Chronic toxicity of polycyclic aromatic compounds to the springtail Folsomia candida and the enchytraeid Enchytraeus crypticus.
An urgent need exists for incorporating heterocyclic compounds and (bio)transformation products in ecotoxicological test schemes and risk assessment of polycyclic aromatic compounds (PACs). The aim of the present study therefore was to determine the chronic effects of (heterocyclic) PACs on two terrestrial invertebrates, the springtail Folsomia candida and the enchytraeid Enchytraeus crypticus. The effects of 11 PACs were determined in chronic experiments using reproduction and survival as endpoints. The results demonstrated that as far as narcosis-induced mortality is concerned, effects of both homocyclic and heterocyclic PACs are well described by the relationship between estimated pore-water 50% lethal concentrations and log Kow. In contrast, specific effects on reproduction varied between species and between compounds as closely related as isomers, showing up as deviations from the relationship between pore-water 50% effect concentrations and log Kow. These unpredictable specific effects on reproduction force one to test the toxicity of these PACs to populations of soil invertebrates to obtain reliable effect concentrations for use in risk assessment of PACs.


Complexes between linoleate and native or aggregated β-lactoglobulin: interaction parameters and in vitro cytotoxic effect.
The dairy protein β-lactoglobulin (βlg) is known to form a complex with fatty acids (FA). Due to industrial processing, βlg is often in its non-native form in food products, which can modify the FA/βlg complex properties. We investigated the interaction of bovine βlg, in selected structural forms (native βlg, a covalent dimer and as nanoparticles), with linoleate (C18:2). Using fluorescence and Isothermal Titration Calorimetry, linoleate was found to bind βlg at two different binding sites. Regardless of the structural state of βlg, association constants remained in the same order of magnitude. However, the stoichiometry increased up to 6-fold for nanoparticles, compared to that of native βlg. The impact of these structural changes on linoleate uptake in vitro was measured by cytotoxicity assays on Caco-2 cells. The order of cytotoxicity of linoleate was as follows: free>complexed to dimers>complexed to nanoparticles>complexed to native βlg. Therefore, the in vitro cytotoxicity of linoleate could be modulated by altering the state of βlg aggregation, which in turn affects its binding capacity to the FA.


Disease elimination and re-emergence in differential-equation models.
Traditional differential equation models of disease transmission are often used to predict disease trajectories and evaluate the effectiveness of alternative intervention strategies. However, such models cannot account explicitly for probabilistic events, such as those that dominate dynamics when disease prevalence is low during the elimination and re-emergence phases of an outbreak. To account for the dynamics at low prevalence, i.e. the elimination and risk of disease re-emergence, without the added analytical and computational complexity of a stochastic model, we develop a novel application of control theory. We apply our approach to analyze historical data of measles elimination and re-emergence in Iceland from 1923 to 1938, predicting the temporal trajectory of local measles elimination and re-emerge as a result of disease migration from Copenhagen, Denmark.


A simplified procedure for synthesizing nucleoside 1-thiotriphosphates: dATP alpha S, dGTP alpha S, UTP alpha S, and dTTP alpha S.
A procedure for synthesizing a nucleoside 1-thiotriphosphate in a single reaction vessel beginning with the nucleoside, PSCl3, and PPi is described. Reaction of the dried nucleoside with PSCl3 in anhydrous triethylphosphate is followed by addition of the tetrabutylammonium salt of PPi. Addition of excess triethylamine precipitates the nucleotides. The crude product is dissolved in water, and the nucleoside 1-thiotriphosphate is purified in 24% to 50% yield by chromatography. The method is applied to the synthesis of dATP alpha S, dGTP alpha S, UTP alpha S and dTTP alpha S.


Parenting stress and development of late preterm infants at 4 months corrected age.
Parenting stress has been linked to child development issues in early preterm infants, but less is known about its effects on development in infants born late preterm. We examined relationships between parenting stress of 108 mothers and 108 fathers and development of late preterm infants born at 34 0/7 to 36 6/7 weeks gestation. At 4 months corrected age, mothers and fathers completed the Parenting Stress Index (PSI-3); mothers were primary caregivers in almost all families and completed the Ages and Stages Questionnaire (ASQ-2) on child development. Mothers reported significantly more stress than fathers on the PSI-3 Parent Domain. PSI-3 subscale scores from the Child Domain were significant predictors of mother-reported infant development as measured by the ASQ-2 in regression models: Reinforces Parent predicted Gross Motor, Mood predicted Communication, and Acceptability predicted Communication, Fine Motor, Problem Solving, and Personal -Social development scale scores. Experiences of parenting stress differed for mothers and fathers. Further research is required on specific dimensions of parenting stress related to development of late preterm infants.


Endophytic Diaporthe sp. ED2 Produces a Novel Anti-Candidal Ketone Derivative.
This study aimed to examine the anti-candidal efficacy of a novel ketone derivative isolated from Diaporthe sp. ED2, an endophytic fungus residing in medicinal herb Orthosiphon stamieus Benth. The ethyl acetate extract of the fungal culture was separated by open column and reverse phase high-performance liquid chromatography (HPLC). The eluent at retention time 5.64 min in the HPLC system was the only compound that exhibited anti-candidal activity on Kirby-Bauer assay. The structure of the compound was also elucidated by nuclear magnetic resonance and spectroscopy techniques. The purified anti-candidal compound was obtainedas a colorless solid and characterized as 3-hydroxy-5-methoxyhex-5-ene-2,4-dione. On broth microdilution assay, the compound also exhibited fungicidal activity on a clinical strain of Candida albicans at a minimal inhibitory concentration of 3.1 μg/ml. The killing kinetic analysis also revealed that the compound was fungicidal against C. albicans in a concentration- and time-dependent manner. The compound was heat-stable up to 70°C, but its anti-candidal activity was affected at pH 2.


Funding an idea: a workshop on writing a grant proposal for allied health professionals.
A framework for a workshop on grant writing to be presented to allied health professionals who seek to develop or improve their grant writing skills is described. The proposed framework contains eight sections that describe preparation for a grant application. The sections discuss activities that occur before, during, and after completing the application. The framework is flexible in its delivery format. The flexibility of this framework creates unique opportunities to present information to allied health professionals and to encourage them to seek funding for research and clinical projects.


Specialized impulse conduction pathway in the alligator heart.
Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.


Cognition and the menopause transition.
Complaints about forgetfulness, "brain fog," and difficulty concentrating are common in women transitioning through menopause. Women with these cognitive complaints often express concern about whether these problems are normal, related to menopause, or represent a symptom of Alzheimer disease or another serious cognitive disorder. In this Practice Pearl, we provide a brief summary of the scientific literature on the frequency of cognitive complaints in midlife women, the validity of complaints in relation to performance on standardized cognitive tests, and the influence of menopause on cognitive performance. We then offer recommendations for healthcare providers and women to address cognitive concerns.


[The "cold" nodule of the thyroid gland: 20 years experience with 2,071 patients and diagnostic limits of fine needle biopsy].
The files of 2071 patients with (Tc99m)-scintigraphically "cold" thyroid nodules (CTN) attending a teaching hospital were analysed retrospectively. Between 1975 and 1995 altogether 49 endocrinologists with varying degrees of experience carried out the clinical evaluation as well as fine needle aspiration biopsy (FNAB), and 33 pathologists undertook the cytological interpretation. By clinical criteria the CTN of 1272 patients were deemed benign, whilst malignancy was suspected in 301 patients (81% and 19% of evaluable cases, respectively). A cytological diagnosis was made in 47.3% of all FNAB performed ("benign" in 611 patients, "follicular neoplasia" in 86, and "malignant" in 39 patients; 39.3%, 5.5% and 2.5%, respectively). 36.5% of the clinically suspect CTN and all nodules with a cytological diagnosis of either "follicular neoplasia" or "malignant" in patients who could be followed up after the FNAB procedure were treated surgically, leading to a total of 420 histological diagnoses. 76% and 35% of the CTN classified as being suspicious of malignancy in the preoperative clinical and cytological evaluation, respectively, were found to be malignant on histology. A clinical assessment of "no abnormality" and "normal" cytology missed a malignant lesion in 16.3% and 15% of cases, respectively. Thus, under routine teaching hospital conditions, the selection of patients with CTN for surgery cannot be based on cytological criteria alone. The FNAB in this setting should be employed exclusively to supplement the clinical and scintigraphically findings.


Glucose Variability Based on Continuous Glucose Monitoring Assessment Is Associated with Postoperative Complications after Cardiovascular Surgery.
This purpose of this prospective study was to use a continuous glucose monitoring (CGM) system to evaluate the suitability of our institution's glucose management protocol after cardiovascular surgery and to clarify the impact of glycemic variability on postoperative complications. In all, 76 patients who underwent elective cardiovascular surgery and were monitored perioperatively using a CGM system were evaluated. Postoperative glucose management consisted of continuous intravenous insulin infusion (CIII) in the intensive care unit, and subcutaneous insulin injections (SQII) after oral food intake started. CIII and subcutaneous injections were initiated when blood glucose level exceeded 150 mg/dL. CGM data were used to analyze perioperative glycemic variability and association with postoperative complications. Target glucose levels (71-180 mg/dL) were achieved during 97.1 ± 5.5% and 86.4 ± 19.0% of the continuous insulin infusion and subcutaneous injection periods, respectively. Major postoperative complications were surgical site infections, found in 6.6% of total patients, and atrial fibrillation, found in 44% of patients with off-pump coronary artery bypass grafting. High glycemic variability during SQII was associated with increased risk for both complications. Data analysis revealed that our glucose management protocol during CIII was adequate. However, the management protocol during SQII required improvement.


