Uncovering phantom shocks in cardiac patients with an implantable cardioverter defibrillator.
Implantable cardioverter defibrillator recipients sometimes report "phantom shocks" (PSs), defined as a reported shock lacking objective evidence. The aim of this study was to describe the subjective experience of PSs and their psychosocial correlates using a mixed methods approach. PS participants were matched on sex and age with individuals who received objective shocks only (OSO). Participants were interviewed and completed measures of posttraumatic stress disorder (PTSD Checklist-Civilian Version), depression and anxiety (Hospital Anxiety and Depression Scale), disease-specific distress (Cardiac Anxiety Questionnaire-CAQ), and social desirability (Socially Desirable Response Set-SDRS). Interviews were analyzed using interpretative phenomenological analysis (IPA). Seventeen male patients participated (PS: n = 9; OSO: n = 8). Three themes emerged from IPA: (1) PS as a somatic experience, (2) the emotional impact of PSs, and (3) searching for meaning. Quantitative analyses showed that both groups exhibited elevated trauma and anxiety levels. Effect size differences (ESD) suggested a medium ESD on depression (P = 0.176, ηp (2) = 0.118) and PTSD (avoidance: P = 0.383, ηp (2) = 0.055, numbing: P = 0.311, ηp (2) = 0.068), and a large ESD on SDRS (P = 0.081, ηp (2) = 0.189), where PS participants, comparatively, exhibited elevated levels. A medium ESD was detected on CAQ-fear (P = 0.237, ηp (2) = 0.092) where OSO participants exhibited greater heart-focused worry. The qualitative and quantitative findings of this mixed method study show convergence in terms of the emotional factors associated with the experience of PSs. PSs are often reported to be indistinguishable from objective shocks, evoking alarm, frustration, and confusion, forcing the individual to face the uncertainties of what to them is a novel and confusing experience.


Prehospital administration of hydroxocobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade.
This article reports the results of a retrospective study of 8 years of experience of the Paris Fire Brigade with the prehospital use of hydroxocobalamin. The head physician at the Paris Fire Brigade extracted and summarized data from standardized forms completed at the fire scene and, when available, hospital reports to assess survival status and clinical parameters associated with the use of hydroxocobalamin for each patient who received it for smoke inhalation-associated cyanide poisoning from 1995 to 2003. Of the 101 patients administered hydroxocobalamin, 30 survived, 42 died (17 at the fire scene and 25 at the intensive-care unit), and survival status was not known in the remaining 29 patients. Among the 72 patients for whom survival status was known, survival rate was 41.7% after the administration of hydroxocobalamin. Of the 38 patients found in cardiac arrest, 21 had a return of spontaneous circulation during prehospital care. Of the 12 patients who were initially hemodynamically unstable (systolic blood pressure 0 to < or =90 mmHg), 9 recovered systolic blood pressure an average of 30.6 minutes after the start of hydroxocobalamin infusion. Among nonsedated patients in the sample as a whole (n = 52), mean (SD) Glasgow coma scale score improved from 7.9 (5.4) initially to 8.5 (5.7) after administration of hydroxocobalamin. Among nonsedated patients who were initially neurologically impaired (n = 18), Glasgow coma scale score improved in 9 patients, did not change in 8 patients, and worsened in 1 patient. Two adverse events--red or pink coloration of urine or skin (n = 5) and cutaneous rash (n = 1)--were assessed as being possibly related to hydroxocobalamin. Hydroxocobalamin has a risk:benefit ratio rendering it suitable for prehospital use in the management of acute cyanide poisoning caused by smoke inhalation.


Excess mortality among 3302 patients with 'pure' anxiety neurosis.
The survival probability and causes of death before the age of 70 years were analyzed among 3302 inpatients with "pure" anxiety neurosis in Stockholm County, Sweden, who were tracked in case registries by means of automated record linkage during a 14-year period. When all patients with other psychiatric diagnoses and substance abuse were excluded, and marital status controlled for, there was a significant excess of deaths due to verified and undetermined suicides, ie, nearly one third of all deaths. These unnatural deaths preempted any excess in natural causes before the age of 70 years, such as cardiovascular disease. Treatment policy with regard to the use of anxiolytic drugs was not found to influence mortality. We concluded that the risk of suicide in inpatients before the age of 70 years with anxiety disorders may be as high as that in persons with depression or other diagnoses who require inpatient care.


[Information transfer between health structures. How and to whom is the information transferred?].
The evolution of the French health-care system is based on the development of patient management in the health-care system. The public services associate nurses with alternatives to hospitalization in order to favor the emergence of such facilities. This evolution changes the habits and the needs of professionals. Communication between the nurses is the basis of this function. In order to assure the continuity of health-care, both private and hospital nurses need information. However this is either not the case, or is inadequate to the expectations and needs of the nurses. The motives will be analyzed and some proposals offered. In recording and analyzing liaison records, interesting accounts were revealed which foresees the possibilities of an evolution at the information network level between the hospital and the extra-hospital sector. Some propositions will be put forth in order to assure a greater coherence in the endeavor for health-care continuity.


Recurrence Rate and Exploration of Clinical Factors after Pituitary Adenoma Surgery: A Systematic Review and Meta-Analysis based on Computer Artificial Intelligence System.
The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment is quite common. The recurrence of pituitary adenoma is a recognized occurrence in the medical field; however, there is limited comprehensive research and analysis of the predictive factors of recurrence rates and the clinical factors impacting relapse rates. Identifying the recurrence rates of pituitary adenomas and the clinical factors associated with them could help increase the remission rate by increasing focus on the specific aspects for early diagnosis and improved treatment. The objective of the current systematic review and meta-analysis is to assess the recurrent rates based on previous studies and to explore the clinical factors after pituitary surgery. A search was performed on PubMed, APA PsycINFO, Scopus, CENTRAL, and Google Scholar databases for English articles published from 1st January 2010 to 1st August 2022. Systematic reviews, meta-analysis, evidence syntheses, editorials, commentaries, preclinical studies, abstracts, theses, and preprints were excluded. Meta XL statistical software was used to conduct a prevalence meta-analysis. PubMed, PsycINFO, and Medline databases were searched. All of the articles were written between 2012 and 2022. In the beginning, 612 items were recognized. After removing duplicates and analyzing the remaining articles in terms of inclusion and exclusion criteria, 31 articles remained. There is a relationship between recurrence rates and the follow-up period. There were conflicting results about the clinical factors after pituitary adenoma surgery, specifically age and tumor size. Some included studies that there was an association between macroadenomas and high recurrence rates. No study reported that gender was a clinical factor affecting pituitary adenoma surgery outcomes or the recurrence rate. Studies also reported that there was a correlation between the remnant tumor factor and the recurrence rates; adenoma remnants after surgery increased the risk of recurrence rates for patients.


Biomechanical Perspectives on Concussion in Sport.
Concussions can occur in any sport. Often, clinical and biomechanical research efforts are disconnected. This review paper analyzes current concussion issues in sports from a biomechanical perspective and is geared toward Sports Med professionals. Overarching themes of this review include the biomechanics of the brain during head impact, role of protective equipment, potential population-based differences in concussion tolerance, potential intervention strategies to reduce the incidence of injury, and common biomechanical misconceptions.


Disilylphenylene and tetrasilylphenylene as a new building unit for highly fluorescent poly(aryleneethynylene)s.
We report the synthesis and photophysical properties of poly(aryleneethynylene)s (PAEs) containing disilyl- or tetrasilyl-substituted phenylene as the key building unit. The fluorescence spectra of one of the PAEs, consisting of the diethynylbis(trimethylsilyl)phenylene and fluorenylene units, shows an intense blue emission with the maximum at 428 nm. The absolute quantum yield (Phi(F)) and the fluorescence lifetime (tau(s)) are 0.92 and 0.39 ns, respectively. The calculated radiative decay rate constant (k(r)) from the singlet excited state, based on Phi(F) and tau(s), is 2.4x10(9) s(-1), which is extremely large for organic molecules. A series of silyl-substituted PAEs, including a tricyclic tetrasilylphenylene-containing polymer, also show intense emissions with large k(r) values. Theoretical calculations of the model systems with the bis(phenylethynyl)benzene skeleton reveal the general substituent effect of the silyl groups attached to the PAE skeleton.


Discrimination of the spectral structures of sound signals on the background of interference.
Presentation of test signals consisting of sounds with rippled spectra allowed measurements of the frequency-resolving ability (FRA) of hearing to be performed in humans without using frequency-dependent masking techniques. This allowed studies of changes in FRA in the presence of noise interference. In conditions of diotic presentation (to both ears in parallel) of the test signal and noise, FRA decreased significantly if the interference frequency was lower or equal to the test signal frequency. The relationship between this effect and the sound intensity and noise:signal ratio varied for low-frequency noise and for noise at the same frequency as the test signal, which indicates that these two types of interference have different mechanisms. However, in both cases, noise of sufficient intensity led to a complete inability to discriminate the fine spectral structure of the test signal. In dichotic presentation (test signal to one ear, noise to the other), noise had virtually no effect on FRA over a wide range of test signal and noise frequencies and noise:signal ratios. Thus, there was essentially complete dichotic release of FRA from the effects noise, which has potential to be used in constructing prosthetic hearing devices.


