Orthobiologic Management Options for Degenerative Disc Disease.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient's own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.

Effectiveness of patient reminders on influenza vaccination coverage among adults with chronic conditions: A feasibility study in Australian general practices.

BACKGROUND: Influenza vaccination is recommended for Australians 18+ years old with medical risk factors, but coverage is suboptimal. We aimed to examine whether automatic, opportunistic patient reminders (SMS and/or printed) before appointments with a general practitioner increased influenza vaccination uptake. METHODS: This clustered non-randomised feasibility study in Australian general practice included patients aged 18-64 years with at least one medical risk factor attending participating practices between May and September 2021. Software installed at intervention practices identified unvaccinated eligible patients when they booked an appointment, sent vaccination reminders (SMS on booking and 1 h before appointments), and printed automatic reminders on arrival. Control practices provided usual care. Clustered analyses adjusted for sociodemographic differences among practices were performed using logistic regression. RESULTS: A total of 12,786 at-risk adults attended 16 intervention practices (received reminders = 4066; 'internal control' receiving usual care = 8720), and 5082 individuals attended eight control practices. Baseline influenza vaccination uptake (2020) was similar in intervention and control practices (∼34%). After the intervention, uptake was similar in all groups (control practices = 29.3%; internal control = 30.0%; intervention = 31.6% (p-value = 0.203). However, SMS 1 h before appointments increased vaccination coverage (39.3%, adjusted OR = 1.65; 95%CI 1.20;2.27; number necessary to treat = 13), especially when combined with other reminder forms. That effect was more evident among adults with chronic respiratory, rheumatologic, or inflammatory bowel disease. CONCLUSION: These findings indicate that automated SMS reminders delivered at proximate times to appointments are a low-cost strategy to increase influenza vaccination among adults at higher risk of severe disease attending Australian general practices.

Cytoskeletal ß-tubulin and cysteine cathepsin L deregulation by SARS-CoV-2 spike protein interaction with the neuronal model cell line SH-SY5Y.

SARS-CoV-2 mainly infects the respiratory tract but can also target other organs, including the central nervous system. While it was recently shown that cells of the blood-brain-barrier are permissive to SARS-CoV-2 infection in vitro, it remains debated whether neurons can be infected. In this study, we demonstrate that vesicular stomatitis virus particles pseudotyped with the spike protein of SARS-CoV-2 variants WT, Alpha, Delta and Omicron enter the neuronal model cell line SH-SY5Y. Cell biological analyses of the pseudo-virus treated cultures showed marked alterations in microtubules of SH-SY5Y cells. Because the changes in ß-tubulin occurred in most cells, but only few were infected, we further asked whether interaction of the cells with spike protein might be sufficient to cause molecular and structural changes. For this, SH-SY5Y cells were incubated with trimeric spike proteins for time intervals of up to 24 h. CellProfiler™-based image analyses revealed changes in the intensities of microtubule staining in spike protein-incubated cells. Furthermore, expression of the spike protein-processing protease cathepsin L was found to be up-regulated by wild type, Alpha and Delta spike protein pseudotypes and cathepsin L was found to be secreted from spike protein-treated cells. We conclude that the mere interaction of the SARS-CoV-2 with neuronal cells can affect cellular architecture and proteolytic capacities. The molecular mechanisms underlying SARS-CoV-2 spike protein induced cytoskeletal changes in neuronal cells remain elusive and require future studies.

Establishing national clinical diagnostic reference levels and achievable doses for CT examinations in Brazil: A prospective study.

