epinephrine, and extracorporeal membrane oxygenation. The time duration for ROSC was shorter in patients with IHCA than in those with OHCA. The IHCA group was more likely associated with mild thrombocytopenia during TTM than the OHCA group. Survival after discharge and favorable neurological outcomes did not differ between the two groups. Among all patients who had cardiac arrest treated with TTM, the initial shockable rhythm, time to ROSC, and medical history of heart failure were independent outcome predictors for survival to hospital discharge. The only factor to predict favorable neurological outcomes at discharge was initial shockable rhythm. The beneficial effects of TTM in eligible patients with IHCA were similar with those with OHCA. Initial shockable rhythm was the only independent predictor of both survival and favorable neurological outcomes at discharge in all cardiac arrest survivors receiving TTM.


Lipids as Regulators of Cellular Senescence.
Lipids are key macromolecules that perform a multitude of biological functions ranging from maintaining structural integrity of membranes, energy storage, to signaling molecules. Unsurprisingly, variations in lipid composition and its levels can influence the functional and physiological state of the cell and its milieu. Cellular senescence is a permanent state of cell cycle arrest and is a hallmark of the aging process, as well as several age-related pathologies. Senescent cells are often characterized by alterations in morphology, metabolism, chromatin remodeling and exhibit a complex pro-inflammatory secretome (SASP). Recent studies have shown that the regulation of specific lipid species play a critical role in senescence. Indeed, some lipid species even contribute to the low-grade inflammation associated with SASP. Many protein regulators of senescence have been well characterized and are associated with lipid metabolism. However, the link between critical regulators of cellular senescence and senescence-associated lipid changes is yet to be elucidated. Here we systematically review the current knowledge on lipid metabolism and dynamics of cellular lipid content during senescence. We focus on the roles of major players of senescence in regulating lipid metabolism. Finally, we explore the future prospects of lipid research in senescence and its potential to be targeted as senotherapeutics.


Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat astrocytes.
The Ca2+/calmodulin-dependent phosphatase calcineurin may have physiological and pathological roles in neurons, but little is known about the roles of the enzyme in glial cells. We have previously reported that reperfusion of cultured astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium caused Ca2+ influx followed by delayed cell death. In this study, we examined if calcineurin is involved in this Ca2+-mediated astrocytic injury. FK506, an inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical Ca2+ challenge-induced injury in a dose-dependent manner (10(-10)-10(-8) M). Cyclosporin A at 1 microM mimicked the effect of FK506. Rapamycin (1 microM) did not affect astrocyte injury, but it blocked the protective effect of FK506. Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca2+ challenge-induced increase in cytosolic Ca2+ level nor Na+-Ca2+ exchange activity in the cells, suggesting that the calcineurin is involved in processes downstream of increased cytosolic Ca2+ level. Immunochemical studies showed that both calcineurin A (probably the A beta2 isoform) and B subunits were expressed in the cells. It is concluded that calcineurin is present in cultured astrocytes and it has a pathological role in the cells.


Combination strategies for pain management.
At least two factors relating to pain management using oral analgesics suggest that combination strategies merit consideration: many pains arise from more than one physiological cause and current analgesics have adverse effect profiles that might be reduced by combination with another agent in smaller doses or with less frequent dosing. In addition to increased convenience, combinations sometimes also result in the unexpected benefit of synergy. But not all pains, clinical settings or combinations merit the extra expense or other potential negative features of fixed-ratio products. This review examines the multiple basic science, clinical and pharmacoeconomic issues relating to analgesic combinations and the methodologies available for assessing these issues.


Optimized DNA preparation from mycobacteria.
Extraction of genomic DNA from mycobacteria requires special consideration because (i) many mycobacterial species exhibit extremely slow growth, and thus produce only small amounts of starting material, and (ii) a robust and waxy cell wall renders mycobacteria difficult to lyse. Hence, mycobacterial DNA extraction often results in low DNA yields of unsuitable quality. Published protocols for mycobacterial DNA preparations and commercially available extraction kits are mainly designed for the isolation of small amounts of genomic material suitable for polymerase chain reaction (PCR)-based applications like species identification. However, such DNA quantities and qualities are usually not sufficient for contemporary genomic analyses such as whole genome sequence analysis, single nucleotide polymorphism (SNP) detection, or DNA microarrays, or for investigations of bacterial evolution, virulence, or epidemiology on a world-wide population level. Moreover, most protocols that achieve a high standard in DNA recovery typically employ large reaction volumes and thus require milliliter-scale plasticware and centrifugal equipment as well as large amounts of chemicals, all of which are costly both in purchase and disposal. The DNA extraction method described here was established to address the challenges that result from the slow growth and distinct cell wall composition of mycobacteria, and to greatly enhance both yield and purity of mycobacterial DNA preparations in a small extraction volume. Designed to be performed using 1.5-mL reaction tubes and the corresponding equipment, the method is economical and practical, and reliably yields large amounts of pure genomic DNA--increases of at least 10-fold as compared to earlier protocols.


Heterocellular cadherin connections: coordinating adhesive cues in homeostasis and cancer.
This short insight covers some of the recent topics relevant to the field of cadherin-catenin adhesion in mediating connections between different cell types, so-called heterotypic or heterocellular connections, in both homeostasis and cancer. These scientific discoveries are increasing our understanding of how multiple cells residing in complex tissues can be instructed by cadherin adhesion receptors to regulate tissue architecture and function and how these cadherin-mediated heterocellular connections spur tumor growth and the acquisition of malignant characteristics in tumor cells. Overall, the findings that have emerged over the past few years are elucidating the complexity of the functional roles of the cadherin-catenin complexes. Future exciting research lies ahead in order to understand the physical basis of these heterotypic interactions and their influence on the behavior of heterogeneous cellular populations as well as their roles in mediating phenotypic and genetic changes as cells evolve through complex environments during morphogenesis and cancer.


Determination of onset temperature from the entropy for fragile to strong liquids.
In this paper, we establish a connection between the onset temperature of glassy dynamics with the change in the entropy for a wide range of model systems. We identify the crossing temperature of pair and excess entropies as the onset temperature. Below the onset temperature, the residual multiparticle entropy, the difference between excess and pair entropies, becomes positive. The positive entropy can be viewed as equivalent to the larger phase space exploration of the system. The new method of onset temperature prediction from entropy is less ambiguous, as it does not depend on any fitting parameter like the existing methods.


An Arabic language version of the health promotion lifestyle profile.
The purpose of this study was to assess the validity and reliability of an Arabic version of the Health-Promoting Lifestyle Profile instrument in Jordan, whose society and culture differ from that of North America, where the instrument was developed. The instrument was translated into Arabic, back-translated, and pilot tested to ascertain cultural sensitivity. The Arabic version was then evaluated using a convenience sample of 950 adults in the northern part of Jordan using a principal components factor analysis. The order of factors was not entirely identical to those isolated previously during the psychometric assessment of the English language version. Only the structure of three factors--self actualization, health responsibility--and exercise were the same as those obtained in the English version. The forced, six factor solution explained only 39.3% of the variance in the measure. The alpha reliability coefficients were 0.89 for the total scale and ranged from 0.85 to 0.60 for the subscales. It was concluded that the Arabic version of the Health-Promoting Lifestyle Profile has demonstrated initial reliability and validity. Further testing is recommended.


PEEK-Halo effect in interbody fusion.
Recent developments have seen poly[aryl-ether-ether-ketone] (PEEK) being increasingly used in vertebral body fusion. More novel approaches to improve PEEK have included the introduction of titanium-PEEK (Ti-PEEK) composites and coatings. This paper aims to describe a potential complication of PEEK based implants relating to poorer integration with the surrounding bone, producing a "PEEK-Halo" effect which is not seen in Ti-PEEK composite implants. We present images from two patients undergoing anterior lumbar interbody fusion (ALIF). The first patient underwent an L5/S1 ALIF using a PEEK implant whilst the second patient underwent L4/L5 ALIF using a Ti-PEEK composite implant. Evidence of osseointegration was sought using CT imaging and confirmed using histological preparations of a sheep tibia model. The PEEK-Halo effect is demonstrated by a halo effect between the PEEK implant and the bone graft on CT imaging. This phenomenon is secondary to poor osseointegration of PEEK implants. The PEEK-Halo effect was not demonstrated in the second patient who received a Ti-PEEK composite graft. Histological analysis of graft/bone interface surfaces in PEEK versus Ti-PEEK implants in a sheep model further confirmed poorer osseointegration of the PEEK implant. In conclusion, the PEEK-Halo effect is seen secondary to minimal osseointegration of PEEK at the adjacent vertebral endplate following a PEEK implant insertion. This effect is not seen with Ti-PEEK implants, and may support the role of titanium in improving the bone-implant interface of PEEK substrates.


Inhibitors of the PD-1/PD-L1 axis for the treatment of head and neck cancer: current status and future perspectives.
Head and neck cancer (HNC) is a common malignant tumor, but traditional therapeutic methods have unsatisfactory curative effects and many complications occur. Hence, there is an urgent need to develop therapeutic methods that can elicit curative effects as well as low toxic and few side effects. With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for HNC treatment. Groundbreaking progress has been achieved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). This review describes current treatment by PD-1- and PD-L1-targeted drugs for HNC.