Maxillary arch changes with transpalatal arch treatment followed by full fixed appliances.
To evaluate short- and long-term maxillary dental arch dimensional changes in patients treated with a transpalatal arch (TPA) during mixed dentition followed by full fixed appliances in the permanent dentition compared with an untreated sample. Dental casts and lateral cephalograms obtained from 36 consecutively treated patients before TPA treatment (T0), after TPA treatment (T1), after fixed appliance treatment (T2), and a minimum of 3 years after fixed appliance treatment (T3) were analyzed. The control group was matched as closely as possible. Arch widths, perimeter, and length, as well as crowding and incisor proclination, were evaluated. In the treated group, intercanine, interpremolar, and intermolar widths and arch perimeter increased significantly at T1. At T2, only the intercanine width increase was still significant. At T3 all arch dimensions decreased, remaining larger than they were at T0. The arch length increased after T1, significantly decreased at T2, and slightly decreased at T3. The crowding decreased significantly at T1, was eliminated at T2, and increased at T3. At T3, 50% of the patients showed relapse with crowding ranging from 0.5 to 2 mm. In the control group at T1, only slight changes were noted but crowding increased. At T2, crowding and upper incisor inclination increased but arch length decreased. At T3, intercuspid width, arch perimeter, and arch length continued to decrease, thereby increasing crowding. Maxillary dental arch dimensions changed significantly after TPA followed by treatment with fixed appliances. Relapse occurred to some extent, especially in intercanine width and arch perimeter, but most of the dental arch changes remained stable.


Antigenic selection of IgG precursor subpopulations.
The temporal increase in the antigen-binding characteristic of the IgG antibody synthesized after primary immunization is thought to result from antigen preferentially selecting those precursors of the antibody-forming cells with higher affinity receptors. We have investigated this regulatory role of antigen on the selection and expression of IgG precursor subpopulations in rabbit lymph node populations undergoing the secondary anti-bovine serum albumin (BSA) response in vitro. The data indicate that although immunologic memory increased between 1 and 4 months after immunization there was not an increase in antigen sensitivity. We also determined the avidity of the IgG antibody secreted by PFC elicited in the cell cultures. Although the avidity of antibody secreted by PFC elicited with low concentrations of antigen was 2-fold greater than when high concentrations of antigen were employed, analyses of the avidity subpopulations of IgG PFC revealed that memory potential was not restricted to high affinity-primed cells. Moreover, populations of PFC that gave differing avidity values were similar in terms of their plaque diameters and IgG secretion rates.


Immunohistochemical analysis of matrix metalloproteinase-9 predicts papillary thyroid carcinoma prognosis.
The present study aimed to explore the association between immunohistochemical matrix metalloproteinase-9 (MMP-9) expression and the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC), and to determine whether it may be used as a diagnostic or prognostic tool for PTC. Immunohistochemical staining of MMP-9 was performed in thyroid tissues obtained from 112 patients with PTC and 42 subjects with benign thyroid nodules (BTNs). The receiver operating characteristic curve was used to evaluate the legitimacy of MMP-9 as a diagnostic tool for PTC, and a predictor for structurally persistent/recurrent disease (SPRD) and disease status. Cox regression was applied to identify the risk factors of disease status and SPRD. The present study revealed that MMP-9 was overexpressed in PTC tissues, compared with in BTN tissues. Furthermore, MMP-9 scores yielded an area under the curve (AUC) of 0.842 (95% CI, 0.776-0.908) for differentially diagnosing PTC from BTN. In addition, the MMP-9 score was greater if patients previously had central lymph node metastasis, lateral lymph node metastasis or an advanced tumor-node-metastasis stage (III+IV). When MMP-9 was employed to predict disease status and SPRD, an AUC of 0.811 (95% CI, 0.706-0.917) and 0.806 (95% CI, 0.620-0.992) was obtained, respectively. A tumor size of >2 cm and an MMP-9 staining score of ≥6 were independent risk factors for predicting disease status, whereas vascular invasion and an MMP-9 staining score of ≥8 were risk factors for predicting SPRD. Furthermore, an MMP-9 staining score of ≥6 and ≥8 indicated shortened disease-free survival and survival without SPRD, respectively. In conclusion, the assessment of MMP-9 expression in thyroid carcinoma samples may represent a potential and supplementary tool for the diagnosis and prognostic prediction of PTC.


Lifespan differences between queens and workers are not explained by rates of molecular damage.
The biological processes that underlie senescence are of universal biological importance, yet they remain poorly understood. A popular theory proposes that senescence is the result of limited investment into mechanisms involved in the prevention and repair of molecular damage, leading to an accumulation of molecular damage with age. In ants, queen and worker lifespans differ by an order of magnitude, and this remarkable difference in lifespan has been shown to be associated with differences in the expression of genes involved in DNA and protein repair. Here we use the comet assay and Western Blotting for poly-ubiquitinated proteins to explore whether these differences in expression lead to differences in the accumulation of DNA damage (comet assay) or protein damage (protein ubiquitination) with age. Surprisingly, there was no difference between queens and workers in the rate of accumulation of DNA damage. We also found that levels of ubiquitinated proteins decreased with age, as previously reported in honeybees. This is in contrast to what has been found in model organisms such as worms and flies. Overall, these results reveal that the link between investment into macromolecular repair, age-related damage accumulation and lifespan is more complex than usually recognised.


Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups.
In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution. In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups. Correlations with DFS and DSS in univariate analysis included < or = 2 mitoses per 50 high-power fields (P =.001, P =.002), vascular invasion (P =.02, P =.04), size < or = 2 cm (P =.01, P =.05), metastases (P =.0002, P =.07), necrosis (P =.002, P =.16), and nuclear grade (P =.04, P =.33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P =.01, P =.04, respectively). For DSS, only mitotic rate was a prognostic factor (P =.02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P =.3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P =.0007, P =.006, respectively). Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.


Differences in performance in CAMCOG-R domains between old and oldest old patients with Alzheimer's disease.
The purpose of this study is to evaluate the neuropsychological performance in a ≥90-year-old population with Alzheimer disease (AD) in comparison with younger elderly patients. We retrospectively studied all patients with AD attended in a specialized clinic between 1999 and 2011. Age, sex, educational level, and sensory loss data were collected. Neuropsychological evaluation included Mini-Mental State Examination and Global Deterioration Scale. We used the eight Cambridge Cognitive Assessment (CAMCOG-R) domains to evaluate and compare the neuropsychological performance in the younger than 90 years old (<90) and older than 90 years old (≥90) groups. We selected 2931 patients, 2897 <90 (98.83%) and 34 ≥90 years old (1.17%). The ≥90 group had significant lower punctuations in memory, praxis, and abstract thinking CAMOCG-R domains with 1.49, 0.75, and 0.58 less points, respectively, (p < 0.05). Neuropsychological characteristics of cognitive decline seem to be different in ≥90 compared to <90 years old patients. According to age, the biggest differences in the CAMCOG-R performance are in the memory, praxis, and abstract thinking domains.


Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions.
The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14(low)CD16(-) precursor to form CD14(high)CD16(+) cells without producing the CD14(high)CD16(-) cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.


Differentiation between Pseudomonas cepacia and Pseudomonas pseudomallei in clinical bacteriology.
If only conventional laboratory tests are used, the widely occurring species Pseudomonas cepacia may, due to its variability, sometimes be difficult to differentiate from the dangerous pathogen Pseudomonas pseudomallei. In a comparative study using fresh isolates it is shown that animal inoculation seems to be a useful additional method in the differentiation. Also the determination of the ability to utilize selected carbon sources such as starch, hydroxybenzoate and uracil is helpful in reaching a correct identification.


Total Anterior Uncinatectomy During Anterior Discectomy and Fusion for Recurrent Cervical Radiculopathy: A Two-dimensional Operative Video and Technical Report.
A common cause of cervical radiculopathy from degenerative foraminal stenosis is severe uncovertebral hypertrophy. It is difficult to accomplish complete foraminal decompression in these cases with posterior techniques without the removal of a large portion of the facet joint. Total removal of the uncovertebral joint from an anterior approach allows for complete decompression of the exiting cervical nerve root and has been shown to be a safe technique. In this surgical video and technical report, we demonstrate the surgical anatomy and operative technique of a two-level anterior uncinatectomy during anterior discectomy and fusion (ACDF) for recurrent cervical radiculopathy after a previous multi-level posterior foraminotomy. The patient is a 67-year-old male with a progressive left arm and neck pain with radiographic, clinical, and electrophysiologic diagnostic evidence of active C6 and C7 radiculopathies from degenerative foraminal stenosis at the C5-6 and C6-7 levels. Posterior foraminotomies had been performed without significant improvement in his radicular pain. A repeat MRI demonstrated lateral foraminal stenosis from severe uncovertebral joint hypertrophy at the C5-6 and C6-7 levels. After acquiring informed consent from the patient, an anterior approach was performed with complete removal of the uncovertebral joints at both levels with discectomy and fusion. Postoperatively, the patient had complete resolution of his radicular pain and remained pain-free at the latest follow-up. Complete uncinatectomy and ACDF is an effective technique for complete foraminal decompression in cases of refractory radiculopathy and neck pain after unsuccessful posterior decompression.


