ABSTRACT
BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. METHODS: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. RESULTS: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. CONCLUSIONS: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.
Subject(s)
Aminophenols , Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Drug Combinations , Pseudomonas Infections , Pseudomonas aeruginosa , Quinolones , Sputum , Humans , Cystic Fibrosis/microbiology , Cystic Fibrosis/complications , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/genetics , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Aminophenols/therapeutic use , Aminophenols/pharmacology , Quinolones/therapeutic use , Quinolones/pharmacology , Sputum/microbiology , Indoles/therapeutic use , Indoles/pharmacology , Benzodioxoles/therapeutic use , Benzodioxoles/pharmacology , Adult , Female , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Male , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mutation , Persistent Infection/microbiology , Pyridines , QuinolinesABSTRACT
BACKGROUND: To improve the healthfulness of foods offered while accelerating the use of environmental sustainability practices, it is important to engage hospital food service operators in the adoption of such practices. The purpose of this study was to explore barriers, facilitators and best practices for implementing environmental sustainability standards in food service among veterans affairs (VA) hospitals in the United States. METHODS: We conducted an online survey with 14 VA hospital food service directors and then 11 qualitative interviews. The survey assessed motivations for initiating sustainability standards and included a self-rating of implementation for each of five standards: increasing plant-forward dishes, procuring and serving sustainable foods that meet organic/fair trade and other certifications, procuring and serving locally produced foods, reducing food waste and reducing energy consumption. Interviews were transcribed verbatim. Qualitative analysis, including coding of themes and subthemes, was conducted by two coders to determine barriers, facilitators and best practices for each of these five standards. Quantitative methods (counts and frequencies) were used to analyse the survey data. RESULTS: Participants had an average of 5 years of experience implementing sustainability standards. The top three motivators cited were reducing food waste, serving healthier foods and increasing efficiency or cost savings. Barriers revolved around patient preferences, contractual difficulties and costs related to reducing waste. Facilitators included taste testing new recipes that include more sustainable food options and easy access to sustainable products from the prime vendor. Best practices included making familiar dishes plant-forward and plate waste studies to prevent overproduction. CONCLUSIONS: Although there were many barriers to implementation, food service directors had solutions for overcoming challenges and implementing food service sustainability standards, which can be tested in future sustainability initiatives.
ABSTRACT
Purpose and Objectives: Although considered a promising model of practice, integrating healthy nutrition standards and practices into a large county government's contracting process with food vendors has not been widely described in empirical literature. We conducted an implementation evaluation project to address this gap. Intervention Approach: County of Los Angeles food vendors provide food or meals annually to more than 100,000 employees and millions of clients and visitors. In 2011, the County of Los Angeles Board of Supervisors adopted a policy to integrate healthy nutrition standards and practices into its requests for proposals (RFPs) and contracting process with food vendors. The policy required all contracts awarded to adhere to these new standards. Evaluation Methods: In 2011, the Los Angeles County Department of Public Health (DPH) began reviewing RFPs for food services for county departments that procured, served, or sold food. From 2011 through 2021, DPH applied a 4-pronged formative-evaluative approach to help county departments implement the Board of Supervisors policy and ensure that nutritional requirements were appropriately integrated into all RFPs for new and renewing contracts with food vendors. We focused our evaluation on understanding the process and tracking the progress of this policy intervention. Our evaluation included 13 key informant interviews, a 2-part survey, reviews of contract data, and synthesis of lessons learned. Results: Based on reviews and subsequent actions taken on more than 20 RFPs, DPH successfully assisted 7 county departments to incorporate healthy nutrition standards and practices into their food vendor contracts. Implementation of the food policy encountered several challenges, including staffing and training constraints and a limited infrastructure. An iterative approach to program improvement facilitated the process. Implications for Public Health: Although the model for integrating healthy nutrition standards and practices into a government contracting process is promising, more work is needed to make it less resource-intensive and to increase user buy-in.