Do interindividual differences in cardiac output during submaximal exercise explain differences in exercising muscle oxygenation and ratings of perceived exertion?
Considerable interindividual differences in the Q˙-V˙O2 relationship during exercise have been documented but implications for submaximal exercise tolerance have not been considered. We tested the hypothesis that these interindividual differences were associated with differences in exercising muscle deoxygenation and ratings of perceived exertion (RPE) across a range of submaximal exercise intensities. A total of 31 (21 ± 3 years) healthy recreationally active males performed an incremental exercise test to exhaustion 24 h following a resting muscle biopsy. Cardiac output (Q˙ L/min; inert gas rebreathe), oxygen uptake (V˙O2 L/min; breath-by-breath pulmonary gas exchange), quadriceps saturation (near infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were measured. The Q˙-V˙O2 relationship from 40 to 160 W was used to partition individuals post hoc into higher (n = 10; 6.3 ± 0.4) versus lower (n = 10; 3.7 ± 0.4, P < 0.001) responders. The Q˙-V˙O2 difference between responder types was not explained by arterial oxygen content differences (P = 0.5) or peripheral skeletal muscle characteristics (P from 0.1 to 0.8) but was strongly associated with stroke volume (P < 0.05). Despite considerable Q˙-V˙O2 difference between groups, no difference in quadriceps deoxygenation was observed during exercise (all P > 0.4). Lower cardiac responders had greater leg (P = 0.027) and whole body (P = 0.03) RPE only at 185 W, but this represented a higher %peak V˙O2 in lower cardiac responders (87 ± 15% vs. 66 ± 12%, P = 0.005). Substantially lower Q˙-V˙O2 in the lower responder group did not result in altered RPE or exercising muscle deoxygenation. This suggests substantial recruitment of blood flow redistribution in the lower responder group as part of protecting matching of exercising muscle oxygen delivery to demand.


Botulinum toxin: poisoning the spastic bladder and urethra.
Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine.


Determination of ploidy level and isolation of genes encoding acetyl-CoA carboxylase in Japanese Foxtail (Alopecurus japonicus).
Ploidy level is important in biodiversity studies and in developing strategies for isolating important plant genes. Many herbicide-resistant weed species are polyploids, but our understanding of these polyploid weeds is limited. Japanese foxtail, a noxious agricultural grass weed, has evolved herbicide resistance. However, most studies on this weed have ignored the fact that there are multiple copies of target genes. This may complicate the study of resistance mechanisms. Japanese foxtail was found to be a tetraploid by flow cytometer and chromosome counting, two commonly used methods in the determination of ploidy levels. We found that there are two copies of the gene encoding plastidic acetyl-CoA carboxylase (ACCase) in Japanese foxtail and all the homologous genes are expressed. Additionally, no difference in ploidy levels or ACCase gene copy numbers was observed between an ACCase-inhibiting herbicide-resistant and a herbicide-sensitive population in this study.


Structural and biochemical characterization of the key components of an auxin degradation operon from the rhizosphere bacterium Variovorax.
Plant-associated bacteria play important regulatory roles in modulating plant hormone auxin levels, affecting the growth and yields of crops. A conserved auxin degradation (iad) operon was recently identified in the Variovorax genomes, which is responsible for root growth inhibition (RGI) reversion, promoting rhizosphere colonization and root growth. However, the molecular mechanism underlying auxin degradation by Variovorax remains unclear. Here, we systematically screened Variovorax iad operon products and identified 2 proteins, IadK2 and IadD, that directly associate with auxin indole-3-acetic acid (IAA). Further biochemical and structural studies revealed that IadK2 is a highly IAA-specific ATP-binding cassette (ABC) transporter solute-binding protein (SBP), likely involved in IAA uptake. IadD interacts with IadE to form a functional Rieske non-heme dioxygenase, which works in concert with a FMN-type reductase encoded by gene iadC to transform IAA into the biologically inactive 2-oxindole-3-acetic acid (oxIAA), representing a new bacterial pathway for IAA inactivation/degradation. Importantly, incorporation of a minimum set of iadC/D/E genes could enable IAA transformation by Escherichia coli, suggesting a promising strategy for repurposing the iad operon for IAA regulation. Together, our study identifies the key components and underlying mechanisms involved in IAA transformation by Variovorax and brings new insights into the bacterial turnover of plant hormones, which would provide the basis for potential applications in rhizosphere optimization and ecological agriculture.


Developing an Interdisciplinary, Team-Based Quality Improvement Leadership Training Program for Clinicians: The Partners Clinical Process Improvement Leadership Program.
Although there has been tremendous progress in quality improvement (QI) education for students and trainees in recent years, much less has been published regarding the training of active clinicians in QI. The Partners Clinical Process Improvement Leadership Program (CPIP) is a 6-day experiential program. Interdisciplinary teams complete a QI project framed by didactic sessions, interactive exercises, case-based problem sessions, and a final presentation. A total of 239 teams composed of 516 individuals have graduated CPIP. On completion, participant satisfaction scores average 4.52 (scale 1-5) and self-reported understanding of QI concepts improved. At 6 months after graduation, 66% of survey respondents reported sustained QI activity. Three opportunities to improve the program have been identified: (1) increasing faculty participation through online and tiered course offerings, (2) integrating the faculty-focused program with the trainee curriculum, and (3) developing a postgraduate curriculum to address the challenges of sustained improvement.


Connexin 26 mutations and nonsyndromic hearing impairment in northern Finland.
The aims of the present study were to evaluate the role of the gap junction protein beta-2 gene (GJB2), encoding connexin 26 (Cx26), in children with moderate to profound prelingual nonsyndromic sensorineural hearing impairment (HI) and to investigate the carrier frequencies of the GJB2 gene mutations in a control population in Northern Finland. Mutation analysis was performed by direct sequencing and carrier detection by conformation sensitive gel electrophoresis further confirmed by direct sequencing. Cx26 mutations were found in 15 of 71 (21.1%) (67 families) children with HI. Homozygosity for the mutation 35delG was shown to be the cause of HI in 13 of 15 (86.7%) children. Homozygosity for the M34T genotype was found in one child, and compound heterozygosity for the M34T/V37I genotype was found in another. Five families of those with suspected familial HI (29.4%) and six families out of those with sporadic HI (12.0%) had a homozygous or compound heterozygous mutation. The carrier frequency for the mutation 35delG was 1 of 78 (4 of 313) and that for the M34T was 1 of 26 (12 of 313). 35delG/35delG genotype was found to be a significant cause of moderate to profound prelingual nonsyndromic sensorineural HI in Northern Finland. M34T/M34T genotype was seen in only one child, but the carrier frequency of the M34T allele was about three times higher than that of the 35delG mutation.


Ultrasonographic diagnosis of ovarian tumors through the deep convolutional neural network.
The objective of this study was to develop and validate an ovarian tumor ultrasonographic diagnostic model based on deep convolutional neural networks (DCNN) and compare its diagnostic performance with that of human experts. We collected 486 ultrasound images of 192 women with malignant ovarian tumors and 617 ultrasound images of 213 women with benign ovarian tumors, all confirmed by pathological examination. The image dataset was split into a training set and a validation set according to a 7:3 ratio. We selected 5 DCNNs to develop our model: MobileNet, Xception, Inception, ResNet and DenseNet. We compared the performance of the five models through the area under the curve (AUC), sensitivity, specificity, and accuracy. We then randomly selected 200 images from the validation set as the test set. We asked three expert radiologists to diagnose the images to compare the performance of radiologists and the DCNN model. In the validation set, AUC of DenseNet was 0.997 while AUC was 0.988 of ResNet, 0.987 of Inception, 0.968 of Xception and 0.836 of MobileNet. In the test set, the accuracy was 0.975 with the DenseNet model versus 0.825 (p < 0.0001) with the radiologists, and sensitivity was 0.975 versus 0.700 (p < 0.0001), and specificity was 0.975 versus 0.908 (p < 0.001). DensNet performed better than other DCNNs and expert radiologists in identifying malignant ovarian tumors from benign ovarian tumors based on ultrasound images, a finding that needs to be further explored in clinical trials.


Wild Caught Nematode Identification and Early Embryo Development: An accessible undergraduate research experience.
Ample evidence suggests that participation in undergraduate research in community college is critical for stimulating interest and retention in STEM careers. Guided skill development and practice in a collaborative lab setting allows students to be competitive when applying to future research opportunities. The goals of this undergraduate research experience (URE) was for student-driven discovery with unknown outcomes including: introduction to primary literature, developmental biology, developing hypotheses, learning worm maintenance, microscopy, PCR, and sequencing analysis. The use of C. elegans and wild caught nematodes facilitated an exciting and affordable project that can be built on in future UREs.


Sitagliptin attenuates inflammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition.
Glucagon-like peptide-1 (GLP-1) and GLP-1 receptors (GLP-1Rs) are responsible for glucose homeostasis, and have been shown to reduce inflammation in preclinical studies. The aim of the present study was to determine whether sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), as a GLP-1 receptor agonist, exerts an anti-inflammatory effect on cardiomyoblasts during lipopolysaccharide (LPS) stimulation. Exposure to LPS increased the expression levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and IL-1β in H9c2 cells, and also resulted in elevations in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) nuclear translocation. Treatment with the DPP-4 inhibitor sitagliptin dose-dependently downregulated the mRNA levels of IL-6, COX-2 and iNOS in LPS-stimulated H9c2 cells. In addition, sitagliptin inhibited the increased protein expression of IL-6, TNF-α and IL-1β. NF-κB mRNA expression was reduced and its translocation to the nucleus was suppressed by treatment with sitagliptin. The present results demonstrated that sitagliptin exerts a beneficial effect on cardiomyoblasts exposed to LPS by inhibiting expression of inflammatory mediators and suppressing NF-κB activation. These findings indicate that the DPP-4 inhibitor sitagliptin may serve a function in cardiac remodeling attributed to sepsis-induced inflammation.


