Notes

Adjustments to Crisis Division Performance in the course of Hit associated with Senior Medical professionals within Korea.
Mouse models of Down syndrome (DS) have been invaluable tools for advancing knowledge of the underlying mechanisms of intellectual disability in people with DS. The Ts(1716)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with DS, including neuroanatomical changes and impaired learning and memory. In this study, we use rigorous metrics to evaluate multiple cohorts of Ts65Dn ranging from 2014 to the present, including a stock of animals recovered from embryos frozen within ten generations after the colony was first created in 2010. Through quantification of prenatal and postnatal brain development and several behavioral tasks, our results provide a comprehensive comparison of Ts65Dn across time and show a significant amount of variability both across cohorts as well as within cohorts. The inconsistent phenotypes in Ts65Dn mice highlight specific cautions and caveats for use of this model. We outline important steps for ensuring responsible use of Ts65Dn in future research.This article has an associated First Person interview with the first author of the paper.
To explore the perceptions and experiences of FPs with emerging adult (EA) mental health to inform opportunities for improvement in EA mental health care.

Constructivist grounded theory methodology, including theoretical sampling and constant comparative analysis of data to synthesize results.

Southwestern Ontario.

Twenty practising FPs.

In-depth, semistructured, in-person interviews, which were audiorecorded and transcribed verbatim.

Family physicians recognized the unique situation of EAs being between adolescence and adulthood, having heavy psychosocial needs, and lacking a connection to the health care system. Experience and confidence are needed to treat the EA population, but provision of mental health care to EAs is influenced by resources, knowledge, and communication. Family physicians noted that they are the default physician while EAs wait for specialized care, and are often the physicians that the patient is referred back to after specialized care. Often, the FP knows and treats the EA's entire family, which participants described as enabling them to understand the EA's unique context.

Family physicians and EAs are "lost together" in a fragmented health care system. Family physicians have the unique potential to assist EAs with their mental health needs, but that is not being actualized. Family physicians can support mental health outcomes for EAs through an improvement in knowledge and skills, and through forming family practice teams.
Family physicians and EAs are "lost together" in a fragmented health care system. Family physicians have the unique potential to assist EAs with their mental health needs, but that is not being actualized. Family physicians can support mental health outcomes for EAs through an improvement in knowledge and skills, and through forming family practice teams.Question If a child presents to my office with several days of fever and a few features of Kawasaki disease (KD) but does not meet the diagnostic criteria, could they still have KD and is treatment needed?Answer Presentations of KD have a range of clinical signs and symptoms. With the lack of a criterion standard test, the diagnosis of KD relies on syndrome recognition and a high index of suspicion in cases where KD does not present classically. It is still possible to have KD even if not all of the criteria are met, and these children are referred to as having incomplete forms of KD. The diagnosis of incomplete KD is usually made in a child or infant who presents with a history of prolonged fever, a few clinical criteria for KD, and other supportive features such as positive laboratory or echocardiographic findings. It is important to recognize children with incomplete forms of KD to avoid poor outcomes such as coronary artery aneurysms.
To guide family physicians working in a range of primary care clinical settings on how to provide care and support for patients who are vulnerably housed or experiencing homelessness.

The approach integrates recommendations from evidence-based clinical guidelines, the views of persons with lived experience of homelessness, the theoretical tenets of the Patient's Medical Home framework, and practical lessons learned from family physicians working in a variety of clinical practice settings.

Family physicians can use simple and effective approaches to identify patients who are homeless or vulnerably housed; take initial steps to initiate access to housing, income assistance, case management, and treatment for substance use; and work collaboratively using trauma-informed and anti-oppressive approaches to better assist individuals with health and social needs. Family physicians also have a powerful advocacy voice and can partner with local community organizations and people with lived experience of homelessness to advocate for policy changes to address social inequities.