PURPOSE: Diagnostic reference levels (DRL) and achievable doses (AD) are important tools for radiation dose optimization. Therefore, a prospective study was performed which aimed to establish a multi-parametric, clinical indication based - DRL(DRLCI) and clinical indication - AD (ADCI) for adult CT in Brazil. METHODS: The prospective study included 4787 patients (50 ± 18 years old; male:female 2041:2746) at 13 Brazilian sites that have been submitted to head, paranasal sinus, cervical spine, chest, or abdomen-pelvis CT between January and October 2021 for 13 clinical indications. The sites provided the following information: patient age, gender, weight, height, body mass index[BMI], clinical indications, scanner information(vendor, model, detector configuration), scan parameters (number of scan phases, kV, mA, pitch) and dose-related quantities (CT dose index volume- CTDIvol, dose length product- DLP). Median(AD) and 75th(DRL) percentile CTDIvol and DLP values were estimated for each body region and clinical indications. Non-normal data were analyzed with the Kruskal-Wallis test. RESULTS: In majority of Brazilian sites, body region and clinical indications based DRLs were at or lower than the corresponding DRLs in the US and higher than Europe. Although radiation doses varied significantly for patients in different body mass index groups (p < 0.001), within each body region, there were no differences in radiation doses for different clinical indications (p > 0.1). Radiation doses for 7/13 clinical indications were higher using iterative reconstruction technique than for the filtered back projection. CONCLUSIONS: There was substantial variation in Brazil DRLCI across different institutions with higher doses compared to the European standards. There was also a lack of clinical indication-based protocol and dose optimization based on different clinical indications for the same body region.

Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D.

The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.

Asthma, obesity, and microbiota: A complex immunological interaction.

Obesity and allergic asthma are inflammatory chronic diseases mediated by distinct immunological features, obesity presents a Th1/Th17 profile, asthma is commonly associated with Th2 response. However, when combined, they result in more severe asthma symptoms, greater frequency of exacerbation episodes, and lower therapy responsiveness. These features lead to decreased life quality, associated with higher morbidity/mortality rates.  In addition, obesity prompts specific asthma phenotypes, which can be dependent on atopic status, age, and gender. In adults, obesity is associated with neutrophilic/Th17 profile, while in children, the outcome is diverse, in some cases children with obesity present aggravation of atopy, and Th2 inflammation, and in others an association with a Th1 profile, with reduced IgE levels and eosinophilia. These alterations occur due to a complex group of factors among which the microbiome has been recently explored. Particularly, evidence shows its important role in susceptibility or resistance to asthma development, via gut-lung-axis, and demonstrates its relevance to the immune pathogenesis of the syndrome. Few studies address the relevance of the lung microbiome in shaping the immune response, locally. However, specific bacteria, like Moraxella catarrhalis, Haemophilus influenza, and Streptococcus pneumoniae, correlate with important features of the obese-asthmatic phenotype. Although maternal obesity is known to increase asthma risk in offspring, the impact on lung colonization is unknown. This review details the main key immune mechanisms involved in obesity-aggravated asthma, featuring the effect of maternal obesity in the establishment of gut and lung microbiota of the offspring, acting as potential childhood asthma inducer.

Os EPI's adotados para controle local de transmissibilidade da COVID-19 no retorno das atividades presenciais de atendimento à população nos cursos de odontologia em Minas Gerais / Personal protective equipment adopted for local control of transferability by COVID-19 in the return of face-to-face activities to serve the population in dentistry courses in Minas Gerais

Desde o início da pandemia, no final de 2019, até a retomada das atividades presencias de atendimento ao público nos cursos da área de saúde em Minas Gerais, especificamente nos cursos de odontologia; foram elaboradas notas técnicas, recomendações e manuais de biossegurança. Documentos esses que serviram como referencial para a padronização de protocolos de atendimento, incluindo o uso de EPI's mais eficientes no controle da transmissibilidade da Covid-19. A pesquisa de revisão foi realizada na base de dados PubMed/MEDLINE e Scielo, World Health Organization, Ministério da Saúde, Associação Brasileira de Ensino Odontológico, Conselho Federal de Odontologia, Conselhos Regionais de Odontologia dos Estados de São Paulo e Minas Gerais e instituições de ensino superior. Priorizando os conteúdos publicados entre os meses de janeiro a setembro de 2020. Período correspondente ao início da pandemia até o retorno das atividades de atendimento nos cursos de saúde em Minas Gerais. Buscando os documentos que nortearam esse retorno e que justificaram a adoção do uso desses EPI's pelos graduandos.