[Lung pneumatocele in adult patient - case report].
Lung pneumatoceles are characterized by a thin-walled air-filled cavity present in lung parenchyma. Mostly they are the result of acute bronchopneumonia after spontaneous drainage of altered lung parenchyma with subsequent development and progression of cavities due to ventile mechanism. This disease is more prevalent in infants and young children, it is rather rare in adults. In the present case report, videothoracoscopy resection of lung pneumatocele of the right lower lobe was performed a 43-years old man. The operation was indicated for the presence of chronic persisting and progressing pneumatocele as a preventive measure of pneumatocele complications.


Debriefing to improve interprofessional teamwork in the operating room: A systematic review.
Debriefing has been pivotal in medical simulation training, but its application to the real-world operating room environment has been challenging. We reviewed the literature on routine surgical debriefing with special reference to its implementation, barriers, and effectiveness. Descriptive systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were papers pertaining to debriefing in routine surgical practice. Excluded were papers reporting simulation training. We searched Google Scholar, CINAHL, Web of Science Core Collection, PsychINFO, Medline, Embase, and ProQuest Theses & Dissertations Global. The last search was performed on March 14, 2022. Quality was assessed on a 21-point checklist adapted from a standard reporting guideline. Synthesis was descriptive. The search process resulted in 19 papers. Publication dates ranged from 2007-2022. Study methods included surveys, interviews, and analysis of administrative data. Five papers involved a specific intervention. Quality scores ranged from 12-19 out of 21. On synthesis, we identified five topics: explanations of how debriefing had been implemented; the value of coaching and audit; the learning dimensions of debriefing, both team learning and quality improvement at the organizational level; the effect of debriefing on patient safety or the organization's culture; and barriers to debriefing. Successful implementation programs were characterized by strong commitment from management and support by frontline workers. Integration with administrative quality and safety processes, and information feedback to frontline workers are fundamental to successful debriefing programs. Debriefing can improve teamwork, learning, and psychological safety but is difficult to practice in the operating room environment. It is relevant to review the benefits and barriers to debriefing, and to learn from the experience of others, in order to run better debriefing models in our own hospitals.


Separation of ionic liquid cations and related imidazole derivatives by alpha-cyclodextrin modified capillary zone electrophoresis.
The separation and detection of 1-alkyl-3-methylimidazolium, including isomers, and related imidazole derivatives was performed by alpha-cyclodextrin (alpha-CD) modified capillary zone electrophoresis. The separations were carried out in a running buffer comprising 5.0 mM triethylamine and 2.0 mM alpha-CD adjusted to pH 4.5 by acetic acid. All the analytes were baseline separated within 8 min and the detection limits (signal-to-noise ratio = 3) ranged between 0.42 and 1.36 ppm. The method showed good linearity (within 3-50 times the detection limits, r > 0.99) and reproducibility (relative standard deviation < 0.8% for migration times and < 3% for peak areas), which should make it suitable for routine analysis. It was employed in detecting impurities in commercial chemicals, and 0.27% 1-methylimidazole in 1-ethyl-3-methylimidazolium chloride and 0.55% imidazole in 2-ethylimidazole were found. In addition, it was employed in process analysis during synthesis of ionic liquids and demonstrated a potential to provide information on the reaction mechanism.


Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.
Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.


Expression of cyclooxygenase-2 in primary superficial bladder cancer tissue may predict risk of its recurrence after complete transurethral resection.
A new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection (TUR) because of the high recurrence rate even with current prophylaxis protocols. Prostaglandins (PGs) are known to be produced more in transitional cell carcinoma, and etiologically bladder cancer risk is negatively associated with the intake of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), the rate-limiting enzyme of the PG production. We have shown the chemopreventive effect of piroxicam, an NSAID, on the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder cancer model. To avoid gastrointestinal side effects of regular NSAIDs, we also showed the chemopreventive effect of nimesulide, a selective inhibitor of the second isoform of COX, COX-2, which does not affect COX-l house-keeping activity in gastrointestinal mucosa on the same model. We also observed induction of COX-2 protein in the rat bladder tumor. In this study, we screened COX-2 protein expression in primary superficial bladder cancer tissues, to elucidate if COX-2 selective inhibitors can be a candidate chemopreventive agent for bladder cancer recurrence. Five and 6 samples of superficial bladder cancer cases with and without recurrence after complete TUR were examined by immunohistochemical analysis. We found more COX-2 protein positive samples in the cases with recurrence than in cases without recurrence. Even though the number of cases examined is small, this result supports our hypothesis that COX-2 contributes to superficial bladder cancer recurrence, thus, selective COX-2 inhibitors can be a candidate chemopreventive agent for the recurrence.


In vivo monitoring of intracellular expression of human interleukin-2 using green fluorescent protein fusion partner in Pichia pastoris.
The use of Pichia pastoris for protein production was simplified by creation of fusion proteins containing green fluorescent protein (GFP) and the product of interest. Human interleukin-2 (hIL-2) was used as a model product: GFP enabled clear identification of fusion protein expression and, more importantly, the quantification of hIL-2. Although GFP fusions for bioprocess monitoring have been demonstrated in other hosts, this is its first use in P. pastoris.


The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol.
Evidence suggests that prenatal insult may play a role in the etiology of psychotic disorders. Minor physical anomalies (MPA) are an indicator of abnormal fetal development and are elevated in individuals at genetic and behavioral risk for psychosis. Yet, there has been little empirical research on the relationships between MPAs and other neurobiological risk indicators. We hypothesized that the frequency of MPAs (an external marker of prenatal central nervous system [CNS] disruption) would be associated with two other biomarkers suggestive of disruptions in fetal neurodevelopment: movement abnormalities (an indicator of striatal abnormalities) and heightened cortisol secretion (an indicator of hypothalamic-pituitary-adrenal [HPA]/hippocampal function). Participants with schizotypal personality disorder (SPD; n = 39) and both normal (n = 47) and other personality disorders (n = 28) control subjects were administered structured diagnostic interviews and assessed for MPAs, movement abnormalities, and salivary cortisol. Schizotypal personality disorder participants showed significantly greater MPAs and movement abnormalities and higher cortisol than both the normal and other personality disorders groups. Hierarchical linear regression analyses revealed that higher rates of MPAs were linked with greater movement abnormalities and salivary cortisol. The findings suggest that MPAs serve as a marker of neurodevelopmental abnormalities that affect striatal and hippocampal regions.


Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer.
Currently, anti-PD-1/PD-L1 immunotherapy using immune checkpoint inhibitors is widely used in the treatment of multiple cancer types including lung cancer, which is a leading cause of cancer death in the world. However, only a limited proportion of lung cancer patients will benefit from anti-PD-1/PD-L1 therapy. Therefore, it is of importance to predict the response to immunotherapy for the precision treatment of patients. Although the expression of PD-L1 and tumor mutation burden (TMB) are commonly used to predict the clinical response of anti-PD-1/PD-L1 therapy, other factors such as tumor-specific genes, dMMR/MSI, and gut microbiome are also promising predictors for immunotherapy in lung cancer. Furthermore, invasive peripheral blood biomarkers including blood DNA-related biomarkers (e.g., ctDNA and bTMB), blood cell-related biomarkers (e.g., immune cells and TCR), and other blood-related biomarkers (e.g., soluble PD-L1 and cytokines) were utilized to predict the immunotherapeutic response. In this review, the current achievements of anti-PD-1/PD-L1 therapy and the potential biomarkers for the prediction of anti-PD-1/PD-L1 immunotherapy in lung cancer treatment were summarized and discussed.


Acinetobacter baumanii meningitis: a rare complication of incidental durotomy.
Despite the frequency of dural tears in spinal surgery, meningitis is a rare complication reported to occur with a frequency of 0.18%. To the best of our knowledge, no case of Acinetobacter baumanii meningitis has been reported in the literature after a dural tear secondary to lumbar spine discectomy. This case highlights the importance of repairing all dural tears and commencing antibiotics that cover uncommon bacteria in those who develop symptoms of meningitis in this setting.


Antiparallel polypurine phosphorothioate oligonucleotides form stable triplexes with the rat alpha1(I) collagen gene promoter and inhibit transcription in cultured rat fibroblasts.
The rat alpha1(I) collagen promoter contains a unique polypurine-polypyrimidine sequence between -141 and -200 upstream of the transcription start site. The polypurine sequence from -171 to -200 (C2) is on the coding strand and the adjacent polypurine sequence from -141 to -170 (C1) is on the non-coding strand. Earlier we demonstrated triplex formation with a polypurine 30 nt parallel triplex-forming oligonucleotide (TFO) corresponding to C1 and inhibition of transcriptional activity of the rat alpha1(I) collagen promoter. In the present work we have tested triplex-forming abilities of shorter (18 nt) purine and pyrimidine TFOs in parallel and antiparallel orientation to the C1 purine sequence. Our results show that purine antiparallel TFOs formed triplexes with the highest binding affinities, while pyrimidine oligodeoxyribonucleotides (ODNs) did not show appreciable binding. Phosphorothioate modification of purine TFOs did not significantly reduce binding affinity. We also demonstrate that preformed triplexes are quite stable when precipitated with ethanol and resuspended in water. Further analysis was carried out using two purine phosphorothioate antiparallel TFOs, 158 APS and 164 APS, designed to bind to the promoter region from -141 to -158 and -147 to -164, respectively, which were found to form triplexes even under physiological conditions. DNase I footprinting experiments showed the ability of these TFOs to protect target sequences in the promoter region; both purine sequences (C1 and C2) were protected in the case of 158 APS. Transfection experiments using preformed triplexes with a reporter plasmid containing the collagen promoter sequence showed significant inhibition of transcription when compared with a control phosphorothioate ODN. The effect of 164 APS was greater than that of 158 APS. These results indicate that this triplex strategy could be used in the down-regulation of collagen synthesis in cultured cells and offer the potential to control fibrosis in vivo.


1H NMR, mechanism, and mononuclear oxidative activity of the antibiotic metallopeptide bacitracin: the role of D-Glu-4, interaction with pyrophosphate moiety, DNA binding and cleavage, and bioactivity.
The peptidyl antibiotic bacitracin (Bc) is one of the most widely used antibiotics which can bind divalent transition metal ions, including Mn(II), Co(II), Ni(II), Cu(II), and Zn(II). The metal binding is essential for its antimicrobial activity. Previous analysis of the hyperfine-shifted (1)H NMR signals of Co(II)-Bc A(1) revealed the structure of the metal binding environment and a potential hydrophobic site important for the bioactivity of this antibiotic. Co(II)-Bc in DMSO shows relatively sharper hyperfine-shifted (1)H NMR signals compared with the spectrum acquired in an aqueous solution, allowing more thorough analysis of the signals with 1D and 2D NMR methods. Pyrophosphate and derivatives bind to Co(II)-Bc to form kinetically inert ternary complexes. The coordinated D-Glu-4 is found detached from the metal center of metallobacitracin upon trimetaphosphate binding, implying its role in the antibiotic activity of Bc. We further demonstrate in this report the structure-function relationship on desamido-Bc of low antibiotic activity by the use of NMR, wherein D-Glu-4 is suggested to be important for the bioactivity of Bc. The interaction of the phospho-moiety with Bc is also reflected by DNA binding, wherein metal-free Bc does not bind DNA, whereas various metal complexes of Bc do. Cu(II)-Bc was further demonstrated to bind and oxidatively cleave DNA under reduction conditions in the air. It also exhibited a significant oxidative activity toward catechol oxidation, showing enzyme-like saturation kinetics with k(cat) = 7.0 x 10(-3) s(-1) and k(cat)/K(m) = 2.1 M(-1) s(-1) aerobically and k(cat) = 0.38 s(-1) and k(cat)/K(m) = 14.7 M(-1) s(-1) in the presence of 32 mM of H(2)O(2). The binding of pyrophosphate moiety to metallobacitracin, the detachment of d-Glu-4, and the significant oxidative activity of Cu(II)-Bc provide further insights into the bioactivity of this metallopeptide and Cu-oxygen chemistry.


Glucose metabolism and body composition in young adults treated with TBI during childhood.
After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.


Nondestructive assessment of tissue engineered cartilage based on biochemical markers in cell culture media: application of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy.
Tissue engineering of cartilage for tissue repair has many challenges, including the inability to assess when the developing construct has reached compositional maturity for implantation. The goal of this study was to provide a novel analytical approach to nondestructively assess tissue engineered cartilage (TEC) during in vitro development. We applied attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy to establish a quick and straightforward method to evaluate consumption of glucose and secretion of the metabolite lactate in the culture media, processes that are associated with tissue development. Using a series of standards, we showed by principal component analysis (PCA) that ATR-FTIR data was able to distinguish culture media with varying amounts of glucose and lactate. The 2nd derivative spectra displayed specific peaks of glucose at 1035 cm-1 and lactate at 1122 cm-1, and both the spectral first principal component (PC-1) scores and the 1122/1035 peak ratio very strongly correlated with the concentration of these components. TEC was prepared using chondrogenic cells grown in hydrogels, and analyzed for cell viability, distribution, and formation of proteoglycan (PG, a major cartilage protein). ATR-FTIR data of the cell culture media harvested during TEC development showed that the spectral PC-1 and the 1122/1035 peak ratio could significantly distinguish cultures with different amounts of constructs (1, 3 or 5 constructs per well) or with constructs at different developmental stages (3 or 5 weeks of culture). Interestingly, we also found that the PG content of the TEC was significantly correlated with both spectral PC-1 (r = -0.79) and the 1122/1035 peak ratio (r = 0.80). Therefore, monitoring relative glucose and lactate concentrations in cell culture media by ATR-FTIR provides a novel nondestructive approach to assess development of TEC.


Distinctive dermatoscopic features of acral lentiginous melanoma in situ from plantar melanocytic nevi and their histopathologic correlation.
An acral lentiginous melanoma in situ on the sole is often difficult to differentiate with the naked eye from an acquired plantar melanocytic nevus. Recent technical advances in epiluminescence microscopy have contributed to the differentiation of these two pigmented skin lesions. In this study, the correlation between dermatoscopic and histopathologic findings of acral lentiginous melanoma in situ on the sole are compared to those of acquired plantar melanocytic nevi. Three acral lentiginous melanomas in situ on the sole, and two cases of acral lentiginous melanoma were compared with 50 acquired plantar melanocytic nevi by means of dermatoscopy and histopathology. The dermatoscopic surface profiles of acquired melanocytic nevi were composed of linear pigmentation accentuated mainly on the sulcus superficialis. Histologically, some areas of the sulcus superficialis corresponded to rete ridges of the epidermis, and nests of nevus cells were also often located there. In contrast, the acral lentiginous melanomas in situ showed diffuse, irregularly shaped pigmentation distributed in a disorderly fashion over the entire surface. Histologically, isolated areas of proliferation and small nest formations of atypical melanocytes were irregularly distributed in the epidermis. A distinctive dermatoscopic feature of acral lentiginous melanoma in situ is diffuse and irregular pigmentation over the entire surface of the lesion. This feature is helpful for differentiating acral lentiginous melanoma in situ from acquired plantar melanocytic nevi.


Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review.
Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.


A multilevel analysis of diet and socio-economic status in Scotland: investigating the 'Glasgow effect'.
To investigate differences between dietary habits in Glasgow and those in the rest of Scotland and the role that socio-economic factors have in explaining these. Data on age, sex, area deprivation, social class, educational qualifications, economic activity, health board region, postcode sector area and informants' usual intake of foods covering sugary foods, snacks, fibre, starch, meat, fish, spreading fats, dairy products, salt, dietary supplements, fruit and vegetables were available from the 1995, 1998 and 2003 Scottish Health Surveys. Multilevel logistic regression was used to model the relationship between diet and living in Greater Glasgow compared with elsewhere in Scotland, unadjusted and adjusted for age, survey year and socio-economic factors, accounting for the clustering within postcode sector area. Scotland. Subjects comprised 11 075 male and 14 052 female respondents. Lower consumption of high-fibre bread and potatoes/pasta/rice (among men and women), of cakes (men) and of cereals, meat, skimmed/semi-skimmed milk and green vegetables (women) in Glasgow was explained by socio-economic factors, as was higher consumption of non-diet soft drinks among women; lower consumption of ice cream, bread, cereals, meat and green vegetables (men) and high butter and salt consumption (women) in Greater Glasgow were not. Associations between unhealthy eating and deprivation accounted for much of the tendency of people in Glasgow to have poor diets. Policies are needed to encourage improvements in diet in Glasgow and more effort is required to reduce social inequalities in eating habits. Glasgow's poor diet will remain unless problems associated with poverty are tackled.


Elk (Cervus Canadensis) preference for feeds varying in selenium concentration.
Selenium-accumulator plants are reputed to be unpalatable to large ungulates. Elk (Cervus canadensis) populations in southeastern Idaho overlap with populations of Se-rich plants, but there is no information on the influence of plant Se concentration on elk dietary preferences. The objective of this study was to determine, under controlled conditions, the preference of elk for feeds varying in Se concentrations. Seven yearling female elk (128 ± 5 kg) were purchased from a commercial elk farm in southeastern Idaho and adapted to low-Se alfalfa pellets. Three feeding trials using pellets with predetermined Se concentrations were conducted. Alfalfa pellets were commercially made with the addition of Symphyotrichum ascendens (western aster) so that the pellets contained 0.4, 5, 20, 50, or 100 mg/kg (DM basis) Se. In trial 1, 5 Se-containing alfalfa pellets (0.4, 5, 20, 50, and 100 mg/kg Se) were offered for 10 d; trial 2 used 4 Se-containing alfalfa pellet choices (0.4, 20, 50, and 100 mg/kg), and trial 3 used 3 pellet choices (0.4, 50, and 100 mg/kg) for 6 d. In trial 1, consumption of the control pellets by elk was greater than each of the other pellet choices (P < 0.001). Similarly, consumption of the 5-mg/kg Se pellet differed from control pellet and all other Se-containing pellets (P < 0.0001). There were no differences (P > 0.50) in consumption of the 20-, 50-, or 100-mg/kg Se pellets. In trial 2, elk consumed more (P < 0.0001) of the control pellet than the 20-, 50-, and 100-mg/kg Se pellets. Similarly, elk consumed more (P < 0.0001) of the 20-mg/kg Se pellet than the 50- and 100-mg/kg Se pellets. There were no differences (P > 0.99) in elk consumption of the 50- and 100-mg/kg Se pellets. In trial 3, elk consumption of the control and 50- and 100-mg/kg Se pellets differed (P ≤ 0.03) from one another each day except that on d 1 and 2, where elk consumption of the 50- and 100-mg/kg Se pellets did not differ (P ≥ 0.32). Elk clearly discriminated against pellets with the highest Se concentrations when they were given pellets with differing Se concentrations. These results suggest that elk are not likely to select forages with high Se concentrations, particularly when high-Se plants are present in a rangeland situation with numerous other forage choices.