Risk Assessment for Tobacco Regulation.
Risk assessment is a process that uses a transparent, reproducible and pre-established methodology to evaluate alternatives for managing health-related risks. Although an array of federal agencies regularly use risk assessment to inform regulatory decisions, its application to tobacco regulation is new. By comparing examples of FDA risk assessments for food and tobacco, this paper highlights some of the challenges inherent in applying risk assessment methodologies to tobacco regulation. In doing so, it calls upon researchers to work with the FDA to develop a tobacco-specific approach to risk assessment that reflects the Tobacco Control Act's regulatory framework and the distinctive features of tobacco products and tobacco use.


Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China.
Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)-17.8% (16/90). Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital. Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.


Evaluation of Taxol in head and neck squamous carcinoma multicellular tumor spheroids.
Taxol cytotoxicity was evaluated in human head and neck squamous carcinoma cell lines growing as multicellular tumor spheroids (MTS) and compared with monolayered culture using conventional clonogenic assays. End points were respectively the concentration inhibiting 50% of the cellular growth (IC50) in clonogenic assays and the concentration required to induce a 50% decrease in the MTS volume (ID50) or number in the overall spheroid population (SCC50). A significant difference was observed when the cells were exposed for 10 days to Taxol as a consequence of the different growth kinetics of the spheroids. After 16 day exposure of spheroids to Taxol, no difference remained between ID50 and IC50. In addition, a significant correlation was found between individual spheroid sensitivity to Taxol (ID50) and the spheroid population sensitivity (SCC50). Both parameters (ID50 and SCC50) defined in cell models appear useful for the evaluation of chemosensitivity of three-dimensional structures known to be closer to in vivo tumor models.


Evaluation of Neurotoxicity of Multiple Anesthesia in Children Using Visual Evoked Potentials.
Anesthetic applications may cause increased neuronal damage in infants and children. Commonly cognitive or learning disability tests were used to investigate the neurological progress in children. Visual Evoked Potential is a gross electrical signal generated by the occipital regions of the cerebral cortex in response to visual stimulation and an objective assessment of brain function. In this study, to acquire more objective results, Visual Evoked Potential responses of children who had multiple exposures to anesthesia during the treatment of corrosive esophagitis were compared to children who have never received anesthesia before. In this prospective, single-blinded, randomized, controlled study, 25 children, who were admitted to our pediatric surgery clinic because of corrosive esophagitis and who received general anesthesia more than 15 times composed Group-P; 25 children, who admitted to our well-child-clinic and who had never received anesthesia before consisted Group-C. The flash and pattern VEP responses of both groups were measured at the electrophysiology laboratory without any anesthetic drug application. The VEP responses of children in Group-P were recorded at least three days after the last exposure to anesthesia. Latencies and amplitudes of the N2 and P2 components of the pattern and flash VEP responses were statistically significantly different between the two groups (p=0.000). This study shows that in children who had repeated anesthetic applications VEP parameters are significantly altered. We believe that VEP responses may be a reliable objective criterion for the evaluation of anesthesia neurotoxicity.


Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience.
Auxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression. Retrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD. A total of 13 APOLT procedures were performed for MLD during the study period. The underlying aetiologies being propionic acidemia (PA)-5, citrullinemia type 1 (CIT1)-3 and Crigler-Najjar syndrome type 1 (CN1)-5 cases respectively. Children with PA and CIT1 had a median of 8 and 4 episodes of decompensation per year, respectively, before APOLT and had a mean social developmental quotient (DQ) of 49 (<3 standard deviations) as assessed by Vineland Social Maturity Scale prior to liver transplantation. No metabolic decompensation occurred in patients with PA and CIT1 intraoperatively or in the immediate post-transplant period on protein-unrestricted diet. Patients with CN1 were receiving an average 8-15 h of phototherapy per day before APOLT and had normal bilirubin levels without phototherapy on follow-up. We have 100% graft and patient survival at a median follow-up of 32 months. Progressive improvement in neurodevelopment was seen in children within 6 months of therapy with a median social DQ of 90. APOLT is a safe procedure, which provides good metabolic control and improves the neurodevelopment in children with selected MLD.


Long-term stability of Sphyrion lumpi abundance in beaked redfish Sebastes mentella of the Irminger Sea and its use as biological marker.
The main commercial fish species in the Irminger Sea, the beaked redfish Sebastes mentella, is commonly infected with the copepod Sphyrion lumpi. This ectoparasite is often used as a biological marker for stock discrimination to evaluate the still-debated metapopulation structure of beaked redfish. Nevertheless, it is still not understood whether parasite abundances and communities vary over longer time periods. In the present study, we investigated the abundance of S. lumpi in S. mentella of the pelagic zone of the Irminger Sea and adjacent waters. Our analyses revealed that live S. lumpi abundance remained constant during summer over a sampling period from 2001 to 2015, which confirms its validity as a biomarker. As S. mentella forms dense aggregations during mating, our results suggest that host densities are, regardless of a fishery-induced decrease in host biomass, large enough to facilitate the direct transmission of S. lumpi. After correcting for covariate effects, two stock units could be differentiated, which supports a continuation of the current fishery management strategy.


MODULATION OF AUTOPHAGY AND ITS POTENTIAL FOR CANCER THERAPY.
Autophagy is a process in which cellular contents are captured in specialized, membrane-bounded vesicles and delivered to lysosomes for final degradation. Most studies support an inherent connection between autophagy and survival, but increasing evidence also suggests an association between autophagy and cell death. The therapeutic potential of targeting the autophagy pathway in cancer seems clear, but specific strategies for achieving successful eradication of cancer cells are less obvious. Recent developments in the fields of autophagy and programmed cell death, nevertheless, have shed light on therapeutic strategies with significant potential. In this review, we provide an overview of the autophagy process, pathways that modulate autophagy, and promising autophagy-based therapeutic strategies for cancer.


Describing health states. Methodologic issues in obtaining values for health states.
In health status index construction quantitative values for different states of health are frequently obtained by presenting written descriptions to raters whose values are elicited using one or more methods. In this study the authors examined the influence of several aspects of this measurement process upon the quantitative results obtained. They prepared a set of written descriptions of health states, each state being described in both a standard point-form and a narrative format. The narrative format was written in the first person singular, and listed all symptoms or problems associated with the state, whereas the point-form description included only the most severe symptom or problem. Values for these states were elicited from a group of 64 patients using two commonly employed methods, the standard gamble of Von Neumann and Morgenstern and category rating. The results indicate that the type of scenario presented to the rater and the sequence in which the methods of assessment were used had a major influence on the results. This work indicates that there is a need to examine systematically the process of obtaining quantitative values before reliance can be placed upon the results.


Binary Classifier Calibration Using an Ensemble of Linear Trend Estimation.
Learning accurate probabilistic models from data is crucial in many practical tasks in data mining. In this paper we present a new non-parametric calibration method called ensemble of linear trend estimation (ELiTE). ELiTE utilizes the recently proposed ℓ1 trend ltering signal approximation method [22] to find the mapping from uncalibrated classification scores to the calibrated probability estimates. ELiTE is designed to address the key limitations of the histogram binning-based calibration methods which are (1) the use of a piecewise constant form of the calibration mapping using bins, and (2) the assumption of independence of predicted probabilities for the instances that are located in different bins. The method post-processes the output of a binary classifier to obtain calibrated probabilities. Thus, it can be applied with many existing classification models. We demonstrate the performance of ELiTE on real datasets for commonly used binary classification models. Experimental results show that the method outperforms several common binary-classifier calibration methods. In particular, ELiTE commonly performs statistically significantly better than the other methods, and never worse. Moreover, it is able to improve the calibration power of classifiers, while retaining their discrimination power. The method is also computationally tractable for large scale datasets, as it is practically O(N log N) time, where N is the number of samples.


The IL-18 antagonist IL-18-binding protein is produced in the human ovarian cancer microenvironment.
Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN-γ production, T-helper 1 responses, and antitumor effects. In turn, IFN-γ stimulates IL-18-binding protein production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here, we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo. Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas, and the corresponding normal tissues, patients' serum, and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles, and reverse-transcription PCR. Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was detectable in EOC sera and to a greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3-CD20-NKp46-CD13+CD14low phenotype. EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-γ stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation. Together, these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity.


[Studies on the early diagnosis of endometrial carcinoma. Analysis of risk factors and cytological approach].
Clinical, cytological and hormonal studies were performed on 86 cases of endometrial carcinoma and 34 cases of endometrial hyperplasia for their early diagnosis. 68.6% of the endometrial carcinomas were in patients aged 50 to 64 and 3.5% in patients under 45 ages. The figures 17.4% infertility, 20.9% no delivery and 19.8% only one delivery indicate that endometrial carcinoma is associated with no birth or the birth of few child. Almost all cases of endometrial carcinoma had existed for more than ten years since the last pregnancy, when the lesions were detected. 20.9% of endometrial carcinomas belonged to premenopause and 24.4% to within the first 5 years following menopause. In total, 45.3% of them range around menopause and hormonal imbalance in climacteric periods. Clinical stages of endometrial carcinoma revealed no relation to enlargement of the uterus. 61.4% of endometrial carcinoma were found in obese patients. 63.1% of them showed abnormal glucose tolerance titers and preclinical lesions. Hypertension was found in 28.0% of them, but we did not consider it very significant, considering their advanced age. The serum steroid level indicated no hyperestrogenism in endometrial carcinoma. Diagnostic data showing positive and suspecious smears in endometrial carcinoma were 36.5% in vaginal, 67.5% in cervical and 84.3% in endometrial cytology. This means that direct sampling of cells from the uterine cavity is essential in the detection of endometrial carcinoma. The cytological features of endometrial carcinoma were nuclear enlargement, anisokaryosis, irregular distribution of chromatin and prominent nucleoli. Undifferentiated types of endometrial carcinoma were more characterized by these factors than differentiated types.