Since the beginning of the pandemic, at the end of 2019, until the resumption of face-to-face activities to serve the public in health care courses in Minas Gerais, specifically in dentistry courses; technical notes, recommendations and biosafety manuals were prepared. These documents served as a reference for the standardization of care protocols, including the use of more efficient personal protection equipment to control Covid-19's transmissibility. The review search was carried out in the PubMed/MEDLINE and Scielo databases, World Health Organization, Ministry of Health of Brazil, Brazilian Association of Dental Education, Federal Council of Dentistry, Regional Councils of Dentistry of the States of São Paulo and Minas Gerais and college. Prioritizing the contents published between January and September 2020. Period corresponding to the beginning of the pandemic until the return of care activities in health courses in Minas Gerais. Seeking the documents that guided this return and that justified the adoption of the use of this personal protective equipment by college students.

Impact of a radiological protection campaign in emergency paediatric radiology: a multicentric observational study in Brazil.

PURPOSE: To evaluate the impact of a paediatric radiological protection campaign, implemented in the emergency units of a healthcare provider network in Brazil. This campaign aimed to promote awareness among emergency department physicians, regarding justification of paediatric X-ray referrals for paranasal sinus, chest and CT exams, as a strategy to reduce exposure to ionising radiation. METHOD: Frequency analysis of common paediatric imaging referrals from 19 emergency departments was performed for a 3-year period (2015-2018) to coincide with before, during and after the implementation of the radiation protection campaign. The campaign was multifaceted and involved dissemination of educational materials and imaging referral guidelines along with quarterly meetings with participating centres' leaderships. Additionally, patient dose cards were distributed to patients/carers. The Chi-Square test was used to examine the association between the type of examination and the patient's age group. Exact-Fisher test was performed to check for an association between participant engagement and the existence of the radiation protection committee. RESULTS: Referrals reduced by 25% following the campaign with no reports of misdiagnosis. Many referrals in the youngest age groups. In 15 units, a radiological protection committee was created to raise awareness and to create a multi professional team to communicate the risks and benefits of radiological procedure in children. CONCLUSION: The campaign resulted in a substantial reduction in radiological referrals while promoting a radiation protection culture. Simple education initiatives can contribute to savings in both finances and radiation doses, particularly important in radiosensitive cohorts.

Investigating centering, scan length, and arm position impact on radiation dose across 4 countries from 4 continents during pandemic: Mitigating key radioprotection issues.

PURPOSE: Optimization of CT scan practices can help achieve and maintain optimal radiation protection. The aim was to assess centering, scan length, and positioning of patients undergoing chest CT for suspected or known COVID-19 pneumonia and to investigate their effect on associated radiation doses. METHODS: With respective approvals from institutional review boards, we compiled CT imaging and radiation dose data from four hospitals belonging to four countries (Brazil, Iran, Italy, and USA) on 400 adult patients who underwent chest CT for suspected or known COVID-19 pneumonia between April 2020 and August 2020. We recorded patient demographics and volume CT dose index (CTDIvol) and dose length product (DLP). From thin-section CT images of each patient, we estimated the scan length and recorded the first and last vertebral bodies at the scan start and end locations. Patient mis-centering and arm position were recorded. Data were analyzed with analysis of variance (ANOVA). RESULTS: The extent and frequency of patient mis-centering did not differ across the four CT facilities (>0.09). The frequency of patients scanned with arms by their side (11-40% relative to those with arms up) had greater mis-centering and higher CTDIvol and DLP at 2/4 facilities (p = 0.027-0.05). Despite lack of variations in effective diameters (p = 0.14), there were significantly variations in scan lengths, CTDIvol and DLP across the four facilities (p < 0.001). CONCLUSIONS: Mis-centering, over-scanning, and arms by the side are frequent issues with use of chest CT in COVID-19 pneumonia and are associated with higher radiation doses.

Autoetnografias dos entre-mundos: partindo de uma pedagogia freireana da esperança para expandir narrativas e políticas de inclusão / Performing Betweener Autoethnographies Against Persistent Us/ Them Essentializing: Leaning on a Freirean Pedagogy of Hope / Autoetnografías de entre mundos: partiendo de la pedagogía freireana de esperanza para expandir las narrativas y políticas de inclusión

Resumo Betweeners (palavra criada pelos autores): utilizamos essa possibilidade da língua inglesa (de tradução difícil) no decorrer desta versão em português para explicar as condições de pessoas que habitam o espaço entre mundos, entre fronteiras, concretas e socioculturais. Como escrever nossa história entrelaçada com a história de tantos humanos oprimidos, de tantas singularidades e universalidades compartilhadas? Buscamos uma autoetnografia que seja performativa e transgressora diante de desigualdades brutais, injustiças óbvias e justificativas esfarrapadas dadas por aqueles com mais privilégios e poder "para nomear o mundo". Nós procuramos por uma forma de ser e escrever que critica, sem desculpas, as estruturas de poder que moldam e conservam tais sistemas de opressão. Buscamos em nossa autoetnografia um modelo alternativo de escrita que exponha as quebras e as fendas de nossa existência nos tempos neocoloniais. Vemos a autoetnografia de betweeners como uma maneira de ser e de nos escrever na história de resistência contra opressão, injustiça e exclusão, uma que parta de nossa comunalidade humana e de identidades que compartilhamos. Escrevemos aqui uma articulação entre autoetnografia de betweeners e representações essencialistas em constante busca por justiça social.

Abstract How to write our history interlaced with the history of so many oppressed humans from so many singularities and shared universalities? We search for an autoethnography that is performative and transgressive in face of brutal inequalities, obvious injustice, and lame justifications by those with more privilege and power "to name the world." We search for a form of being and writing that goes, without apologies, after the structures of power that shape and maintain such systems of oppression. We search in our autoethnography an alternative model of writing that exposes the breaks and cracks of our existence in neo-colonial times. We see betweener autoethnography as a way of being and writing ourselves into the history of resistance against oppression, injustice, and exclusion, one that starts from our common humanity in betweener identities. We write, here, a joint betweener autoethnography against essentialist representations in name of justice.

Resumen Betweeners (palabra creada por los autores): utilizamos esta posibilidad del idioma inglés (difícil de traducir) a lo largo de esta versión portuguesa para explicar las condiciones de las personas que habitan el espacio entre mundos, entre fronteras, concreto y sociocultural. ¿Cómo escribir nuestra historia entrelazada con la historia de tantos humanos oprimidos, tantas singularidades y universalidades compartidas? Buscamos una autoetnografía performativa y transgresora frente a las desigualdades brutales, injusticias evidentes y justificativas poco convincentes de los que tienen más privilegios y poder para "nombrar el mundo". Buscamos una forma de ser y de escribir que critique sin disculpas las estructuras de poder que dan forma y mantienen tales sistemas de opresión. Buscamos en nuestra autoetnografía un modelo de escritura alternativo que exponga las hendiduras y fisuras de nuestra existencia en la época neocolonial. Vemos la autoetnografía de los Betweeners como una forma de ser y de se escribir en la historia de la resistencia contra la opresión, la injusticia y la exclusión, que parte de nuestra comunidad humana y de identidades compartidas. Aquí escribimos una articulación entre la autoetnografía de los Betweeners y las representaciones esencialistas en constante búsqueda de la justicia social.

Permita-me falar mais alto do que minhas cicatrizes / Allow me to speak louder than my scars / Déjame hablar más fuerte que mis cicatrices

Resumo Neste artigo, escolhi o método autoetnográfico para narrar um processo pós-operatório que mudou minha vida. Compilei uma série de emoções, impressões, poemas e documentos coletados durante cerca de dois anos de recuperação. Ao fazer isso, tentei expandir a discussão e desafiar a noção do modelo médico acerca de um corpo "curado/fixo", e até a ideia capacitista sobre o que seria um corpo "normal/ativo". Este artigo almejou responder a questões como 'o que significa ser um corpo deficiente em recuperação?';'Como o corpo deficiente deveria ser representado?'; e, antes que alguém possa perguntar, 'o que aconteceu com você?', eu busquei uma possível narrativa sobre mim, uma perspectiva centrada no paciente. O artigo está dividido em quatro partes, a saber: 1) 'Aperto de mãos com Dr. Q' - introdução; 2) 'O que está acontecendo?' - diagnóstico médico e suas especificidades; 3) Cura por meio de palavras - processo pós-operatório; e, na sequência, os meus 4) Pensamentos finais. Escrever como pesquisador na interseção entre o pessoal e o acadêmico foi uma decisão combinada da mente e um movimento do coração. Esse modo de escrever é sempre uma linha tênue a ser cruzada, mas com implicações frutíferas tanto para o campo dos estudos da deficiência quanto para a comunidade dos 'não-deficientes'.