Quality attributes and microbial survival on whole cantaloupes with antimicrobial coatings containing chitosan, lauric arginate, cinnamon oil and ethylenediaminetetraacetic acid.
Cantaloupes are susceptible to microbiological contamination in pre- or postharvest environments. Novel intervention strategies, such as antimicrobial coatings, are needed to improve the microbiological safety of cantaloupes. The objective of this study was to prepare whole cantaloupes coated with mixtures containing chitosan, lauric arginate (LAE), cinnamon oil (CO), and ethylenediaminetetraacetic acid (EDTA) and determine survival characteristics of inoculated foodborne pathogens during storage as well as cantaloupe quality attributes. Chitosan coating with 0.1% LAE, 0.1% EDTA, and 1% CO was the most effective for inactivating foodborne pathogens inoculated on cantaloupes. This coating caused a >3logCFU/cm(2) reduction of Escherichia coli O157:H7 and Listeria monocytogenes immediately after coating and reduced Salmonella enterica to below the detection limit during a 14-day storage. Total molds and yeasts also were reduced to the detection limit by the coating. The redness and yellowness of uncoated cantaloupes were significantly higher than coated ones from day 6. The firmness of uncoated cantaloupes and those coated with chitosan only was significantly lower than other treatments from day 10. No significant differences were found in total soluble solids content or weight loss between coated and uncoated cantaloupes. Results showed the potential benefits of applying the coating mixtures to improve the quality and microbiological safety of cantaloupes.


Retroperitoneal lymph node dissection for testicular tumors using the thoracoabdominal approach.
During the past 4 years, 16 patients with testicular tumor underwent retroperitoneal lymph node dissection using the thoracoabdominal extraperitoneal approach described by Scardino. In 4 of them, the lymph node dissection was performed without pleurotomy using our modified technique. No uncontrollable intra- or post-complications or operative deaths occurred in our series. From our experience, it was concluded that the thoracoabdominal approach was suitable for maximum exposure of the retroperitoneal area and was associated with lower mobility. Furthermore, our modified extrapleural extraperitoneal technique also provided an excellent operative field comparable to the thoracoabdominal approach.


Electrochemical and photoelectrochemical investigation of new electrostatic self-assembled films based on Prussian blue and a binuclear Ru(II) complex.
New hybrid multilayer films containing Prussian blue (PB) and a binuclear Ru(II) complex were successfully fabricated using the electrostatic layer-by-layer self-assembly technique. The process was carefully monitored by ultraviolet-visible (UV-vis) spectroscopy. A linear increase in the UV-vis absorbance with the number of deposited layers indicated that the film deposition was uniform and reproducible. The electrochemical and photoelectrochemical properties of these hybrid multilayer films were investigated in an aqueous Na2SO4 solution. PB and the binuclear Ru(II) complex assembled in the film were redox active with surface confined characteristics. The surface concentration and molecular area of RuL in the film were calculated according to a UV-vis absorption spectrum and cyclic voltammetry, respectively. The photocurrent generated by switching on the light irradiation of the film increased linearly as the deposited bilayers increased. The photocurrent action spectrum was in agreement with metal-to-ligand charge-transfer (MLCT) band of RuL in the absorption spectrum, which indicated that the photocurrent was generated based on MLCT excitation of the RuL in the (PB/RuL) film.


High-efficiency modulation of coupling between different polaritons in an in-plane graphene/hexagonal boron nitride heterostructure.
Two-dimensional van der Waals (vdW) materials have a full set of highly confined polariton modes, such as low-loss phonon polaritons and dynamically tunable graphene plasmons, which provide a solution for integrated nanophotonic devices by combining the unique advantages of different polaritons. Highly efficient coupling between these complementary polaritons is key to realize the nanoscale optical integration. However, fluctuations of permittivity or geometry at the abrupt interfaces have been demonstrated as perturbations or scatters of polaritons. Here, in-plane plasmon-phonon polariton coupling in an in-plane graphene/hexagonal boron nitride (BN) heterostructure is studied using a full-wave electromagnetic numerical model. Transmittance between different polaritons is proportional to momentum matching, which can be tuned using the graphene Fermi energy. The transmittance between a graphene plasmon and a BN phonon polariton can be controlled between 0% and 100% within the upper Reststrahlen band of the BN. This is central to many photon devices, such as waveguides, wavefront shapers, filters, modulators and switches. Moreover, we simulate near-field interference patterns in an in-plane heterostructure based on the theoretical dispersion relation of polaritons, enabling scattering scanning near-field optical microscopy a potential experimental method to investigate the coupling between different polaritons. This study provides a theoretical basis for efficient coupling of propagation and modulation between different polaritons in in-plane heterostructures of vdW materials, which could pave a way to design nanoscale multi-functional waveguide devices in integrated photonic systems.


Solutions for solitons in nonlinear optically induced lattices.
We calculate stationary configurations of superposed states "soliton + cnoidal wave lattice" of the vector nonlinear Schrödinger equation, using the Darboux transformation technique. The obtained expressions contain the Jacobi elliptic and theta functions, and are easily manageable. There are five stationary configurations, in which one of the defocusing media is stable, while those of the focusing medium are classified into two weakly unstable and two unstable. The checking of the solutions as well as the construction of their typical shapes is accomplished with the help of symbolic package MATHEMATICA.


Enhancement of stress-induced apoptosis in B-lineage cells by caspase-9 inhibitor.
We have established human B-lineage (BLIN) acute lymphoblastic leukemia cell lines that retain a dependency on fibroblast monolayers for survival and proliferation. Eight hours following removal from adherent cell contact BLIN cells undergo a decrease in mitochondrial transmembrane potential and an increase in annexin V binding. Unexpectedly, the caspase-9 inhibitor (C9i) benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone enhanced the appearance of apoptotic cells within 8 hours following removal of BLIN cells from fibroblast monolayers. C9i enhancement of apoptosis was dose dependent and did not occur with irreversible inhibitors of caspases-2, -3, -6, and -8. C9i also enhanced apoptosis in cord blood-derived CD19(+) B-lineage cells (but not myeloid cells) removed from murine stromal cells. Longer exposure (> 18 hours) to C9i culminated in apoptosis in a panel of B-lineage acute lymphoblastic leukemia (ALL) cell lines in the presence or absence of fibroblast monolayers, as well as in 2 proliferating leukemic cell lines (RAMOS and CEM). BLIN-4L cells made deficient in caspase-9 by RNA interference exhibited no resistance to apoptotic signals and actually showed increased apoptotic sensitivity to staurosporine. These collective results suggest that a 4-amino acid caspase inhibitor of caspase-9 can promote apoptosis and that at least some types of apoptotic pathways in B-lineage ALL do not require caspase-9.


Palifermin in children undergoing autologous stem cell transplantation: a matched-pair analysis.
Keratinocyte growth factor (palifermin) is used for prevention of mucositis in adults following autologous and allogeneic hematopoietic stem cell transplantation (HSCT). It is known that palifermin decreases length of initial hospital stay, mean number of days of total parenteral nutrition (TPN) and the use of opioids for pain control in oral mucositis in adults. There are limited data evaluating palifermin use in children following autologous HSCT. The objective of the present study was the analysis of efficacy and safety of palifermin in children undergoing auto-HSCT. This matched-pair analysis study included 62 pediatric patients undergoing first auto-HSCT receiving palifermin on a compassionate-use basis (study group, n=31) or not (control group, n=31). Palifermin decreased the incidence of severe (grade 3-4 WHO) oral mucositis (p=0.041), length of hospitalization (p=0.047) and contributed to the shorter duration of oral mucositis (p=0.035) and lower incidence of clinically or microbiologically documented infections (p=0.038). There were no differences between groups in opioid use, neutrophil and platelet recovery, TPN use and gastrointestinal hemorrhage. Palifermin decreases the incidence and severity of oral mucositis in children undergoing autologous HSCT.


Perceived racial/ethnic discrimination among young adult college students: Prevalence rates and associations with mental health.
Objective/Participants: In a large, diverse sample of college students (N = 2,230), this online study investigated racial/ethnic differences on type of discriminatory event experienced and perceived stress, and whether discrimination-related stress was associated with mental health symptoms. Methods: Prevalence of lifetime/past year discriminatory events was assessed and frequency of discrimination-related stress was compared across racial/ethnic groups. Correlations between discrimination-related stress and mental health symptoms were also examined. Results: All racial/ethnic groups reported experiencing all types of discriminatory events, though prevalence was lowest for White students. Racial/ethnic minority (i.e., Asian, Black, Latinx) students reported greater discrimination-related perceived stress compared to White, non-Hispanics. Across all racial/ethnic groups, discrimination-related stress was positively associated with negative mental health outcomes (e.g., anxiety/depressive symptoms). Conclusions: These results highlight the need to continue efforts to reduce discriminatory experiences of racial/ethnic minority students and to incorporate antiracism interventions in universities to mitigate the pervasive negative experiences of minority students.


Who Is the Preferred Tutor in Clinical Skills Training: Physicians, Nurses, or Peers?
Phenomenon: Clinical skills centers allow structured training of undergraduate medical students for the acquisition of clinical skills in a simulated environment. Physician, nurse, or peer tutors are employed for training in those centers. All tutors should have appropriate training about the methodology used in the clinical skills training. Many of the studies revealed the effectiveness of various types of tutors. The aim of our study was to evaluate medical students' satisfaction with clinical skills training, and their opinions about the differences in coaching skills among the physician, nurse, and peer tutors. This study was conducted with third-year students (467 students) in 2013-2014 academic year at Hacettepe University Faculty of Medicine. Participation rate was 85 % (397 students). The students attended the suturing skill training in groups of 40 students. First, a faculty member from the Department of Medical Education delivered a video demonstration and conducted discussion. After the demonstration, the students were divided into groups of 5-6 students. A physician, nurse, or a peer tutor facilitated each group. The students were asked to complete the Coaching Skills Evaluation Form after the practicum session. It contained 13 criteria for assessing the coaching skills. Additionally, the form included a question for rating the student's satisfaction with the tutor. The performance of the tutors at each step was rated on a three-point scale. Kruskal Wallis analysis was used to compare students' scores for their tutors. The students' satisfaction with tutors was high for all of the tutors. However, there was no difference between students' scores in suturing skill, and between physician, nurse, and peer tutors' coaching skills. Insights: In this study, we revealed that physician, nurse, and peer tutors were equally effective on the students' performances. They were also regarded as effective in their teaching role by students. But the most important point was that sufficient tutor training and preparation was crucial for the success of models.


Evaluation of 2 whole-brain radiotherapy schedules and prognostic factors for brain metastases in breast cancer patients.
The majority of breast cancer patients with brain metastases receive whole-brain radiotherapy (WBRT) and have a survival of only a few months. A short WBRT regimen would be preferable if it provides survival that is similar to that achieved with longer programs. This retrospective study compared survival and local control within the brain resulting from short-course WBRT with longer programs in 207 breast cancer patients. Sixty-nine patients treated with 5 fractions of 4 grays (Gy) each given within 5 days were compared with 138 patients treated with 10 fractions of 3 Gy each given over 2 weeks or 20 fractions of 2 Gy each given over 4 weeks. Six additional potential prognostic factors were investigated: age, Karnofsky performance score (KPS), number of brain metastases, the presence of extracranial metastases, interval from tumor diagnosis to WBRT, and recursive partitioning analysis (RPA) class. On univariate analysis, the WBRT regimen was not found to be associated with survival (P=.254) or local control (P=.397). Improved survival was associated with a KPS>70 (P<.001), single brain metastasis (P=.023), the absence of extracranial metastases (P<.001), and lower RPA class (P<.001). On multivariate analysis, which was performed without RPA class because this is a confounding variable, KPS (relative risk [RR] of 4.00; P<.001) and the presence of extracranial metastases (RR of 1.54; P=.024) maintained statistical significance. On univariate analysis, local control was associated with KPS (P<.001) and RPA class (P<.001). On multivariate analysis, local control was found to be associated with a KPS>70 (RR of 5.75; P<.001). Short-course WBRT with 5 fractions of 4 Gy each resulted in survival and local control that were similar to longer programs in breast cancer patients with brain metastases. The dose of 5 fractions of 4 Gy each appears preferable for the majority of these patients because it is less time consuming and more convenient.


A Rare Case of Prosopagnosia Related to Intracranial Hemorrhage.
Prosopagnosia describes the inability to recognize others by their faces, which may be hereditary or acquired. Acquired cases result from intracranial lesions such as intracranial hemorrhage or ischemia. This case demonstrates acquired prosopagnosia secondary to an intracranial hemorrhage and thus exemplifies the importance of early symptom recognition for appropriate diagnosis and management. A 58-year-old female presented to the emergency department with a chief complaint of the worst headache of her life along with nausea and vomiting. She also reported that she was unable to recognize her children in photos and although she knew her husband was with her, she did not recognize his face. Physical examination revealed no focal motor deficits. Computed tomography angiography of the brain revealed intracerebral hemorrhage of the right occipital lobe. Acquired prosopagnosia can be the only presenting symptom of intracranial pathology. It is most commonly caused by intracranial hemorrhage, as shown in this case report. This demonstrates a unique symptom of posterior circulation strokes that are commonly misdiagnosed in the emergency department.


The utility of serum gastrin levels in assessing the significance of low serum B12 levels.
Elevated levels of serum gastrin as a consequence of gastric achlorhydria are characteristic of clinical pernicious anemia. In a largely male hospitalized population with an average age of 64 years, 7.7% had low levels of serum B12 (less than 170 pg/mL); only 2.5% of these had frank pernicious anemia. In an attempt to separate a subgroup with low levels of serum B12 in whom pernicious anemia may later develop, their serum gastrin levels were determined. Twenty-two percent had high values and, of these, 70% had low B12 absorptions. In patients with low serum B12 levels, serum gastrin assays may be useful in determining those in whom clinical pernicious anemia seems likely to develop.


Heat Stress Decreases Intestinal Physiological Function and Facilitates the Proliferation of Harmful Intestinal Microbiota in Sturgeons.
Heat is a common source of stress in aquatic environments and can alter the physiological and metabolic functions of aquatic animals, especially their intestinal function. Here, the effects of heat stress on the structure and function of the intestine and the characteristics of the intestinal microbiota were studied in sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂ hybrid F1). Sturgeons were exposed to sub-extreme (24°C) and extreme (28°C) high water temperatures for 12 days. The heat stress caused systemic damage to the intestine of sturgeons, which displayed severe enteritis in the valve intestine. The microbial diversity analysis showed that heat stress led to the disorder in intestinal microbiota, manifesting as an explosive increase in the abundance of thermophilic intestinal pathogens such as Plesiomonas, Cetobacterium, and Aeromonas and causing physiological dysfunction in the sturgeons. The disorder was followed by significant inhibition of intestinal digestion with reduced chymotrypsin, α-amylase, and lipase activities in the valve intestine and of antioxidant function with reduced peroxidase (POD) and catalase (CAT) activities. Simultaneously, heat stress reduced the thermal tolerance of sturgeons by reducing Grp75 expression and damaged the valve intestine's repair ability with increased Tgf-β expression. The results confirmed that heat stress damaged the sturgeon intestines obviously and disturbed the intestinal microbiota, resulting in serious physiological dysfunction. The present study investigated the mechanism of the effect of heat stress on the sturgeon intestine and will help develop strategies to improve the resistance to thermal stress for wild and cultured sturgeons.


Capsule endoscopy of the small bowel in the clinical practice: outpatient management is feasible and cheaper.
Four Italian regions have cost coding for outpatient capsule-endoscopy. Elsewhere it is performed in ordinary hospital admission. To identify, in a cohort of patients of a Gastroenterology Unit, those feasible for outpatient versus inpatient treatment; to analyze costs distribution in both management areas. We retrospectively analysed 100 clinical records of admissions to A.O. San-Carlo-Borromeo, Milan between 2005-2008. Hospitalization criteria (at least 3): 1) occult/obscure gastrointestinal bleeding; 2) hemoglobin ≤ 8 gr/dL; 3) indication for blood transfusions; 4) urgent hospital admission. A total of 62 patients had urgent admission, 60 blood transfusions, 81 underwent EGD and colonoscopy, 8 enteroscopy and 5 surgery. Mean haemoglobin value was 8.67 g/dL. Capsule-endoscopy was positive in 70, uncertain in 8, negative in 22. Positive cases: 33 angiodyplasia, 18 ulcers/erosions, 13 polyps/masses, 5 overt bleeding, 1 celiac disease. 47/100 were appropriate as outpatient, saving 432 days of hospital stays. Admission coding was grouped into 7 DRGs (overall expense: 98,366 Euros). Considering EGD/colonoscopy outpatient costs and 1.100 euros as estimated value for capsule-endoscopy, the total expense could be 53.919. Outpatient capsule-endoscopy small bowel examination is feasible in half of the cases. It is cost saving, (about 45.000 Euros/100 patients), reducing inappropriate hospital stays.


Coupling Constant Corrections in a Holographic Model of Heavy Ion Collisions.
We initiate a holographic study of coupling-dependent heavy ion collisions by analyzing, for the first time, the effects of leading-order, inverse coupling constant corrections. In the dual description, this amounts to colliding gravitational shock waves in a theory with curvature-squared terms. We find that, at intermediate coupling, nuclei experience less stopping and have more energy deposited near the light cone. When the decreased coupling results in an 80% larger shear viscosity, the time at which hydrodynamics becomes a good description of the plasma created from high energy collisions increases by 25%. The hydrodynamic phase of the evolution starts with a wider rapidity profile and smaller entropy.


Transcatheter aortic valve implantation without prior balloon valvuloplasty is associated with less pronounced markers of myocardial injury.
Aortic valve stenosis is the most common valvulopathy in developed countries. Transcatheter aortic valve implantation (TAVI) is a therapeutic alternative in symptomatic patients at high or prohibitive perioperative risk. Predilatation by balloon aortic valvuloplasty (BAV) under rapid ventricular pacing (RVP) has been a routine part of TAVI. However, both RVP and BAV carry substantial risks and an increasing number of interventional centers are performing TAVI without predilatation (direct TAVI). A transient decrease of left ventricular function and elevated markers of myocardial injury after TAVI with predilatation were observed in previous studies. In this study, we investigated whether direct TAVI was associated with a similar increase in cardiac biomarkers and decrease in ejection fraction in a cohort of our patients. Consecutive patients undergoing TAVI without predilatation using a self-expanding system at a single center between April 2013 and December 2015 were followed up for one year and were retrospectively analyzed regarding mortality, safety and efficacy endpoints as well as common laboratory and echocardiographic parameters. A total of 164 patients (83±6 years; 56% female) were included in the analysis. According to the Valve Academic Research Consortium 2 (VARC-2) criteria the technical success rate was 96.3% and 89.1% of patients remained free of a combined safety endpoint at 30 days. Mortality rates at 30 days and 1 year were 3.0% (N.=5) and 10.4% (N.=17), respectively. TAVI without predilatation was highly effective in lowering aortic valve peak velocity from 4.4±0.6 m/s before to 1.7±0.5 m/s (P<0.01), and mean pressure gradient across the valve from 48.7±15.1 mmHg to 8.3±4.5 mmHg (<0.05). Left ventricular function remained unaltered after the intervention (51±10% prior to TAVI and 51±9% post TAVI), whereas high sensitive troponin T (hs-TnT), a well-established marker for myocardial injury, increased significantly from 26 ng/L (interquartile range=18.00-44.00) to 119 ng/L (interquartile range=73.25-166.00, P<0.001) during this time. Notably, an increase in the plasma levels of hs-TnT >15 times the upper limit of normal was associated with mortality both one month and one year after TAVI. TAVI without predilatation is feasible, safe and effective for aortic valve replacement in symptomatic patients with severe aortic stenosis who are at high perioperative risk. In contrast to a cohort of patients who underwent TAVI with predilatation previously published by another center, our patients did not suffer from transient impairment of left ventricular function. As a marker of myocardial injury, hs-TnT showed a less pronounced increase than reported previously. This might be a marker for a prognostic benefit as hs-TnT has been shown to be a strong predictor of outcome in patients undergoing TAVI. We conclude that direct TAVI is a less invasive option involving less myocardial stress.


Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake.
Deletion of acetyl CoA carboxylase-2 (Acc2) reportedly causes leanness in the setting of hyperphagia. To determine the cellular basis for these effects, we generated a mouse model in which Acc2 can be selectively deleted by the action of Cre recombinase. Deletion of Acc2 from skeletal muscle, the predominant site of Acc2 expression, had no effect on body weight, food intake, or body composition. When Acc2 was inactivated in the germline, Acc2 knockout (Acc2KO) mice displayed no differences in body weight, food intake, body composition, or glucose homeostasis as compared to controls on chow or high fat diet. Total malonyl CoA content and fatty acid oxidation rates in skeletal muscle of Acc2KO mice were unchanged, suggesting metabolic compensation in response to the loss of Acc2. The limited impact of Acc2 deletion on energy balance raises the possibility that selective pharmacological inhibition of Acc2 for the treatment of obesity may be ineffective.


A proposal to provide care to the uninsured through a network of community health centers.
While a national health insurance plan is needed, this alone will not provide access for approximately 30 million persons who face geographic, cultural, language, or health care system barriers, or who live in areas with provider shortages. These barriers often coexist with lack of insurance coverage, but they also affect millions who have public, or even private, coverage. Moreover, large segments of this population suffer from health problems not adequately addressed by the traditional medical model: teenage pregnancy, AIDS, injury, substance abuse, and the like. To provide appropriate care for these underserved persons, we propose to expand the existing network of community health centers over the next 10 years to a total of approximately 3,000. Such an expansion would provide a cost-effective approach to improving provider distribution, increasing consumer input, combining personal health services with health promotion, and removing both financial and nonfinancial barriers to care. This model can be implemented either independent of or in conjunction with other health care system reform efforts.


Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium.
Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54μg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (β=0.18, p=0.03 and β=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (β=-12.07, p=0.003 and β=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (β=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects.


KDM5A promotes proliferation and EMT in ovarian cancer and closely correlates with PTX resistance.
The authors initially performed reverse transcription‑quantitative polymerase chain reaction to determine the expression profile of KDM5A in ovarian cancer tissues and adjacent normal tissue. Compared with adjacent normal tissue, it was identified that KDM5A was highly expressed in ovarian cancer tissues. Moreover, human ovarian cell lines also confirmed that KDM5A was highly expressed in ovarian cancer. KDM5A was especially highly expressed in SKOV3/paclitaxel (PTX) cells, which are resistant to PTX. Previous studies demonstrated that chemoresistance in cancer cells facilitates epithelial‑to‑mesenchymal transition (EMT). Following this, whether KDM5A influenced EMT and metastasis was investigated. The expression of KDM5A and N‑cadherin were obviously higher in SKOV3/PTX cells than in SKOV3 cells. The expression of E‑cadherin was decreased and the expression of N‑cadherin was increased following ectopic expression of KDM5A, while the expression of E‑cadherin was increased and the expression of N‑cadherin was decreased following KDM5A depletion. Transwell and wound healing assays were used to explore the function of KMD5A in metastasis. The present results indicated that KDM5A facilitated EMT and metastasis in ovarian cells. Moreover, it was identified that P‑glycoprotein was increased while KDM5A was expressed ectopically in SKOV3 cells. Following fluorescence‑activated cell sorting flow cytometry analysis and CCK‑8 assay all revealed that KDM5A regulated the PTX sensitivity in SKOV3 and SKOV3/PTX cells. In brief, KDM5A is a crucial oncogene that is significantly upregulated in ovarian cancer. Its expression is closely correlated with cancer cell proliferation, EMT and metastasis. KDM5A suppresses ovarian cancer cell apoptosis under PTX treatment.


Why don't we find more polymorphs?
Crystal structure prediction (CSP) studies are not limited to being a search for the most thermodynamically stable crystal structure, but play a valuable role in understanding polymorphism, as shown by interdisciplinary studies where the crystal energy landscape has been explored experimentally and computationally. CSP usually produces more thermodynamically plausible crystal structures than known polymorphs. This article illustrates some reasons why: because (i) of approximations in the calculations, particularly the neglect of thermal effects (see §1.1); (ii) of the molecular rearrangement during nucleation and growth (see §1.2); (iii) the solid-state structures observed show dynamic or static disorder, stacking faults, other defects or are not crystalline and so represent more than one calculated structure (see §1.3); (iv) the structures are metastable relative to other molecular compositions (see §1.4); (v) the right crystallization experiment has not yet been performed (see §1.5) or (vi) cannot be performed (see §1.6) and the possibility (vii) that the polymorphs are not detected or structurally characterized (see §1.7). Thus, we can only aspire to a general predictive theory for polymorphism, as this appears to require a quantitative understanding of the kinetic factors involved in all possible multi-component crystallizations. For a specific molecule, analysis of the crystal energy landscape shows the potential complexity of its crystallization behaviour.


The impact of very late revascularization of occluded infarct-related artery on cardiac mortality and the incidence of sudden death in survivors of acute myocardial infarction - long-term observation.
In survivors of acute myocardial infarction (AMI), an occluded infarct-related artery (IRA) is an important predictor of cardiac death (CD) and sudden death (SD). Early reperfusion of the IRA was associated with improved survival rate. The purpose of the present study was to assess if late IRA revascularization, performed 10-30 days after AMI, also has a beneficial effect on the incidence of CD and SD during an 18-month follow-up. The study population consisted of 93 post-MI patients with occluded IRA on coronary angiography. The patients were divided into 2 groups according to IRA status at discharge -- revascularized (47 patients) or occluded (46 patients) -- and followed. Before revascularization, the two groups of patients did not differ in the prevalence of clinical and angiographic variables, or in the incidence of risk factors for SD. In patients who underwent angioplasty or bypass graft surgery of closed IRA, the markers of electrical instability demonstrated no significant improvement after revascularization. During the 18-month follow-up a significantly lower incidence of CD (0% vs 15%, p<0.01) and SD (0% vs 11%, p<0.03) was observed in the group of patients with revascularized IRA than in the group of patients with occluded IRA. In survivors of AMI, late reperfusion of occluded IRA is associated with reduced 18-month cardiac mortality. The beneficial effect of this procedure on the incidence of sudden death, not associated with improvement in myocardial electrical stability, suggests that ischemia can be considered an important factor modulating the arrhythmogenic substrate.