Subject(s)
Diet, Healthy , Food Services , Humans , Local Government , Nutrition Policy , Surveys and QuestionnairesABSTRACT
As shown by IncuCyte Zoom imaging proliferation assays, invasive triple-negative human breast MDA-MB-231 cancer cells treated with sub-toxic doses (5.0-20â µM, 72â h) of [GaQ3 ] (Q=8-hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical change. This is the first demonstration of potential use of a metal complex in differentiation anti-cancer therapy. Additionally, a trace amount of Cu(II) (0.20â µM) added to the medium dramatically increased [GaQ3 ] cytotoxicity (IC50 ~2â µM, 72â h) due to its partial dissociation and the action of the HQ ligand as a Cu(II) ionophore, as shown with electrospray mass spectrometry and fluorescence spectroscopy assays in the medium. Hence, cytotoxicity of [GaQ3 ] is strongly linked to ligand binding of essential metal ions in the medium, for example, Cu(II). Appropriate delivery mechanisms of such complexes and their ligands could enable a powerful new triple therapeutic approach for cancer chemotherapy, including cytotoxicity against primary tumour, arrest of metastases, and activation of innate and adaptive immune responses.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , Copper/chemistry , Ligands , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Coordination Complexes/chemistry , Metals/pharmacology , Cell Proliferation , Cell Line, TumorABSTRACT
Modifications to UV irradiance for indoor housed herpetofauna can affect behavior and physiology. Low ultraviolet B (UVB) irradiance can result in vitamin D3 deficiency resulting in calcium metabolism disorders including metabolic bone disease and immune suppression. High UVB can result in skin and eye issues, which can be severe enough to cause shock and death. Using tools available for the assessment of UV light, including Ferguson zones and the UV working tool designed by the British and Irish Association of Zoos and Aquaria, we redesigned lighting in our indoor komodo dragon (Varanus komodoensis) habitat to better suit the UV requirements of this species, while studying changes in behavior and physiology. We measured serum vitamin 25-hydroxy D3 values in one male and one female komodo dragon before and after they were housed in indoor and outdoor habitats. We also measured behavior changes in our male komodo as he moved from an outdoor habitat, to an indoor habitat with changing UV irradiance. Our female komodo showed a 98% increase in vitamin D3 values after being moved outdoors, and laid her first clutch of eggs. Our male dragon's vitamin D3 remained consistent 200 days after moving inside. He did show increased activity when higher UV irradiance was available. Importantly, we found the UV lamps we used stopped producing desired UV irradiance within 3.5 months of regular use. We suggest all animal care facilities develop UV monitoring programs to research output and longevity of UVB lamps used in indoor herpetofauna habitats.
Subject(s)
Cholecalciferol , Lizards , Male , Female , Animals , Ultraviolet Rays , Animals, Zoo , Skin , Lizards/physiology , Vitamin DABSTRACT
OBJECTIVE: To assess routine application and clinical value of definitive urine drug monitoring (UDM) for drug detection, inconsistent drug use, and prescription adherence, along with a comparison to immunoassay screening (IAS). METHODS: Direct-to-definitive UDM performance was analyzed retrospectively in 5000 patient specimens. Drug findings, medication inconsistencies, and detection sensitivity were assessed, and definitive UDM versus IAS monitoring was studied. RESULTS: Definitive testing resulted in 18,793 drug findings with 28,403 positive drug and metabolite tests. Definitive testing expanded monitoring with 11,396 drug findings that would not be tested by IAS. The opioids accounted for the highest frequency of inconsistent positive drug-use findings, at 12%. Conversely, inconsistent negative drug findings, used as an index of prescription non-adherence, were determined in 1,751 of 15,409 monitored medications and included a high frequency of antidepressants and antipsychotics inconsistencies. Direct comparison of definitive UDM and IAS showed false-positives by IAS as well as a high rate of false-negatives that would be missed using current confirmation protocols. CONCLUSIONS: Results from routine application of direct-to-definitive UDM demonstrate the clinical value of drug-use identification and the objective evaluation of inconsistencies in drug misuse and medication adherence in pain management and addiction medicine practice. Without conversion to direct-to-definitive UDM, continuing use of IAS will limit the scope of drugs being tested, will result in an indeterminate rate of false negatives and will require confirmation testing to eliminate the reporting of false-positive IAS tests. The findings in this study provide evidence-based support for recommended use of a direct-to-definitive drug testing protocol.
