Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well ...understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses. Antibiotic-mediated depletion or gnotobiotic exclusion of fungi enhances responsiveness to radiation, whereas antibiotic-mediated depletion of bacteria reduces responsiveness and is associated with overgrowth of commensal fungi. Further, elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in patients with breast cancer and is required for the effects of commensal fungi in mouse models of radiation therapy.
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•Commensal bacteria support antitumor T cell responses following radiation therapy•Depletion of intestinal bacteria leads to expansion of commensal fungal populations•Commensal fungi promote pro-tumor macrophage actions by impeding antitumor T cells•Tumor-associated macrophages sense fungi through a Dectin-1-mediated mechanism
Depletion of commensal bacteria leads to expansion of commensal fungi and reduced antitumor immunity following irradiation of tumors. Targeting commensal fungi enhanced the radiation-induced antitumor immune response by reducing macrophage-mediated immunosuppression. Thus, Shiao et al. demonstrate opposing effects of commensal bacteria and fungi on antitumor immunity following radiation.
We describe the discovery and isolation of a paramyxovirus, feline morbillivirus (FmoPV), from domestic cat (Felis catus). FmoPV RNA was detected in 56 (12.3%) of 457 stray cats (53 urine, four ...rectal swabs, and one blood sample) by RT-PCR. Complete genome sequencing of three FmoPV strains showed genome sizes of 16,050 bases, the largest among morbilliviruses, because of unusually long 5' trailer sequences of 400 nt. FmoPV possesses identical gene contents (3'-N-P/V/C-M-F-H-L-5') and is phylogenetically clustered with other morbilliviruses. IgG against FmoPV N protein was positive in 49 sera (76.7%) of 56 RT-PCR-positive cats, but 78 (19.4%) of 401 RTPCR-negative cats (P < 0.0001) by Western blot. FmoPV was isolated from CRFK feline kidney cells, causing cytopathic effects with cell rounding, detachment, lysis, and syncytia formation. FmoPV could also replicate in subsequent passages in primate Vero E6 cells. Infected cell lines exhibited finely granular and diffuse cytoplasmic fluorescence on immunostaining for FmoPV N protein. Electron microscopy showed enveloped virus with typical "herringbone" appearance of helical N in paramyxoviruses. Histological examination of necropsy tissues in two FmoPV-positive cats revealed interstitial inflammatory infiltrate and tubular degeneration/necrosis in kidneys, with decreased cauxin expression in degenerated tubular epithelial cells, compatible with tubulointerstitial nephritis (TIN). Immunohistochemical staining revealed FmoPV N protein-positive renal tubular cells and mononuclear cells in lymph nodes. A casecontrol study showed the presence of TIN in seven of 12 cats with FmoPV infection, but only two of 15 cats without FmoPV infection (P < 0.05), suggesting an association between FmoPV and TIN.
To date, little is known about the sustainability and scalability of MyDiabetesPlan, an eHealth innovation designed to facilitate shared decision-making within diabetes care. To avoid the possibility ...of its short-lived implementation and promote wider adoption so as to promote patient-centred diabetes care, it is critical to understand MyDiabetesPlan's sustainability and scalability in order to ensure its long-term impact at a greater scale. We sought to identify the sustainability and scalability potential of MyDiabetesPlan and its limiting factors.
Using a concurrent triangulation mixed-methods approach, data were collected from 20 individuals involved in the development and implementation of MyDiabetesPlan. The National Health Services Sustainability Model (NHSSM) and the Innovation Scalability Self-administered Questionnaire (ISSaQ) were administered using a 'think-aloud' approach and subsequently, short semi-structured interviews were conducted. Mean aggregate scores and stakeholder-specific scores were generated for the NHSSM and ISSaQ, to quantitatively determine facilitating and limiting factors to sustainability and scalability. Content analysis occurred iteratively with qualitative data, to examine commonalities and differences with the quantitative findings.
The top facilitating factor to sustaining MyDiabetesPlan was "Staff involvement and training to sustain the process.", whereas the top limiting factors were: "Adaptability of Improved Process", "Senior Leadership Engagement" and "Infrastructure for Sustainability". The top three facilitating factors for scale-up were "Acceptability", "Development with Theory" and "Consistency with Policy Directives." Conversely, the top three limiting factors were "Financial and Human Resources", "Achievable Adoption" and "Broad Reach". Qualitative findings corroborated the limiting/facilitating factors identified.