Shotgun injury to the arm: a staged protocol for upper limb salvage.
Low-energy shotgun fractures involving the arm are complex injuries. Previously published reports have emphasized various problems associated with these injuries. This case report describes a low-energy shotgun wound managed by a staged treatment protocol involving: (1) a spanning external fixator and immediate soft tissue management, followed by (2) osteosynthesis and autogenous bone grafting and (3) epineural suturing of injured radial nerve, with a successful outcome. Although adequate debridement of the fracture and soft tissue wound is the key to open fracture management, some difference of opinion exists with regard to the timing of bone reconstruction and grafting. In severe type III open fractures, or in wounds that are marginal, it may be best to delay cancellous bone grafting until soft tissue has stabilized following acute trauma when the risk of infection has been minimized. If early coverage of vital structures is not possible, local or remote flap coverage may be necessary.


Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV). A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases. Secondary endpoints included use of rescue medication, quality of life (QoL) and incidence of adverse events. Seventeen RCTs were identified. Among patients receiving radiotherapy to abdomen/pelvis, our meta-analysis showed that prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA) was significantly more efficacious than placebo and dopamine receptor antagonists in both complete control of vomiting [OR 0.49; 95% confidence interval (CI): 0.33-0.72 and OR 0.17; 95% CI: 0.05-0.58 respectively] and complete control of nausea (OR 0.43; 95% CI: 0.26-0.70 and OR 0.46; 95% CI: 0.24-0.88 respectively). 5HT3 RAs were also more efficacious than rescue therapy and dopamine receptor antagonists plus dexamethasone. The addition of dexamethasone to 5HT3 RA compared to 5HT3 RA alone provides a modest improvement in prophylaxis of RINV. Among patients receiving TBI, 5HT3 RA was more effective than other agents (placebo, combination of metoclopramide, dexamethasone and lorazepam). 5HT3 RAs are more effective than other antiemetics for prophylaxis of RINV in patients receiving radiotherapy to abdomen/pelvis and TBI. Future RCTs should investigate the efficacy of newer agents such as substance P neurokinin 1 receptor antagonists in addition to 5HT3 RAs in prophylaxis of RINV during both acute and delayed phases.


Toward a Stable and Potent Coenzyme A-Targeting Antiplasmodial Agent: Structure-Activity Relationship Studies of N-Phenethyl-α-methyl-pantothenamide.
Pantothenamides (PanAms) are potent antiplasmodials with low human toxicity currently being investigated as antimalarials with a novel mode of action. These structural analogues of pantothenate, the vitamin precursor of the essential cofactor coenzyme A, are susceptible to degradation by pantetheinase enzymes present in serum. We previously discovered that α-methylation of the β-alanine moiety of PanAms increases their stability in serum and identified N-phenethyl-α-methyl-pantothenamide as a pantetheinase-resistant PanAm with potent, on-target, and selective antiplasmodial activity. In this study, we performed structure-activity relationship investigations to establish whether stability and potency can be improved further through alternative modification of the scissile amide bond and through substitution/modification of the phenyl ring. Additionally, for the first time, the importance of the stereochemistry of the α-methyl group was evaluated in terms of stability versus potency. Our results demonstrate that α-methylation remains the superior choice for amide modification, and that while monofluoro-substitution of the phenyl ring (that often improves ADME properties) was tolerated, N-phenethyl-α-methyl-pantothenamide remains the most potent analogue. We show that the 2S,2'R-diastereomer is far more potent than the 2R,2'R-diastereomer and that this cannot be attributed to preferential metabolic activation by pantothenate kinase, the first enzyme of the coenzyme A biosynthesis pathway. Unexpectedly, the more potent 2S,2'R-diastereomer is also more prone to pantetheinase-mediated degradation. Finally, the results of in vitro studies to assess permeability and metabolic stability of the 2S,2'R-diastereomer suggested species-dependent degradation via amide hydrolysis. Our study provides important information for the continued development of PanAm-based antimalarials.


The Visceral Adiposity Index Is a Better Predictor of Excess Visceral Fat in Military Pilots: A Cross-sectional Observational Study.
Visceral adipose tissue (VAT) is related to cardiometabolic risk. Estimating it using the visceral adiposity index (VAI) could identify this risk in the Brazilian Air Force (BAF) aviator population. The aim here is to verify the predictive capacity of the VAI for identifying visceral fat areas compared to traditional obesity indicators in BAF pilots. Forty male BAF pilots were recruited. The study was conducted in two stages: the first applied a structured questionnaire to characterize the sample and identify sedentary behavior and the second obtained nutritional, anthropometric, and body composition data, carrying out biochemical and magnetic resonance imaging tests and investigating physical activity level in this stage. The comparison of the predictive capacity of the VAI with that of other adiposity indicators (body mass index [BMI], waist circumference, waist-height ratio, waist-hip ratio, and neck circumference) for detecting increased VAT and the determination of the optimal cutoff points for the different adiposity indicators were carried out using receiving operating characteristic (ROC) curves. An association was verified between the adiposity indicators and excess visceral fat using Poisson regression analysis with robust variance. The VAI presented a better predictive capacity for VAT (area under the ROC curve = 0.941), while the BMI did not present diagnostic accuracy (95% CI < 0.5). The strength of the association with high visceral fat was also greater for the VAI than for the other indicators evaluated. The VAI was shown to be a better predictor of excess VAT in relation to the other indicators studied. As it is a more easy-access and lower-cost technique than resonance, it enables greater applicability in tracing and monitoring the visceral obesity of a large contingent of military personnel.


Characteristics Associated with Hospitalization Among Patients with COVID-19 - Metropolitan Atlanta, Georgia, March-April 2020.
The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.


Diagnosing Cardiac Amyloidosis: From Heart Failure to Electrical Storm.
Cardiac amyloidosis is a condition when amyloid fibers are deposited in the extracellular space of the heart causing tachyarrhythmias, heart failure, or sudden cardiac death. We present a 71-year-old woman presenting with dyspnea on admission. Echocardiogram revealed diastolic heart failure and left ventricular hypertrophy with strain pattern concerning for an infiltrative process. She was discharged with diuretic therapy and scheduled for a cardiac magnetic resonance imaging. One week after discharge, she was readmitted with progressive shortness of breath and syncope. She was found to be in shock and had multiple episodes of cardiac arrest with both ventricular tachycardia and pulseless electrical activity. She developed electrical storm and eventually passed within 24 hours. Autopsy revealed gross cardiomegaly and left ventricular hypertrophy with Congo red staining revealing amyloid fibrils with apple-green birefringence. This case demonstrates the rapid progression of cardiac amyloidosis from acute-onset diastolic heart failure to uncontrollable ventricular tachycardia, and eventually death. We review the literature regarding multiple diagnostic modalities that facilitate the confirmation of cardiac amyloidosis.


Normalization of network connectivity in hemispatial neglect recovery.
We recently reported that spatial and nonspatial attention deficits in stroke patients with hemispatial neglect are correlated at 2 weeks postonset with widespread alterations of interhemispheric and intrahemispheric functional connectivity (FC) measured with resting-state functional magnetic resonance imaging across multiple brain networks. The mechanisms underlying neglect recovery are largely unknown. In this study, we test the hypothesis that recovery of hemispatial neglect correlates with a return of network connectivity toward a normal pattern, herein defined as "network normalization." We measured attention deficits with a neuropsychological battery and FC in a large cohort of stroke patients at, on average, 2 weeks (n = 99), 3 months (n = 77), and 12 months (n = 64) postonset. The relationship between behavioral improvement and changes in FC was analyzed both in terms of a priori regions and networks known to be abnormal subacutely and in a data-driven manner. Attention deficit recovery was mostly complete by 3 months and was significantly correlated with a normalization of abnormal FC across many networks. Improvement of attention deficits, independent of initial severity, was correlated with improvements of previously depressed interhemispheric FC across attention, sensory, and motor networks, and a restoration of the normal anticorrelation between dorsal attention/motor regions and default-mode/frontoparietal regions, particularly in the damaged hemisphere. These results demonstrate that abnormal network connectivity in hemispatial neglect is behaviorally relevant. A return toward normal network interactions, and presumably optimal information processing, is therefore a systems-level mechanism that is associated with improvements of attention over time after focal injury. Ann Neurol 2016;80:127-141.


Measuring Violence Against Women: A Global Index.
Violence against women (VaW) is a widespread crime and violation of the rights of women. It is present in every country without exception and crosses boundaries of culture, class, education, income, and race. Despite the magnitude of the literature and the abundance of publications on this problem, the field lacks a comprehensive and homogeneous way to measure and compare the extent of VaW across countries. Proper quantification of this problem is needed to develop preventive policies and strategies to reduce it. This article develops an index of VaW (VAWI) with global scope and multidimensional approach for 102 countries. It is an original index that calculates the total level of VaW by capturing information from the main VaW types (physical, sexual, psychological, and economic violence) in a single value between 0 and 1, where 0 denotes complete absence of violence and 1 the highest level of violence in a country. The proposed index is easy to compute and is comparable across countries. Our main results show that the nations with the highest levels of global VaW are Yemen, Senegal, Oman, Cameroon, and Uganda. The countries with the lowest levels are the Northern European Countries, Canada, and Malta. This VAWI makes a novel and important contribution to the study of gender issues. It can be used not only to monitor the statistics on VaW data within countries over time but also to make comparisons among countries. Further, it could be useful in designing new policy initiatives to reduce VaW.


