Coral reefs benefit from reduced land-sea impacts under ocean warming.

Coral reef ecosystems are being fundamentally restructured by local human impacts and climate-driven marine heatwaves that trigger mass coral bleaching and mortality1. Reducing local impacts can increase reef resistance to and recovery from bleaching2. However, resource managers lack clear advice on targeted actions that best support coral reefs under climate change3 and sector-based governance means most land- and sea-based management efforts remain siloed4. Here we combine surveys of reef change with a unique 20-year time series of land-sea human impacts that encompassed an unprecedented marine heatwave in Hawai'i. Reefs with increased herbivorous fish populations and reduced land-based impacts, such as wastewater pollution and urban runoff, had positive coral cover trajectories predisturbance. These reefs also experienced a modest reduction in coral mortality following severe heat stress compared to reefs with reduced fish populations and enhanced land-based impacts. Scenario modelling indicated that simultaneously reducing land-sea human impacts results in a three- to sixfold greater probability of a reef having high reef-builder cover four years postdisturbance than if either occurred in isolation. International efforts to protect 30% of Earth's land and ocean ecosystems by 2030 are underway5. Our results reveal that integrated land-sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.

How to communicate large-scale social challenges: The problem of the disappearing American corporation.

Social science has distinct advantages and challenges when it comes to communicating its findings to the public. Its topics are often highly accessible to the general public, yet its findings may be counterintuitive and politically contentious. Conveying recent changes in the organization of the American economy provides an illustration of the difficulties and opportunities for engaging the public. The declining number of public corporations in the United States is associated with a shrinking middle class, lower opportunities for upward mobility, and a fraying social safety net, with important implications for individuals and public policy. Attempting to convey this set of findings to a broad public has demonstrated that some strategies and communication channels work better than others, and that some online media are particularly effective.

Implementing and evaluating a community-based, inter-institutional, interprofessional education pilot programme.

Many health professions programmes have begun integrating interprofessional learning into their curricula; however, community-based interprofessional education (IPE) initiatives are relatively scarce. The Meharry-Vanderbilt Alliance IPE Faculty Collaborative, comprised of faculty from five institutions, developed a community-based IPE programme that allowed students to engage in meaningful interprofessional activities while exposing them to social determinants of health. Thirty students from ten professions were divided into six teams and paired with three community organisations. Each team engaged community organisation staff and clients to develop practical solutions to their priorities. Teams participated in debriefings and team-building exercises to further support interprofessional learning. Students' comfort working with others (CWO), value in working with others (VWO), and self-perceived ability (SPA) to work with others were assessed using the Interprofessional Socialisation and Valuing Scale (ISVS). Mean rank scores in all three subcategories increased significantly from baseline (CWO: z = -4.11, p < 0.0001; VWO: z = -3.41. p = 0.001; SPA: z = -2.79, p = 0.005). In addition, programme evaluations suggest the programme improved students' understanding of social determinants of health. Our findings align with those of two other community-based IPE initiatives and support the expansion of IPE efforts beyond traditional settings.

Black and Hispanic predoctoral dental students' perceptions and considerations of careers in academic dentistry.

BACKGROUND: Dental schools aim to train and support a diverse dentist workforce. Among all faculty, full-time and part-time faculty who identify as members of historically underrepresented groups are 13.9% and 8.4%, respectively. The recruitment and retention of faculty is a known challenge, with growing faculty vacancies at dental schools. This study explored dental student perceptions of academic careers, specifically focusing on Black and Hispanic predoctoral students. METHODS: From August to November 2022, we conducted focus group with second-, third-, and fourth-year predoctoral dental students who identified as Black or Hispanic using a semi-structured interview guide that was developed for this study. Data were analyzed using inductive thematic analysis. RESULTS: Four themes emerged: (1) students perceived academic dental dentistry as inclusive but not diverse spaces for Black and Hispanic people; (2) academic dental careers were perceived as secondary careers; (3) academic dental careers were perceived as a career option with a lack of autonomy and less income, compared to clinical practice in other settings; (4) students expressed a lack of knowledge about pathways to academic dental careers. Despite these challenges, students expressed interest in academic dental careers and noted being inspired by younger faculty members. CONCLUSION: Dental schools must do more to encourage dental students to consider careers in academic dentistry. Pathway programs, mentoring, and the presentation of academic careers as a viable career option for students by faculty should be further emphasized practices. Increasing the diversity of faculty members is also key. Students cannot be who they cannot see.

Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation.

RATIONALE: Transforming growth factor (TGF)-beta has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin alpha(v)beta6, a key activator of TGF-beta in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF-beta at sites of alpha(v)beta6 up-regulation without affecting other homeostatic roles of TGF-beta. OBJECTIVES: To analyze the expression of alpha(v)beta6 in human pulmonary fibrosis, and to functionally test the efficacy of therapeutic inhibition of alpha(v)beta6-mediated TGF-beta activation in murine bleomycin-induced pulmonary fibrosis. METHODS: Lung biopsies from patients with a diagnosis of systemic sclerosis or idiopathic pulmonary fibrosis were stained for alpha(v)beta6 expression. A range of concentrations of a monoclonal antibody that blocks alpha(v)beta6-mediated TGF-beta activation was evaluated in murine bleomycin-induced lung fibrosis. MEASUREMENTS AND MAIN RESULTS: Alpha(v)beta6 is overexpressed in human lung fibrosis within pneumocytes lining the alveolar ducts and alveoli. In the bleomycin model, alpha(v)beta6 antibody was effective in blocking pulmonary fibrosis. At high doses, there was increased expression of markers of inflammation and macrophage activation, consistent with the effects of TGF-beta inhibition in the lung. Low doses of antibody attenuated collagen expression without increasing alveolar inflammatory cell populations or macrophage activation markers. CONCLUSIONS: Partial inhibition of TGF-beta using alpha(v)beta6 integrin antibodies is effective in blocking murine pulmonary fibrosis without exacerbating inflammation. In addition, the elevated expression of alpha(v)beta6, an activator of the fibrogenic cytokine, TGF-beta, in human pulmonary fibrosis suggests that alpha(v)beta6 monoclonal antibodies could represent a promising new therapeutic strategy for treating pulmonary fibrosis.

Topographic distribution of idiopathic pulmonary fibrosis: a hybrid physics- and agent-based model.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by excessive deposition of collagen and associated stiffening of lung tissue. While it is known that inflammation and dysfunction of fibroblasts are involved in disease development, it remains poorly understood how cells and their microenvironment interact to produce a characteristic subpleural pattern of high and low tissue density variations, called honeycombing, on CT images of patients with IPF. Since the pleura is stiffer than the parenchyma, we hypothesized that local stiffness of the underlying extracellular matrix can influence fibroblast activation and consequently the deposition of collagen, which in turn influences tissue stiffness in a positive feedback loop. APPROACH: We tested this hypothesis by developing a hybrid physics-based/agent-based computational model in which aberrant fibroblast activation is induced when cells migrate on stiff tissue. This activation then feeds back on itself via the altered mechanical environment that it creates by depositing collagen. MAIN RESULTS: The model produces power law distributions of both low- and high-attenuation area clusters and predicts the development of honeycombing only when mechanical rupture is allowed to take place in highly strained normal tissue surrounded by stiff fibrotic tissue. These predictions compare well with histologic data computed from CT images of patients with IPF. SIGNIFICANCE: We conclude that the clinical manifestation of subpleural honeycombing in IPF may result from fibroblasts entering into a positive feedback loop induced by the abnormally high tissue stiffness near the pleura.

Refining a Church-Based Lifestyle Intervention Targeting African-American Adults at Risk for Cardiometabolic Diseases: A Pilot Study.

OBJECTIVE: The pilot study was intended to test the feasibility of a multiple-component lifestyle intervention targeting African American adults in a weight control and cardiometabolic risk reduction program on diet, activity, and stress, using community-engagement principles. METHODS: Applying mixed qualitative and quantitative measures, the intervention had a two-part sequential study design consisting of 12 weekly small group sessions that provided individual and group counseling in nutrition, exercise, and mindfulness, while incorporating focus group and interactive techniques to learn about barriers and acceptable practices for this population. The program was implemented at an African-American church in Nashville, Tennessee. RESULTS: Thirty-four participants (aged 56.1 ± 11 years, body mass index (BMI) 36.7 ± 6.6 kg/m2) completed the intervention. Lifestyle changes after the 12 weekly sessions showed some positive trends including reduced sodium intake (from 2725.3 ± 326.5 to 2132 ± 330, mg/day, P = 0.008), increased walking steps (from 4392.1 ± 497.2 to 4895.3 ± 497.9, steps/day, not significant), and slightly decreased Perceived Stress Scale (PSS) scores (from 13.7 ± 1.4 to 12.4 ± 1.5, not significant). Body fat % among male participants decreased significantly (from 33.8 ± 2.6 to 28 ± 2.6, %, P = 0.043). Among cardiometabolic risk biomarkers, hemoglobin A1c (HbA1c) decreased significantly (from 6.6 ± 0.2 to 6.1 ± 0.2, %, P < 0.001). The baseline PSS score was positively associated with baseline adiposity levels (e.g., weight, ß = 2.4, P = 0.006). Twenty-one participants took part in focus groups during the program to identify barriers to healthy lifestyle changes. Primary barriers reported were price, time for preparing healthy meals, unfamiliarity with mindfulness activities, their health condition, and daily schedule available for physical activities. CONCLUSIONS: This church-based pilot intervention was proven feasible by showing modest progress in reducing adiposity and decreasing HbA1c levels. The focus group and interactive methods facilitated program direction. Future full-scale studies are warranted to identify key strategies that provide more personalized approaches and supportive environments to sustain a healthy lifestyle among these at risk minorities with limited resources.

Changes in fibrinolysis following exercise above and below lactate threshold.

This study sought to compare fibrinolytic responses to exercise above lactate threshold (LT) to longer-duration, equicaloric exercise below LT. Fifteen males performed cycle ergometer tests above (77% VO(2)peak) and below LT (41% VO(2)peak) to comparatively evaluate tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) responses. tPA activity significantly (P < 0.05) increased during the >LT test (pre-exercise = 1.57 +/- 0.44 IU ml(-1), post-exercise = 3.85 +/- 4.72 IU ml(-1)), but not the LT (pre-exercise = 8.32 +/- 4.48 ng ml(-1), post-exercise = 14.23 +/- 5.40 ng ml(-1)) and LT test. PAI-1 activity significantly (P < 0.05) decreased during both the >LT (pre-exercise = 15.00 +/- 2.73 AU ml(-1), post-exercise = 10.12 +/- 2.90 AU ml(-1)) and LT test. Our results suggest that exercise

Interleukin-12 is not essential for silicosis in mice.

BACKGROUND: Silicosis features foci of inflammation where macrophages and lymphocytes precede and accompany fibroblast proliferation, alveolar epithelial hyperplasia, and increased deposition of connective tissue matrix material. In the mouse following silica inhalation there is recruitment of natural killer-, B-, and CD4+ and CD8+ lymphocytes to the alveolar spaces, enlargement of bronchial-associated lymphoid tissues (BALT), and aggregation of lymphocytes surrounding small airways and blood vessels. A substantial fraction of the recruited lung lymphocytes produce interferon-gamma (IFN-gamma), and IFN-gamma gene-deleted mice develop less silicosis than wild-type mice. Interleukin-12 (IL-12) is an important pathway for driving the adaptive immune response towards a TH1-like phenotype. We hypothesized that IL-12 might stimulate lymphocyte activation and the up-regulation of IFN-gamma, and consequently be an essential mediator for silicosis. RESULTS: C57Bl/6 wild-type (WT) and IL-12 deficient (IL-12 KO) mice were exposed to sham-air or crystobalite silica (61 mg/m3) by inhalation for 5 hours/day for 12 days and then studied from 1 to 112 days after exposure. Mice exposed to sham-air had normal lung histology at all time points. WT mice exposed to titanium dioxide (72 mg/m3) showed pulmonary macrophage recruitment but no increase in lung collagen. Both WT and IL-12 KO mice exposed to silica showed similar progressive lung pathology, increased wet lung weight and increased total lung collagen (hydroxyproline). IL-12 p35 mRNA was not increased in either strain after silica exposure; IL-12 p40 mRNA was up-regulated after silica in WT mice and constitutively absent in the IL-12 KO mice. IL-18 mRNA was not increased after silica exposure. The expression of IL-15 (an important driver for innate immunity, Natural Killer cell activation, and IFN-gamma production) was abundant in air-exposed mice and was increased slightly in the lungs of mice with silicosis. CONCLUSION: The axis of IL-12 driving IFN-gamma production is not essential for the full manifestations of silicosis in mice exposed to a crystobalite silica aerosol.

Elimination of instrument-driven reflex manual differential leukocyte counts. Optimization of manual blood smear review criteria in a high-volume automated hematology laboratory.

Automated peripheral blood leukocyte differential counts (LDCs) are widely accepted in routine practice. However, many laboratories still reflexively perform manual LDCs based solely on abnormal automated results or instrument "flags," before any manual triage step. We describe our transition to a procedure that uses manual methods to validate, rather than to replace, automated LDCs (an approach recommended early in the development of automated methods, but still not used in many clinical laboratories). Manual microscopic scans were performed in lieu of manual LDCs. Each scan that revealed cell types not quantifiable by the instrument triggered a manual LDC. However, if the manual scan simply confirmed the cell types seen on automated LDC, then the automated result was released, even if clinically significant quantitative abnormalities were present. This policy reduced manual LDCs by more than 70% and was validated by a manual retrospective audit. Patient care and laboratory operations can be optimized by using manual microscopic examination as a validation procedure rather than as a reflexive substitute for automated methods. There is no clinical rationale for reflex performance of manual LDCs based solely on instrument warnings.

A bronchoscopic oddity: nodular tracheobronchial amyloidosis.

Tracheobronchial amyloidosis is a rare disorder of unknown cause associated with the extracellular deposition of amyloid protein in a characteristic spatial structure of ß-sheet fibrils assembled into bundles. We present a case that represents the nodular form of tracheobronchial amyloidosis, which is the least common form of pulmonary amyloidosis with less than 20 cases reported so far. Patients with tracheobronchial amyloidosis may present with symptoms of dyspnea, localized wheezing, cough, hemoptysis, or recurrent pneumonias. The mainstay of the therapy is debridement of the symptomatic luminal obstruction with neodymium-doped yttrium aluminium garnet laser therapy. Other treatment strategies include airway stenting, external beam radiation therapy, bypass tracheostomy, or open surgical resection.

Linking parenchymal disease progression to changes in lung mechanical function by percolation.

RATIONALE: The mechanical dysfunction accompanying parenchymal diseases such as pulmonary fibrosis and emphysema may follow a different course from the progression of the underlying microscopic pathophysiology itself, particularly in the early stages. It is tempting to speculate that this may reflect the geographical nature of lung pathology. However, merely ascribing mechanical dysfunction of the parenchyma to the vagaries of lesional organization is unhelpful without some understanding of how the two are linked. OBJECTIVES: We attempt to forge such a link through a concept known as percolation, which has been invoked to account for numerous natural processes involving transmission of events across complex networks. METHODS: We numerically determined the bulk stiffness (corresponding to the inverse of lung compliance) of a network of springs representing the lung parenchyma. We simulated the development of fibrosis by randomly stiffening individual springs in the network, and the development of emphysema by preferentially cutting springs under the greatest tension. MEASUREMENTS AND MAIN RESULTS: When the number of stiff springs was increased to the point that they suddenly became connected across the network, the model developed a sharp increase in its bulk modulus. Conversely, when the cut springs became sufficiently numerous, the elasticity of the network fell to zero. These two conditions represent percolation thresholds that we show are mirrored structurally in both tissue pathology and macroscopic computed tomography images of human idiopathic fibrosis and emphysema. CONCLUSIONS: The concept of percolation may explain why the development of symptoms related to lung function and the development of parenchymal pathology often do not progress together.

Asbestos-induced peribronchiolar cell proliferation and cytokine production are attenuated in lungs of protein kinase C-delta knockout mice.

The signaling pathways leading to the development of asbestos-associated diseases are poorly understood. Here we used normal and protein kinase C (PKC)-delta knockout (PKCdelta-/-) mice to demonstrate multiple roles of PKC-delta in the development of cell proliferation and inflammation after inhalation of chrysotile asbestos. At 3 days, asbestos-induced peribronchiolar cell proliferation in wild-type mice was attenuated in PKCdelta-/- mice. Cytokine profiles in bronchoalveolar lavage fluids showed increases in interleukin (IL)-1beta, IL-4, IL-6, and IL-13 that were decreased in PKCdelta-/- mice. At 9 days, microarray and quantitative reverse transcriptase-polymerase chain reaction analysis of lung tissues revealed increased mRNA levels of the profibrotic cytokine, IL-4, in asbestos-exposed wild-type mice but not PKCdelta-/- mice. PKCdelta-/- mice also exhibited decreased lung infiltration of polymorphonuclear cells, natural killer cells, and macrophages in bronchoalveolar lavage fluid and lung, as well as increased numbers of B lymphocytes and plasma cells. These changes were accompanied by elevated mRNA levels of immunoglobulin chains. These data show that modulation of PKC-delta has multiple effects on peribronchiolar cell proliferation, proinflammatory and profibrotic cytokine expression, and immune cell profiles in lung. These results also implicate targeted interruption of PKC-delta as a potential therapeutic option in asbestos-induced lung diseases.

Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement.

RATIONALE: Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis. OBJECTIVES: To assess the efficacy of infliximab in sarcoidosis. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment. CONCLUSIONS: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.

Review: occupational and environmental lung disease.

Occupational and environmental lung disease is a vast topic. Therefore, this review focuses on areas that represent new clinical insights that have not been addressed recently in Current Opinion in Pulmonary Medicine. The topics are considered important for the future and emphasize diseases that strike large numbers of people or exposures that affect large segments of the population. This review highlights literature published between the years 2000 to 2001 related to air pollution, occupational asthma, lung diseases in agricultural workers, nylon flock workers lung disease, pneumoconiosis, and environmental exposure to biomass smoke, including environmental tobacco smoke. These publications highlight the changing world of occupational and environmental lung diseases. Traditionally, this field dealt with chronic diseases caused by very high levels of exposure to materials that affected virtually all workers to a similar degree. Disease could be recognized readily by characteristic symptoms, signs, and radiographic abnormalities. Dose-effect relationships were usually clear, and the solution to disease was generally to limit exposure for all workers. This approach served well for conditions such as coal workers pneumoconiosis or toxic responses to chlorine gas. The new world of occupational and environmental lung diseases often involves low levels of exposure to complex mixtures of materials that produce nonspecific or intermittent symptoms in a subgroup of exposed individuals. Interactions between genetic susceptibility, concomitant tobacco smoke exposure, and co-morbid diseases hugely complicate both diagnosis and prevention. New tools, and possibly new thought paradigms, are needed to detect, treat, and prevent occupational and environmental lung diseases in a changing world.