Is Performance of a Modified Eucapnic Voluntary Hyperpnea Test in High Ventilation Athletes Reproducible?
Exercise-induced bronchoconstriction (EIB) is common in "high ventilation" athletes, and the Eucapnic Voluntary Hyperpnea (EVH) airway provocation test is the standard EIB screen. Although the EVH test is widely used, the in-test performance in high ventilation athletes as well as the reproducibility of that performance has not been determined. Reproducibility of pre- and post-test spirometry and self-reported atopy/cough was also examined. High ventilation athletes (competitive swimmers; n=11, 5 males) completed an atopy/cough questionnaire and EVH testing (operator controlled FiCO₂) on 2 consecutive days. Swimmers achieved 85%±9% and 87%±9% of target FEV1 volume on days 1 and 2, respectively, (P=0.45; ICC 0.57 [0.00-0.86]) resulting in a total ventilation of 687 vs 684 L [P=0.89, ICC 0.89 (0.65-0.97]) equating to 83%±8% and 84%±9% of predicted total volume (ICC 0.54 [0.00-0.85]) between days 1 and 2. FiCO₂ required to maintain eucapnic conditions was 2.5%. Pre-test FEV1 was less on day 2 (P=0.04; ICC >0.90). Day 1 to 2 post-test FEV1 was not different, and 4 swimmers were EIB positive (>10% fall in pre-post FEV1) on day 1 (3 on day 2). EVH in-test performance is reproducible however required less FiCO₂ than standard protocol and the swimmers under-ventilated by 125 and 139 L/min for days 1 and 2, respectively. How this affects EIB diagnosis remains to be determined; however, our results indicate a post-test FEV1 fall of ≥20% may be recommended as the most consistent diagnostic criterion.


Squalomix: shark and ray genome analysis consortium and its data sharing platform.
The taxon Elasmobranchii (sharks and rays) contains one of the long-established evolutionary lineages of vertebrates with a tantalizing collection of species occupying critical aquatic habitats. To overcome the current limitation in molecular resources, we launched the Squalomix Consortium in 2020 to promote a genome-wide array of molecular approaches, specifically targeting shark and ray species. Among the various bottlenecks in working with elasmobranchs are their elusiveness and low fecundity as well as the large and highly repetitive genomes. Their peculiar body fluid composition has also hindered the establishment of methods to perform routine cell culturing required for their karyotyping. In the Squalomix consortium, these obstacles are expected to be solved through a combination of in-house cytological techniques including karyotyping of cultured cells, chromatin preparation for Hi-C data acquisition, and high fidelity long-read sequencing. The resources and products obtained in this consortium, including genome and transcriptome sequences, a genome browser powered by JBrowse2 to visualize sequence alignments, and comprehensive matrices of gene expression profiles for selected species are accessible through https://github.com/Squalomix/info.


Waiting times in a tertiary paediatric nephrology clinic.
To the authors' knowledge, paediatric nephrology waiting times have not been previously studied. Given the high incidence of new referrals each year, the evaluation of the current waiting times would be beneficial in the management and triaging of new appointments. Using descriptive statistics, data from all appropriate paediatric nephrology referrals to the Children's Hospital of Eastern Ontario (Ottawa, Ontario) from 2003 to 2005 (n=1446) were retrospectively analyzed. The median waiting time from receipt of initial request for referral to first appointment was 111 days (range zero to 364 days). No significant variation existed throughout the duration of the study, despite the variation in the number of paediatric nephrology staff. Infants were seen significantly sooner than older children. There were no assigned priority classification levels based on referral reason. Critical conditions, such as macrohematuria, were seen on an urgent basis; all other patients were seen at the next available appointment slot, which was usually four months away. A significant proportion of patients were referred for dysfunctional voiding and enuresis (25.9%). These diagnoses are not generally considered a part of core nephrology. The waiting times for a paediatric nephrology appointment are long. Focusing on core nephrology business and appropriate triaging of consult would be necessary to implement a priority classification level-based appointment assignment. Additional resources would allow for more patients to be seen in a more timely fashion.


Heavy Metal Resistance in Salmonella Typhimurium and Its Association With Disinfectant and Antibiotic Resistance.
Metals are widely used in animal feed for their growth-stimulating and antimicrobial effects, yet their use may potentially promote the proliferation of antibiotic resistance through co-selection. We studied the prevalence and associations of metal, antibiotic, and disinfectant resistances of 300 Salmonella Typhimurium isolates from pig meat, pig manure, chicken meat, poultry manure, and human stool from Sichuan, China. Seventy four percent of the 300 Salmonella Typhimurium isolates were considered resistant to Cu, almost 50% to Zn and Cr, over 25% to Mn and Cd, and almost 10% to Co. Most of the isolates carried at least one heavy metal resistance gene (HMRG). The Cr-Zn-Cd-resistance gene czcD was carried by 254 isolates and the Cu-resistance genes pcoR and pcoC by 196 and 179 isolates, respectively. Most of the isolates were resistant to at least one antibiotic and almost 80% were multidrug-resistant. The prevalence of resistance to six antibiotics was higher among the pig meat and manure isolates than among other isolates, and that of streptomycin and ampicillin were highest among the pig meat isolates and that of ciprofloxacin and ofloxacin among the pig manure isolates. From 55 to 79% of the isolates were considered resistant to disinfectants triclosan, trichloroisocyanuric acid, or benzalkonium chloride. The metal resistances and HMRGs were associated with resistance to antibiotics and disinfectants. Especially, Cu-resistance genes were associated with resistance to several antibiotics and disinfectants. The transfer of the Cr-Zn-Cd-resistance gene czcD, Cu-resistance gene pcoC, and Co-Ni-resistance gene cnrA into Escherichia coli and the increased Cu-resistance of the transconjugants implied that the resistance genes were located on conjugative plasmids. Thus, the excessive use of metals and disinfectants as feed additives and in animal care may have the potential to promote antibiotic resistance through co-selection and maintain and promote antibiotic resistance even in the absence of antibiotics.


High School Students' Experiences in School Toilets or Restrooms.
Previous research about school toilets is based on studies of children in elementary school. Thus, the aim of this study was to explore the experiences when using the school toilets reported by students aged 16-18 years. Qualitative interviews with 21 students were conducted and analyzed using content analysis. The data revealed that the toilets were considered insecure, dirty, and unpleasant. Additionally, students refrained from drinking during school hours and remained in constant movement or jumped up and down to withhold urine and stool. This was illustrated in the following categories: assessing the toilet environment, coping with the situation, and feeling exposed Hence, there is an urgent need to improve the school toilet environment in order to respect the rights of all students to void or defecate when necessary, a process which will require involvement of students, teachers, and other school staff as well as the School Health Service.


Partition function, metastability, and kinetics of the escape transition for an ideal chain.
An end-tethered polymer chain squeezed between two pistons undergoes an abrupt transition from a confined coil state to an inhomogeneous flower-like conformation partially escaped from the gap. We present a rigorous analytical theory for the equilibrium and kinetic aspects of this phenomenon for a Gaussian chain. Applying the analogy with the problem of the adsorption of an ideal chain constrained by one of its ends, we obtain a closed analytical expression for the exact partition function. Various equilibrium thermodynamic characteristics (the fraction of imprisoned segments, the average compression, and lateral forces) are calculated as a function of the piston separation. The force versus separation curve is studied in two complementary statistical ensembles, the constant force and the constant confinement width ones. The differences in these force curves are significant in the transition region for large systems, but disappear for small systems. The effects of metastability are analyzed by introducing the Landau free energy as a function of the chain stretching, which serves as the order parameter. The phase diagram showing the binodal and two spinodal lines is presented. We obtain the barrier heights between the stable and metastable states in the free energy landscape. The mean first passage time, i.e., the lifetime of the metastable coil and flower states, is estimated on the basis of the Fokker-Planck formalism. Equilibrium analytical theory for a Gaussian chain is complemented by numerical calculations for a lattice freely jointed chain model.


Transition of Homer isoforms during skeletal muscle regeneration.
Homer represents a new and diversified family of proteins that includes several isoforms, Homer 1, 2, and 3; some of these isoforms have been reported to be present in striated muscles. In this study, the presence of Homer isoforms 1a, 1b/c/d, 2b, and 3 was thoroughly investigated in rat skeletal muscles under resting conditions. Transition in Homer isoforms compositon was studied under experimental conditions of short-term and long-term adaptation, e.g., fatigue and regeneration, respectively. First, we show that Homer 1a was constitutively expressed and was transiently upregulated during regeneration. In C(2)C(12) cell cultures, Homer 1a was also upregulated during formation of myotubes. No change of Homer 1a was observed in fatigue. Second, Homer 1b/c/d and Homer 2b were positively and linearly related to muscle mass change during regeneration, and third, Homer 3 was not detectable under resting conditions but was transiently expressed during regeneration although with a temporal pattern distinct from that of Homer 1a. Thus a switch in Homer isoforms is associated to muscle differentiation and regeneration. Homers may play a role not only in signal transduction of skeletal muscle, in particular regulation of Ca(2+) release from sarcoplasmic reticulum, but also in adaptation.


Clinical features and prognosis of breast cancer with gastric metastasis.
Breast cancer rarely metastasizes to the gastrointestinal tract, including the stomach. Due to the rarity of this metastasis, it is occasionally confused with a primary stomach malignancy. However, discriminating characteristic features with clinical implications may exist. The aim of the current study was to analyze the clinical features and prognosis of breast cancer with gastric metastasis. Between January 1994 and October 2016, 13 patients at Samsung Medical Center (Seoul, Korea) were clinically or pathologically determined to have breast cancer with gastric metastasis. The present study retrospectively collected clinicopathological data from the electronic medical records of these 13 female patients. At breast cancer diagnosis, the median patient age was 45 years. A total of 7 patients (53.8%) presented with invasive lobular carcinoma (ILC) and 6 (46.2%) with invasive ductal carcinoma. Of the 13 patients, 11 were stage I-III at initial breast cancer diagnosis and underwent surgery. Positivity of breast cancer tissue samples for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) was 92.3, 76.9 and 0%, respectively. Positivity of gastric metastasis lesions, based on immunohistochemistry results, was 81.8, 50 and 0% for ER, PR and HER2, respectively. The stomach was the location of the first metastatic lesion in 6 out of the 11 patients (54.5%) with de novo stage I-III cancer. The median time interval from initial breast cancer diagnosis to stomach metastasis was 77.5 months. The 3-year survival rate was 79.1%, and the estimated mean survival time was 35.1 months. Breast cancer with gastric metastasis is rare, and due to this fact, a thorough pathological review and greater clinical suspicion are required in these cases.


