Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature.
The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.


A novel management proposal for intrinsic brainstem neurenteric cysts: case report.
Neurenteric cysts (NCs) are rare congenital lesions with epithelial mucin-secreting walls. They can occur anywhere along the neural axis, and an intrinsic midbrain cyst is extraordinary. Surgical management may pose a challenge due to the location of the lesion and adhesion of the cyst wall to the surrounding brainstem. The authors describe the first case of pediatric NC that was treated successfully with intracystic interferon-α (IFN-α).A 16-month-old baby girl presented with a 2-week history of progressive croup, vomiting, and swallowing difficulty. MRI revealed a 1.8-cm cystic intrinsic lesion in the pontomedullary region. She initially underwent posterior fossa craniotomy and drainage of the cyst under intraoperative neurophysiology monitoring. Three weeks following the procedure, her symptoms recurred, and follow-up MRI demonstrated cystic recurrence. She underwent repeat aspiration of the cyst and biopsy of the cyst wall, and INF-α-2b was injected into the cystic cavity. Her symptoms improved and completely resolved after 5 months. A 9-month follow-up brain MRI study showed complete resolution of the NC. Intracystic IFN-α injection after cystic content aspiration may be a safe treatment option for the management of intrinsic brainstem NCs. Long-term clinical and radiological follow-up is recommended.


The snapshot pre-registration assessment tool. Part 2: data, discussion and future directions.
This paper is the second of a two-part article presenting a new assessment tool (the snapshot) for pre-registration nurses in clinical practice that is being used at Kingston University/St George's University of London during year 3 of the Diploma and BSc programme. Part 1 of this article presented background to the snapshot tool and the research approach used in the evaluative research study. Part 2 will present the data collection, findings and discussion which show that the snapshot is perceived positively by students in terms of the criteria, documentation and process. However, mentor understanding of these factors varied with some mentors having an inadequate understanding and additional questions of assessment validity also arose and need to be addressed. Both parts of this article make a contribution to the practice assessment agenda and to the continuous clinical assessment methods currently in use that tests students' competence against agreed criteria. The snapshot reflects the reality of practice and assesses skills in a realistic environment.


Lysozyme binding with amikacin and levofloxacin studied by tritium probe, fluorescence spectroscopy and molecular docking.
Lysozyme complexes with amikacin and levofloxacin were studied by spectroscopy approaches as well as using a tritium probe. Tritium was used as a labeling agent to trace labeled compound concentration in a system of two immiscible liquids and in the atomic form to determine the possible position of the binding site. Co-adsorption of protein and drug at the liquid-liquid interface was analyzed by scintillation phase method that allowed us to directly determine the amount of protein and drug in the mixed adsorption layer. Also, tensiometric measuring of the interfacial tension was used for calculation of binding parameters accordingly to Fainerman model. The treatment of complexes with atomic tritium followed by trypsinolysis and analysis of tritium distribution in the lysozyme peptides reveals the binding sites, binding energies in which were analyzed using molecular docking. Formation of complexes with amikacin and levofloxacin preserves secondar structure of protein. However, the formation of complex with amikacin leads to the almost total loss of the enzymatic activity of lysozyme and the redshift of the maximum on the lysozyme fluorescence band. A slight decrease in the distribution coefficient of lysozyme in the presence of amikacin assumes that the complex has higher hydrophilicity in comparison to lysozyme without additives. The most favorable for binding were the positions of the active centers that included amino acids Asp52 and Glu35, as well as in the vicinity of peptide His15-Arg21, with the participation of amino acids Tyr20, Arg14. In the case of levofloxacin, the formation of lysozyme-ligand complex in aqueous solution is possible without changing the microenvironment of the active center of the protein. Binding of levofloxacin to the active center of the enzyme was the most favorable, but Asp52 and Glu35 that are responsible for the enzymatic activity of lysozyme, were not affected.


Novel Fitc-Labeled Igy Antibody: Fluorescence Imaging Toxoplasma Gondii In Vitro.
Toxoplasmosis is caused by T. gondii and can create serious health problems in humans and also worldwide economic harm. Because of the clinical and veterinary importance of toxoplasmosis, its timely and accurate diagnosis has a major impact on disease-fighting strategies. T. gondii surface antigen 1 (SAG1), an immunodominant-specific antigen, is often used as a diagnostic tool. Therefore, the aim of this study was the optimization of novel fluorescein isothiocyanate (FITC) labeling of the SAG1-specific IgY antibody to show the potential for immunofluorescence imaging of T. gondii in vitro. The specificity of IgY antibodies was controlled by an enzyme-linked immunosorbent assay (ELISA), and the concentration of the IgY antibody was detected using a spectrophotometer. The optimum incubation time and FITC concentration were determined with a fluorescence spectrometer. The obtained FITC-labeled IgY was used for marking T. gondii tachyzoites, which were cultured in vitro and viewed using light microscopy. The interaction of the fluorescence-labeled antibody and the T. gondii tachyzoites was examined with a fluorescence microscope. In this study, for the first time, a FITC-labeled anti-SAG1 IgY antibody was developed according to ELISA, fluorescence spectrometer, and fluorescence imaging of cell culture. In the future, the obtained FITC-labeled T. gondii tachyzoites' specific IgY antibodies may be used as diagnostic tools for the detection of T. gondii infections in different samples.


[Post-photosynthetic use of labeled assimilates in fiber flax].
The distribution of 14C in various tissues of fiber flax was assayed 1, 17, and 21 days after 30-min assimilation of 14CO@2 by the whole rapidly growing plant. Polymeric photosynthetic products were largely hydrolyzed in the 14C-donor part of the shoot and the hydrolysates were transported upward. The content of 14C in pigments and lipids of the donor leaves (that absorbed 14CO2) was significantly higher than that in the 14C-acceptor ones. An additional nitrogen feeding decreased the labeled sucrose: hexose ratio and inhibited transport of the assimilates from both 14C-donor and acceptor leaves. 14C transported to the shoot tip was largely used for synthesis of poorly soluble proteins (extractable with alkali and Triton X-100) in the acceptor tissues. In the donor part of the shoot, particularly in the bast, cellulose was mainly synthesized from the "new" assimilates.


Utrecht work engagement scale: Construct validity and reliability in Chilean health science students.
The Utrecht Work Engagement Scale-Student (UWES-S) has been extensively applied in different countries to assess engagement in students, but there are discrepancies about its factor structure outcomes. To analyse the factor structure of Utrecht Work Engagement Scale-Student as construct validity evidence and reliability in medical students. The non-experimental cross-sectional study was conducted at the public-sector University of Concepción in the Bio-Bio region in central Chile at the end of the first academic semester, between July and August 2017, and comprised students of health science undergraduate degree programmes in Medicine, Kinesiology, Pharmacy, and Speech and Language Therapy. Data was collected using a sociodemographic proforma and the Utrecht Work Engagement Scale-Student. The subjects were randomly divided into groups A and B. With group A, exploratory factor analysis was performed using the method of extraction of the main axis analysis. With group B, confirmatory factor analysis was performed using the maximum likelihood method. Data was analysed using STATA 11 SE. Of the 898 students, 538(59.91%) were females and 360(40.09%) were males. The overall mean age was 21.29±2.51 years (range: 17-34 years). Two factors, 'involvement with studies' and 'enthusiasm for the career', with eigenvalues 7.59 and 1.18 were identified with the potential to explain majority of the total variance of items. Comparative fit index, Tucker-Lewis index and the root mean square error of approximation showed the solution having the best fit. Involvement with studies and enthusiasm for career were found to be critical factors, but did not show adequate adjustment even though confirmatory factor analysis found this to be the solution with the best fit.


Typus melancholicus and the Temperament and Character Inventory personality dimensions in patients with major depression.
Although many clinical studies have been conducted to determine the etiological role and clinical implications of typus melancholicus for unipolar depression, maladaptive personality features in depressive patients have not been well described. This study explores typus melancholicus, as measured by the rigidity subscale of the Munich Personality Test, and maladaptive personality features, as measured by the Temperament and Character Inventory (TCI), in 131 remitted patients with DSM-IV major depression and 154 normal controls. The patients reported significantly higher scores on rigidity and harm avoidance and significantly lower scores on self-directedness and cooperativeness. Only 23.6% of the variance of the rigidity scale was explained by the variance of the seven TCI scales, in which only persistence was significantly correlated positively to rigidity. Cluster analysis identified four subgroups, two of which were characterized by a high rigidity score. One of these two subgroups showed no maladaptive personality features, as measured by the TCI, while the other showed high harm avoidance and low self-directedness. These results indicate that the personality of depressive patients is characterized not only by typus melancholicus but also by maladaptive personality features, that typus melancholicus is not well represented by any TCI scale, and that typus melancholicus and maladaptive personality features can coexist in some depressive patients.