Abstract In this paper, I have chosen the auto-ethnographic method to narrate a life-changing post-surgery process, compiling a range of emotions, impressions, poems, and documents collected over the last two years of a significant recovery. In doing so, I attempt to expand the discussion and challenge the medical model notion of a 'cured/fixed' body, even the ableist idea of a 'normal/active' body. This paper aims to answer questions like 'what does it mean to be a disabled body in recovery?' 'How should the disabled body be represented?' And before someone can ask, 'What happened to you?' I will answer, controlling the narrative about me by giving a patient-process perspective. The paper is divided into four parts 1) 'Our handshake' - the introduction; 2) 'What is going on?' - The illness and medical technicalities; 3) Recovering through words - The after-surgery process, and; 4) Final thoughts - always an ongoing process. It was a concerted decision of the mind and a move from the heart to write as a researcher at the intersection between the personal and academic; it is always a blurred line to cross, but one with fruitful implications for the 'not-disabled' and Disability Studies community.

Resumen En este artículo, elegí el método autoetnográfico para narrar un proceso posoperatorio que cambió mi vida, recopilé una serie de emociones, impresiones, poemas y documentos recopilados durante aproximadamente dos años de recuperación. Al hacerlo, traté de expandir la discusión y desafiar la noción del modelo médico de un cuerpo "curado / fijo", e incluso la idea capacitiva de lo que sería un cuerpo "normal / activo". Este artículo tenía como objetivo responder preguntas como '¿qué significa ser un cuerpo discapacitado en recuperación? "¿Cómo debería representarse el cuerpo discapacitado? Y antes de que alguien pueda preguntar: '¿Qué me pasó?', Busqué una posible narrativa sobre mí, una perspectiva centrada en el paciente. El artículo se divide en cuatro partes, a saber: 1) "Apretón de manos con el Dr. Q": introducción; 2) "¿Qué está pasando?": Diagnóstico médico y sus especificidades; 3) Curación a través de palabras - proceso postoperatorio; y luego mis 4) Pensamientos finales. Escribir como investigador en la intersección de lo personal y lo académico fue una decisión combinada de la mente y un movimiento del corazón; Esta forma de escribir es siempre una línea muy fina que cruzar, pero con implicaciones fructíferas tanto para el campo de los estudios de la discapacidad como para la comunidad "no discapacitada".

Network integration and modelling of dynamic drug responses at multi-omics levels.

Uncovering cellular responses from heterogeneous genomic data is crucial for molecular medicine in particular for drug safety. This can be realized by integrating the molecular activities in networks of interacting proteins. As proof-of-concept we challenge network modeling with time-resolved proteome, transcriptome and methylome measurements in iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms of anthracycline cardiotoxicity measured with four different drugs (doxorubicin, epirubicin, idarubicin and daunorubicin). Dynamic molecular analysis at in vivo drug exposure levels reveal a network of 175 disease-associated proteins and identify common modules of anthracycline cardiotoxicity in vitro, related to mitochondrial and sarcomere function as well as remodeling of extracellular matrix. These in vitro-identified modules are transferable and are evaluated with biopsies of cardiomyopathy patients. This to our knowledge most comprehensive study on anthracycline cardiotoxicity demonstrates a reproducible workflow for molecular medicine and serves as a template for detecting adverse drug responses from complex omics data.

Changes in perceived knowledge about childbirth among pregnant women participating in the Senses of Birth intervention in Brazil: a cross-sectional study.

BACKGROUND: Senses of Birth (SoB) is a health education intervention in Brazil that aims to reduce unnecessary cesareans in the country by providing information on reproductive rights, benefits and risks of childbirth, and use of intrapartum evidence-based practices (EBP) which are recommended by the World Health Organization (WHO) to improve childbirth outcomes and satisfaction. This study evaluates the impact of the SoB on pregnant women's perceived knowledge about normal birth (NB), cesarean, and use of EBP. METHODS: 1287 pregnant women answered a structured survey immediately after their visit to the intervention, between March 2015 and March 2016. To estimate the potential impact of the intervention on women's perceived knowledge, and possible associations between sociodemographic characteristics and perceived knowledge, statistical analyses were performed, including paired T-tests, ANOVA, and logistic and linear regressions. RESULTS: The mean score (MS) of perceived knowledge after the intervention was higher than the MS before experiencing the intervention for all three knowledge domains: Normal Birth (MS Before = 3.71 x MS After = 4.49), Cesarean (MS Before = 3.54 x MS After = 4.26) and EBPs (MS Before = 3.14 x MS After = 4.14). The results suggest that perceived knowledge increased more for low-income women (B = 0.206; p < 0.001 for EBP), women without private health insurance (OR 2.47, 95% CI: 1.49-4.09 for NB), with private prenatal care (OR 2.42, 95% CI: 1.59-3.66 for NB), experiencing their first pregnancy (OR 1.92, 95% CI: 1.31-2.82 for EBP; OR 1.37, 95% CI: 1.03-1.84 for NB; OR 1.37, 95% CI: 1.03-1.84 for cesarean), and in their first or second trimester (OR 1.64, 95% CI: 1.13-2.39 for EBP; OR 1.48, 95% CI: 1.11-1.97 for NB; OR 1.85, 95% CI: 1.40-2.41 for cesarean). CONCLUSION: The study showed that participation in the SoB was associated with an increase in perceived knowledge among Brazilian pregnant women. The intervention gains relevance considering the lack of evidence of the impact of non-clinical interventions to reduce unnecessary cesareans in middle and low-income countries.

Osmophobia and Odor-Triggered Headaches in Children and Adolescents: Prevalence, Associated Factors, and Importance in the Diagnosis of Migraine.

OBJECTIVE: The objectives of this study are to study osmophobia and odor-triggered headaches among headache pediatric patients. BACKGROUND: Achieving the correct diagnosis for headaches in younger children can be challenging. The presence of osmophobia could constitute a helpful piece of information for making the correct diagnosis of headaches among adults. METHODS: This was a cross-sectional study. Children and adolescents with headaches who were seen consecutively at a pediatric outpatient service and had at least 1 headache attack over the previous 12 months were included. We used a semi-structured questionnaire, Pediatric Migraine Disability Assessment, State-Trait Anxiety Inventory, and Children's Depression Inventory. RESULTS: About 300 patients were included; 253 had migraine, 47 had a tension-type headache; 137 had osmophobia during headaches (135 were migraineurs). "Osmophobia during headaches" for diagnosing migraine: Sensitivity: 54.4% (95% CI: 48.2%-60.5%); specificity: 95.8% (95% CI: 85.8%-98.8%); positive predictive value (PPV): 98.5% (95% CI: 94.8%-99.6%); negative predictive value (NPV): 28.5% (95% CI: 22.0%-36.0%). Osmophobia was associated with higher intensity (OR: 2.90; 95% CI: 1.63, 5.15; P < .001) and duration of the headache (OR: 5.73; 95% CI: 2.29, 14.3; P < .001) and with vomiting (OR: 3.56; 95% CI: 1.83, 6.96; P < .001) (logistic regression). There were 62 patients (all of them migraineurs) with odor-triggered headaches: sensitivity for diagnosing migraine: 24.9% (95% CI: 19.9%-30.6%); specificity: 100% (95% CI: 92.4%-100%), PPV: 100% (95% CI: 94.8%-100%), NPV: 20% (95% CI: 16%-26.0%). Odor-triggered headaches were associated with higher intensity (OR: 3.47; 95% CI: 1.64, 7.35; P = .001) and duration of the headache (OR: 3.28; 95% CI: 1.37, 7.86; P = .001), vomiting (OR: 2.37; 95% CI: 1.19, 4.74; P = .014), and phonophobia (OR: 2.40; 95% CI: 1.08, 5.32; P = .031) (logistic regression). Osmophobia was associated with higher-impact migraine (OR: 4.65; 95% CI: 1.30, 16.6; P = .018) and emergency care (OR: 4.65; 95% CI: 1.81, 12.0; P = .001) (logistic regression). CONCLUSIONS: Osmophobia and odors as triggers for headaches are useful in diagnosing migraine and are markers for the severity of migraine in the pediatric population.

Antioxidants Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and, here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyze the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week for 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week for 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

Interobserver Variability in the Computed Tomography Assessment of Pulmonary Injury and Tumor Recurrence After Stereotactic Body Radiotherapy.