Spinal Cord Injury without Radiographic Abnormality (SCIWORA) - Clinical and Radiological Aspects.
The acronym SCIWORA (Spinal Cord Injury Without Radiographic Abnormality) was first developed and introduced by Pang and Wilberger who used it to define "clinical symptoms of traumatic myelopathy with no radiographic or computed tomographic features of spinal fracture or instability". SCIWORA is a clinical-radiological condition that mostly affects children. SCIWORA lesions are found mainly in the cervical spine but can also be seen, although much less frequently, in the thoracic or lumbar spine. Based on reports from different authors, SCIWORA is responsible for 6 to 19% and 9% to 14% of spinal injuries in children and adults, respectively. Underlying degenerative changes, including spondylosis or spinal canal stenosis, are typically present in adult patients. The level of spinal cord injury corresponds to the location of these changes. With recent advances in neuroimaging techniques, especially in magnetic resonance imaging, and with increasing availability of MRI as a diagnostic tool, the overall detection rate of SCIWORA has significantly improved.


Workshops that Work: Physician Involvement in Service Training.
Physician involvement in service training initiatives can have a significant impact on the patient experience. This paper highlights some of the key components of what makes physician involvement in training engagements successful and includes anecdotes and data to support the findings. Our service training program emerged from a desire to help clinic sections improve the patient experience. Our workshops contained customized materials that addressed service priority areas, as identified by patient satisfaction survey results, for individual clinic sections and included opportunities to practice the concepts introduced in each session. However, we were missing one key ingredient in the recipe for a successful training program - physician involvement. This paper focuses on a best practice in which two physicians took an active role in creating, customizing and delivering service training for their clinic section and made a tremendous impact on their overall patient satisfaction scores and section morale.


[Lipids and skin inflammation: role of phospholipases A2].
Phospholipases A2 (PLA2) are enzymes that catalyse the hydrolysis of glycerophospholipids at the sn-2 position, generating free fatty acids and lysophospholipids. At present, PLA2 family consists of 12 groups. PLA2 are involved in many pathophysiological processes such as barrier function, eicosanoid production, and inflammation. They are implicated in inflammatory diseases of the skin: psoriasis, eczema, atopy. The presence of PLA2 activity has been demonstrated several years ago, however the precise localization of all these PLA2 in the epidermis and its appendages has to be determined. Further studies have shown that these enzymes are expressed in various layers of epidermis. This differential localization suggests different roles for each PLA2 in skin physiology and during inflammation.


Evaluation and management of corticotropin allergy.
Subsequent use of an adrenocorticotropic hormone (ACTH) preparation may be considered in some instances in a patient who has demonstrated a suspected or proven allergic reaction to corticotropin on prior administration. We describe a patient with multiple sclerosis with a history of anaphylaxis to porcine ACTH in whom another course of treatment with ACTH was being considered. The patient had immediate cutaneous reactivity to porcine ACTH but not to the synthetic ACTH peptide, cosyntropin. With a test-dose schedule, we were able to uneventfully administer cosyntropin to the patient. The presence of serum IgE antibody directed against porcine ACTH and absence of IgE antibody against cosyntropin were demonstrated by ELISA technique, corroborating the skin test results. These studies are consistent with previous evidence that immediate hypersensitivity reactions to corticotropin are IgE mediated and support the value of skin testing in the clinical evaluation and management of known or suspected corticotropin hypersensitivity.


Detection of staphylococcal superantigenic toxins by a CD69-specific cytofluorimetric assay measuring T-cell activation.
The presence of staphylococcal superantigenic toxins in the supernatants of liquid cultures was detected by an easy and rapid method assessing the activation of T lymphocytes by cytofluorimetric measurement of CD69 expression. Staphylococcus aureus cells were grown in Eagle's minimum essential medium supplemented with 5% heat-inactivated fetal calf serum. Supernatant fluids from all S. aureus strains producing superantigen-related toxins, including enterotoxins A to E, toxic shock syndrome toxin, and exfoliative toxins A and B, induced CD69 expression in a significantly higher number of T cells than a cutoff of 2%. This CD69 assay might be used for initial detection of superantigens from S. aureus strains isolated in the context of staphylococcal toxemia or related chronic human diseases such as atopic dermatitis or Kawasaki syndrome.


The quick-implantable-defibrillator trial.
Earlier ICD therapy included an electrophysiological study (EPS), an extensive defibrillation threshold test (DFT), and a pre-discharge test. Now that ICD-therapy is widely accepted, an EPS is no longer performed in most patients, extensive DFT-tests have been reduced to a minimum of two effective shocks and discharge tests have been discarded in most centres. However, it has never been demonstrated prospectively that this simplification is safe. The Quick-Implantable-Defibrillator (Quick-ICD) Trial was a prospective multi-centre trial, which randomized patients, who had survived a cardiac arrest (SCD) or an unstable ventricular tachycardia (VT), to two different clinical strategies: (a) The extensive strategy included an EPS, an extensive DFT-test, and a pre-discharge test; (b) In the simplified approach (quick strategy) the ICD was implanted without an EPS and a pre-discharge test. Two effective shocks during implantation at 21 J were sufficient. The primary endpoint of this trial was a cluster of adverse events related to the diagnostic approach and to ICD-therapy. One hundred and ninety patients were included, 97 randomized to the extensive-, 93 to the quick strategy. Mean follow-up was 12 +/- 7 months. Twenty-seven patients reached the endpoint in the quick group and 32 in the extensive group. During follow-up, the event-free survival was equal in the two study arms (test for equivalence, P = 0.0044). The initial hospital stay was significantly shorter in the quick population (8.4 +/- 4.7 vs. 11.2 +/- 7.4 days, P = 0.004) It is safe and cost-effective to implant an ICD without an EPS, an extensive DFT-, and a pre-discharge test in carefully selected patients after survived SCD or unstable VTs.


Impact of Solar Radiation on Gene Expression in Bacteria.
Microorganisms often regulate their gene expression at the level of transcription and/or translation in response to solar radiation. In this review, we present the use of both transcriptomics and proteomics to advance knowledge in the field of bacterial response to damaging radiation. Those studies pertain to diverse application areas such as fundamental microbiology, water treatment, microbial ecology and astrobiology. Even though it has been demonstrated that mRNA abundance is not always consistent with the protein regulation, we present here an exhaustive review on how bacteria regulate their gene expression at both transcription and translation levels to enable biomarkers identification and comparison of gene regulation from one bacterial species to another.


Recent studies on insect hormone metabolic pathways mediated by cytochrome P450 enzymes.
In insects molting and metamorphosis are primarily under the control of two insect hormones, ecdysone and juvenile hormone (JH). Physiological and biochemical studies of insect hormone metabolic pathways suggested the involvement of P450 (CYP) enzymes in the pathways, but molecular details of the enzymes were unclear. In recent years, the genome information and studies using molecular biology and genetics have allowed us to understand enzymes in the ecdysteroid and JH metabolic pathways. Genome sequencing has been accomplished in several insect species, and has shown the presence of 36-180 CYP enzymes. To date, six and one CYP enzymes have been revealed in the biosynthesis and inactivation pathways of 20-hydroxyecdysone (20E), respectively. In the 20E biosynthetic pathway, correlation among the enzymes, substrates and metabolites is elucidated in the late steps, but the enzyme(s) and intermediates in the early steps have not been fully understood and are referred to as the 'Black Box'. The gene expression of some CYP enzymes in the 20E biosynthesis is modulated by neuropeptides and JH. Furthermore, involvement of a CYP enzyme is found in both JH biosynthesis and inactivation pathways. Thus, recent studies have shown the importance of CYP enzymes in insect hormone metabolisms.


Desiccation time during drought is highly predictable across species of Eucalyptus from contrasting climates.
Catastrophic failure of the water transport pathway in trees is a principal mechanism of mortality during extreme drought. To be able to predict the probability of mortality at an individual and landscape scale we need knowledge of the time for plants to reach critical levels of hydraulic failure. We grew plants of eight species of Eucalyptus originating from contrasting climates before allowing a subset to dehydrate. We tested whether a trait-based model of time to plant desiccation tcrit , from stomatal closure gs90 to a critical level of hydraulic dysfunction Ψcrit is consistent with observed dry-down times. Plant desiccation time varied among species, ranging from 96.2 to 332 h at a vapour-pressure deficit of 1 kPa, and was highly predictable using the tcrit model in conjunction with a leaf shedding function. Plant desiccation time was longest in species with high cavitation resistance, strong vulnerability segmentation, wide stomatal-hydraulic safety, and a high ratio of total plant water content to leaf area. Knowledge of tcrit in combination with water-use traits that influence stomatal closure could significantly increase our ability to predict the timing of drought-induced mortality at tree and forest scales.


Protein degradation in human fibroblasts (WI-38). Effects of aging, viral transformation, and amino acid analogs.
Protein degradation occurs more rapidly in senescent WI-38 cultures than in phase II cultures or in SV-40 transformed WI-38 cells (VA-13). The first differences are found in early phase III, when short lived but not long lived proteins are degraded more rapidly. At the end of phase III long lived proteins are also degraded more rapidly as shown by both intermittent perfusion and approach to equilibrium methods. By both methods the rates of protein degradation for the virally transformed derivative are the same as those for phase II WI-38, implying that transformation has not altered these characteristics of protein degradation. WI-38 cells incorporate canavanine, an analog of arginine, into protein. This analog, as well as p-fluorophenylalanine and azetidine carboxylic acid, accelerates the degradation of proteins labeled with [3H]leucine in their presence but does not alter the degradation rates of proteins prelabeled with [14C]leucine in the absence of the analogs. These results imply that the analogs increase the intracellular degradation rates of proteins because they render them more susceptible to the degradative system. Late phase III WI-38 cells may not selectively catabolize proteins containing canavanine as rapidly as do phase II and VA-13 cells. These results imply that the phase III protein degradative system becomes partially defective, thereby losing its ability to rapidly catabolize altered protein which leads to increased levels of abnormal proteins and decreased cell function.