Subject(s)
Addiction Medicine , Substance-Related Disorders , Drug Monitoring/methods , Humans , Pain Management , Retrospective Studies , Substance Abuse Detection/methods , Substance-Related Disorders/diagnosisABSTRACT
BACKGROUND: Amiodarone is a common intravenous medication and a known irritant to the vessel wall when administered peripherally. LOCAL PROBLEM: Nurses identified an increase in phlebitis associated with peripheral amiodarone leading to multiple catheter replacements and interruptions in drug therapy. Central venous access is recommended by the manufacturer but not practical for a short-term infusion based on the risk to the patient, time, and cost. METHODS: A 4-phased approach was used to identify a more suitable peripheral intravenous catheter. INTERVENTIONS: A collaborative effort between bedside nurses and the vascular access team evolved to look at alternative products for peripheral intravenous catheters. RESULTS: The extended dwell peripheral catheter decreased phlebitis from 54% to 5%. It also decreased interruptions in drug therapy and improved patient comfort and satisfaction. CONCLUSIONS: A practice change was implemented utilizing extended dwell peripheral catheters for intravenous amiodarone and disseminated to other units.
Subject(s)
Amiodarone , Catheterization, Peripheral , Phlebitis , Amiodarone/adverse effects , Humans , Infusions, Intravenous , Patient Safety , Phlebitis/chemically induced , Phlebitis/prevention & controlABSTRACT
Background and Objectives: Rowing is a sport that involves constant gripping, pulling/pushing, and rotational movements of the hands, in a cyclic periodic manner with every stroke, with hundreds of strokes being taken within a short period of time. Dermatological issues on rowers' hands (fingers and palms) in the form of blisters and calluses are common knowledge within the community, but their prevalence and the rower's perceptions and pain tolerance to them has never been systematically evaluated. This work addresses these lacunae. Materials and Methods: Analysis of data collected from a survey on a sample of competitive (117) and noncompetitive rowers (28) who row on-water (total 145). Results: It was found that approximately 69% of rowers participating in this study have calluses on their hands for most of their time (considered by them as not painful). The incidence of blisters was found to be lower (but perceived as more painful). Their incidence was found to be fairly independent of the frequency and intensity of training, but they seem to affect most rowers equally at the beginning of season or during a change of position (nonconditioned hands). Blisters and calluses were reported to be mainly located on the proximal phalanges and metacarpo-phalangeal joint area of both hands, i.e., on the lower parts of the fingers and the upper inner palms. Conclusions: Rowers demonstrated a sense of acceptance of these dermatological issues, even a sense of pride in what they represent. The incidence of blisters becoming infected was estimated to be so low that most rowers would not have encountered such serious, albeit rare, consequences.
Subject(s)
Sports , Water Sports , Blister/epidemiology , Blister/etiology , Humans , Pain/epidemiology , Pain/etiology , PrevalenceABSTRACT
BACKGROUND: The 2013 update of the Infection Prevention and Control (IP&C) Guideline outlined recommendations to prevent the spread of CF respiratory pathogens. We aimed to investigate the current infection control practices used in Australian and New Zealand (NZ) CF centers. METHODS: Two online surveys were distributed to Australian and NZ CF centers regarding the uptake of selected IP&C recommendations. One survey was distributed to all the Medical Directors and Lead CF Nurses and the second survey was distributed to all the Lead CF Physiotherapists. RESULTS: The response rate was 60% (60/100) for medical/nursing and 58% (14/24) for physiotherapy. Over 90% (55/60) of CF centers followed CF-specific infection control guidelines and consistent infection control practices were seen in most CF centers; 76% (41/54) had implemented segregation strategies for ambulatory care and no CF centers housed people with CF in shared inpatient accommodation. However, the application of contact precautions (wearing gloves and apron/gown) by healthcare professionals when reviewing a CF person was variable between CF center respondents but was most often used when seeing CF persons with MRSA infection in both ambulatory care and hospital admission (20/50, 40% and 42/45, 93% of CF centers, respectively). Mask wearing by people with CF was implemented into 61% (36/59) of centers. Hospital rooms were cleaned daily in 79% (37/47) of CF centers and the ambulatory care consult rooms were always cleaned between consults (49/49, 100%) and at the end of the clinic session (51/51, 100%); however the staff member tasked with cleaning changed with 37% (18/49) of CF centers responding that CF multidisciplinary team (MDT) members cleaned between patients whereas at the end of the clinic session, only 12% (6/51) of the CF MDT cleaned the consult room. CONCLUSIONS: Overall, Australian and NZ CF centers have adopted many recommendations from the IP&C. Although, the application of contact precautions was inconsistent and had overall a low level of adoption in CF centers. In ~ 25% of centers, mixed waiting areas occurred in the ambulatory care. Given the variability of responses, additional work is required to achieve greater consistency between centers.
