Evaluating the relationship between health-related social needs, patient demographics, and access to biologics in patients with moderate-to-severe asthma in Bronx, NY.

OBJECTIVES: This study assesses the relationship between patient age, gender, race, socioeconomic status, social determinants of health (SDoH), and access to biologics (products isolated from natural sources that target specific molecules, proteins, and cells) in patients with moderate-to-severe asthma in Bronx, NY. METHODS: Cohort of 289 patients with moderate-to-severe asthma treated at Montefiore Medical Center (MMC) from 2018 to 2020 was used. Patient demographics, self-reported social needs, and neighborhood socioeconomic characteristics were analyzed. Neighborhood socioeconomic status was estimated by determining median income in patients' residential zip codes using 2020 Census data and grouping patients based on whether neighborhood median income was above or below New York State (NYS) median ($71,117/year). Area Deprivation Index tool (ADI) was used as an additional measure of neighborhood socioeconomic status. RESULTS: Patients living in regions with incomes below NYS median found to have longer wait times between biologic approval to administration than patients living in regions above median income (p = 0.012). Mean time from insurance approval to biologic administration was significantly different between Black and Latinx patients (p = 0.009). No significant difference found for patient regional income status and time from biologic prescription to approval. No significant differences in access to biologics were found for age, gender, number of health-related social needs, or patient ADI quartile. CONCLUSIONS: Patients who live in areas of NYC where median income is below NYS median are more likely to experience delays in access to biologics, specifically due to time between approval and administration of medication.

Effects of fossil fuel and total anthropogenic emission removal on public health and climate.

Anthropogenic greenhouse gases and aerosols are associated with climate change and human health risks. We used a global model to estimate the climate and public health outcomes attributable to fossil fuel use, indicating the potential benefits of a phaseout. We show that it can avoid an excess mortality rate of 3.61 (2.96-4.21) million per year from outdoor air pollution worldwide. This could be up to 5.55 (4.52-6.52) million per year by additionally controlling nonfossil anthropogenic sources. Globally, fossil-fuel-related emissions account for about 65% of the excess mortality, and 70% of the climate cooling by anthropogenic aerosols. The chemical influence of air pollution on aeolian dust contributes to the aerosol cooling. Because aerosols affect the hydrologic cycle, removing the anthropogenic emissions in the model increases rainfall by 10-70% over densely populated regions in India and 10-30% over northern China, and by 10-40% over Central America, West Africa, and the drought-prone Sahel, thus contributing to water and food security. Since aerosols mask the anthropogenic rise in global temperature, removing fossil-fuel-generated particles liberates 0.51(±0.03) °C and all pollution particles 0.73(±0.03) °C warming, reaching around 2 °C over North America and Northeast Asia. The steep temperature increase from removing aerosols can be moderated to about 0.36(±0.06) °C globally by the simultaneous reduction of tropospheric ozone and methane. We conclude that a rapid phaseout of fossil-fuel-related emissions and major reductions of other anthropogenic sources are needed to save millions of lives, restore aerosol-perturbed rainfall patterns, and limit global warming to 2 °C.

Elevated temperature inhibits Mycobacterium shottsii infection and Mycobacterium pseudoshottsii disease in striped bass Morone saxatilis.

Mycobacteriosis occurs with high prevalence in the wild striped bass Morone saxatilis of Chesapeake Bay, USA. Etiologic agents of mycobacteriosis in this system are dominated by Mycobacterium pseudoshottsii and Mycobacterium shottsii, both members of the M. ulcerans/M. marinum clade of mycobacteria. Striped bass occupying Chesapeake Bay during summer months where water temperatures regularly approach and occasionally exceed 30°C are thought to be near their thermal maximum, a condition hypothesized to drive high levels of disease and increased natural mortality due to temperature stress. M. shottsii and M. pseudoshottsii, however, do not grow or grow inconsistently at 30°C on artificial medium, potentially countering this hypothesis. In this work, we examine the effects of temperature (20, 25, and 30°C) on progression of experimental infections with M. shottsii and M. pseudoshottsii in striped bass. Rather than exacerbation of disease, increasing temperature resulted in attenuated bacterial density increase in the spleen and reduced pathology in the spleen and mesenteries of M. pseudoshottsii infected fish, and reduced bacterial densities in the spleen of M. shottsii infected fish. These findings indicate that M. pseudoshottsii and M. shottsii infections in Chesapeake Bay striped bass may be limited by the thermal tolerance of these mycobacteria, and that maximal disease progression may in fact occur at lower water temperatures.

The future of UK healthcare: problems and potential solutions to a system in crisis.

The UK's Health System is in crisis, central funding no longer keeping pace with demand. Traditional responses-spending more, seeking efficiency savings or invoking market forces-are not solutions. The health of our nation demands urgent delivery of a radical new model, negotiated openly between public, policymakers and healthcare professionals. Such a model could focus on disease prevention, modifying health behaviour and implementing change in public policy in fields traditionally considered unrelated to health such as transport, food and advertising. The true cost-effectiveness of healthcare interventions must be balanced against the opportunity cost of their implementation, bolstering the central role of NICE in such decisions. Without such action, the prognosis for our healthcare system-and for the health of the individuals it serves-may be poor. Here, we explore such a new prescription for our national health.

The effect of ambient temperature on type-2-diabetes: case-crossover analysis of 4+ million GP consultations across England.

BACKGROUND: Given the double jeopardy of global increases in rates of obesity and climate change, it is increasingly important to recognise the dangers posed to diabetic patients during periods of extreme weather. We aimed to characterise the associations between ambient temperature and general medical practitioner consultations made by a cohort of type-2 diabetic patients. Evidence on the effects of temperature variation in the primary care setting is currently limited. METHODS: Case-crossover analysis of 4,474,943 consultations in England during 2012-2014, linked to localised temperature at place of residence for each patient. Conditional logistic regression was used to assess associations between each temperature-related consultation and control days matched on day-of-week. RESULTS: There was an increased odds of seeking medical consultation associated with high temperatures: Odds ratio (OR) = 1.097 (95% confidence interval = 1.041, 1.156) per 1 °C increase above 22 °C. Odds during low temperatures below 0 °C were also significantly raised: OR = 1.024 (1.019, 1.030). Heat-related consultations were particularly high among diabetics with cardiovascular comorbidities: OR = 1.171 (1.031, 1.331), but there was no heightened risk with renal failure or neuropathy comorbidities. Surprisingly, lower odds of heat-related consultation were associated with the use of diuretics, anticholinergics, antipsychotics or antidepressants compared to non-use, especially among those with cardiovascular comorbidities, although differences were not statistically significant. CONCLUSIONS: Type-2 diabetic patients are at increased odds of medical consultation during days of temperature extremes, especially during hot weather. The common assumption that certain medication use heightens the risk of heat illness was not borne-out by our study on diabetics in a primary care setting and such advice may need to be reconsidered in heat protection plans.

Determining Relative Importance and Effective Settings for Genetic Algorithm Control Parameters.

Setting the control parameters of a genetic algorithm to obtain good results is a long-standing problem. We define an experiment design and analysis method to determine relative importance and effective settings for control parameters of any evolutionary algorithm, and we apply this method to a classic binary-encoded genetic algorithm (GA). Subsequently, as reported elsewhere, we applied the GA, with the control parameter settings determined here, to steer a population of cloud-computing simulators toward behaviors that reveal degraded performance and system collapse. GA-steered simulators could serve as a design tool, empowering system engineers to identify and mitigate low-probability, costly failure scenarios. In the existing GA literature, we uncovered conflicting opinions and evidence regarding key GA control parameters and effective settings to adopt. Consequently, we designed and executed an experiment to determine relative importance and effective settings for seven GA control parameters, when applied across a set of numerical optimization problems drawn from the literature. This paper describes our experiment design, analysis, and results. We found that crossover most significantly influenced GA success, followed by mutation rate and population size and then by rerandomization point and elite selection. Selection method and the precision used within the chromosome to represent numerical values had least influence. Our findings are robust over 60 numerical optimization problems.

Chlamydia trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion.

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease and a global health burden. As an obligate intracellular pathogen, Chlamydia has evolved many strategies to manipulate its host and establish its intracellular niche called the inclusion. C. trachomatis reorganizes the host actin cytoskeleton to form scaffolds around the inclusion and reinforce the growing inclusion membrane. To control the kinetics and formation of actin scaffolds, Chlamydia expresses the effector InaC/CT813, which activates the host GTPase RhoA. Here, we have discovered that InaC stabilizes actin scaffolds through the host actin cross-linking proteins α-actinins 1 and 4. We demonstrate that α-actinins are recruited to the inclusion membrane in an InaC-dependent manner and associate with actin scaffolds that envelop the inclusion. Small interfering RNA (siRNA)-mediated knockdown of α-actinins differentially regulate the frequency of actin scaffolds and impair inclusion stability, leaving them susceptible to rupture and to nonionic detergent extraction. Overall, our data identify new host effectors that are subverted by InaC to stabilize actin scaffolds, highlighting the versatility of InaC as a key regulator of the host cytoskeletal network during Chlamydia infection. IMPORTANCE Despite antibiotics, recurrent C. trachomatis infections cause significant damage to the genital tract in men and women. Without a preventative vaccine, it is paramount to understand the virulence mechanisms that Chlamydia employs to cause disease. In this context, manipulation of the host cytoskeleton is a critical component of Chlamydia development. Actin scaffolds reinforce the integrity of Chlamydia's infectious vacuole, which is a critical barrier between Chlamydia and the host environment. Having previously established that InaC co-opts RhoA to promote the formation of actin scaffolds around the inclusion, we now show that Chlamydia hijacks a new class of host effectors, α-actinins, to cross-link these scaffolds and further stabilize the inclusion. We also establish that a core function of the chlamydial effector InaC is the regulation of cytoskeletal stability during Chlamydia infection. Ultimately, this work expands our understanding of how bacterial pathogens subvert the actin cytoskeleton by targeting fundamental host effector proteins.

