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The NLRP3 inflammasome is activated in the lung during influenza viral infection; however the impact of aging on inflammasome function during influenza infection has not been examined. Here, we show that elderly mice infected with a mouse adapted strain of influenza produced lower levels of IL-1β during in vitro and in vivo infection. Dendritic cells from elderly mice exhibited decreased expression of ASC, NLRP3, and capase-1, but increased expression of pro-IL-1β, pro-IL-18, and pro-IL-33 when compared to young infected mice. Treatment with nigericin during influenza infection augmented IL-1β production, increased caspase-1 activity, and decreased morbidity and mortality in elderly mice. Our study demonstrates for the first time that during influenza viral infection, elderly mice have impaired NLRP3 inflammasome activity and that treatment with nigericin rescues NLRP3 activation in elderly hosts.

Highly pathogenic avian influenza A (HPAI), subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203) induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483) induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.

Sensory abnormalities in autism has been noted clinically, with pain insensitivity as a specified diagnostic criterion. However, there is limited research using psychophysically robust techniques. Thirteen adults with ASD and 13 matched controls completed an established quantitative sensory testing (QST) battery, supplemented with measures of pain tolerance and central modulation. The ASD group showed higher thresholds for light touch detection and mechanical pain. Notably, the ASD group had a greater range of extreme scores (the number of z-scores outside of the 95% CI > 2), dynamic mechanical allodynia and paradoxical heat sensation; phenomena not typically seen in neurotypical individuals. These data support the need for research examining central mechanisms for pain in ASD and greater consideration of individual difference.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights d Representative sequencing (Rep-Seq) is a new method for tumor molecular profiling d Rep-Seq homogenizes residual tumor tissue not taken for standard pathology d Representative sampling of tumors generates accurate tumor mutation burden scores d Rep-Seq detects more mutations and accurately resolves clonal from subclonal variants

Individuals living with spinal cord injury or disease (SCI/D) are at increased risk for sleep-disordered breathing (SDB), with a prevalence that is three-to fourfold higher than the general population. The main features of SDB, including intermittent hypoxemia and sleep fragmentation, have been linked to adverse cardiovascular outcomes including nocturnal hypertension in patients with SCI/D. The relationship between SDB and SCI/D may be multifactorial in nature given that level and completeness of injury can affect central control of respiration and upper airway collapsibility differently, promoting central and/or obstructive types of SDB. Despite the strong association between SDB and SCI/D, access to diagnosis and management remains limited. This review explores the role of SCI/D in the pathogenesis of SDB, poor sleep quality, the barriers in diagnosing and managing SDB in SCI/D, and the alternative approaches and future directions in the treatment of SDB, such as novel pharmacologic and nonpharmacologic treatments.

Participation by people of color in research studies is important for generalizability and to mitigate health disparities. Barriers to recruitment are well documented, but less well known is how to succeed. This paper describes successful strategies for recruitment and retention of pregnant Black women for a multisite study of preterm birth. Recruiters provided input on strategies. Participant level strategies include: commitment to being respectful, friendly, and reliable; addressing concerns regarding confidentiality; acknowledging competing priorities; and when possible, matching recruiters by gender and race. Clinical level strategies include: the formation of a good working relationship with the clinical staff; prioritizing clinical care above research activities; and obtaining access to the electronic medical record systems. Protocol level strategies include: a wide enrollment window; coordinating biospecimen collection with the clinical laboratory tests; collecting survey data on an electronic tablet; text messaging; and providing compensation for the time needed to complete study activities.

Aims & Objectives: This paper critically examines the nature and benefits of a therapeutic alliance created between a fluent, bilingual woman who had suffered a period of extreme bullying and her monolingual therapist. Method: The paper uses a case study approach to consider the underpinning psycho-neurology and describes the theoretical frameworks used to inform the therapeutic process and facilitate recovery. Results: The therapeutic approach proved successful in dealing with the physical, emotional and psychological impact of the bullying and has enabled the subject to return to work successfully. Conclusions: The emotional distancing provided by language switching can be invaluable in enabling a traumatised person to make sense of their experience.