[Multiple PCR ALLPLEX TM ENTERO-DR for multidrug-resistant Enterobacteriaceae management at Albacete University Hospital].
Multi-resistant Enterobacteriaceae (MRE) are a public health threat, with screening and isolation strategies being important to stop its dissemination. Multiplex PCR is a novel method capable of rapid diagnosis with high sensitivity and specificity. In this study, our objective was to evaluate its application to multidrug-resistant Enterobacteriaceae management since its implementation in our hospital. An observational retrospective descriptive study of multiplex PCR ALLPLEX TM ENTERO-DR results to screen inpatients colonized by MRE took place from November 2019 to May 2021. We calculated the percentage of positive, negative, non-identifiable or invalid results, identified microorganisms, reason for requesting it and subsequent actions. Median and I.R. from sampling time to partial and theoretical culture time, and since last colonization/infection depending on test results were calculated. Resistance mechanisms were detected in 31.47% of tests, being E. coli ESBL (68.99%) the most frequently isolated microorganism. Median time to partial result was 5.75 hours (I.R.: 2.67), having statistically significant differences with theoretical time. The most important reason to request the test was screening (80.12%) and the most frequent action taken was not to isolate (41.70 %). Whenever forty-nine months or more since last colonization/infection have passed, only 14.81% of the samples tested positive. Multiplex PCR is a useful test to manage colonized patients, capable of giving a rapid result and allowing for quicker decision-making, contributing to a good use of resources and patient comfort.


Imaging of the atlas (C1) and axis (C2).
In imaging the atlantoaxial region in injured patients, the initial modality is plain radiography. The lateral C-spine as well as the open-mouth view are essential in this regard. On these views, it is not only important to examine the bony contour but also to look for indirect signs of injury such as prevertebral soft-tissue swelling, air in the prevertebral space, an increased width of the anterior atlantodental interval, and overriding of the C1-C2 joint on one side (the so-called wink sign of atlantoaxial rotatory subluxation). In patients in whom there is a high index of suspicion for occult trauma, but without fractures suggested or adequately visualized on routine films, or in those with severe cranial trauma, further studies should be pursued. CT scan is the modality of choice in optimally imaging the bony contours of the axis and atlas. It has limitations in visualizing transversely oriented fractures such as high dens fractures, transverse fractures of the facet joints (although widening of the facet joint is an indirect indication of facet fracture), or transverse arch fractures. Plain tomography may better demonstrate such transverse fractures but has several disadvantages. Plain tomography is often not as readily available as CT; it requires that the patient be placed in lateral decubitus position to obtain lateral tomograms, which may be contraindicated in such clinical circumstances; and it is not as easy to appreciate three-dimensional relationships on plain tomography as it is on CT. CT clearly defines the location of displaced bone fragments in relationship to the spinal canal as well as often demonstrating disc injuries. Ligamentous injury, though potentially visualized directly on MR imaging, is more commonly addressed with flexion-extension films. Flexion-extension studies should, obviously, be performed only in awake, oriented patients who are without neurologic deficit, and the studies should be done with close physician supervision and stopped at the first onset of pain. MR imaging may be helpful in demonstrating soft-tissue injuries such as hemorrhage, disc herniation, nerve root impingement, and direct spinal cord damage.


Authenticity as a Resilience Factor Against CV-19 Threat Among Those With Chronic Pain and Posttraumatic Stress Disorder.
The novel coronavirus (2019; CV-19) is linked to increases in emotional distress and may be particularly problematic for those with pre-existing mental and physical conditions, such as chronic pain and posttraumatic stress disorder (PTSD). However, little empirical research has been published on resilience factors in these individuals. The present study aims to examine authenticity as a resilience factor among those with chronic pain and/or PTSD. Prior to the national response to the pandemic (January 10-24, 2020), participants were screened for pain-related disability (Oswestry Disability Index; ODI) and PTSD symptoms (Posttraumatic Checklist for DSM-5; PCL-5), and on the basis of those responses were categorized into one of four groups: healthy, chronic pain only, PTSD only, or comorbid chronic pain and PTSD. During the CV-19 pandemic (May 5-May 13, 2020), participants responded again to the ODI and PCL-5, in addition to the Wood Authenticity Scale, Brief Pain Inventory, and items related to the CV-19 pandemic. A total of 110 participants (54.55% women), aged 42.19 (SD = 13.16), completed the survey during the pandemic. The comorbid group endorsed higher levels of CV-19 Threat and Impact compared to all other groups. Authenticity moderated this relationship relevant to CV-19 Threat among those in the chronic pain only group, and not in any other group. The comorbid group endorsed higher levels of CV-19 Threat and Impact compared to all other groups. Importantly, greater authenticity was associated with less CV-19 Threat in the chronic pain only group, and not in any other group. The present study also highlights the importance of engaging authentically for those with chronic pain during the pandemic.


Endothelial Cell APOE3 Regulates Neurovascular, Neuronal, and Behavioral Function.
Specialized brain endothelial cells and human APOE3 are independently important for neurovascular function, yet whether APOE3 expression by endothelial cells contributes to brain function is currently unknown. In the present study, we determined whether the loss of endothelial cell APOE3 impacts brain vascular and neural function. We developed APOE3fl/fl/Cdh5(PAC)-CreERT2+/- (APOE3Cre+/-) and APOE3fl/fl/Cdh5(PAC)-CreERT2-/- (APOE3Cre-/-, control) mice and induced endothelial cell APOE3 knockdown with tamoxifen at ≈4 to 5 weeks of age. Neurovascular and neuronal function were evaluated by biochemistry, immunohistochemistry, behavioral testing, and electrophysiology at 9 months of age. We found that the loss of endothelial APOE3 expression was sufficient to cause neurovascular dysfunction including higher permeability and lower vessel coverage in tandem with deficits in spatial memory and fear memory extinction and a disruption of cortical excitatory/inhibitory balance. Our data collectively support the novel concept that endothelial APOE3 plays a critical role in the regulation of the neurovasculature, neural circuit function, and behavior.


Redox regulation of Cdc25C.
The Cdc25 family of dual specific phosphatases are critical components of cell cycle progression and checkpoint control. Certain stresses such as ultraviolet light stimulate the rapid and selective destruction of Cdc25A protein through a Chk1 protein kinase-dependent pathway. We demonstrate that in contrast to cellular stresses previously examined, hydrogen peroxide exposure affects Cdc25C but not Cdc25A levels. Pharmacological inhibition of Chk1 activity or a mutant of Cdc25C that lacks the Chk1 phosphorylation site still undergoes degradation in response to oxidants. We also demonstrate that in vitro hydrogen peroxide stimulates an intramolecular disulfide bond between the active site cysteine at position 377 and another invariant cysteine at position 330. The in vivo stability of Cdc25C is substantially reduced by the mutation of either of these two cysteine residues. In contrast, a double (C2) mutant of both cysteine 330 and cysteine 377 results in a protein that is more stable than wild type Cdc25C and is resistant to oxidative stress-induced degradation. In addition, the C2 mutant, which is unable to form an intramolecular disulfide bond, has reduced binding to 14-3-3 in vitro and in vivo. These results suggest that oxidative stress may induce cell cycle arrest in part through the degradation of Cdc25C.


Bacteriophage-mediated protein delivery into the central nervous system and its application in immunopharmacotherapy.
Cocaine addiction continues to be a major health and social problem in spite of governmental efforts devoted towards educating the public in the dangers of illicit drug use. A variety of pharmacotherapies and psychosocial programmes have been proposed in an effort to provide a method for alleviating the physical and psychological symptoms of cocaine abuse. Unfortunately, these methods have been met with limited success, illustrating a critical need for new effective approaches for the treatment of cocaine addiction. The authors have recently disclosed an alternative cocaine abuse treatment strategy using intranasal administration of an engineered filamentous bacteriophage displaying cocaine-sequestering antibodies on its surface. These phage particles are an effective vector for central nervous system penetration and are capable of binding cocaine, thereby blocking its behavioural effects in a rodent model.


Elevated serotonin in mouse spinal dorsal horn is pronociceptive.
Serotonergic neurons in the rostral ventral medulla (RVM) contribute to bidirectional control of pain through modulation of spinal and trigeminal nociceptive networks. Deficits in this pathway are believed to contribute to pathological pain states, but whether changes in serotonergic mechanisms are pro or anti-nociceptive are debated. We used a combination of optogenetics and fiber photometry to examine these mechanisms more closely. We find that optogenetic activation of RVM serotonergic afferents in the spinal cord of naïve mice produces mechanical hypersensitivity and conditioned place aversion. Neuropathic pain, produced by chronic constriction injury of the infraorbital nerve (CCI-ION), evoked a tonic increase in serotonin concentrations within the spinal trigeminal nucleus caudalis (SpVc), measured with liquid chromatography-tandem mass spectroscopy (LC-MS/MS). By contract, CCI-ION had no effect on the phasic serotonin transients in SpVc, evoked by noxious pinch, and measured with fiber photometry of a serotonin sensor. These findings suggest that serotonin release in the spinal cord is pronociceptive and that an increase is sustained serotonin signaling, rather than phasic or event driven increases, potentiate nociception in models of chronic pain.


Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5.
Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat (Felis catus), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV). The FIV Vif protein interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C (ELOC) to form an E3 ubiquitination complex to induce the degradation of feline A3s. However, the functional domains in FIV Vif for the interaction with Cullin are poorly understood. Here, we found that the expression of dominant negative CUL5 prevented the degradation of feline A3s by FIV Vif, while dominant negative CUL2 had no influence on the degradation of A3. In coimmunoprecipitation assays, FIV Vif bound to CUL5 but not CUL2. To identify the CUL5 interaction site in FIV Vif, the conserved amino acids from positions 47 to 160 of FIV Vif were mutated, but these mutations did not impair the binding of Vif to CUL5. By focusing on a potential zinc-binding motif (K175-C161-C184-C187) of FIV Vif, we found a conserved hydrophobic region (174IR175) that is important for the CUL5 interaction. Mutation of this region also impaired the FIV Vif-induced degradation of feline A3s. Based on a structural model of the FIV Vif-CUL5 interaction, the 52LW53 region in CUL5 was identified as mediating binding to FIV Vif. By comparing our results to the human immunodeficiency virus type 1 (HIV-1) Vif-CUL5 interaction surface (120IR121, a hydrophobic region that is localized in the zinc-binding motif), we suggest that the CUL5 interaction surface in the diverse HIV-1 and FIV Vifs is evolutionarily conserved, indicating a strong structural constraint. However, the FIV Vif-CUL5 interaction is zinc independent, which contrasts with the zinc dependence of HIV-1 Vif.IMPORTANCE Feline immunodeficiency virus (FIV), which is similar to human immunodeficiency virus type 1 (HIV-1), replicates in its natural host in T cells and macrophages that express the antiviral restriction factor APOBEC3 (A3). To escape A3s, FIV and HIV induce the degradation of these proteins by building a ubiquitin ligase complex using the viral protein Vif to connect to cellular proteins, including Cullin 5. Here, we identified the protein residues that regulate this interaction in FIV Vif and Cullin 5. While our structural model suggests that the diverse FIV and HIV-1 Vifs use conserved residues for Cullin 5 binding, FIV Vif binds Cullin 5 independently of zinc, in contrast to HIV-1 Vif.


Population-Based Incidence of Ocular Neovascularization Following Central Retinal Artery Occlusion in Olmsted County, Minnesota.
To determine the population-based incidence of ocular neovascularization (NV) following central retinal artery occlusion (CRAO) and systemic risk factors associated with its development. Diagnosis of CRAO between January 1, 1976, and September 9, 2016, was identified using the Rochester Epidemiology Project, a medical records linkage system for all medical care provided to residents of Olmsted County, Minnesota. Records were reviewed to confirm the diagnosis of CRAO, and data were collected on ocular NV and associated systemic diseases. There were 89 patients with CRAO. Subsequent ocular neovascularization developed in 14 (16%) patients. Neovascularization of the iris (NVI) was present in 9/14 (64%) of these patients, neovascularization of the angle (NVA) in 10/14 (71%), neovascularization of the disc (NVD) in 2/14 (14%), and neovascularization elsewhere (NVE) in 1/14 (7%). Of these 14 patients with NV, 9 (64%) developed neovascular glaucoma (NVG). The mean time from CRAO diagnosis to NV was 82 days (range 22 to 268 days). Excluding the patients with proliferative diabetic retinopathy or CRAO caused by CRVO, the mean time to NV diagnosis was 80 days and the shortest time to NV diagnosis was 22 days. Diabetes mellitus was present in 64% of those with NV compared to 23% of those without NV (P = 0.003). The population-based incidence of ocular neovascularization following CRAO is 16% and developed within 2 months in half the cohort. Patients with diabetes mellitus are at increased risk for NV complications.


Strategic planning for employee happiness: a business goal for human service organizations.
Employee happiness can impact substantially on an organization's performance. It can influence employee retention, absenteeism, and work performance. Because of this importance, such happiness is inseparable from the real business of the organization and should be considered a business goal. Implementation and development of the strategic plan associated with this goal becomes the responsibility of a highly placed project team that has as its mission ensuring employee satisfaction. The strategic plan includes procedures that allow management to listen effectively to employees, assessing and responding to their values and needs. In this paper we discuss the workforce and environmental characteristics that are involved planning for employee happiness and the steps in creating an organizational culture in which this can become a business goal.


[Ampicillin pharmacokinetics in prostatic adenoma patients].
Studies on ampicillin pharmacokinetics in patients with prostate adenoma showed that adenoma did not influence the antibiotic kinetics. The ampicillin maximum concentration in tissues and organs of the urinary corresponded to the peak concentrations in blood. Therefore, development of dosage regimens providing the drug efficient concentrations in tissues and organs of the urinary tract should be based on ampicillin kinetics in the blood.


The tractable cognition thesis.
The recognition that human minds/brains are finite systems with limited resources for computation has led some researchers to advance the Tractable Cognition thesis: Human cognitive capacities are constrained by computational tractability. This thesis, if true, serves cognitive psychology by constraining the space of computational-level theories of cognition. To utilize this constraint, a precise and workable definition of "computational tractability" is needed. Following computer science tradition, many cognitive scientists and psychologists define computational tractability as polynomial-time computability, leading to the P-Cognition thesis. This article explains how and why the P-Cognition thesis may be overly restrictive, risking the exclusion of veridical computational-level theories from scientific investigation. An argument is made to replace the P-Cognition thesis by the FPT-Cognition thesis as an alternative formalization of the Tractable Cognition thesis (here, FPT stands for fixed-parameter tractable). Possible objections to the Tractable Cognition thesis, and its proposed formalization, are discussed, and existing misconceptions are clarified.


Stability and change in sexual orientation identity over a 10-year period in adulthood.
We examined reports of sexual orientation identity stability and change over a 10-year period drawing on data from the National Survey of Midlife Development in the United States (MIDUS I and II) and tested for three patterns: (1) heterosexual stability, (2) female sexual fluidity, and (3) bisexual fluidity. Fifty-four percent of the 2,560 participants were female and the average age was approximately 47 years. At Wave 1, 2,494 (97.42%) reported a heterosexual identity, 32 (1.25%) a homosexual identity, and 34 (1.33%) a bisexual identity and somewhat more than 2% reported a different sexual orientation identity at Wave 2. Although some support for each hypothesis was found, initial sexual orientation identity interacted with gender to predict a more complex pattern. For the sample as a whole, heterosexuality was the most stable identity. For women, bisexuality and homosexuality were equally unstable and significantly less stable than heterosexuality, suggesting that sexual orientation identity fluidity is a pattern that applies more to sexual minority women than heterosexual women. For men, heterosexuality and homosexuality were both relatively stable compared to bisexuality, which stood out as a particularly unstable identity. This pattern of results was consistent with previous findings and helps to address methodological limitations of earlier research by showing the characteristics of a population-based sample of heterosexual, homosexual, and bisexual identified men and women over time.


Treatment of opioid-dependent pregnant women: clinical and research issues.
This article addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance, based on both research evidence and the collective clinical experience of the authors, which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, is provided to aid clinical decision making. The MOTHER project is a double-blind, double-dummy, flexible-dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the treatment of opioid dependence in pregnant women and their neonates. The article begins with a discussion of appropriate assessment during pregnancy and then addresses clinical management stages including maintenance medication selection, induction, and stabilization; opioid agonist medication management before, during, and after delivery; pain management; breast-feeding; and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed.


The relationship between literacy and glycemic control in a diabetes disease-management program.
This study examined the role of literacy in patients with poorly controlled diabetes who were participating in a diabetes management program that included low-literacy-oriented interventions. A before-after analysis was performed of a pharmacist-led diabetes management program for 159 patients with type 2 diabetes and poor glycemic control (hemoglobin A1c [A1C] > or = 8.0%). Clinic-based pharmacists offered one-to-one education and medication management for these patients using techniques that did not require high literacy. Literacy was measured by the Rapid Estimate of Adult Literacy in Medicine (REALM) test and dichotomized at the 6th-grade level. The A1C values were collected prior to enrollment, at enrollment, and approximately 6 months after enrollment. Of the 111 patients with follow-up data, 55% had literacy levels at the 6th-grade level or below. Lower literacy was more common among African Americans, older patients, and patients who required medication assistance. There was no significant relationship between literacy status and A1C prior to enrollment or at enrollment. Over the 6-month study period, patients with low and high literacy had similar improvements in A1C. This diabetes care program, which used individualized teaching with low-literacy techniques, significantly improved A1C values independent of literacy status.


Collagen and muscle pathology in fibromyalgia patients.
To measure collagen concentration and search for muscle pathology in muscle non-tender-point areas from fibromyalgia (FM) patients. Muscle biopsies were obtained from m. vastus lateralis of 27 carefully selected, female fibromyalgia patients, and from eight age-matched female control subjects. Amino acids were determined by HPLC and electron microscopy was performed. The FM patients had lower hydroxyproline and lower total concentration of the major amino acids of collagen than the controls. No significant difference was seen in the concentration of the major amino acids of myosin or of total protein. Electron microscopy showed no significant differences between FM patients and controls although atrophied muscle fibrils occurred in FM patients only, but frequencies were not significantly different. Fibromyalgia patients had a significantly lower amount of intramuscular collagen. This may lower the threshold for muscle micro-injury and thereby result in non-specific signs of muscle pathology.


Characteristics of annual mold variations and association with childhood allergic symptoms/diseases via combining surveys and home visit measurements.
The presence of dampness and visible molds leads to concerns of poor indoor air quality which has been consistently linked with increased exacerbation and development of allergy and respiratory diseases. Due to the limitations of epidemiological surveys, the actual fungal exposure characteristics in residences has not been sufficiently understood. This study aimed to characterize household fungal diversity and its annual temporal and spatial variations. We developed combined cross-sectional survey, repeated air sampling around a year, and DNA sequencing methods. The questionnaire survey was conducted in 2019, and 4943 valid cases were received from parents; a follow-up case-control study (11 cases and 12 controls) was designed, and onsite measurements of indoor environments were repeated in typical summer, transient season, and winter; dust from floor and beddings in children's room were collected and ITS based DNA sequencing of totally 68 samples was conducted. Results from 3361 children without changes to their residences since birth verified the significant associations of indoor dampness/mold indicators and prevalence of children-reported diseases, with increased adjusted odd ratios (aORs) >1 for studied asthma, wheeze, allergic rhinitis, and eczema. The airborne fungal concentrations from air sampling were higher than 1000 CFU/m3 in summer, regardless of indoors and outdoors, indicating an intermediate pollution level. The DNA sequencing for dust showed the Aspergillus was the predominant at genus level and the Aspergillus_penicillioides was the most common at species level; while the fungal community and composition varied significantly in different homes and seasons, according to α and β diversity analyses. The comprehensive research methods contribute to a holistic understanding of indoor fungal exposure, including the concentrations, seasonal variations, community, and diversity, and verifies the relations with children's adverse health outcomes. The study further elucidates the role of microbiome in human health, which helps setting health-protective thresholds and managing mold treatments in buildings, to promote indoor air quality and human well-beings.


Abnormal membrane cation transport in pregnancy-induced hypertension.
An abnormality of sodium handling has been suggested as one of the mechanisms responsible for the development of pregnancy-induced hypertension. We analysed the plasma and urinary concentrations, and the intraerythrocyte activities of Na and K, and the RBC membrane Na+/K+-ATPase activity of 77 hypertensive and 133 normal pregnant women. Umbilical cord blood of infants from 21 hypertensive and 28 control women was studied. The Na+/K+-ATPase activity was determined by measuring the inorganic phosphate released by incubation in a reaction medium in the presence and absence of K ions or ouabain. The intra-erythrocyte sodium and potassium activities were measured by ion-selective electrode analysis of the haemolysates, after washing the RBCs in 110 mmol/l MgCl2. We found a significant increase in intracellular sodium and a reduction in Na+/K+-ATPase activity in the hypertensive women in comparison with the control subjects during pregnancy. No difference was observed in early puerperium. Cord blood from infants of pregnancy-induced hypertensive women showed an increase in intracellular Na+ activity and a decrease in the erythrocyte membrane Na+/K+-ATPase activity in comparison with cord blood samples from control subjects. The observed abnormalities in the plasma membrane sodium transport may play a major role in the pathophysiology of pregnancy-induced hypertension.


Characterization of Leptin Secretion in Premenopausal Obese Women Treated with Bromocriptine.
Leptin, a hormone secreted by adipose tissue, is primarily responsible for inhibiting hunger and maintaining energy balance. Improper leptin secretion may result in hyperleptinemia (excess secretion of leptin) or leptin resistance, both of which contribute to obesity. Diagnosing abnormal leptin secretion may help treat this underlying cause of obesity. Therefore, continuous monitoring of the level of leptin may help characterize its secretion dynamics and also help devise an appropriate treatment. In this research, we consider leptin hormone concentration data taken over a 24 hour time period from eighteen healthy premenopausal obese women before and after treatment with a dopamine agonist, bromocriptine, and deconvolve the observed leptin hormone levels to estimate the number, timing, and magnitude of the underlying leptin secretory pulses. We find that there is an overall decrease in leptin secretion, particularly during sleep, but the changes in the secretory and clearance rates, and the number of pulses underlying the secretion process are not statistically significant.Clinical relevance- This work seeks to understand the effect of bromocriptine on leptin secretory dynamics and will help further current understanding of the effect of bromocriptine in relation to obesity.


Influencing the Conversation About Masculinity and Suicide: Evaluation of the Man Up Multimedia Campaign Using Twitter Data.
It has been suggested that some dominant aspects of traditional masculinity are contributing to the high suicide rates among Australian men. We developed a three-episode documentary called Man Up, which explores the complex relationship between masculinity and suicide and encourages men to question socially imposed rules about what it means to be a man and asks them to open up, express difficult emotions, and seek help if and when needed. We ran a three-phase social media campaign alongside the documentary using 5 channels (Twitter, Facebook, Instagram, YouTube, and Tumblr). This study aimed to examine the extent to which the Man Up Twitter campaign influenced the social media conversation about masculinity and suicide. We used Twitter insights data to assess the reach of and engagement with the campaign (using metrics on followers, likes, retweets, and impressions) and to determine the highest and lowest performing tweets in the campaign (using an aggregated performance measure of reactions). We used original content tweets to determine whether the campaign increased the volume of relevant Twitter conversations (aggregating the number of tweets for selected campaign hashtags over time), and we used a subset of these data to gain insight into the main content themes with respect to audience engagement. The campaign generated a strong following that was engaged with the content of the campaign; over its whole duration, the campaign earned approximately 5000 likes and 2500 retweets and gained around 1,022,000 impressions. The highest performing tweets posted by the host included video footage and occurred during the most active period of the campaign (around the screening of the documentary). The volume of conversations in relation to commonly used hashtags (#MANUP, #ABCMANUP, #LISTENUP, and #SPEAKUP) grew in direct relation to the campaign activities, achieving strongest growth during the 3 weeks when the documentary was aired. Strongest engagement was found with content related to help-seeking, masculinity, and expressing emotions. A number of followers tweeted personal stories that revealed overwhelmingly positive perceptions of the content of the documentary and strongly endorsed its messages. The Man Up Twitter campaign triggered conversations about masculinity and suicide that otherwise may not have happened. For some, this may have been game-changing in terms of shifting attitudes toward expressing emotions and reaching out to others for help. The campaign was particularly effective in disseminating information and promoting conversations in real time, an advantage that it had over more traditional health promotion campaigns. This sort of approach could well be adapted to other areas of mental (and physical) health promotion campaigns to increase their reach and effectiveness.


The hypothesis of 'biophysical matrix contraction': wound contraction revisited.
Wound contraction is an orchestrated phenomenon that contributes to closure of wounds that heal by secondary intention. However, excessive and premature contraction results in scarring. Although the exact mechanism of contraction is unknown, the wound closure process is accompanied by and followed by changes in the physical and mechanical properties of the wound and periwound tissues during the biological transformation. Transforming growth factor-beta (TGF-beta) induces a contractile phenotype in the cellular-extracellular matrix. Meanwhile, various external and internal mechanical stresses lead to microdeformations of the wound milieu with resultant upregulation of TGF-beta. Furthermore, the mechanical strain exerted on collagen fibres and other piezoelectric tissues leads to development of piezoelectric current in the wound site, which acts synergistically with TGF-beta. TGF-beta and mechanical strain regulate the orientation of collagen fibres parallel with the skin surface, which minimises the induction of piezoelectricity through the action of internal forces because of improper angulation of collagen fibres and these forces. The resulting dominance of external forces guides the contractile activity towards restoration of the original unwounded tissue architecture and functional activity of the previously wounded milieu. The aforementioned contractile activity proceeds into the remodelling phase of wound healing as the level of TGF-beta is reduced and myofibroblasts undergo apoptosis.


Homogeneous bulk, surface, and edge nucleation in crystalline nanodroplets.
The birth of a crystal is initiated by a nucleus from which the crystal grows--a dust grain in a snowflake is a familiar example. These nuclei can be heterogeneous defects, like the dust grain, or homogeneous nuclei which are intrinsic to the material. Here we study homogeneous nucleation in nanoscale polymer droplets on a substrate which itself can be crystalline or amorphous. We observe a large difference in the nucleating ability of the substrate. Furthermore, the scaling dependence of nucleation on the size of the droplets proves that the birth of the crystalline state can be directed to originate predominantly within the bulk, at the substrate surface, or at the droplets' edge, depending on how we tune the substrate.


The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patients.
The combination of Hydroxychloroquine (HCQ) and azithromycin showed effectiveness as a treatment for COVID-19 and is being used widely all around the world. Despite that those drugs are known to cause prolonged QT interval individually there is no study assessing the impact of this combination on electrocardiography (ECG). This study aimed to assess the impact of a 5-day course of HCQ and azithromycin combination on ECG in non-ICU COVID19(+) patients. In this retrospective observational study, we enrolled 109 COVID19(+) patients who required non-ICU hospitalization. All patients received 5-day protocol of HCQ and azithromycin combination. On-treatment ECGs were repeated 3-6 h after the second HCQ loading dose and 48-72 h after the first dose of the combination. ECGs were assessed in terms of rhythm, PR interval, QRS duration, QT and QTc intervals. Baseline and on-treatment ECG findings were compared. Demographic characteristics, laboratory results were recorded. Daily phone call-visit or bed-side visit were performed by attending physician. Of the 109 patients included in the study, the mean age was 57.3 ± 14.4 years and 48 (44%) were male. Mean baseline PR interval was 158.47 ± 25.10 ms, QRS duration was 94.00 ± 20.55 ms, QTc interval was 435.28 ± 32.78 ms, 415.67 ± 28.51, 412.07 ± 25.65 according to Bazett's, Fridericia's and Framingham Heart Study formulas respectively. ∆PR was -2.94 ± 19.93 ms (p = .55), ∆QRS duration was 5.18 ± 8.94 ms (p = .03). ∆QTc interval was 6.64 ± 9.60 ms (p = .5), 10.67 ± 9.9 ms (p = .19), 14.14 ± 9.68 ms (p = .16) according to Bazett's, Fridericia's and Framingham Heart Study formulas respectively. There were no statistically significant differences between QTc intervals. No ventricular tachycardia, ventricular fibrillation or significant conduction delay was seen during follow-up. There was no death or worsening heart function. The 5-day course of HCQ- AZM combination did not lead to clinically significant QT prolongation and other conduction delays compared to baseline ECG in non-ICU COVID19(+) patients.


Exercise induced asthma and endogenous opioids.
Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma.


Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group.
The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection. A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices. Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718). The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.


Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes.
Type 1 diabetes (T1D) is a chronic autoimmune disease leading to immune-mediated destruction of pancreatic beta cells, resulting in the need for insulin therapy. The incidence of T1D is increasing worldwide, thus prompting researchers to investigate novel immunomodulatory strategies to halt autoimmunity and modify disease progression. T1D is considered as a multifactorial disease, in which genetic predisposition and environmental factors interact to promote the triggering of autoimmune responses against beta cells. Over the last decades, it has become clear that vitamin D exerts anti-inflammatory and immunomodulatory effects, apart from its well-established role in the regulation of calcium homeostasis and bone metabolism. Importantly, the global incidence of vitamin D deficiency is also dramatically increasing and epidemiologic evidence suggests an involvement of vitamin D deficiency in T1D pathogenesis. Polymorphisms in genes critical for vitamin D metabolism have also been shown to modulate the risk of T1D. Moreover, several studies have investigated the role of vitamin D (in different doses and formulations) as a potential adjuvant immunomodulatory therapy in patients with new-onset and established T1D. This review aims to present the current knowledge on the immunomodulatory effects of vitamin D and summarize the clinical interventional studies investigating its use for prevention or treatment of T1D.


Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique.
The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with beta-cyclodextrin (betaCD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyleneglycol 6000 were investigated. The phase solubility profile of lamotrigine with betaCD was classified as AL-type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96+/-2.26 M(-1). Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine.


Phorbal-12-mysristate-13-acetate-induced inflammation is restored by protectin DX through PPARγ in human promonocytic U937 cells.
Protectin DX (PDX), a specialized pro-resolving mediator, is an important pharmaceutical compound with potential antioxidant and inflammation-resolving effects. However, the fundamental mechanism by which PDX's ameliorate chronic inflammatory diseases has not yet been elucidated. This study aims to evaluate the anti-inflammatory properties and PPARγ-mediated mechanisms of PDX in phorbal-12-mysristate-13-acetate (PMA)-stimulated human promonocytic U937 cells. We confirmed the effects of PDX on expressions of pro-inflammatory cytokines, mediators, and CD14 using conventional PCR, RT-qPCR, ELISA, and flow cytometry. Using western blotting, immunofluorescence, and reactive oxygen species (ROS) determination, we observed that PDX regulated PMA-induced signaling cascades. Molecular docking analysis and a cellular thermal shift assay were conducted to verify the interaction between PDX and the proliferator-activated receptor-γ (PPARγ) ligand binding domain. Western blotting was then employed to explore the alterations in PPARγ expression levels and validate PDX as a PPARγ full agonist. PDX attenuated protein and mRNA expression levels of interleukin-6, tumor necrosis factor-α, and cyclooxygenase-2 in PMA-treated U937 cells. PDX acts as a PPARγ agonist, exerting a modulating effect on the ROS/JNK/c-Fos signaling pathways. Furthermore, PDX reduced human monocyte differentiation antigen CD14 expression levels. PPARγ exhibits pro-resolving effects to regulate the excessive inflammation. These results suggest that PDX demonstrates the resolution of inflammation, indicating the potential for therapeutic targeting of chronic inflammatory diseases.


Pediatric golf-related ophthalmic injuries.
To document ophthalmic morbidity of golf-related injuries in children and to report specific injury patterns. A noncomparative, interventional, retrospective case series of 11 pediatric patients treated at 2 institutions for ophthalmic trauma resulting from golf-related injuries during 15 years. Eleven eyes of 11 patients were injured. There were 6 boys and 5 girls, with a mean age of 10.2 years (age range, 7-14 years). Ten patients were injured by golf clubs and 1 patient by a golf ball. One injury occurred on a golf course. At the initial ophthalmic examination, visual acuity was 20/20 in 4 eyes (36%), 20/25 to 20/80 in 3 eyes (27%), no light perception in 3 eyes (27%), and undeterminable in 1 eye (9%). Nine of 11 patients required surgery. Follow-up ranged from 0 to 66 months (mean follow-up, 12 months). Three of 11 subjects had permanent deficits, including blindness, decreased vision, and anophthalmia. Final visual acuity was no light perception in 2 eyes (18%), 20/70 in 1 eye (9%), and 20/20 or better in 8 eyes (73%). The findings from this series reveal that pediatric ophthalmic golf injuries, although rare, may be devastating to the eye, periocular adnexa, and visual system. Among our cases, most injuries occurred off the golf course, many required surgery, and some resulted in permanent loss of vision.


Electron spectroscopic imaging of chromatin.
The analytical electron microscope technique called electron spectroscopic imaging (ESI) has a number of applications in the study of DNA:protein complexes. The method offers an intermediate level of spatial resolution for in vitro structural studies of complexes that may be too large or heterogeneous to study by crystallography or magnetic resonance spectroscopy. An advantage of ESI is that the distribution of nucleic acids can be resolved in a nucleoprotein complex by mapping the element phosphorus, present at high levels in nucleic acid compared to protein. Measurements of phosphorus content together with mass determination allows estimates to be made of stoichiometric relationships of protein and nucleic acids in these complexes. ESI is also suited to in situ studies of nuclear structure. Mass-sensitive images combined with nitrogen and phosphorus maps can be used to distinguish nucleic acid components from nuclear structures that are predominantly protein based. Interactions between chromatin on the periphery of interchromatin granule clusters (IGC) with the protein substructure that connects the exterior of the IGC to its core can be studied with this technique. The method also avoids the use of heavy atom stains, agents required in conventional electron microscopy, that preclude the distinguishing of structures on the basis of their biochemical composition. The principles of ESI and technical aspects of the method are discussed.


Hypoxanthine and adenosine in murine ovarian follicular fluid: concentrations and activity in maintaining oocyte meiotic arrest.
The concentrations of hypoxanthine and adenosine in ovarian follicular fluid were estimated, using high-performance liquid chromatography, for three groups of mice: 1) pregnant mare's serum gonadotropin (PMSG)-primed mice; 2) PMSG-primed mice 2 h after injection with human chorionic gonadotropin (hCG); and 3) PMSG-primed mice 5 h after injection with hCG. The concentration of hypoxanthine in follicular fluid of Group 1 mice was 2-4 mM and of adenosine was 0.35-0.70 mM. There was no difference in the concentrations of these purines in the follicular fluid of Group 2 mice, in which maturation had been induced with hCG but the samples were taken just before germinal vesicle breakdown (GVBD). Therefore, a decrease in the concentrations of these purines does not appear to induce GVBD. A significant decrease in the concentrations of hypoxanthine and adenosine was observed in the follicular fluid of Group 3 mice in which GVBD had already occurred. This decrease was probably a result of an increase in follicular fluid volume. Adenosine had a significant, but transient, effect in maintaining both cumulus cell-enclosed and denuded oocytes in meiotic arrest; all oocytes had undergone GVBD by 100 min incubation in 1 mM adenosine. When GVBD was assessed after 3 h culture, concentrations up to 5 mM adenosine failed to maintain meiotic arrest. In contrast, hypoxanthine (2-5 mM) had a dose-dependent effect in maintaining both cumulus cell-enclosed and denuded oocytes in meiotic arrest that was sustained up to 24 h. Cumulus cell-enclosed oocytes were always more sensitive to hypoxanthine than were denuded oocytes. There was a strong synergistic effect of adenosine and hypoxanthine in maintaining meiotic arrest; 4 mM hypoxanthine and 0.75 mM adenosine maintained more than 95% of the oocytes in meiotic arrest for culture periods up to 24 h. This action was completely reversible by withdrawal of the purines. It is hypothesized that the synergistic effect of these purines may result both by promoting cyclic adenosine monophosphate synthesis (adenosine), and by preventing its hydrolysis (hypoxanthine).


[Amizon in the treatment of nervous system involvement in herpes zoster].
The authors submit results of treatment of patients having suffered from postherpetic pain syndrome (herpetic ganglionitis of the cervical, thoracic, lumbosacral localization, postherpetic intercostal neuralgia, ganglionitis of the trigeminal nerve). In viral diseases, amizone has marked analgetic, antiinflammatory, and immunomodulating effects. The drug is well tolerated by patients, is not associated with side effects under prescribed doses (0.25-0.75 as one dose on a three- or four-times daily schedule during the course of treatment lasting three or four weeks). The drug preparation in question is less effective in the treatment of chronic recurring post-therapeutic intercostal neuralgias, radiculalgia.


