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Abstract Background Epilepsy remains a significant public health concern in Tanzania, with affected individuals enduring stigma, whether through actions or perceptions. Myths, misunderstandings, and misconceptions about epilepsy have persisted due to a multitude of factors. Here, we assessed attitudes and perceptions toward epilepsy in Mahenge. Methods A cross-sectional study utilising a mixed-methods approach was undertaken in eight villages in the Ulanga district of Mahenge, integrating a semi-structured questionnaire and focus group discussions (FGDs). The questionnaire involved 778 community members, and 15 FGDs were conducted (seven groups with people with epilepsy and eight without). Descriptive statistics, chi-square, and logistic regression were used for quantitative analysis, while we used NVivo version 14 for thematic analysis of qualitative data. Results Of 778 participants, over half were women (425, 54.6%) with a median age of 41 years (IQR: 30–55) and most had completed primary education (79.9%). The majority of participants were aware of epilepsy (96.8%), yet they displayed low knowledge (51%), negative attitudes (45.5%), and perceptions (42.1%) towards the disorder. A low level of understanding was significantly associated with negative attitudes (Adjusted Odds Ratio [AOR] = 1.89, 95%CI: 1.41–2.53) and perceptions (AOR = 3.22, 95%CI: 2.05–5.04) towards epilepsy. In the qualitative analysis, often hereditary factors and infections were named as causes of epilepsy, along with misconceptions involving witchcraft and divine punishment. There was also a misconception about the contagiousness of epilepsy. Traditional healers were often the initial point of treatment. Epilepsy-related stigma was evident, with individuals with epilepsy facing derogatory labels, social isolation, and barriers to education. Lastly, there was a lack of understanding regarding a possible association between epilepsy and onchocerciasis. Conclusions Despite high awareness of epilepsy, there is insufficient understanding, negative attitudes, and perceptions, including misconceptions and stigma about this neurologic condition. Community-based education programmes are essential for promoting proper healthcare-seeking behaviour and dispelling myths.

Abstract Background Exploration of client identity negotiations during treatment for Anorexia Nervosa (AN) is a relatively new area of research. Research suggests that difficulties with identity negotiations may present as a barrier to treatment. This study sought to explore individuals’ identity negotiations during therapy sessions using Compulsive Exercise Activity Therapy (LEAP) combined with Cognitive Behaviour Therapy for Anorexia Nervosa (CBT-AN). Analysis focused on moments in therapy where individuals’ identities were dominated or defined by AN and where alternative identities could be generated. Method 40 in-session transcripts from sessions at early, mid and end points of the CBT-AN (with LEAP) treatment were qualitatively analysed for nine of the 78 participants in the original randomised control trial. Through a constructivist framework, thematic analysis was used to identify surface and latent meanings and discursive material participants used to negotiate their identities in the context of therapy sessions. Results Analysis of in-therapy transcripts generated two themes pertaining to identity negotiations: (1) troubled identities and (2) rebuilding identities and lives outside of AN. Early therapy sessions explored fragmented and AN dominated identities, including how AN was troubling to participants’ sense of self, contributed to conflicted identities, positioned them outside of normality, and was associated with isolated and othering identities. Within therapy sessions, participants engaged in a recursive process of shifting relationships with AN and themselves and building identities and lives outside of the AN identity. This included generating hopes for recovery and the future more frequently in mid- to late- therapy sessions. Conclusion Identity negotiations evident in the therapeutic conversations aligned with the key components of the CBT-AN intervention, including addressing (1) the characterisation of oneself as ‘an anorexic’ and (2) the diversification of roles and activities to broaden and enhance self-concepts. Future developments of therapeutic interventions for AN would benefit from greater consideration of ways to assist individuals to more comprehensively address problematic identities, including uncovering identities hidden by the AN identity and generating preferred identities. Trial Registration: Ethics approval was obtained at the time of the initial study and for this embedded research by the HREC at the Western Sydney University (HR777332).

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Background: It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk.Methods: We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the women's medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child.Results: Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7).Conclusions: The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself. [ABSTRACT FROM AUTHOR]

Iron-sulfur (Fe-S) clusters are ubiquitous inorganic cofactors required for numerous essential cellular pathways. Since they cannot be scavenged from the environment, Fe-S clusters are synthesized de novo in cellular compartments such as the apicoplast, mitochondrion, and cytosol. The cytosolic Fe-S cluster biosynthesis pathway relies on the transport of an intermediate from the mitochondrial pathway. An ATP-binding cassette (ABC) transporter called ABCB7 is responsible for this role in numerous commonly studied organisms, but its role in the medically important apicomplexan parasites has not yet been studied. Here we identify and characterize a Toxoplasma gondii ABCB7 homolog, which we name ABCB7-like (ABCB7L). Genetic depletion shows that it is essential for parasite growth and that its disruption triggers partial stage conversion. Characterization of the knock-down line highlights a defect in the biogenesis of cytosolic and nuclear Fe-S proteins leading to defects in protein translation and other pathways including DNA and RNA replication and metabolism. Our work provides support for a broad conservation of the connection between mitochondrial and cytosolic pathways in Fe-S cluster biosynthesis and reveals its importance for parasite survival., Importance: Iron-sulfur (Fe-S) clusters are inorganic cofactors of proteins that play key roles in numerous essential biological processes, for example, respiration and DNA replication. Cells possess dedicated biosynthetic pathways to assemble Fe-S clusters, including a pathway in the mitochondrion and cytosol. A single transporter, called ABCB7, connects these two pathways, allowing an essential intermediate generated by the mitochondrial pathway to be used in the cytosolic pathway. Cytosolic and nuclear Fe-S proteins are dependent on the mitochondrial pathway, mediated by ABCB7, in numerous organisms studied to date. Here, we study the role of a homolog of ABCB7, which we name ABCB7-like (ABCB7L), in the ubiquitous unicellular apicomplexan parasite Toxoplasma gondii . We generated a depletion mutant of Toxoplasma ABCB7L and showed its importance for parasite fitness. Using comparative quantitative proteomic analysis and experimental validation of the mutants, we show that ABCB7L is required for cytosolic and nuclear, but not mitochondrial, Fe-S protein biogenesis. Our study supports the conservation of a protein homologous to ABCB7 and which has a similar function in apicomplexan parasites and provides insight into an understudied aspect of parasite metabolism., Competing Interests: The authors declare no conflict of interest.

Introduction: Mild traumatic brain injury (mTBI) is a common injury that can lead to temporary and, in some cases, life-long disability. Magnetic resonance imaging (MRI) is widely used to diagnose and study brain injuries and diseases, yet mTBI remains notoriously difficult to detect in structural MRI. mTBI is thought to be caused by microstructural or physiological changes in the function of the brain that cannot be adequately captured in structural imaging of the gray and white matter. However, structural MRIs may be useful in detecting significant changes in the cerebral vascular system (e.g., the blood-brain barrier (BBB), major blood vessels, and sinuses) and the ventricular system, and these changes may even be detectable in images taken by low magnetic field strength MRI scanners (<1.5T)., Methods: In this study, we induced a model of mTBI in the anesthetized rat animal model using a commonly used linear acceleration drop-weight technique. Using a 1T MRI scanner, the brain of the rat was imaged, without and with contrast, before and after mTBI on post-injury days 1, 2, 7, and 14 (i.e., P1, P2, P7, and P14)., Results: Voxel-based analyses of MRIs showed time-dependent, statistically significant T2-weighted signal hypointensities in the superior sagittal sinus (SSS) and hyperintensities of the gadolinium-enhanced T1-weighted signal in the superior subarachnoid space (SA) and blood vessels near the dorsal third ventricle. These results showed a widening, or vasodilation, of the SSS on P1 and of the SA on P1-2 on the dorsal surface of the cortex near the site of the drop-weight impact. The results also showed vasodilation of vasculature near the dorsal third ventricle and basal forebrain on P1-7., Discussion: Vasodilation of the SSS and SA near the site of impact could be explained by the direct mechanical injury resulting in local changes in tissue function, oxygenation, inflammation, and blood flow dynamics. Our results agreed with literature and show that the 1T MRI scanner performs at a level comparable to higher field strength scanners for this type of research., Competing Interests: JB, BK, MS, CC, and DF were employed by General Dynamics Information Technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burns, Kalinosky, Sloan, Cerna, Fines, Valdez and Voorhees.)

Biological effects in the microwave band of the radiofrequency (RF) spectrum are thermally mediated. For acute high-power microwave exposures, these effects will depend on transient time-temperature histories within the tissue. In this article, we summarize the transient temperature response of rats exposed to RF energy emanating from an open-ended rectangular waveguide. These exposures produced specific absorption rates of approximately 36 and 203 W/kg in the whole body and brain, respectively. We then use the experimentally measured thermal data to infer the baseline perfusion rate in the brain and modify a custom thermal modeling tool based upon these findings. Finally, we compare multi-physics simulations of rat brain temperature against empirical measurements in both live and euthanized subjects and find close agreement between model and experimentation. This research revealed that baseline brain perfusion rates in rat subjects could be larger than previously assumed in the RF thermal modeling literature, and plays a significant role in the transient thermal response to high-power microwave exposures. © 2021 Bioelectromagnetics Society., (© 2021 Bioelectromagnetics Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

The acquisition and storage of metals has been a preoccupation of life for millennia. Transition metals, in particular iron, copper and zinc, have vital roles within cells. However, metals also make dangerous cargos; inappropriate uptake or storage of transition metals leads to cell death. This paradox has led to cells developing elegant and frequently redundant mechanisms for fine-tuning local metal concentrations. In the context of infection, pathogens must overcome further hurdles, as hosts act to weaponize metal availability to prevent pathogen colonization and spread. Here, we detail the methods used by the Apicomplexa, a large family of eukaryotic parasites, to obtain and store essential metals.

Background: Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that affects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control require a better understanding of the key step for transmission, namely the establishment of infection inside the fly., Methods: The aim of this work was to identify sand fly systemic transcriptomic signatures associated with Leishmania infection. We used next generation sequencing to describe the transcriptome of whole Phlebotomus papatasi sand flies when fed with blood alone (control) or with blood containing one of three trypanosomatids: Leishmania major, L. donovani and Herpetomonas muscarum, the latter being a parasite not transmitted to humans., Results: Of the trypanosomatids studied, only L. major was able to successfully establish an infection in the host P. papatasi. However, the transcriptional signatures observed after each parasite-contaminated blood meal were not specific to success or failure of a specific infection and they did not differ from each other. The transcriptional signatures were also indistinguishable after a non-contaminated blood meal., Conclusions: The results imply that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. Alternatively, Leishmania could suppress host responses. These results will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). With resistance to both vector-targeted pesticides and trypanocidal drugs being reported, there is a need for novel transmission blocking strategies to be developed. Studies using the blood-feeding vectors themselves are not broadly accessible, as such, new model systems are being developed to unpick insect-trypanosmatids interactions. One such case is the interactions between the model dipteran Dr osophila melanogaster and its natural trypanosomatid Herpetomonas muscarum Our previous work has found that much of the transcriptomic changes triggered in H. muscarum after ingestion by Drosophila reflect what is known for disease-causing trypanosomatids. Here we describe a set of tools to genetically manipulate the parasite and therefore create a truly tractable insect-parasite interaction system from both sides of this association. These include transgenic fluorescently tagged parasites to follow infection dynamics in the fly gut as well as iterations of plasmids that can be used for generating knock-in and knock-out strains. The tools presented in this short report will facilitate further characterization of trypanosomatid establishment in a model dipteran., (Copyright © 2020 Sloan, Ligoxygakis.)

Introduction: Timely management of sepsis has become an urgent concern among most hospitals. Institutions have been searching for unique ways to increase the quality of care and timely adherence to proven therapies. The objective of this study was to determine the impact of an Adult Code Sepsis Protocol on the rate of SEP-1 perfect score attainment (PSA) among patients who presented to the emergency department (ED) with severe sepsis or septic shock, as defined by the Centers for Medicare and Medicaid Services (CMS)., Methods: This was a retrospective, observational cohort study in a 35-bed tertiary care hospital ED from December 2016 to February 2018. Adults (≥18 years of age) who met the CMS-case definition of severe sepsis or septic shock presenting to the ED either prior to or after implementation of an Adult Code Sepsis Protocol were included., Results: The primary outcome of SEP-1 PSA, which was abstracted in an all-or-none fashion, increased from 30.7% to 71.3% (p < 0.001). Inpatient mortality was reduced from 4% to 0% (p = 0.011) after protocol implementation. Protocol initiation also resulted in a significant reduction in both time to initiation of appropriate, empiric and effective antimicrobial therapy, based on culture results by 48 and 111 min, respectively (p < 0.001). There were no significant differences in other secondary outcomes including ICU length-of-stay, readmission, or economic outcome measures., Conclusions: The addition of an Adult Code Sepsis Protocol in the ED significantly increased the rate of SEP-1 PSA, reduced inpatient mortality, and improved the time to initiation of effective antimicrobial therapy., Competing Interests: Declaration of Competing Interest Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Global health security depends on effective surveillance systems to prevent, detect, and respond to disease threats. Real-time surveillance initiatives aim to develop electronic systems to improve reporting and analysis of disease data. Sierra Leone, with the support of Global Health Security Agenda partners, developed an electronic Integrated Disease Surveillance and Response (eIDSR) system capable of mobile reporting from health facilities. We estimated the economic costs associated with rollout of health facility eIDSR in the Western Area Rural district in Sierra Leone and projected annual direct operational costs. Cost scenarios with increased transport costs, decreased use of partner personnel, and altered cellular data costs were modeled. Cost data associated with activities were retrospectively collected and were assessed across rollout phases. Costs were organized into cost categories: personnel, office operating, transport, and capital. We estimated costs by category and phase and calculated per health facility and per capita costs. The total economic cost to roll out eIDSR to the Western Area Rural district over the 14-week period was US$64,342, a per health facility cost of $1,021. Equipment for eIDSR was the primary cost driver (45.5%), followed by personnel (35.2%). Direct rollout costs were $38,059, or 59.2% of total economic costs. The projected annual direct operational costs were $14,091, or $224 per health facility. Although eIDSR equipment costs are a large portion of total costs, annual direct operational costs are projected to be minimal once the system is implemented. Our findings can be used to make decisions about establishing and maintaining electronic, real-time surveillance in Sierra Leone and other low-resource settings.

The Global Health Security Agenda aims to improve countries' ability to prevent, detect, and respond to infectious disease threats by building or strengthening core capacities required by the International Health Regulations (2005). One of those capacities is the development of surveillance systems to rapidly detect and respond to occurrences of diseases with epidemic potential. Since 2015, the US Centers for Disease Control and Prevention (CDC) has worked with partners in Sierra Leone to assist the Ministry of Health and Sanitation in developing an Integrated Disease Surveillance and Response (IDSR) system. Beginning in 2016, CDC, in collaboration with the World Health Organization and eHealth Africa, has supported the ministry in the development of Android device mobile data entry at the health facility for electronic IDSR (eIDSR), also known as health facility-based eIDSR. Health facility-based eIDSR was introduced via a pilot program in 1 district, and national rollout began in 2018. With more than 1,100 health facilities now reporting, the Sierra Leone eIDSR system is substantially larger than most mobile-device health (mHealth) projects found in the literature. Several technical innovations contributed to the success of health facility-based eIDSR in Sierra Leone. Among them were data compression and dual-mode (internet and text) message transmission to mitigate connectivity issues, user interface design tailored to local needs, and a continuous-feedback process to iteratively detect user or system issues and remediate challenges identified. The resultant system achieved high user acceptance and demonstrated the feasibility of an mHealth-based surveillance system implemented on a national scale.

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied-despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania., Competing Interests: The authors have declared that no competing interests exist.

Background: Hemorrhage is the leading cause of death on the battlefield. Damage control resuscitation guidelines in the US military recommend whole blood as the preferred resuscitation product. The Armed Services Blood Program (ASBP) has initiated low-titer group O whole blood (LTOWB) production and predeployment donor screening to make whole blood more available to military forces., Study Design and Methods: ASBP donor centers updated procedures and labeling for LTOWB production. Donors are screened according to US Food and Drug Administration regulations and standard operating procedures. Group O donors are tested for anti-A and anti-B titer levels. Additionally, military personnel notified for pending deployment coordinate with their local ASBP donor center to complete whole blood donor prescreening. The process consists of completing a donor history questionnaire, processing of blood samples for blood group and infectious disease testing, and titer determination for group O personnel., Results: Since March 2016, 7940 LTOWB units have been manufactured at ASBP donor centers and shipped in support of combat operations. Additionally, ASBP donor centers have screened several thousand service members before deployment. From these screenings, the donor low titer rate was 68% and infectious disease reactive test rate was extremely low (≤0.004)., Conclusion: Whole blood is now the preferred blood product for resuscitation of combat trauma patients. The ASBP partnered with combat forces to screen personnel before deployment. Additionally, LTOWB is manufactured and shipped in support of combat operations. These efforts are expanding the availability of LTOWB for the warfighter., (© 2019 AABB.)

Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids., Competing Interests: The authors have declared that no competing interests exist.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials., (Copyright © 2017. Published by Elsevier Ltd.)

The levamisole-sensitive nicotinic acetylcholine receptor present at nematode neuromuscular junctions is composed of multiple different subunits, with the exact composition varying between species. We tested the ability of two well-conserved nicotinic receptor subunits, UNC-38 and UNC-29, from Haemonchus contortus and Ascaris suum to rescue the levamisole-resistance and locomotion defects of Caenorhabditis elegans strains with null deletion mutations in the unc-38 and unc-29 genes. The parasite cDNAs were cloned downstream of the relevant C. elegans promoters and introduced into the mutant strains via biolistic transformation. The UNC-38 subunit of H. contortus was able to completely rescue both the locomotion defects and levamisole resistance of the null deletion mutant VC2937 (ok2896), but no C. elegans expressing the A. suum UNC-38 could be detected. The H. contortus UNC-29.1 subunit partially rescued the levamisole resistance of a C. elegans null mutation in unc-29 VC1944 (ok2450), but did cause increased motility in a thrashing assay. In contrast, only a single line of worms containing the A. suum UNC-29 subunit showed a partial rescue of levamisole resistance, with no effect on thrashing., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Transcranial Doppler (TCD) is a physiological ultrasound test with established safety and efficacy. Although imaging devices may be used to depict intracranial flow superimposed on structural visualization, the end-result provided by imaging duplex or nonimaging TCD is sampling physiological flow variables through the spectral waveform assessment., Summary of Results: Clinical indications considered by this multidisciplinary panel of experts as established are: sickle cell disease, cerebral ischemia, detection of right-to-left shunts (RLS), subarachnoid hemorrhage, brain death, and periprocedural or surgical monitoring. The following TCD-procedures are performed in routine in- and outpatient clinical practice: complete or partial TCD-examination to detect normal, stenosed, or occluded intracranial vessels, collaterals to locate an arterial obstruction and refine carotid-duplex or noninvasive angiographic findings; vasomotor reactivity testing to identify high-risk patients for first-ever or recurrent stroke; emboli detection to detect, localize, and quantify cerebral embolization in real time; RLS-detection in patients with suspected paradoxical embolism or those considered for shunt closure; monitoring of thrombolysis to facilitate recanalization and detect reocclusion; monitoring of endovascular stenting, carotid endarterectomy, and cardiac surgery to detect perioperative embolism, thrombosis, hypo- and hyperperfusion., Conclusion: By defining the scope of practice, these standards will assist referring and reporting physicians and third parties involved in the process of requesting, evaluating, and acting upon TCD results., (© 2010 by the American Society of Neuroimaging.)

Acute low back pain with or without radiculopathy is one of the most common health problems in the United States, with high annual costs of evaluation and treatment, not including lost productivity. Multiple reports show that uncomplicated acute low back pain or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Guidelines for recognition of patients with more complicated status can be used to identify those who require further evaluation for suspicion of more serious problems and contribute to appropriate imaging utilization.

Transcranial Doppler ultrasonography (TCD) is the only noninvasive real-time neuroimaging modality for the evaluation of characteristics of blood flow in basal intracerebral vessels that adds physiologic information to structural imaging. TCD has been rapidly evolving from a simple noninvasive diagnostic tool to an imaging modality with a broad spectrum of clinical applications. In acute stroke, TCD can provide rapid information about vascular stenosis and occlusion, the hemodynamic status of the cerebral circulation, and real-time monitoring of recanalization. Extended applications such as vasomotor reactivity testing, emboli monitoring, and right-to-left shunt detection help clinicians ascertain stroke mechanisms at the bedside, plan and monitor treatment, and determine prognosis. In the neurointensive care unit, TCD is useful for detecting increased intracranial pressure and confirming cerebral circulatory arrest. TCD is of established value for screening children with sickle cell disease and detecting and monitoring vasospasm after spontaneous subarachnoid hemorrhage.

Background: Black-white disparities in stroke mortality are well documented, but few recent studies have examined racial/ethnic disparities in stroke hospitalizations among young adults. We analyzed recent (2001-2006) trends in stroke hospitalizations and hospital case-fatality for black, Hispanic, and white adults aged 25-49 years in Florida., Methods: Hospitalization rates were calculated using population estimates from the census, and hospital discharges with a primary diagnosis of stroke (ICD-9-CM 430, 431, 434, 436) (n = 16,317). Multivariate logistic regression modeling was used to examine racial/ethnic disparities in stroke mortality prior to discharge, after adjustment for patient sociodemographics, stroke subtype, risk factors, and comorbidities., Results: Age-adjusted stroke hospitalization rates for blacks were over 3 times higher than rates for whites, while rates for Hispanics were slightly higher than rates for whites. Hemorrhagic strokes were proportionally greater among Hispanics compared with blacks and whites (p < 0.0001). Blacks were most likely to have diagnosed hypertension (62.3%), morbid obesity (10.9%) or drug abuse (13.6%). Whites were most likely to have diagnosed hyperlipidemia (21.0%), alcohol abuse (9.5%), and to be smokers (30.6%). The in-hospital fatality rate for all strokes was highest among blacks (10.0%) compared with whites (9.0%) and Hispanics (8.2%). After adjustment for age, gender, insurance status, and all diagnosed risk factors and comorbidities, the black excess was no longer observed [odds ratio (OR) 1.01, 95% confidence interval (CI) 0.88-1.15, p = 0.93]. However, the Hispanic advantage in case-fatality was strengthened (OR 0.66, 95% CI 0.55-0.79, p < 0.0001). Separate case-fatality analyses for ischemic versus hemorrhagic strokes yielded similar results., Conclusions: Our study found a strong and persistent black-white disparity in stroke hospitalization rates for young adults. In contrast, rates were similar for Hispanics and whites. Multivariate adjustment explained the 15% excess case-fatality for blacks; the short-term mortality advantage among Hispanics was strengthened after adjustment.

Indications for the clinical use of transcranial Doppler (TCD) continue to expand while scanning protocols and quality of reporting vary between institutions. Based on literature analysis and extensive personal experience, an international expert panel started the development of guidelines for TCD performance, interpretation, and competence. The first part describes complete diagnostic spectral TCD examination for patients with cerebrovascular diseases. Cranial temporal bone windows are used for the detection of the middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA), C1 segment of the internal carotid arteries (ICA), and collateralization of flow via the anterior (AComA) and posterior (PComA) communicating arteries; orbital windows-for the ophthalmic artery (OA) and ICA siphon; the foraminal window-for the terminal vertebral (VA) and basilar (BA) arteries. Although there is a significant individual variability of the circle of Willis with and without disease, the complete diagnostic TCD examination should include bilateral assessment of the M2 (arbitrarily located at 30-40 mm depth), M1 (40-65 mm) MCA [with M1 MCA mid-point at 50 mm (range 45-55 mm), average length 16 mm (range 5-24 mm), A1 ACA (60-75 mm), C1 ICA (60-70 mm), P1-P2 PCA (average depth 63 mm (range 55-75 mm), AComA (70-80 mm), PComA (58-65 mm), OA (40-50 mm), ICA siphons (55-65 mm), terminal VA (40-75 mm), proximal (75-80), mid (80-90 mm), and distal (90-110 mm) BA]. The distal ICA on the neck (40-60 mm) can be located via submandibular windows to calculate the VMCA/VICA index, or the Lindegaard ratio for vasospasm grading after subarachnoid hemorrhage. Performance goals of diagnostic TCD are to detect and optimize arterial segment-specific spectral waveforms, determine flow direction, measure cerebral blood flow velocities and flow pulsatility in the above-mentioned arteries. These practice standards will assist laboratory accreditation processes by providing a standard scanning protocol with transducer positioning and orientation, depth selection and vessel identification for ultrasound devices equipped with spectral Doppler and power motion Doppler.

All neuromonitoring techniques, although imperfect, provide useful information for monitoring cardiothoracic and carotid vascular operations. They may be viewed as providing complementary information, which may help surgical technique and, as a result, possibly improve clinical outcomes. As of this writing, the efficacy of TCD and NIRS monitoring during cardiothoracic and vascular surgery cannot be considered established. Well designed, prospective, adequately powered, double-blind, and randomized outcome studies are needed to determine the optimal neurologic monitoring modality (or modalities), in specific surgical settings.

The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call working group, consisting of experts in stroke and cerebrovascular biology on January 28, 2005. The purpose of this working group was to develop a prioritized set of recommendations for NHLBI to establish a focused and comprehensive set of research activities in cerebrovascular biology and disease. Three thematic areas of research emerged: (1) molecular and cellular neurobiology of cerebral blood vessels, focusing on genomics and proteomics, neurovascular signaling and cerebrovascular embryogenesis, development and plasticity; (2) resource development, involving the development of new methodological approaches for normal and altered function of the neurovascular unit, collaborative research, and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases and translational approaches, addressing vascular mechanisms of disease, the role of risk factors, importance of biomarkers with the ultimate goal of developing new treatments.