Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.
Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.


The effect of a segmental gastrectomy with proximal gastric vagotomy on gastric secretion and gastric emptying.
Gastric acid secretory responses to graded doses of pentagastrin were measured in duodenal ulcer patients before and after either proximal gastric vagotomy (17 patients) or proximal gastric vagotomy associated with a segmental gastrectomy (11 patients). Calculated maximal output of acid and responsiveness of the acid-secreting cells to pentagastrin were reduced by both operations; after surgery, maximal acid output was lower in the proximal gastric vagotomy plus segmental gastrectomy group than in the proximal gastric vagotomy group. Gastric emptying of a liquid meal was assessed before and after either proximal vagotomy (13 patients) or proximal gastric vagotomy plus segmental gastrectomy (9 patients). The early phase of emptying was equally accelerated by both operations, and at later stages the emptying was only slightly, but not significantly, faster following proximal gastric vagotomy associated with segmental gastrectomy.


[Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy].
Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.


[H2O2 induces changes in the plasma membrane of Saccharomyces cerevisiae].
This article reviews the recent studies on H2O2 adaptation of Saccharomyces cerevisiae. When the cell exposed in the H2O2 sub-lethal doses, the plasma membrane permeability decreased, meanwhile the plasma membrane fluidity is minished. These changes resulted in a gradient across the plasma membrane, which conferring a higher resistance to oxidative stress. Recent work has also shown that the yeast cells adapted to H2O2 would lead to several changes in the expression of genes coding the key enzymes involved in the biosynthesis of lipid profile and in the organization of lipid microdomains of the plasma membrane, which finally decreased its' permeability and fluidity. The reorganization of the plasma membrane might be the major mechanism of the H2O2 adaptation. Once the yeast cells adapted to the external H2O2, changes in plasma occurred. The H2O2 dependent signaling pathways in the plasma membrane might be activated by high levels of H2O2. But the details of the signaling events should still be further studies.


Probabilistic performance estimators for computational chemistry methods: Systematic improvement probability and ranking probability matrix. II. Applications.
In Paper I [P. Pernot and A. Savin, J. Chem. Phys. 152, 164108 (2020)], we introduced the systematic improvement probability as a tool to assess the level of improvement on absolute errors to be expected when switching between two computational chemistry methods. We also developed two indicators based on robust statistics to address the uncertainty of ranking in computational chemistry benchmarks: Pinv, the inversion probability between two values of a statistic, and Pr, the ranking probability matrix. In this second part, these indicators are applied to nine data sets extracted from the recent benchmarking literature. We also illustrate how the correlation between the error sets might contain useful information on the benchmark dataset quality, notably when experimental data are used as reference.


Genetic analysis of female preference functions as function-valued traits.
The genetic analysis of female preferences has been seen as a particularly challenging empirical endeavor because of difficulties in generating suitable preference metrics in experiments large enough to adequately characterize variation. In this article, we take an alternative approach, treating female preference as a function-valued trait and exploiting random-coefficient models to characterize the genetic basis of female preference without measuring preference functions in each individual. Applying this approach to Drosophila bunnanda, in which females assess males through a multivariate contact pheromone system, we gain three valuable insights into the genetic basis of female preference functions. First, most genetic variation was attributable to one eigenfunction, suggesting shared genetic control of preferences for nine male pheromones. Second, genetic variance in female preference functions was not associated with genetic variance in the pheromones, implying that genetic variation in female preference did not maintain genetic variation in male traits. Finally, breeding values for female preference functions were skewed away from the direction of selection on the male traits, suggesting directional selection on female preferences. The genetic analysis of female preference functions as function-valued traits offers a robust statistical framework for investigations of female preference, in addition to alleviating some experimental difficulties associated with estimating variation in preference functions.


Mitochondrial Control for Healthy and Autoimmune T Cells.
T cells are critical players in adaptive immunity, driving the tissue injury and organ damage of patients with autoimmune diseases. Consequently, investigations on T cell activation, differentiation, and function are valuable in uncovering the disease pathogenesis, thus exploring promising therapeutics for autoimmune diseases. In recent decades, accumulating studies have pinpointed immunometabolism as the fundamental determinant in controlling T cell fate. Specifically, mitochondria, as a hub of intracellular metabolism, connect glucose, lipid, and amino acid metabolic pathways. Herein, we summarize metabolic adaptations of mitochondrial oxidative phosphorylation and the relevant glucose, lipid, and amino acid metabolism during T cell activation, differentiation, and function. Further, we focused on current updates of the molecular bases for metabolic reprogramming in autoimmune T cells and advances in exploring metabolic-targeted therapeutics against autoimmune diseases. This might facilitate the in-depth understanding of autoimmune pathogeneses and the clinical management of autoimmune diseases.


Implementation of Two Developmental Screening Programs in Sickle Cell Disease Specialty Care.
Developmental screening is a critical component of care for children with sickle cell disease (SCD), who are at elevated risk for neurodevelopmental disorders. This report describes the implementation of two related developmental screening programs implemented in different SCD specialty care settings with the purpose of describing screening protocols, outcomes, and lessons learned. Program One reviewed medical records for 201 children with SCD screened at ages 2 and 4 years. Program Two reviewed program tracking and visit notes for 155 screenings across 67 children screened between 9 and 66 months of age. Key outcomes included characteristics of children screened, screening results, concordance between parent concerns and screening outcomes, and access to evaluation and intervention services. Each program identified a substantial number of children with developmental concerns, including 42% of screenings in Program One and 36% of unique children screened in Program Two. Program One resulted in 56% of identified children receiving follow-up developmental services and 62% receiving developmental monitoring. Program Two resulted in 58% of identified children receiving further evaluation following developmental screening, with 67-75% of children with neurodevelopmental diagnoses receiving intervention services following evaluation. While parent concerns were related to screening outcomes, screening instruments detected many children whose parents did not express developmental concerns. Routine developmental screening is a feasible, acceptable, and effective method for identifying concerns in children with SCD in specialty care. Flexible and collaborative care and sustainability are key considerations for effective programming, with pediatric psychologists uniquely positioned to provide optimal integrated care.


Emotional reactivity and risk for psychopathology among adolescents.
Various aspects of personality or dispositional style predict risk for psychiatric disorders among adults. In particular, signs of neuroticism, emotional reactivity, or sensitivity to stress are strong predictors of later mood or anxiety disorders. The current report extends this literature to adolescents. An epidemiologic sample of 776 young people living in upstate New York received psychiatric assessments based on the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R) and a self-report assessment of personality style in 1983 and 1985. Psychopathology was again assessed in 1992. The current study first examined demographic correlates of emotional reactivity. The study then considered the predictive relationship between emotionally reactive personality style at one study wave and psychopathology at later waves. In middle but not early adolescence, girls showed higher levels of emotional reactivity than boys. In turn, high levels of emotional reactivity predicted a range of psychiatric disorders at follow-up. The most consistent associations emerged for major depression and fearful spells, a term the authors use to describe a subclinical form of panic attacks. As in adults, midadolescent girls rate themselves as more emotionally reactive than midadolescent boys. Moreover, adolescents who rate themselves as emotionally reactive face a high risk for mood and anxiety disorders. High levels of emotional reactivity may represent a manifestation of underlying neurobiologic risk for mood and anxiety disorders.


[Anesthetic Management of a Patient with Langerhans Cell Histiocytosis during Cesarean section].
Langerhans cell histiocytosis is a rare disease, associated with histiocyte increases, and granuloma, in various organs. About 160 patients are reported in Japan. A pregnant patient with a pulmonary Langerhans cell histiocytosis underwent cesarean section under spinal anesthesia. She had repeated pneumothorax with bilateral pulmonary cysts rapidly becoming worse during pregnancy. She was treated with continuous oxygen after 28 weeks of the pregnancy. On 34 weeks of the pregnancy, spinal anesthesia with 0.5% hyperbaric bupivacaine (2 ml) and fentanyl (25 μg) for cesarean section was performed, and provided excellent analgesia without any side-effects.


Barriers of Female Breast, Colorectal, and Cervical Cancer Screening Among American Indians-Where to Intervene?
Female breast, colorectal, and cervical cancer are three common cancers among people in the United States. Both their incidence and mortality rates can be dramatically reduced if effective prevention and intervention programs are developed and implemented, because these cancers are preventable through regular screenings. American Indians in the United States especially in the Northern Plains have a disproportionally high burden of these cancers. As a hard-to-reach population group, less attention has been paid to American Indians regarding cancer screening compared with other population groups. This study examined barriers experienced by American Indians residing in South Dakota regarding three cancer sites: female breast, colorectal, and cervical cancer through a community-based survey. A total of 199 participants were recruited and factors significantly associated with cancer screening included knowledge about cancer screening, geographic access to PCPs, encouragement by doctors, as well as socioeconomic barriers. Meanwhile, integrating geographic access, socioeconomic deprivation, and geographic distribution of American Indians, the study identified geographic areas of low access to cancer screening where hard-to-reach populations resided. Results from the study will provide crucial information for the development of targeted intervention programs to increase the acceptability and uptake of cancer screening among American Indians.