Attempted suicide in Hong Kong.
In 1986, psychiatrists saw a total of 307 attempted suicide cases presented to a regional general hospital in Hong Kong, whether admitted or not. Compared with suicide attempts in Hong Kong in 1954 and those in Western countries, suicide attempts in Hong Kong in 1986 were significantly more likely to be precipitated by interpersonal conflicts, and significantly less likely to be precipitated by economic stress. Compared with the methods of attempted suicide in Hong Kong in 1986, those in Hong Kong in 1954 were significantly more likely to be fatal, while those in Western countries are significantly more likely to be ingestion of hyponotics and sedatives. Suicide attempters in Hong Kong are significantly more likely to be diagnosed as schizophrenics or paranoid psychotics than those in Western countries.


Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
Human endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, yet their activity in nondiseased tissue is largely unknown. Using the GTEx RNA-seq dataset from normal tissue sampled at autopsy, we characterized individual expression of the recent HERV-K (HML-2) provirus group across 13,000 different samples of 54 different tissues from 948 individuals. HML-2 transcripts could be identified in every tissue sampled and were elevated in the cerebellum, pituitary, testis, and thyroid. A total of 37 different individual proviruses were expressed in 1 or more tissues, representing all 3 LTR5 subgroups. Nine proviruses were identified as having long terminal repeat (LTR)-driven transcription, 7 of which belonged to the most recent LTR5HS subgroup. Proviruses of different subgroups displayed a bias in tissue expression, which may be associated with differences in transcription factor binding sites in their LTRs. Provirus expression was greater in evolutionarily older proviruses with an earliest shared ancestor of gorilla or older. HML-2 expression was significantly affected by biological sex in 1 tissue, while age and timing of death (Hardy score) had little effect. Proviruses containing intact gag, pro, and env open reading frames (ORFs) were expressed in the dataset, with almost every tissue measured potentially expressing at least 1 intact ORF (gag).


A calcar collar is protective against early periprosthetic femoral fracture around cementless femoral components in primary total hip arthroplasty: a registry study with biomechanical validation.
The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model. A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an in vitro model using paired fresh frozen cadaveric femora. The prevalence of early revision for periprosthetic fracture was 0.34% (1180/337 647) and 44.0% (520/1180) occurred within 90 days of surgery. Implant risk factors included: collarless stem, non-grit-blasted finish, and triple-tapered design. In the in vitro model, a medial calcar collar consistently improved the stability and resistance to fracture. Analysis of features of stem design in registry data is a useful method of identifying implant characteristics that affect the risk of early periprosthetic fracture around a cementless femoral stem. A collar on the calcar reduced the risk of an early periprosthetic fracture and this was confirmed by biomechanical testing. This approach may be useful in the analysis of other uncommon modes of failure after THA. Cite this article: Bone Joint J 2019;101-B:779-786.


Effect of self - care education on quality of life in patients with primary hypertension: comparing lecture and educational package.
Hypertension is a dangerous risk factor for public health. It profoundly affects the patients' quality of life. However, there is lack of agreement on the best method for self-care management in patients with hypertension. This study was conducted to compare the effect of lecture and educational pamphlets on quality of life (QOL) in patients with primary hypertension. A quasi-experimental study was performed on 90 patients with chronic primary hypertension referred to two outpatient clinics in Kashan city. Patients were randomly divided into three groups including lecture group, educational package group, and control group. The participants' quality of life was measured using the SF-36 questionnaire at the beginning of the study, and two months later. Data was analyzed using ANOVA and Chi-Square tests. No significant differences were observed between the three groups for demographics characteristics and QOL before the intervention except for marital status. Mean scores of QOL dimensions of the intervention groups were increased at the end of the study, except for the dimension of bodily pain. Tukey post-Hoc test showed that except for general health, the two intervention groups were not significantly different in other dimensions, and significant differences were observed between the control group and the two intervention groups (P < 0.05). At start and the end of the study, the mean differences in the general health dimension in three groups were 2.25 ± 0.1, 0.07 ± 0.01, and -1.70 ± 0.01 respectively. There were significant differences among groups (P = 0.04). Lecture and educational package can both improve some dimensions of the QOL in patients with hypertension. However, as pamphlets are cheap and easy to use, this method may be used as an effective method for self-care education in health care settings in Iran, where the system is faced with nursing shortage.


Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses.
Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway.


Radiation safety and future innovative diagnostic modalities.
One must demand an accurate, safe, radiation-free, and noninvasive method for reflux examination as the ideal possibility for reflux screening. Of course the available different imaging modalities are far from this ideal situation, but minimal radiation exposure is indeed a permanent objective. Additionally since all of these studies might be quite stressful to the child and the family, a specially designed and equipped environment is obligatory for the comfort of all involved. An absolute ideal modality in the diagnosis of VUR would be the definition of a certain marker in serum or urine that could identify children with VUR without the need for any interventional screening modality. Therefore more and more efforts have to be made in the future to investigate different markers for this purpose. Since reflux is one of the most frequent congenital conditions pediatric urologist have to deal with potential risks that might lead to renal insufficiency, noninvasive and radiation-free modalities should become the methods of choice, hopefully in the near future.


A comparative study of nutrition and health of mothers in Japan and the Philippines.
When comparing nutrition and health among mothers in both Japan and Philippines, it can be concluded that, in regard to nutrition, the results of the total dietary scores for mothers in divided into pregnant and after-delivery stages showed that pregnant Filipino mothers' average are lower than those of pregnant Japanese mothers. Pregnant Filipino mothers and those just after delivery to 4 months had lower average dietary scores than Filipino mothers 5 months and later after delivery. These results are thought to be an important factor in the improvement of health condition and life expectancy of Filipino mothers and their children. In Japanese mothers, such differences were not found. When comparing individual dietary scores and the rate of nutrients consumed to the optimum amounts, significant differences were found among mothers in both countries. Analysis of food diaries of mothers from both countries found that Japanese mothers had average intakes of nutrients such as energy, protein, fat, vitamin B1 and vitamin B2 and were deficient in calcium, iron and vitamin A. Filipino mothers took in average amounts of protein, calcium, iron, vitamin B2 and vitamin C and were deficient in energy, fat and vitamin B1.


Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation.
We sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (HCMV) incidence and replication dynamics in a cohort of 256 patients after liver transplantation. A time-updated approach was used to determine the risk of developing HCMV replication (>200 genomes/mL blood) within the first 100 days after liver transplantation according to the immunosuppressive regimen being received at specific time points. In patients receiving tacrolimus, the addition of prednisolone was associated with a significant increased risk of HCMV replication both at baseline (relative rate of infection [RRI]=4.34; P=0.0001) and in a time-updated analysis (RRI=4.68; P=0.0001). However, the addition of azathioprine substantially reduced the risk of HCMV replication to that observed with tacrolimus alone. As expected donor/recipient HCMV serostatus was also a risk factor for viraemia. Multivariable models showed that the tacrolimus plus prednisolone regimen and donor/recipient serostatus were independent risk factors for HCMV replication. Viral replication dynamics showed that the duration of HCMV viraemia, the peak viral load, and the growth rate of HCMV were greatest in patients receiving tacrolimus plus prednisolone although these differences did not reach statistical significance. The combination of prednisolone plus tacrolimus as baseline immunosuppression after liver transplantation is associated with a high risk of HCMV replication. This effect can be negated by the addition of azathioprine.


Surface expression of toll-like receptor 4 on THP-1 cells is modulated by Bu-Zhong-Yi-Qi-Tang and Shi-Quan-Da-Bu-Tang.
Human Toll-like receptor 4 (TLR4) has recently been identified and has been shown to be the main protein involved in recognizing Gram-negative bacteria. We examined the regulation of TLR4 surface expression in a human monocytic cell line (THP-1 cells) by two traditional Chinese herbal medicines. Bu-Zhong-Yi-Qi-Tang (TJ-41) and Shi-Quan-Da-Bu-Tang (TJ-48). TJ-41 and TJ-48 upregulated TLR4 surface expression in THP-1 cells, as well as enhanced TLR4 surface expression in these cells both dose- and time-dependently. These findings suggest that TJ-41 and TJ-48 increase the receptor involved in the response to Gram-negative bacteria and may enhance defenses against these pathogens.


Modeling Patient No-Show History and Predicting Future Appointment Behavior at the Veterans Administration's Outpatient Mental Health Clinics: NIRMO-2.
No-shows are detrimental to both patients' health and health care systems. Literature documents no-show rates ranging from 10% in primary care clinics to over 60% in mental health clinics. Our model predicts the probability that a mental health clinic outpatient appointment will not be completed and identifies actionable variables associated with lowering the probability of no-show. We were granted access to de-identified administrative data from the Veterans Administration Corporate Data Warehouse related to appointments at 13 Veterans Administration Medical Centers. Our modeling data set included 1,206,271 unique appointment records scheduled to occur between January 1, 2013 and February 28, 2017. The training set included 846,668 appointment records scheduled between January 1, 2013 and December 31, 2015. The testing set included 359,603 appointment records scheduled between January 1, 2016 and February 28, 2017. The dependent binary variable was whether the appointment was completed or not. Independent variables were categorized into seven clusters: patient's demographics, appointment characteristics, patient's attendance history, alcohol use screening score, medications and medication possession ratios, prior diagnoses, and past utilization of Veterans Health Administration services. We used a forward stepwise selection, based on the likelihood ratio, to choose the variables in the model. The predictive model was built using the SAS HPLOGISTIC procedure. The best indicator of whether someone will miss an appointment is their historical attendance behavior. The top three variables associated with higher probabilities of a no-show were: the no-show rate over the previous 2 years before the current appointment, the no-show probability derived from the Markov model, and the age of the appointment. The top three variables that decrease the chance of no-showing were: the appointment was a new consult, the appointment was an overbook, and the patient had multiple appointments on the same day. The average of the areas under the receiver operating characteristic curves was 0.7577 for the training dataset, and 0.7513 for the test set. The National Initiative to Reduce Missed Opportunities-2 confirmed findings that previous patient attendance is one of the key predictors of a future attendance and provides an additional layer of complexity for analyzing the effect of a patient's past behavior on future attendance. The National Initiative to Reduce Missed Opportunities-2 establishes that appointment attendance is related to medication adherence, particularly for medications used for treatment of mood disorders or to block the effects of opioids. However, there is no way to confirm whether a patient is actually taking medications as prescribed. Thus, a low medication possession ratio is an informative, albeit not a perfect, measure. It is our intention to further explore how diagnosis and medications can be better captured and used in predictive modeling of no-shows. Our findings on the effects of different factors on no-show rates can be used to predict individual no-show probabilities, and to identify patients who are high risk for missing appointments. The ability to predict a patient's risk of missing an appointment would allow for both advanced interventions to decrease no-shows and for more efficient scheduling.


3D anatomical and perfusion MRI for longitudinal evaluation of biomaterials for bone regeneration of femoral bone defect in rats.
Magnetic Resonance Imaging (MRI) appears as a good surrogate to Computed Tomography (CT) scan as it does not involve radiation. In this context, a 3D anatomical and perfusion MR imaging protocol was developed to follow the evolution of bone regeneration and the neo-vascularization in femoral bone defects in rats. For this, three different biomaterials based on Pullulan-Dextran and containing either Fucoidan or HydroxyApatite or both were implanted. In vivo MRI, ex vivo micro-CT and histology were performed 1, 3 and 5 weeks after implantation. The high spatially resolved (156 × 182 × 195 µm) anatomical images showed a high contrast from the defects filled with biomaterials that decreased over time due to bone formation. The 3D Dynamic Contrast Enhanced (DCE) imaging with high temporal resolution (1 image/19 s) enabled to detect a modification in the Area-Under-The-Gadolinium-Curve over the weeks post implantation. The high sensitivity of MRI enabled to distinguish which biomaterial was the least efficient for bone regeneration, which was confirmed by micro-CT images and by a lower vessel density observed by histology. In conclusion, the methodology developed here highlights the efficiency of longitudinal MRI for tissue engineering as a routine small animal exam.


Viral vaccines and CTL response.
Immune induction by successful vaccine formulations seems to involve stimulation of both humoral and cellular arms of immunity. Nevertheless, CD8+ CTLs are of critical relevance in the context of intracellular infection and tumor for many reasons. The task of exerting antipathogen activity by CD8+ T cells, which principally function to control and eradicate intracellular pathogens, is enabled by constitutive expression of MHC class-I molecules on all tissue types. CTL induction offers hope for vaccines against pathogens that are resistant to neutralizing activity. This review discusses the mechanism of immune induction by some successful vaccines and based on the accrued evidence suggests ideas for improved design of CTL-inducing vaccines.


Inflectional spelling deficits in developmental dyslexia.
The goal of this study was to examine past-tense spelling deficits in developmental dyslexia and their relationship to phonological abilities, spoken morphological awareness and word specific orthographic memory. Three groups of children (28 9-year-old dyslexic, 28 chronological age-matched and 28 reading/spelling age-matched children) completed a battery of tests including spelling regularly inflected words (e.g., kissed) and matched one-morpheme words (e.g., wrist). They were also assessed on a range of tests of reading and spelling abilities and associated linguistic measures. Dyslexic children were impaired in relation to chronological age-matched controls on all measures. Furthermore, they were significantly poorer than younger reading and spelling age-matched controls at spelling inflected verbs, supporting the existence of a specific deficit in past-tense spelling in dyslexia. In addition to under-using the -ed spelling on inflected verbs, the dyslexic children were less likely to erroneously apply this spelling to one-morpheme words than younger controls. Dyslexics were also poorer than younger controls at using a consistent spelling for stems presented in isolation versus as part of an inflected word, indicating that they make less use of the morphological relations between words to support their spelling. In line with this interpretation, regression analyses revealed another qualitative difference between the spelling and reading age-matched group and the dyslexic group: while both spoken morphological awareness and orthographic word specific memory were significant predictors of the accuracy of past-tense spelling in the former group, only orthographic memory (irregular word reading and spelling) was a significant factor in the dyslexic group. Finally, we identified a subgroup of seven dyslexic children who were severely deficient in past-tense spelling. This subgroup was also significantly worse than other dyslexics and than younger controls on scores of orthographic memory. The implications of our findings for teaching and remediation strategies are discussed.


Why should cancer biologists care about tRNAs? tRNA synthesis, mRNA translation and the control of growth.
Transfer RNAs (tRNAs) are essential for mRNA translation. They are transcribed in the nucleus by RNA polymerase III and undergo many modifications before contributing to cytoplasmic protein synthesis. In this review I highlight our understanding of how tRNA biology may be linked to the regulation of mRNA translation, growth and tumorigenesis. First, I review how oncogenes and tumour suppressor signalling pathways, such as the PI3 kinase/TORC1, Ras/ERK, Myc, p53 and Rb pathways, regulate Pol III and tRNA synthesis. In several cases, this regulation contributes to cell, tissue and body growth, and has implications for our understanding of tumorigenesis. Second, I highlight some recent work, particularly in model organisms such as yeast and Drosophila, that shows how alterations in tRNA synthesis may be not only necessary, but also sufficient to drive changes in mRNA translation and growth. These effects may arise due to both absolute increases in total tRNA levels, but also changes in the relative levels of tRNAs in the overall pool. Finally, I review some recent studies that have revealed how tRNA modifications (amino acid acylation, base modifications, subcellular shuttling, and cleavage) can be regulated by growth and stress cues to selectively influence mRNA translation. Together these studies emphasize the importance of the regulation of tRNA synthesis and modification as critical control points in protein synthesis and growth. This article is part of a Special Issue entitled: Translation and Cancer.


Utilization of recombinant adenovirus and dominant negative mutants to characterize hepatocyte nuclear factor 4-regulated apolipoprotein AI and CIII expression.
Using recombinant adenoviral vectors and a dominant negative mutant of HNF-4, we have examined the contribution of hepatocyte nuclear factor 4 (HNF-4) to endogenous apolipoprotein AI and CIII mRNA expression. Overexpression of HNF-4 leads to a 7.4-fold increase in apolipoprotein CIII expression, while infection with the dominant negative mutant of HNF-4 reduces the level of apolipoprotein CIII mRNA by 80%, demonstrating that endogenous HNF-4 is necessary for apolipoprotein CIII expression. Experiments using the hepatoma cell lines, HepG2 and Hep3B, indicate that HNF-4 is also involved in the regulation of apolipoprotein AI expression in these lines. However, the effect of HNF-4 on apolipoprotein AI expression is much more dramatic in cell lines derived from intestinal epithelium. Infection of the intestinal-derived cell line IEC-6 with the HNF-4 adenovirus resulted in a greater than 20-fold increase in the level of apolipoprotein AI mRNA. These results indicate that HNF-4 does regulate apolipoprotein AI and CIII mRNA expression and suggest that HNF-4 is critical for intestinal apolipoprotein AI expression.


[Expression purification and verification of HBscFv-IFNgamma in Pichia pastoris x33].
In order to effectively cure hepatitis B virus (HBV), we studied on fusion protein HBscFv-IFNgamma, which was connected with single-chain Fv against HBV surface antigen(HBscFv) and gamma-interferon(IFNgamma) of being used in clinic against HBV. Adopting overlap PCR, the hbscfv and the ifngamma were connected into hbscfv-ifngamma. Then the pPICZalphaA/(hbscfv-ifngamma)(1,2,4) of multi-copy recombinant plasmid were constructed and transformed into Pichia pastoris x33. The engineering strain x4 was screened from transformed x33 and could secretively express HBscFv-IFNgamma. The preliminary verification indicates that HBscFv-IFNgamma has the bioactivity of HBscFv and IFNgamma by SDS-PAGE, Western blotting and ELISA. The supernatant of culturing X4 was purified by 14F7 affinity chromatography to HBscFv-IFNgamma with purity of 95%-98%. The HBscFv-IFNgamma is able to bind 27.9% HBV surface antigen (HBsAg) in the serum of HBV transgenic mice, which shows the antibody of HBscFv-IFNgamma has bioactivity in vivo. Therefore HBscFv-IFNgamma can shed light on the development of a new promising HBV-targeted drug.