Subject(s)
Ambulatory Care , Cystic Fibrosis/therapy , Disinfection , Hospitalization , Infection Control/methods , Personal Protective Equipment , Australia , Guideline Adherence , Humans , Infection Control/standards , Masks , Methicillin-Resistant Staphylococcus aureus , New Zealand , Nurse Administrators , Organizational Policy , Patient Isolation , Patients' Rooms , Physical Therapists , Physician Executives , Physicians' Offices , Respiratory Protective Devices , Staphylococcal Infections/prevention & control , Surveys and QuestionnairesABSTRACT
The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non-Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.
Subject(s)
Cystic Fibrosis/microbiology , Gram-Negative Bacterial Infections/transmission , Staphylococcal Infections/transmission , Staphylococcus aureus/growth & development , Achromobacter/isolation & purification , Adult , Aerosols , Burkholderia/isolation & purification , Colony Count, Microbial , Cough/microbiology , Cross-Sectional Studies , Female , Gram-Negative Bacterial Infections/microbiology , Humans , Male , Pseudomonas Infections/transmission , Pseudomonas aeruginosa/growth & development , Sputum/microbiology , Staphylococcus aureus/isolation & purification , Stenotrophomonas maltophilia/isolation & purification , Time Factors , Young AdultABSTRACT
BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts. METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness. RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified. CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.
Subject(s)
Aerosols , Bronchiectasis/complications , Cough/microbiology , Pseudomonas Infections/complications , Pseudomonas aeruginosa , Pulmonary Disease, Chronic Obstructive/complications , Aged , Colony Count, Microbial , Cough/etiology , Female , Genotype , Humans , Male , Middle Aged , Phylogeny , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Sputum/microbiologyABSTRACT
RATIONALE: People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimize pathogen transmission between patients with CF. OBJECTIVES: To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolized during coughing. METHODS: Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Cascade Impactor was used to sample the aerosol at 2 meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed, and participants rated the mask comfort levels during the cough maneuvers. MEASUREMENTS AND MAIN RESULTS: During uncovered coughing (reference maneuver), 19 of 25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (measured as cfu/ml) and aerosol P. aeruginosa colony-forming units. There was a reduction in aerosol P. aeruginosa load during coughing with a surgical mask, coughing with an N95 mask, and cough etiquette compared with uncovered coughing (P < 0.001). A similar reduction in total colony-forming units was observed for both masks during coughing; yet, participants rated the surgical masks as more comfortable (P = 0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary coughing. Talking was a low viable aerosol-producing activity. CONCLUSIONS: Face masks reduce cough-generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.
Subject(s)
Cough/microbiology , Cystic Fibrosis/microbiology , Inhalation Exposure/prevention & control , Masks , Pseudomonas Infections/prevention & control , Pseudomonas aeruginosa/isolation & purification , Adult , Australia , Cohort Studies , Disease Transmission, Infectious/prevention & control , Female , Humans , Male , Pseudomonas Infections/transmission , Reference ValuesABSTRACT
PURPOSE: Expanded genetic carrier screening (ECS) is an important part of gynecological practice and preconception planning. We evaluated the awareness and attitudes among women regarding ECS and factors that may influence decision-making in a family planning context. METHODS: A 32-question survey in an academic university practice was given to 521 women who were either currently pregnant (n = 108), undergoing gynecologic care who were considering future fertility (n = 308), and considering or receiving fertility treatment (n = 105). Data are reported descriptively. RESULTS: Forty-seven percent (n = 246) of patients were aware of ECS. Though most reported feeling positive or neutral towards ECS, 51% (n = 263) reported no desire for testing. Fifty-eight percent (n = 303) felt it beneficial to know their carrier status, and 55% (n = 257) said it was their responsibility to undergo testing. Those considering future fertility were found to have a more positive attitude towards ECS (51.4%) than those considering or receiving fertility treatment (34%). For positive carriers of a genetic disorder, 228 (49%) of patients would proceed with having their partner screened, 58 (13%) would undergo prenatal screening only and 12 (2.6%) would continue with vitro fertilization (IVF). Related to cost for ECS, 53.5% (n = 191) would be willing to pay at least $50-100 for testing, while 29% (n = 146) would not pay anything out of pocket. CONCLUSIONS: Despite patients' beliefs that it would be beneficial and their responsibility to undergo carrier status testing, the majority reported no desire for ECS and many were unwilling to pay out of pocket. Further education is necessary to reconcile the gap between technology and patient decision-making.
Subject(s)
Genetic Carrier Screening/methods , Genetic Counseling/methods , Infertility/genetics , Prenatal Diagnosis/methods , Adolescent , Adult , Decision Making , Female , Fertilization in Vitro , Health Knowledge, Attitudes, Practice , Heterozygote , Humans , Infertility/diagnosis , Infertility/physiopathology , Male , Physicians , Pregnancy , Prospective Studies , Young AdultABSTRACT
Although there are no effective disease-modifying therapies for mitochondrial diseases, an increasing number of trials are being conducted in this rare disease group. The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments. There is no consensus on which outcome measures to use in children with mitochondrial disease. The aims of this two-day Delphi-based workshop were to (i) define the protocol for an international, multi-centre natural history study in children with mitochondrial myopathy and (ii) to select appropriate outcome measures for a validation study in children with mitochondrial encephalopathy. We suggest two sets of outcome measures for a natural history study in children with mitochondrial myopathy and for a proposed validation study in children with mitochondrial encephalopathy.
Subject(s)
Delphi Technique , Mitochondrial Encephalomyopathies/therapy , Mitochondrial Myopathies/therapy , Child , Consensus , Humans , Internationality , Multicenter Studies as Topic , Muscle Development , Treatment Outcome , Validation Studies as TopicABSTRACT
In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.
Subject(s)
Cross Infection , Cystic Fibrosis , Workplace , Adult , Australia , Cross Infection/classification , Cross Infection/complications , Cross Infection/epidemiology , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Female , Health Personnel/statistics & numerical data , Humans , Male , Needs Assessment , New Zealand/epidemiology , Patient Care TeamABSTRACT
Large flying foxes (Pteropus vampyrus) are a socially complex species. In situ colonies typically comprise thousands of individuals in small harems of one male to many females. In ex situ environments, all-male colonies are becoming more common due to a surplus of males in the population. There is limited information describing the hormonal and behavioral patterns of all-male colonies during the breeding season. We assessed seasonal changes in hormones and behavior in an all-male colony of 12 large flying foxes at Disney's Animal Kingdom® . We validated hormone assays using morning urine and fecal samples to assess seasonal changes in excreted immunoreactive testosterone and glucocorticoid metabolites. We collected behavior data using an all-occurrence method, recording agonistic behaviors related to territorial defense (hooking, biting, wing flexing, vocalizing, and wrestling), and sexual behavior (mounting and frontal grabbing). Results indicated that (i) we could reliably measure testosterone and glucocorticoid metabolites concentrations from fecal and urine samples collected from individual bats; (ii) there were distinct relationships between changes in levels of agonism and hormone concentrations throughout the year; and (iii) three agonistic behaviors (chasing, wrestling, and open-mouth threat) peaked prior to the increase in testosterone and glucocorticoid hormones measured during the breeding season. These three behaviors could potentially be used as early indicators to signal the onset of the breeding season and allow time to implement ex situ management changes to reduce the incidence of agonism between individuals.