Quality of life in social phobia.
The person's perception of his or her quality of life has been neglected in studies of mental health in general and anxiety disorders in particular. However, the judgement of the impact of a mental disorder based on symptomatic distress while ignoring one's overall quality of life is incomplete. In the present study, we examined social phobic patients' judgments of their satisfaction with various domains of life they deem important using the Quality of Life Inventory (QOLI; Frisch, unpublished). Social phobics judged their overall quality of life lower than Frisch's (unpublished) normative sample. Quality of life was inversely associated with various measures of severity of social phobia (especially social interaction anxiety), functional impairment, and depression. It was not, however, related to performance anxiety or trait anxiety. Quality of life also varied across combinations of subtype of social phobia and the presence/absence of avoidant personality disorder, and as a function of marital status. Patients showed significant improvement in quality of life scores after completion of cognitive-behavioral group therapy for social phobia.


Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes.
Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.


Opportunities, Challenges, and Future Directions of Generative Artificial Intelligence in Medical Education: Scoping Review.
Generative artificial intelligence (AI) technologies are increasingly being utilized across various fields, with considerable interest and concern regarding their potential application in medical education. These technologies, such as Chat GPT and Bard, can generate new content and have a wide range of possible applications. This study aimed to synthesize the potential opportunities and limitations of generative AI in medical education. It sought to identify prevalent themes within recent literature regarding potential applications and challenges of generative AI in medical education and use these to guide future areas for exploration. We conducted a scoping review, following the framework by Arksey and O'Malley, of English language articles published from 2022 onward that discussed generative AI in the context of medical education. A literature search was performed using PubMed, Web of Science, and Google Scholar databases. We screened articles for inclusion, extracted data from relevant studies, and completed a quantitative and qualitative synthesis of the data. Thematic analysis revealed diverse potential applications for generative AI in medical education, including self-directed learning, simulation scenarios, and writing assistance. However, the literature also highlighted significant challenges, such as issues with academic integrity, data accuracy, and potential detriments to learning. Based on these themes and the current state of the literature, we propose the following 3 key areas for investigation: developing learners' skills to evaluate AI critically, rethinking assessment methodology, and studying human-AI interactions. The integration of generative AI in medical education presents exciting opportunities, alongside considerable challenges. There is a need to develop new skills and competencies related to AI as well as thoughtful, nuanced approaches to examine the growing use of generative AI in medical education.


Mental health problems of children: analysis of a cumulative psychiatric case register.
The advent of community mental health centers has brought a marked increase in treatment of mental health problems of children, especially for minorities. The number of children receiving care and the prevalence and the utilization rates by age, sex, and race from 1960 to 1977 in a large metropolitan county in upstate New York have been described previously. For the same time and community, the episodes of care by diagnostic grouping, type and length of treatment, and health status at the end of an episode have now been examined. An increase in treatment occurred in two areas: situational disorders and behavioral disorders. The number of treatments for psychotic, neurotic, and personality disorders remained stable. Affective and psychotic disorders emerged as qualitatively unique problems which often required multiple treatments and predicted high adult utilization. The average length of treatment for all episodes was 110 days. One third of the treatment episodes were associated with an improved health status. Most contacts were for first episodes, but a few patients had an extraordinarily large number of treatment episodes. A comparison with mental health problems seen in pediatric practice is presented.


Bacterial synthesis of a novel human leukocyte interferon.
A novel human leukocyte interferon cDNA clone (LeIF B) was identified in a cDNA library prepared using polyadenylated mRNA of a myeloblastoid cell line. The nucleotide sequence of LeIF B differs significantly from other published leukocyte interferon cDNA sequences. An expression plasmid was constructed which directs the synthesis in E. coli of 8 x 10(7) interferon units per liter of culture. LeIF B exhibits markedly different specificities from another bacterially synthesized human leukocyte interferon, LeIF A.


Surgical treatment of skeletal metastases in 31 melanoma patients.
The authors retrospectively studied 31 patients with malignant melanoma who were surgically treated for 34 skeletal metastases between 1987 and 2007. The aim was to evaluate the role of orthopaedic surgery and to identify factors related to survival. The patients were operated on for spinal cord compression (n = 12) and metastatic destruction in a long bone (n = 17), or other locations (n = 5). The median survival after surgery was 1.9 months (range: 0-40). The survival rate was 039 at 3 months, and 0.13 at 1 year. Four of 34 operations led to failure necessitating reoperation. A prolonged delay between diagnosis and surgery, radical excision, a solitary skeletal metastasis, radiotherapy, a perioperative lactate dehydrogenase (LDH) level < or = 8 microkat/L (p = 0.04) and a preoperative haemoglobin level > 11.5 mg/dL (p = 0.003) had a favourable prognostic impact. A vertebral localization was unfavourable. These prognostic factors may help identify which melanoma patients with symptomatic skeletal metastases will benefit from orthopaedic surgery. This study represents the largest reported cohort surgically treated for skeletal metastasis of malignant melanoma at a single institution.


The effect of aggressive nutrition on infection rates in patients maintained on peritoneal dialysis.
Aggressive nutrition has been reported to improve growth parameters in children undergoing peritoneal dialysis. The current study reports the effect of a program of aggressive nutrition, started in 1/1988, on catheter-related infection rates in children undergoing chronic peritoneal dialysis. A combination of high calorie foods, supplements, "candy bar diets", and, when necessary, modular gastrostomy feedings, to provide 3-4 gm/kg/d and 100-120 kcal/kg/d was used. Peritonitis and catheter infection rates were assessed. A total of 37 pediatric patients underwent peritoneal dialysis from 1/1986-7/1990, with a total cumulative experience of 596 patient months. The peritonitis rate decreased from 1 episode/5.53 patient-month in 1987 to 1 episode per 46 patient-month in 1990. There was no significant effect on the catheter infections or the number of admissions/patient month. However, there was a 55% decline in the number of hospitalization days/patient month (p less than 0.01). The decrease in the peritonitis rate was independent of the modality of peritoneal dialysis or the usage of ultraviolet connecting devices. In 10 patients followed sequentially, the peritonitis rate was less (1 episode/23.5 patient months) after gastrostomy tube placement and feedings than before gastrostomy tube placement (1 episode/8.28 patient months) (p less than 0.01). There were no significant differences in serum albumin or total protein levels between the two observation periods. We conclude that adequate nutrition may play a role in decreasing the peritonitis rate in children maintained on peritoneal dialysis and speculate improved white cell function as a possible underlying mechanism.


What we know and what we don't know about the perioperative use of methadone in children and adolescents.
Postoperative pain control is essential to optimizing patient outcomes, improving satisfaction, and allowing patients to resume their baseline functional activities. Methadone, a synthetic mu-opioid agonist, has multiple pharmacologic properties that may be optimal for perioperative use. Compared to other opioids, methadone has a longer duration of action, rapid onset, extended dosing intervals, high oral bioavailability, low cost, lack of active metabolites, and action on multiple receptors. The current literature examining the use of methadone in the perioperative care of children and adolescents is limited and most often reported within the context of spine or cardiothoracic surgery. Overall, these studies support the hypothesis that perioperative methadone in pediatric patients may decrease postoperative pain, opioid consumption, length-of-stay, and the incidence of some opioid-related side effects, like constipation and urinary retention. A variety of protocols for the perioperative use of methadone have been described, including a single intraoperative dose as well as multiple small doses within multimodal pain protocols. The superiority of these protocols has not been established. Like all opioids, methadone has a side effect profile which includes nausea, vomiting, reduced GI motility, sedation, and respiratory depression at high doses. There is also a concern that it can cause QTc prolongation in patients. The primary aim of this educational review is to examine the pharmacologic data, published perioperative protocols, dosing considerations, and risks and benefits associated with inclusion of methadone in analgesic regimens for surgical patients. A secondary aim is to introduce opportunities for research around the perioperative use of methadone in children and adolescents. Based on our review, we would prioritize establishing optimal procedure-specific methadone protocols, determining generalizability for use in routine pediatric surgeries, and investigating methadone safety and efficacy prospectively as the primary opioid for pain management in the postanesthesia care unit or postsurgical floors.


One-Pot Unsymmetrical {[4 + 2] and [4 + 2]} Double Annulations of o/ o'-C-H Bonds of Arenes: Access to Unusual Pyranoisoquinolines.
With the aid of a transformable sulfoximine directing group, unprecedented one-pot unsymmetrical double annulations {[4 + 2] and [4 + 2]} of hetero(arenes) with alkynes are revealed under Ru(II) catalysis. Functionalization of both ortho-C-H bonds of (hetero)arene is reflected in the building of unusual 6,6-fused pyranoisoquinoline skeletons. Construction of four [(C-C)-(C-N) and (C-C)-(C-O)] bonds occurs in one step under single catalytic conditions. The challenging unsymmetrical double annulations of both o-C-H bonds of arenes with two distinct alkynes is effectively demonstrated. Control experiments and deuterium scrambling findings are shown.