Flipped learning: A shift in graduate nursing education.
The coronavirus (COVID-19) pandemic has caused a shift in education. Nursing education must respond to these changing times by redesigning classroom instruction. Flipped learning (FL) is a proposed method for teaching advanced practice nurses that is student-centered and engaging, both critical areas for contemporary learners. This qualitative study explored the perspectives and experiences of the family nurse practitioner faculty and the family nurse practitioner nursing students who participated in FL. The type and level of FL practices faculty can apply to support students coming to class prepared to engage in active learning activities was also investigated. The study used an insider action research design. There were two arms of the study, faculty and student. Ten faculty-led learning circles with four faculty and three family nurse practitioner student focus groups, each with six students, were held over the course of the study. Thematic findings were developed from both student and faculty data. The results revealed that family nurse practitioner students had a positive attitude toward FL. Many expressed FL provided perceptions of gained confidence, personalized learning, increased engagement, and preparedness for classroom instruction. Overall, faculty preferred FL over traditional teaching approaches. Several active learning activities were used by faculty with clinical case studies being the most preferred by student participants. This study confirms FL is a plausible and promising approach to traditional classroom instruction. However, more robust studies are needed to determine its benefits in advanced practice nursing education.


An essential EBV latent antigen 3C binds Bcl6 for targeted degradation and cell proliferation.
The latent EBV nuclear antigen 3C (EBNA3C) is required for transformation of primary human B lymphocytes. Most mature B-cell malignancies originate from malignant transformation of germinal center (GC) B-cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is Bcl6, a key regulator of this process. We now demonstrate that EBNA3C contributes to B-cell transformation by targeted degradation of Bcl6. We show that EBNA3C can physically associate with Bcl6. Notably, EBNA3C expression leads to reduced Bcl6 protein levels in a ubiquitin-proteasome dependent manner. Further, EBNA3C inhibits the transcriptional activity of the Bcl6 promoter through interaction with the cellular protein IRF4. Bcl6 degradation induced by EBNA3C rescued the functions of the Bcl6-targeted downstream regulatory proteins Bcl2 and CCND1, which resulted in increased proliferation and G1-S transition. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction, and raises the possibility of developing new targeted therapies against EBV-associated cancers.


Evaluation of efficacy of simvastatin in bone regeneration following local application in third molar extraction socket: A randomized control trial.
The aim of this study is to study the efficacy of simvastatin in bone regeneration following the local application in third molar extraction sockets. This is a randomized controlled trial done on 50 patients involving 100 third molar teeth extraction sockets. The patients were randomly divided based on the placement of simvastatin. Extraction sockets which were treated with simvastatin were considered study sockets and without simvastatin were considered control sockets. The study socket was assigned for the placement of simvastatin (10 mg) powder along with gelfoam as carrier moistened with normal saline solution and control socket was assigned for the placement of gelfoam moistened with saline. Intraoral periapical radiographs were taken on the 1st, 4th, 8th, and 12th weeks, and mean gray scale values indicating bone density were evaluated for both the groups. Cone-beam computed tomography (CBCT) was taken by the end of the 12th week to further evaluate the osseous regeneration. Patients were compared and evaluated for bone density, pain, and swelling. Pain and swelling were evaluated on postoperative days 1 and 7. The mean gray-level histogram values (bone density) were statistically highly significant in the study group compared to the control group in the 1st, 4th, 8th, and 12th weeks, and CBCT also showed statistically significant difference between the control and study group by the end of the 12th week. The present data suggest that the local application of simvastatin promotes and enhances bone formation in the extraction sockets, which provides a very cost-effective way for faster bone regeneration.


Improving Flame Retardant Properties of Aliphatic Polyketone (POK)-Based Composites.
The effect of zinc borate (ZB) and high-molecular-weight siloxane (SIL) on flame retardancy, mechanical, and thermal properties of aliphatic polyketone (POK)-containing aluminum diethyl phosphinate (OF) was investigated in this study. Ten wt % OF is sufficient to obtain V0 rating according to the UL94 test. As the weight fraction of OF was increased, the flame retardancy properties and LOI values improved, while the tensile and impact properties decreased. To avoid the degradation in mechanical and impact properties as much as possible and obtain the same and better flame retardancy properties, synergists such as SIL and ZB were used. Flame retardancy of POK-based composites was determined by the limiting oxygen index (LOI) test, UL94 measurement, and cone calorimeter test. The additions of 1 wt % SIL and ZB have not led to a considerable decrease in the tensile strength and impact properties of POK-10OF. While ZB and SIL are very efficient in decreasing the smoke density, ZB is more efficient than SIL in increasing the LOI value of the composite. The addition of 1, 2, and 4 wt % ZB and SIL synergists did not lower their UL94 ratings. Moreover, it can be added that ZB is more efficient than SIL in decreasing the fire growth rate (FIGRA) and maximum average rate of heat emission (MARHE) values. Using OF (10 wt %) and ZB (4 wt %), LOI values higher than 32% and smoke density values lower than 150 were obtained.


Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons.
A remarkable molecular and functional heterogeneity of the primary sensory neurons and dorsal horn interneurons transmits pain- and or itch-relevant information, but the molecular signature of the projection neurons that convey the messages to the brain is unclear. Here, using retro-TRAP (translating ribosome affinity purification) and RNA sequencing, we reveal extensive molecular diversity of spino- and trigeminoparabrachial projection neurons. Among the many genes identified, we highlight distinct subsets of Cck+ -, Nptx2+ -, Nmb+ -, and Crh+ -expressing projection neurons. By combining in situ hybridization of retrogradely labeled neurons with Fos-based assays, we also demonstrate significant functional heterogeneity, including both convergence and segregation of pain- and itch-provoking inputs into molecularly diverse subsets of NK1R- and non-NK1R-expressing projection neurons.


Closing-in Phenomenon in Huntington's Disease: A Neuropsychological Marker of Frontal/Executive Dysfunction.
In visuo-constructional tasks, patients may reproduce drawings near-to or superimposed on a model, showing the so-called "Closing-in" (CI), often ascribed to a defect in inhibitory control. CI has been described in neurological conditions, but no studies have explored CI in Huntington's disease (HD), a neurodegenerative disorder often involving the frontal cortical-subcortical circuits. We searched for the occurrence of CI in HD patients and systematically investigated its correlates to find a clinical marker of the frontal/executive dysfunctions in the early examination of HD patients. We assessed 130 HD participants, who performed a graphic coping task and a neuropsychological, psychiatric, motor, and functional assessment. CI occurred in 52/130 (40%) HD patients, with 43/52 (82.7%) superimposing their copy directly on the model. MANOVA showed that HD patients with CI scored significantly poorer on Symbol digit modality test, Stroop-color word - reading test, Stroop-color word - interference test, Trail making test - part B, and Phonological verbal fluency test. However, a logistic regression analysis revealed that the significant predictor of the occurrence of CI was the score on Stroop-color word - interference test. HD patients may show CI in graphic tasks, and it could be related to a defect in inhibitory control impeding the switch of attention from the model to the copying space, and releasing a default tendency which causes an attraction of hand movement towards the focus of visual attention. CI might be a useful clinical marker for the early detection of frontal/executive defects in HD patients.


Sigmoid cancer versus chronic diverticular disease: differentiating features at CT colonography.
To retrospectively identify morphologic findings at computed tomographic (CT) colonography that are the most reliable in the differentiation of masslike chronic diverticular disease from sigmoid carcinoma in a large patient cohort. This study was approved by the institutional review boards. The need for signed consent was waived for this retrospective study. The cohort consisted of 212 patients (mean age, 68 years; 113 women, 99 men) with focal masslike findings in the sigmoid colon at CT colonography, representing chronic diverticular disease (n = 97) or sigmoid carcinoma (n = 115). CT colonography studies were scored according to presence or absence of potential discriminators by a panel of four readers in consensus. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated, and multivariate analysis was performed. Absence of diverticula in the affected segment showed high NPV and PPV (0.95 and 0.93, respectively). Also, shoulder phenomenon showed a high NPV (0.92) and PPV (0.75). Segment length of 10 cm or less (NPV, 0.85; PPV, 0.61) and destroyed mucosal folds (NPV, 1.00; PPV, 0.62) had a high NPV but a low PPV. Although segments affected by carcinoma often showed straightened and eccentric growth patterns, no thick fascia sign, and more and larger local-regional lymph nodes (all P < .05), NPV was insufficient for discrimination (NPV ≤ 0.66). Combination of absence of diverticula and presence of shouldering showed a high diagnostic certainty (93%). Carcinoma is best differentiated from masslike diverticular disease by the absence of diverticula in the affected segment and the presence of shoulder phenomenon.


Blunted inflammatory response to lipopolysaccharide endotracheal instillation due to thermal preconditioning.
Heat shock proteins (HSPs), induced by thermal stress, make the cells more resistant to following stress. We aimed to verify if rats heating reduces the production of TNF-alpha in a model of acute respiratory distress syndrome (ARDS). We divided 34 Wistar rats in Group A and Group B. The rats of Group A received thermal shock and tracheal instillation of lipopolysaccharide (LPS), the rats of Group B only tracheal instillation of LPS. All the rats have been then subdivided in 6 subgroups sacrificed at different times after instillation of LPS: A30 and B30 at 30 min, A90 and B90 at 90 min and A180 and B180 at 180 min. We dosed the serum concentration of TNF-alpha and the values of every subgroup have been compared with the Student t-test. The serum concentration of TNF-alpha in the subgroup A90 resulted significantly lower than in the subgroup B90. The exposure to thermal stress resulting in the production of HSPs reduced the concentration of TNF-alpha in this model of ARDS.


Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog.
The present study used a model of cardiac tamponade to investigate the effects of endotoxin on the oxygen extraction capabilities of the body during an acute reduction in blood flow, when blood volume and arterial oxygen content were maintained. In 21 pentobarbital anesthetized, mechanically ventilated dogs, two catheters were introduced into the pericardial space to induce cardiac tamponade, and simultaneously to measure the intrapericardial pressure. Oxygen uptake (VO2) was determined from the expired gases. Oxygen delivery (DO2) was calculated by the product of the thermodilution cardiac index and the arterial oxygen content. Eleven dogs received 2 mg/kg Escherichia coli endotoxin, followed by generous saline infusion (20 ml/kg.hr). Ten dogs served as a control group. In each dog, DO2 was progressively reduced by pericardial saline infusion at a rate of 40 ml/hr for the first hour and 30 ml/hr thereafter. Critical O2 delivery (DO2crit) and critical O2 extraction ratio (O2ERcrit) were determined from a plot of VO2/DO2 for each individual dog. The DO2crit was greater in the endotoxic than in the control group (12.1 +/- 3.1 ml/kg.min vs. 9.6 +/- 1.6 ml/kg.min; P < 0.05). Endotoxin at the dose used did not alter VO2 (or critical VO2). Accordingly, O2ERcrit was significantly lower in the endotoxic than in the control animals (47.2% +/- 5.7% vs. 60.3% +/- 10.6%; P < 0.01). The mixed venous PO2 levels at DO2crit were higher in the endotoxic than in the control group (30.6 +/- 6.1 mm Hg vs. 25.4 +/- 5.2 mm Hg; P < 0.05). Arterial blood lactate concentration was higher in the endotoxic than in the control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous Formation of CdSe Photoluminescent Nanotubes with Visible-Light Photocatalytic Performance.
Two-dimensional (2D) colloidal CdSe nanocrystals (NCs) with precise atomic-scale thickness have attracted intensive attention in recent years due to their optical properties and quantum confinement effects originating from their particular band structure. Here, we report a solution-based and template-free protocol to synthesize CdSe nanotubes (NTs) having 3-6 walls, each of which has 3.5 molecular monolayers. Their crystal structure is zincblende, with Cd-terminated {100} planes at the top and bottom surfaces of each wall, which are passivated by short-chain acetate ligands. After verifying the prominent role of the acetate ligand for NT synthesis, we elucidated the formation mechanism of these NTs. It starts by heterogeneous nucleation of 2D plateletlike nanoseeds from the amorphous Cd precursor matrix, followed by the growth via lateral and angular attachment of nanoplatelet building blocks into curved nanosheets, eventually resulting in NTs with sharp absorption and photoluminescence peak at around 460 nm. Moreover, the NTs show remarkable visible-light photocatalytic activity, as demonstrated by the reduction of the reddish Rhodamine B into its leuco form with a conversion rate of 92% in 1 min.


The requirement for calcium ions and the effect of other ions on axoplasmic transport in mammalian nerve.
1. Until recently it was believed that axoplasmic transport in vitro was not affected by Ca2+, transport being normal in Ca2+-free medium. This was found due to the presence of the relatively impermeable perineurial sheath around the nerve trunks. Using a desheathed cat peroneal nerve preparation, axoplasmic transport was shown to require an adequate level of Ca2+ in the external medium. In a buffered Ca2+-free medium, transport began to decline within 30 min and a complete block occurred in 2 . 6 hr. A concentration of 5 mM-Ca2+ added to a buffered isotonic sucrose of NaCl solution was able to maintain transport. With lower concentrations of Ca2+ of 1 . 5-3 . 0 mM, those usually present in the extracellular fluid or in a Ringer medium, some impairment of transport was seen but the addition of 4 mM-K+ restored the normal pattern of axoplasmic transport. With Ca2+ concentrations below 0 . 75 mM, however, 4 mM-K+ was unable to sustain transport. 2. Potassium by itself at a concentration of 4 mM when added to a buffered isotonic sucrose of NaCl medium was unable to prolong the time of transport block beyond that seen in buffered isotonic NaCl or sucrose solutions. In concentrations of K+ up to 25 mM, 1 . 5-5 mM-Ca2+ was required for normal transport. With moderately higher concentrations of K+ in the range of 50-100 mM, normal appearing transport was seen with or without Ca2+. This was seen whether or not Na+ was present in the medium. At higher levels of K+, 120-150 mM, decreased transport was seen, with or without the addition of either 15 mM-Na+ or Ca2+ in concentrations of 1 . 5-3 . 0 mM. 3. While Mg2+ could not substitute completely for Ca2+ in maintaining transport, it was able to prolong the time before block occurred. An extra 30-60 min of downflow was seen when 5 mM-Mg2+ was added to a buffered isotonic NaCl medium. Magnesium also acts synergistically with Ca2+. Concentration of Ca2+ as low as 0 . 25 mM was, with the addition of 1 . 5 mM-Mg2+, able to maintain transport. 4. The results are interpreted in the light of studies of the mechanism of Ca2+ regulation known to occur in giant nerve fibres and other clls controlling the level of free Ca2+. The relationship of Ca2+ to the mechanism considered to underlie axoplasmic transport in nerve fibres is also discussed.


Two Solitudes: Wilder Penfield, Ewen Cameron, and the Search for a Better Lobotomy.
In the 1940s, Wilder Penfield carried out a series of experimental psychosurgeries with the psychiatrist D. Ewen Cameron. This article explores Penfield's brief foray into psychosurgery and uses this episode to re-examine the emergence of his surgical enterprise. Penfield's greatest achievement - the surgical treatment of epilepsy - grew from the same roots as psychosurgery, and the histories of these treatments overlap in surprising ways. Within the contexts of Rockefeller-funded neuropsychiatry and Adolf Meyer's psychobiology, Penfield's frontal lobe operations (including a key operation on his sister) played a crucial role in the development of lobotomy in the 1930s. The combination of ambiguous data and the desire to collaborate with a psychiatrist encouraged Penfield to try to develop a superior operation. However, unlike his collaboration with psychiatrists, Penfield's productive working relationship with psychologists encouraged him to abandon the experimental "gyrectomy" procedure. The story of Penfield's attempt to find a better lobotomy can help us to examine different forms of interdisciplinarity within biomedicine.


Utility of free alpha-subunit as an alternative neuroendocrine marker of gonadotropin-releasing hormone (GnRH) stimulation of the gonadotroph in the human: evidence from normal and GnRH-deficient men.
To examine the hypothesis that the secretion of free alpha-subunit (FAS) can serve as an alternative to LH as a neuroendocrine marker of gonadotroph stimulation by GnRH in euthyroid humans, we have investigated the relationship of pulsatile FAS secretion in euthyroid GnRH-deficient men (n = 10) before and after exogenous GnRH stimulation and in normal men under the influence of endogenous GnRH secretion (n = 18). Before GnRH exposure, the GnRH-deficient men showed a complete absence of both LH and FAS pulses. During the initial 7 days of GnRH exposure, all GnRH-deficient men exhibited pulsatile release of FAS by the third day, whereas the appearance of pulsatile release of LH and FSH was more variable. Long term administration of GnRH led to pulses of LH and FAS that were 100% concordant with a demonstrable dose-response relationship between GnRH and FAS, which was quantitatively similar to but more exuberant than that for LH. All doses of GnRH that produced LH pulses within the normal adult range yielded supraphysiological FAS pulses. Analysis of distribution histograms of interpulse intervals and pulse amplitudes of LH and FAS in both normal and GnRH-deficient subjects demonstrated no significant difference between these glycoproteins in interpulse intervals in either the normal or GnRH-deficient groups or in the pulse amplitudes in the GnRH-deficient subjects. There was, however, a significant difference (P less than 0.01) between the distribution histogram of LH and FAS pulse amplitudes in normal men. We conclude that the pulsatile secretion of FAS in euthyroid men 1) is determined by GnRH secretion, 2) is the initial glycoprotein to be secreted in a pulsatile fashion from the gonadotroph during early GnRH exposure in GnRH-deficient men, 3) demonstrates a dose-response relationship to exogenous GnRH which is more robust than that of LH in GnRH-deficient men receiving GnRH, and 4) can, therefore, serve as a complementary and powerful tool with LH for the study of GnRH neurosecretory dynamics.


Fast scanning calorimetry studies of the glass transition in doped amorphous solid water: evidence for the existence of a unique vicinal phase.
The fast scanning calorimetry (FSC) was employed to investigate glass transition phenomena in vapor deposited amorphous solid water (ASW) films doped with acetic acid, pentanol, and carbon tetrachloride. In all three cases, FSC thermograms of doped ASW films show well pronounced glass transitions at temperatures near 180 K. Systematic FSC studies of the glass transition temperature and the excess heat capacity dependence on the concentration of impurities indicate the possible existence of two distinct non-crystalline phases of H2O in binary aqueous solutions. According to our conjecture, bulk pure ASW is a glass at temperatures up to its crystallization near 205 K. However, guest molecules in the ASW matrix may be enveloped in an H2O phase which undergoes a glass transition prior to crystallization. In the case of CH3COOH, we estimate that such a viscous liquid shell contains approximately 25 H2O molecules. We discuss the implications of these findings for past studies of molecular kinetics in pure vitreous water and in binary aqueous solutions.