ABSTRACT
The lineage relationships of fetal adrenal cells and adrenal capsular cells to the differentiated adrenal cortex are not fully understood. Existing data support a role for each cell type as a progenitor for cells of the adult cortex. This report reveals that subsets of capsular cells are descendants of fetal adrenocortical cells that once expressed Nr5a1. These fetal adrenocortical cell descendants within the adrenal capsule express Gli1, a known marker of progenitors of steroidogenic adrenal cells. The capsule is also populated by cells that express Tcf21, a known inhibitor of Nr5a1 gene expression. We demonstrate that Tcf21-expressing cells give rise to Nr5a1-expressing cells but only before capsular formation. After the capsule has formed, capsular Tcf21-expressing cells give rise only to non-steroidogenic stromal adrenocortical cells, which also express collagen 1a1, desmin and platelet-derived growth factor (alpha polypeptide) but not Nr5a1. These observations integrate prior observations that define two separate origins of adult adrenocortical steroidogenic cells (fetal adrenal cortex and/or the adrenal capsule). Thus, these observations predict a unique temporal and/or spatial role of adult cortical cells that arise directly from either fetal cortical cells or from fetal cortex-derived capsular cells. Last, the data uncover the mechanism by which two populations of fetal cells (fetal cortex derived Gli1-expressing cells and mesenchymal Tcf21-expressing mesenchymal cells) participate in the establishment of the homeostatic capsular progenitor cell niche of the adult cortex.
Subject(s)
Adrenal Cortex/cytology , Adrenal Cortex/embryology , Cell Lineage , Fetus/cytology , Stem Cells/cytology , Steroids/metabolism , Aging/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Homeostasis , Mice , Models, Biological , Steroidogenic Factor 1/metabolism , Stromal Cells , Transcription Factors/metabolism , Zinc Finger Protein GLI1ABSTRACT
Erythropoietin (EPO), used to treat anemia in cancer patients, has been reported to accelerate tumor progression and increase mortality. Research of the mechanism for this effect has focused upon EPOR expression by tumor cells. We model the high macrophage to lymphocyte ratio found in tumor microenvironments (TMEs) by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to T cell ratio. Following TCR ligation, C57BL/6J PerC T cell proliferation is suppressed due to IFNγ-triggered inducible nitric oxide synthase (iNOS) expression. EPO was tested in the PerC culture model and found to increase T cell suppression. This effect could be abrogated by inhibiting iNOS by enzyme inhibition, genetic ablation, or blocking IFNγ signaling. Flow cytometry revealed the EPOR on CD11b(+)F4/80(+) macrophages. These results suggest that EPO could increase T cell suppression in the TME by acting directly on macrophages.
Subject(s)
Erythropoietin/metabolism , Macrophages/immunology , Peritoneal Cavity/pathology , Receptors, Erythropoietin/metabolism , T-Lymphocytes/immunology , Animals , CD11b Antigen , Cell Proliferation , Cells, Cultured , Female , Humans , Immune Tolerance , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Receptors, Interferon/genetics , Receptors, Interferon/metabolism , Tumor Microenvironment , Interferon gamma ReceptorABSTRACT
Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.
Subject(s)
Cystic Fibrosis/therapy , Patient Compliance/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Physical Therapy Modalities , Australia/epidemiology , Consensus , Cystic Fibrosis/epidemiology , Cystic Fibrosis/physiopathology , Exercise , Guideline Adherence , Health Knowledge, Attitudes, Practice , Humans , Mucociliary Clearance , New Zealand/epidemiology , Noninvasive Ventilation , Practice Guidelines as Topic , Quality of Life , Respiratory Function Tests , Respiratory Therapy , Treatment OutcomeABSTRACT
BACKGROUND: People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf). METHODS: Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001-2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf. RESULTS: A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P <0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 - 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf. CONCLUSIONS: The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions.