Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification.

BACKGROUND: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. RESULTS: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. CONCLUSIONS: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

The PAPHIO study protocol: a randomised controlled trial with a 2 x 2 crossover design of physical activity adherence, psychological health and immunological outcomes in breast cancer survivors.

BACKGROUND: The PAPHIO study; a randomized controlled trial with 2X2 crossover design will implement a self-directed physical activity program in which participants will engage in self-monitoring and receive motivational interviewing to enhance physical activity adherence. The study aims to determine the effects of 24 weeks self-directed activity combined with motivational interviewing (MI) on (i) psychological health, (ii) quality of life (QoL) and (iii) immune function in female breast cancer survivors. METHODS: The study will recruit 64 female breast cancer survivors within 3 years of diagnosis and at least 6 months post primary treatments at Western Health Sunshine Hospital, Melbourne, Australia. They will be randomly allocated to immediate intervention (IIG group) or delayed intervention groups (DIG group) in a 1:1 ratio. All participants will be given a wearable device (Fitbit Alta HR) and undertake self-directed physical activity for 24 weeks and will receive MI for 12 weeks (IIG; during week 0 to week 12 and DIG; during week 13 to week 24). Participants' daily step count and the changes of immune cell functionality will be assessed at the beginning (week 1: T1), week 12 (T2) and week 24 (T3) of the program. Physical activity adherence will be assessed at T2 and T3. Participants will also complete four questionnaires assessing exercise self-regulation (BREQ2), exercise barrier and task self-efficacy, mental health (DASS-21) and QoL (FACT-B) at three time points (T1 to T3). Linear-mixed models will be used to assess the relationship between physical activity volume by step counting and mental health (DASS-21), QoL (FACT-B), immune biomarkers, self-regulation (BREQ2) and self-efficacy at T1, T2 and T3;between 2 groups. DISCUSSION: We expect this physical activity intervention to be acceptable and beneficial to the participants in terms of psychological and immunological well-being with the potential outcomes to be implemented more widely at relatively low cost to these or other patient populations. TRIAL REGISTRATION: Australian New Zealand Clinical trials Registry- ACTRN12619001271190. Prospectively registered on 13 September 2019.

Intimate Partner Violence Experiences Among Men Living with HIV in Rural Appalachia.

There has been limited study of the syndemic link between HIV and intimate partner violence (IPV) among rural populations in the United States. We utilized the Revised Conflict Tactics Scale-2 to examine the past year prevalence, type (psychological aggression, physical assault, and sexual assault), and the impact of IPV on HIV clinical outcomes among men living with HIV in rural Appalachia. Approximately 39% of participants experienced some type of IPV in the preceding year, with 67% of those individuals experiencing more than 1 type of IPV. Approximately 77% of participants endorsing IPV exposure experienced psychological aggression. Most participants exposed to psychological aggression (70%) and/or physical assault (57%) were both victims and perpetrators, and those experiencing sexual assault reported being exclusively victims (65%). There were no significant differences in clinical outcomes including viral load and CD4 count, which may be secondary to small sample size derived from a clinic population with a high rate of virologic suppression (94%). This study demonstrates the need to assess IPV exposure in men living with HIV and further highlights the intricacies of relationship violence in these individuals.

Vertebral osteomyelitis due to Candida species.

OBJECTIVE: We have noted an increased number of cases of vertebral osteomyelitis secondary to Candida species over the past few years at our facility. Our aim was to identify and review these cases to elucidate risk factors, treatment regimens and outcomes. METHODS: We performed a retrospective chart review using our electronic medical record and microbiology laboratory database to identify cases of vertebral osteomyelitis due to Candida at a single teaching hospital from 2006-2018. RESULTS: We found 15 cases of Candida vertebral osteomyelitis. The majority of cases were due to Candida albicans and affected either the lumbar or the thoracic spine. Injection drug use and previous spine surgery were the two most common risk factors identified. Treatment was largely with intravenous antifungal induction followed by prolonged therapy with oral fluconazole. There was no short-term mortality though we lacked long-term follow-up on most patients. CONCLUSIONS: The number of vertebral infections due to Candida may be increasing. This may be partially driven by both a rise in intravenous drug use as well as the growing rate of spine surgery. Management following currently available guidelines seems favorable, though further studies are necessary to determine the optimal treatment regimen.

Barriers to using new needles encountered by rural Appalachian people who inject drugs: implications for needle exchange.

BACKGROUND: Using a new needle for every injection can reduce the spread of infectious disease among people who inject drugs (PWID). No previous study has examined new needle use barriers among PWIDs residing in the rural Appalachian part of the United States, an area currently in the midst of a heroin epidemic. OBJECTIVE: Therefore, our primary aim was to explore self-reported barriers to using a new needle by PWID attending a needle exchange program (NEP). METHODS: We conducted a cross-sectional survey of PWID attending two NEPs in rural West Virginia located in the heart of Central Appalachia. A convenience sample of PWID (n = 100) completed the Barriers to Using New Needles Questionnaire. RESULTS: The median number of barriers reported was 5 (range 0-19). Fear of arrest by police (72% of PWID "agreed" or "strongly agreed") and difficulty with purchasing needles from a pharmacy (64% "agreed" or "strongly agreed") were the most frequently cited barriers. CONCLUSIONS/IMPORTANCE: Congruent with previous findings from urban locations, in rural West Virginia, the ability of PWID to use a new needle obtained from a needle exchange for every injection may be compromised by fear of arrest. In addition, pharmacy sales of new needles to PWID may be blunted by an absence of explicit laws mandating nonprescription sales. Future studies should explore interventions that align the public health goals of NEPs with the occupational safety of law enforcement and health outreach goals of pharmacists.

Needle exchange programs for the prevention of hepatitis C virus infection in people who inject drugs: a systematic review with meta-analysis.

BACKGROUND: Previous research on the effectiveness of needle exchange programs (NEP) in preventing hepatitis C virus (HCV) in people who inject drugs (PWID) has shown mixed findings. The purpose of this study was to use the meta-analytic approach to examine the association between NEP use and HCV prevention in PWIDs. METHODS: Study inclusion criteria were (1) observational studies, (2) PWIDs, (3) NEP use, (4) HCV status ascertained by serological testing, (5) studies published in any language since January 1, 1989, and (6) data available for measures of association. Studies were located by searching four electronic databases and cross-referencing. Study quality was assessed using the Newcastle Ottawa (NOS) scale. A ratio measure of association was calculated for each result from cohort or case-control studies and pooled using a random effects model. Odds ratio (OR) and hazard ratio (HR) models were analyzed separately. Results were considered statistically significant if the 95% confidence interval (CI) did not cross 1. Heterogeneity was estimated using Q and I 2 with alpha values for Q ≤ 0.10 considered statistically significant. RESULTS: Of the 555 citations reviewed, 6 studies containing 2437 participants were included. Studies had an average NOS score of 7 out of 9 (77.8%) stars. Concerns over participant representativeness, unclear adjustments for confounders, and bias from participant nonresponse and loss to follow-up were noted. Results were mixed with the odds ratio model indicating no consistent association (OR, 0.51, 95% CI, 0.05-5.15), and the hazard ratio model indicating a harmful effect (HR, 2.05, 95% CI, 1.39-3.03). Substantial heterogeneity (p ≤ 0.10) and moderate to large inconsistency (I 2 ≥ 66%) were observed for both models. CONCLUSIONS: The impact of NEPs on HCV prevention in PWIDs remains unclear. There is a need for well-designed research studies employing standardized criteria and measurements to clarify this issue. TRIAL REGISTRATION: PROSPERO CRD42016035315.

Lyme Disease in West Virginia: An Assessment of Distribution and Clinicians' Knowledge of Disease and Surveillance.

Lyme disease case misclassification, a top public health concern, may be attributed to the current disconnect between clinical diagnosis and surveillance. This study examines Lyme disease distribution in West Virginia (WV) and determines clinicians' knowledge of both disease and surveillance. Lyme disease surveillance data for 2013 were obtained from the WV Bureau for Public Health. A validated survey, distributed to clinicians at an academic medical center, assessed clinicians' knowledge of disease diagnosis and surveillance. There were 297 adult Lyme disease cases of which 83 were confirmed. Clinician survey responses resulted in a correct response rate of 70% for Lyme disease knowledge questions. Fewer than half of all clinicians were aware of the surveillance criteria for confirming Lyme disease cases. Neither medical specialty nor previous treatment of patients with Lyme disease were significantly associated with clinicians' knowledge of the disease. Clinicians in WV are familiar with symptoms and clinical management of Lyme disease. However, they are less knowledgeable about diagnosis and public health surveillance comprising reporting and confirming cases of the disease. Clinicians and public health authorities should collaborate more closely to promote education and awareness as a key step to successfully reducing the burden of Lymne disease.

Cat scratch disease of the eye: a case report and literature review.

This is the case of a middle-aged male with no other medical issues who presented with acute, unilateral visual disturbance. In lieu of specific ophthalmologic findings, his age and presentation, he was treated for presumed inflammatory process. It was only after steroids and the results of serological testing that an infectious agent was determined. He was eventually diagnosed with ocular Bartonellosis. He was treated with oral doxycycline and rifampin and slowly improved. The thesis of this case report is that a thorough history prior to rapid and somewhat presumptive treatment may have prevented unnecessary immunosuppression and delay in appropriate antimicrobial therapy.

Mitochondria-ER contact sites expand during mitosis.

Mitochondria-ER contact sites (MERCS) are involved in energy homeostasis, redox and Ca2+ signaling, and inflammation. MERCS are heavily studied; however, little is known about their regulation during mitosis. Here, we show that MERCS expand during mitosis in three cell types using various approaches, including transmission electron microscopy, serial EM coupled to 3D reconstruction, and a split GFP MERCS marker. We further show enhanced Ca2+ transfer between the ER and mitochondria using either direct Ca2+ measurements or by quantifying the activity of Ca2+-dependent mitochondrial dehydrogenases. Collectively, our results support a lengthening of MERCS in mitosis that is associated with improved Ca2+ coupling between the two organelles. This augmented Ca2+ coupling could be important to support the increased energy needs of the cell during mitosis.

Skeletal abnormalities caused by a Connexin43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and flaring metaphyses of long bones. Many patients with CMD suffer from neurological symptoms. To date, the pathogenesis of CMD is not fully understood. Treatment is limited to decompression surgery. Here, we report a knock in (KI) mouse model for AR CMD carrying a R239Q mutation in CX43. Cx43KI/KI mice replicate many features of AR CMD in craniofacial and long bones. In contrast to Cx43+/+ littermates, Cx43KI/KI mice exhibit periosteal bone deposition and increased osteoclast (OC) numbers in the endosteum of long bones, leading to an expanded bone marrow cavity and increased cortical bone thickness. Although formation of Cx43+/+ and Cx43KI/KI resting OCs are comparable, on bone chips the actively resorbing Cx43KI/KI OCs resorb less bone. Cortical bones of Cx43KI/KI mice have an increase in degenerating osteocytes and empty lacunae. Osteocyte dendrite formation is decreased with reduced expression levels of Fgf23, Sost, Tnf-α, IL-1ß, Esr1, Esr2, and a lower Rankl/Opg ratio. Female Cx43KI/KI mice display a more severe phenotype. Sexual dimorphism in bone becomes more evident as mice age. Our data show that the CX43R239Q mutation results in mislocalization of CX43 protein and impairment of gap junction and hemichannel activity. Different from CX43 ablation mouse models, the CX43R239Q mutation leads to the AR CMD-like phenotype in Cx43KI/KI mice not only by loss-of-function but also via a not yet revealed dominant function.

Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma.