PURPOSE: To evaluate the interobserver agreement of chest computed tomography (CT) findings in the diagnosis of expected changes and local recurrence after stereotactic body radiation therapy (SBRT) in patients with early-stage lung cancer or a single pulmonary metastasis. MATERIALS AND METHODS: A total of 54 patients with early-stage lung cancer or pulmonary metastasis who were treated with SBRT from 2007 to 2015 were included. The exclusion criteria were patients who presented with pulmonary infection during follow-up and patients who underwent a single CT during follow-up. The imaging features on CT were assessed by 3 blinded radiologists at the following 2 time points after SBRT: (a) early follow-up and (b) late follow-up (≥6 mo). The radiologists classified the findings as expected changes after SBRT or recurrence. Interobserver agreement was assessed by kappa and Wilcoxon statistics. RESULTS: A total of 13 women and 41 men with a mean age of 75.3 (±8.9) years were selected. The total and per fraction SBRT doses were 54 Gy (interquartile range: 45 to 54) and 18 Gy (interquartile range: 15 to 18), respectively. All expected changes and findings suggestive of recurrence had an almost perfect agreement (κ>0.85) among readers, except for diffuse consolidation in the early period (κ=0.65). CONCLUSION: CT findings demonstrate high interobserver agreement for expected changes and for findings indicating recurrence after SBRT.

Impact of funding influenza vaccination on coverage among Australian children: a national study using MedicineInsight, a large general practice database.

Influenza contributes to morbidity and mortality worldwide. Children are at a higher risk of influenza-related complications and vaccination promotes direct protection and limits transmission. This study aimed to explore influenza vaccination coverage among children in Australian general practice from 2015 to 2018, and patterns in coverage before and after the implementation of state-funded immunization programs. Data from 196,520 'active' patients (3+ consultations in two consecutive years) aged <5 years from 542 Australian general practices were included (MedicineInsight database). Logistic regression models were used to identify associations between vaccination with patient and practice characteristics. The overall vaccination coverage increased more than five times from 2015 (3.9%) to 2018 (19.6%) and varied among states. Children attending practices located in the wealthiest areas were more likely to receive the vaccine and appeared to benefit most from the funding, as the increase in coverage from 2017 to 2018 was greater among them than those attending practices in the least advantaged areas (17 vs. 11 percentage points, respectively). This relationship was not evident when analyzing the patient's socioeconomic level. In conclusion, free influenza vaccinations increase coverage in at-risk populations. Promotional campaigns may be required to maintain higher coverage and target practices located in low-income areas.

Pneumococcal vaccination uptake among patients aged 65 years or over in Australian general practice.

In Australia, pneumococcal vaccine is provided free to all adults aged ≥65 years and Indigenous people aged 15-65 years, and is subsidized for non-Indigenous adults <65 years of age with risk factors. This study aimed to explore pneumococcal vaccination uptake in older patients attending 550 Australian general practices from 2010-2017 by patient sociodemographics, presence of comorbidities and practice characteristics. Study 1: a cross-sectional analysis of 'active' patients aged ≥65 years in each year was performed to calculate annual pneumococcal vaccination uptake. Study 2: a cohort of 58,589 'every year' patients aged 60-65 years in 2010 was analyzed to identify the number of patients immunized during the study period. Logistic regression models assessed associations between vaccination, patient and practice characteristics. Annual pneumococcal vaccine uptake varied by patient's age (65-74 or ≥75 years), presence of comorbidities and regularity of practice visits (range 36% to 76%), and it declined slowly from 2011-2016 amongst all groups. Cohort analyses showed that 69% of those aged 60-65 years in 2010 had a recorded pneumococcal vaccination by 2017 (peak age of vaccination = 66 years), and vaccination was more likely among those with comorbidities, ex-smokers and frequent attenders to practices. Findings demonstrate that the NPS MedicineInsight database provides estimates of vaccination uptake consistent with past surveys, reproducible every year and at low cost. It has the advantage of additional clinical information compared to the Australian Immunization Register. Whilst vaccination uptake was adequate among 'every year' patients, interventions are needed to improve pneumococcal vaccination for all older Australians.