Spot sign number is the most important spot sign characteristic for predicting hematoma expansion using first-pass computed tomography angiography: analysis from the PREDICT study.
The spot sign score (SSS) provides risk stratification for hematoma expansion in acute intracerebral hemorrhage; however, external validation is needed. We sought to validate the SSS and assess prognostic performance of individual spot characteristics associated with hematoma expansion from a prospective multicenter intracerebral hemorrhage study. Two hundred twenty-eight intracerebral hemorrhage patients within 6 hours after ictus were enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, a multicenter prospective intracerebral hemorrhage cohort study. Patients were evaluated with baseline noncontrast computerized tomography, computerized tomography angiography, and 24-hour follow-up computerized tomography. Primary outcome was significant hematoma expansion (>6 mL or >33%) and secondary outcome was absolute and relative expansion. Blinded computerized tomography angiography spot sign characterization and SSS calculation were independently performed by 2 neuroradiologists and a radiology resident. Diagnostic performance of the SSS and individual spot characteristics were examined with multivariable regression, receiver operating characteristic analysis, and tests for trend. SSS and spot number independently predicted significant, absolute, and relative hematoma expansion (P<0.05 each) and demonstrated near perfect interobserver agreement (κ=0.82 and κ=0.85, respectively). Incremental risk of hematoma expansion among spot-positive patients was not identified for SSS (P trend=0.720) but was demonstrated for spot number (P trend=0.050). Spot number and SSS demonstrated similar area under the curve (0.69 versus 0.68; P=0.306) for hematoma expansion. Multicenter external validation of the SSS demonstrates that the spot number alone provides similar prediction but improved risk stratification of hematoma expansion compared with the SSS.


Mitochondrial genomes of the Baltic clam Macoma balthica (Bivalvia: Tellinidae): setting the stage for studying mito-nuclear incompatibilities.
Allopatric divergence across lineages can lead to post-zygotic reproductive isolation upon secondary contact and disrupt coevolution between mitochondrial and nuclear genomes, promoting emergence of genetic incompatibilities. A previous F ST scan on the transcriptome of the Baltic clam Macoma balthica highlighted several genes potentially involved in mito-nuclear incompatibilities (MNIs). As proteins involved in the mitochondrial oxidative phosphorylation (OXPHO) chain are prone to MNIs and can contribute to the maintenance of genetic barriers, the mitochondrial genomes of six Ma. balthica individuals spanning two secondary contact zones were sequenced using the Illumina MiSeq plateform. The mitogenome has an approximate length of 16,806 bp and encodes 13 protein-coding genes, 2 rRNAs and 22 tRNAs, all located on the same strand. atp8, a gene long reported as rare in bivalves, was detected. It encodes 42 amino acids and is putatively expressed and functional. A large unassigned region was identified between rrnS and tRNA (Met) and could likely correspond to the Control Region. Replacement and synonymous mutations were mapped on the inferred secondary structure of all protein-coding genes of the OXPHO chain. The atp6 and atp8 genes were characterized by background levels of replacement mutations, relative to synonymous mutations. However, most nad genes (notably nad2 and nad5) were characterized by an elevated proportion of replacement mutations. Six nearly complete mitochondrial genomes were successfully assembled and annotated, providing the necessary roadmap to study MNIs at OXPHO loci. Few replacement mutations were mapped on mitochondrial-encoded ATP synthase subunits, which is in contrast with previous data on nuclear-encoded subunits. Conversely, the high population divergence and the prevalence of non-synonymous mutations at nad genes are congruent with previous observations from the nuclear transcriptome. This further suggest that MNIs between subunits of Complex I of the OXPHO chain, coding for NADH dehydrogenase, may play a role in maintaining barriers to gene flow in Ma. balthica.


Morphological Characteristics of Dimples of Ductile Fracture of VT23M Titanium Alloy and Identification of Dimples on Fractograms of Different Scale.
The authors developed a method for the automated detection and calculation of quantitative parameters of dimples of ductile fracture on the digital images of fracture surfaces obtained at different scales. The processing algorithm of fractographic images was proposed, which allowed high quality recognition of the shape and size of dimples to be achieved, taking into account the morphological features of their digital images. The developed method for identifying dimples of various physical and morphological characteristics was tested on the VT23M alloy. The test results showed that the method meets the quality requirements for the automated diagnostics of fracture mechanisms of titanium alloys.


Epidermal growth factor receptor in human epidermal cells: direct demonstration in cultured cells.
The interaction of [125I] labeled murine epidermal growth factor (EGF)( with cultured human keratinocytes has been studied. Epidermal cells from neonatal foreskins were propagated to confluence in 24-well culture trays and incubated with [125I] EGF for binding assays. Association reached equilibrium within 2-4 hr at 4 degrees and slightly earlier at 37 degrees. EGF bound at 37 degrees dissociates very slowly from cells, since it can be shown to enter cells and is degraded to trichloracetic-acid-soluble material. Cells exposed to chloroquine, an inhibitor of lysosomal enzymes, fail to degrade internalized [125I] EGF. Scatchard plots of the binding data yield a dissociation constant of 1 X 10(-9) m and show that epidermal cells bind approximately 3-4 X 10(4) molecules of EGF. Cells exposed to EGF alter their ability to bind EGF by decreasing the number of binding sites in a time- and concentration-dependent manner. Differentiation of epidermal cells in culture poses a problem in assessment of binding of EGF and possibly of other biologically active ligands, since cells lose the ability to bind EGF as they differentiate. These findings indicate that isolated epidermal cells possess a functional receptor for EGF which binds and responds to EGF in a manner similar to that described for other cells.


[Polypoid pseudosarcoma of the tongue].
Polypoid pseudosarcoma (PP) is a rare type of squamous-cell carcinoma of mouth, fauces and larynx with sarcoma-like reaction. Clinically PP is characterized by large pedunculated or sessile masses of rapid growing. This tumour recurs easily but rarely provokes metastasis. A case of polypoid pseudosarcoma of the tongue is reported. Differential diagnosis with spindle-cell carcinoma can be made following the criteria: a) the frequency and the sarcomatous appearance of the metastasis in the spindle-cell carcinoma, while PP rarely provokes metastasis which have a squamous-cell pattern; b) the gradual transition within the epithelial and the sarcomatous aspects in the spindle-cell carcinoma, not present in PP; and c) the presence of tonofilaments and desmosomes in the sarcomatous cells of the spindle-cell carcinoma, which lack in the sarcoma-like masses of PP.


Synthesis and antibacterial activities of some chloro analogs of 3 amino-3,4-dihydro-1-hydroxycarbostyril.
The effects of a chloro substituent upon the microbiological activities of 3-amino-3,4-dihydro-1-hydroxycarbostyril were determined. The 5-, 6-, and 7-chloro analogs were synthesized by reductive cyclizations of the appropriately chloro-substituted o-nitrophenylalanines, while the 8-chloro analog was obtained from the N-trifluoroacetyl-3-chloro-2-nitrophenylalanine ethyl ester. All of these compounds were observed to inhibit the growth of Escherichia coli 9723, Leuconostoc dextranicum 8086, and Lactobacillus plantarum 8014. The relative inhibitory activities of the chloro analogs were 7-Cl greater than 6-Cl greater than 8-Cl greater than 5-Cl in E. coli and 7-Cl greater than 6-Cl greater than 8-Cl = 5-Cl in L. dextranicum and L. plantarum. In each of the three microorganisms, the 7-Cl analog was a more effective growth inhibitor than the parent unsubstituted compound. The growth inhibitory activities of this class of compounds were demonstrated to be much more effective than those of the four corresponding lactams, the 5-, 6-, 7-, and 8-chloro analogs of 3-amino-3,4-dihydrocarbostyril.


A theoretical description of the polarization dependence of the sum frequency generation spectroscopy of the water/vapor interface.
An improved time correlation function (TCF) description of sum frequency generation (SFG) spectroscopy was developed and applied to theoretically describing the spectroscopy of the ambient water/vapor interface. A more general TCF expression than was published previously is presented-it is valid over the entire vibrational spectrum for both the real and imaginary parts of the signal. Computationally, earlier time correlation function approaches were limited to short correlation times that made signal processing challenging. Here, this limitation is overcome, and well-averaged spectra are presented for the three independent polarization conditions that are possible for electronically nonresonant SFG. The theoretical spectra compare quite favorably in shape and relative magnitude to extant experimental results in the O-H stretching region of water for all polarization geometries. The methodological improvements also allow the calculation of intermolecular SFG spectra. While the intermolecular spectrum of bulk water shows relatively little structure, the interfacial spectra (for polarizations that are sensitive to dipole derivatives normal to the interface--SSP and PPP) show a well-defined intermolecular mode at 875 cm(-1) that is comparable in intensity to the rest of the intermolecular structure, and has an intensity that is approximately one-sixth of the magnitude of the intense free O-H stretching peak. Using instantaneous normal mode methods, the resonance is shown to be due to a wagging mode localized on a single water molecule, almost parallel to the interface, with two hydrogens displaced normal to the interface, and the oxygen anchored in the interface. We have also uncovered the origin of another intermolecular mode at 95 cm(-1) for the SSP and PPP spectra, and at 220 cm(-1) for the SPS spectra. These resonances are due to hindered translations perpendicular to the interface for the SSP and PPP spectra, and translations parallel to the interface for the SPS spectra. Further, by examining the real and imaginary parts of the SFG signal, several resonances are shown to be due to a single spectroscopic species while the "donor" O-H region is shown to consist of three distinct species-consistent with an earlier experimental analysis.


