Background There is evidence to suggest that the broad discrepancy in the ratio of males to females with diagnosed ADHD is due, at least in part, to lack of recognition and/or referral bias in females. Studies suggest that females with ADHD present with differences in their profile of symptoms, comorbidity and associated functioning compared with males. This consensus aims to provide a better understanding of females with ADHD in order to improve recognition and referral. Comprehensive assessment and appropriate treatment is hoped to enhance longer-term clinical outcomes and patient wellbeing for females with ADHD. Methods The United Kingdom ADHD Partnership hosted a meeting of experts to discuss symptom presentation, triggers for referral, assessment, treatment and multi-agency liaison for females with ADHD across the lifespan. Results A consensus was reached offering practical guidance to support medical and mental health practitioners working with females with ADHD. The potential challenges of working with this patient group were identified, as well as specific barriers that may hinder recognition. These included symptomatic differences, gender biases, comorbidities and the compensatory strategies that may mask or overshadow underlying symptoms of ADHD. Furthermore, we determined the broader needs of these patients and considered how multi-agency liaison may provide the support to meet them. Conclusions This practical approach based upon expert consensus will inform effective identification, treatment and support of girls and women with ADHD. It is important to move away from the prevalent perspective that ADHD is a behavioural disorder and attend to the more subtle and/or internalised presentation that is common in females. It is essential to adopt a lifespan model of care to support the complex transitions experienced by females that occur in parallel to change in clinical presentation and social circumstances. Treatment with pharmacological and psychological interventions is expected to have a positive impact leading to increased productivity, decreased resource utilization and most importantly, improved long-term outcomes for girls and women.
These results shed light on the susceptibility of pigs to ZEBOV infection and identify an unexpected site of virus amplification and shedding linked to transmission of infectious virus.
Widespread circulation of SARS-CoV-2 in humans raises the theoretical risk of reverse zoonosis events with wildlife, reintroductions of SARS-CoV-2 into permissive nondomesticated animals. Here we report that North American deer mice (Peromyscus maniculatus) are susceptible to SARS-CoV-2 infection following intranasal exposure to a human isolate, resulting in viral replication in the upper and lower respiratory tract with little or no signs of disease. Further, shed infectious virus is detectable in nasal washes, oropharyngeal and rectal swabs, and viral RNA is detectable in feces and occasionally urine. We further show that deer mice are capable of transmitting SARS-CoV-2 to naïve deer mice through direct contact. The extent to which these observations may translate to wild deer mouse populations remains unclear, and the risk of reverse zoonosis and/or the potential for the establishment of Peromyscus rodents as a North American reservoir for SARS-CoV-2 remains unknown.
SUMMARY Recent and ongoing outbreaks of Ebola virus disease (EVD) underscore the unpredictable nature of ebolavirus reemergence and the urgent need for antiviral treatments. Unfortunately, available experimental vaccines and immunotherapeutics are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against other ebolaviruses associated with EVD, including Sudan virus (SUDV) and Bundibugyo virus (BDBV). Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs), affords unprecedented effectiveness and potency as a therapeutic countermeasure to antigenically diverse ebolaviruses. MBP134AF could fully protect ferrets against lethal EBOV, SUDV, and BDBV infection, and a single 25-mg/kg dose was sufficient to protect NHPs against all three viruses. The development of MBP134AF provides a successful model for the rapid discovery and translational advancement of immunotherapeutics targeting emerging infectious diseases.
SUMMARY Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge. The DMAb platform represents a simple, rapid, and reproducible approach for evaluating the activity of mAb during clinical development. DMAbs have the potential to be a mAb delivery system, which may be advantageous for protection against highly pathogenic infectious diseases, like EBOV, in resource-limited and other challenging settings.
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