Infectious arthritis in renal transplant patients.
Infectious complications in the renal transplant patient are common, and infecting agents include opportunistic organisms as well as common pathogens. However, we were only able to document 6 patients who had septic arthritis from more than 800 who received a renal transplant at our institution over an 18-year period. Furthermore, only 16 other cases of infectious arthritis have been reported in the literature. All of our patients had an apparent predisposing factor and 3 patients had prior infection with the same organism. The knee was the most commonly infected joint. The initial synovial fluid white blood cell count was usually greater than 30,000 cells/mm3, but 1 patient with viral arthritis initially had noninflammatory fluid. The peripheral blood white blood cell count may not be elevated. All of our cases of initial joint infection occurred by 18 months posttransplant. Blood cultures were positive in 3 of 4 patients with bacterial infection. Followup of these 6 patients averaged 4.3 years. Numerous other rheumatologic syndromes and disorders peculiar to the posttransplant period may mimic a septic joint. Consequently, despite the low frequency of occurrence of septic arthritis, persistent attention to the locomotor system in the transplant patient is warranted.


pH in expired breath condensate of patients with inflammatory airway diseases.
Endogenous airway acidification, as assessed by pH in expired breath condensate, has been implicated in asthma pathophysiology. We measured pH in breath condensate of patients with inflammatory airway diseases in stable condition and examined its relationship with the inflammatory process (as assessed by differential cell counts in induced sputum), oxidative stress (as assessed by H(2)O(2) and 8-isoprostane), and nitric oxide metabolism (as assessed by total nitrate/nitrite). We studied 40 patients with bronchial asthma (20 with moderate disease, forced expiratory volume in 1 second 60 [10]% SD predicted), 20 patients with bronchiectasis, 20 patients with chronic obstructive pulmonary disease (COPD), and 10 normal subjects. Mean (95% confidence intervals) pH values were significantly lower in patients with COPD and bronchiectasis compared with patients with asthma and control subjects (7.16, 7.09-7.23 and 7.11, 7.04-7.19 versus 7.43, 7.35-7.52 and 7.57, 7.51-7.64, respectively, p < 0.0001). Patients with moderate asthma had significantly lower values compared with mild and control subjects. In patients with COPD and bronchiectasis, the values of pH were significantly correlated with both sputum neutrophilia and oxidative stress. Respectively, in patients with moderate asthma, a significant correlation was observed between pH and sputum eosinophilia, total nitrate/nitrite, and oxidative stress. The pH of the expired breath condensate might be a simple, noninvasive, inexpensive, and easily repeatable procedure for the evaluation of the inflammatory process in airway diseases.


NADPH Producing Enzymes as Promising Drug Targets for Chagas Disease.
Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is a cofactor used in different anabolic reactions, such as lipid and nucleic acid synthesis, and for oxidative stress defense. NADPH is essential for parasite growth and viability. In trypanosomatid parasites, NADPH is supplied by the oxidative branch of the pentose phosphate pathway and by enzymes associated with the citric acid cycle. The present article will review recent achievements that suggest glucose-6-phosphate dehydrogenase and the cytosolic isoform of the malic enzyme as promising drug targets for the discovery of new drugs against Trypanosoma cruzi and T. brucei. Topics involving an alternative strategy in accelerating T. cruzi drug-target validation and the concept of drug-target classification will also be revisited.


Association between access to full-service restaurants and childhood obesity.
The lack of access to full-service restaurants (FSRs) is generally thought to be a risk factor for childhood obesity, as it could discourage healthful eating-out behaviours while increasing the exposure to unhealthful food venues as "compensatory" options. However, the association between FSR access and childhood obesity has not been comprehensively reviewed previously. A literature search was conducted on PubMed and Web of Science for articles published before 1 January 2019 that examined the association between FSR access and weight-related behaviours and outcomes among children and adolescents. Eighteen studies conducted in three countries were identified, published from 2006 to 2018 with a median sample size of 2352 (ranging from 323 to 529 367). Findings were mixed among these 18 studies that reported on the association between access to FSRs and weight-related outcomes. Our meta-analyses showed that there were no significant associations of FSR access with the level of body mass index (BMI) and the BMI z-score among children. Also, there was no apparent evidence on the association between FSR access and the risk of overweight/obesity. Our results need to be interpreted with caution, considering the menu quality of FSRs and heterogeneity of eligible studies in this meta-analysis. Well-designed epidemiologic studies are warranted to further elaborate on the potential association between FSR access and children's weight status.


FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines.
FOLFIRINOX [fluorouracil (5-FU), irinotecan, oxaliplatin] and gemcitabine plus nab-paclitaxel are standard treatments for patients with pancreatic ductal adenocarcinoma (PDAC). Despite efficacy rates of less than 32%, evidence is lacking to guide the use of one drug over the other. Herein, we compared the sensitivity of patient-derived PDAC cell lines to each of these regimens. Changes in the growth of 19 low-passage patient-derived PDAC cell lines were evaluated in response to treatment with FOLFIRINOX and gemcitabine plus paclitaxel (Gem-Pac). Six cell lines exhibited optimal sensitivity (high EMax and low GI50) to FOLFIRINOX and three cell lines exhibited optimal sensitivity to Gem-Pac. Several cell lines that were optimally sensitive to one drug regimen exhibited very poor response to the other. Further characterization of cancer cells exhibiting preferential sensitivity to each of these regimens may allow the identification of biomarkers to guide the selection of appropriate chemotherapy for a given patient.


Comparative genomics of four strains of the edible brown alga, Cladosiphon okamuranus.
The brown alga, Cladosiphon okamuranus (Okinawa mozuku), is one of the most important edible seaweeds, and it is cultivated for market primarily in Okinawa, Japan. Four strains, denominated S, K, O, and C, with distinctively different morphologies, have been cultivated commercially since the early 2000s. We previously reported a draft genome of the S-strain. To facilitate studies of seaweed biology for future aquaculture, we here decoded and analyzed genomes of the other three strains (K, O, and C). Here we improved the genome of the S-strain (ver. 2, 130 Mbp, 12,999 genes), and decoded the K-strain (135 Mbp, 12,511 genes), the O-strain (140 Mbp, 12,548 genes), and the C-strain (143 Mbp, 12,182 genes). Molecular phylogenies, using mitochondrial and nuclear genes, showed that the S-strain diverged first, followed by the K-strain, and most recently the C- and O-strains. Comparisons of genome architecture among the four strains document the frequent occurrence of inversions. In addition to gene acquisitions and losses, the S-, K-, O-, and C-strains possess 457, 344, 367, and 262 gene families unique to each strain, respectively. Comprehensive Blast searches showed that most genes have no sequence similarity to any entries in the non-redundant protein sequence database, although GO annotation suggested that they likely function in relation to molecular and biological processes and cellular components. Our study compares the genomes of four strains of C. okamuranus and examines their phylogenetic relationships. Due to global environmental changes, including temperature increases, acidification, and pollution, brown algal aquaculture is facing critical challenges. Genomic and phylogenetic information reported by the present research provides useful tools for isolation of novel strains.


Intra-aortic balloon pumps.
Intra-aortic balloon pumps (IABPs) are circulatory assist devices used to treat a number of cardiovascular conditions. IABPs provide temporary circulatory support by reducing the resistance to blood flow out of the heart during systole and by providing added pressure to aid in perfusing the heart during diastole. In this Evaluation, we tested three IABPs from three suppliers. We examined the units' technical performance, safety and monitoring, human factors design, transport operation, and supplier support. Rather than test all the triggering (activation) modes available, we focused our testing on the modes most commonly used on each unit. We also provide information on an IABP currently available only in Japan; although we did not test this unit, we do provide a preliminary judgment based on the information provided to us by the supplier. In the Technology Overview also included in the Evaluation, we describe the basic operation and use of an IABP, as well as review the state of the art of this technology. And in the Selection, Purchasing, and Use Guide at the conclusion of the Evaluation, we discuss such topics as balloon costs and sizing, interfacing IABPs with patient monitors, and the use of IABPs in community hospitals.


Computational Modeling to Support Surgical Decision Making in Single Ventricle Physiology.
Many of the advances in congenital heart surgery were built upon lessons and insights gained from model simulations. While animal and mock-circuit models have historically been the main arena to test new operative techniques and concepts, the recognition that complex cardiovascular anatomy and circulation can be modeled mathematically ushered a new era of collaboration between surgeons and engineers. In 1996, the computational age in congenital heart surgery began when investigators in London and Milan tapped the power of the computer to simulate the Fontan procedure and introduced operative improvements. Since then, computational modeling has led to numerous contributions in congenial heart surgery as continuing sophistication and advances in numerical and imaging methods furthered the ability to refine anatomic and physiologic details. Idealized generic models have given way to precise patient-specific simulations of the 3-dimensional anatomy, reconstructed circulation, affected hemodynamics, and altered physiology. Tools to perform virtual surgery, and predict flow dynamic and circulatory results, have been developed for some of the most complex defects, such as those requiring single ventricle palliation. In today's quest for personalized medicine and precision care, computational modeling's role to assist surgical planning in complex congenital heart surgery will continue to grow and evolve. With ever closer collaboration between surgeons and engineers, and clear understanding of modeling limitations, computational simulations can be a valuable adjunct to support preoperative surgical decision making.