Designing large-scale conservation corridors for pattern and process.
A major challenge for conservation assessments is to identify priority areas that incorporate biological patterns and processes. Because large-scale processes are mostly oriented along environmental gradients, we propose to accommodate them by designing regional-scale corridors to capture these gradients. Based on systematic conservation planning principles such as representation and persistence, we identified large tracts of untransformed land (i.e., conservation corridors) for conservation that would achieve biodiversity targets for pattern and process in the Subtropical Thicket Biome of South Africa. We combined least-cost path analysis with a target-driven algorithm to identify the best option for capturing key environmental gradients while considering biodiversity targets and conservation opportunities and constraints. We identified seven conservation corridors on the basis of subtropical thicket representation, habitat transformation and degradation, wildlife suitability, irreplaceability of vegetation types, protected area networks, and future land-use pressures. These conservation corridors covered 21.1% of the planning region (ranging from 600 to 5200 km2) and successfully achieved targets for biological processes and to a lesser extent for vegetation types. The corridors we identified are intended to promote the persistence of ecological processes (gradients and fixed processes) and fulfill half of the biodiversity pattern target. We compared the conservation corridors with a simplified corridor design consisting of a fixed-width buffer along major rivers. Conservation corridors outperformed river buffers in seven out of eight criteria. Our corridor design can provide a tool for quantifying trade-offs between various criteria (biodiversity pattern and process, implementation constraints and opportunities). A land-use management model was developed to facilitate implementation of conservation actions within these corridors.


[Pig-slaughtering at home. Customs do not change. An infectological case report from a historical point of view].
We report a case of a 41-year-old female patient presenting with watery diarrhoea and myalgia in the winter-season. Before her symptoms started she had participated in a pig slaughtering with her family. Some of the family members also became ill. On her physical examination periorbital odema and myalgia were found. Eosinophilia, hypalbuminaemia, elevated lactate dehydrogenase and creatin kinase levels were detected on laboratory investigations. The clinical picture, the laboratory findings and background epidemiological data implied the diagnosis of trichinellosis and albendazol was started. Serum gained on the 22nd post-infectious day turned out to be equivocal for trichinellosis. For this reason and because of the refractory fever a muscle-biopsy was done. Granulomatous myositis described by histology and Trichinella seropositivity from the repeated serum sample on the 62nd post-infectious day finally confirmed the diagnosis. During the course of the disease, we experienced elevation of troponin I suggesting myocarditis, but it was accompanied neither with abnormal ECG signs nor characteristic symptoms. Almost a century ago, a case report was published in Hungarian with a similar introduction. Trichinellosis in that epidemic setting led to the death of five people. Orv Hetil. 2019; 160(24): 952-957.


Bee venom protects SH-SY5Y human neuroblastoma cells from 1-methyl-4-phenylpyridinium-induced apoptotic cell death.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by progressive selective loss of dopaminergic neurons in the substantia nigra. Recently, bee venom was reported to protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mice PD model, however, the underlying mechanism is not fully understood. The objective of the present study is to investigate the neuroprotective mechanism of bee venom against Parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP(+)), in SH-SY5Y human neuroblastoma cells. Our results revealed that bee venom pretreatment (1-100 ng/ml) increased the cell viability and decreased apoptosis assessed by DNA fragmentation and caspase-3 activity assays in MPP(+)-induced cytotoxicity in SH-SY5Y cells. Bee venom increased the anti-apoptotic Bcl-2 expression and decreased the pro-apoptotic Bax, cleaved PARP expressions. In addition, bee venom prevented the MPP(+)-induced suppression of Akt phosphorylation, and the neuroprotective effect of bee venom against MPP(+)-induced cytotoxicity was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. These results suggest that the anti-apoptotic effect of bee venom is mediated by the cell survival signaling, the PI3K/Akt pathway. These results provide new evidence for elucidating the mechanism of neuroprotection of bee venom against PD.


Rudimentary physiological effects of mere observation.
Complex social factors can influence physiological activity, behavior, and health, but little is known about how essential components of these factors (e.g., human association, observation) affect human physiology. To begin to address this issue, an experiment was conducted to contrast predictions from social facilitation, distraction/conflict, and physiological reactivity formulations regarding the physiological effects of mere observation. Skin conductance and heart rate were measured surreptitiously from 27 women during a period in which they believe that the experimenter was simply calibrating auditory and physiological recording equipment. Approximately half of the subjects were led to believe that they could be observed by the experimenter during this period, and the remainder were led to believe that they could not be observed. Following baseline recordings, a series of 10 orienting tones were presented. Predictions from the physiological reactivity formulation were supported: (a) no differences in basal levels of somatovisceral activity were found as a function of mere observation; (b) mere observation enhanced the skin conductance response to the initial orienting tone; and (c) these physiological differences were punctate, quickly dissipating and quickly habituating. Hence, mere observation has subtler physiological effects than thought previously. Implications are discussed regarding the possible mechanism underlying the stress-enhancing and stress-buffering effects of human association, and regarding the effects social and contextual factors may have in psychophysiological research. Results from an international survey, based on the responses of 57 authors of articles that have appeared in Psychophysiology since 1983, are reported to inform the latter discussion. Results suggest that, even when social factors in psychophysiological research are minimized or held constant within studies, subtle differences in the social context across studies within and across laboratories may contribute to the appearance that psychophysiological relationships are unreliable.


[Acid-base state in rats with different resistance to hypoxia in experimental tracheal stenosis].
Rats with different resistance to hypoxic hypoxia differ in parameters of their acid-base state: in high resistance, lower values for blood pH are recordable together with slightly higher pCO2 and content of non-volatile acids. Development of experimental stenosis of trachea in low- and high-resistant animals has been shown to significantly disturb the acid-base state (particularly in low-resistant rats). This process is compensatory-adaptive; it is characterized by development of respiratory acidosis at day 1 to 3, with the indices tending to return to the normal range at day 7, mixed acidosis developing later on.


[Pharmacodynamics of a nitroglycerin ointment in patients with stenocardia of effort].
Antianginal efficiency and the duration of effect of a 2% nitroglycerin ointment were assessed in 20 patients with angina of effort, using repeated bicycle ergometric tests. It was demonstrated that the 2% nitroglycerin ointment was an effective antianginal agent, the effect of its minimal dose (2 cm) exceeding considerably that of 10 mg isosorbide dinitrate. The antianginal effect of nitroglycerin ointment became apparent 15 minutes after the application and lasted for 6 hours of follow-up in most patients. There was individual variation in the duration of the ointment's effect, which was, however, less pronounced, as compared to the variation observed with oral prolonged-action nitroglycerin preparations.


Fecal Elastase Levels Predict Honeycombing in Pancreas Detected with Endoscopic Ultrasound.
We aimed to demonstrate the association between fecal elastase levels and Rosemont categories in patients with chronic changes in pancreas detected with endoscopic ultrasound. Patients were selected consecutively from endosonography examinations performed for upper gastrointestinal subepithelial lesions and for pancreas evaluation. Pancreas imaging findings were categorized according to the Rosemont criteria using echoendoscope. Patients who were indeterminate of, suggestive of, and consistent with chronic pancreatitis were included in the study. Fecal elastase measurements were performed after the patients were qualified to participate in the study according to endosonography findings. Seventy patients were included in the study. 54 of them were male. Mean age of the patients was 51.7 ± 10.2 year. There were 36 patients in the indetermine group for chronic pancreatitis. Mean fecal elastase level was 507.1 ± 14.6 μg/g in the indeterminate group. There were 24 patients in the suggestive group of chronic pancreatitis. Mean fecal elastase level was 400.4 ± 121.4 μg/g in the suggestive group of chronic pancreatitis. There were 10 patients, in the consistent group with chronic pancreatitis. Mean fecal elastase level was 134.8 ± 86.1. The difference between the three groups of fecal elastase values was statistically significant compared with Kruskal Wallis test. Ordinal logistic regression analysis showed that there was a significant relation between endosonografic categories and fecal elastase values with Nagelkerke value of 0.704. Fecal elastase levels of each of the endosonographic categories were significantly different from each other. Also, fecal elastase values can predict chronic changes in pancreas detected with endoscopic ultrasound.


Hardware-in-the-loop simulation of vascular cannula interaction.
Traditionally, the functional development, testing and verification of higher level automation, control and safety functions in extracorporeal circulations systems relies very much on the conduction of animal experiments. This especially applies to functions requiring interaction with the patients physiology. Besides ethical aspects, animal experiments have the disadvantage of higher complexity, limited reproducibility and certain pathological conditions can only be represented with difficulty. An alternative to this can be Hardware-in-the-loop (HIL) simulators.In this paper we present a HIL solution to simulate the hydraulic interaction between the cannula and the connected blood vessel. We derive a hydraulic model for an elastic vessel with particular emphasis on negative transmural pressure. In this case the resistance is mainly determined by collapse phenomena. The next section describes the design of an universal resistance actuator that can simulate vascular resistances in the expected range. Combined in the HIL simulator, the simulation model then generates the setpoint for the actuator while simultaneously receiving the resulting internal states of the hydraulic interface. This creates a truly interactive HIL simulator where the device under test interacts in the same way as with a physiological system.


Substrate- and inhibitor-induced conformational changes in the yeast V-ATPase provide evidence for communication between the catalytic and proton-translocating sectors.
The vacuolar-type H(+)-ATPases (V-ATPases) are composed of two distinct sectors, a catalytic complex (V(1)) involved in ATP hydrolysis and a membrane-associated complex (V(0)) mediating proton translocation across a lipid bilayer. To date, little is known about the mechanism by which these two functions are coupled. We sought to examine the impact of nucleotide and cation binding on the structure of the core components of the catalytic complex and to determine whether conformational changes within the catalytic complex impact subunits of the membrane-associated complex. Nucleotide- and cation- induced changes in the catalytic core of the V-ATPase were investigated by monitoring changes in the rate and pattern of tryptic digests. ATP.Mg-induced changes were detected in both the catalytic (Vma1p or 69 kDa) and the regulatory subunits (Vma2p or 60 kDa) of the V(1) sector. ATP alone increased the rate of trypsinization of the regulatory subunit, but did not have any effect on Vma1p. Surprisingly, ATP also had an impact on the 95-kDa subunit, a component of the V(0) sector of the V-ATPase. Although the presence of divalent cations had no impact on the V(1) sector, the rate of trypsinization of the 95-kDa subunit was greatly enhanced. The effect of divalent cations on the structure of the 95-kDa subunit was abrogated when trypsinization was performed in the absence of the catalytic sector. Addition of bafilomycin A(1), a V-ATPase inhibitor that putatively binds to the 95-kDa subunit, increased the rate of trypsinization of the catalytic subunit. These data suggest that structural alterations within the V(1) sector result in alterations within the V(0) sector and vice versa. Clearly, a structural link must exist to couple the two sectors. The 95-kDa subunit is ideally suited to fulfill this role. Hydropathy analysis suggests a bipartite structure, with the NH(2)-terminal portion predicted to lie in an aqueous environment and the C-terminal portion predicted to contain 6 transmembrane segments. Tryptic digests of sealed vacuolar vesicles and immunofluorescence studies revealed that the large hydrophilic NH(2)-terminal domain of the 95-kDa subunit is localized toward the cytosol. This region therefore is ideally positioned to interact with components of the V(1) complex, potentially functioning as the elusive link between the two sectors of the V-ATPase.


Growth and Cd uptake by rice (Oryza sativa) in acidic and Cd-contaminated paddy soils amended with steel slag.
Contamination of rice (Oryza sativa) by Cd is of great concern. Steel slag could be used to amend Cd-contaminated soils and make them safe for cereal production. This work was conducted to study the effects of steel slag on Cd uptake and growth of rice plants in acidic and Cd-contaminated paddy soils and to determine the possible mechanisms behind these effects. Pot (rhizobag) experiments were conducted using rice plants grown on two acidic and Cd-contaminated paddy soils with or without steel slag amendment. Steel slag amendment significantly increased grain yield by 36-45% and root catalase activity, and decreased Cd concentrations in brown rice by 66-77% compared with the control, in both soils. Steel slag amendment also markedly decreased extractable soil Cd, Cd concentrations in pore-water and Cd translocation from roots to above-ground parts. It also significantly increased soil pH, extractable Si and Ca in soils and Ca concentrations in roots. Significant positive correlations were found between extractable soil Cd and Cd concentrations in rice tissues, but it was negatively correlated with soil pH and extractable Si. Calcium in root tissues significantly and negatively correlated with Cd translocation factors from roots to straw. Overall, steel slag amendment not only significantly promoted rice growth but decreased Cd accumulation in brown rice. These benefits appear to be related to improvements in soil conditions (e.g. increasing pH, extractable Si and Ca), a reduction in extractable soil Cd, and suppression of Cd translocation from roots to above-ground parts.


Sensorimotor integration in healthy aging: Baseline differences and response to sensory training.
Sensorimotor integration is the process through which somatosensory information is incorporated to inform motor output. Given its important behavioural implications, understanding the influence of healthy aging on the underlying neurophysiology of sensorimotor integration and whether it is modifiable through intervention is important. The aims of the current work were to: 1) profile aging-related differences in sensorimotor integration, and 2) to determine if sensorimotor integration in older adults can be modulated in response to sensory training. A group of older healthy individuals and younger healthy individuals participated in two experimental sessions. First, baseline neurophysiology of sensorimotor integration was assessed. Short-latency afferent inhibition, afferent facilitation, and long-latency afferent inhibition provided nerve-based assessment of sensorimotor integration. Vibration-based measures of sensorimotor integration combined vibration of abductor pollicis brevis with single and paired-pulse transcranial magnetic stimulation techniques. In the second experimental session, a 15-min block of sensory training designed to modulate sensorimotor integration preceded the same neurophysiological assessment. Results indicate that there are aging-related differences in nerve-based measures of sensorimotor integration, specifically short- and long-latency afferent inhibition. In contrast, there are not aging-related differences when peripheral muscle belly vibration is used to probe sensorimotor integration. Following sensory training there is a reduction in the cortical response to vibration. These results suggest that there is differential aging-related modulation of sensorimotor integration, based on the type of afferent information. Additionally, sensorimotor integration is modifiable with a single session of sensory training, and this ability for neuroplastic change is retained with healthy aging.


Treatment of mechanical valve thrombosis in the right heart: overview of the requirements for the new thrombolytic protocols.
Prosthetic valve thrombosis (PVT) is a rare but serious complication of implanted mechanical valves. Intravenous thrombolytic treatment has emerged as an alternative to surgical therapy in the management of patients with stuck valves. As tricuspid valve replacement is a rare venture, the indications for such therapy and appropriate patient selection are evolving. As the type, dose, and route of administration of thrombolytic agents differ, major complications can be seen in the rapid infusion protocols. In patients with PVT, especially with right-sided valves, thrombolysis with intravenous slow infusion has given discrete, successive sessions guided by serial transthoracic echocardiography and cine/fluoroscopy which may be achieved with a low risk of complications and a high rate of success. Our report describes the management of two patients with PVT and discusses the current status of thrombolysis in such patients.


Specimen Collection for Translational Studies in Hidradenitis Suppurativa.
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.


CTCF regulates asynchronous replication of the imprinted H19/Igf2 domain.
Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/Igf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/Igf2 domain.


Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.
Systemic modalities are crucial in the management of disseminated malignancies and liquid tumours. However, patient responses and tolerability to treatment are generally poor and those that enter remission often return with refractory disease. Combination therapies provide a methodology to overcome chemoresistance mechanisms and address dose-limiting toxicities. A deeper understanding of tumorigenic processes at the molecular level has brought a targeted therapy approach to the forefront of cancer research, and novel cancer biomarkers are being identified at a rapid rate, with some showing potential therapeutic benefits. The Karyopherin superfamily of proteins is soluble receptors that mediate nucleocytoplasmic shuttling of proteins and RNAs, and recently, nuclear transport receptors have been recognized as novel anticancer targets. Inhibitors against nuclear export have been approved for clinical use against certain cancer types, whereas inhibitors against nuclear import are in preclinical stages of investigation. Mechanistically, targeting nucleocytoplasmic shuttling has shown to abrogate oncogenic signalling and restore tumour suppressor functions through nuclear sequestration of relevant proteins and mRNAs. Hence, nuclear transport inhibitors display broad spectrum anticancer activity and harbour potential to engage in synergistic interactions with a wide array of cytotoxic agents and other targeted agents. This review is focussed on the most researched nuclear transport receptors in the context of cancer, XPO1 and KPNB1, and highlights how inhibitors targeting these receptors can enhance the therapeutic efficacy of standard of care therapies and novel targeted agents in a combination therapy approach. Furthermore, an updated review on the therapeutic targeting of lesser characterized karyopherin proteins is provided and resistance to clinically approved nuclear export inhibitors is discussed.


Noradrenergic afferents facilitate the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus.
The role of ascending noradrenergic projections of medullary origin in regulating the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus (PVN) was examined in pentobarbital-anesthetized male Sprague-Dawley rats. Discrete electrical stimulation of either the A1 or the A2 noradrenaline cell group areas of the caudal medulla enhanced the probability of firing in a substantial proportion of antidromically identified tuberoinfundibular PVN cells tested. Notably, no inhibitory effects were observed. Destruction of the PVN noradrenergic terminal plexus by local application of the neurotoxin 6-hydroxydopamine 1 day prior to electrophysiological experiments abolished the effects of both A1 and A2 stimulation. These findings indicate that noradrenergic afferents can exert a facilitatory influence on the activity of a population of tuberoinfundibular PVN neurons, thus supporting earlier suggestions that central noradrenergic structures can enhance the release of certain anterior pituitary hormones.


Cancer dormancy: studies of the murine BCL1 lymphoma.
Dormancy in the murine BCL1 lymphoma can be induced by several strategies including cytoreductive therapy of mice with large tumor burdens and challenge of allogeneic chimeric mice or idiotype-immunized mice with BCL1 tumor. Dormant tumor cells were isolated from the spleens of the chimeric mice and the majority were shown to be noncycling. In idiotype-immunized mice that had lost dormancy, tumor growth occurred at a relatively rapid rate. A proportion of idiotype-immunized mice that had lost dormancy spontaneously regressed and then again relapsed; in these mice, the serum antiidiotypic levels were inversely related to the tumor burden.


Medicalizing to demedicalize: lactation consultants and the (de)medicalization of breastfeeding.
This paper uses the domain of breastfeeding in the U.S. and the work of International Board Certified Lactation Consultants to refine the concept of medicalization-demedicalization. Given lactation consultants' origins and current role in maternity care, they provide a unique lens on these processes because they are positioned at the crossroads of medicalization and demedicalization. Using 150 h of ethnographic observation and 39 interviews conducted between 2008 and 2012, I identify aspects of medicalization-demedicalization in the work of lactation consultants according to four dimensions: medical definition, medical control, pathology, and medical technology. Lactation consultants work to demedicalize breastfeeding by challenging the construction of breastfeeding pathology and limiting intervention. At the same time, they hold a position of medical control and medicalize breastfeeding by reinforcing a medical definition and using medical technology to treat breastfeeding problems. However, lactation consultants are not only working toward demedicalization and medicalization simultaneously, but are also medicalizing to demedicalize. Their position of medical control over breastfeeding provides them with a certain measure of authority that they can use in their efforts to depathologize breastfeeding and limit medical intervention. These findings build upon previous research that has identified cases of medicalization and demedicalization occurring simultaneously and draw attention to the need for an understanding of medicalization-demedicalization as a continuous process. Furthermore, the concept of "medicalizing to demedicalize" provides a novel contribution to the literature.


The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.
Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.


[Early exercise test after revascularization and rehabilitation].
Ergospirometry was performed on 51 patients before their discharge from hospital, that is between the seventh and tenth days after myocardial revascularization by cardiac bypass surgery. The aim of our study is to show that this type of measurement can be performed with reasonable safety and that it gives an accurate assessment of the patient's ability to withstand exercise. It employs a metabolic approach: study of oxygen consumption (V'O2), carbon dioxide release (V'CO2), the respiratory quotient (RQ), the minute ventilation (V'E) and the respiratory equivalent for oxygen (REO2). The patients withstood a mean load of 82 +/- 17.7 watts for a mean V'O2 of 1.186 +/- 0.258 l/min STPD and a mean V'E of 46.5 +/- 10 l/min BTPS. Changes in respiratory and metabolic parameters as a function of load are discussed, as is the advice that can be given to the patient regarding physical rehabilitation.


A new low-turbulence wind tunnel for animal and small vehicle flight experiments.
Our understanding of animal flight benefits greatly from specialized wind tunnels designed for flying animals. Existing facilities can simulate laminar flow during straight, ascending and descending flight, as well as at different altitudes. However, the atmosphere in which animals fly is even more complex. Flow can be laminar and quiet at high altitudes but highly turbulent near the ground, and gusts can rapidly change wind speed. To study flight in both laminar and turbulent environments, a multi-purpose wind tunnel for studying animal and small vehicle flight was built at Stanford University. The tunnel is closed-circuit and can produce airspeeds up to 50 m s-1 in a rectangular test section that is 1.0 m wide, 0.82 m tall and 1.73 m long. Seamless honeycomb and screens in the airline together with a carefully designed contraction reduce centreline turbulence intensities to less than or equal to 0.030% at all operating speeds. A large diameter fan and specialized acoustic treatment allow the tunnel to operate at low noise levels of 76.4 dB at 20 m s-1. To simulate high turbulence, an active turbulence grid can increase turbulence intensities up to 45%. Finally, an open jet configuration enables stereo high-speed fluoroscopy for studying musculoskeletal control in turbulent flow.


The detrimental effect of vaccinating parentally immune broilers with a modified liver virus vaccine for infectious bursal disease.
The experiment involved 392,955 broilers from breeders vaccinated with a commercially available killed infectious bursal disease (KIBD) virus vaccine (Treatments 1 and 2) and 373,371 broilers from breeders not vaccinated with a KIBD virus vaccine (Treatment 2). The broilers from the KIBD-vaccinated breeders were divided into two treatment groups: Treatment 1 consisted of 209,457 broilers and Treatment 2 consisted of 183,498 broilers. Treatment 2 broilers were vaccinated at 10 days of age intraocularly with a commercially available modified liver infectious bursal disease virus (IBD-MLV) vaccine. Broilers in all three treatments were raised on commercially contracted farms serviced by the same company representative. Broiler performance was based on mortality, body weight, feed efficiency, condemnations, and how each farm ranked with respect to contract settlements. Compared with birds in Treatments 2 and 3 respectively, Treatment 1 broilers had 1.65% and 0.89% less mortality; 0.22 lbs. and 0.09 lbs. increased weight per bird; 0.03 and 0.03 increased feed efficiency; 0.09% and 0.32% fewer air sacculitis condemnations; and 0.57% and 0.83% fewer total condemnations. Treatment 1 broilers ranked in the top 37%; Treatment 2 ranked in the bottom 36%; and Treatment 3 ranked in the lower 57% of contract settlements for all broilers processed. The results clearly showed that Treatment 1 broilers outperformed Treatment 2 amd 3 birds and that the IBD-MLV vaccine had a detrimental effect on Treatment 2 broilers.


A specific requirement of Arc/Arg3.1 for visual experience-induced homeostatic synaptic plasticity in mouse primary visual cortex.
Visual experience scales down excitatory synapses in the superficial layers of visual cortex in a process that provides an in vivo paradigm of homeostatic synaptic scaling. Experience-induced increases in neural activity rapidly upregulates mRNAs of immediate early genes involved in synaptic plasticity, one of which is Arc (activity-regulated cytoskeleton protein or Arg3.1). Cell biological studies indicate that Arc/Arg3.1 protein functions to recruit endocytic machinery for AMPA receptor internalization, and this action, together with its activity-dependent expression, rationalizes a role for Arc/Arg3.1 in homeostatic synaptic scaling. Here, we investigated the role of Arc/Arg3.1 in homeostatic scaling in vivo by examining experience-dependent development of layer 2/3 neurons in the visual cortex of Arc/Arg3.1 knock-out (KO) mice. Arc/Arg3.1 KOs show minimal changes in basal and developmental regulation of excitatory synaptic strengths but display a profound deficit in homeostatic regulation of excitatory synapses by visual experience. As additional evidence of specificity, we found that the visual experience-induced regulation of inhibitory synapses is normal, although the basal inhibitory synaptic strength is increased in the Arc/Arg3.1 KOs. Our results demonstrate that Arc/Arg3.1 plays a selective role in regulating visual experience-dependent homeostatic plasticity of excitatory synaptic transmission in vivo.


Stabilization of a Clayey Soil with Ladle Metallurgy Furnace Slag Fines.
The research study described in this paper investigated the potential to use steel furnace slag (SFS) as a stabilizing additive for clayey soils. Even though SFS has limited applications in civil engineering infrastructure due to the formation of deleterious expansion in the presence of water, the free CaO and free MgO contents allow for the SFS to be a potentially suitable candidate for clayey soil stabilization and improvement. In this investigation, a kaolinite clay was stabilized with 10% and 15% ladle metallurgy furnace (LMF) slag fines by weight. This experimental study also included testing of the SFS mixtures with the activator calcium chloride (CaCl2), which was hypothesized to accelerate the hydration of the dicalcium silicate phase in the SFS, but the results show that the addition of CaCl2 was not found to be effective. Relative to the unmodified clay, the unconfined compressive strength increased by 67% and 91% when 10% and 15% LMF slag were utilized, respectively. Likewise, the dynamic modulus increased by 212% and 221% by adding 10% and 15% LMF slag, respectively. Specifically, the LMF slag fines are posited to primarily contribute to a mechanical rather than chemical stabilization mechanism. Overall, these findings suggest the effective utilization of SFS as a soil stabilization admixture to overcome problems associated with dispersive soils, but further research is required.


Chronic inflammatory demyelinating polyradiculoneuropathy and anesthesia: a case series.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired autoimmune demyelinating polyneuropathy characterized by symmetrical diffuse weakness that also can rarely affect bulbar and respiratory muscles. The study objective was to describe perioperative outcomes of patients with CIDP who received general anesthesia. This retrospective observational study evaluated patients with active (diagnosed or treated within the previous year) CIDP who underwent general anesthesia at our institution between January 1, 2010, and December 31, 2015. Medical records were reviewed for perioperative outcomes with emphasis on respiratory complications or unexpected reactions to muscle relaxants. Seventeen patients with CIDP underwent general anesthesia, of whom 16 had muscle weakness. Succinylcholine was used in 5 cases (29.4%) and nondepolarizing muscle relaxants in 11 cases (64.7%). Two patients required postoperative mechanical ventilation; one was critically ill and the other had open heart surgery. One patient had aspiration on the second postoperative day and required endotracheal intubation and mechanical ventilation for 3 days. Three patients had worsening CIDP symptoms: 1 acutely after surgery; 1 several months later; and 1 who died in the hospital. The patient who died underwent lengthy abdominal exploration, had acute worsening of neurologic symptoms, and died after 46 days of malnutrition. Anesthetic concerns of patients with CIDP include frailty, bulbar dysfunction, and the effects of immunosuppressive therapy. Although our patients tolerated neuromuscular drugs, substantial theoretical concerns with these medications in patients with demyelinating neuropathies preclude safety in this population without further study.