I see the light! Fluorescent proteins suitable for cell wall/apoplast targeting in Nicotiana benthamiana leaves.
Correct subcellular targeting is crucial for protein function. Protein location can be visualized in vivo by fusion to a fluorescent protein (FP). Nevertheless, despite intense engineering efforts, most FPs are dim or completely quenched at low pH (<6). This is particularly problematic for the study of proteins targeted to acidic compartments such as vacuoles (pH ~ 3-6) or plant cell walls (pH ~ 3.5-8.3). Plant cell walls play important roles (e.g. structural/protective role, control of growth/morphogenesis), are diverse in structure and function, and are highly dynamic (e.g. during cell growth, in response to biotic/abiotic stresses). To study and engineer plant cell walls, it is therefore critical to identify robust tools which can be used to locate proteins expressed in the apoplast. Here we used a transient expression assay in Nicotiana benthamiana leaves to test a range of FPs in vivo, and determined which ones retained strong fluorescence in the acidic environment of the apoplast. We selected 10 fluorescent proteins with a range of in vitro properties; two historical FPs and eight FPs with in vitro properties suggesting lower pH sensitivity or improved brightness, some of which had never been tested in plants prior to our study. We targeted each FP to the cytosol or the apoplast and compared the fluorescence in both compartments, before testing the in vivo pH sensitivity of FPs across a pH 8-4 gradient. Our results suggest that mTurquoise2, mNeonGreen, and mCherry are suited to tracking proteins in the apoplast under dynamic pH conditions. These fluorescent proteins may also be useful in other acidic compartments such as vacuoles.


"Gilbert's-like" syndrome as part of a spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.
Gilbert's syndrome (GS) patients present with remittent unconjugated hyperbilirubinemia. In this study, we investigated the correlation between polymorphisms in the gene encoding UDP-glucuronosyltransferase, UGT1A1, and the development of unconjugated hyperbilirubinemia in clinical GS and post-hepatitis hyperbilirubinemia. Blood samples were collected from 285 patients, including 85 patients who were clinically diagnosed with GS, 70 patients who had indirect hyperbilirubinemia during the recovery period of chronic liver diseases, 109 patients with normal hepatic function and 21 chronic active hepatitis patients. All samples were tested for the presence of the *28/*6 UGT1A1 genotype by pyrosequencing. Compared with the GS-control group, a significant difference in variations of the UGT1A1*28/*6 allele gene was found in GS patients. The post-hepatitis group showed a significant difference in the UGT1A1*28/*6 allele gene frequency distribution relative to that in the hepatitis control group. There were no significant differences between the GS group and post-hepatitis group in the distribution of the UGT1A1*28/*6 allele gene frequency and UGT1A1 diplotypes. UGT1A1*28/*6 gene polymorphisms in patients who had indirect hyperbilirubinemia while recovering from chronic liver diseases presented similar patterns as those seen for GS patients. These findings suggest that a "Gilbert's-like" syndrome might be part of the spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.


Conduct Problems As a Pathway From Childhood Adversity to Community Violence Exposure: The Protective Roles of Caregiver Knowledge and Involvement.
Exposure to community violence (ECV) poses a prevalent threat to the health and development of adolescents. Research indicates those who have more Adverse Childhood Experiences (ACEs) are at higher risk for ECV, which further exacerbates risk of negative mental and physical health impacts. Additionally, those with more ACEs are more likely to exhibit conduct problems, which has also been linked to risk for ECV. Despite the prevalence and impact of ECV, there is limited longitudinal research on the risk factors that precede this exposure as well as family-level factors that may prevent it. The current study examined conduct problems as a potential mediator between ACEs and future indirect (i.e. witnessing) ECV in adolescents. Additionally, this study included caregiver factors, such as caregiver knowledge about their adolescent, caregiver involvement, and caregiver-adolescent relationship quality as potential protective moderators. Participants included (N = 1137) caregiver-adolescent dyads identified as at-risk for child maltreatment prior to child's age four for inclusion in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Conduct problems at age 14 mediated the relationship between ACEs from ages 0-12 and indirect ECV at age 16 (standardized indirect effect = .03, p = .005). Caregiver knowledge moderated the indirect relationship (b = -.40, p = .030), and caregiver involvement moderated the direct relationship between ACEs and indirect ECV (b = -.03, p = .033). Findings expand our knowledge about the longitudinal pathways that increase risk of violence exposure over the course of adolescent development, as well as the protective benefits caregivers can offer to disrupt these pathways and reduce risk of future traumatization. Implications are discussed for interventions that aim to address and prevent trauma and adverse outcomes among youth exposed to child maltreatment, household dysfunction, and community violence.


Open vs. closed reduction combined with minimally invasive plate osteosynthesis in humeral fractures.
Aim To explore a more effective surgical procedure, the outcomes of closed manipulative reduction (CMR) combined with minimally invasive plate osteosynthesis (MIPO) and conventional open reduction and internal fixation (ORIF) for treating proximal humeral fractures were compared. Material and methods In a retrospective study of patients operated for humerus shaft fractures from April 2008 to July 2011, the outcomes of 33 patients treated with CMR/MIPO were compared with the outcomes of 42 patients treated with ORIF. The fractures were classified, and the incision length, blood transfusion, operating time, as well as the VAS (Visual Analog Scale) pain scores were analyzed. The neck-shaft angles of the proximal humerus were detected, and the postoperative function of the shoulder was evaluated. Results The mean values of incision length, blood transfusion, and VAS pain scores at the 1st and 3rd day after CMR/MIPO and operation time were lower than that of ORIF. The postoperative radiographs verified good position of all screws and satisfactory bone fracture reduction in both groups. Meanwhile, in the ORIF group, nonunion (three cases) and humeral head necrosis (four cases) were detected. Conclusions The MR/MIPO technique showed smaller incisions, easier operation, less blood transfusion and more effective recovery of shoulder joint function for treating proximal humeral fractures than ORIF.


Control of metallic corrosion through microbiological route.
Involvement of biofilm or microorganisms in corrosion processes is widely acknowledged. Although majority of the studies on microbiologically induced corrosion (MIC) have concentrated on aerobic/anaerobic bacteria. There are numerous aerobic bacteria, which could hinder the corrosion process. The microbiologically produced exopolymers provide the structural frame work for the biofilm. These polymers combine with dissolved metal ions and form organometallic complexes. Generally heterotrophic bacteria contribute to three major processes: (i) synthesis of polymers (ii) accumulation of reserve materials like poly-beta-hydroxy butrate (iii) production of high molecular weight extracellular polysaccharides. Poly-beta-hydroxy butyrate is a polymer of D(-)beta-hydroxy butrate and has a molecular weight between 60,000 and 2,50,000. Some extracellular polymers also have higher molecular weights. It seems that higher molecular weight polymer acts as biocoating. In the present review, role of biochemistry on corrosion inhibition and possibilities of corrosion inhibition by various microbes are discussed. The role of bacteria on current demand during cathodic protection is also debated. In addition, some of the significant contributions made by CECRI in this promising area are highlighted.


Green synthesis of silver nanoparticles using Prosopis juliflora bark extract: reaction optimization, antimicrobial and catalytic activities.
In the present study, silver nanoparticles (PJB-AgNPs) have been biosynthesized employing Prosopis juliflora bark extract. The biosynthesis of silver nanoparticles was monitored on UV-vis spectrophotometer. The size, charge and polydispersity index (PDI) of PJB-AgNPs were determined using dynamic light scattering (DLS). Different parameters dictating the size of PJB-AgNPs were explored. Nanoparticles biosynthesis optimization studies suggested efficient synthesis of highly dispersed PJB-AgNPs at 25 °C when 9.5 ml of 1 mM AgNO3 was reduced with 0.5 ml of bark extract for 40 min. Characterization of PJB-AgNPs by SEM showed spherical-shaped nanoparticles with a size range ∼10-50 nm along with a hydrodynamic diameter of ∼55 nm as evaluated by DLS. Further, characterizations were done by FTIR and EDS to evaluate the functional groups and purity of PJB-AgNPs. The antibacterial potential of PJB-AgNPs was tested against E. coli and P. aeruginosa. The PJB-AgNPs remarkably exhibited anticancer activity against A549 cell line as evidenced by Alamar blue assay. The dye degradation activity was also evaluated against 4-nitrophenol that has carcinogenic effect. The results thus obtained suggest application of PJB-AgNPs as antimicrobial, anticancer and catalytic agents.


Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists.
Many diseases of the cornea and ocular surface are manifestations of an underlying autoimmune process and require systemic immunosuppression for their management. These cases often present to a general ophthalmologist before being referred to an ocular immunologist or rheumatologist. However, the patients do need to be followed by the ophthalmologist to assess disease progression or for management of ocular co-morbidities and for taking care of ocular complications of the disease. Undeniably, there is a certain hesitance to promptly initiate them on systemic therapy because the literature regarding the indications, dosages, and side effects of this group of drugs is vast and dispersed.The aim of this review is to provide a source of ready reference for the general ophthalmologist as well as trainees and residents, on systemic immunosuppression for corneal and ocular surface disease. This review included 153 studies which were published as randomized controlled trials, systematic reviews, or as nonrandomized comparative studies (cohort or case-control series) on the topic of systemic immunosuppression in cornea and ocular surface disorders. This review provides a concise summary of both the types of drugs and the common indications where they would be indicated, along with treatment and monitoring algorithms for each specific disease condition. The most used group of drugs are corticosteroids, which have significant side effects, particularly when administered systemically or for longer periods of time. To overcome this, steroid-sparing immunosuppressants are recommended. The four main classes of immunosuppressants used today are antimetabolites, T-cell inhibitors, alkylating agents and biologic agents. This review details the use of these drugs in ocular surface inflammation, including the dosing schedule, side effects and monitoring in allergic conjunctivitis, mucous membrane pemphigoid, peripheral ulcerative keratitis, immunological rejection against corneal allografts, anterior scleritis and aqueous deficiency dry eyes. This review provides an uncluttered and wholesome understanding of systemic immunosuppression in cornea and ocular surface diseases, with the hope that this will serve as a ready reckoner and help bridge the gap between ophthalmology and rheumatology for the betterment of our patients.