Addressing staff involvement throughout the dynamic care contexts, and resource constraints impacting scale-up can enhance the sustainability and scalability of MyDiabetesPlan. As such, future plans will focus on garnering organizational leadership buy-in and support, which may address the resource constraints associated with sustainability and scalability and improve the capacity for adequate staff involvement. eHealth researchers will be able to prioritize these limiting factors from the outset of their tool development to purposefully optimize its sustainability and scalability performance.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To examine the relationship between socioeconomic factors and outcomes of developmental dysplasia of the hip (DDH).
A retrospective review of patients with DDH at a tertiary pediatric hospital from ...2003 to 2012 with 2 years minimum follow-up was conducted. The relationship between socioeconomic factors with late presentation, treatment, and outcomes was examined. Socioeconomic factors included insurance status, language, and ethnicity.
In total, 188 patients met criteria. Patients with late presentations were more likely to be Hispanic (P = .02). However, public insurance and a non-English language were not associated with late presentation. Hispanic patients (P = .01) and patients with a non-English language (P = .01) had a lower nonoperative treatment success rate. Hispanic patients had more surgical procedures performed than non-Hispanic patients (P = .04). Patients with range of motion limitations were more likely to have public insurance (P = .05) and be Hispanic (P = .04). On multiple logistic regression analysis controlling for late presentation, patients with public insurance had increased odds of range of motion limitations (OR 2.22, P = .04). Patients with public insurance (OR 0.44, P = .04), a non-English primary language (OR 0.30, P < .01), and Hispanic ethnicity (OR 0.37, P = .01) had decreased odds of successful nonoperative treatment.
Public insurance, a non-English language, and Hispanic ethnicity are risk factors for inferior outcomes for DDH. When controlling for late presentation, these were significant risk factors for nonoperative treatment failure.
Compared to the enormous species diversity of bats, relatively few parvoviruses have been reported. We detected diverse and potentially novel parvoviruses from bats in Hong Kong and mainland China. ...Parvoviruses belonging to Amdoparvovirus, Bocaparvovirus and Dependoparvovirus were detected in alimentary, liver and spleen samples from 16 different chiropteran species of five families by PCR. Phylogenetic analysis of partial helicase sequences showed that they potentially belonged to 25 bocaparvovirus, three dependoparvovirus and one amdoparvovirus species. Nearly complete genome sequencing confirmed the existence of at least four novel bat bocaparvovirus species (Rp-BtBoV1 and Rp-BtBoV2 from Rhinolophus pusillus, Rs-BtBoV2 from Rhinolophus sinicus and Rol-BtBoV1 from Rousettus leschenaultii) and two novel bat dependoparvovirus species (Rp-BtAAV1 from Rhinolophus pusillus and Rs-BtAAV1 from Rhinolophus sinicus). Rs-BtBoV2 was closely related to Ungulate bocaparvovirus 5 with 93, 72.1 and 78.7 % amino acid identities in the NS1, NP1 and VP1/VP2 genes, respectively. The detection of bat bocaparvoviruses, including Rs-BtBoV2, closely related to porcine bocaparvoviruses, suggests recent interspecies transmission of bocaparvoviruses between bats and swine. Moreover, Rp-BtAAV1 and Rs-BtAAV1 were most closely related to human AAV1 with 48.7 and 57.5 % amino acid identities in the rep gene. The phylogenetic relationship between BtAAVs and other mammalian AAVs suggests bats as the ancestral origin of mammalian AAVs. Furthermore, parvoviruses of the same species were detected from multiple bat species or families, supporting the ability of bat parvoviruses to cross species barriers. The results extend our knowledge on the diversity of bat parvoviruses and the role of bats in parvovirus evolution and emergence in humans and animals.
Translation of eHealth research findings and successful implementation into clinical care is limited. We used a multitiered approach (individual, organizational, societal) to assess the ...implementation potential of MyDiabetesPlan within Ontario’s primary care system and applied the normalization process theory (NPT) to explicate our findings.
Data were collected from 15 individuals through interviews with primary care administrative end-users and a focus group discussion with Ministry of Health decision-makers, then qualitatively analyzed using thematic analysis for emergent themes.
We identified 3 themes corresponding to our multitiered approach: 1) stakeholder buy-in was critical to engagement and was impacted by perceptions/capacities; 2) clinical integration of MyDiabetesPlan depended on alignment with clinic philosophy of care, pre-existing technologies and workflow; and 3) political climate and trends were important considerations for eHealth implementation. Application of NPT to findings revealed that interplay between buy-in and perceptions/capacities of clinical practice stakeholders was critical to engaging them for eHealth implementation. In contrast, evaluation of costs and outcomes was critical to inform operational-management stakeholders’ perceptions. Findings at the organizational and societal levels best aligned with the factors influencing operationalization of MyDiabetesPlan. Overall, our findings show that the synergistic operationalization of MyDiabetesPlan into practice was a prerequisite to implementation at all health-care levels.