Background: The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS. Methods: Transcriptomic analysis of a murine schwannoma allograft model and immunohistochemical analysis of 17 human VS were performed. MMP9 abundance was assessed in mouse and human schwannoma cell lines. Transwell studies were performed to evaluate the effect of MMP9 on schwannoma invasion in vitro. Plasma biomarkers were identified from a multiplexed proteomic analysis in 45 prospective VS patients and validated in primary culture. The therapeutic efficacy of MMP9 inhibition was evaluated in a mouse schwannoma model. Results: MMP9 was the most highly upregulated protease in mouse schwannomas and was significantly enriched in adherent VS, particularly around tumor vasculature. High levels of MMP9 were found in plasma of patients with adherent VS. MMP9 outperformed clinical and radiographic variables to classify adherent VS with outstanding discriminatory ability. Human schwannoma cells secreted MMP9 in response to TNF-α which promoted cellular invasion and adhesion protein expression in vitro. Lastly, MMP9 inhibition decreased mouse schwannoma growth in vivo. Conclusions: We identify MMP9 as a preoperative biomarker to classify adherent VS. MMP9 may represent a new therapeutic target in adherent VS associated with poor surgical outcomes that lack other viable treatment options.

HIV/AIDS patient migration in North-Central West Virginia.

INTRODUCTION: Many HIV/AIDS patients rely on the Ryan White CARE Act, a federally-funded program to cover the costs of their medical care. The dispersal of this funding is dependent on a complex algorithm, which factors in the number of people that test positive for HIV in each state. However, demographic and migration studies have suggested that HIV/AIDS patients in rural America are first diagnosed in urban areas and then later moved to more rural areas. METHODS: The participant pool was identified from adult patients who have received care from the West Virginia University (WVU) Positive Health Clinic from January 1, 2004 to July 26, 2012 and knew the location where they had initially tested positive for HIV. RESULTS: The place of initial HIV diagnosis could be determined for 398 out of 433 patients and fewer than half (48%) were initially diagnosed in West Virginia. CONCLUSIONS: Because over half of the patients who are treated at WVU were initially tested outside of West Virginia, this could negatively impact the federal funding opportunities for our state through the Ryan White CARE Act using the current algorithm.

Quantity and size distribution of cough-generated aerosol particles produced by influenza patients during and after illness.

The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza. In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 µm. Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143). When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6). The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042). The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308,600 particles/cough after recovery. When the subjects had influenza, an average of 63% of each subject's cough aerosol particle volume in the detection range was in the respirable size fraction (SD 22%), indicating that these particles could reach the alveolar region of the lungs if inhaled by another person. This enhancement in aerosol generation during illness may play an important role in influenza transmission and suggests that a better understanding of this phenomenon is needed to predict the production and dissemination of influenza-laden aerosols by people infected with this virus. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a PDF file of demographic information, influenza test results, and volume and peak flow rate during each cough and a PDF file containing number and size of aerosol particles produced.].

Ocular manifestations and full house membranous nephropathy as a rare presentation of secondary syphilis.

Syphilis is an often-overlooked diagnosis and without timely diagnosis and treatment, can have serious repercussions. Although its prevalence had decreased with the introduction of penicillin, it has had a resurgence over the years. Discerning the proper patient population to test for syphilis should be led by a patient's risk factors. Here, we present a patient diagnosed with secondary syphilis, with initial concern for a possible concomitant lupus diagnosis. He initially presented with visual symptoms and optic nerve inflammation, along with a positive antinuclear antibody (ANA). Due to an unprotected sexual encounter, there was suspicion for a sexually transmitted infection. Testing revealed reactive rapid plasma reagin (RPR) (≥1:256 titer) and reactive treponemal antibody, consistent with active syphilis. He was immediately started on intravenous Penicillin G. Lumbar puncture was consistent with a reactive venereal disease research laboratory test (VDRL). Urinalysis revealed nephrotic range proteinuria, which along with the positive ANA, prompted renal biopsy. This showed membranous nephropathy with full house staining, which is seen primarily in lupus nephritis and further confounded the diagnosis. He completed a two-week course of penicillin and steroids inpatient with clinical improvement. On follow up, his RPR improved (≥1:64 titer), and lumbar puncture showed a non-reactive VDRL. Due to the resolution of proteinuria, decrease of the ANA titer and no further positive testing or symptoms convincing for a concomitant rheumatologic disorder, the presence of lupus was collectively determined to be of low concern. and the sole diagnosis of secondary syphilis was made.

Sex Differences in Characteristics of Patients with Infective Endocarditis: A Multicenter Study.

Infectious diseases like infective endocarditis (IE) may manifest or progress differently between sexes. This study sought to identify the differences in demographic and clinical characteristics among male and female patients with IE. Data were obtained from a newly developed registry comprising all adult patients with first IE admission at the four major tertiary cardiovascular centers in West Virginia, USA during 2014−2018. Patient characteristics were compared between males and females using Chi-square test, Fisher's exact test, and Wilcoxon rank-sum test. A secondary analysis was restricted to IE patients with drug use only. Among 780 unique patients (390 males, 390 females), significantly more women (a) were younger than males (median age 34.9 vs. 41.4, p < 0.001); (b) reported drug use (77.7% vs. 64.1%, p < 0.001); (c) had tricuspid valve endocarditis (46.4% vs. 30.8%, p < 0.001); and (d) were discharged against medical advice (20% vs. 9.5%, p < 0.001). These differences persisted even within the subgroup of patients with drug use-associated IE. In a state with one of the highest incidences of drug use and overdose deaths, the significantly higher incident IE cases in younger women and higher proportion of women leaving treatment against medical advice are striking. Differential characteristics between male and female patients are important to inform strategies for specialized treatment and care.

Steep rise in drug use-associated infective endocarditis in West Virginia: Characteristics and healthcare utilization.

INTRODUCTION: Life-threatening infections such as infective endocarditis (IE) are increasing simultaneously with the injection drug use epidemic in West Virginia (WV). We utilized a newly developed, statewide database to describe epidemiologic characteristics and healthcare utilization among patients with (DU-IE) and without (non-DU-IE) drug use-associated IE in WV over five years. MATERIALS AND METHODS: This retrospective, observational study, incorporating manual review of electronic medical records, included all patients aged 18-90 years who had their first admission for IE in any of the four university-affiliated referral hospitals in WV during 2014-2018. IE was identified using ICD-10-CM codes and confirmed by chart review. Demographics, clinical characteristics, and healthcare utilization were compared between patients with DU-IE and non-DU-IE using Chi-square/Fisher's exact test or Wilcoxon rank sum test. Multivariable logistic regression analysis was conducted with discharge against medical advice/in-hospital mortality vs. discharge alive as the outcome variable and drug use as the predictor variable. RESULTS: Overall 780 unique patients had confirmed first IE admission, with a six-fold increase during study period (p = .004). Most patients (70.9%) had used drugs before hospital admission, primarily by injection. Compared to patients with non-DU-IE, patients with DU-IE were significantly younger (median age: 33.9 vs. 64.1 years; p < .001); were hospitalized longer (median: 25.5 vs. 15 days; p < .001); had a higher proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates (42.7% vs. 29.9%; p < .001), psychiatric disorders (51.2% vs. 17.3%; p < .001), cardiac surgeries (42.9% vs. 26.6%; p < .001), and discharges against medical advice (19.9% vs. 1.4%; p < .001). Multivariable regression analysis showed drug use was an independent predictor of the combined outcome of discharge against medical advice/in-hospital mortality (OR: 2.99; 95% CI: 1.67-5.64). DISCUSSION AND CONCLUSION: This multisite study reveals a 681% increase in IE admissions in WV over five years primarily attributable to injection drug use, underscoring the urgent need for both prevention efforts and specialized strategies to improve outcomes.

Chondrocytes respond both anabolically and catabolically to impact loading generally considered non-injurious.

We aimed to determine the longitudinal effects of low-energy (generally considered non-injurious) impact loading on (1) chondrocyte proliferation, (2) chondroprogenitor cell activity, and (3) EGFR signaling. In an in vitro study, we assessed 127 full-thickness, cylindrical osteochondral plugs of bovine cartilage undergoing either single, uniaxial unconfined impact loads with energy densities in the range of 1.5-3.2mJ/mm3 or no impact (controls). We quantified cell responses at two, 24, 48, and 72 h via immunohistochemical labeling of Ki67, Sox9, and pEGFR antibodies. We compared strain, stress, and impact energy density as predictors for mechanotransductive responses from cells, and fit significant correlations using linear regressions. Our study demonstrates that low-energy mechanical impacts (1.5-3.2mJ/mm3) generally stimulate time-dependent anabolic responses in the superficial zone of articular cartilage and catabolic responses in the middle and deep zones. We also found that impact energy density is the most consistent predictor of cell responses to low-energy impact loading. These spatial and temporal changes in chondrocyte behavior result directly from low-energy mechanical impacts, revealing a new level of mechanotransductive sensitivity in chondrocytes not previously appreciated.

Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic.

BACKGROUND: Considerable controversy exists with regard to whether influenza virus and respiratory syncytial virus (RSV) are spread by the inhalation of infectious airborne particles and about the importance of this route, compared with droplet or contact transmission. METHODS: Airborne particles were collected in an urgent care clinic with use of stationary and personal aerosol samplers. The amounts of airborne influenza A, influenza B, and RSV RNA were determined using real-time quantitative polymerase chain reaction. Health care workers and patients participating in the study were tested for influenza. RESULTS: Seventeen percent of the stationary samplers contained influenza A RNA, 1% contained influenza B RNA, and 32% contained RSV RNA. Nineteen percent of the personal samplers contained influenza A RNA, none contained influenza B RNA, and 38% contained RSV RNA. The number of samplers containing influenza RNA correlated well with the number and location of patients with influenza (r= 0.77). Forty-two percent of the influenza A RNA was in particles < or = 4.1 microm in aerodynamic diameter, and 9% of the RSV RNA was in particles < or = 4.1 microm. CONCLUSIONS: Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted.

Walking the boundaries: using the 6-min walk test for accurate assessment of the level of fitness in breast clinic outpatients.

BACKGROUND: Healthy levels of physical activity and improved fitness have shown better quality of life outcomes and improved survival in women with breast cancer. There is a lack of baseline data for fitness levels in breast cancer outpatients in Australia. METHODS: A single centre cross-sectional study was performed to provide a snapshot of the fitness levels of women attending the Surgical and Oncology Breast Outpatient Clinic at Western Health, Melbourne. A total of 200 women (aged 18-85 years) were surveyed and the 6-min walk test (6MWT) was performed. Single and multiple linear regression analyses were performed. RESULTS: The mean 6-min walk distance (6MWD) was 486.6 m (95% CI ±12.8 m), which was comparable with reference ranges. The mean age of participants was 47.5 years. Ninety-seven (48.5%) participants had diagnosis of breast cancer. Breast cancer diagnosis had a negative effect on 6MWD of -33.6 m walked (P = 0.010). However, multiple regression analysis showed that only age (-2.6 m walked per year older; P < 0.001), body mass index (-4.2 m walked per unit of body mass index increase; P < 0.001) and presence of comorbidities (-56.9 m walked; P < 0.001) had statistically significant negative effects on 6MWD. Self-reported exercise tolerance correlated significantly with 6MWD (walking: P < 0.001 and stairs: P = 0.014). CONCLUSION: The 6MWT was easily performed within outpatient environment to accurately assess baseline level of fitness in breast cancer clinic outpatients. This indicates that 6MWT can be used as a valuable adjunctive tool to assess the level of fitness in breast cancer patients to make therapeutic recommendations in improving breast cancer outcomes.