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Abstract Background It is unknown whether high-intensity interval exercise (HIIE) may potentiate or attenuate the cardiotoxic effect of chemotherapy agents such as doxorubicin (DOX) when performed shortly after treatment. The study aimed to investigate the effect of acute HIIE on cardiac function and structure performed either 1, 2 or 3 days after DOX injection in an animal model. Methods Female C57bl/6 mice (n = 28), 70 days old, received a bolus 20 mg/kg intravenous tail vein DOX injection. Three exercise groups performed 1 HIIE session (16 sets of 1 min at 85–90% of peak running speed) at 1 (n = 7), 2 (n = 7), and 3 days (n = 8) following the DOX injection. A sedentary (SED) group of mice (n = 6) did not exercise. Animals underwent echocardiography under light anesthesia (isoflurane 0.5-1%) before and 7 days after the DOX injection. Animals were sacrificed on day 9 and hearts were collected for morphometric and histological analysis. Results Animals exercising on day 3 had the smallest pre-post reduction in left ventricular fractional shortening (LVFS) (MΔ= -1.7 ± 3.3; p = 0.406) and the SED group had the largest reduction (MΔ=-6.8 ± 7.5; p = 0.009). After reclassification of animals according to their exercise compliance (performing > 8/16 of high-intensity bouts), LVFS in compliant mice was unchanged over time (LVFS MΔ= -1.3 ± 5.6; p = 0.396) while non-compliant animals had a LVFS reduction similar to sedentary animals. There were no significant differences in myocardial histology between groups. Conclusions In this pilot murine study, one single HIIE session did not exacerbate acute doxorubicin-induced cardiotoxicity. The timing of the HIIE session following DOX injection and the level of compliance to exercise could influence the negative impact of DOX on cardiac function.

The odontogenic keratocyst (OKC) is a frequently developing odontogenic cyst that accounts for 10%–14% of all jaw cysts. Due to the high recurrence rate, aggressive therapeutic techniques such as jaw resection and marsupialization are indicated. Following a conservative marsupialization procedure in which Carnoy's solution and an iodoform packing were used, the clinical, radiological, and histological evaluation of OKC in a 12-year-old female patient revealed no evidence of recurrence over the subsequent year of follow-up.

The Sydney Children’s Hospitals Network (SCHN) addressed the challenges of the COVID-19 pandemic by implementing innovative changes which made their health system resilient and responsive. For other healthcare systems, there are important takeaways. In the United States and Canada, an urgent widespread response is needed to address the overdose crisis, driven by potent synthetic opioids (ie, fentanyl and its derivates). We project the COVID-19 System Shock Framework (CSSF) on to the North American healthcare systems and suggest a Fentanyl System Shock Framework, which provides a framework for necessary changes and innovations to address the overdose crisis. To become resilient to the fentanyl system shock, core components as well as overarching values, health policy, and online technologies need to be adapted to reduce the death count and meet the evolving needs of marginalised individuals who use opioid. Future research should focus on scientifically assessing such implementations to guide evidence-based decision making.

Abstract Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies.

Abstract Background Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). Methods A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. Results In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. Conclusions The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

ObjectivesFentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use.MethodsThe search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included.ResultsThe search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability.ConclusionsAmong PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.

Abstract African swine fever (ASF) caused by ASF virus (ASFV) is an infectious transboundary animal disease notifiable to the World Organization for Animal Health causing high mortality in domestic pigs and wild boars threatening the global domestic pig industry. To date, twenty-four ASFV genotypes have been described and currently genotypes II, IX, X, XV and XVI are known to be circulating in Tanzania. Despite the endemic status of ASF in Tanzania, only one complete genome of ASFV from the country has been described. This study describes the first complete genome sequence of ASFV genotype XV. In addition, the first Tanzanian complete genome of ASFV genotype IX and three ASFV strains belonging to genotype II collected during ASF outbreaks in domestic pigs in Tanzania were determined in this study using Illumina sequencing and comparative genomics analysis. The generated ASFV complete genome sequences ranged from 171,004 to 184,521 base pairs in length with an average GC content of 38.53% and encoded 152 to 187 open reading frames. The results of this study provide insights into the genomic structure of ASFV and can be used to monitor changes within the ASFV genome and improve our understanding of ASF transmission dynamics.

Abstract Background Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT. Methods This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health. Conclusions The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.

This paper seeks and examines N-symmetric vortical solutions of the two-layer geostrophic model for the special case when the vortices (or eddies) have vanishing summed strength (circulation anomaly). This study is an extension [Sokolovskiy et al. Phys. Fluids 2020, 32, 09660], where the general formulation for arbitrary N was given, but the analysis was only carried out for N=2. Here, families of stationary solutions are obtained and their properties, including asymptotic ones, are investigated in detail. From the point of view of geophysical applications, the results may help interpret the propagation of thermal anomalies in the oceans.

The emergence of new virulent genotypes and the continued genetic drift of Newcastle disease virus (NDV) implies that distinct genotypes of NDV are simultaneously evolving in different geographic locations across the globe, including throughout Africa, where NDV is an important veterinary pathogen. Expanding the genomic diversity of NDV increases the possibility of diagnostic and vaccine failures. In this review, we systematically analyzed the genetic diversity of NDV genotypes in Africa using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information published between 1999 and 2022 were used to obtain the genetic background of different genotypes of NDV and their geographic distributions in Africa. The following genotypes were reported in Africa: I, II, III, IV, V, VI, VII, VIII, XI, XIII, XIV, XVII, XVIII, XX, and XXI. A new putative genotype has been detected in the Democratic Republic of the Congo. However, of 54 African countries, only 26 countries regularly report information on NDV outbreaks, suggesting that this number may be vastly underestimated. With eight different genotypes, Nigeria is the country with the greatest genotypic diversity of NDV among African countries. Genotype VII is the most prevalent group of NDV in Africa, which was reported in 15 countries. A phylogeographic analysis of NDV sequences revealed transboundary transmission of the virus in Eastern Africa, Western and Central Africa, and in Southern Africa. A regional and continental collaboration is recommended for improved NDV risk management in Africa.

The global spread of African swine fever (ASF) in recent decades has led to the need for technological advances in sampling and diagnostic techniques. The impetus for these has been the need to enable sampling by lay persons and to obtain at least a preliminary diagnosis in the field for early control measures to be put in place before final laboratory confirmation. In rural Africa, rapid diagnosis is hampered by challenges that include lack of infrastructure as well as human and financial resources. Lack of animal health personnel, access to affordable means to transport field samples to a laboratory, and lack of laboratories with the capacity to make the diagnosis result in severe under-reporting of ASF, especially in endemic areas. This review summarizes the challenges identified in gap analyses relevant to low- and middle-income countries, with a focus on Africa, and explore the opportunities provided by recent research to improve field diagnosis and quality of diagnostic samples used. Sampling techniques include invasive sampling techniques requiring trained personnel and non-invasive sampling requiring minimal training, sampling of decomposed carcass material, and preservation of samples in situations where cold chain maintenance cannot be guaranteed. Availability and efficacy of point-of-care (POC) tests for ASF has improved considerably in recent years and their application, as well as advantages and limitations, are discussed. The adequacy of existing laboratory diagnostic capacity is evaluated and opportunities for networking amongst reference and other laboratories offering diagnostic services are discussed. Maintaining laboratory diagnostic efficiency in the absence of samples during periods of quiescence is another issue that requires attention, and the role of improved laboratory networking is emphasized. Early diagnosis of ASF is key to managing the disease spread. Therefore, the establishment of the Africa Chapter of the Global African Swine Fever Research Alliance (GARA) increases opportunities for collaboration and networking among the veterinary diagnostic laboratories in the region.

Abstract Background Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM. Methods This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated. Results Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported. Conclusions After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.

BackgroundMental disorders pose a high risk for the occurrence of sexual dysfunctions (SD). This study aimed to investigate prevalence of risk factors and help-seeking behavior for sexual dysfunctions in patients with opioid use disorder compared to patients seeking psychotherapeutic help.MethodsNinety-seven patients at two opioid agonist treatment (OAT) centers and 65 psychotherapeutic patients from a psychiatric practice (PP) in Switzerland were included in the study. Self-report assessments comprised sexual functioning (IIEF: International Index of Erectile Function; FSFI: Female Sexual Function Index), depressive state, psychological distress, alcohol consumption, nicotine use, and a self-designed questionnaire on help-seeking behavior. We used chi-squared and Mann–Whitney U tests for group comparisons and binary logistic regression models to identify variables predicting the occurrence of sexual dysfunctions.ResultsThere was no statistically significant difference (p = 0.140) in the prevalence of SD between OAT (n = 64, 66.0%) and PP sample (n = 35, 53.8%). OAT patients scored significantly higher in scales assessing nicotine use (p

Abstract Background Since the outbreak of COVID-19 pandemic in Rwanda, a vast amount of SARS-COV-2/COVID-19-related data have been collected including COVID-19 testing and hospital routine care data. Unfortunately, those data are fragmented in silos with different data structures or formats and cannot be used to improve understanding of the disease, monitor its progress, and generate evidence to guide prevention measures. The objective of this project is to leverage the artificial intelligence (AI) and data science techniques in harmonizing datasets to support Rwandan government needs in monitoring and predicting the COVID-19 burden, including the hospital admissions and overall infection rates. Methods The project will gather the existing data including hospital electronic health records (EHRs), the COVID-19 testing data and will link with longitudinal data from community surveys. The open-source tools from Observational Health Data Sciences and Informatics (OHDSI) will be used to harmonize hospital EHRs through the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The project will also leverage other OHDSI tools for data analytics and network integration, as well as R Studio and Python. The network will include up to 15 health facilities in Rwanda, whose EHR data will be harmonized to OMOP CDM. Expected results This study will yield a technical infrastructure where the 15 participating hospitals and health centres will have EHR data in OMOP CDM format on a local Mac Mini (“data node”), together with a set of OHDSI open-source tools. A central server, or portal, will contain a data catalogue of participating sites, as well as the OHDSI tools that are used to define and manage distributed studies. The central server will also integrate the information from the national Covid-19 registry, as well as the results of the community surveys. The ultimate project outcome is the dynamic prediction modelling for COVID-19 pandemic in Rwanda. Discussion The project is the first on the African continent leveraging AI and implementation of an OMOP CDM based federated data network for data harmonization. Such infrastructure is scalable for other pandemics monitoring, outcomes predictions, and tailored response planning.

Abstract Background Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset (“rush”) but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts. Case presentation A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff. Conclusions Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

Abstract Background Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention. Design and method This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.4% females and mean BMI 26.6 ± 3.7 SD. Data were collected through a screening campaign in rural area of Kirehe District, Eastern of Rwanda, with the objective to characterize and examine the prevalence of elevated blood pressure (BP) and other CVD risk factors. An adapted tool from the World Health Organization STEPwise Approach was used for data collection. Elevated BP was defined as ≥ 140/90 mm/Hg and elevated blood glucose as blood glucose ≥ 100 mg/dL after a 6-h fast. Results Of the sampled population, 21.2% (n = 910) had an elevated BP at screening; BP was elevated among individuals not previously known to have HTN in 18.7% (n = 752). Among individuals with a prior diagnosis of HTN, 62.2% (n = 158 of 254) BP was uncontrolled. Age, weight, smoking, alcohol history and waist circumference were associated with BP in both univariate analyses and multivariate analysis. Conclusion High rates of elevated BP identified through a health screening campaign in this Rwandan district were surprising given the rural characteristics of the district and relatively low population age. These data highlight the need to implement an adequate strategy for the prevention, diagnosis, and control of HTN that includes rural areas of Rwanda as part of a multicomponent strategy for CVD prevention.

Abstract Background An increasing number of individuals who use drugs in North America are preferentially consuming fentanyl over other opioids. This has significant consequences on the treatment and management of opioid use disorder (OUD) and its concurrent disorders, especially in acute care if opioid requirements are not met. Case presentation We present a patient with severe OUD and daily injection of fentanyl, admitted to hospital for management of acute physical health issues. Due to high opioid requirements and history of patient-initiated discharge, intravenous fentanyl was administered for treatment of opioid withdrawal, and management of pain, which supported continued hospitalization for acute care treatment and aligned with substance use treatment goals. Conclusion This case demonstrates that intravenous fentanyl for management of OUD in hospital can be a feasible approach to meet opioid requirements and avoid fentanyl withdrawal among patients with severe OUD and daily fentanyl use, thereby promoting adherence to medical treatment and reducing the risk of patient-initiated discharge. There is an urgent need to tailor current treatment strategies for individuals who primarily use fentanyl. Carefully designed research is needed to further explore the use of IV fentanyl for acute care management of severe opioid withdrawal in a hospital setting.

Abstract Drug markets are dynamic systems which change based on demand, competition, legislation and revenue. Shifts that are not met with immediate and appropriate responses from the healthcare system can lead to public health crises with tragic levels of morbidity and mortality, as experienced Europe in the early 1990s and as is the case in North America currently. The major feature of the current drug market shift in North America is towards highly potent synthetic opioids such as fentanyl and fentanyl analogues. An additional spike in stimulant use further complicates this issue. Without understanding the ever-changing dynamics of drug markets and consequent patterns of drug use, the healthcare system will continue to be ineffective in its response, and morbidity and mortality will continue to increase. Economic perspectives are largely neglected in research and clinical contexts, but better treatment alternatives need to consider the large-scale macroeconomic conditions of drug markets as well as the behavioural economics of individual substance use. It is important for policy makers, health authorities, first responders and medical providers to be aware of the clinical implications of drug market changes in order to best serve people who use drugs. Only with significant clinical research, a comprehensive reorganization of the system of care across all sectors, and an evidence-driven governance, will we be successful in addressing the challenges brought on by the recent shifts in drug markets.

Abstract Aim To examine factors of a hypothetical model related to stressors, burnout and turnover in nurses from developed and developing countries—Canada, Japan, the United States, Malaysia and Thailand. Design A cross‐sectional questionnaire‐based study. Methods Conducted between April 2016 and October 2017, the Maslach Burnout Inventory, Intention to Leave Scale, and Nursing Stress Scale collected data from acute care hospital nurses in Canada (n = 309), Japan (n = 319), Malaysia (n = 242), Thailand (n = 211) and the United States (n = 194). Results Compared to other countries, burnout “exhaustion” was the highest in Japan and “cynicism” and intention to leave the job were the highest in Malaysia. Thailand had lower burnouts and turnover than other countries and higher professional efficacy than Japan and Malaysia. In all countries, reducing stressors is important for reducing burnout and intention to leave jobs, especially as they relate to “lack of support.”

Newcastle disease virus is a significant avian pathogen with the potential to decimate poultry populations all over the world and cause enormous economic losses. Distinct NDV genotypes are currently causing outbreaks worldwide. Due to the high genetic diversity of NDV, virulent strains that may result in a lack of vaccine protection are more likely to emerge and ultimately cause larger epidemics with massive economic losses. Thus, a more comprehensive understanding of the circulating NDV genotypes is critical to reduce Newcastle disease (ND) burden. In this study, NDV strains were isolated and characterized from backyard poultry farms from Tanzania, East Africa in 2021. Reverse-transcription polymerase chain reaction (RT-PCR) based on fusion (F) gene amplification was conducted on 79 cloacal or tracheal swabs collected from chickens during a suspected ND outbreak. Our results revealed that 50 samples out 79 (50/79; 63.3%) were NDV-positive. Sequencing and phylogenetic analyses of the selected NDV isolates showed that 39 isolates belonged to subgenotype VII.2 and only one isolate belonged to subgenotype XIII.1.1. Nucleotide sequences of the NDV F genes from Tanzania were closely related to recent NDV isolates circulating in southern Africa, suggesting that subgenotype VII.2 is the predominant subgenotype throughout Tanzania and southern Africa. Our data confirm the circulation of two NDV subgenotypes in Tanzania, providing important information to design genotype-matched vaccines and to aid ND surveillance. Furthermore, these results highlight the possibility of the spread and emergence of new NDV subgenotypes with the potential of causing future ND epizootics.

[13N]Ammonia is one of the most commonly used Positron Emission Tomography (PET) radiotracers in humans to assess myocardial perfusion and measure myocardial blood flow. Here, we report a reliable semi-automated process to manufacture large quantities of [13N]ammonia in high purity by proton-irradiation of a 10 mM aqueous ethanol solution using an in-target process under aseptic conditions. Our simplified production system is based on two syringe driver units and an in-line anion-exchange purification for up to three consecutive productions of ~30 GBq (~800 mCi) (radiochemical yield = 69 ± 3% n.d.c) per day. The total manufacturing time, including purification, sterile filtration, reformulation, and quality control (QC) analyses performed before batch release, is approximately 11 min from the End of Bombardment (EOB). The drug product complies with FDA/USP specifications and is supplied in a multidose vial allowing for two doses per patient, two patients per batch (4 doses/batch) on two separate PET scanners simultaneously. After four years of use, this production system has proved to be easy to operate and maintain at low costs. Over the last four years, more than 1000 patients have been imaged using this simplified procedure, demonstrating its reliability for the routine production of large quantities of current Good Manufacturing Practices (cGMP)-compliant [13N]ammonia for human use.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Results This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

Abstract Background Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD. Methods This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is the completion of buprenorphine/naloxone induction with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction. Discussion This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis. Trial registration ClinicalTrials.gov, NCT04234191; date of registration: January 21, 2020; https://clinicaltrials.gov/ct2/show/NCT04234191

Although the relationship between autoimmunity and microorganisms is complex, there is evidence that microorganisms can prevent the development of various autoimmune diseases. Lactobacilli are beneficial gut bacteria that play an important role in immune system development. The goals of this study were to assess the ability of three different strains of lactobacilli (L. casei B255, L. reuteri DSM 17509 and L. plantarum LP299v) to control lupus development/progression in (NZBxNZW)F1 (BWF1) lupus-prone mice before and after disease onset, and identify the mechanisms mediating protection. BWF1 mice fed with individual L. casei or L. reuteri before disease onset exhibited delayed lupus onset and increased survival, while feeding L. plantarum had little impact. In vitro treatment of BWF1 dendritic cells with individual lactobacilli strains upregulated IL-10 production to various extents, with L. casei being the most effective. The protection mediated by L. casei was associated with upregulation of B7-1 and B7-2 by antigen presenting cells, two costimulatory molecules important for regulatory T cell (Treg) induction. Moreover, feeding L. casei lead to increased percentages of CD4+Foxp3+ Tregs and IL10-producing T cells in the lymphoid organs of treated mice. More importantly, mice fed L. casei after disease onset remained stable for several months, i.e. exhibited delayed anti-nucleic acid production and kidney disease progression, and increased survival. Therefore, feeding lactobacilli appears to delay lupus progression possibly via mechanisms involving Treg induction and IL-10 production. Altogether, these data support the notion that ingestion of lactobacilli, with immunoregulatory properties, may be a viable strategy for controlling disease development and progression in patients with lupus, i.e. extending remission length and reducing flare frequency.

Current research efforts require a broad range of immune reagents, but those available for pigs are limited. The goal of this study was to generate priority immune reagents for pigs and pipeline them for marketing. Our efforts were aimed at the expression of soluble swine cytokines and the production of panels of monoclonal antibodies (mAbs) to these proteins. Swine interleukin-17A (IL-17A) and Interferon-gamma (IFNγ) recombinant proteins were produced using yeast expression and used for monoclonal antibody (mAb) production resulting in panels of mAbs. We screened each mAb for cross-species reactivity with orthologs of IL-17A or IFNγ and checked each mAb for inhibition by other related mAbs, to assign mAb antigenic determinants. For porcine IL-17A, the characterization of a panel of 10 mAbs identified eight different antigenic determinants; interestingly, most of the mAbs cross-reacted with the dolphin recombinant ortholog. Likewise, the characterization of a panel of nine anti-PoIFNγ mAbs identified four different determinants; most of the mAbs cross-reacted with dolphin, bovine, and caprine recombinant orthologs. There was a unique reaction of one anti-PoIFNγ mAb that cross-reacted with the zebrafish recombinant ortholog. The αIL-17A mAbs were used to develop a quantitative sandwich ELISA detecting the yeast expressed protein as well as native IL-17A in stimulated peripheral blood mononuclear cell (PBMC) supernatants. Our analyses showed that phorbol myristate acetate/ionomycin stimulation of PBMC induced significant expression of IL-17A by CD3+ T cells as detected by several of our mAbs. These new mAbs expand opportunities for immunology research in swine.

We numerically determine equilibrium states for three-dimensional quasi-geostrophic vortex arrays. The vortex arrays consist of five or eight equal volume and equal uniform potential vorticity peripheral eddies whose center lies equally spaced along a circle and of a similar vortex at the center of the array. We are specifically interested in the influence of the height-to-width aspect ratio of the vortices on the arrays’ properties. The linear stability of the vortex arrays is addressed and the vortex arrays are shown to be sensitive to instabilities when the vortices are close enough together. The onset of instability corresponds to a threshold for the distance between the peripheral vortices and the center of the array. Measured as a fraction of the mean vortex horizontal radius, the stability threshold increases as the height-to-width aspect ratio of the vortices increases. For a separation larger than the stability threshold between the vortices, the arrays are linearly stable, hence robust and long-lived in the nonlinear regime. We also show that prolate peripheral vortices exhibit a concave outer side when they are close to the center of the array, while it is convex otherwise. The nonlinear evolution of a selection of unstable vortex arrays is examined. In such cases, the vortices deform and some vortices merge, breaking the symmetry of the vortex array. The later evolution of the unstable vortex arrays can be convoluted.

Abstract Background The free-fatty acid receptor-1 (FFA-1) is expressed by β-cells and is a promising target for molecular imaging of functional β-cell mass. Recently, the ((3-[18F]fluoropropyl)sulfonyl)propoxy-derivative of the high-affinity FFA-1 agonist TAK-875 ([ 18 F]7) was reported. Here we describe the preparation of this tracer in high molar activity using a purification method permitting separation of [ 18 F]7 from a structurally-related by-product and evaluation of the tracer in rats as a potential FFA-1 PET imaging agent. Results The radiotracer was produced by nucleophilic radio-fluorination of the tosylate precursor and deprotection of the methyl ester. Semi-preparative HPLC with a C18 column revealed that [ 18 F]7 co-eluted with a non-radioactive impurity. Mass spectrometry identified the impurity as the alkene-containing elimination by-product. A pentafluorophenyl-functionalized HPLC column was found to separate the two compounds and allowed for purification of [ 18 F]7 in high molar activity. A strong anion-exchange resin was used to reformulate [ 18 F]7 in high concentration. Starting from 96 to 311 GBq of [18F]fluoride, 3.8–15.4 GBq of pure [ 18 F]7 (end of synthesis (EOS)) was prepared (RCY 8.3% ± 1.1% decay-corrected, n = 4) in high molar activity (166–767 GBq/μmol at EOS). This PET agent was evaluated in rats using dynamic microPET/CT imaging, ex vivo biodistribution, and radio-metabolite studies. MicroPET/CT exhibited high uptake of the tracer in the abdominal area. There was no measurable decrease of the PET signal in the pancreatic area in rats pre-treated with saturating doses (30 mg/kg) of TAK-875. Biodistribution studies corroborated the microPET/CT results. Radiometabolism analyses revealed high compound stability with only the parent molecule detected in the pancreas. Conclusions Analysis of the crude reaction mixture and identification of the elimination by-product allowed for the development of a fully automated process to prepare the TAK-875-derived PET agent [ 18 F]7 in high purity and high molar activity. Even though the radiotracer exhibited high in vivo stability, microPET/CT and biodistribution results confirmed recent reports demonstrating that lipophilic analogs of TAK-875 display a high degree of non-specific binding, masking any specific binding to FFA-1 in pancreatic β-cells. Future development of TAK-875-derived PET tracers should focus on reducing non-specific binding in the pancreatic tissue.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

African swine fever (ASF) is a contagious viral disease that causes high mortality, approaching 100%, in domestic pigs and wild boars. The disease has neither a cure nor a vaccine, and it is caused by an ASF virus (ASFV), the only member of the family Asfarviridae, genus Asfivirus, and the only known DNA arbovirus. Twenty-four genotypes of ASFV have been described to date, and all of them have been described in Africa. ASF is endemic in Burundi, and several outbreaks have been reported in the country; the disease continues to economically impact on small-scale farmers. This study aimed at genetic characterization of ASFV that caused an ASF outbreak in the Rutana region, Burundi, in the year 2018. Tissue samples from domestic pigs that died as a result of a severe hemorrhagic disease were collected in order to confirm the disease using polymerase chain reaction (PCR) and to conduct partial genome sequencing. Nucleotide sequences were obtained for the B646L (p72) gene, the intergenic fragment between the I73R and I329L genes, and the central variable region (CVR) of the B602L gene. Phylogenetic analysis of the Burundian 2018 ASFV grouped the virus within B646L (p72) genotype X and clustered together with those reported during the 1984 and 1990 outbreaks in Burundi with high nucleotide identity to some ASFV strains previously reported in neighboring East African countries, indicating a regional distribution of this ASFV genotype. Analysis of the intergenic fragment between I73R and I329L genes showed that the Burundian 2018 ASFV described in this study lacked a 32–base pair (bp) fragment present in the reference genotype X strain, Kenya 1950. In addition, the strain described in this study had the signature AAABNAABA at the CVR (B602L) gene and showed 100% amino acid sequence identity to viruses responsible for recent ASF outbreaks in the region. The virus described in this study showed high genetic similarities with ASFV strains previously described in domestic pigs, wild suids, and soft ticks in East African countries, indicating a possible common wild source and continuous circulation in domestic pigs in the region.

Abstract Background The compressional modulus of elasticity is an important mechanical property for understanding stalk lodging, but this property is rarely available for thin-walled plant stems such as maize and sorghum because excised tissue samples from these plants are highly susceptible to buckling. The purpose of this study was to develop a testing protocol that provides accurate and reliable measurements of the compressive modulus of elasticity of the rind of pith-filled plant stems. The general approach was to relying upon standard methods and practices as much as possible, while developing new techniques as necessary. Results Two methods were developed for measuring the compressional modulus of elasticity of pith-filled node–node specimens. Both methods had an average repeatability of ± 4%. The use of natural plant morphology and architecture was used to avoid buckling failure. Both methods relied up on spherical compression platens to accommodate inaccuracies in sample preparation. The effect of sample position within the test fixture was quantified to ensure that sample placement did not introduce systematic errors. Conclusions Reliable measurements of the compressive modulus of elasticity of pith-filled plant stems can be performed using the testing protocols presented in this study. Recommendations for future studies were also provided.

For over 100 years after the description of the first case of African swine fever (ASF) in Kenya, ASF virus (ASFV) cross-border spread in eastern and southern Africa has not been fully investigated. In this manuscript, we reviewed systematically the available literature on molecular epidemiology of ASF in Tanzania and its eight neighboring countries in order to establish the transmission dynamics of ASFV between these countries. Data were retrieved from World Animal Health Information System (WAHIS), Google Scholar, PubMed, Scopus, and CrossRef databases, using the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and reviewed to document ASF outbreaks and ASFV genotypes distribution. Using phylogeographic approach applied to ASFV p72 sequence dataset, the evolutionary history and the dispersal pattern of the ASFV strains were assessed. From 2005 to 2019, a total of 1588 ASF outbreaks affecting 341,742 cases that led to 302,739 domestic pig deaths were reported. The case fatality rates (CFR) varied from 15.41% to 98.95% with an overall CFR of 88.58%. Fifteen different p72 ASFV genotypes were reported and the time to the most recent common ancestor (TMRCA) for ASFV strains dated back to 1652.233 (1626.473, 1667.735) with an evolutionary rate of 4.805 × 10−5 (2.5857 × 10−5, 9.7789 × 10−5). Phylogeographic dispersal analysis revealed several transboundary spread events of ASFV strains between these countries. These results suggest persistent circulation of ASFV in these countries and advocate for more research to improve our understanding of the transmission dynamics of the virus and for a regional approach to mitigate the spread of ASFV.

ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18-20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies.

In the present study, we carried out experiments on the diet of the freshwater prawn Macrobrachium equidens. We tested which type of food and which density of food is suitable for larval development. For the experiment on the type of food, eight treatments were carried out: (I) starvation, (AL) microalgae, (RO) rotifers, (AN) Artemia, (RO + AN) rotifers + Artemia, (AL + RO) microalgae + rotifers, (AL + AN) microalgae + Artemia, (AL + RO + AN) microalgae + rotifers + Artemia. For the experiment on the density of food, we used the type of food, which had resulted in a high survival rate in the previous experiment. Three treatments were carried out: 4, 8 and 16 Artemia nauplii /mL. The rate of feeding during larval development was observed. The survival, weight and percentage of juveniles of each feeding experiment were determined. We found that larvae are carnivores; however, they have requirements with respect to the type of food, because larvae completed their cycle from the zoeal to the juvenile stage only when Artemia nauplii were available. We also verified that the larvae feed mainly during the day-time, and are opportunistic with respect to the density of food offered.

Introduction: Allostatic load score (ALS) summarizes the physiological effect of stress on cardiovascular, metabolic and immune systems. As immigration is stressful, ALS could be affected.Objective: Associations of age of immigration, reason for immigration and unhealthy assimilation behavior with ALS were determined in 238 African immigrants to the United States (US) (age 40±10, mean±SD, range 21-64y). Methods: ALS was calculated using ten variables from three domains; cardiovascular (SBP, DBP, cholesterol, triglyceride, homocysteine), metabolic (BMI, A1C, albumin, eGFR) and immunological (hsCRP). Variables were divided into sex-specific quartiles with high-risk defined as the highest quartile for each variable except for albumin and eGFR which used the lowest quartile. One point was assigned if the variable was in the high-risk range and zero if not. Unhealthy assimilation behavior was defined by a higher prevalence of smoking, alcohol consumption or sedentary activity in immigrants who lived in the US for ≥10y compare to

Reduced cardiac β-adrenoceptor (β-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac β-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac β-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats.Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of β-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured.At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced β-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal β1-AR (98±9%), reduced β2-AR (76±10%), and elevated β3-AR (108±6). At 16 weeks, β1-AR expression became reduced (69±16%), β2-AR expression decreased further (68±14%), and β3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function.Cardiac β-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and β1- and β2-AR expression are inversely correlated with the progression of type-2 diabetes.

We study the influence of bottom topography on the interaction of two identical vortices in a two-layer, quasi-geostrophic model. The two vortices have piecewise-uniform potential vorticity and are lying in the upper layer of the model. The topography is a smooth bottom slope. For two cyclones, topography modifies the merger critical distance and the merger efficiency: the topographic wave and vortices can advect the two cyclones along the shelf when they are initially far from it or towards the shelf when they are initially closer to it. They can also advect the two cyclones towards each other and thus favour merger. The cyclones deform, and the potential vorticity field undergoes filamentation. Regimes of partial vortex merger or of vortex splitting are then observed. The interaction of the vorticity poles in the two layers are analysed to explain the evolution of the two upper layer cyclones. For taller topography, two new regimes appear: vortex drift and splitting; and filamentation and asymmetric merger. They are due to the hetonic coupling of lower layer vorticity with the upper layer vortices (a heton is a baroclinic vortex dipole, carrying heat and momentum and propagating horizontally in the fluid), or to the strong shear that the former exerts on the latter. The interaction of two anticyclones shows regimes of co-rotation or merger, but specifically, it leads to the drift of the two vortices away from the slope, via a hetonic coupling with oppositely-signed vorticity in the lower layer. This vorticity originates in the breaking of the topographic wave. The analysis of passive tracer evolution confirms the inshore or offshore drift of the fluid, the formation of tracer fronts along filaments and its stirring in regions of vortex merger. The trajectories of particles indicate how the fluid initially in the vortices is finally partitioned.

We investigate the interaction between a heton and a current generated by a filament of buoyancy anomaly at the surface. Hetons are baroclinic dipoles consisting of a pair of vortices of opposite signs lying at different depths. Such structures have self-induced motion whenever the pair of vortices are offset horizontally. A surface buoyancy filament generates a shear flow since the density perturbation locally modifies the pressure field. The vertical shear induced by the filament offsets the vortices of the heton if vertically aligned initially. Moreover, if the vortex nearer the surface is in adverse horizontal shear with the buoyancy filament, the heton tends to move towards the filament. Conversely, if the upper vortex is in cooperative horizontal shear with the buoyancy filament, the heton moves away from it. The filament is also naturally unstable and eventually breaks into a series of billows as it is perturbed by the heton. Moderate to large intensity surface buoyancy distributions separate the vortices of the heton, limiting its advection as a baroclinic dipole. Instead, the vortices of the heton start to interact strongly with surface billows. Additionally, the vortices of the heton can be partially destroyed by the filament if the shear it induces is sufficiently large.

Many aspects of physiology and gene regulation can be studied by examining the levels of enzymes harvested from cultured cells. We found that the yield from cultured cells of two different cytosolic enzymes, creatine kinase and the common reporter gene product chloramphenicol acetyltransferase (CAT), could be highly variable despite superficially identical harvest procedures. Analysis of multiple harvest and assay parameters disclosed that fluctuations in enzyme yield were correlated with the time cells that were allowed to remain in an EDTA-containing buffered saline solution prior to scraping from the dishes with a rubber policeman. The highest and most consistent yields were obtained when the cells were allowed to remain in the solution for 6–10 min before scraping; this protocol has cut variability approximately by a factor of three.

