Search

Transcription elongation requires elaborate coordination between the transcriptional machinery and chromatin regulatory factors to successfully produce RNA while preserving the epigenetic landscape. Recent structural and genomic studies have highlighted that suppressor of Ty 6 (Spt6), a conserved histone chaperone and transcription elongation factor, sits at the crux of the transcription elongation process. Other recent studies have revealed that Spt6 also promotes DNA replication and genome integrity. Here, we review recent studies of Spt6 that have provided new insights into the mechanisms by which Spt6 controls transcription and have revealed the breadth of Spt6 functions in eukaryotic cells. Spt6 is a structural hub of the activated RNA polymerase II (RNAPII) elongation complex and forms critical contacts with RNAPII as well as other elongation factors, including DRB sensitivity-inducing factor (DSIF), polymerase-associated factor 1 complex (Paf1C), Iws1, and FACT. Spt6 directly interacts with all four core histones and nucleosomes and can assemble nucleosomes in vitro. Spt6 promotes processivity and elongation rate past nucleosomal barriers. Spt6 regulates nucleosome positioning and several histone post-translational modifications, thereby repressing intragenic transcription. Spt6 is necessary for genome stability, likely due to its roles in both transcription and DNA replication. [ABSTRACT FROM AUTHOR]

3Y-TZP along with Hydroxyapatite (HAp) are common bioceramics used in bone tissue engineering scaffolds to yield better patient outcomes and faster healing times. However, significant differences in thermal expansion of these ceramics result in challenges to co-sintering these materials without losing functionality and strength. In this work, a two-step sintering (TSS) process was utilised to co-sinter composites using (1-x)3Y-TZP and xHAp where x varies between 20 and 80 wt%. A peak temperature of 1300 °C, a plateau temperature of 1175 °C, a holding time of 600 min and heating rate of 10 °C/min were the optimum TSS conditions for all compositions. The TSS process produced specimens with grain sizes between 0.5 and 1.2 µm and a compression strength between 88 and 176 MPa. The similarity in compression strength of these zirconia-hydroxyapatite composites with natural bone and the retention of HAp make them suitable for bone tissue engineering applications in load bearing areas. [Display omitted] [ABSTRACT FROM AUTHOR]

The evolution of bipedalism and reduced reliance on arboreality in hominins resulted in larger lower limb joints relative to the joints of the upper limb. The pattern and timing of this transition, however, remains unresolved. Here, we find the limb joint proportions of Australopithecus afarensis, Homo erectus, and Homo naledi to resemble those of modern humans, whereas those of A. africanus, Australopithecus sediba, Paranthropus robustus, Paranthropus boisei, Homo habilis, and Homo floresiensis are more ape-like. The homology of limb joint proportions in A. afarensis and modern humans can only be explained by a series of evolutionary reversals irrespective of differing phylogenetic hypotheses. Thus, the independent evolution of modern human-like limb joint proportions in A. afarensis is a more parsimonious explanation. Overall, these results support an emerging perspective in hominin paleobiology that A. afarensis was the most terrestrially adapted australopith despite the importance of arboreality throughout much of early hominin evolution. [ABSTRACT FROM AUTHOR]

Health profession programs routinely utilize traditional interviews in admissions as a means of assessing important non-academic characteristics (e.g., critical thinking, interpersonal skills, judgment) of candidates. However, the reliability and validity of traditional interviews is highly questionable. Given this, multiple health profession programs (e.g., medicine, nursing, pharmacy, physical therapy) have implemented multiple mini-interviews as an alternative for assessing non-academic characteristics. This paper describes the development and implementation of multiple mini-interviews in the admissions process for a doctoral clinical psychology program, one of the health professions yet to use multiple mini-interviews. This paper also examines the feasibility and acceptability of the multiple mini-interviews in this program. Results of a mixed-method survey of all 120 candidates who participated in admissions days are presented along with discussion of factors associated with satisfaction and dissatisfaction. Recommendations for program refinement and application to other graduate psychology programs for improved admissions processes are discussed. [ABSTRACT FROM AUTHOR]

The main emphasis of this paper is on the use of Retarding Potential Analyzers (RPAs) for measuring the electron and ion distribution functions, density, and temperature of space plasmas and the charging level of spacecraft surfaces interacting with the plasmas. Multiple grids of progressively negative potential are used to suppress the secondary electrons produced at the entrance of an RPA. We point out that it is impossible to achieve complete suppression. The secondary electrons collected by the receiver may produce a spurious lump in the distribution measured. Improved designs and space applications for spacecraft charging and ionic liquid ion beam diagnostics are discussed. Spacecraft charging will be very important for planetary explorations, whereas ionic liquid ion beams will be important for spacecraft propulsion in the future. [ABSTRACT FROM AUTHOR]

Ionic liquid ion sources utilize electric fields to evaporate and accelerate ions and ion clusters to ∼1 keV energies. Ion clusters may dissociate after evaporation, which is not a well-characterized phenomenon and has relevant consequences in many applications. We measure the dissociation rate-constants of ion clusters for several ionic liquids. It is found that ion cluster dissociation occurs on timescales of the order of 1–5 μs and follows a constant-rate equation in the region outside the ion source. Using the measured rate-constants, we estimate the post-emission ion cluster temperatures. We also qualify the way the electric field enhances the rate-constants. Finally, our work supports the hypothesis that ion clusters with many degrees of freedom have lower dissociation rates. [ABSTRACT FROM AUTHOR]

Neonatal compartment syndrome (NCS) is extremely rare, with less than 100 cases reported. The affected limb usually presents with significant swelling and sentinel skin changes such as desquamation, blisters and skin necrosis. Risk factors that predispose infants to a hypercoagulable state or trauma have been implicated, but the exact cause remains elusive. We report two neonates with no family history of note, except for oligohydramnios in patient 1, who presented with congenital bullae over the upper extremity which led to an open wound. They were both referred to our service with a provisional diagnosis of epidermolysis bullosa (EB). Patient 1 also presented with a reduction in spontaneous movements of the hand shortly after birth. The wound took weeks to heal with scaring and subcutaneous tissue and muscle loss resulting in significant ulnar deviation by age 9 weeks. This was managed with stretching exercises, splints and surgical intervention. Despite this there remained noticeable limb length discrepancy and functional limitations to date. Patient 2 had a lack range of motion and restricted passive motion on the affected limb by the age of 4 weeks. Subsequent neurophysiological studies showed evidence of a severe chronic median and ulnar neuropathy with distal axonal loss and a right radial neuropathy at the site of the scar. Clinically, both cases were in keeping with NCS. A skin biopsy and molecular analysis ruled out EB. NCS requires early recognition and intervention as it can lead to long-term sequelae including Volkmann contracture, limb length discrepancies and permanent nerve damage. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is among one of the most common causes of vasculitis in children. Since KD was first described in 1967, there have been several reports of patients who did not meet the full diagnostic criteria for KD but who ultimately developed significant coronary artery lesions. Children with incomplete KD are at similar risk of developing coronary artery abnormalities to those with complete Kawasaki. A previously healthy 13-year-old Asian male was seen at a clinic for fever, pharyngitis, and conjunctivitis. He was given antibiotics for a presumed streptococcal pharyngitis. Two weeks later, the decedent complained of chest pain, collapsed, and was transported by Emergency Medical Services to a nearby hospital where he was pronounced deceased on arrival. A complete autopsy was done by the local medical examiner. Histologically, all three coronary arteries showed varying degrees of severe transmural lymphoplasmacytic inflammation, marked vascular smooth muscle intimal proliferation, focal destruction of muscular and elastic layers, and luminal stenosis. Some vessels had recent thrombi. We present an example of incomplete KD in an older child and reiterate the importance of obtaining relevant medical history in sudden death cases that come to the Medical Examiner Office, especially in the pediatric age group. [ABSTRACT FROM AUTHOR]

Objectives: To determine the extent to which clinically significant prostate cancer (csPCa) can be detected in a routine National Health Service setting in men with no previous biopsy, when multiparametric magnetic resonance imaging (mpMRI) is introduced into the diagnostic pathway. Patients and Methods: In all, 1 090 mpMRIs were performed between July 2013 and April 2016 in biopsy‐naïve men with an abnormal prostate‐specific antigen level and/or digital rectal examination. Data were collected from patient records at the Royal Devon and Exeter NHS Foundation Trust. mpMRI Prostate Imaging Reporting and Data System (PI‐RADS) scores were compared to transperineal or transrectal ultrasonography (TRUS)‐guided biopsy findings as the reference standard. csPCa was defined as Gleason score of ≥3+4. The diagnostic accuracy of mpMRI was also assessed. Results: The mpMRI was interpretable in 1 023 men and 792 underwent biopsy, of which 106 were transperineal. The median number of cores taken in transperineal and TRUS‐guided biopsy were 10 and 6, respectively. The detection rate of csPCa was 37%; csPCa rose from 15% of PI‐RADS 1 and 2 to 86% of PI‐RADS 5. The sensitivity, negative predictive value, specificity, and positive predictive value were 82%, 85%, 59% and 54%, respectively. The study is limited by its retrospective nature and lack of reporting of follow‐up for 'missed cancers'. Men with low mpMRI PI‐RADS were also less likely to undergo biopsy. Whilst this selection bias may overestimate the detection rate of csPCa, this reflects the shared decisions patients and clinicians make in day‐to‐day practice outside of research centres. Conclusion: In a routine clinical setting, the higher the mpMRI PI‐RADS, the greater the detection rate of csPCa in biopsy‐naïve men. A normal mpMRI does not exclude csPCa; however, mpMRI may have utility in informing shared‐decision making on whether to proceed to biopsy and subsequent treatment. [ABSTRACT FROM AUTHOR]

Objectives: To describe contemporary radical prostatectomy (RP) practice using the British Association of Urological Surgeons (BAUS) data and audit project and to observe differences in practice in relation to surgeon or centre case-volume. Patients and Methods: Data on 13 920 RP procedures performed by 179 surgeons across 86 centres were recorded on the BAUS data and audit platform between 1 January 2014 and 31 December 2015. This equates to ~95% of total RPs performed over this period when compared to Hospital Episode Statistics (HES) data. Centre case-volumes were categorised as 'high' (>200), 'medium' (100-200) and 'low' (<100); surgeon case-volumes were categorised as 'high' (>100) and 'low' (<100). Differences in surgical practice and selected outcome measures were observed between groups. All data and volume categories were for the combined 2-year period. Results: The median number of RPs performed over the 2-year period was 63.5 per surgeon and 164 per centre. Overall, surgical approach was robot-assisted laparoscopic RP (RALP) in 65%, laparoscopic RP (LRP) in 23%, and open RP (ORP) in 12%. The dominant approach in high-case-volume centres and by high-case-volume surgeons was RALP (74.3% and 69.2%, respectively). There was a greater percentage of ORPs reported by low-volume surgeons and centres when compared to higher volume equivalents. In all, 51.6% of all patients in this series underwent RP in high-case-volume centres using robot-assisted surgery (RAS). High-case-volume surgeons performed nerve-sparing (NS) procedures on 57.3% of their cases; low-volume surgeons performing NS on 48.2%. Overall, lymph node dissection (LND) rates were very similar across the groups. An 'extended' LND was more commonly performed in high-volume centres (22.1%). The median length of stay (LOS) was lowest in patients undergoing RALP at high-volume centres (1 day) and highest in ORP across all volume categories (3-4 days). Reported pT2 positive surgical margin (PSM) rate varied by technique, centre volume, and surgeon volume. In general, observed PSM rates were lower when RALP was the surgical approach (14.4%) and when high-volume surgeons were compared to low-volume surgeons (13.6% vs 17.7%). Transfusion rates were highest in ORP across all centres and surgeons (2.96-4.49%) compared to techniques using a minimally-invasive approach (0.25-2.41%). Training cases ranged from 0.5% in low-volume centres to 6.0% in high-volume centres. Conclusions: Compliance with data registration for centres and surgeons performing RP is high in the present series. Most RPs were performed in high-case-volume centres and by high-case-volume surgeons, with the most common approaches being minimally invasive and specifically RAS. High-casevolume centres and surgeons reported higher rates of extended LND and training cases. Higher-case-volume surgeons reported lower pT2 PSM rates, whilst the most marked differences in transfusion rates and LOS were seen when ORP was compared to minimally invasive approaches. Caution must be applied when interpreting these differences on the basis of this being registry data - causality cannot be assumed. [ABSTRACT FROM AUTHOR]

Objectives To describe the implementation phase of a robot-assisted radical cystectomy ( RARC) programme including side-effect profiles and impact on length of stay ( LOS). Patients and Methods In all, 114 consecutive patients (82% male) underwent RARC and urinary diversion between April 2013 and December 2015 [ileal conduit (97 patients) and orthotopic neobladder (17)]. Surgery was performed by two surgeons within a designated regional cancer centre. No exclusion criteria were applied. All patients were managed on the Exeter Enhanced Recovery Pathway ( ERP) in a unit where embedded enhanced recovery practice was already established. Data were collected prospectively on the national cystectomy registry - the British Association of Urological Surgeons ( BAUS) Complex Operations Dataset. Results RARC was technically feasible in all but one case. The mean operating time was 3-5 h with an overall transfusion rate of 8.8%. There were higher-grade complications (Clavien-Dindo grade III- IV) in 18.4% of patients, with a 30-day mortality rate of 0.9%. The median (range) LOS after RARC was 7 (3-68) days, with a re-admission rate of 18.4%. Conclusions The present series shows that RARC can be safely implemented in a unit experienced in robot-assisted surgery ( RAS). Case-selection in this setting is not deemed necessary. There are benefits in terms of lower transfusion rates and reduced LOS. The side-effect profile appears to differ from that of open RC, and despite the fact that complication rate is equivalent; 'technical' complications are over-represented in the RAS group. As such, they should improve with experience, recognition, and modification of surgical technique. ERPs can be safely applied to all patients undergoing RARC to maximise the benefits of minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Projectile components that are traditionally radiolucent can be of considerable importance in determination of weapon type and caliber, but they are often missed on evaluation of postmortem radiographs. We hypothesized that these components would be significantly better visualized by evaluation of computed tomography (CT) scans compared to the practice standard of radiography alone. In this project, potentially radiolucent projectile components were both pulled apart and fired, and the radiolucent components were recovered. These components were embedded in blocks of ballistics gelatin and were imaged using both radiography and CT. The scans were evaluated by three blinded, board‐certified radiologists for the presence/absence of projectile components and true‐negative regions in each block. If a radiologist indicated visualization of a projectile component, they were further requested to describe their observation. It was found that traditionally radiolucent projectile components are not significantly more often identified on CT scans than radiography (p < 0.05). [ABSTRACT FROM AUTHOR]

Purpose: Dural sinus malformations (DSMs) are rare pediatric vascular lesions that have variable presentations and outcomes. We present three cases of midline DSMs and discuss the treatment strategy employed for each lesion. A review of the literature was completed to summarize current literature and treatment practices. Methods: A retrospective review of the electronic medical record and all available imaging studies was performed for each of our patients. Results: Patient 1 had a prenatally diagnosed DSM which decreased in size despite no intervention. She was born without complication and continues to do well at 15 months of age. Patient 2 presented 2 weeks after birth with cardiac failure, intracranial hemorrhage, and seizures and imaging showed a large midline DSM with multiple high-flow shunts. She required multiple endovascular embolizations with complete occlusion of the lesion. At her 3-year follow-up, she was neurologically normal. The third patient was diagnosed prenatally with an enlarging DSM. Multiple endovascular embolizations, surgical decompression, cranial expansion, and CSF diversion were required for treatment. At her 2.5-year follow-up, she was meeting developmental milestones, with some motor delay. Conclusion: Early diagnosis and treatment, if necessary, of DSMs are critical to prevent cardiac failure or parenchymal injury from chronic venous hypertension. Management should be decided on individual case basis depending on the angioarchitecture and progression of the lesion and can involve observation, endovascular embolization, surgical interventions, or a combination of treatments. A personalized approach to treating these variable lesions can be associated with good outcomes. [ABSTRACT FROM AUTHOR]

Background: T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T cell-deficient athymic nude (AN) rats exhibit improved functional recovery when compared to immunocompetent Sprague-Dawley (SD) rats following spinal cord transection.Methods: In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery.Results: Athymic nude rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for T(h)2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate.Conclusions: We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue. [ABSTRACT FROM AUTHOR]

The article discusses the introduction of Prisoner's Dilemma game and other related situation games as well as classroom activities which will promote students engagement. Topics discussed include encouraging students to play and discover the paradox, discussion on strategies about students playing for the iterated version and the outcome of the game, and encouraging students to develop strategies and reasons for their actions.

Background: Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. Principal Findings: Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. Conclusions: Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation. [ABSTRACT FROM AUTHOR]

This paper presents a state of the Arts of religious/sectarian dialectal differentiation and sociolinguistic variation in the Arabic-speaking countries. It is based on the studies that have been conducted so far in the fields of dialectology and sociolinguistics to investigate this issue. The first section reminds the reader of the diversity of sociolinguistic situations in the region in terms of the extent of religious differentiation within a city/area. The second section summarizes the trigger of situations of major religious/sectarian differentiation and the factors that led to their stability for many decades or centuries. It also presents three contemporary evolution processes observable in the areas with major differentiation and some contemporary loci of observation of sectarian/religious variation in areas of minor differentiation. [ABSTRACT FROM AUTHOR]

This multi-case study sought to construct meaning using a cultural capital lens in relation to educational leadership preparation programs building the capacities of social justice leaders in demographically changing schools. Data revealed principals’ perceptions about preparation, expectations and general beliefs and assumptions related to leadership for social justice emphasizing contradictions between principals’ equity-oriented rhetoric and their underlying beliefs and assumptions affecting their diverse school populations. The implications for research and practice include opportunities that principals and principal preparation programs have to implement to keep leadership for social justice at the forefront of the charge to equitably educate all children. [ABSTRACT FROM PUBLISHER]

Recent amendments to the Child Abuse Prevention and Treatment Act tie the receipt of federal block grants to mandatory reporting of substance-exposed newborns. To determine rates of screening, testing, and reporting of drug and alcohol use at the time of delivery, we administered a telephone survey of nursing managers and perinatal social workers at Maryland birthing hospitals. Of the 34 hospitals, 31 responded (response rate 91%). Although 97% of hospitals reported universal screening, only 6% used a validated instrument. Testing was reported by 94% with 45% reporting universal maternal testing and 7% universal newborn testing. Only 32% reported obtaining maternal consent prior to testing. There is significant heterogeneity in screening and testing for substance use in birthing hospitals. Given federal reporting mandates, state-level practices need to be standardized. [ABSTRACT FROM AUTHOR]

R4229 --> 649.14 --> Viral infections continue to be the bane of human medicine, often with minimal options for treatment. Of particular concern are arboviruses, or viruses transmitted by an arthropod vector, such as a mosquito. Recently, Zika virus (ZIKV), a mosquito borne arbovirus, has emerged as a major threat to public health in many parts of the world. It is unknown what protein(s) ZIKV uses to bind to and infect cells within its mosquito vector. The receptor used by ZIKV to bind to and infect human cells has been identified as the tyrosine kinase receptor family Axl. A homolog of the Axl gene is not present within the mosquito genome. However, genes for the Down‐Syndrome Cell Adhesion Molecule family members (DSCAMs) found within multiple mosquito species share key functional modular ectodomains with the human Axl gene. Here, we extracted total RNA from Culex and Aedes species of mosquitos, reverse transcribed the RNA into cDNA and then cloned the mosquito DSCAM cDNA with the highest homology to human Axl into a eukaryotic expression vector. The vector will then be transfected into a mammalian cell line void of human DSCAM and human Axl expression to determine if the mosquito DSCAM molecule is expressed as a surface protein. Finally, we will determine if ZIKV is capable of binding to the mammalian cell line that now expresses the mosquito DSCAM protein. This project will allow us to learn if ZIKV is capable of binding to the mosquito DSCAM protein. In turn, this information could lead to the possibility that the mosquito DSCAM protein allows infection by ZIKV as well. Ultimately, this research could assist vaccine development for Zika, or lead to treatments that could block ZIKA from infecting its mosquito vector. [ABSTRACT FROM AUTHOR]

From 1997 until his retirement in 2011, Michel Hersen served as the dean of the School of Professional Psychology (SPP) at Pacific University in Oregon. Through teaching, supervision, and modeling, Michel promoted his vision of a professional school that could compete on the national stage. He grew the program from a regional focus to one with a strong national presence through careful faculty hires and by anticipating national trends in diversity issues and interprofessional education. His decisions as an administrator were sometimes counterintuitive and challenged the status quo, but they often were correct and advanced the program. His footprint as an administrator was quite large and will be difficult to fill. The SPP benefited greatly from his leadership, and it will continue to grow by following the plans he set in place for us. [ABSTRACT FROM AUTHOR]

ATP is an extracellular signal for the immune system, particularly during an inflammatory response. It is sensed by the P2X7 receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the P2X7 receptor opens a cation-specific channel that alters the ionic environment of the cell, activating several pathways, including (i) the inflammasome, leading to production of IL-1β and IL-18; (ii) the stress-activated protein kinase pathway, resulting in apoptosis; (iii) the mitogen-activated protein kinase pathway, leading to generation of reactive oxygen and nitrogen intermediates; and (iv) phospholipase D, stimulating phagosomelysosome fusion. The P2X7 receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the P2X7 receptor may be subverted by pathogens to modulate host responses. Moreover, recent genetic studies have demonstrated significant associations between susceptibility or resistance to parasites and bacteria, and loss-of-function or gain-of-function polymorphisms in the P2X7 receptor, underscoring its importance in infectious disease. [ABSTRACT FROM AUTHOR]

The article describes various activity programs for mathematics education that teaches students about Collatz conjecture.

Abstract: The P2X7 receptor (P2X7R) is a two transmembrane receptor that is highly expressed on the surface of immune cells. Loss of function polymorphisms in this receptor have been linked to increased susceptibility to intracellular pathogens. P2X7R gene knockout (P2X7R−/−; on a C57Bl/6J background), C57Bl/6J and BALB/c mice were infected with the avirulent ME49 strain of the intracellular parasite, Toxoplasma gondii, and susceptibility determined by monitoring weight loss. P2X7R−/− mice lost significantly more weight than C57Bl/6J mice from day 8p.i. C57Bl/6J, in turn, lost significantly more weight than BALB/c mice. Thus, by day 10p.i., P2X7R−/− mice had lost 5.7±0.7% of their weight versus 2.4±0.6% for C57Bl/6J mice, whereas BALB/c mice had gained 1.9±0.5%; by day 12p.i., P2X7R−/− mice had lost 15.1±0.6%, C57Bl/6J had lost 10.1±0.8% and BALB/c had lost 4.8±0.8% of their weight. Neither parasite burden nor liver pathology was greater in the P2X7R−/− mice than in C57Bl/6J mice but BALB/c mice had significantly smaller numbers of parasites and less pathology in their livers than these strains. Absence of the P2X7 receptor did not affect IFN-γ, IL-12, IL-1β, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X7R−/− and C57Bl/6J mice produced more IL-1β and TNF than BALB/c mice. There was one important point of differentiation between the P2X7R−/− and C57Bl/6J mice, namely the significantly enhanced and prolonged production of nitric oxide, accompanied by delayed production of IL-10 in the P2X7R-deficient mice. [Copyright &y& Elsevier]

Background: The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-γ, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine howthe various facets of the immune responses induced by each may influence or counter-regulate that of the other. Principal Findings: Regardless, of whether F. hepatica infection preceded or succeeded T. gondii infection, there was little impact on the production of the Th1 cytokines IL-12, IFN-γ or on the development of classically-activated macrophages induced by T. gondii. By contrast, the production of helminth-specific Th2 cytokines, such as IL-4 and IL-5, was suppressed by infection with T. gondii. Additionally, the recruitment and alternative activation of macrophages by F. hepatica was blocked or reversed by subsequent infection with T. gondii. The clinical symptoms of toxoplasmosis and the survival rate of infected mice were not significantly altered by the helminth. Conclusions: Despite previous studies showing that F. hepatica suppressed the classical activation of macrophages and the Th1-driven responses of mice to bystander microbial infection, as well as reduced their ability to reject these, here we found that the potent immune responses to T. gondii were capable of suppressing the responses to helminth infection. Clearly, the outcome of particular infections in polyparasitoses depends on the means and potency by which each pathogen controls the immune response. [ABSTRACT FROM AUTHOR]

Abstract: Toxoplasma gondii is a unique intracellular parasite. It can infect a variety of cells in virtually all warm-blooded animals. It has a worldwide distribution and, overall, around one-third of people are seropositive for the parasite, with essentially the entire human population being at risk of infection. For most people, T. gondii causes asymptomatic infection but the parasite can cause serious disease in the immunocompromised and, if contracted for the first time during pregnancy, can cause spontaneous abortion or congenital defects, which have a substantial emotional, social and economic impact. Toxoplasma gondii provokes one of the most potent innate, pro-inflammatory responses of all infectious disease agents. It is also a supreme manipulator of the immune response so that innate immunity to T. gondii is a delicate balance between the parasite and its host involving a coordinated series of cellular interactions involving enterocytes, neutrophils, dendritic cells, macrophages and natural killer cells. Underpinning these interactions is the regulation of complex molecular reactions involving Toll-like receptors, activation of signalling pathways, cytokine production and activation of anti-microbial effector mechanisms including generation of reactive nitrogen and oxygen intermediates. [Copyright &y& Elsevier]

Abstract: Abortion, resulting from infections by the parasite Neospora caninum, is a major cause of economic loss to both the dairy and beef industries of cattle-producing countries of the world. Vaccination as a means of preventing abortion and/or infection represents a viable control strategy; indeed a commercial vaccine is available in some countries, albeit of unknown efficacy. The commercial vaccine is based on inactivated tachyzoites of N. caninum but other approaches based on lysates and recombinant antigens of N. caninum may also be feasible. In this study we have used an immunisation/challenge model of transplacental transmission, based on the Qs mouse with an Nc-Liverpool challenge, to investigate the vaccine potential of a number of formulations based on four recombinant proteins of N. caninum (GRA1, GRA2, MIC10, and p24B). All formulations studied were immunogenic in the mouse when assessed by ELISA using sonicated tachyzoite antigen as the target antigen. In one experiment, a mixture of MIC10 and p24B produced partial protection against transplacental transmission of N. caninum in this mouse model; in contrast a live infection of tachyzoites of NC-Nowra given before pregnancy always induces very high levels of protective immunity. The field of vaccines against Neospora-associated abortion in cattle is discussed. [Copyright &y& Elsevier]

Objective: Though virtual outpatient psychotherapy for eating disorders is likely effective, less is known about virtual higher levels of care. The current study examined the clinical outcomes of a family‐based virtual intensive outpatient program (vIOP) for youth with eating disorders which was developed in response to the COVID‐19 pandemic, compared to the same institution's in‐person partial hospital program (PHP). Methods: Treatment outcomes were assessed via chart review in 102 patients between the ages of 9–23 (M = 15.2, SD = 2.5) who were predominantly cisgender female (84.3%) and primarily diagnosed with anorexia nervosa (64.7%) or atypical anorexia (23.5%). Participants were either treated in the in‐person PHP before the pandemic (n = 49) or the vIOP during the pandemic (n = 53). Percent expected body weight (%EBW) was examined at baseline, end of treatment, 3‐months post‐treatment, and 6‐months post‐treatment, as well as the frequency of medical, psychiatric, and residential admissions before, during, and after vIOP or PHP participation. Results: Linear mixed models demonstrated no effect of treatment modality (in‐person versus virtual) on %EBW over time. The duration of the vIOP was, on average, 12 calendar days longer, though the amount billed for the vIOP was lower. Survival analyses and Cox regression models did not suggest differences in the frequency of hospital and residential treatment admissions during treatment (vIOP: 9.4%, PHP: 10.0%) or post‐treatment (vIOP: 15.0%, PHP: 10.2%). Discussion: Findings support virtual family‐based programs as suitable alternatives to in‐person treatment and underscore the potential cost‐effectiveness of a family‐based IOP versus PHP. Public Significance: This study demonstrates that a virtual, family‐based, intensive outpatient program for youth with eating disorders had similar treatment outcomes to an in‐person partial hospitalization program. Specifically, the virtual and in‐person programs had similar weight restoration outcomes and rates of medical, psychiatric, or residential treatment admissions during or after treatment initiation. Findings support the use of virtual treatment, even for youth requiring a high level of intervention. [ABSTRACT FROM AUTHOR]

The article provides a new method for mathematics teachers to use in looking at a traditional routine mathematical problem. It proposes the use of problem analysis as a way to explore mathematical content significantly, allowing students' familiarity with a problem to serve as a basis of understanding for more complexity in the next. Problem analysis is one technique to use in making connections, and by completing it, teachers can find ways to extend and generalize most problems. Through this analysis, students can better appreciate the algebra or calculus they use and become more able to apply problem-solving techniques.

The article presents several activities that will lead students to discover interesting connections between matrices and Fibonacci numbers while practicing various skills, including matrix multiplication, pattern recognition, and proof by induction. These activities could be used in an algebra 2 course, once matrices have been introduced. The Fibonacci numbers have fascinated artists, scientists, and mathematicians for centuries. Some patterns in the Fibonacci numbers are based solely on mathematical concepts. This sequence is named for Leonardo da Pisa, one of the most well-known mathematicians from the Middle Ages. He is better known as Fibonacci, which is short for "filius Bonacci," meaning "the son of Bonaccio." Fibonacci wrote several books on mathematics. For pre-calculus students who have studied induction, proofs of these interesting patterns could be discussed. The off-diagonal of a matrix begins in the upper-right corner of the matrix and continues diagonally to the lower-left entry. While students consider this list of prime numbers, ask if they think more prime numbers could be found later in the sequence. The current emphasis on real-world mathematics helps students connect mathematics to their lives, but those students who appreciate the beauty of patterns and proofs may not have many opportunities to see the beauty of pure mathematics.

This article analyzes processes of dialectal accommodation among Upper Egyptian migrants in Cairo-Egypt. Rural and provincial migration have played an important role in the demographic growth of the capital from the mid-nineteenth century up to the 1970s. Although migration is today receding, the social and cultural integration of the migrants is far from being completed, and it has raised a number of socioeconomic challenges. Due to underdevelopment, poverty, and religious traditionalism, Upper Egypt is often described as a problematic area, and this perception reflects on the relationship between Cairene and Upper Egyptian migrants. Cairene Arabic and Upper Egyptian varieties are linguistically quite distinct and they do not have the same status, Cairene being a national prestige variety. Based on data recorded among seven adult speakers, this article analyzes the realization of 21 features, taking into account not only Cairo and Upper Egyptian variants but also the influence of fus̥ḥā (Classical Arabic). It shows that the degree of accommodation to Cairo Arabic among the first migrant generation varies according to type of linguistic features (phonological, morphological, lexical), as well as type of interaction/topics and individual personal profile. [ABSTRACT FROM AUTHOR]

Abstract: Infection with the protozoan parasite Neospora caninum is an important cause of abortion in cattle. A major source of infection is transplacental transfer of the parasite from mother to offspring during pregnancy. This study describes investigations on the immunisation of outbred Qs mice before pregnancy with live or a crude lysate of N. caninum (NC-Nowra isolate) to prevent transplacental transfer of a challenge infection administered during pregnancy. Parasites present in the brains of pups from mice challenged with N. caninum (NC-Liverpool) were detected by PCR. Injection of live NC-Nowra tachyzoites before pregnancy dramatically reduced transplacental transfer from 75 to 0.8% in one experiment and from 76 to 8% in a second experiment. Injection of a crude lysate of NC-Nowra tachyzoites reduced transplacental transfer from 67 to 53% in one experiment and from 76 to 63% in a second experiment. Analysis of N. caninum-specific IgG1 and IgG2a antibody levels prior to pregnancy and challenge showed that NC-Nowra lysate induced a response skewed towards IgG1 whereas live parasites induced both IgG1 and IgG2a antibodies. After pregnancy and a challenge infection, a similar IgG1/IgG2a response was seen in all challenged groups. These results provide further positive support for the hypothesis that transplacental transmission of this parasite is preventable by vaccination. [Copyright &y& Elsevier]

Summary: We here identify and characterize an extracellular modulator of Hedgehog signaling in Drosophila, Shifted. Shifted is required for high levels of long-range signaling in the developing wing imaginal disc. Surprisingly, shifted encodes the only Drosophila ortholog of the secreted vertebrate protein Wnt Inhibitory Factor-1 (WIF-1), whose known role is to bind to extracellular Wnts and inhibit their activity. However, Shifted does not regulate Hedgehog signaling by affecting Wingless or Wnt signaling. We show instead that Shifted is a secreted protein that acts over a long distance and is required for the normal accumulation of Hh protein and its movement in the wing. Our data further indicate that Shf interacts with Hh and the heparan sulfate proteoglycans. Therefore, we propose that Shf stabilizes the interaction between Hh and the proteoglycans, an unexpected role for a member of the WIF-1 family. [Copyright &y& Elsevier]

The experience of being stalked is markedly higher among college students than in the general population. A clear understanding of stalking in this population will guide prevention and intervention efforts for both perpetrators and victims. Specifically, this article reviews the literature on the prevalence of stalking behaviors among young adults, the psychological effects on young victims, how these victims cope with being stalked, and possible reasons for this behavior. In order to provide context for data on young adults, comparisons with the adult literature will be provided where possible. At the conclusion of this review, we address topics in need of further research. [Copyright &y& Elsevier]

This paper reviews the literature that addresses the impact of an abusive family context on childhood animal cruelty and adult violence. In the first section, literature is presented that outlines possible abusive family contextual factors associated with childhood animal cruelty and adult violence. In the second section, theories presented in the literature conjecturing about the impact of an abusive family context on childhood animal cruelty and adult violence are reviewed. Section 3 addresses the predictive validity of an abusive family context on adult violence. In the final section, assessment measures and interventions of childhood animal cruelty are discussed. Such discussion focuses on the acknowledgement of an abusive family context in the assessment and intervention of childhood animal cruelty. Overall, the literature suggests that an abusive family context may be a better predictor of adult violence than childhood animal cruelty. [Copyright &y& Elsevier]

Foreign language

There have been several conflicting reports as to the scavenging nature of glutathione toward the nitro radical anion of the drug nitrofurantoin. We produced the radical anion enzymatically using the xanthine oxidase/hypoxanthine system at pH 7.4 and pH 9.0 in the presence of various levels of glutathione from 10 to 100 mM and monitored any changes in the radical concentration via electron spin resonance spectroscopy. Independent of glutathione concentration, there was no decrease in the steady-state concentration of the radical. In fact, there was an average 30% increase in the concentration of the radical anion, which suggests enhanced enzyme activity in the presence of glutathione (GSH). These results, together with observations of the effects of glutathione on the stability of the radical anion generated by radiolysis or dithionite, rule out any detectable reaction between the nitrofurantoin radical anion and GSH under physiologically relevant conditions. [Copyright &y& Elsevier]

Analyzes data from the Toxics Release Inventory (TRI), a United States report which requires manufacturers to disclose to the public their routine toxic releases. Political pressures resulting from the perceived success of TRI in reducing toxic releases; Economic and political factors which helped create different trends in toxic releases; Strengths and limitations of the architecture of TRI. INSET: Navigators Gain Political Power.

The article presents a study which compares the two main methods of formal-empirical classification--cluster analysis and Q-Factor analysis in patients with psychological disorder. Both cluster analysis and Q-factor analysis are indices, which indicates the degree tween every possible pair of persons. The mathematical basis of Q-factor analysis has been worked out in greater detail; it is better understood and more sophisticated. The Minnesota Multiphasic Personality Inventory data were collected to make possible such an analysis of the substantive nature of the cluster and factor types obtained. The results, as well as methodological considerations, suggest that Q-factor analysis is the more useful method for the purpose of classifying patients.

Presents a telephone survey conducted by Hampshire Research Institute on whether reported reductions of Toxics Release Inventory-listed toxic chemicals by industrial facilities in the United States are factual. Percentage which changes in plant operations and production levels accounted for in reductions; Amount facilities reduced production-related waste by. INSETS: Why amounts reported to TRI can change;Data reported to TRI.

The article offers information on how to use a nurse-controlled intravenous insulin protocol in preventing complications and support healing.

The article discusses the pathophysiology of hyperglycemia and its effects on the tissues. Glucose becomes irreversibly bound to collagen and other proteins in the blood vessel walls and intestinal tissues. Hyperglycemia produces an inappropriate activation of the protein kinase C enzyme. It interferes with the normal functioning of red blood cells, white blood cells and endothelium and helps cover up various illness-related microbes. Drugs linked to hyperglycemia are presented.

Presents information on a project that enables the students to experience problem-solving strategies. Overview on the research assignment; Discussion on sharing and making sense of the data in class; How the research is used.

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient's response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value. [ABSTRACT FROM AUTHOR]

Introduction: Persistence to multiple sclerosis (MS) disease-modifying therapy is fundamental for maximal treatment outcomes. Diroximel fumarate (DRF) is approved in the USA for relapsing MS. Following oral administration, DRF is metabolized to monomethyl fumarate, the active metabolite of dimethyl fumarate (DMF). DRF showed clinically significant improvements in gastrointestinal (GI) tolerability versus DMF in a head-to-head clinical trial; however, real-world persistence/adherence has not been assessed. We evaluated persistence/adherence in DRF-treated patients in a real-world clinical practice. Methods: This retrospective analysis of the AcariaHealth Specialty Pharmacy Program included patients initiating DRF from 4 December 2019 through 3 April 2020 and followed until data extraction (31 August 2020). Exclusion criteria included undetermined treatment status (e.g., DRF prescription transfer to a different pharmacy). Endpoints included persistence (overall proportion of patients remaining on DRF), discontinuation rate due to GI adverse events (AEs), and adherence (proportion of days covered [PDC]). GI AEs included GI-related AEs occurring at any time, or any unknown AE without details about the nature of the event if the unknown AE occurred ≤ 90 days after DRF initiation. Results: Overall, 160 patients with MS were included. Median (range) patient age was 51 (20−79) years, 80.6% (129/160) of patients were female, and 16.3% (26/160) had prior DMF treatment. Median (range) treatment duration was 7.6 (0.1−10.4) months. Estimated proportion of patients remaining persistent on DRF treatment at 8 months was 88.6% (95% confidence interval [CI] 82.5–2.7). Overall, 3.8% (6/160) of patients discontinued due to GI AEs. Mean PDC was 91.4% (95% CI 89.1−93.7). In a DMF-to-DRF switch subgroup, 92.3% (24/26) remained persistent on DRF, and 3.8% (1/26) discontinued DRF due to GI AEs. Conclusion: This real-world analysis of DRF-treated patients showed high overall persistence, low discontinuation rate due to GI AEs, and high adherence to therapy, aligning with expectations based on DRF clinical trials. Data were consistent in the DMF-to-DRF subgroup. Infographic: [ABSTRACT FROM AUTHOR]