Characterizing a century of genetic diversity and contemporary antigenic diversity of N1 neuraminidase in influenza A virus from North American swine.

Influenza A viruses (IAVs) of the H1N1 classical swine lineage became endemic in North American swine following the 1918 pandemic. Additional human-to-swine transmission events after 1918, and a spillover of H1 viruses from wild birds in Europe, potentiated a rapid increase in genomic diversity via reassortment between introductions and the endemic classical swine lineage. To determine mechanisms affecting reassortment and evolution, we conducted a phylogenetic analysis of N1 and paired HA swine IAV genes in North America between 1930 and 2020.

Swine-to-Ferret Transmission of Antigenically Drifted Contemporary Swine H3N2 Influenza A Virus Is an Indicator of Zoonotic Risk to Humans.

Human-to-swine transmission of influenza A (H3N2) virus occurs repeatedly and plays a critical role in swine influenza A virus (IAV) evolution and diversity. Human seasonal H3 IAVs were introduced from human-to-swine in the 1990s in the United States and classified as 1990.1 and 1990.

Interspecies Transmission from Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A Viruses with Reduced Reactivity to Candidate Vaccine Virus Antisera as Measures of Relative Zoonotic Risk.

During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population.

Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells.

Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (T) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating T in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs.

The applicability of grading systems for guidelines.

Rationale: This study focused on factors that most concern specialist societies when choosing an evidence grading system, such as methodological strengths and weaknesses, applicability and ease of use. The grading systems chosen were the Scottish Intercollegiate Guidelines Network (SIGN), the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the National Service Framework for long-term neurological conditions critical appraisal tool (NSF-LTC).

Methodology: Twelve assessors, representing typical members of society-based guideline development groups, graded papers and a recommendation using a key question as a guide.

A review of grading systems for evidence-based guidelines produced by medical specialties.

The development of evidence-based guidelines requires scrupulous attention to the method of critical appraisal. Many critical appraisal systems give 'gold standard' status to randomised controlled trials (RCTs) due to their ability to limit bias. While guidelines with a prominent research base consisting of RCTs have been well served by such systems, specialist societies with research bases consisting of a wide range of study designs have been at a disadvantage, potentially leading to inappropriately low grades being given for recommendations.

Vitiligo: concise evidence based guidelines on diagnosis and management.

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind.

The prevalence and moderators of fatigue in people who have been successfully treated for cancer.

Objective: The aims of this study were to estimate the prevalence of severe fatigue in disease-free breast cancer patients according to draft International Classification of Disease, Tenth Edition (ICD-10) criteria for cancer-related fatigue (CRF) and to obtain further information on the validity of these criteria. Furthermore, hypotheses derived from psychosocial theories of fatigue regarding the association of fatigue with activity level, psychological distress, and cognitive constructs were also tested.

Methods: Sixty-nine disease-free breast cancer patients were assessed at least 6 months posttreatment, using self-report questionnaires and a structured interview.

BMP signaling controls PASMC KV channel expression in vitro and in vivo.

Bone morphogenetic proteins (BMPs) have been implicated in the pathogenesis of familial pulmonary arterial hypertension. The type 2 receptor (BMPR2) is required for recognition of all BMPs. Transgenic mice with a smooth muscle cell-targeted mutation in this receptor (SM22-tet-BMPR2(delx4+)) developed increased pulmonary artery pressure, associated with a modest increase in arterial muscularization, after 8 wk of transgene activation (West J, Fagan K, Steudel W, Fouty B, Lane K, Harral J, Hoedt-Miller M, Tada Y, Ozimek J, Tuder R, and Rodman DM.

Modulation of skeletal and cardiac voltage-gated sodium channels by calmodulin.

Calmodulin (CaM) has been shown to modulate different ion channels, including voltage-gated sodium channels (NaChs). Using the yeast two-hybrid assay, we found an interaction between CaM and the C-terminal domains of adult skeletal (NaV1.4) and cardiac (NaV1.