Cell therapy is expected to restore perfusion and improve function in the ischemic/infarcted myocardium; however, the biological mechanisms and local effects of transplanted cells remain unclear. To assess cell fate in vivo, hexadecyl-4-[ 18 F]fluorobenzoate ( 18 F-HFB) cell labeling was evaluated for tracking human circulating progenitor cells (CPCs) with positron emission tomography (PET) and was compared to the commonly used 2-[ 18 F]fluoro-2-deoxy-d-glucose ( 18 F-FDG) labeling method in a rat myocardial infarction model. CPCs were labeled with 18 F-HFB or 18 F-FDG ex vivo under the same conditions. 18 F-HFB cell-labeling efficiency (23.4 ± 7.5%) and stability (4 h, 88.4 ± 6.0%) were superior to 18 F-FDG (7.6 ± 4.1% and 26.6 ± 6.1%, respectively; p < 0.05). Neither labeling approach significantly altered cell viability, phenotype or migration potential up to 24 h postlabeling. Two weeks after left anterior descending coronary artery ligation, rats received echo-guided intramyocardial injection in the infarct border zone with 18 F-HFB-CPCs, 18 F-FDG-CPCs, 18 F-HFB, or 18 F-FDG. Dynamic PET imaging of both 18 F-HFB-CPCs and 18 F-FDG-CPCs demonstrated that only 16–37% of the initial injection dose (ID) was retained in the injection site at 10 min postdelivery, and remaining activity fell significantly over the first 4 h posttransplantation. The 18 F-HFB-CPC signal in the target area at 2 h (23.7 ± 14.7% ID/g) and 4 h (17.6 ± 13.3% ID/g) postinjection was greater than that of 18 F-FDG-CPCs (5.4 ± 2.3% ID/g and 2.6 ± 0.7% ID/g, respectively; p < 0.05). Tissue biodistribution confirmed the higher radioactivity in the border zone of 18 F-HFB-CPC rats. Immunostaining of heart tissue sections revealed no significant difference in cell retention between two labeled cell transplantation groups. Good correlation with biodistribution results was observed in the 18 F-HFB-CPC rats ( r = 0.81, p < 0.05). Compared to 18 F-FDG, labeling human CPCs with 18 F-HFB provides a more efficient, stable, and accurate way to quantify the distribution of transplanted cells. 18 F-HFB cell labeling with PET imaging offers a better modality to enhance our understanding of early retention, homing, and engraftment with cardiac cell therapy.

Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology that underlies this observation is poorly understood. We previously reported that "atypical" memory B cells are increased in children and adults exposed to intense Pf transmission in Mali, similar to what has been observed in individuals infected with HIV. In this study we examined B cell subsets of Pf -infected adults in Peru and Mali to determine if Pf transmission intensity correlates with atypical memory B cell expansion.In this cross-sectional study venous blood was collected from adults in areas of zero (U.S., n = 10), low (Peru, n = 18) and high (Mali, n = 12) Pf transmission. Adults in Peru and Mali were infected with Pf at the time of blood collection. Thawed lymphocytes were analyzed by flow cytometry to quantify B cell subsets, including atypical memory B cells, defined by the cell surface markers CD19(+) CD20(+) CD21(-) CD27(-) CD10(-). In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61-7.28]; U.S. mean: 1.4% [95% CI: 0.92-1.81]; p

Dendritic cells (DCs) from NOD mice produced high levels of IL-12 that induce IFNγ-producing T cells involved in diabetes development. We propose to utilize the microorganism ability to induce tolerogenic DCs to abrogate the proinflammatory process and prevent diabetes development. NOD DCs were stimulated with Lactobacilli (nonpathogenic bacteria targeting TLR2) or lipoteichoic acid (LTA) from Staphylococcus aureus (TLR2 agonist). LTA-treated DCs produced much more IL-12 than IL-10 and accelerated diabetes development when transferred into NOD mice. In contrast, stimulation of NOD DCs with L. casei favored the production of IL-10 over IL-12, and their transfer decreased disease incidence which anti-IL-10R antibodies restored. These data indicated that L. casei can induce NOD DCs to develop a more tolerogenic phenotype via production of the anti-inflammatory cytokine, IL-10. Evaluation of the relative production of IL-10 and IL-12 by DCs may be a very useful means of identifying agents that have therapeutic potential.

Critical qualitative methodology provides a strategy to examine the human experience and its relationship to power and truth. Cultural safety is a concept that has been applied to nursing education and practice and refers to interactions that acknowledge and respect the unique cultural background of patients. It recognizes power inequities between caregivers who belong to dominant cultures and patients who may belong to oppressed groups. Culture is interpreted from a critical constructivist perspective as a fluid relational process that is enacted contextually. The purpose of this paper is to examine the congruence between and

BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, we used the well-documented ability of complete Freund's adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4(+)CD25(+) regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4(+)CD25(+) cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD cells, and also increased the percentages of CD4(+)CD25(+)Foxp3(+) cells infiltrating the pancreas compared to untreated NOD mice. Moreover, CD4(+)CD25(+) cells from pancreatic LN of CFA-treated, but not untreated, NOD mice transferred protection from diabetes. Finally, APC isolated from CFA-treated mice increased Foxp3 and granzyme B expression as well as regulatory function by NOD CD4(+)CD25(+) cells in vitro compared to APC from untreated NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that regulatory T cell function and ability to control pathogenic cells can be enhanced in NOD mice by activating NOD APC.