Application of NPT revealed context- and stakeholder-specific interactions that should be synergistically leveraged to promote MyDiabetesPlan normalization into routine clinical practice. Our findings provide further insight into how researchers can comprehensively assess eHealth implementation potential within Ontario and can be extrapolated to similar single-payer health-care jurisdictions.
Le transfert des résultats issus de la recherche en télésanté et la mise en œuvre fructueuse dans les soins cliniques sont limités. Nous avons utilisé une approche à plusieurs niveaux (individuel, organisationnel, sociétal) pour évaluer le potentiel de la mise en œuvre de MyDiabetesPlan dans les soins primaires en Ontario et appliqué la théorie du processus de normalisation (NPT, de l’anglais normalizationprocesstheory) pour expliquer nos résultats.
Les données collectées qui provenaient d’entretiens avec des utilisateurs administratifs finaux des soins primaires et d’un groupe de discussion avec les décideurs du ministère de la Santé, soit un total de 15 individus, ont fait l’objet d’une analyse qualitative, sous la forme de l’analyse thématique, pour dégager les thèmes émergents.
Nous avons déterminé 3 thèmes qui correspondaient à notre approche à plusieurs niveaux : 1) l’adhésion des parties prenantes était essentielle à l’engagement et subissait les répercussions des perceptions/capacités; 2) l’intégration clinique de MyDiabetesPlan reposait sur l’harmonisation avec la philosophie clinique des soins, les technologies préexistantes et le flux de travaux; 3) le climat politique et les tendances étaient des considérations importantes pour la mise en œuvre de la télésanté. L’application de la NPT aux résultats a révélé que les interactions entre l’adhésion et les perceptions/capacités des parties prenantes en matière de pratique clinique étaient essentielles à leur engagement dans la mise en œuvre de la télésanté. En revanche, l’évaluation des coûts et des résultats était essentielle pour façonner les perceptions des parties prenantes à la gestion des opérations. Les résultats au niveau organisationnel et au niveau sociétal correspondaient davantage aux facteurs qui influençaient l’opérationnalisation de MyDiabetesPlan. Dans l’ensemble, nos conclusions montrent que l’opérationnalisation synergique de MyDiabetesPlan dans la pratique était une condition préalable à la mise en œuvre à tous les niveaux des soins de santé.
L’application de la NPT a révélé les interactions entre le contexte et les parties prenantes qui devraient être exploitées de façon synergique pour favoriser la normalisation de MyDiabetesPlan dans la pratique clinique courante. Nos résultats permettent d’élucider davantage la façon avec laquelle les chercheurs peuvent évaluer de façon exhaustive le potentiel de mise en œuvre de la télésanté en Ontario et la façon avec laquelle ils peuvent être extrapolés aux administrations de soins de santé à payeur unique similaires.
This study compared the outcomes of four salvage procedures in treating painful dislocated hips in patients with cerebral palsySchanz osteotomy, Girdlestone, Castle, and McHale procedures. A ...retrospective review of cerebral palsy patients treated between 1990 and 2014 with minimum 6-month follow-up was carried out. Of 69 hips (62 patients), there were 36 McHales, 24 Castles, four Girdlestones, and five Schanz procedures at a mean age of 13.9 years. All four procedures provided pain relief. Proximal femoral migration was similar following the procedures, but heterotopic ossification was more common after the Castle procedure. Bone resorption and revision surgery were more frequent after the McHale procedure.
Abnormal uterine bleeding in premenopausal women is a common gynaecological symptom and composes of abnormality in the frequency, duration, regularity, and flow volume of menstruation. It could ...constitute the presentation of various gynaecological malignancies. An appropriate history and physical examination are mandatory to ascertain the diagnosis. Depending on the clinical condition, a complete blood picture, thyroid function test, clotting profile, chlamydia test, cervical smear, and pregnancy test can be performed. Ultrasound should be performed in cases with a pelvic mass, unsatisfactory physical examination, persistent symptoms, or no response to medical treatment. In women aged ≥40 years, an out-patient endometrial biopsy with Pipelle should be performed. In women aged <40 years with risk factors for endometrial cancer, persistent symptoms, or no response to medical treatment, an endometrial biopsy should be performed to rule out endometrial cancer. Hysteroscopy or saline infusion sonohysterography is more sensitive than ultrasound for diagnosing endometrial pathology. Details of the above recommendations are presented.
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