Elastosis in breast carcinoma: I. Immunohistochemical characterization of elastic fibres.
Elastosis associated with invasive ductal and lobular carcinomas of the breast was examined by tinctorial and immunohistochemical staining methods, enzyme digestion, and electron microscopy. The elastotic material exhibited the tinctorial staining properties of elastic fibres, and the ultrastructural appearances were those of elastic fibres although there was a higher proportion of microfibrils than in normal mature elastic fibres. The elastosis was immunostained by antisera to human fetal elastin, lysozyme and amyloid P component, as in other sites where elastic fibres are found. These findings indicate that immunohistochemically intact elastic fibres are present in the elastosis of breast cancer. They also demonstrate that lysozyme and amyloid P component are co-distributed with elastic fibres in elastosis of breast carcinoma, as distinct components with different susceptibilities to enzyme digestion. The cellular origin of elastosis in breast carcinoma remains uncertain.


Interaction between gamma delta T cells and B cells regulating IgG production.
Despite profound knowledge about the molecular structure of the gamma delta T-cell receptor (TCR), the physiological function of gamma delta T cells remains enigmatic. Participation of these cells in complex immune reactions, however, is suggested by the appearance of gamma delta T cells in sites of infectious and autoimmune-induced inflammations. Only a few in vitro models of gamma delta T-cell stimulation have been established: besides a reactivity in the presence of microbial ligands, human gamma delta T cells proliferate upon in vitro challenge with cells from an allogeneic B-lymphoblastic cell line (B-LCL). We present data here demonstrating that this reactivity is not confined to allogenic B-LCL. Autologous B-LCL are also very strong stimulators for gamma delta T cells; more important, autologous B cells can stimulate gamma delta T cells after a period of mitogen-activation but not in a resting state. This activation seems to address a subgroup of gamma delta T cells, as the percentage of V delta 1+ cells is increased after stimulation. Activated gamma delta T cells, on the other hand, are able to exert an influence on B cells by inhibiting the secretion of IgG in coculture experiments. These data define a simple regulatory circle of B cells and gamma delta T cells in vitro and propose a model for gamma delta T-cell function which could explain many in vivo observations of gamma delta T-cell activation.


Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control.
Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1. We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated. The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures. Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.


Differential effects of sex steroids on T and B cells: modulation of cell cycle phase distribution, apoptosis and bcl-2 protein levels.
Sex steroids have dramatic and differential effects on classic endocrine organ proliferation and apoptosis. In this investigation we sought to delineate similar effects of sex steroids on proliferation, cell cycle phase and apoptosis in lymphocyte cell lines as models for T and B cells. Estrogen and testosterone inhibited T cell line proliferation, induced accumulation of cells in S/G(2)M phases of the cell cycle, and increased apoptosis in a concentration- and time-dependent manner. There was a more modest effect of estrogen and testosterone on cell cycling and apoptosis in B lymphocyte cell lines, suggesting that estrogen and testosterone are inhibitory to T but not B cell lines. In comparison, progesterone induced cytostasis and modestly increased apoptosis in both T and B cell lines. Estrogen and testosterone were not antagonistic or synergistic to each other in their effects on cell cycle phase distribution, and only minimally synergistic for apoptosis. In contrast, progesterone antagonized cell cycle and apoptotic effects of estrogen in T cells. Estrogen-induced cell cycle and apoptotic effects in T cell lines were associated with suppression of bcl-2 protein levels, which were unaffected in Raji B cells. Progesterone also antagonized the estrogen-induced changes in T cell bcl-2 protein levels. These results suggest that there may be significant and differential sex steroid effects on T and B lymphocytes that may be important to sexual dichotomies in immune and autoimmune responses.


The control region of the F plasmid transfer operon: DNA sequence of the traJ and traY genes and characterisation of the traY leads to Z promoter.
The complete nucleotide sequence of the F plasmid transfer genes traJ and traY, together with the promoter-proximal region of the traA gene has been determined. The traJ reading frame has been confirmed by sequencing the traJ90 amber mutant allele. The predicted amino acid sequence of the TraJ protein shows that this outer-membrane protein lacks a signal sequence. The pattern of codon usage within the traJ gene is different from that of genes for abundant outer-membrane proteins and is closer to that of genes that are expressed at relatively low levels. We have located the traY leads to Z operon promoter by in vitro run-off transcription experiments and have developed in vivo assays for the activity of the promoter by fusing it to galactokinase and kanamycin-resistance genes.


The burden of and factors associated with misclassification of intrapartum stillbirth: Evidence from a large scale multicentric observational study.
Global estimates suggest 2.6 million stillbirths and 2.5 million neonatal deaths occur annually worldwide. The majority of these deaths occur in low resource settings where analysis of health metrics and outcomes measurements may be challenging. We examined the misclassification of documented intrapartum stillbirth and factors associated with misclassification. A prospective observational study was performed in 12 public hospitals in Nepal. Data were extracted from the medical records of all births that occurred during the 6-month period of the study. For the study purpose, we classified birth outcome based on the presence of fetal heart sound (FHS) at admission and use of neonatal resuscitation. The health worker-documented intrapartum stillbirths were considered potentially misclassified when there were FHS present at admission and no resuscitation initiated after birth. The association between potentially misclassified intrapartum stillbirth and complications during labor, birthweight and gestational age was assessed using Pearson's chi-square test, bivariate and multivariate logistic regression. A total of 39 562 mother-infant dyads were enrolled in the study, all of whom had FHS at admission. Among the 391 intrapartum stillbirths recorded during the study, 180 (46.0%) of them had FHS at admission with no resuscitation initiated after birth and were considered potentially misclassified intrapartum stillbirths. Among these potentially misclassified intrapartum stillbirths, 170 (43.5%) had FHS present 15 minutes before birth and 10 had no FHS 15 minutes before birth Among the potentially misclassified intrapartum stillbirths, 23.3% had complications during labor, 93.3% had birthweight less than 2500 g and 90.0% were born preterm. The risk of intrapartum misclassification was nearly four times higher among low birthweight babies (adjusted odds ratio [aOR] 3.5, 95% confidence interval [CI] 1.8 to 7.0, P < 0.001) and five times higher among preterm babies (aOR 5.3, 95% CI 3.0 to 9.3, P < 0.001). We estimate that 46% of intrapartum stillbirths were potentially misclassified intrapartum stillbirths. Improving quality of both FHS monitoring and neonatal resuscitation as well as measurement of the care will reduce the risk of potentially misclassified intrapartum stillbirth and consequently intrapartum stillbirth.


The Monoclonal Antibody Program of the Cuban Institute of Oncology and Radiobiology.
A Monoclonal Antibody Program was launched at the National Institute of Oncology and Radiobiology (INOR) in Cuba in 1985. Eleven MAbs have been obtained which recognize different leukocyte antigens. Four MAbs a series of reagents raised against different types of cytokeratins, carcino-embryonic antigen and the membrane receptor for Epidermal Growth Factor. These MAbs are especially useful in immunohistochemistry for the study of human tumours, leukemias and lymphomas. Three ultramicro-ELISA systems have being deviced using MAbs. First trials are being made with radioactive MAbs for immunoscintigraphy. The use of anti T-cell MAbs for the prevention of rejection crisis in patients receiving organ transplantation and for the treatment of patient with cutaneous T-cell lymphoma is still mostly a matter for research.


Metabolism of cigarette smoke condensates by human and rat homogenates to form mutagens detectable by Salmonella typhimurium TA1538.
Nineteen fractions of whole condensate of smoke from the University of Kentucky Reference Cigarette IRI were tested for mutagenicity in vitro using a bacterial indicator system. As little as 25 mug of the active fractions were mutagenic toward histidine-requiring Salmonella typhimurium TA1538, if the condensates were incubated in the presence of rat or human liver homogenates of lung were relatively inactive. Homogenates from livers of rats that had been treated with 3-methylcholanthrene converted condensates to mutagens more efficiently than did liver homogenates from man or from normal or phenobarbital-treated rats. Use of homogenates from animals treated with 3-methylcholanthrene gave much more reproducible results in smoke fraction assays because larger numbers of revertants were obtained, and dose-response curves were linear over the range 25 to 250 mug condensate. The linear dose-response curves permitted quantitative comparison of the various fractions. The mutagenicity per mg of basic fractions of whole smoke condensate is very high and that of neutral polycyclic hydrocarbons is very low. Because of the exquisite preferential sensitivity of the TA1538 test system to polycyclic amines and insensitively to alkyl polycyclics, there is a poor quantitative correlation between mutagenicity and carcinogenicity, as measured by skin painting or in vitro cell transformation. There is substantial evidence that many carcinogens are mutagens but that most of these compounds require metabolism before they are biologically active. If further development improves the sensitivity of the bacterial testing system to mutagenic derivatives of alkyl polycyclic and heteropolycyclic hydrocarbons, it may provide a convenient, rapid, quantitative, and inexpensive bioassay for the detection of potentially carcinogenic substances in tobacco smoke condensates.


The true impact of fatigue in primary biliary cirrhosis: a population study.
Patient surveys suggest that fatigue is a common problem in primary biliary cirrhosis (PBC). The actual extent of the problems caused by fatigue in PBC has yet to be determined as previous studies addressing this question have tended to use selected patient subgroups and subjective or non-quantitative fatigue assessment tools. Here, we have attempted to more accurately assess the extent of fatigue in PBC, and the specificity of the symptom for this disease, by the application of an objective measure of fatigue impact (the fatigue impact score [FIS]) to a geographically based patient cohort, age- and sex-matched normal controls, and chronic liver disease controls. Postal completion of the FIS and linked symptom assessment tools. Median FIS was significantly higher in patients (n = 136) than community controls (40 [0-138] vs. 28 [0-156]; P < 0.0001) and chronic liver disease controls (n = 38) (20.5 [0-145]; P < 0.05). Fatigue scores in the 11 patients who had undergone liver transplantation (median 3.5 years previously) were the same as those in non-transplanted patients with advanced disease. Fatigue is a significant and specific problem in PBC. It is not, however, universal and affects fewer patients than has previously been thought to be the case based on data from selected patient cohorts. This definition of the "normal range" for fatigue in PBC will assist in future studies of etiology and therapy.


PTEN-induced kinase 1-induced dynamin-related protein 1 Ser637 phosphorylation reduces mitochondrial fission and protects against intestinal ischemia reperfusion injury.
Intestinal ischemia reperfusion (I/R) occurs in various diseases, such as trauma and intestinal transplantation. Excessive reactive oxygen species (ROS) accumulation and subsequent apoptotic cell death in intestinal epithelia are important causes of I/R injury. PTEN-induced putative kinase 1 (PINK1) and phosphorylation of dynamin-related protein 1 (DRP1) are critical regulators of ROS and apoptosis. However, the correlation of PINK1 and DRP1 and their function in intestinal I/R injury have not been investigated. Thus, examining the PINK1/DRP1 pathway may help to identify a protective strategy and improve the patient prognosis. To clarify the mechanism of the PINK1/DRP1 pathway in intestinal I/R injury. Male C57BL/6 mice were used to generate an intestinal I/R model via superior mesenteric artery occlusion followed by reperfusion. Chiu's score was used to evaluate intestinal mucosa damage. The mitochondrial fission inhibitor mdivi-1 was administered by intraperitoneal injection. Caco-2 cells were incubated in vitro in hypoxia/reoxygenation conditions. Small interfering RNAs and overexpression plasmids were transfected to regulate PINK1 expression. The protein expression levels of PINK1, DRP1, p-DRP1 and cleaved caspase 3 were measured by Western blotting. Cell viability was evaluated using a Cell Counting Kit-8 assay and cell apoptosis was analyzed by TUNEL staining. Mitochondrial fission and ROS were tested by MitoTracker and MitoSOX respectively. Intestinal I/R and Caco-2 cell hypoxia/reoxygenation decreased the expression of PINK1 and p-DRP1 Ser637. Pretreatment with mdivi-1 inhibited mitochondrial fission, ROS generation, and apoptosis and ameliorated cell injury in intestinal I/R. Upon PINK1 knockdown or overexpression in vitro, we found that p-DRP1 Ser637 expression and DRP1 recruitment to the mitochondria were associated with PINK1. Furthermore, we verified the physical combination of PINK1 and p-DRP1 Ser637. PINK1 is correlated with mitochondrial fission and apoptosis by regulating DRP1 phosphorylation in intestinal I/R. These results suggest that the PINK1/DRP1 pathway is involved in intestinal I/R injury, and provide a new approach for prevention and treatment.


The anatomy of free paper sessions.
The interaction between speakers, audience, and chairmen was studied by 13 investigators during a medical meeting at which 356 free papers were given before a total audience of 2483 in 48 sessions. A protocol was used to score 21 questions relating to the presentation, 15 to the chairman of the session, and nine to the audience. Many speakers made technical faults in presentation and their use of slides. Most chairmen failed to comply with simple rules of procedure and with the expectations of speakers and audience. The interest of the audience was affected by the performance of speakers and chairman. Speakers should pay more attention to the technique of presentation, and organising committees of medical meetings should provide instructions to both speakers and chairmen.


Dolichol pathway in lymphocytes from rat spleen. Influence of the glucosylation on the cleavage of dolichyl diphosphate oligosaccharides into phosphooligosaccharides.
Incubation of rat-spleen lymphocytes with UDP-glucose together with GDP-mannose and UDP-N-acetylglucosamine leads to the formation of glucosylated lipid intermediates characterized as dolichyl phosphate glucose and dolichyl diphosphate oligosaccharides. This latter can be either transferred onto endogenous protein acceptors or cleaved into phosphooligosaccharides. The striking fact is that phosphooligosaccharide populations contain far less glucosylated products than the dolichyl diphosphate oligosaccharide ones from which they are derived. Two hypotheses have been investigated: either a rapid action of glucosidases on the liberated phosphooligosaccharides or a preferential splitting of the non-glucosylated population of dolichyl diphosphate oligosaccharides. Addition of p-nitrophenyl-alpha-D-glucoside inhibits glucosidase activities and allows the production of a major population of dolichyl diphosphate oligosaccharides containing three glucose residues. Using these conditions, it is shown that the amount of phosphooligosaccharides generated from the splitting of dolichyl diphosphate oligosaccharides is greatly decreased and that the major part of these remaining phosphooligosaccharides do not contain glucose. These results show that the presence of glucosyl units prevent dolichyl diphosphate oligosaccharides from further degradation into phosphooligosaccharides.


[Comparison between magnetic resonance angiography and duplex ultrasound for preoperative planning of lower limb revascularisation].
The purpose of this study was to compare magnetic resonance angiography with duplex ultrasound for defining anatomical features relevant to performing lower limb revascularisation. From June 2003 to June 2004, 30 consecutive patients with chronic lower limb ischaemia underwent magnetic resonance angiography and duplex ultrasound investigations before undergoing lower limb revascularisation procedures. The mean age was 72 years (range: 45-93). Indications for the procedure included resting pain (6 cases), ischaemic ulcer (8 cases), and gangrene (16 cases). We compared magnetic resonance angiography and duplex ultrasonography findings and the differences in the aorto-iliac, femoro-popliteal and infrapoliteal segments were noted. Magnetic resonance angiography and duplex ultrasound findings agreed in 13/15 cases (86%) in the aorto-iliac segment, in 14/17 (82%) in the femoro-popliteal segment, and in 8/11 (74%) in the infrapopliteal segment. In all, duplex ultrasound agreed with intraoperative findings in 97% of cases while magnetic resonance angiography agreed in 81%. These data show that magnetic resonance angiography is less accurate than duplex ultrasound in the infrapopliteal segment. Adeguate training is necessary before duplex ultrasound can be used as the only preoperative imaging procedure.


Antipsychotic Use Pattern in People with Psychotic Disorder Living in Board and Care Facilities.
The aim of this survey is to determine the pattern of antipsychotic drug use in patients with psychotic disorders, living in board and care facilities and to investigate the related factors. We evaluated the antipsychotic drug use pattern in outpatients with psychotic disorders according to DSM-IV, living in board and care facilities. Patients using polypharmacy at least one month were compared with patients using monotherapy in terms of clinical and demographic characteristics. Antipsychotic polypharmacy (with two: 34%, with more than two: 28%) was identified in 62% of the patients. The most frequently prescribed combination was olanzapine+quetiapine (13%), the rate of first and second generation combination was 50%, the rate of second generation antipsychotic combination was 44%, and the rate of first generation anytipsychotic combination was 4% in the two antipsychotic drug combination group. The rate of clozapine use was 3%. Use of polypharmacy was associated with the diagnosis of schizophrenia and schizoaffective disorder, young age, suicidal behavior, multiple hospitalizations, clinical severity, and the need of anticholinergic drug. The ratio of using more than two antipsychotic drug combination is high (28%) in psychotic patients living in board and care, and rate of clozapine use is low, which shows that clinical practice is inconsistent with the treatment guidelines recommendations. It appears that further education to rationale antipsychotic drug use in psychiatric practices is required.


Time-resolved and photoluminescence spectroscopy of θ-Al₂O₃ nanowires for promising fast optical sensor applications.
Herein, we have demonstrated the high yield facile growth of Al2O3 nanowires of uniform morphology with different polymorph phases (e.g. γ, δ and θ) via a hydrothermal method with varying calcination temperatures. The synthesized θ-Al2O3 nanowires were well characterized by XRD, FTIR, SEM/EDAX, AFM and HRTEM techniques. Microstructural analysis confirmed that the dimensions of the individual θ-Al2O3 nanowires are approximately in the ranges 5-20 nm in width and 40-150 nm in length, and the aspect ratio is up to 20. AFM results evidenced the uniform distribution of the nanowires with controlled morphology. Furthermore, UV-vis spectroscopic data reveal that the estimated optical band gap of the θ-Al2O3 nanowires was ~5.16 eV. The photoluminescence spectrum exhibits blue emission upon excitation at a wavelength of 252 nm. Time-resolved spectroscopy demonstrates that these nanowires illustrate a decay time of ~2.23 nanoseconds. The obtained photoluminescence results with a decay time of nanoseconds suggest that the θ-Al2O3 phase could be an exceptional choice for next generation fast optical sensors.


Molecular pathogenesis of pulmonary arterial hypertension.
Recent investigations have suggested that it might be possible to reverse the pathology of pulmonary arterial hypertension (PAH), a disorder that can be rapidly progressive and fatal despite current treatments including i.v. prostacyclin. This review will address the cellular and molecular processes implicated in clinical, genetic, and experimental studies as underlying the pulmonary vascular abnormalities associated with PAH. Emerging treatments are aimed at inducing apoptosis of abnormal vascular cells that obstruct blood flow and at promoting regeneration of "lost" distal vasculature.


Anti-hepatitis C virus dinorditerpenes from the roots of Flueggea virosa.
Along with four known terpenoids (1-4), eight new dinorditerpenes (5-12) were isolated and identified from the roots of Flueggea virosa. The absolute configurations of 4-6 were determined by the Mosher's method, and that of 5 was confirmed by single-crystal X-ray diffraction analysis. Using the hepatitis C virus cell culture infection system, compounds 1, 3, 11, and 12 exhibited significant anti-HCV activity with EC50 values of 5.6, 5.0, 7.5, and 6.6 μM, respectively. Compounds 11 and 12 were nontoxic toward the tested Huh7.5 cell lines.


Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells.
Although epidemiological evidence indicates that a daily supplement of vitamin E may reduce the risk of prostate cancer, the detailed mechanism underlying this effect remains unclear. Here we demonstrate that alpha-tocopheryl succinate (VES) can suppress the expression of prostate-specific antigen (PSA), a marker for the progression of prostate cancer. VES can also suppress androgen receptor (AR) expression by means of transcriptional and posttranscriptional modulation, but not ligand binding, nuclear translocation, or AR dimerization. This VES-mediated inhibition of AR is selective because VES does not repress the expression of other nuclear receptors. Cell growth studies further show that VES inhibits the growth of prostate cancer LNCaP cells. In contrast, hydroxyflutamide (HF), an antiandrogen currently used to treat prostate cancer patients, only slightly inhibits LNCaP cell growth. Interestingly, simultaneous addition of HF and VES results in a more significant inhibition of LNCaP cell growth. Moreover, selenomethionine (SM), a prostate cancer treatment adjuvant, shows an inhibitory effect on LNCaP cell growth, yet has no effect on the AR/PSA pathway. Together, our data indicate that VES may suppress androgen/AR-mediated cell growth and PSA expression by inhibiting AR expression at both the transcription and translation levels. This previously undescribed mechanism may explain how VES inhibits the growth of prostate cancer cells and help us to establish new therapeutic concepts for the prevention and treatment of prostate cancer.


[Seasonal influenza in children].
Influenza in children is now recognized as a yearly burden, with severe symptoms or complications responsible for hospitalizations in young children and at risk groups. Clinical diagnosis, similar to adults in children over 4-5 years of age, is much less feasible in young infants due to overlap of symptoms with other respiratory or digestive viral epidemics. Rapid diagnostic tests could thus be useful. Prevention relies on vaccination but recommendations are restricted (at risk groups, professional and familial surroundings), vaccine schedule is a constraint, and the vaccine protective efficacy is increasing with the children age. Thus, specific anti-virals could be useful as curative treatment or even prophylaxis.


Oral Bisphosphonate Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta-Analysis of Six Randomized Placebo-Controlled Trials.
To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI). Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo-group in OI patients. Data synthesis regarding to bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta-analysis done when possible. From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta-analysis. Pooled meta-analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32-0.89, P = 0.02). Pooled meta-analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T-score) (mean difference 28.43, 95% confidence interval 7.09-49.77, P = 0.009). The similar effect was shown in the term of mean change (Z-score) in spine BMD. Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well-designed, adequately-powered, placebo-controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.


Localized surface plasmon resonance-mediated fluorescence signals in plasmonic nanoparticle-quantum dot hybrids for ultrasensitive Zika virus RNA detection via hairpin hybridization assays.
The current epidemic caused by the Zika virus (ZIKV) and the devastating effects of this virus on fetal development, which result in an increased incidence of congenital microcephaly symptoms, have prompted the World Health Organization (WHO) to declare the ZIKV a public health issue of global concern. Efficient probes that offer high detection sensitivity and specificity are urgently required to aid in the point-of-care treatment of the virus. In this study, we show that localized surface plasmon resonance (LSPR) signals from plasmonic nanoparticles (NPs) can be used to mediate the fluorescence signal from semiconductor quantum dot (Qdot) nanocrystals in a molecular beacon (MB) biosensor probe for ZIKV RNA detection. Four different plasmonic NPs functionalized with 3-mercaptopropionic acid (MPA), namely MPA-AgNPs, MPA-AuNPs, core/shell (CS) Au/AgNPs, and alloyed AuAgNPs, were synthesized and conjugated to L-glutathione-capped CdSeS alloyed Qdots to form the respective LSPR-mediated fluorescence nanohybrid. The concept of the plasmonic NP-Qdot-MB biosensor involves using LSPR from the plasmonic NPs to mediate a fluorescence signal to the Qdots, triggered by the hybridization of the target ZIKV RNA with the DNA loop sequence of the MB. The extent of the fluorescence enhancement based on ZIKV RNA detection was proportional to the LSPR-mediated fluorescence signal. The limits of detection (LODs) of the nanohybrids were as follows: alloyed AuAgNP-Qdot646-MB (1.7 copies/mL)) > CS Au/AgNP-Qdot646-MB (LOD =2.4 copies/mL) > AuNP-Qdot646-MB (LOD =2.9 copies/mL) > AgNP-Qdot646-MB (LOD =7.6 copies/mL). The LSPR-mediated fluorescence signal was stronger for the bimetallic plasmonic NP-Qdots than the single metallic plasmonic NP-Qdots. The plasmonic NP-Qdot-MB biosensor probes exhibited excellent selectivity toward ZIKV RNA and could serve as potential diagnostic probes for the point-of care detection of the virus.


Surgical resection of a giant mass pushing the boundaries of the chest wall: An Askin's tumor.
Intrathoracic masses may arise from the chest wall, mediastinum, pleura, and pulmonary parenchyma. Primary malign tumors of the chest wall and pleura usually present with chest pain; however, the tumor may sometimes remain asymptomatic, until it grows large enough to cause compression-related symptoms. Herein, we present a 35-year-old female case with a giant intrathoracic mass. The patient was diagnosed with an Askin"s tumor and underwent extended surgical resection.


Coronary artery spasm.
Variant angina with ST elevation indicates transmural myocardial ischaemia and is due to spasm of a large epicardial coronary artery. Spasm occurs in arteries with varying degrees of fixed obstruction, giving rise to different clinical profiles of variant angina. However, coronary angiography is required to differentiate between those with minor coronary disease, and those with significant (greater than 70%) obstruction. In patients with minor coronary disease or normal arteries, beta-blockers are contraindicated, and treatment with calcium antagonist vasodilators should be commenced after documentation of spontaneous or ergonovine induced spasm. Patients with significant fixed coronary obstructions require bypass grafting if technically feasible. The role of coronary spasm is not confined to variant angina, as it causes angina at rest with ST depression, and may also cause myocardial infarction and sudden death.


Multifocal systemic sporotrichosis with lobar pulmonary involvement.
Multifocal systemic sporotrichosis (disseminated sporotrichosis) with lobar pulmonary involvement is uncommon. We describe successful treatment with amphotericin B in such a patient and review data from 1 other similar case previously reported and 7 with nonlobar pulmonary involvement.


Aortic arch geometry predicts outcome in patients with Loeys-Dietz syndrome independent of the causative gene.
This study aimed to investigate the potential association between imaging features and cardiovascular outcomes in patients with Loeys–Dietz syndrome (LDS). We performed a retrospective cohort study of 36 patients with LDS and described cardiovascular events and imaging data. We observed different clinical courses in patients with LDS, irrespective of the causative gene. Angular or elongated aortic arch geometry correlated with aortic dissection (R = .39, p = .02), occurrence of the first cardiovascular event before 45 years of age (R = .36, p = .03), and the number of operations (R = 0.47, p = .004), but not with age (R = −.05, p = .79) or the causative gene (R = −0.04, p = .79). Relative absences of cardiovascular events at ages 20, 40, and 60 were 100, 75, and 56%, respectively, in patients with "romanesque" aortic arches, and 74, 39, and 21%, respectively, in patients with "gothic" and "elongated" aortic arches (p = .03). Angular or elongated aortic arch geometry is associated with early‐onset of disease and a worse cardiovascular outcome in LDS patients. Large multicenter studies are warranted to elucidate the impact of aortic arch morphology evaluation in clinical practice.


The intersection of video capsule endoscopy and artificial intelligence: addressing unique challenges using machine learning.
Technical burdens and time-intensive review processes limit the practical utility of video capsule endoscopy (VCE). Artificial intelligence (AI) is poised to address these limitations, but the intersection of AI and VCE reveals challenges that must first be overcome. We identified five challenges to address. Challenge #1: VCE data are stochastic and contains significant artifact. Challenge #2: VCE interpretation is cost-intensive. Challenge #3: VCE data are inherently imbalanced. Challenge #4: Existing VCE AIMLT are computationally cumbersome. Challenge #5: Clinicians are hesitant to accept AIMLT that cannot explain their process. An anatomic landmark detection model was used to test the application of convolutional neural networks (CNNs) to the task of classifying VCE data. We also created a tool that assists in expert annotation of VCE data. We then created more elaborate models using different approaches including a multi-frame approach, a CNN based on graph representation, and a few-shot approach based on meta-learning. When used on full-length VCE footage, CNNs accurately identified anatomic landmarks (99.1%), with gradient weighted-class activation mapping showing the parts of each frame that the CNN used to make its decision. The graph CNN with weakly supervised learning (accuracy 89.9%, sensitivity of 91.1%), the few-shot model (accuracy 90.8%, precision 91.4%, sensitivity 90.9%), and the multi-frame model (accuracy 97.5%, precision 91.5%, sensitivity 94.8%) performed well. Each of these five challenges is addressed, in part, by one of our AI-based models. Our goal of producing high performance using lightweight models that aim to improve clinician confidence was achieved.


Nitrous oxide inactivates methionine synthetase activity in rat testis.
Methionine synthetase (MS) activity in the brain and liver is decreased following nitrous oxide (N2O) exposure. Since MS is important for DNA synthesis, this interaction would be expected to have the most serious consequences on actively replicating tissue. The authors therefore measured MS activity in rat testes following 1 h exposure to either 10% or 50% N2O. Animals exposed to 10% N2O had a 29% reduction in MS activity, and exposure to 50% N2O caused a 63% reduction in enzyme activity. Testicular MS activity returned to normal by 24-48 h in the 10% exposure group and by 72 h in the 50% exposure group. This biochemical effect on testicular enzyme activity could be the basis for the reported deleterious effects of N2O on spermatogenesis.