Peer review of the pesticide risk assessment of the active substance heptamaloxyloglucan.
The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, France, and co-rapporteur Member State, Spain, for the pesticide active substance heptamaloxyloglucan and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative use of heptamaloxyloglucan as a plant elicitor on grapevines for protection against frost damage (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are not identified.


Holographic x-ray image reconstruction through the application of differential and integral operators.
We introduce a noniterative image-reconstruction technique for coherent diffractive imaging. Through the application of differential and integral operators, an extended reference can be used to recover the complex-valued transmissivity of an object, in closed form, from a measurement of its far-field (Fraunhofer) diffraction intensity. We demonstrate the feasibility of this approach, using a reference of a pair of crossed wires and slits, through numerical simulations and a soft x-ray coherent diffractive imaging experiment.


Professional Stress and Burnout in U.S. Military Medical Personnel Deployed to Afghanistan.
Studies of medical staff members have consistently documented high levels of burnout compared to those in other professions. Although there are studies of burnout in military medical staff, there are gaps in understanding the experience of medical staff while they are deployed and few occupationally-related factors associated with decreased burnout have been identified in this population. To assess work-related variables accounting for burnout over and above rank, post-traumatic stress disorder (PTSD) symptoms, and professional stressors in the deployed environment. U.S. military medical staff members were surveyed in Afghanistan. The survey assessed burnout (emotional exhaustion and depersonalization), PTSD symptoms, perception of professional stressors, self-care behaviors, taking care of team members (team care), general leadership, and health-promoting leadership. Participants provided informed consent under a protocol approved by the institutional review board at Walter Reed Army Institute of Research, and coordinated through the Washington Headquarters Service and the Joint Casualty Care Research Team located in Afghanistan. A total of 344 individuals provided their consent (83.3%) and completed the survey. Correlations found significant positive relationships between perception of professional stressors and levels of burnout. Significant negative correlations were found between burnout and self-care, team care, general leadership, and health-promoting leadership. Regression analyses found self-care and team care accounted for less burnout even after controlling for rank, PTSD symptoms, and professional stressors. Health-promoting leadership accounted for less burnout even after controlling for these same covariates and general leadership as well. Although a cross-sectional survey, results provide three specific directions for reducing burnout in deployed medical staff. By emphasizing self-care, team care, and health-promoting leadership, policy makers, researchers, and leaders can address factors that influence burnout in this, and other occupational contexts. In addition, the constructs of team care and leadership offer novel contributions to the study of burnout in medical personnel.


Cardiovascular effects of green tea catechins: progress and promise.
Recently, there is a growing interest in the cardiovascular beneficial effects of green tea. Epidemiological and clinical studies have suggested that consumption of green tea is inversely associated with the risk of developing cardiovascular diseases. Catechins, the major flavonoid constituents of green tea, exert cardioprotective effects through diverse mechanisms that include reversal of endothelial dysfunctions, decreasing inflammatory biomarkers, and providing antioxidant, antiplatelet and antiproliferative effects. Moreover, dietary consumption of green tea catechins has beneficial effects on blood pressure and lipid parameters. This review will focus on discussing the latest research on the cardioprotective effects of green tea catechins and their underlying molecular mechanisms. Several recent patents pertinent to green tea and cardiovascular health will also be discussed. It is noteworthy that clinical studies involving green tea are fraught with multiple complexity and confounding factors. Therefore, a rigorous assessment of the effects of green tea catechins in well-controlled human trials will be required for better understanding of the effects of green tea in cardiovascular health.


A personal account of depressive illness and its antidepressant treatment.
Depression crept quietly over me as a shadow lengthens towards dusk. Probable contributory factors include familial predisposition, multiple bereavement, physical illness and being abused online. The first few days of antidepressant drug treatment were unsettling, but I responded steadily, the medication side effects proved tolerable, and my depressive and anxiety symptoms had remitted within 4 weeks. Insights from literature were helpful in recovery. I hope this experience of illness and treatment will enhance my clinical practice and contribute to discussions about depression and antidepressant medicines.


Nucleotide sequence analysis of a 21-kbp region of the genome of human herpesvirus-6 containing homologues of human cytomegalovirus major immediate-early and replication genes.
Human herpesvirus-6 (HHV-6) is a CD4+ T-lymphotropic herpesvirus that is a member of the betaherpesvirus subgroup. This laboratory has reported previously the results of large-scale sequence analyses of the HHV-6 genome and has identified putative immediate-early (IE) regulatory genes and associated transactivation functions. In this report I present the sequence analysis of a 21-kbp region of the genome of HHV-6 strain U1102 that is contiguous with the proximal region of the putative major IE (MIE) locus. Within this region (genomic positions 109-130 kbp) is a homologue of the human cytomegalovirus (HCMV) IE2 MIE gene (UL122), in addition to genes encoding probable virus DNA replication functions. The latter include components of the helicase-primase complex, corresponding to HCMV UL102 and UL105 gene products, and a homologue of the origin binding protein conserved among the alphaherpesviruses. Several genes unique to HHV-6 also have been identified within the sequenced locus. These findings will contribute to efforts to identify and functionally characterize the complete repertoire of HHV-6 transcriptional regulatory genes and will provide a basis for the further analysis of the molecular biology of this betaherpesvirus.


The clinical pattern of renal diseases in the nephrology in-patient unit of the Yaounde General Hospital in Cameroon: a five-year audit.
Kidney diseases are a growing worldwide problem and one of the major public health threats. We analyzed the spectrum of kidney diseases seen over a five-year period in the nephrology in-patient unit of the Yaounde general hospital. This was a retrospective analysis of 225 medical records of patients admitted from January 2005 to December 2009 in the unit with a discharge diagnosis of kidney and urinary tract diseases. The first hospitalization was considered for patients admitted several times for the same disease. Socio-demographic and clinical patient data were recorded. The patients mean age was 44.8±16 years with 135 (60%) males and 211 (93.8%) emergency admissions. All 139 (61.8%) patients with chronic kidney disease (CKD) had chronic renal failure. Acute kidney injury (AKI) (28%), nephrotic syndrome (7.6%), renal colic (1.3%) and acute pyelonephritis (1.3%) were other patterns observed. Chronic glomerulonephritis (25.9%), hypertension (22.3%) and diabetes (20.1%) were the main etiological factors of CKD. All AKI patients were in stage RIFLE-F. AKI was secondary to parenchymal (58.7%), functional (25.4%) and obstructive (15.9%) etiologies. Black water fever (36.4%), sepsis (22.7%), drugs (18.2%), eclampsia (13.6%) and herbal concoctions (9.1%) were the etiologies of acute tubular necrosis while enterocolitis (56.2%), heart failure (31.3%) and digestive hemorrhage (12.5%) were the etiologies of functional AKI. The clinical pattern of renal diseases is dominated by advanced CKD and AKI secondary to preventable causes. This study suggests a need for an array of actions including sensitization, continuous medical education and strengthening of the health system.


The Archean Nickel Famine Revisited.
Iron formations (IF) preserve a history of Precambrian oceanic elemental abundance that can be exploited to examine nutrient limitations on early biological productivity. However, in order for IF to be employed as paleomarine proxies, lumped-process distribution coefficients for the element of interest must be experimentally determined or assumed. This necessitates consideration of bulk ocean chemistry and which authigenic ferric iron minerals controlled the sorption reactions. It also requires an assessment of metal mobilization reactions that might have occurred in the water column during particle descent and during post-depositional burial. Here, we summarize recent developments pertaining to the interpretation and fidelity of the IF record in reconstructions of oceanic trace element evolution. Using an updated compilation, we reexamine and validate temporal trends previously reported for the nickel content in IF (see Konhauser et al., 2009 ). Finally, we reevaluate the consequences of methanogen Ni starvation in the context of evolving views of the Archean ocean-climate system and how the Ni famine may have ultimately facilitated the rise in atmospheric oxygen.


[Impact of living in the West Bank and the Gaza Strip on chronic disease among the Jewish population].
To assess chronic physical morbidity in the terror-prone Jewish population of the West Bank and the Gaza Strip (WBGS). We conducted a cross-sectional study based on electronic medical records. Included in the study were 24,551 members aged 26 years or older: 8,304 inhabitants of eleven Jewish settlements in the WBGS and 16,247 inhabitants of eleven settlements inside the 1967 borders of Israel. Main outcome measures were prevalence of selected chronic diseases. The age and gender adjusted prevalence of diabetes and hypertension was lower in the WBGS group (relative risk 0.85 (0.80-0.90, 95% CI) and 0.87 (0.78-0.97, 95% CI) respectively). The prevalence of the diagnosis of peptic disease and headache was higher in the WBGS group (relative risk 1.64 (1.33-2.00, 95% CI) and 1.18 (1.05-1.32, 95% CI) respectively). Complaints of headache and peptic disease were more common in communities under a continuous threat of terror; this may represent somatic response to stress and violence.


In-house-Prepared Semisolid Bolus for Esophageal Transit Scintigraphy in Normal Volunteers and its Comparison with Liquid Bolus.
Esophageal transit scintigraphy (ETS) is a useful tool for evaluating esophageal motility disorders, although conflicting results are seen due to lack of ideal bolus. Semisolid/solid boluses have shown superiority over liquid boluses, and the present study aims to establish the utility of in-house-prepared bolus in normal volunteers and its comparison with liquid bolus. Thirty-three healthy volunteers were selected for ETS with in-house-prepared semisolid bolus jelly containing 99mTc-sulfur colloid. Dynamic studies were acquired in anterior projection with single swallow for both supine and sitting positions. T90% esophageal emptying time (EET) was calculated for whole and three equally divided segments of esophagus and also done with liquid bolus on different day. The median value of EET for semisolid bolus for whole esophagus in sitting and supine positions was 11.7 s (interquartile range [IQR]: 8.0-16.7) and 17.7 s (IQR: 12.0-33.0). EET of liquid bolus for whole esophagus in sitting and supine positions was 9.3 s (IQR: 8.0-13.3) and 13.0 s (IQR: 9.7-25.0), respectively. Significantly different EET for whole esophagus and lower one-third esophagus between sitting and supine positions was seen for semisolid (whole esophagus;P = 0.003, lower one-third esophagus; P = 0.025) and liquid boluses (whole esophagus; P = 0.032, lower one-third esophagus; P = 0.016). Comparing EET using semisolid and liquid boluses, only lower one-third esophagus in supine position showed significant difference (P = 0.033). In-house-prepared semisolid radiolabeled jelly is inexpensive, easy to prepare with good radiolabeling. Condensed dynamic images from semisolid bolus were better, sharper, and reproducible in comparison to liquid bolus without fragmentation. This study standardized semisolid bolus and verified its suitability for clinical use.


TP53I13 promotes metastasis in glioma via macrophages, neutrophils, and fibroblasts and is a potential prognostic biomarker.
TP53I13 is a protein coding tumor suppression gene encoded by the tumor protein p53. Overexpression of TP53I13 impedes tumor cell proliferation. Nevertheless, TP53I13 role and expression in the emergence and progression of glioma (low-grade glioma and glioblastoma) are yet to be identified. Thus, we aim to use comprehensive bioinformatics analyses to investigate TP53I13 and its prognostic value in gliomas. Multiple databases were consulted to evaluate and assess the expression of TP53I13, such as the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GeneMANIA, and Gene Expression Profiling Interactive. TP53I13 expression was further explored using immunohistochemistry (IHC) and multiplex immunohistochemistry (mIHC). Through Gene Set Enrichment Analysis (GSEA), the biological functions of TP53I13 and metastatic processes associated with it were studied. The expression of TP53I13 was higher in tumor samples compared to normal samples. In samples retrieved from the TCGA and CGGA databases, high TP53I13 expression was associated with poor survival outcomes. The analysis of multivariate Cox showed that TP53I13 might be an independent prognostic marker of glioma. It was also found that increased expression of TP53I13 was significantly correlated with PRS type, status, 1p/19q codeletion status, IDH mutation status, chemotherapy, age, and tumor grade. According to CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcript), the expression of TP53I13 correlates with macrophages, neutrophils, and dendritic cells. GSEA shows a close correlation between TP53I13 and p53 signaling pathways, DNA replication, and the pentose phosphate pathway. Our results reveal a close correlation between TP53I13 and gliomas. Further, TP53I13 expression could affect the survival outcomes in glioma patients. In addition, TP53I13 was an independent marker that was crucial in regulating the infiltration of immune cells into tumors. As a result of these findings, TP53I13 might represent a new biomarker of immune infiltration and prognosis in patients with gliomas.


Tetrabromobisphenol A induces cellular damages in pancreatic β-cells in vitro.
Tetrabromobisphenol A (TBBPA) is a well-known organobrominated flame retardant. TBBPA has been detected in the environment. The roles played by environmental pollutants in increasing the prevalence of metabolic syndrome are attracting increasing concern. In the present work, we investigated the effects of TBBPA on rat pancreatic β-cells (the RIN-m5F cell line). RIN-m5F cells were incubated with different concentrations of TBBPA for 48 h, and cell viability and the extent of apoptosis were determined. We also measured the levels of inflammatory cytokines, reactive oxygen species (ROS), mitochondrial adenosine triphosphate (ATP), and cardiolipin, as well as the extent of cytochrome c release from mitochondria. TBBPA reduced the ATP level, induced cardiolipin peroxidation and cytochrome c release, and triggered apoptotic cell death. Moreover, TBBPA increased the levels of inflammatory cytokines (TNF-α and IL-1β), nitric oxide, intracellular ROS, and mitochondrial superoxide. Together, our results indicate that TBBPA damages pancreatic β-cells by triggering mitochondrial dysfunction and inducing apoptosis.


Impact of drug therapy on brachioradial pruritus.
Few studies have described therapeutic options in brachioradial pruritus. We describe a cross-sectional study of brachioradial pruritus patients treated in an outpatient unit. We reviewed medical records and interviewed brachioradial pruritus patients without indication for decompressive surgery, in order to access the perceptions of intensity of pruritus prior to treatment and response to therapy. We found that antidepressants and anticonvulsants were the most frequently prescribed drugs. Best reductions in pruritus were associated with its highest intensities prior to treatment, and with longer periods of therapy.


Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) colonization as a risk factor for developing ESBL infections in pediatric cardiac surgery patients: "retrospective cohort study".
Children with cardiac defects need many hospitalizations and repetitive antibiotic therapies, with an increasing risk of colonization with multidrug-resistant bacteria (MDRB) such as extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) Post-operative infections with these bacteria in paediatric cardiac surgery are life threatening. This article aims to study the prevalence of ESBL colonization among paediatric cardiac surgery patients, and to compare occurrence of post-operative infections with and without ESBL colonization. We also aim to study the correlation between the onset of postoperative infection and other parameters such as age, length of stay and preoperative antibiotic therapy. A retrospective cohort study included paediatric cardiac surgery patients in Cheikh Zaid hospital in Rabat, Morocco, between the 1st of January 2011 and 31 December 2014. A screening for ESBL colonization was requested for children who had a risk factor (previous hospitalization and/or taking antibiotics) at admission. Swabs were collected from three sites (throat, nose and anus). Two groups were compared - patients colonized and not colonized with ESBLs. Statistical analysis was performed using R software. ESBL colonization screening was performed in 111 patients. Positive colonization was detected in 17 cases (15%). Klebsiella pneumoniae (KP): 9 (53%) was the most frequently isolated species. Among the 17 patients, 23.5% (4/17) developed a postoperative infection due to ESBLs versus only one patient without colonization (1%). There was a statically significant difference in terms of occurrence of postoperative infection between the two groups (p = 0.001). Relative risk of developing a postoperative infection with positive colonization was 22 (95% CI, 8.37-58.5). The analysis of colonization with multidrug-resistant bacteria and the prevention of nosocomial infections appear to be important challenges for paediatric cardiac surgery. Systematic screening of ESBL colonization for cardiac surgery could have a significant contribution, on one hand to guide prophylactic antibiotic therapy of patients, and on the other, to prevent spread of those infections.


Papillary fibroelastoma of the cardiac valves: a rare cause of embolic stroke.
Papillary fibroelastomas are rare, primary, benign cardiac tumours most frequently located in the heart valves. They are a potential cause of systemic emboli, stroke, myocardial infarction and sudden death. We present two cases of papillary fibroelastomas located in the mitral and aortic valves of patients who had suffered multiple strokes. The fibroelastomas were diagnosed using transoesophageal echocardiography and the patients were treated surgically, with broad excision of the tumours and preservation of the valves. The echocardiographic and microscopic characteristics of the fibroelastomas are analysed and methods for their differential diagnosis from other cardiac tumours are discussed in the context of the available literature.


Structural investigation and application of Tween 80-choline chloride self-assemblies as osmotic agent for water desalination.
Forward osmosis (FO) process has been extensively considered as a potential technology that could minimize the problems of traditional water desalination processes. Finding an appropriate osmotic agent is an important concern in the FO process. For the first time, a nonionic surfactant-based draw solution was introduced using self-assemblies of Tween 80 and choline chloride. The addition of choline chloride to Tween 80 led to micelles formation with an average diameter of 11.03 nm. The 1H NMR spectra exhibited that all groups of Tween 80 were interacted with choline chloride by hydrogen bond and Van der Waals' force. The influence of adding choline chloride to Tween 80 and the micellization on its osmotic activity was investigated. Despite the less activity of single components, the average water flux of 14.29 L m‒2 h‒1 was obtained using 0.15 M of Tween 80-choline chloride self-assembly as draw solution in the FO process with DI water feed solution. Moreover, various concentrations of NaCl aqueous solutions were examined as feed solution. This report proposed a possible preparation of nonionic surfactant-based draw solutions using choline chloride additive with enhanced osmotic activities that can establish an innovative field of study in water desalination by the FO process.


Cholesteryl esters associated with acyl-CoA:cholesterol acyltransferase predict coronary artery disease in patients with symptoms of acute coronary syndrome.
Identifying the likelihood of a patient having coronary artery disease (CAD) at the time of emergency department (ED) presentation with chest pain could reduce the need for stress testing or coronary imaging after myocardial infarction (MI) has been excluded. The authors aimed to determine if a novel cardiac biomarker consisting of plasma cholesteryl ester (CE) levels typically derived from the activity of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT2) are predictive of CAD in a clinical model. A single-center prospective cohort design enrolled participants with symptoms of acute coronary syndrome (ACS) undergoing coronary computed tomography angiography (CCTA) or invasive angiography. Plasma samples were analyzed for CE composition with mass spectrometry. The primary endpoint was any CAD determined at angiography. Multivariable logistic regression analyses were used to estimate the relationship between the sum of the plasma concentrations from cholesteryl palmitoleate (16:1) and cholesteryl oleate (18:1) (defined as ACAT2-CE) and the presence of CAD. The added value of ACAT2-CE to the model was analyzed comparing the C-statistics and integrated discrimination improvement (IDI). The study cohort was composed of 113 participants with a mean (± standard deviation [SD]) age of 49 (±11.7) years, 59% had CAD at angiography, and 23% had an MI within 30 days. The median (interquartile range [IQR]) plasma concentration of ACAT2-CE was 938 μmol/L (IQR = 758 to 1,099 μmol/L) in patients with CAD and 824 μmol/L (IQR = 683 to 998 μmol/L) in patients without CAD (p = 0.03). When considered with age, sex, and the number of conventional CAD risk factors, ACAT2-CE levels were associated with a 6.5% increased odds of having CAD per 10 μmol/L increase in concentration. The addition of ACAT2-CE significantly improved the C-statistic (0.89 vs. 0.95, p = 0.0035) and IDI (0.15, p < 0.001) compared to the reduced model. In the subgroup of low-risk observation unit patients, the CE model had superior discrimination compared to the Diamond-Forrester classification (IDI = 0.403, p < 0.001). Plasma levels of ACAT2-CE have strong potential to predict a patient's likelihood of having CAD when considered in a clinical model but not when used alone. In turn, a clinical model containing ACAT2-CE could reduce the need for cardiac imaging after the exclusion of MI.


Simplification of electrospray mass spectra of Polysorbate 80 via cation transfer to carborane anions.
Mass spectrometric analysis of polymer mixtures via electrospray ionization can be complicated due the presence of multiple ion types, multiple charge states and multiple oligomeric distributions that complicate the detection and identification of mixture components. Polysorbate 80 (commercially known as Tween(®) 80) provides an example of this type, where the presence of polyoxyethylene sorbitan monooleate (PSO) byproducts gives rise to overlapping polymer distributions. It is desirable to simplify the spectrum in order to identify each component of what is inherently a complex mixture of fatty esters bound to different head groups. In this work, we show that gas-phase ion/ion reactions with carborane anions allow for the charge reduction of Tween(®) 80 peaks by selectively removing metal adducts bound to the synthetic polymer. The resulting singly charged spectrum reduces overlapping distributions and thus simplifies the identification of the components found in a Tween(®) 80 sample. The overall approach described here would likely lead to similar benefits in the analysis of other polymers that tend to ionize via metal ion adduction. Copyright © 2016 John Wiley & Sons, Ltd.


[EFFICACY OF SCHEDULED INTRAVENOUS OR ORAL ACETAMINOPHEN ADMINISTRATION AFTER ROBOTIC-ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY].
(Purpose) To determine the efficacy of scheduled intravenous or oral acetaminophen administration after robotic-assisted laparoscopic radical prostatectomy (RARP) in our hospital. (Subjects and methods) We retrospectively analyzed 173 patients who underwent RARP at our hospital between April 2019 and December 2020. The patients were divided into three groups (A, B, and C) according to the use of postoperative analgesia. Group A patients were administered acetaminophen only when needed. Group B patients were administered intravenous acetaminophen every 6 h from the day of surgery to postoperative day 2. Group C patients were prescribed oral acetaminophen from 3 to 7 days postoperatively in addition to being administered intravenous acetaminophen (similar to group B). Multivariate analysis was performed to determine whether scheduled intravenous or oral acetaminophen administration reduced unscheduled analgesic use. (Results) There were 110, 33, and 30 patients in groups A, B, and C, respectively. Significant differences in lymph node dissection rates were observed between groups A and B (70.9% vs 36.4%; P=0.001) and groups A and C (70.9% vs 33.3%; P< 0.001); furthermore, significant differences in the frequency of preoperative androgen blockade therapy were observed between groups A and C (20% vs 3.3%; P=0.029). Logistic regression analysis showed that only scheduled intravenous and oral administration of acetaminophen on postoperative days 0 to 2 was an independent factor for postoperative pain (group A vs group B: OR=0.127; 0.046-0.355; P< 0.001 and group A vs group C: OR=0.133; 0.046-0.390; P< 0.001). On postoperative days 3 to 7, there was no significant difference in the unscheduled use of analgesics between groups A and B. Only 1 of the 30 group C patients received unscheduled analgesia. (Conclusions) Scheduled intravenous or oral administration of acetaminophen may reduce unscheduled analgesic use after RARP.


Nursing education and implications for left ventricular assist device destination therapy.
The HeartMate VE Left Ventricular Assist Device (vented electric abdominally positioned pulsatile blood pump; Thoratec Corp., Pleasanton, CA), approved as a permanent support, or destination therapy, by the US Food and Drug Administration in 2002 and Medicare in 2003, is now a potential therapy for numerous patients. Postimplantation nursing care is crucial to the success of left ventricular support device therapy and long-term recipient outcome. Nurses also contribute to cost containment, making this a viable treatment for the facility and the patient. Consequently, nurses must be educated about left ventricular assist device concepts and challenges, the benefits of device placement, intensive care unit and postintensive care unit daily care requirements, and outpatient preparation. This knowledge will enable nurses to provide necessary care and to educate recipients, families, and community health care providers on how to give appropriate posthospital care.


Exploratory Study of the Current Status of the Rights and Welfare of Ghanaian Women: Taking Stock and Mapping Gaps for New Actions.
This paper assesses the progress Ghanaian women have made in terms of rights and welfare in the last three decades or more when democratic politics was introduced in the country. It examines the legislative and policy environment that exist to combat all forms of discrimination against women and assesses women"s rights and welfare on a number of indicators: women"s rights to life, marriage, participation and representation in politics, access to justice, right to education, reproductive health, and sustainable development. The study revealed that there is a robust legislative and policy environment for pursuing women"s issue in Ghana. There are constitutional and legal provisions and state institutions as well as a number of NGOs acting as duty bearers to combat all forms of discrimination against women. However, the evidence from these indicators, suggests that there is a gap between the legal and policy environment on the one hand and the rights and welfare of women on the other hand. Women in Ghana are still threatened by early and forced marriages, deficit in political participation, limited access to health services, and harmful traditional norms and cultural practices. We conclude that duty bearers such as the policymakers and other stakeholders need to scale-up their activities and programmes that advance the rights and social well-being of Ghanaian women.


Assessment of the potential impact of dose rounding parenteral chemotherapy agents on cost savings and drug waste minimization.
Background Fiscally responsible utilization of anticancer treatments is necessary to combat their continually increasing cost. Dose rounding is one strategy that has been explored to minimize cost and waste without losing clinical effectiveness. Objectives To determine if dose rounding chemotherapy agents is a feasible cost-containment strategy at an institution with a small oncology clinic. Methods This study is a retrospective chart review of all body surface area dosed parenteral chemotherapy prescribed for an oncological diagnosis over a 12-month period (1 October 2015-30 September 2016). Chemotherapy doses were rounded down by 5%. Doses for patients with metastatic diagnoses were also rounded down by 10%. Rounded doses were evaluated for a potential decrease in vial size. Cost was represented as dollar/milligram of drug. Potential for drug waste minimization was also calculated. Results There were 877 total doses of chemotherapy administered to 70 unique patients throughout the 12-month duration of the study. When doses were rounded down by 5%, 140 doses qualified for a decrease in vial number. The potential for cost savings was $22,849 with 83,802 mg saved from wastage. A 10% decrease resulted in the reduction of vials for 248 doses, a potential savings of $30,911 with 129,011 milligrams saved. The targeted agents accounted for the majority of savings, $16,920 of the $22,849 with 5% rounding and $20,086 of the $30,911 with 10% rounding. Conclusion Dose rounding has the potential to be an effective cost-containment strategy in low volume oncology clinics.


Design and use of multiplexed chemostat arrays.
Chemostats are continuous culture systems in which cells are grown in a tightly controlled, chemically constant environment where culture density is constrained by limiting specific nutrients.(1,2) Data from chemostats are highly reproducible for the measurement of quantitative phenotypes as they provide a constant growth rate and environment at steady state. For these reasons, chemostats have become useful tools for fine-scale characterization of physiology through analysis of gene expression(3-6) and other characteristics of cultures at steady-state equilibrium.(7) Long-term experiments in chemostats can highlight specific trajectories that microbial populations adopt during adaptive evolution in a controlled environment. In fact, chemostats have been used for experimental evolution since their invention.(8) A common result in evolution experiments is for each biological replicate to acquire a unique repertoire of mutations.(9-13) This diversity suggests that there is much left to be discovered by performing evolution experiments with far greater throughput. We present here the design and operation of a relatively simple, low cost array of miniature chemostats-or ministats-and validate their use in determination of physiology and in evolution experiments with yeast. This approach entails growth of tens of chemostats run off a single multiplexed peristaltic pump. The cultures are maintained at a 20 ml working volume, which is practical for a variety of applications. It is our hope that increasing throughput, decreasing expense, and providing detailed building and operation instructions may also motivate research and industrial application of this design as a general platform for functionally characterizing large numbers of strains, species, and growth parameters, as well as genetic or drug libraries.


Evaluation of the sterility of thermodilution room-temperature injectate preparations.
This study assessed the bacteriologic safety of room-temperature injectate used for cardiac output measurement in a surgical ICU, and compared its cost/benefit relationship to that of prefilled packaged syringes and a closed-loop injectate system. Ninety-five samples of injectate were obtained at four time intervals from staff-prepared syringes, and cultured for microbiologic growth. About 29% (27/95) of samples yielded bacterial growth, ranging from two colony-forming units to those too numerous to count. All positive samples contained skin flora, including coagulase-negative staphylococci and coryneforms. Additionally, five plates contained colonies of Gram-negative bacteria. Extended storage time increased the risk of contamination: 16.2% were contaminated within the first 24 h, whereas 45% were contaminated when stored for more than 72 h. Switching to a closed injectate system significantly (p less than .001) decreased the incidence of contamination by 1.2%, and also allowed a cost savings of $1.52/patient.


Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells.
In pursuit of fast bioorthogonal reactions, reactive moieties have been increasingly employed for selective labeling of biomolecules in living systems, posing a challenge in attaining reactivity without sacrificing selectivity. To address this challenge, here we report a bioinspired strategy in which molecular shape controls the selectivity of a transient, highly reactive nitrile imine dipole. By tuning the shape of structural pendants attached to the ortho position of the N-aryl ring of diaryltetrazoles-precursors of nitrile imines, we discovered a sterically shielded nitrile imine that favors the 1,3-dipolar cycloaddition over the competing nucleophilic addition. The photogenerated nitrile imine exhibits an extraordinarily long half-life of 102 s in aqueous medium, owing to its unique molecular shape that hinders the approach of a nucleophile as shown by DFT calculations. The utility of this sterically shielded nitrile imine in rapid (∼1 min) bioorthogonal labeling of glucagon receptor in live mammalian cells was demonstrated.


Long-term treatment of duodenal ulcer.
Eighty per cent, or more, of duodenal and gastric ulcers which have healed after a course of treatment with drugs relapse when therapy is discontinued. Only gastric operations or continuous maintenance treatment with H2 receptor antagonists have so far been shown to produce sustained remission in the majority of patients. Maintenance treatment with drugs is safer than gastric surgery, since the adverse effects of medical therapy are uncommon, mild and reversible while the after-effects of surgery are common and may be severe and irreversible. The maintenance treatment of ulcer patients must be continued for many years and may, perhaps, have to be life-long.


Plasma fibrinogen is associated with cognitive decline and risk for dementia in patients with mild cognitive impairment.
This study was aimed to investigate the relationship between plasma fibrinogen level and risk for cognitive decline and dementia in patients with mild cognitive impairment (MCI). Elderly patients with suspected cognitive impairment were screened and evaluated periodically. One hundred and eighty-five patients who met the criteria for MCI were enrolled. Blood coagulation functions and plasma fibrinogen levels were measured at baseline. Hyperfibrinogenaemia was defined as plasma fibrinogen > or =3.0 g/l. Global cognitive function was assessed serially with Mini-Mental State Examination (MMSE). The enrolled patients were followed for 2 years to observe if dementia was developed. There were 185 patients diagnosed as MCI, of which 17 (9.2%) deceased, 15 (8.1%) lost to follow-up, and 68 (36.8%) developed dementia during follow-up. Mean of MMSE score of the enrolled patients declined significantly during follow-up (22.0 +/- 3.0 vs. 18.1 +/- 5.8, p < 0.001). Patients with hyperfibrinogenaemia at baseline had greater MMSE decrement during follow-up than patients with normal fibrinogen level (-5.4 +/- 5.4 vs. -3.5 +/- 4.5, p < 0.05). Linear regression indicated that plasma fibrinogen level was associated with cognitive decline (R = 0.17, p < 0.05). Patients with hyperfibrinogenaemia had an increased risk for dementia and vascular dementia compared with patients with normal level of plasma fibrinogen (log rank test, p < 0.05). There was a trend that hyperfibrinogenaemia also increased risk for dementia of Alzheimer's type (p = 0.061). It can be concluded that plasma fibrinogen level may be associated with cognitive decline, and hyperfibrinogenaemia may increase risk for dementia in patients with MCI.


Symmetry-based recoupling in double-rotation NMR spectroscopy.
In this contribution, we extend the theory of symmetry-based pulse sequences of types CN(n) (nu) and RN(n) (nu) in magic-angle-spinning nuclear resonance spectroscopy [M. H. Levitt, in Encyclopedia of Nuclear Magnetic Resonance, edited by D. M. Grant and R. K. Harris (Wiley, Chichester, 2002), Vol. 9]. to the case of rotating the sample simultaneously around two different angles with respect to the external magnetic field (double-rotation). We consider the case of spin-1/2 nuclei in general and the case of half-integer quadrupolar nuclei that are subjected to weak radio frequency pulses operating selectively on the central-transition polarizations. The transformation properties of the homonuclear dipolar interactions and J-couplings under central-transition-selective spin rotations are presented. We show that the pulse sequence R2(2) (1)R2(2) (-1) originally developed for homonuclear dipolar recoupling of half-integer quadrupolar nuclei under magic-angle-spinning conditions [M. Eden, D. Zhou, and J. Yu, Chem. Phys. Lett. 431, 397 (2006)] may be used for the same purpose in the case of double rotation, if the radio frequency pulses are synchronized with the outer rotation of the sample. We apply this sequence, sandwiched by central-transition selective 90 degrees pulses, to excite double-quantum coherences in homonuclear spin systems consisting of (23)Na and (27)Al nuclei.


The Protective Effects of Melatonin Against LPS-Induced Septic Myocardial Injury: A Potential Role of AMPK-Mediated Autophagy.
Aim: Melatonin is an indolamine secreted by the pineal gland, as well as most of the organs and tissues. In addition to regulating circadian biology, studies have confirmed the multiple pharmacological effects of melatonin. Melatonin provides a strong defense against septic myocardial injury. However, the underlying mechanism has not been fully described. In this study, we investigated the protective effects of melatonin against lipopolysaccharide (LPS)-induced myocardial injury as well as the mechanisms involved. Methods: Mice were intraperitoneally injected with LPS to induce a septic myocardial injury model or an LPS shock model, depending on the dose of LPS. Melatonin was given (20 mg/kg/day, via intraperitoneal injection) for a week prior to LPS insult. 6 h after LPS injection, echocardiographic analysis, TUNEL staining, transmission electron microscopy (TEM), western blot, quantitative real-time PCR and ELISA were used to investigate the protective effects of melatonin against LPS induced myocardial injury. AMPK inhibitor, autophagy activator and inhibitor, siRNAs were used for further validation. Results: Survival test showed that melatonin significantly increased the survival rate after LPS-induced shock. In the sepsis model, melatonin markedly ameliorated myocardial dysfunction, decreased the release of inflammatory cytokines, activated AMP-activated protein kinase (AMPK), improved mitochondrial function, and activated autophagy. To confirm whether the protection of melatonin was mediated by AMPK and autophagy, Compound C, an AMPK inhibitor; 3-MA, an autophagy inhibitor; and Rapamycin (Rapa), an autophagy activator, were used in this study. AMPK inhibition down-regulated autophagy, abolished protection of melatonin, as indicated by significantly decreased cardiac function, increased inflammation and damaged mitochondrial function. Furthermore, autophagy inhibition by 3-MA significantly impaired the protective effects of melatonin, whereas autophagy activation by Rapa reversed LPS + Compound C induced myocardial injury. In addition, in vitro studies further confirmed the protection of melatonin against LPS-induced myocardial injury and the mechanisms involving AMPK-mediated autophagy signaling. Conclusions: In summary, our results demonstrated that melatonin protects against LPS-induced septic myocardial injury by activating AMPK mediated autophagy pathway.


Middle turbinate primary mucocele in a child masquerading as a nasal tumour.
Middle turbinate primary mucocele in a child masquerading as a nasal tumour. Nasal obstruction in children is a very common complaint in daily ENT consultations. The common cold, rhinosinusitis, allergic rhinitis, hypertrophy and inflammation of the adenoid pad are very common causes of nasal obstruction, but there are numerous other causes for which the clinician must be aware. The authors report a very unusual case of a primary mucocele of the middle turbinate of a 7-year-old girl masquerading as a nasal tumour. The mucocele was successfully marsupialized surgically using an endonasal endoscopic approach. The authors report the case, imaging, and review the pertinent literature. Clinicians must be aware of less common aetiologies of nasal obstruction in order to orientate the diagnostic work-up and to propose adequate management.


Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient.
Nesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM). Demographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples. The results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1. These findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.


Standardization of transfusion practice in organ donors using the Digital Intern, an electronic decision support algorithm.
Prospective clinical trials support restrictive thresholds for red blood cell (RBC) transfusion. Nonsurvivable donors are a major source of organs for transplantation. The Digital Intern (DI) is a computer algorithm to standardize donor care that includes a more restrictive transfusion threshold. The impact of standardized and restrictive RBC transfusion in organ donors, as determined by the DI, has not been reported. We conducted a retrospective cohort study to compare the transfusion practice of the DI (n = 100) to a historic group of physician-managed donors (n = 90). Transfusion rates, the number of units transfused, and pretransfusion laboratory values were compared between groups. The variability of these parameters was also compared between groups. Finally, the number of transplanted organs per donor in each group was compared. The mean time as a donor was 25.9 ± 15.2 hours and was not different between the groups. In the DI group 19% were transfused compared to 26% in the control group (p = 0.3). The number of units transfused was less in the DI group (1 unit vs. 2 units per transfusion, p = 0.03) and the pretransfusion hematocrit was lower in the DI group (23% vs. 27%, p = 0.01). The variability in the latter two parameters was significantly lower in the DI group. The number of transplanted organs per donor was similar in both groups (3.24 [DI] vs. 3.03 [control], p = 0.37). The DI provides a more standardization transfusion practice in organ donors and reduces blood use without compromising transplantable organs.


Historical perspectives.
The phenomenon of yawning is just as intriguing and fascinating as sleep, yet understanding of its causes and consequences has defied the human mind for centuries. Hippocrates, Sennert, Boerhaave and de Gorter each advanced a theory in his time. From the release of tainted humor to the awakening of animal spirits and improved brain oxygenation, the metaphors that developed from these theories are all characterized by their popular success, which endured until the time of J.M. Charcot and even into our own day. However, starting in the early 19th century, a neuromuscular theory developed from the experimental physiology of Broussais and Flourens, which Dumpert (working in Germany after World War I) explained in detail. Experimental ethology and pharmacology in the 20th century brought the neuromediators and subcortical structures involved in yawning and pandiculation to light. Phylogenetically and ontogenetically primitive, these motor behaviors have been remarkably well preserved during evolution and are nearly universal in vertebrates. They are closer to an emotional stereotypy than to a reflex. Originating in the diencephalon, they appear to exteriorize homeostatic processes in the systems controlling arousal, hunger and sexuality.


Effect of platelet depletion and inhibition of platelet cyclooxygenase on C5a-mediated myocardial ischemia.
Activation of the complement cascade is involved in the myocardial injury resulting from transient ischemia and reperfusion. We previously showed that the complement anaphylatoxin C5a causes myocardial ischemia in vivo, mediated in part via thromboxane (Tx) A2. In the present study, we assess the role of platelets in the C5a-induced myocardial ischemia and Tx release. The left anterior descending coronary artery of anesthetized pigs was perfused with arterial blood at constant pressure and measured flow (coronary blood flow). Segment function (percent segment shortening) was measured with sonomicrometry, and regional coronary venous blood was sampled and assayed for TxB2 (by radioimmunoassay). We found that the C5a-induced decrease in coronary blood flow and percent segment shortening and the release of Tx were indistinguishable whether the left anterior descending coronary artery bed was perfused with normal arterial blood, with arterial blood obtained from animals depleted of platelets (cyclophosphamide, n = 6), or with arterial blood from aspirin-treated animals (n = 9) in which the platelets were unable to produce Tx. These data demonstrate that platelet-derived Tx does not contribute to the C5a-induced myocardial ischemia and Tx release in this model and that these cells do not play an integral role in this phenomenon.


Stability domains for time-delay feedback control with latency.
We generalize a known analytical method for determining the stability of periodic orbits controlled by time-delay feedback methods when latencies associated with the generation and injection of the feedback signal cannot be ignored. We discuss the case of extended time-delay autosynchronization and show that nontrivial qualitative features of the domain of control observed in experiments can be explained by taking into account the effects of both the unstable eigenmode and a single stable eigenmode in the Floquet theory.


Electromagnetic interference of automatic implantable cardioverter defibrillator and HeartWare left ventricular assist device.
The use of continuous-flow left ventricular assist devices (LVAD) have markedly improved outcomes in patients with advanced heart failure (HF). The HeartWare LVAD is a miniaturized centrifugal pump implanted within the pericardial space. Implantable cardioverter-defibrillators (ICDs) are susceptible to oversensing of extracardiac signals (electromagnetic interference [EMI]). We report two cases of EMI in patients that received a HeartWare LVAD as destination therapy for advanced HF. The patients were 75 and 78 years old, both with severe ischemic dilated cardiomyopathy (ejection fraction < 0.20) and New York Heart Association class 4 heart failure. Both patients had a St. Jude Medical Unify ICD with a 7 Fr dual coil St. Jude Medical Durata ICD lead. In both patients, the lead location was in the right ventricular apex with an inferior orientation. Both patients experienced immediate ICD therapies after LVAD placement, requiring the tachytherapies to be disabled. ICD programming changes to increase sensitivity and the detection windows were ineffective. Both patients underwent ICD system revision. In one patient, the existing lead was moved to an anteroseptal location that stopped the EMI. In the other patient, the ICD system was changed to allow a separate right ventricular sensing lead in an anteroseptal location and a dual coil ICD lead placed in an apical location, a strategy used to obtain an acceptable defibrillation threshold. The patients have had no subsequent EMI detected on clinical and remote monitoring. Patients with a right ventricular apical ICD lead placement that undergo placement of a HeartWare LVAD are susceptible to EMI and inappropriate ICD therapies. These cases suggest the primary mechanism is proximity of the ICD lead to the device and as such relocation to an anteroseptal location can overcome the problem. These data suggest that all patients that receive a HeartWare LVAD with an ICD should have the device carefully checked at maximum LVAD output to determine if EMI may be present. ASAIO Journal 2013;59:136-139. Key Words: left ventricular assist device, electromagnetic interference, improper ICD shocks, end-stage heart failure.


Fast Hadamard transforms for compressive sensing of joint systems: measurement of a 3.2 million-dimensional bi-photon probability distribution.
We demonstrate how to efficiently implement extremely high-dimensional compressive imaging of a bi-photon probability distribution. Our method uses fast-Hadamard-transform Kronecker-based compressive sensing to acquire the joint space distribution. We list, in detail, the operations necessary to enable fast-transform-based matrix-vector operations in the joint space to reconstruct a 16.8 million-dimensional image in less than 10 minutes. Within a subspace of that image exists a 3.2 million-dimensional bi-photon probability distribution. In addition, we demonstrate how the marginal distributions can aid in the accuracy of joint space distribution reconstructions.


[Psychosocial dwarfism--a rare form of growth disorder].
Psychosocial dwarfism is a syndrome caused by emotional deprivation (maternal deprivation), characterized by symptoms of delayed motor and intellectual development, abnormal eating and drinking habits, enuresis and encopresis, aggressiveness and a pathological family structure. Diagnosis of psychosocial dwarfism is easy if the case history is carefully elicited and the growth hormone level is determined within the first few days following change in environment (e.g. hospitalization). Difficulty in reaching the correct diagnosis or misdiagnosis can occur if the symptomatology is not studied in its entirety. Diagnosis at the earliest possible stage is very important for the further development of the child, since behavioural disturbances and growth retardation are reversible with environmental change. This is demonstrated by the presentation of the case history of a 6 year-old boy--the third case reported in the German literature.


Chronic nerve root entrapment: compression and degeneration.
Electrode mounts are being developed to improve electrical stimulation and recording. Some are tight-fitting, or even re-shape the nervous structure they interact with, for a more selective, fascicular, access. If these are to be successfully used chronically with human nerve roots, we need to know more about the possible damage caused by the long-term entrapment and possible compression of the roots following electrode implantation. As there are, to date, no such data published, this paper presents a review of the relevant literature on alternative causes of nerve root compression, and a discussion of the degeneration mechanisms observed. A chronic compression below 40 mmHg would not compromise the functionality of the root as far as electrical stimulation and recording applications are concerned. Additionally, any temporary increase in pressure, due for example to post-operative swelling, should be limited to 20 mmHg below the patient's mean arterial pressure, with a maximum of 100 mmHg. Connective tissue growth may cause a slower, but sustained, pressure increase. Therefore, mounts large enough to accommodate the root initially without compressing it, or compliant, elastic, mounts, that may stretch to free a larger cross-sectional area in the weeks after implantation, are recommended.


A comparison of extraluminal and intraluminal use of the Uniblocker in left thoracic surgery: A CONSORT-compliant article.
The aim of this study was to assess the feasibility and safety issues concerning extraluminal use of the Uniblocker for one-lung ventilation (OLV) in the left thoracic surgery. Forty patients undergoing elective left thoracic surgery were included in this study, and all patients were randomly allocated to extraluminal use of Uniblocker group (E group, n = 20) or intraluminal use of Uniblocker group (I group, n = 20). Time for intubation, time for verification of the correct position of Uniblocker, incidence of Uniblocker displacement, index of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, bronchial damage after OLV, sore throat, and hoarseness postoperative were recorded. The time for positioning Uniblocker was 112.6 ± 31.2 seconds in intraluminal use group, whereas the time for positioning Uniblocker was significantly shorter in extraluminal use group (63.4 ± 15.8 seconds). The incidence of main bronchial injury, the time of intubation, the incidence of Uniblocker malposition after initial placement, the time of OLV, the degree of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, the incidence of sore throat and hoarseness postoperative have no statistical significance (P > .05). Extraluminal use of the Uniblocker was proved to be a more rapid and more accurate method than conventional intraluminal use of the Uniblocker for OLV in left thoracic surgery.


Pyomyositis in childhood-systemic lupus erythematosus.
Pyomyositis is a pyogenic infection of skeletal muscle that arises from hematogenous spread and usually presents with localized abscess. This muscle infection has been rarely reported in adult-onset systemic lupus erythematous and, to the best of our knowledge, has not been diagnosed in pediatric lupus population. Among our childhood-onset systemic lupus erythematous population, including 289 patients, one presented pyomyositis. This patient was diagnosed with childhood-onset systemic lupus erythematous at the age of 10 years-old. After six years, while being treated with prednisone, azathioprine and hydroxychloroquine, she was hospitalized due to a 30-day history of insidious pain in the left thigh and no apparent trauma or fever were reported. Her physical examination showed muscle tenderness and woody induration. Laboratory tests revealed anemia, increased acute phase reactants and normal muscle enzymes. Computer tomography of the left thigh showed collection on the middle third of the vastus intermedius, suggesting purulent stage of pyomyositis. Treatment with broad-spectrum antibiotic was initiated, leading to a complete clinical resolution. In conclusion, we described the first case of pyomyositis during childhood in pediatric lupus population. This report reinforces that the presence of localized muscle pain in immunocompromised patients, even without elevation of muscle enzymes, should raise the suspicion of pyomyositis. A prompt antibiotic therapy is strongly recommended.


Glaucomatous-Type Optic Discs in High Myopia.
To assess the prevalence of glaucoma in patients with high myopia defined as myopic refractive error of >-8 diopters or axial length ≥26.5 mm. The hospital-based observational study included 172 patients (336 eyes) with a mean age of 61.9±12.3 years and mean axial length of 30.1±2.3 mm (range: 24.7-39.1mm). Glaucomatous-type optic discs were defined by glaucomatous optic disc appearance. Glaucoma was defined by glaucomatous optic disc appearance and glaucomatous Goldmann visual field defects not corresponding with myopic macular changes. Larger disc area (mean: 3.18±1.94 mm2) was associated with longer axial length (P<0.001; standardized correlation coefficient: 0.45). Glaucoma was detected in 94 (28%; 95% Confidence intervals: 23%, 33%) eyes. In multivariate analysis, glaucoma prevalence was 3.2 times higher (P<0.001) in megalodiscs (>3.79 mm2) than in normal-sized discs or small discs (<1.51 mm2) after adjusting for older age. Axial length was not significantly (P = 0.38) associated with glaucoma prevalence in that model. Glaucoma prevalence increased by a factor of 1.39 for each increase in optic disc area by one mm2. Again, axial length was not significantly (P = 0.38) associated with glaucoma prevalence when added to this multivariate model. Within highly myopic individuals, glaucoma prevalence increased with larger optic disc size beyond a disc area of 3.8 mm2. Highly myopic megalodiscs as compared to normal sized discs or small discs had a 3.2 times higher risk for glaucomatous optic nerve neuropathy. The increased glaucoma prevalence in axial high myopia was primarily associated with axial myopia associated disc enlargement and not with axial elongation itself.


Ten-Year Changes in the Hepatitis B Prevalence in the Birth Cohorts in Korea: Results From Nationally Representative Cross-Sectional Surveys.
To compare the prevalence of hepatitis B virus (HBV) infection over a 10-year period in terms of population-level trends, we established hypothetical birth cohorts that represented each 10-year interval age group.We used data from the Korean National Health and Nutrition Examination Surveys conducted between 1998 to 2001 and 2008 to 2011. Trends in the HBV infection were calculated using data from individuals aged 20 to 59 years in 1998 to 2001 and those aged 30 to 69 years in 2008 to 2011.In 2008 to 2011, the prevalence of HBV infection, as measured using serum HBV surface antigen (HBsAg) seroprevalence, among participants aged 30 to 69 years was 4.2% (95% CI = 3.7-4.7%), which represents a 1.3% absolute change and 20% change in prevalence ratio, which was significant compared with the prevalence among those aged 20 to 59 years in 1998 to 2001 (5.5%, 95% CI = 4.7-6.3%). The prevalence of HBV infection decreased most in the lowest income group, with marginal significance in males (P = 0.06) and significance in females (P = 0.03). In terms of education, females with at least a high school education showed a significant decrease (P = 0.03).Using a birth cohort approach, the prognosis for HBV infection in terms of death or hospitalization, or resolution upon antiviral treatment of their HBV infections, identified by a decrease in the HBsAg seroprevalence was worse in the lower income group and in females with higher education. We postulate that these socioeconomic inequalities were caused by alcohol consumption, disparities in liver cancer surveillance, and access to antiviral treatment because of cost and reimbursement guidelines.


The importance of peer review: thoughts on Knudson, Morrow, and Thomas (2014).
Knudson, Morrow, and Thomas ( 2014 ) recently summarized a number of important issues related to the quality of peer review and current peer-review practice in kinesiology. This writer endorses their six recommendations for improving peer review in kinesiology journals. The purpose of this commentary is to further highlight the importance of reviewer and associate editor recommendations to the editor, and the importance of editor decisions, in determining what becomes part of a discipline's body of knowledge. These recommendations and decisions ultimately affect what students learn, and what professionals practice, in their disciplines. This kind of power over the control of knowledge and the application of that knowledge is cause for all involved in science to do everything possible to improve our stewardship over peer review.


Pulmonary hemodynamic and ultrastructural changes associated with Group B streptococcal toxemia in adult sheep and newborn lambs.
A toxin isolated from Group B beta-hemolytic streptococci, Type III was infused into adult sheep and newborn lambs. A two-phased reaction was observed. There was an initial phase of pulmonary hypertension and high flow of protein-poor lymph. This was followed by a second phase when pressures returned to baseline but lymph flow remained twice the baseline values and protein concentration in lymph increased. During the second phase there was a significant increase in lymph protein clearance, suggestive of increased microvascular permeability to protein. The absolute granulocyte count decreased to 10% of baseline values by 60 min after the infusion, and was followed by a variable return to baseline. The sheep with the largest changes in protein clearance were those who had the slowest return to baseline values. Pathologic examination of lung tissue revealed there was capillary dilation, interstitial edema, and large numbers of granulocytes in the lungs. The basement membranes of both capillaries and arterioles showed disruption and widening, along with fragmentation of the internal elastic membrane. This study provides morphologic and physiologic evidence of increased pulmonary vascular permeability after injection of streptococcal toxin associated with granulocyte trapping in the lung. We postulate that granulocytes may be involved as mediators of the pulmonary vascular injury.


Tuning peptide affinity for biofunctionalized surfaces.
The control of the interaction between biological systems and surfaces plays a major role in the development of bioactive implants. Random absorbance of different compounds of the body liquids attach at the implant site after surgery. This protein layer triggers the activation of immune cells and is a breeding ground for pathogens, which may induce inflammation processes. Many efforts have been made to block these fouling processes such as PEGylation and unspecific coatings. These systems lead to bioinert implant surfaces that lower the inflammation potential of implanted materials. In contrast, the biomimetic approach attempts the functionalization of implant surfaces with compounds such as peptides, proteins, or sugars that form an artificial layer on the implant that corresponds to the naturally occurring extracellular matrix. This enables the controlled recruitment of cells that improve the healing processes or enhance the osseointegration into the implanted material. An improved connection of implants with cells that enhances the healing processes or tightens the connection of implants with the surrounding tissue is obtained by this approach. However, for bioactive functionalization of implant materials, efficient and robust immobilization techniques are required. Peptides owing to their low-toxicity and their multifunctionality are interesting agents that can act as molecular glue to surfaces. Here, an overview is provided of the development of surface binding peptides, the molecular mechanisms of peptide-surface interactions, and the application of surface binding peptides in the development of multifunctional biomaterials that facilitate beneficial characteristics in vitro and in vivo.


The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization.
Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin β-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock.