Healthy people, healthy places : incorporating a health focus into the practice of planning

textA significant number of studies have identified clear links between chronic health issues, including asthma, obesity, and diabetes, and the design of the built environment. As shapers of the built environment, urban planners can play a central role in ameliorating these current health epidemics. Indeed, during the early history of the planning profession the fields of planning and public health were closely connected, and improved public health was seen as a key mission of the planning profession. Today, however, public health issues are not a central concern in planning, neither as a normative value of the field nor as a core element of daily planning practice. Instead, health is a value-based cause taken up by concerned practicing planners, who face numerous challenges in incorporating a health focus into their daily work. This research argues that there is a need for a focus on health outcomes within the planning field, based on the initial mission of planning discipline and current research showing the impact of the built environment on public health. Through a nationwide survey of planners and interviews with planning and health professionals in five cities, findings show that collaboration between health and planning departments is key to instilling a health focus within the practice of planning. Planners who seek to promote a health focus in planning are pursuing this value-based imperative through a variety of ad-hoc strategies, since existing regulations and professional guidelines are inadequate in terms of facilitating collaboration between public health and planning in order to systematically address health issues related to land use and the built environment. Research also shows that collaboration between planning and public health departments, when this does occur, is often initiated and driven by processionals in the public health discipline. Though planners and health professionals who have sought to collaborate have faced institutional, political, and awareness challenges, there are opportunities that can be leveraged to overcome these obstacles. These opportunities include the professional expertise available in the public health field, the availability of health data in order to reframe planning issues, and the potential of individual champions of health to drive health considerations in planning projects, and promote health as a normative value. Ultimately, individual planners who see the creation of healthier communities as central to their professional practice pursue collaborative strategies with health professionals despite the challenges they face. From the perspective of collaborative planning theory and theories of institutional change, this individual engagement and initiative by planners through their everyday practice has the potential to effect institutional change by forging a focus on health as a normative value central to the planning discipline.Community and Regional Plannin

Chronic renal failure as predictive factor for acute elevation of systolic blood pressure after fluorescein angiography in patients with retinal diseases

Purpose: To investigate the influence of fluorescein angiography (FA) on blood pressure (BP) in patients with retinal diseases, and analyze the predictive factors for acute elevation of systolic BP after FA. Design: and Methods: A prospective study was conducted with 636 patients undergoing FA between April 2021 and October 2021. BP and pulse were measured in each patient before and 20 min after FA. The baseline characteristics of patients who developed an acute elevation in systolic BP (>10 mmHg) were compared with those of the remaining patients to detect factors that may predict this acute elevation. Results: Overall, mean systolic BP changed from 142 ± 17 mmHg to 140 ± 20 mmHg after 20 min (p = 0.1). Mean diastolic BP changed from 79 ± 15 mmHg to 78 ± 13 mmHg after 20 min (p = 0.45). Mean pulse rate changed from 73 ± 14 bpm to 70 ± 12 bpm after 20 min (p = 0.001). 103 patients (16 %) had acute elevation of systolic BP (>10 mmHg). Mean systolic BP changed from 143 ± 17 mmHg to 162 ± 19 mmHg after 20 min in this group (p = 0.001). Patients in this group were significantly older compared to the rest (73 ± 12 vs 67 ± 15, p = 0.001). The rate of chronic renal failure was significantly higher in this group compared to the rest of the patients (42/7.8 % vs 15/14.6 %, p = 0.01). Conclusions: This study demonstrated that fluorescein angiography is a relatively safe procedure with regards to blood pressure changes. However, chronic renal failure could be considered as predictive factor for acute elevation of systolic blood pressure after this procedure

Heterogeneous antimicrobial activity in broncho-alveolar aspirates from mechanically ventilated intensive care unit patients

Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pus and fluid. Although ventilated patients are at risk, not all ventilated patients develop pneumonia. This suggests that the sputum environment may possess antimicrobial activities. Despite the generally acknowledged importance of antimicrobial activity in protecting the human lung against infections, this has not been systematically assessed to date. Therefore, the objective of the present study was to measure antimicrobial activity in broncho-alveolar aspirate ('sputum") samples from patients in an intensive care unit (ICU) and to correlate the detected antimicrobial activity with antibiotic levels, the sputum microbiome, and the respective patients' characteristics. To this end, clinical metadata and sputum were collected from 53 mechanically ventilated ICU patients. The antimicrobial activity of sputum samples was tested against Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus anginosus. Here we show that sputa collected from different patients presented a high degree of variation in antimicrobial activity, which can be partially attributed to antibiotic therapy. The sputum microbiome, although potentially capable of producing antimicrobial agents, seemed to contribute in a minor way, if any, to the antimicrobial activity of sputum. Remarkably, despite its potentially protective effect, the level of antimicrobial activity in the investigated sputa correlated inversely with patient outcome, most likely because disease severity outweighed the beneficial antimicrobial activities.</p

A phase II study of palbociclib plus letrozole plus trastuzumab as neoadjuvant treatment for clinical stages II and III ER+ HER2+ breast cancer (PALTAN)

Patients with ER+/HER2+ breast cancer (BC) are less likely to achieve pathological complete response (pCR) after chemotherapy with dual HER2 blockade than ER-/HER2+ BC. Endocrine therapy plus trastuzumab is effective in advanced ER+/HER2+ BC. Inhibition of CDK4/6 and HER2 results in synergistic cell proliferation reduction. We combined palbociclib, letrozole, and trastuzumab (PLT) as a chemotherapy-sparing regimen. We evaluated neoadjuvant PLT in early ER+/HER2+ BC. Primary endpoint was pCR after 16 weeks. Research biopsies were performed for whole exome and RNA sequencing, PAM50 subtyping, and Ki67 assessment for complete cell cycle arrest (CCCA: Ki67 ≤ 2.7%). After 26 patients, accrual stopped due to futility. pCR (residual cancer burden-RCB 0) was 7.7%, RCB 0/I was 38.5%. Grade (G) 3/4 treatment-emergent adverse events occurred in 19. Among these, G3/4 neutropenia was 50%, hypertension 26.9%, and leucopenia 7.7%. Analysis indicated CCCA in 85% at C1 day 15 (C1D15), compared to 27% at surgery after palbociclib was discontinued. Baseline PAM50 subtyping identified 31.2% HER2-E, 43.8% Luminal B, and 25% Luminal A. 161 genes were differentially expressed comparing C1D15 to baseline. MKI67, TK1, CCNB1, AURKB, and PLK1 were among the genes downregulated, consistent with CCCA at C1D15. Molecular Signatures Database gene-sets analyses demonstrated downregulated processes involved in proliferation, ER and mTORC1 signaling, and DNA damage repair at C1D15, consistent with the study drug\u27s mechanisms of action. Neoadjuvant PLT showed a pCR of 7.7% and an RCB 0/I rate of 38.5%. RNA sequencing and Ki67 data indicated potent anti-proliferative effects of study treatments. ClinicalTrials.gov- NCT02907918

Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy

Acknowledgements The authors are grateful to Nils Lindstrom and members of the Gillingwater laboratory for advice and assistance with this study and helpful comments on the manuscript; Neil Cashman for the NSC-34 cell line; and Ji-Long Liu for the DrosophilasmnA and smnB lines. This work was supported by grants from the SMA Trust (to T.H. Gillingwater, P.J. Young, and R. Morse), BDF Newlife (to T.H. Gillingwater and S.H. Parson), the Anatomical Society (to T.H. Gillingwater and S.H. Parson), the Muscular Dystrophy Campaign (to T.H. Gillingwater), the Jennifer Trust for Spinal Muscular Atrophy (to H.R. Fuller), the Muscular Dystrophy Association (to G.E. Morris), the Vandervell Foundation (to P.J. Young), the Medical Research Council (GO82208 to I.M. Robinson), Roslin Institute Strategic Grant funding from the BBSRC (to T.M. Wishart), the BBSRC (to C.G. Becker), the Deutsche Forschungsgemeinschaft and EU FP7/2007-2013 (grant no. 2012-305121, NeurOmics, to B. Wirth), the Center for Molecular Medicine Cologne (to B. Wirth and M. Hammerschmidt), and SMA Europe (to M.M. Reissland). We would also like to acknowledge financial support to the Gillingwater lab generated through donations to the SMASHSMA campaign.Peer reviewedPublisher PD

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A regulatory pathway involving retinoic acid and calcineurin demarcates and maintains joint cells and osteoblasts in regenerating fin

During zebrafish fin regeneration, blastema cells lining the epidermis differentiate into osteoblasts and joint cells to reconstruct the segmented bony rays. We show that osteoblasts and joint cells originate from a common cell lineage, but are committed to different cell fates. Pre-osteoblasts expressing runx2a/b commit to the osteoblast lineage upon expressing sp7, whereas the strong upregulation of hoxa13a correlates with a commitment to a joint cell type. In the distal regenerate, hoxa13a, evx1 and pthlha are sequentially upregulated at regular intervals to define the newly identified presumptive joint cells. Presumptive joint cells mature into joint-forming cells, a distinct cell cluster that maintains the expression of these factors. Analysis of evx1 null mutants reveals that evx1 is acting upstream of pthlha and downstream of or in parallel with hoxa13a. Calcineurin activity, potentially through the inhibition of retinoic acid signaling, regulates evx1, pthlha and hoxa13a expression during joint formation. Furthermore, retinoic acid treatment induces osteoblast differentiation in mature joint cells, leading to ectopic bone deposition in joint regions. Overall, our data reveal a novel regulatory pathway essential for joint formation in the regenerating fin

Chronic renal failure as predictive factor for acute elevation of systolic blood pressure after fluorescein angiography in patients with retinal diseases

Purpose: To investigate the influence of fluorescein angiography (FA) on blood pressure (BP) in patients with retinal diseases, and analyze the predictive factors for acute elevation of systolic BP after FA. Design: and Methods: A prospective study was conducted with 636 patients undergoing FA between April 2021 and October 2021. BP and pulse were measured in each patient before and 20 min after FA. The baseline characteristics of patients who developed an acute elevation in systolic BP (>10 mmHg) were compared with those of the remaining patients to detect factors that may predict this acute elevation. Results: Overall, mean systolic BP changed from 142 ± 17 mmHg to 140 ± 20 mmHg after 20 min (p = 0.1). Mean diastolic BP changed from 79 ± 15 mmHg to 78 ± 13 mmHg after 20 min (p = 0.45). Mean pulse rate changed from 73 ± 14 bpm to 70 ± 12 bpm after 20 min (p = 0.001). 103 patients (16 %) had acute elevation of systolic BP (>10 mmHg). Mean systolic BP changed from 143 ± 17 mmHg to 162 ± 19 mmHg after 20 min in this group (p = 0.001). Patients in this group were significantly older compared to the rest (73 ± 12 vs 67 ± 15, p = 0.001). The rate of chronic renal failure was significantly higher in this group compared to the rest of the patients (42/7.8 % vs 15/14.6 %, p = 0.01). Conclusions: This study demonstrated that fluorescein angiography is a relatively safe procedure with regards to blood pressure changes. However, chronic renal failure could be considered as predictive factor for acute elevation of systolic blood pressure after this procedure

Pré-fragilidade em idosos e a habilitação para direção de veículos automotores

Objective: to investigate the association between the condition of physical pre-frailty in elderly people and the final results of the driver license test for motor vehicles. Methods: cross-sectional study carried out with 347 elderly who underwent driver license tests. A questionnaire and tests were applied, and information on the result of the driver license test was collected. A descriptive statistical analysis and a non-parametric test were performed. Results: 163 (47.0%) were found to be pre-frail, 71 (43.6%) had reduced hand grip strength, 65 (39.9%) had reduced level of physical activity and 62 (38.0%), reduced gait speed. The result of the driver test indicated 115 (70.6%) pre-frail elderly to be able to drive with restriction. Pre-frailty was not associated with the results of the driver license test (p=0.744). Conclusion: although the pre-frail condition was frequent, there was no significant association with the result of the driver test