Compensating for oblique ear-probe insertions in ear-canal reflectance measurements.
Measurements of the ear-canal reflectance using an ear probe require estimating the characteristic impedance of the ear canal in situ. However, an oblique insertion of the ear probe into a uniform waveguide prevents accurately estimating its characteristic impedance using existing time-domain methods. This is caused by the non-uniformity immediately in front of the ear probe when inserted at an oblique angle, resembling a short horn loading, and introduces errors into the ear-canal reflectance. This paper gives an overview of the influence of oblique ear-probe insertions and shows how they can be detected and quantified by estimating the characteristic impedance using multiple truncation frequencies, i.e., limiting the utilized frequency range. Additionally, a method is proposed to compensate for the effects on reflectance of an oblique ear-probe insertion into a uniform waveguide. The incident impedance of the horn loading is estimated, i.e., were the uniform waveguide anechoic, which replaces the characteristic impedance when calculating reflectance. The method can compensate for an oblique ear-probe insertion into a uniform occluded-ear simulator and decrease the dependency of reflectance on insertion depth in an ear canal. However, more research is required to further assess the method in ear canals.


Rational design of benzotrithiophene-diketopyrrolopyrrole-containing donor-acceptor polymers for improved charge carrier transport.
Two new donor-acceptor polymers containing benzo[2,1-b:3,4-b':5,6-c'']trithiophene (BTT) as donor and diketopyrrolopyrrole (DPP) as acceptor are synthesized and applied in OFETs. By tuning the alkyl substituents of the polymers, a striking difference in packing order, thin-film arrangement, and charge carrier transport is observed. The polymer without substituents at the BTT exhibits a hole mobility two orders of magnitude higher than that with alkyl chains therein.


Insecticide exposure of mothers and newborns in a rural agricultural area.
Pregnant women in a rural agricultural area were found to have levels of residues of chlorinated hydrocarbon insecticides in their serum which were comparable to those found in occupationally exposed men. Cord blood of offspring also had significant residue levels. Residues were higher in blacks and in mothers living in rural areas where exposure was more intense. In newborns no signs or symptoms compatible with acute chlorinated hydrocarbon poisoning were found. Despite the lack of DDT use during most of the study period, over 90% of the mothers. 84% of the black newborns, and 45% of the white newborns demonstrated evidence of recent DDT exposure.


The Moral Status of the Human Embryo.
Moral status ascribes equal obligations and rights to individuals on the basis of membership in a protected group. Substance change is an event that results in the origin or cessation of individuals who may be members of groups with equal moral status. In this paper, two substance changes that affect the moral status of human embryos are identified. The first substance change begins with fertilization and ends with the formation of the blastocyst, a biological individual with moral status comparable to that ascribed to human organs. The second substance change begins at implantation and ends late in embryological development with the formation of the human body, an organism with moral status as a human being. The bioethical implications of each substance change are explored. The Two Substance Change theory is contrasted with continuity theories, which recognize no substance change in embryological development and with fertilization-only substance change theories.


A Poisson distribution-based general model of cancer rates and a cancer risk-dependent theory of aging.
This article presents a formula for modeling the lifetime incidence of cancer in humans. The formula utilizes a Poisson distribution-based "np" model to predict cancer incidence, with "n" representing the effective number of cell turnover and "p" representing the probability of single-cell transformation. The model accurately predicts the observed incidence of cancer in humans when a reduction in cell turnover due to aging is taken into account. The model also suggests that cancer development is ultimately inevitable. The article proposes a theory of aging based on this concept, called the "np" theory. According to this theory, an organism maintains its order by balancing cellular entropy through continuous proliferation. However, cellular "information entropy" in the form of accumulated DNA mutations increases irreversibly over time, restricting the total number of cells an organism can generate throughout its lifetime. When cell division slows down and fails to compensate for the increased entropy in the system, aging occurs. Essentially, aging is the phenomenon of running out of predetermined cell resources. Different species have evolved separate strategies to utilize their limited cell resources throughout their life cycle.


Structural and dynamical aspects of the phase transition in the new thiourea thiazolium bromide inclusion compound.
A new thiourea thiazolium bromide inclusion compound is presented here. Detailed investigations of its phase transition were performed by differential scanning calorimetry, x-ray diffraction, and dielectric and nuclear magnetic resonance spectroscopy methods, completed by calculation of the steric hindrances for molecular reorientations and simulations of the second moment of the nuclear magnetic resonance line by the Monte Carlo method. A second order ferrielectric structural phase transition has been detected at 190.5 K as thiazolium cations collectively reorient inside channels. The dynamics is discussed in terms of inequivalent energy barriers associated with cation rotation as the symmetry breaking occurs. Oscillations of thiourea molecules and NH(2) groups have been also observed.


Photoacoustic Brain Imaging: from Microscopic to Macroscopic Scales.
Human brain mapping has become one of the most exciting contemporary research areas, with major breakthroughs expected in the following decades. Modern brain imaging techniques have allowed neuroscientists to gather a wealth of anatomic and functional information about the brain. Among these techniques, by virtue of its rich optical absorption contrast, high spatial and temporal resolutions, and deep penetration, photoacoustic tomography (PAT) has attracted more and more attention, and is playing an increasingly important role in brain studies. In particular, PAT complements other brain imaging modalities by providing high-resolution functional and metabolic imaging. More importantly, PAT's unique scalability enables scrutinizing the brain at both microscopic and macroscopic scales, using the same imaging contrast. In this Review, we present the state-of-the-art PAT techniques for brain imaging, summarize representative neuroscience applications, outline the technical challenges in translating PAT to human brain imaging, and envision potential technological deliverables.


Bisimidazolium ionic liquids as the high-performance antiwear additives in poly(ethylene glycol) for steel-steel contacts.
Bisimidazolium ionic liquids [C(10)(m(2)im)(2)(NTf(2))(2), C(10)(m(2)im)(2)(PF(6))(2), and C(10)(m(2)im)(2)(BF(4))(2)] with different anions were evaluated as the antiwear additives in poly(ethylene glycol) at room temperature. Results showed that they could effectively reduce the friction and wear of sliding pairs compared with the cases without these additives. Especially, C(10)(m(2)im)(2)(NTf(2))(2) showed better antiwear properties with an optimum concentration of 3 wt %, by which a significant improvement of its antiwear property by dozens of times with respect to the base oil was achieved. The excellent tribological properties are attributed to the formation of high-quality physical adsorption films and tribochemical product during friction and the good miscibility of ionic liquids with base oil.


Suffering in psoriasis patients: its relation with illness severity and subjective well-being.
The aim of the present study was to explore the relationship among subjective illness impact, subjective well-being, and psoriasis severity as assessed by dermatologists. Furthermore, subjective well-being of psoriasis patients was compared to available norm data. Fifty-nine psoriasis patients participated in this study. The following measures were administered: (a) the Pictorial Representation of Illness and Self Measure - Revised (PRISM-R), yielding Self-Illness Separation (SIS), and Illness Perception Measure (IPM); (b) subjective health status; (c) life satisfaction, and (d) psychological well-being. In addition, the Psoriasis Area and Severity Index (PASI) was determined by dermatologists. Psoriasis patients scored significantly below the norm data on subjective health status and psychological well-being. No differences were found concerning life satisfaction. PASI failed to correlate significantly with any of the disease impact and subjective health measures. Neither did SIS correlate significantly with any of the subjective health measures, whereas IPM was negatively associated with subjective health status, life satisfaction, and psychologic well-being. In a regression analysis with PASI as the dependent measures, none of the subjective health measures showed up as a relevant predictor. In comparison with the norm data, psoriasis patients report less subjective health status and well-being whereas their life satisfaction is not affected. There is no clear association among illness impact, subjective well-being, and illness severity as assessed by dermatologists.


Ovarian response prediction in controlled ovarian stimulation for IVF using anti-Müllerian hormone in Chinese women: A retrospective cohort study.
The predictive value of anti-Müllerian hormone (AMH) in Chinese women undergoing in vitro fertilization (IVF) treatment is data deficient. To determine the attributes of AMH in IVF, oocyte yield, cycle cancellation, and pregnancy outcomes were analyzed. All patients initiating their first IVF cycle with gonadotropin-releasing hormone agonist treatment in our center from October 2013 through December 2014 were included, except patients diagnosed with polycystic ovarian syndrome. Serum samples collected prior to IVF treatment were used to determine serum AMH levels. A total of 4017 continuous cycles were analyzed. The AMH level was positively correlated with the number of oocytes retrieved. Overall, AMH was significantly correlated with risk of cycle cancellation, poor ovarian response (POR, 3, or fewer oocytes retrieved) and high response (>15 oocytes), with an area under the curve (AUC) of 0.83, 0.89, and 0.82 respectively. An AMH cutoff of 0.6 ng/mL had a sensitivity of 54.0% and a specificity of 90.0% for the prediction of cycle cancellation, and cutoff of 0.8 ng/mL with a sensitivity of 55.0% and a specificity of 94.0% for the prediction of POR. Compared with AMH >2.0 ng/mL, patients with AMH < 0.6 ng/mL had a 53.6-fold increased risk of cancellation (P < 0.001), and AMH <0.80 ng/mL were 17.5 times more likely to experience POR (P < 0.001). However, AMH was less predictive of pregnancy and live birth, with AUCs of 0.55 and 0.53, respectively. Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate per retrieval according to the AMH level (≤0.40, 0.41-0.60, 0.61-0.80, 0.81-1.00, 1.01-1.50, 1.51-2.00, and >2.00 ng/mL) showed no significant differences. Even with AMH≤0.4 ng/mL, 50.0% of all the patients achieved pregnancy and 34.8% of patients achieved live birth after transfer. Our results suggested that AMH is a fairly robust metric for the prediction of cycle cancellation and oocyte yield for Chinese women, but it is a relatively poor test for prediction of pregnancy outcomes. Patients with low levels of AMH still can achieve reasonable treatment outcomes and low AMH levels in isolation do not represent an appropriate marker for withholding fertility treatment.