Family physicians can directly address the physical health, mental health, and social needs of patients who are homeless or vulnerably housed. Moreover, they can champion outreach and onboarding programs that assist individuals who have experienced homelessness in accessing patient medical homes and can advocate for broader action on the underlying structural causes of homelessness.
Family physicians can directly address the physical health, mental health, and social needs of patients who are homeless or vulnerably housed. Moreover, they can champion outreach and onboarding programs that assist individuals who have experienced homelessness in accessing patient medical homes and can advocate for broader action on the underlying structural causes of homelessness.Glioma stem-like cells (GSC) in glioblastoma (GBM) structure tumor cells into a hierarchical organization and are postulated to be recalcitrant to conventional treatments, resulting in fatal relapse of the disease. A better understanding of these cells would be essential for meaningful and lasting treatments. In this issue of Cancer Research, Virolle and colleagues report a fascinating phenotype whereby the extracellular signal-regulated kinase (ERK) pathway regulates a mechanism of dedifferentiation of GBM cells into a stem-like state expressing markers of pluripotency through an EGFR-ERK-EGR1-dependent axis. This aptly termed "toggle switch" may contribute to maintenance of GSCs, promote intratumor heterogeneity, and potentially provide innovative treatment options.See related article by Almairac et al., p. 3236.Senescent cells release a mélange of factors that drive multiple forms of pathology, including cancer aggressiveness. In this issue of Cancer Research, Han and colleagues show that small extracellular vesicles (sEV), membrane-enclosed bubbles that carry signaling molecules, from senescent stromal cells can promote tumorigenesis and multidrug resistance in prostate or breast cancer cells. They find that loss of SIRT1 activity drives senescence-associated sEV release, and treatment with a SIRT1 agonist prevented this effect. 1Methyl3nitro1nitrosoguanidine This adds another mechanism by which senescent cells can promote tumorigenesis and offers another activity of senescent cells that might be targeted to limit the spread of cancer.See related article by Han et al., p. 3383.
Enzyme-inducing antibacterial drugs can impair the efficacy of hormonal contraceptives. Suspicion that other antibiotics might do likewise led to advice that extra contraceptive precautions should be taken during a course of antibiotics. However, current advice is that the purported interaction does not occur, based on small studies observing few pregnancies, assuming that all women are susceptible, and without measuring unbound hormone concentrations.

To test the null hypothesis that antibiotics do not impair the effectiveness of oral contraceptives.

A database review of Yellow Card reports to the UK's Medicines and Healthcare products Regulatory Agency.

Spontaneous reports of suspected adverse drug reactions in people taking antibacterial drugs (n=74 623), enzyme-inducing medicines (n=32 872), or control medicines (n=65 578).

Reports of the primary outcome-unintended pregnancies; reports of cardiac arrhythmias and headaches (control events); reports of congenital abnormalities (positive control evan unintended pregnancy is a life-changing event.
Antibiotic over prescription for upper respiratory tract infections (URTIs) in primary care exacerbates antimicrobial resistance. There is a need for effective alternatives to antibiotic prescribing. Honey is a lay remedy for URTIs, and has an emerging evidence base for its use. Honey has antimicrobial properties, and guidelines recommended honey for acute cough in children.

To evaluate the effectiveness of honey for symptomatic relief in URTIs.

A systematic review and meta-analysis. We searched Pubmed, Embase, Web of Science, AMED, Cab abstracts, Cochrane Library, LILACS, and CINAHL with a combination of keywords and MeSH terms.

We identified 1345 unique records, and 14 studies were included. Overall risk of bias was moderate. Compared with usual care, honey improved combined symptom score (three studies, mean difference -3.96, 95% CI -5.42 to -2.51, I
=0%), cough frequency (eight studies, standardised mean difference (SMD) -0.36, 95% CI -0.50 to -0.21, I
=0%) and cough severity (five studies, SMD -0.44, 95% CI -0.64 to -0.25, I
=20%). We combined two studies comparing honey with placebo for relieving combined symptoms (SMD -0.63, 95% CI -1.44 to 0.18, I
=91%).

Honey was superior to usual care for the improvement of symptoms of upper respiratory tract infections. It provides a widely available and cheap alternative to antibiotics. Honey could help efforts to slow the spread of antimicrobial resistance, but further high quality, placebo controlled trials are needed.

Study ID, CRD42017067582 on PROSPERO International prospective register of systematic reviews (https//www.crd.york.ac.uk/prospero/).
Study ID, CRD42017067582 on PROSPERO International prospective register of systematic reviews (https//www.crd.york.ac.uk/prospero/).Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.
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