Serotype B/C Cryptococcus neoformans isolated from patients in nonendemic areas.
Of 90 clinical isolates of Cryptococcus neoformans studied, 3 were determined to be serotype B/C. The patients from whom these B/C isolates were obtained were identified as never having lived in or visited the areas associated with B/C serotypes. This finding suggests a broader geographic distribution of this serotype group than previously believed. The glycine-cycloheximide-phenol red medium described by Salkin and Hurd (J. Clin. Microbiol. 15:169-171, 1982) was shown to be more accurate in differentiating A/D and B/D serotype pairs of C. neoformans than the creatinine-dextrose-bromthymol blue medium described by Kwon-Chung et al. (Int. J. Syst. Bacteriol. 28:616-620, 1978).


Emergency department services use among immigrant and non-immigrant groups in the United States.
Immigrants have disproportionate lack of access to healthcare and insurance. Emergency departments could serve as a healthcare substitute and increased demand can negatively affect the US emergency services system. Medical Expenditures Panel Survey (2000-2008) data was modeled to compare emergency departments (ED) use between non-citizens, foreign-born (naturalized), and US-born citizens. Group differences were assessed using non-linear decomposition techniques. Non-citizens were less likely to use ED services (8.7 %) compared to naturalized immigrants (10.6 %) and US-born Americans (14.7 %). Differences in ED use persisted after adjusting for the Behavioral Model covariates. Healthcare need and insurance partially explained the differences in ED use between the groups. Between 2000 and 2008 non-citizen immigrants used markedly less ED services compared to US citizens, regardless of their nation of origin. We also found that demographic and healthcare need profiles contributed to the divergence in use patterns between groups. A less restrictive healthcare policy environment can potentially contribute to lower population disease burden and greater efficiencies in the US health care system.


Insufficiency of self-phosphorylation for the activation of epidermal growth factor receptor.
Polyclonal immunoglobulins were produced against the carboxy terminus, -SEFIGA, of the receptor for epidermal growth factor (EGF). The addition of these immunoglobulins to a solution containing EGF receptor resulted in the activation of its protein tyrosine kinase. The levels of activation were assessed by measuring the initial velocities of the phosphorylation of the tyrosine in angiotensin II. The enzymatic activity induced by the immunoglobulins was significant, usually 50-70% of the maximum activity induced by EGF, and the induction occurred over a narrow range of concentration of the immunoglobulins. In order to achieve the activation, the immunoglobulins had to be bivalent; the addition of monovalent Fab fragments to EGF receptor did not produce any activation of the protein tyrosine kinase. The activation produced by the immunoglobulins was found to be reversible upon the addition of the synthetic peptide SEFIGA against which the immunoglobulins had been produced. Self-phosphorylation of the EGF receptor also occurred as the enzyme was activated by the immunoglobulins. Tryptic peptide maps demonstrated that the self-phosphorylation caused by the immunoglobulins had the same signature as that produced by EGF. When the synthetic peptide that had been used as the hapten was added to EGF receptor that had been self-phosphorylated in the presence of the immunoglobulins, the stimulated enzymatic activity was lost even though the protein remained phosphorylated. It follows from the results of deletion mutation [Walton, G. M., Chen, W. S., Rosenfeld, M. G., & Gill, G. N. (1990) J. Biol. Chem. 265, 1750-1754] and the results reported here that self-phosphorylation is neither necessary nor sufficient for the activation of EGF receptor.


Osteocalcin and deoxyribonucleic acid synthesis in vitro and histomorphometric indices of bone formation in postmenopausal osteoporosis.
The aim of this study was to determine whether abnormal osteoblastic growth and/or differentiation play a role in the decreased bone formation in women with postmenopausal osteoporosis. To do so, we compared bone formation evaluated by histomorphometric methods and the proliferation kinetics and phenotypic expression of osteoblastic cells isolated from the trabecular bone surface. We found that osteoblastic cells isolated from women whose trabecular bone had low double tetracycline-labeled surface and decreased mean wall thickness had a reduced rate of cell proliferation. The peak of [3H]thymidine incorporation into DNA, the maximal DNA synthesis, and the area under the curve of bone cell proliferation were significantly lower in these women than in those with high double tetracycline-labeled surface. In addition, the parameters of bone cell replication correlated with osteoblastic surface and mean wall thickness. By contrast, the initial osteocalcin production and alkaline phosphatase activity and the response to 10 nmol/L 1,25-dihydroxyvitamin D (48 h) in vitro were similar in women with low, normal, or high bone formation. These results indicate that reduction of bone formation in women with postmenopausal osteoporosis results from an impaired proliferative capacity of cells of osteoblastic lineage present at the trabecular bone surface level.


Quality of life and scar evolution after negative pressure or conventional therapy for wound dehiscence following post-bariatric abdominoplasty.
No studies have examined scars and quality of life after different treatments of wound dehiscence in patients undergoing post-bariatric abdominoplasty. Scars and quality of life of patients with postoperative wound dehiscence managed with negative pressure wound therapy (group A) and conventional wound therapy (group B) were reviewed 6 months after wound healing. Of 38 patients undergoing treatment for wound dehiscence after 203 abdominoplasty, 35 (group A = 14 versus group B = 21) entered the study. Wound healing in group A was significantly faster than group B (P = 0·001). Patients (P = 0·0001) and observers (P = 0·0001) reported better overall opinions on a scar assessment scale for group A. Better overall quality of life and general health satisfaction were observed in group A (P < 0·05). A significant correlation was observed between the World Health Organization Quality of Life scores and Patient and Observer Scar Assessment Scale scores (r=-0·68, P < 0·0001) in all 35 patients. Negative pressure wound therapy is feasible and effective in patients with wound dehiscence following post-bariatric abdominoplasty. An adequate post-treatment outcome is achieved compared with conventional wound therapy in light of a strong association found between worse patient scar self-assessment and poor overall quality of life, regardless of the received treatment.


Myeloid-derived suppressor cells: paradoxical roles in infection and immunity.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature suppressor cells that are generated due to aberrant myelopoiesis under pathological conditions. Although MDSCs have been recognized for more than 20 years under the guise of different monikers, these particular populations of myeloid cells gained more attention recently due to their immunosuppressive properties, which halt host immune responses to growing cancers or overwhelming infections. While MDSCs may contribute to immune homeostasis after infection or tissue injury by limiting excessive inflammatory processes, their expansion may be at the expense of pathogen elimination and thus may lead to disease persistence. Therefore, MDSCs may be either damaging or obliging to the host by attenuating, for example, antitumor or anti-infectious immune responses. In this review, we recapitulate the biological and immunological aspects of MDSCs, including their generation, distribution, trafficking and the factors involved in their activation, expansion, suppressive functions, and interplay between MDSCs and regulatory T cells, with a focus on the perspectives of infection and inflammation.


Intrasplenic Transplantation of Hepatocytes After Partial Hepatectomy in NOD.SCID Mice.
Partial hepatectomy is a versatile and reproducible method to study liver regeneration and the effect of cell based therapeutics in various pathological conditions. Partial hepatectomy also facilitates the increased engraftment and proliferation of transplanted cells by accelerating neovascularization and cell migration towards the liver. Here, we describe a simple protocol for performing 30% hepatectomy and transplantation of cells in the spleen of a non-obese diabetic/severe combined immunodeficient NOD.SCID (NOD.CB17-Prkdcscid/J) mouse. In this procedure, two small incisions are made. The first incision is to expose and resect the left lobe of the liver, and another small incision is made to expose the spleen for the intrasplenic transplantation of cells. This procedure does not require any specialized surgical skills, and it can be completed in 5-7 minutes with less stress and pain, faster recovery, and better survival. We have demonstrated the transplantation of hepatocytes isolated from a green fluorescent protein (GFP) expressing mouse (Transgenic C57BL/6-Tg (UBC-GFP) 30Scha/J), as well as hepatocyte like cells of human origin (NeoHep) in partially hepatectomized NOD.SCID mice.


Strategic effects of future environmental policy commitments: climate change, solar radiation management and correlated air pollutants.
We study the effects of environmental policy commitments in a futuristic world in which solar radiation management (SRM) can be utilized to reduce climate change damages. Carbon and sulfur dioxide emissions (correlated pollutants) can be reduced through tradable permits. We show that if nations simultaneously commit to carbon permit policies, national SRM levels rise with carbon quotas. Alternatively, if they simultaneously commit to SRM policies, the global temperature falls with each unit increase in the global SRM level. A nation always wishes to be a leader in policymaking, but prefers carbon to SRM policymaking. The globe prefers SRM policy commitments.


Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex.
The location of short-term memory in mammalian neocortex remains elusive. Here we show that distinct neocortical areas maintain short-term memory depending on behavioral strategy. Using wide-field and single-cell calcium imaging, we measured layer 2/3 neuronal activity in mice performing a whisker-based texture discrimination task with delayed response. Mice either deployed an active strategy-engaging their body toward the approaching texture-or passively awaited the touch. Independent of strategy, whisker-related posterior areas encoded choice early after touch. During the delay, in contrast, persistent cortical activity was located medio-frontally in active trials but in a lateral posterior area in passive trials. Perturbing these areas impaired performance for the associated strategy and also provoked strategy switches. Frontally maintained information related to future action, whereas activity in the posterior cortex reflected past stimulus identity. Thus, depending on behavioral strategy, cortical activity is routed differentially to hold information either frontally or posteriorly before converging to similar action.