Factors influencing survival after gamma knife radiosurgery for patients with single and multiple brain metastases.
Radiosurgery has been reported to yield high local control rates for brain metastases. However, further work is needed to define which subgroups of patients may benefit from this treatment modality. We reviewed 116 patients who underwent stereotactic radiosurgery for initial management or recurrence of solitary or multiple brain metastases from September 1991 through December 1994 at the University of California, San Francisco. Survival time and time to local-regional failure were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Median survival was 40 weeks from radiosurgery. In multivariate analysis, smaller total tumor volume, absence of extracranial metastases, higher Karnofsky score, and age < or = 70 had a positive effect on survival. In patients initially managed for brain metastases, the addition of whole brain radiotherapy to radiosurgery had no significant effect on survival. Although the presence of multiple metastases was associated with a significantly worse survival rate in patients initially managed with radiosurgery in univariate analysis, it was not as a significant factor in multivariate analysis. An analysis of patients within this series treated with radiosurgery who would have been eligible for Patchell's study on the role of surgery in the treatment of solitary brain metastasis revealed a favorable median survival of 70 weeks. We conclude that radiosurgical treatment of brain metastases results in survival times that compare favorably with the historic experience in patients treated with whole brain radiotherapy alone or with surgical resection. In patients presenting initially with brain metastases, radiosurgery alone may yield survival results equivalent to radiosurgery with whole brain radiotherapy, but intracranial control and quality of life also need to be evaluated. Also, the presence of multiple brain metastases should not be a contraindication for the use of radiosurgery given the good survival achieved with such patients in this series. Each such case should therefore be evaluated based on other factors such as patient's age, Karnofsky score and systemic disease.


Colles' type distal radial fractures undergoing manipulation in the ED: a multicentre observational cohort study.
Colles' type fractures of the distal radius are one of the most commonly manipulated fractures in the ED. Local audit data suggest that a high proportion of these injuries undergo subsequent surgical fixation. If widespread, this could represent a potential burden on patients and the NHS worthy of further research. The aims of this study were to estimate the rate of surgical fixation of Colles' type distal radial fractures after ED fracture manipulation and explore variations in their management in UK EDs. We conducted a multicentre observational study in 16 EDs in the UK from 4 February 2019 to 31 March 2019. All adult patients with a Colles' fracture who underwent fracture manipulation in the ED were included. Patients who could not be followed up and those with volar displaced fractures were excluded. We measured the rate of wrist fracture surgery at 6 weeks, patient demographics and variations in anaesthetic technique used. During the study period, 328 adult patients attended the participating EDs with a distal radial fracture. Of these, 83 patients underwent fracture manipulation in the ED and were eligible for the study. Their mean age (SD) was 65.3 (17.0) years, 84.3% were female and the most common method of anaesthesia used was haematoma block (38.6%). 34 (41.0%, 95 % CI 30.3 to 52.3) patients had subsequent surgical fixation of their fracture. Younger age was associated with higher rates of surgical fixation but ED anaesthetic technique did not affect the subsequent need for surgery in this sample. Subsequent surgical fixation was carried out in 41% of patients who underwent manipulation of Colles' type wrist fractures in this cohort. This merits further research and represents a potential target to rationalise repeat procedures.


Long non-coding RNA transcriptome of uncharacterized samples can be accurately imputed using protein-coding genes.
Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are increasingly being recognized as crucial mediators of disease pathogenesis. However, the vast majority of published transcriptome datasets lack high-quality lncRNA profiles compared to protein-coding genes (PCGs). Here we propose a framework to harnesses the correlative expression patterns between lncRNA and PCGs to impute unknown lncRNA profiles. The lncRNA expression imputation (LEXI) framework enables characterization of lncRNA transcriptome of samples lacking any lncRNA data using only their PCG profiles. We compare various machine learning and missing value imputation algorithms to implement LEXI and demonstrate the feasibility of this approach to impute lncRNA transcriptome of normal and cancer tissues. Additionally, we determine the factors that influence imputation accuracy and provide guidelines for implementing this approach.


Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.
Several epidemiological studies have shown an inverse relation between high-density lipoprotein (HDL) cholesterol levels and coronary heart disease. Recently, observational studies have suggested a similar inverse relation between HDL and restenosis after coronary balloon angioplasty. Despite these observations, it is unclear whether this inverse relation reflects a direct vascular protective effect of HDL or apolipoprotein (apo) A-I, the major apolipoprotein component of HDL. Therefore, to determine whether HDL directly influences neointima formation, we investigated the effect of recombinant apo A-I Milano (apo A-I M), a mutant of human apo A-I with Arg-173 to Cys substitution, on intimal thickening after balloon injury in cholesterol-fed rabbits. Cholesterol feeding was initiated 18 days before injury and continued until the time of death. Eight rabbits received intravenous injections of 40 mg of apo A-I M linked to a phospholipid carrier on alternate days, beginning 5 days before and continuing for 5 days after balloon injury of femoral and iliac arteries. Eight rabbits received the carrier alone, and four received neither apo A-I M nor the carrier. Three weeks after balloon injury, apo A-I M-treated rabbits had significantly reduced intimal thickness compared with the two control groups (mean +/- SD): 0.49 +/- 0.29 versus 1.14 +/- 0.38 mm2 and 1.69 +/- 0.43 mm2, P < .002 by ANOVA). The intima-to-media ratio was also significantly reduced by apo A-I M (0.7 +/- 0.2 versus 1.5 +/- 0.5 and 2.1 +/- 0.1, P < .002 by ANOVA) compared with the two controls. The fraction of intimal lesion covered by macrophages, as identified by immunohistochemistry using macrophage-specific monoclonal antibody, was significantly less in apo A-I M-treated rabbits compared with carrier-treated animals (25.3 +/- 17% versus 59.4 +/- 12.3%, P < .005). Aortic cholesterol content, measured in an additional 10 rabbits, did not differ significantly between apo A-I M-treated animals (n = 5) and carrier-treated controls (n = 5). Apo A-I M significantly reduced intimal thickening and macrophage content after balloon injury in cholesterol-fed rabbits without a change in arterial total cholesterol content. Although the precise mechanism of action remains to be defined, these findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications.


Preparatory Mechanisms for Salinity Tolerance in Two Congeneric Anuran Species Inhabiting Distinct Osmotic Habitats.
Anurans occupy a wide variety of habitats of diverse salinities, and their osmoregulatory ability is strongly regulated by hormones. In this study, we compared the adaptability and hormonal responses to osmotic stress between two kajika frogs, Buergeria japonica (B.j.) and B. buergeri, (B.b.), which inhabit coastal brackish waters (BW) in the Ryukyu Islands and freshwater (FW) in the Honshu, respectively. Both hematocrit and plasma Na+ concentration were significantly higher in B.j. than in B.b. when both were kept in FW. After transfer to one-third seawater (simulating the natural BW environment), which is slightly hypertonic to their body fluids, their body mass decreased and plasma Na concentration increased significantly in both species. After transfer, plasma Na+ concentration increased significantly in both species. We examined the gene expression of two major osmoregulatory hormones, arginine vasotocin (AVT) and atrial natriuretic peptide (ANP), after partial cloning of their cDNAs. ANP mRNA levels were more than 10-fold higher in B.j. than in B.b. in FW, but no significant difference was observed for AVT mRNA levels due to high variability, although the mean value of B.j. was twice that of B.b. Both AVT and ANP mRNA levels increased significantly after transfer to BW in B.b. but not in B.j., probably because of the high levels in FW. These results suggest that B.j. maintains high plasma Na+ concentration and anp gene expression to prepare for the future encounter of the high salinity. The unique preparatory mechanism may allow B.j. wide distribution in oceanic islands.


Effects of beta 1- and beta 2-adrenoceptor stimulation on hemodynamics in the anesthetized rat.
The role of beta 1-adrenoceptors in mediation of vasodilatation is not clear. The microsphere technique was used to compare the effects of mixed beta-, beta 1-, and beta 2-stimulation on blood flow and conductance changes in five groups of pentobarbital-anesthetized rats: I, vehicle; II, mixed beta-stimulation; III, beta 1-stimulation; IV, beta 2-stimulation; and V, mixed beta-blockade. Isoproterenol (32 ng/kg/min) was infused into rats either without (group II) or with ICI 118,551 (beta 2-blocker, 30 micrograms/kg, group III), atenolol (beta 1-blocker, 100 micrograms/kg, group IV), or both blockers (group V), respectively. At the doses selected, ICI 118,551 shifted the dose-vasodepressor response curve of salbutamol (beta 2-agonist) to the right but had no effect on the dose-chronotropic response curve of dobutamine (beta 1-agonist), whereas atenolol shifted the dose-chronotropic response curve of dobutamine to the right and had no effect on the dose-vasodepressor response curve of salbutamol. The results show that isoproterenol increased heart rate (HR) and arterial conductances in the coronary and skeletal muscle beds but had no effects in other beds. Combined with ICI 118,551, isoproterenol caused similar increases in HR and coronary arterial conductance but markedly less increase in skeletal muscle conductance. Atenolol abolished the increase in HR by isoproterenol but did not affect the increases in coronary and muscular arterial conductances. With both blockers, isoproterenol produced no increase in coronary and skeletal muscle conductance. Therefore, both beta 1- and beta 2-adrenoceptors play a role in coronary and skeletal muscle vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)


Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).
To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.


Small molecules and antibodies for the treatment of psoriasis: a patent review (2010-2015).
Psoriasis is a chronic condition whose therapeutic armamentarium is increasingly being discussed, particularly when compared to past decades. The use of biologic agents has profoundly changed the history of this disease, as well as the management of psoriatic patients. Due to the enormous interest in psoriasis, as demonstrated within the scientific community and pharmaceuticals, new therapeutic targets have been identified and novel patented therapeutics are being tested. This review sought to give an overview of small molecules and antibodies patented in the last five years for the treatment of psoriasis. Therapeutic agents either in the early or advanced phase of development have been described, primarily based on a systematic search using the PubMed Medline database. Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm.


Palmitoylation promotes chaperone-mediated autophagic degradation of NLRP3 to modulate inflammation.
The critical intracellular pattern recognition receptor NLRP3 senses pathogenic organisms and endogenous danger signals via forming inflammasomes to orchestrate innate immune responses. Dysfunction of NLRP3 inflammasomes is implicated in several inflammatory disorders. Hence, it is important to uncover the mechanisms preventing sustained NLRP3 inflammasome activation. Recently, we revealed that ZDHHC12-mediated palmitoylation enhances NLRP3 degradation through the chaperone-mediated autophagy pathway, and identified gain-of-function variants of NLRP3 in autoinflammatory diseases, which induce excessive NLRP3 inflammasome activation through decreased NLRP3 palmitoylation level and impaired chaperone-mediated autophagic degradation of NLRP3.


Idiopathic adrenal hematoma masquerading as neoplasm.
We report herein a case of idiopathic adrenal hematoma. A 59-year-old Japanese man was referred to our hospital for evaluation of a 7.0 cm mass in the right upper abdominal cavity. The tumor was suspected to originate from either the posterior segment of the liver or the right adrenal gland. His chief complaint was weight loss of 8 kg over the previous 6 months. He had no past medical history and took no medications, including no anticoagulants. Laboratory data were almost normal except for a slight elevation of PIVKA-II. The origin of the tumor was found to be the adrenal gland, as angiography revealed the blood supply to the mass to derive from the right superior and inferior adrenal arteries. A fine needle biopsy of the lesion was unable to confirm the diagnosis. Open right adrenalectomy was performed. The histopathological findings of the surgical specimen revealed a hematoma with normal adrenal tissue. In the absence of any obvious etiology, the diagnosis was idiopathic adrenal hematoma.


Developing an algorithm for treating heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a serious and common complication of heparin therapy that can lead to significant losses of life and limb. It is often under-recognized and, therefore, goes untreated until thrombosis develops. This article is meant to provide specific recommendations for treating patients with immune-mediated HIT, whether or not it is associated with thrombosis. These recommendations are based on our clinical experience treating patients with HIT and our evaluation of the published data on the efficacy and safety of lepirudin and argatroban, the 2 drugs approved by the Food and Drug Administration for treating HIT. Based on these criteria, we consider lepirudin the treatment of choice in all patients with HIT except those with severe or deteriorating renal function.


Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus.
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.


Nanaomycin A Treatment Promotes Hepatoblast Differentiation from Human iPS Cells.
Human induced pluripotent stem cell-derived hepatocyte-like cells (HLCs) are expected to be utilized in pharmaceutical research, including drug screening. However, the hepatocyte functions of the HLCs are still lower than those of human hepatocytes. Therefore, we attempted to improve the hepatocyte differentiation method by modulating the DNA epigenetic status. We first examined the expression profiles of the maintenance DNA methyltransferase (DNMT) 1 and the de novo DNMTs DNMT3A and DNMT3B, all of which are essential for mammalian development. Among these DNMTs, the expression levels of DNMT3B were significantly decreased during the hepatoblast differentiation. To accelerate the hepatoblast differentiation, a DNMT3B-selective inhibitor, nanaomycin A, was treated during the hepatoblast differentiation. The gene expression levels of hepatoblast markers (such as alpha-fetoprotein and hepatocyte nuclear factor 4 alpha) were increased by the nanaomycin A treatment. On the other hand, the gene expression levels of hepatoblast markers were decreased by DNMT3B overexpression. These results suggest that it might be possible to promote the hepatoblast differentiation by DNMT3B inhibition using nanaomycin A. Importantly, we also confirmed that the hepatocyte differentiation potency of nanaomycin A-treated hepatoblast-like cells was higher than that of dimethyl sulfoxide-treated hepatoblast-like cells. Our findings should assist in the future generation of functional HLCs for pharmaceutical research.


Magnetic resonance imaging of the brain in childhood herpesvirus infections.
We used magnetic resonance imaging (MRI) to evaluate nine children with neurologic disorders caused by infections with members of the herpesvirus family. MRI studies were abnormal in eight children and demonstrated a wide range of central nervous system lesions, including cystic encephalomalacia, ventricular enlargement, cerebral atrophy and focal parenchymal lesions. When compared with conventional computed tomographic scanning, MRI was more sensitive in detecting abnormalities of white matter and in defining the extent of parenchymal lesions. These studies indicate that MRI scans are highly useful in children with herpesvirus infections involving the central nervous system.


First Elastic Electron Scattering from ^{132}Xe at the SCRIT Facility.
The first elastic electron scattering has been successfully performed at the self-confining radioactive-isotope ion target (SCRIT) facility, the world's first electron scattering facility for SCRIT technique achieved high luminosity (over 10^{27} cm^{-2} s^{-1}, sufficient for determining the nuclear shape) with only 10^{8} target ions. While ^{132}Xe used in this time as a target is a stable isotope, the charge density distribution was first extracted from the momentum transfer distributions of the scattered electrons by comparing the results with those calculated by a phase shift calculation.


Mycobacteriophage D29 induced association of Mycobacterial RNA polymerase with ancillary factors leads to increased transcriptional activity.
Mycobacteriophage D29 infects species belonging to the genus Mycobacterium including the deadly pathogen Mycobacterium tuberculosis. D29 is a lytic phage, although, related to the lysogenic mycobacteriophage L5. This phage is unable to lysogenize in mycobacteria as it lacks the gene encoding the phage repressor. Infection by many mycobacteriophages cause various changes in the host that ultimately leads to inactivation of the latter. One of the host targets often modified in the process is RNA polymerase. During our investigations with phage D29 infected Mycobacterium smegmatis (Msm) we observed that the promoters from both phage, and to a lesser extent those of the host were found to be more active in cells that were exposed to D29, as compared to the unexposed. Further experiments indicate that the RNA polymerase purified from phage infected cells possessed higher affinity for promoters particularly those that were phage derived. Comparison of the purified RNA polymerase preparations from infected and uninfected cells showed that several ancillary transcription factors, Sigma factor F, Sigma factor H, CarD and RbpA are prominently associated with the RNA polymerase from infected cells. Based on our observations we conclude that the higher activity of RNA polymerase observed in D29 infected cells is due to its increased association with ancillary transcription factors.


Longitudinal, Interdisciplinary Home Visits Versus Usual Care for Homebound People With Advanced Parkinson Disease: Protocol for a Controlled Trial.
The current understanding of advanced Parkinson disease (PD) and its treatment is largely based on data from outpatient visits. The most advanced and disabled individuals with PD are disconnected from both care and research. A previous pilot study among older, multimorbid patients with advanced PD demonstrated the feasibility of interdisciplinary home visits to reach the target population, improve care quality, and potentially avoid institutionalization. The aim of this study protocol is to investigate whether interdisciplinary home visits can prevent a decline in quality of life of patients with PD and prevent worsening of caregiver strain. The protocol also explores whether program costs are offset by savings in health care utilization and institutionalization compared with usual care. In this single-center, controlled trial, 65 patient-caregiver dyads affected by advanced PD (Hoehn and Yahr stages 3-5 and homebound) are recruited to receive quarterly interdisciplinary home visits over 1 year. The 1-year intervention is delivered by a nurse and a research coordinator, who travel to the home, and it is supported by a movement disorder specialist and social worker (both present by video). Each dyad is compared with age-, sex-, and Hoehn and Yahr stage-matched control dyads drawn from US participants in the longitudinal Parkinson's Outcome Project registry. The primary outcome measure is the change in patient quality of life between baseline and 1 year. Secondary outcome measures include changes in Hoehn and Yahr stage, caregiver strain, self-reported fall frequency, emergency room visits, hospital admissions, and time to institutionalization or death. Intervention costs and changes in health care utilization will be analyzed in a budget impact analysis to explore the potential for model adaptation and dissemination. The protocol was funded in September 2017 and approved by the Rush Institutional Review Board in October 2017. Recruitment began in May 2018 and closed in November 2019 with 65 patient-caregiver dyads enrolled. All study visits have been completed, and analysis is underway. To our knowledge, this is the first controlled trial to investigate the effects of interdisciplinary home visits among homebound individuals with advanced PD and their caregivers. This study also establishes a unique cohort of patients from whom we can study the natural course of advanced PD, its treatments, and unmet needs. ClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459. PRR1-10.2196/31690.


Carcinoembryonic antigen in pleural effusions. Diagnostic value in malignant mesothelioma.
The usefulness of the determination of carcinoembryonic antigen (CEA) in pleural effusion was assessed as an aid to the diagnosis of malignant mesothelioma. The concentration of CEA was determined by radioimmunoassay (RIA) in pleural fluid of 213 adult patients, of which 140 had malignant pleural disease and 73 had nonmalignant pleural disease. Pleural fluid CEA (PF CEA) was lower than 12 ng/ml in all 15 mesotheliomas. The statistical probability of a mesothelioma associated with PF CEA greater than 15 ng/ml was found to be zero. The CEA assay in pleural effusion proved to be a valuable adjunct to other diagnostic procedures in differentiating the malignant mesothelioma from metastatic serosal spread.


Production of ethanol by immobilized Saccharomyces bayanus in an extractive fermentation system.
An extractive fermentation system using immobilized yeast cells was developed to study the ethanol production at high sugar concentrations. Organic acids were used as extracting solvents of ethanol and their toxicity was tested in free and k-carrageenan entrapped cell preparations. Immobilization seems to protect cells against solvent toxicity, when long-chain organic acids, e.g., oleic acid, were used, probably due to steric and diffusional limitations, the free cells not being viable at high oleic acid concentrations. The entrapped cells also present a higher metabolic activity than their free counterparts at high glucose concentrations. A solution of 300 g/L of glucose was totally fermented by the immobilized yeast cells, which when free cannot normally convert more than 200 g/L. In situ recovery of ethanol by oleic acid in a batch immobilized cell system led to higher ethanol productivities and to the fermentation of 400 g/L, when an oleic acid/medium ratio of 5 was used.


Appropriate referral timing to specialized palliative care service: survey of bereaved families of cancer patients who died in palliative care units.
Few studies have investigated appropriate referral timing of specialized palliative care (SPC) from the perspective of cancer patients' and families' experiences. We aimed to clarify appropriate SPC referral timing for patients with advanced cancer and their families. We used data from a nationwide bereaved family survey in Japan. We sent a questionnaire to 999 bereaved families of cancer patients who died in 164 palliative care units (PCUs) and analyzed the first SPC referral timing and how patients evaluated it. We defined SPC as outpatient or inpatient palliative care service comprising certified palliative care physicians, advanced-practice nurses, and multidisciplinary practitioners. Finally, 51.6% (n = 515) of all responses were analyzed. The SPC referral timing was evaluated as appropriate (26.1%), late or too late (20.2%), early or too early (1.2%), or none of these (52.5%). Of these, 32.3% reported that they were referred to an SPC when diagnosed with advanced or incurable cancer or during anti-cancer treatment, and 62.6% reported they were referred after anti-cancer treatment. Patient-perceived appropriateness of SPC referral timing was associated with their good death process. After excluding "none of these" responses, a significantly higher proportion of respondents who reported being referred to SPC at diagnosis and during anti-cancer treatment evaluated the response timing as appropriate, compared to those who reported being referred after anti-cancer treatment. Appropriate timing for SPC referrals relates to quality of death; findings suggest that appropriate timing is at the time of diagnosis or during anti-cancer treatment.


Biozeolite capping for reducing nitrogen load of the ancient canal in Yangzhou City.
Biozeolite capping for reducing nitrogen (N) load of an eutrophic canal in Yangzhou City was studied. Biofilm formation on biozeolite was cultivated by use of isolated nitrifiers and denitrifiers. Varying conditions including dissolved oxygen (DO) and origins of isolated bacteria were considered in our experiments. Long-term sediment incubation experiment results showed that the reduction efficiency of total nitrogen (TN) of overlying water by biozeolite capping were in the range of 47.61-57.64% under the condition of DO<1 mg L(-1). There was no obvious difference in TN reduction efficiency between natural biozeolite (indigenous bacteria) and artificial biozeolite (isolated bacteria). However, the reduction efficiency of TN and nitrate nitrogen (NO(3)(-)-N) were respectively in the ranges of 67.38-76.12% and 69.38-76.12% under the condition of DO 1.5-5 mg L(-1). The reduction efficiencies of TN and NO(3)(-)-N by artificial biozeolite were improved by 25.99-27.25% and 17.50-24.15% respectively than those by natural biozeolite. Moreover, no significant difference was found for reducing N load by the isolated bacteria with different origins. TN contents of surface sediments and ammonia nitrogen concentrations of sediment interstitial water in biozeolite capping systems declined obviously after experiments. Biozeolite capping is an effective technique for reducing N load of the Yangzhou canal.


Effect of on-pump versus off-pump coronary bypass surgery on cardiac function assessed by intraoperative transesophageal echocardiography.
To compare cardiac function assessed by intraoperative transesophageal echocardiography in patients undergoing cardiac revascularization with or without cardiopulmonary bypass. Forty-one patients scheduled for elective, isolated cardiac revascularization (21 on-pump and 20 off-pump) were prospectively analyzed. Patients were matched for demographic (age and gender), anthropometric (BMI), clinical (co-morbidities, EuroScore) and laboratory variables (blood counts, renal function, left ventricular function). Transesophageal echocardiography was performed after induction of anesthesia, protamine sulfate administration, and chest closure. Left ventricular wall motion score index, end-diastolic area, fractional area change, right ventricular area change and end-diastolic area were assessed. Troponin I and C-reactive protein concentrations were measured. Regarding echocardiographic parameters of left and right ventricular function no significant differences between on-pump and off-pump groups at any point-of-time measurements were found. Troponin I and C-reactive protein were higher in on-pump as compared to off-pump group (p=0.001 and p=0.002; p=0.003 and p=0.001, respectively). In elective patients scheduled for cardiac revascularization there were no difference in cardiac performance assessed by intraoperative echocardiography regardless of surgical method used.


Mitomycin-C induced hemolytic uremic syndrome: a case report and literature review.
Hemolytic uremic syndrome spontaneously arises in a few patients with advanced cancer, but it is more commonly related to the use of certain chemotherapeutic agents. Mitomycin-C is, etiologically, the most common causative agent inducing hemolytic uremic syndrome, in a dose dependent manner. We report this syndrome, attributable to mitomycin-C at a cumulative dose of 40 mg/m2, in a gastric cancer patient. A 42-year-old female with stage III gastric cancer underwent radical gastrectomy and was given mitomycin-C at 10 mg/m2 intravenously every four weeks as adjuvant therapy. Hemolytic uremic syndrome was diagnosed three months after the last dose of mitomycin-C administration. The most prominent symptoms included pallor, hypertension and anasarca, with laboratory evidence of microangiopathic hemolytic anemia, azotemia and hyperkalemia. Her disease was progressive, but fortunately stabilized after staphylococcus column A dialysis. Her disease remained in remission for 24 months from the time of diagnosis, and then relapsed in the form of peritoneal carcinomatosis with partial intestinal obstruction.


Optimum pure intrusion of a mandibular canine with the segmented arch in lingual orthodontics.
Approximately 50% patients with a deep bite possess anatomically extruded mandibular canines. The objective of this study was to specify an optimum toe (Θ) of the vertical segment of a cantilever from the distal aspect to achieve pure intrusion of a mandibular canine with the segmented arch in lingual orthodontics (LiO). The geometrical model of a mandibular canine was developed to compute the required values of Θ (positive values - toe-in, negative values - toe-out). Different positions of the cantilever attachment on the lingual bracket top (occlusal) surface were considered according to different heights (h) from the cusp of a canine i.e. 2, 3, 4 and 5 mm in each case of horizontal distance (x) from canine surface i.e. 2 and 3 mm. In x=2mm case, the required values of Θ at h=2,3,4 and 5mm were -5°, 0°, +6° and +11° respectively. While, in x=3mm case, the required values of Θ at h=2,3,4 and 5mm were 0°, +5°, +12° and +17° respectively. In finite element analysis (FEA), the computed values of Θ were verified by displaying the results of a mandibular canine movement in the form of vectors of nodal displacements along with undeformed and deformed models. In the cases of x=2mm and 3mm, no toe angles were required at heights h=3mm and 2mm respectively. Hence, these can be considered as better positions of the cantilever attachment than others.


Notch signaling in the immune system.
Notch signaling plays a preeminent role during development in not only regulating cell fate decisions, but it can also influence growth and survival of progenitor cells. In the immune system, Notch is required for the maintenance of hematopoietic stem cells and in directing T- versus B-lineage commitment. In this review, I will summarize some of the recent findings relating to the function of Notch in the immune system during lymphocyte development and in the generation and function of mature cells.


Duration of colonization with vancomycin-resistant Enterococcus.
To determine the duration of colonization with vancomycin-resistant Enterococcus (VRE) and the adequacy of 3 consecutive negative cultures to determine clearance. Retrospective cohort study. A university hospital. Patients identified by perirectal cultures as VRE carriers who had follow-up cultures. Follow-up perirectal cultures were collected in inpatient and outpatient settings, at least 1 week apart, when patients were not receiving antibiotics with activity against VRE. The likelihood of culture positivity was analyzed given prior culture results and time from the initial positive culture. A total of 116 patients colonized with VRE had 423 follow-up cultures, a mean of 204 days (range, 4 to 709 days) after their initial isolate. The first follow-up culture, collected a mean of 125 days after the initial positive isolate, was negative in 64%. After 1 negative follow-up culture, the next one was negative in 92% of the patients. After 2 negative cultures, 95% remained culture-negative. After 3 sequential negative cultures, 35 (95%) of 37 patients remained culture-negative. As the interval between the initial and the follow-up isolates increased, the probability that a subsequent culture would be positive decreased (P < .001, chi square for trend). Prolonged hospitalization, intensive care, and antibiotic use each decreased the likelihood of clearing VRE. These data support the Centers for Disease Control and Prevention criterion of 3 sequential negative cultures, at least 1 week apart, to remove patients from VRE isolation. Nevertheless, this may reflect a decrease in the quantity of VRE to an undetectable level and these patients should be observed for relapse, especially when re-treated with antibiotics.


Decision-making process of nursing home placement among Chinese family caregivers.
To understand the process and difficulties that Chinese family caregivers experience when making a nursing home placement decision for their loved ones with dementia. Using a grounded theory approach, data were collected through individual interviews with 30 Chinese family caregivers in Taiwan. A stage-based framework was generated that described how caregivers went through the decision-making process, what specific challenges they encountered within the process, and how they overcame difficulties to reach their decisions. By identifying the stages of the decision-making process and various challenges that caregivers experience, clinicians can enhance discussions with caregivers to decrease the decision-making burden. Clinicians might develop family-centered interventions for the decision-making process through the post-placement stage while taking into account cultural influences.


Fully integrated [18F]FDG PET/MR in large vessel vasculitis.
The aim of this study is to evaluate the usefulness of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) in large vessels vasculitis (LVV) patients. We performed an observational retrospective study based on our records. Images were acquired on a PET/MR scanner using [18F]FDG-PET whole body imaging. For each PET scan, a qualitative analysis and a semi-quantitative measure using the maximum of the standardized uptake value (SUV<inf>max</inf>) were performed. SUV<inf>max</inf> measurements normalized to the liver uptake were categorized using a grading scale. Vessel's wall thickness (WT) was measured at five fixed points (inferior margin of T5, T9, T12, L3, thickest area [max WT]). Twenty-three LVV patients were included, 56.5% giant cells arteritis, 34.8% Takayasu's arteritis and 8.7% isolated aortitis, all Caucasian, mostly females (82%). We considered 32 PET scans for the LVV group (from a minimum of one to a maximum of three scans per patient) mainly during follow-up (29/32 scans), and 23 PET scans from a control group of non-metastatic malignancies patients. We found higher SUV<inf>max</inf> compared to controls, in all sites, irrespective of clinical disease activity. Mean WT resulted higher in patients than in controls but was not correlated to SUV<inf>max</inf>. Mean WT positively correlated with age in both cohorts, inversely correlated to disease duration, while no correlation with SUV<inf>max</inf> was observed. The concordance between clinically active disease and PET hypermetabolism was poor (Cohen' κ=0.33). PET/MR is a safe imaging technique capable of detecting inflammation in aortic wall. Low radiological exposure of PET/MR should be considered especially in young women receiving follow-up studies.


Suppression of Ru (S = 1) spin dimerization in La2RuO5 by Ti substitution.
La2RuO5 shows a magneto-structural phase transition at 161 K with spin dimerization and concomitant formation of a non-magnetic singlet ground state. To gain a deeper insight into the origin of this transition systematic substitution of Ru by Ti has been carried out. Polycrystalline samples have been synthesized by thermal decomposition of citrate precursors leading to La2Ru(1-y)Ti(y)O5 (0 ≤ y ≤ 0.45). The crystal structure was investigated by x-ray powder diffraction at room temperature and at 100 K. The valences of Ti and Ru were obtained from x-ray absorption near edge structure spectroscopy at the Ti-K and the Ru-LIII absorption edges, respectively. The magnetic phase transition was investigated by magnetic susceptibility measurements as a function of Ti substitution, revealing a decreasing transition temperature on increasing the level of substitution. The step-like feature in the magnetic susceptibility reflecting the Ru-Ru spin dimerization transition becomes smeared out close to y = 0.3 and completely vanishes at y = 0.45, indicating complete suppression of spin-dimer formation. Additional specific-heat measurements show a continuous decrease of the magnetic entropy peak with increasing Ti substitution mirroring the reduced number of spin dimers due to the magnetic dilution. A magnetic anomaly of the dimerization transition can hardly be detected for y ≥ 0.3. Density functional theory calculations were carried out to study changes of the electronic band structure caused by the substitution. A possibly preferred distribution of Ti and Ru and the magnetic interactions as well as the change of the density of states close to the Fermi level are investigated. Based on these experimental results a detailed (y,T) phase diagram is proposed.


Prevalence and determinants of anxiety, depression and comorbid anxiety-depression symptoms among adolescents in Ebola-affected zones.
Ebola virus disease (EVD) has been shown to be associated with poor mental health in affected zones. However, no study has yet explored its impact on adolescents' mental health. This study aimed to assess the prevalence and risk factors associated with depression and anxiety symptoms among adolescents in EVD-affected areas in the Equateur Province of the Democratic Republic of the Congo during the COVID-19 pandemic. A provincial sample of adolescents aged 12-17 years (M = 14.84, s.d. = 1.49) living in the 18 urban and rural areas affected by the 2018 EVD outbreak completed a two-wave longitudinal survey. Surveys assessed symptoms of depression and anxiety, exposure to Ebola, social support and sociodemographic information. A total of 490 participants completed the baseline and follow-up surveys, 50% of whom were female. Elevated and worsened depressive symptoms were observed among participants from the baseline (56.94%) to the follow-up (91.43%; z = -11.37, P < 0.001), whereas anxiety symptoms decreased from the baseline (36.33%) to follow-up (24.90%; z = 4.06, P < 0.001). The final generalised estimating equation model showed that anxiety symptoms decreased over time (B = -3.92, P < 0.001), while depression symptoms increased (B = 4.79, P < 0.001). Stigmatisation related to Ebola positively predicted anxiety (B = 5.41, P < 0.001) and depression symptoms (B = 0.4452, P = 0.009). Social support negatively predicted anxiety (B = -1.13, P = 0.004) and depression (B = -0.98, P < 0.001) symptoms but only moderated the association between stigmatisation and depression symptoms (B = -0.67, P < 0.001). Most adolescents living in EVD-affected areas experience mental health issues. Stigmatisation related to EVD and living in urban areas are the most consistent predictors of mental health problems. Nevertheless, social support remains a protective factor for depression and anxiety symptoms and a necessary resource for building resilience.


Cytotoxicity and mutagenicity of sidestream cigarette smoke particulate matter of different particle sizes.
Sidestream cigarette smoke, the major component of environmental tobacco smoke, is a complex and reactive aerosol. The particulate matter (PM) in sidestream smoke is one of the carriers of chemical constituents. However, particle size-dependent toxicological effects of PM are poorly understood. In this study, we evaluated the relationship between the PM size and in vitro cytotoxicity and mutagenicity of sidestream cigarette smoke. A NanoMoudi-II(™) 125A was used to collect PM samples ranging from 10 nm to 10 μm. The in vitro toxicity of PM was evaluated using a neutral red cytotoxicity assay and Salmonella mutagenicity assay. The results showed that the cytotoxicity and mutagenicity of PM larger than 1 μm was significantly lower than PM sized 10 nm-1 μm. Furthermore, there was a noticeable trend that the smaller the size of the PM of sidestream cigarette smoke, the greater the toxicity. This study suggests that the toxicity of PM in sidestream cigarette smoke is size-dependent.


Slowly activating voltage-dependent K+ conductance is apical pathway for K+ secretion in vestibular dark cells.
Dark cell epithelium secretes K+ into the lumen of the vestibular labyrinth by a previously unidentified apical transport mechanism. Previous single-channel patch-clamp studies demonstrated nonselective cation channels and maxi-K+ channels in the apical membrane, but in too low a density to account for transepithelial K+ transport. In this report, we demonstrated with the cell-attached macro-patch-clamp technique an outward apical membrane current at 0-mV pipette voltage, which was stimulated by elevating bath K+ concentration from 3.6 to 25 mM and inhibited by 10 microM bumetanide, similar to their known effects on transepithelial short-circuit current and K+ secretion. Furthermore, the patch current was activated over several seconds by a sustained depolarization and deactivated over several hundred milliseconds by a hyperpolarization. Current-voltage relationships from tail currents were obtained with either NaCl or KCl in the pipette. Depolarization from -40 to +40 mV led to an increased conductance by a factor of 7.3 +/- 1.7 (n = 7) and 19.2 +/- 7.6 (n = 6) for NaCl and KCl, respectively, and to a reversal voltage near the presumed equilibrium potential for K+. The results demonstrate that dark cell K+ secretion occurs via K(+)-selective channels with characteristics similar to those associated with the IsK protein.


Use of an Objective Structured Clinical Examination (OSCE) to measure improvement in clinical competence during the surgical internship.
Traditional ward ratings and multiple-choice tests do not reliably assess clinical competence. This study determined the reliability of the Objective Structured Clinical Examination (OSCE) and its sensitivity in detecting the performance gains and deficits in surgical interns. A comprehensive 35-station OSCE was administered to 23 incoming interns and seven outgoing interns. The OSCE comprised 17 two-part clinical problems, relying primarily on actual or simulated patients. The reliability of the examination was assessed by coefficient alpha. Significant differences in performance between the two intern groups, between parts A and B, and among the 17 problems were determined by a three-way ANOVA: OSCE performance was also correlated with National Board of Medical Examiners Part II scores. The reliabilities of part A, part B, and parts A and B combined were 0.72, 0.70, and 0.82, respectively. Overall, the outgoing interns performed significantly better than the incoming interns: 58% +/- 1% mean OSCE score versus 47% +/- 1% (p = 0.0001). The 17 clinical problems differed significantly in difficulty; major performance deficits were seen in both groups of trainees. The correlation of OSCE scores with National Board of Medical Examiners Part II scores was not significant (r = 0.11, p = 0.633). We conclude that the OSCE is an innovative, reliable tool for evaluating resident competence. Although outgoing interns performed better than did incoming interns, the OSCE scores clearly indicated major performance deficits in all interns.