Searching the cytochrome p450 enzymes for the metabolism of meranzin hydrate: a prospective antidepressant originating from Chaihu-Shugan-San.
Meranzin hydrate (MH), an absorbed bioactive compound from the Traditional Chinese Medicine (TCM) Chaihu-Shugan-San (CSS), was first isolated in our laboratory and was found to possess anti-depression activity. However, the role of cytochrome P450s (CYPs) in the metabolism of MH was unclear. In this study, we screened the CYPs for the metabolism of MH in vitro by human liver microsomes (HLMs) or human recombinant CYPs. MH inhibited the enzyme activities of CYP1A2 and CYP2C19 in a concentration-dependent manner in the HLMs. The Km and Vmax values of MH were 10.3±1.3 µM and 99.1±3.3 nmol/mg protein/min, respectively, for the HLMs; 8.0±1.6 µM and 112.4±5.7 nmol/nmol P450/min, respectively, for CYP1A2; and 25.9±6.6 µM and 134.3±12.4 nmol/nmol P450/min, respectively, for CYP2C19. Other human CYP isoforms including CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 showed minimal or no effect on MH metabolism. The results suggested that MH was simultaneously a substrate and an inhibitor of CYP1A2 and CYP2C9, and MH had the potential to perpetrate drug-drug interactions with other CYP1A2 and CYP2C19 substrates.


Behavioral and neuronal study of inhibition of return in barn owls.
Inhibition of return (IOR) is the reduction of detection speed and/or detection accuracy of a target in a recently attended location. This phenomenon, which has been discovered and studied thoroughly in humans, is believed to reflect a brain mechanism for controlling the allocation of spatial attention in a manner that enhances efficient search. Findings showing that IOR is robust, apparent at a very early age and seemingly dependent on midbrain activity suggest that IOR is a universal attentional mechanism in vertebrates. However, studies in non-mammalian species are scarce. To explore this hypothesis comparatively, we tested for IOR in barn owls (Tyto alba) using the classical Posner cueing paradigm. Two barn owls were trained to initiate a trial by fixating on the center of a computer screen and then turning their gaze to the location of a target. A short, non-informative cue appeared before the target, either at a location predicting the target (valid) or a location not predicting the target (invalid). In one barn owl, the response times (RT) to the valid targets compared to the invalid targets shifted from facilitation (lower RTs) to inhibition (higher RTs) when increasing the time lag between the cue and the target. The second owl mostly failed to maintain fixation and responded to the cue before the target onset. However, when including in the analysis only the trials in which the owl maintained fixation, an inhibition in the valid trials could be detected. To search for the neural correlates of IOR, we recorded multiunit responses in the optic tectum (OT) of four head-fixed owls passively viewing a cueing paradigm as in the behavioral experiments. At short cue to target lags (<100 ms), neural responses to the target in the receptive field (RF) were usually enhanced if the cue appeared earlier inside the RF (valid) and were suppressed if the cue appeared earlier outside the RF (invalid). This was reversed at longer lags: neural responses were suppressed in the valid conditions and were unaffected in the invalid conditions. The findings support the notion that IOR is a basic mechanism in the evolution of vertebrate behavior and suggest that the effect appears as a result of the interaction between lateral and forward inhibition in the tectal circuitry.


Human Breast Phantoms: Test Beds for the Development of Microwave Diagnostic and Therapeutic Technologies.
Over the past two decades, there has been enormous growth in research activity for microwave diagnostic and therapeutic technologies that target the breast. The clinical need for new tools in the breast cancer armamentarium, combined with the promising lowcost, nonionizing nature of microwave technologies, has fueled these investigations. High-fidelity breast phantoms are essential components of computational and experimental test beds for investigating and accurately assessing the performance of new devices, algorithms, and systems related to microwave breast cancer detection and/or treatment.


ESBL and carbapenemase-producing Enterobacteriaceae in infectious pleural effusions: current epidemiology at Hôpital du Mali.
Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali. Pleural fluid samples from 526 patients with pleuritis were analyzed. Enterobacterial species were isolated and identified, and the prevalence of resistance genes (blaOXA-48, blaNDM-1, blaKPC, blaTEM, blaSHV) and virulence factors was determined. Among the patients, 110 were diagnosed with enterobacterial pleuritis. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the main pathogens identified. Resistance to β-lactams and cephalosporins was high, while carbapenems showed good activity. ESBL production was detected in 33.6% of isolates, with blaTEM being the most common gene. Carbapenemase gene (blaNDM-1) was found in three isolates. The study highlights the high prevalence of multidrug-resistant bacteria and the need for appropriate antibiotic selection based on local resistance patterns. Understanding the molecular characteristics of resistance is crucial for optimizing patient care and developing effective therapeutic strategies. Further research is needed to monitor and control AMR in PIs in Mali.


A Novel Matrix-Array-Based MR-Conditional Ultrasound System for Local Hyperthermia of Small Animals.
The goal of this work was to develop a novel modular focused ultrasound hyperthermia (FUS-HT) system for preclinical applications with the following characteristics: MR-compatible, compact probe for integration into a PET/MR small animal scanner, 3D-beam steering capabilities, high resolution focusing for generation of spatially confined FUS-HT effects. For 3D-beam steering capabilities, a matrix array approach with 11 × 11 elements was chosen. For reaching the required level of integration, the array was mounted with a conductive backing directly on the interconnection PCB. The array is driven by a modified version of our 128 channel ultrasound research platform DiPhAS. The system was characterized using sound field measurements and validated using tissue-mimicking phantoms. Preliminary MR-compatibility tests were performed using a 7T Bruker MRI scanner. Four 11 × 11 arrays between 0.5 and 2 MHz were developed and characterized with respect to sound field properties and HT generation. Focus sizes between 1 and 4 mm were reached depending on depth and frequency. We showed heating by 4 °C within 60 s in phantoms. The integration concept allows a probe thickness of less than 12 mm. We demonstrated FUS-HT capabilities of our modular system based on matrix arrays and a 128 channel electronics system within a 3D-steering range of up to ±30°. The suitability for integration into a small animal MR could be demonstrated in basic MR-compatibility tests. The developed system presents a new generation of FUS-HT for preclinical and translational work providing safe, reversible, localized, and controlled HT.


Synthesis and biochemical evaluation of a series of aminoflavones as potential inhibitors of protein-tyrosine kinases p56lck, EGFr, and p60v-src.
A series of nitroflavones, 8a-p, and their corresponding aminoflavone hydrochloride salts, 10a-p, was synthesized. The preparation of nitroflavones 8b-i,o,p began with commercially available o-hydroxyacetophenones 2b-f which were converted to o-hydroxynitroacetophenones 3a-h via a variety of nitration methods, followed by condensation with nitrobenzoyl chlorides and cyclization under acidic condition. The nitroflavones 8aj-n were prepared by nitration of the corresponding flavones 7a-e. These new compounds were evaluated for their abilities to inhibit the in vitro protein-tyrosine kinase activities of p56lck, EGFr, and p60v-src, and all of the active compounds were amino-substituted flavones. None of the nitroflavones inhibited the enzymes. The most active substance in this series against p56lck was compound 10j, which had an IC50 of 18 microM. When tested versus EGFr, compounds 10a,m displayed IC50's of 8.7 and 7.8 microM, respectively. Against p60v-src, 10a,m showed IC50 values of 28.8 and 38.4 microM, respectively.


Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination with Cisplatin Versus Temozolomide for the Treatment of Non-small Cell Lung Cancer with Brain Metastases.
The aim of this study was to explore the efficacy and safety of high-dose pemetrexed with cisplatin versus combination with temozolomide in patients with brain metastases (BM) of lung adenocarcinoma. After standard whole-brain radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung cancer (NSCLC) were given high-dose pemetrexed (900 mg/m2) on day 1 of each cycle (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated group. The temozolomide-treated group was treated as follows: 75 mg/m2 temozolomide orally with concurrent WBRT followed by 150 mg/m2 temozolomide on days 1-5 with high-dose pemetrexed (900 mg/m2) on day 1 of each cycle (3 weeks). Six cycles later, high-dose pemetrexed (900 mg/m2) monotherapy or the best available supportive therapy was administered to both groups. An evaluation was carried out every 2-3 cycles. The primary end-points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end-points included safety and tolerability. Thirty-two patients in the pemetrexed plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8% and 75%, in the PC and PT groups, respectively, and there was no statistically significant difference between the two groups (p=0.711). The median PFS rates of the PC and PT groups were 13.6 months and 16.9 months, respectively, and the median OS rates of the PC and PT groups were 18.9 months and 19.3 months, respectively. There were no differences in PFS and OS between the two groups. There were no grade 4 or higher side-effects in either group, but grade 3 side-effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were observed in the PC group, whereas the PT-group-only showed the following grade 3 side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data showed that the PT group achieved the same efficacy in PFS and OS as the PC group but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may be a better regimen for treating NSCLC with BM due to its better safety.


Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers.
The stability of taxol (NSC-125973) in various diluents and containers was determined, and the extent of leaching of di(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) bags caused by the taxol formulation was measured. A taxol formulation consisting of a 6-mg/mL solution of taxol in 50% polyoxyethylated castor oil and 50% dehydrated ethanol was added to 50- and 100-mL glass bottles, PVC infusion bags, and polyolefin containers containing 5% dextrose injection or 0.9% sodium chloride injection to give initial nominal taxol concentrations of 0.3, 0.6, 0.9, and 1.2 mg/mL. The containers were maintained at 20-23 degrees C for 12-24 hours. Samples were assayed by stability-indicating high-performance liquid chromatography, and clarity was determined visually. An experiment was run to ascertain whether DEHP would leach from a PVC administration set during a simulated infusion. There was no substantial loss of taxol over 24 hours. Filtration through a membrane resulted in no loss of taxol. All the solutions initially appeared hazy. Solutions stored in PVC bags became more hazy with time than solutions stored in glass or polyolefin containers. The haze seen in PVC bags was traced to leaching of DEHP. Agitation had no effect on the extent of leaching. Leaching was also seen during simulated delivery through PVC administration sets. No DEHP was detected when solutions were stored in glass or polyolefin containers and infused through polyethylene-lined sets. At the dilutions studied, taxol was visually and chemically stable for up to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


Case report: Novel transtemporal transverse sinus decompression surgery to alleviate transverse sinus stenosis in a pulsatile tinnitus patient with restricted bilateral venous outflow.
Transverse sinus (TS) stenosis is common in individuals with venous pulsatile tinnitus (PT). While PT can be addressed by endoluminal or extraluminal methods, the former has shown promise in alleviating symptoms associated with increased intracranial pressure. This study explores the potential of extraluminal methods to alleviate TS stenosis and eliminate PT caused by sigmoid sinus diverticulum. A 31-year-old male patient presenting with left-sided PT, attributed to a large, pedunculated sigmoid sinus diverticulum along with severe ipsilateral TS stenosis and contralateral TS hypoplasia, underwent ipsilateral extraluminal TS decompression surgery following sigmoid sinus wall reconstruction under local anesthesia. Postoperative CT and MR angiography revealed a significant increase in the TS lumen from 0.269 to 0.42 cm2 (56.02%) 2 years after surgery. Cervical Doppler ultrasound demonstrated a 36.07% increase in ipsilateral outflow volume to 16.6 g/s and a 77.63% increase in contralateral outflow volume to 1.35 g/s. In conclusion, this pioneering study showcases the potential of transtemporal TS decompression surgery in creating space for adaptive expansion of the TS lumen. However, the procedure should be reserved for individuals with severely compromised venous return.


Lamellar Ionenes with Highly Dissociative, Anionic Channels Provide Lower Barriers for Cation Transport.
Solid polymer electrolytes have the potential to enable safer and more energy-dense batteries; however, a deeper understanding of their ion conduction mechanisms, and how they can be optimized by molecular design, is needed to realize this goal. Here, we investigate the impact of anion dissociation energy on ion conduction in solid polymer electrolytes via a novel class of ionenes prepared using acyclic diene metathesis (ADMET) polymerization of highly dissociative, liquid crystalline fluorinated aryl sulfonimide-tagged ("FAST") anion monomers. These ionenes with various cations (Li+, Na+, K+, and Cs+) form well-ordered lamellae that are thermally stable up to 180 °C and feature domain spacings that correlate with cation size, providing channels lined with dissociative FAST anions. Electrochemical impedance spectroscopy (EIS) and differential scanning calorimetry (DSC) experiments, along with nudged elastic band (NEB) calculations, suggest that cation motion in these materials operates via an ion-hopping mechanism. The activation energy for Li+ conduction is 59 kJ/mol, which is among the lowest for systems that are proposed to operate via an ion conduction mechanism that is decoupled from polymer segmental motion. Moreover, the addition of a cation-coordinating solvent to these materials led to a >1000-fold increase in ionic conductivity without detectable disruption of the lamellar structure, suggesting selective solvation of the lamellar ion channels. This work demonstrates that molecular design can facilitate controlled formation of dissociative anionic channels that translate to significant enhancements in ion conduction in solid polymer electrolytes.


Transnational Child Sexual Abuse: Outcomes from a Roundtable Discussion.
The phenomenon of men who travel across international borders to engage in child sexual abuse presents significant public health, legal, diplomatic, cultural, and research challenges. Briefed in the current scope of this issue by relevant stakeholders across legislation, research, and social policy, a roundtable discussion held in London aimed to synthesise plenary discussions from multidisciplinary attendees across law enforcement, academia, non-profit, and industry sectors with direct relevance to the UK. Specifically, the roundtable discussions aimed to gather the central themes relating to attendee discussions on the key challenges, affected countries, response strategies, and knowledge gaps. Four key themes were identified from the data, relating to the definition of Transnational Child Sexual Abuse (TCSA), criminal justice, geographical considerations, and issues surrounding tourism/hospitality. The data highlighted four priorities for future development and research, namely developing offender typologies, victim-centric investigative practice, prevalence and definitions, and collaborations. These themes provide insight into the issue of transnational child sexual abuse from the perspective of different disciplines and offer a strategy to prioritise, and collaborate, in the efforts against transnational child sexual abuse.


Increased protein aggregation in Zucker diabetic fatty rat brain: identification of key mechanistic targets and the therapeutic application of hydrogen sulfide.
Diabetes and particularly high blood glucose levels are implicated in neurodegeneration. One of the hallmarks of neurodegeneration is protein aggregation. We investigated the presence of protein aggregation in the frontal brain of Zucker diabetic fatty (ZDF) rats, an animal model for diabetes. Further, the effect of NaHS in suppressing protein aggregation in cultured brain slices from ZDF was assessed. The levels of protein synthesis, protein/gene expression, autophagy and anti-oxidant defense were evaluated in ZDF and control (Lean) brains.Compared to Lean, ZDF brains displayed a significant increase in protein aggregates, p-tau, fibronectin expression and protein glycosylation. Increased phosphorylation of mTOR and S6 ribosomal protein in ZDF indicated higher protein synthesis, while the increase in ubiquitinated proteins and LC3-I in ZDF brains accompanied by lower LC3-II expression and LC3-II/LC3-I levels indicated the blockage of proteolytic pathways. CBS (cystathionine beta synthase) protein and mRNA expression and thiol group levels in ZDF brains were lower compared to Lean. ZDF brains show a higher level of reactive oxygen species. In vitro NaHS treatment normalized proteostasis while counteracting oxidative stress. Our data demonstrate increased protein synthesis and aggregation in the diabetic ZDF rat brain, which was reversible by NaHS treatment.This is the first report on the potential use of NaHS as a novel strategy against protein aggregation in diabetic brain.


Antibiotic biosynthetic pathways and pathway engineering--a growing research field in China.
This review describes the recent research activities in China in relation to studies on antibiotic biosynthetic pathways and pathway engineering in actinomycetes. 75 references are cited.


[Cloning and characterization of the gene encoding IMPDH of Streptococcus suis serotype 2].
Given the lack of effective vaccines to control Streptococcus suis infection and the lack of a rapid and reliable molecular diagnostic assay to detect its infection, S. suis serotype 2 was sequenced partly in an effort to identify important virulence factors. Two new open reading frames were found located between orf2 and mrp. One of new open reading frame (2738 - 3694) that encoded a polypeptide of 319 amino acid residues with a calculated molecular mass of 33.5kDa was identified by Western blot. GenBank database search revealed that the derived amino acid sequence shared low homology with sequences of known function from other genes. Second structure was analyzed by InterPro, PHD, DNAstar software, the deduced protein had functional domains typical of IMP dehydrogenase (IMPDH). The PCR product of the open reading frame was transformed into E. coli BL21 and the fusion protein of 48kDa was expressed. The recombinant protein was reactive with serum from pigs experimentally infected with virulent strains of S. suis type 2, suggesting that the protein is immunogenic. IMPDH activity staining confirmed that the protein has IMPDH function and can catalyze the rate-limiting reaction of GTP biosynthesis, the NAD-dependent reduction of IMP into XMP. Flow cytometry (FCM) revealed that the protein had apparent effect on HEp-2 cell cycle.


Chemical contrasting in a single polymer molecule AFM experiment.
We developed a simple contrasting procedure to improve the AFM visualization of single positively charged polymer chains deposited on substrates of a relatively high roughness via the decoration of the molecules with hexacyanoferrate anions or negatively charged clusters of cyanide-bridged complexes.


To bleed or not to bleed? Is that the question for the PTT?
The activated partial thromboplastin time (PTT) is the grandchild of the Lee-White whole blood clot time (WBCT). Both tests were developed to assist the diagnostic process for patients who exhibited features consistent with hemophilia, i.e., the pretest probability was extremely high. Probably <0.1%-1.0% of PTTs ordered in current medical practice fit that indication with the most common indication now being routine admission order; i.e., a pretest probability that is extremely low. The question asked of the PTT has evolved from 'why does this patient bleed?' to 'will this patient bleed?' As the PTT was never intended to answer that question, one must be careful regarding interpretation of results of that test. As many situations not related to hemorrhage are associated with perturbations of the PTT, a prolonged PTT is not strongly predictive of hemorrhage nor does a normal PTT provide shelter against hemorrhagic risk.


Ultrafast Photoinduced Symmetry-Breaking Charge Separation and Electron Sharing in Perylenediimide Molecular Triangles.
We report on a visible-light-absorbing chiral molecular triangle composed of three covalently linked 1,6,7,12-tetra(phenoxy)perylene-3,4:9,10-bis(dicarboximide) (PDI) units. The rigid triangular architecture reduces the electronic coupling between the PDIs, so ultrafast symmetry-breaking charge separation is kinetically favored over intramolecular excimer formation, as revealed by femtosecond transient absorption spectroscopy. Photoexcitation of the PDI triangle dissolved in CH2Cl2 gives PDI(+•)-PDI(-•) in τCS = 12.0 ± 0.2 ps. Fast subsequent intramolecular electron/hole hopping can equilibrate the six possible energetically degenerate ion-pair states, as suggested by electron paramagnetic resonance/electron-nuclear double resonance spectroscopy, which shows that one-electron reduction of the PDI triangle results in complete electron sharing among the three PDIs. Charge recombination of PDI(+•)-PDI(-•) to the ground state occurs in τCR = 1.12 ± 0.01 ns with no evidence of triplet excited state formation.


Advertisements of follow-on formula and their perception by pregnant women and mothers in Italy.
To assess how follow-on formula milks for infants aged 6-12 months are presented to and understood by mothers. A quantitative and qualitative cross-sectional study including (1) an analysis of advertisements in three magazines for parents; (2) in-depth semistructured qualitative interviews to pregnant women on their perception of two advertisements for follow-on formula and (3) self-administered questionnaires for mothers to explore their exposure to and perception of formula advertisements. Eighty pregnant women 32-36 weeks of gestation with no previous children and 562 mothers of children <3 years old. Maternal and child health centres in eight cities of Italy. Advertisements of formula (n=89) represented about 7% of all advertisements in the three magazines, the majority (58%) being for follow-on formula. Advertisements were parent-oriented, aimed at helping parents solve health problems of their babies or at eliciting good feelings, or both. The qualitative interviews to pregnant women showed inability to define the advertised products at first glance due to the ambiguity of the numeral 2 and the presumed age of the portrayed baby; this inability did not disappear after carefully viewing the advertisements and reading the text. When asked in the self-administered questionnaires whether they had ever come across advertisements of infant formula, 81% of mothers reported that they had, despite the legal inexistence of such advertisements, and 65% thought that it was for a product to be used from birth. Advertisements of follow-on formula are perceived by pregnant women and mothers as promoting infant formula.