Mortality Attributable to Ambient Air Pollution: A Review of Global Estimates.

Since the publication of the first epidemiological study to establish the connection between long-term exposure to atmospheric pollution and effects on human health, major efforts have been dedicated to estimate the attributable mortality burden, especially in the context of the Global Burden of Disease (GBD). In this work, we review the estimates of excess mortality attributable to outdoor air pollution at the global scale, by comparing studies available in the literature. We find large differences between the estimates, which are related to the exposure response functions as well as the number of health outcomes included in the calculations, aspects where further improvements are necessary. Furthermore, we show that despite the considerable advancements in our understanding of health impacts of air pollution and the consequent improvement in the accuracy of the global estimates, their precision has not increased in the last decades. We offer recommendations for future measurements and research directions, which will help to improve our understanding and quantification of air pollution-health relationships.

Clinical presentation, diagnostic investigations, treatment protocols and outcomes of dogs diagnosed with tick-borne diseases living in the United Kingdom: 76 cases (2005-2019).

OBJECTIVES: To report the presence of tick-borne diseases in dogs living in the United Kingdom. MATERIALS AND METHODS: Dogs with a final diagnosis of tick-borne diseases made between January 2005 and August 2019 at seven referral institutions in the United Kingdom were included in the study. RESULTS: Seventy-six dogs were included: 25 were diagnosed with ehrlichiosis, 23 with babesiosis, eight with Lyme borreliosis and six with anaplasmosis. Fourteen dogs had co-infections with two or three pathogens. Except for those dogs with anaplasmosis and Lyme borreliosis, most dogs with tick-borne diseases had a history of travel to or from endemic countries. However, three dogs with ehrlichiosis, and one dog each infected with Babesia canis and Babesia vulpes did not have any history of travel. A variety of non-specific clinical signs and laboratory abnormalities were reported. Targeted treatment was successful at achieving clinical remission in 64 (84%) dogs. CLINICAL SIGNIFICANCE: Even in non-endemic areas, veterinary surgeons should consider tick-borne diseases in dogs with compatible clinical presentation and laboratory findings and especially where there is a history of travel. As autochthonous transmission of tick-borne-pathogens does occur, an absence of travel should not rule out tick-borne diseases. Specific diagnostic testing is required to confirm infection, and this enables prompt targeted treatment and often a positive outcome.

Health benefits of a low carbon economy.

This article summarizes a presentation given at 'Health and Well-being: the 21st Century Agenda', which focused on the potential to make progress by making appropriate connections between activity to promote health and respond to the threat of climate change. It argues that a transition to a low carbon economy would bring together two of our greatest public health challenges, supporting action to improve public health within resource constraints and action to avert climate change as far as possible. Deep cuts in emissions are needed to prevent dangerous consequences arising from climate change. In addition, many of the policies to reduce greenhouse gas emissions will, in themselves, have beneficial effects on public health. This article provides an overview of several modelling studies which demonstrate that well-designed initiatives that curb greenhouse gas emissions in energy, residential construction, urban transport and agricultural systems can enhance global public health, including improving health among poor populations. Some of these health co-benefits can be achieved in a relatively short time frame, and they can help offset the costs of climate change mitigation policies.

Environmental impacts of dietary shifts in India: A modelling study using nationally-representative data.

Food production is a major driver of environmental change, and unhealthy diets are the leading cause of global disease burden. In high-income countries (HICs), modelling studies suggest that adoption of healthy diets could improve population health and reduce environmental footprints associated with food production. We assessed whether such benefits from dietary change could occur in India, where under-nutrition and overweight and obesity are simultaneously prevalent. We calculated the potential changes in greenhouse gas (GHG) emissions, blue and green water footprints (WFs), and land use (LU), that would result from shifting current national food consumption patterns in India to healthy diets (meeting dietary guidelines) and to "affluent diets" (those consumed by the wealthiest quartile of households, which may represent future purchasing power and nutritional trajectories). Dietary data were derived from the 2011-12 nationally-representative household expenditure survey, and we assessed dietary scenarios nationally and across six Indian sub-regions, by rural or urban location, and for those consuming above or below recommended dietary energy intakes. We modelled the changes in consumption of 34 food groups necessary to meet Indian dietary guidelines, as well as an affluent diet representative of those in the highest wealth quartile. These changes were combined with food-specific data on GHG emissions, calculated using the Cool Farm Tool, and WF and LU adapted from the Water Footprint Network and Food and Agriculture Organization, respectively. Shifting to healthy guidelines nationally required a minor increase in dietary energy (3%), with larger increases in fruit (18%) and vegetable (72%) intake, though baseline proportion of dietary energy from fat and protein was adequate and did not change significantly. Meeting healthy guidelines slightly increased environmental footprints by about 3-5% across GHG emissions, blue and green WFs, and LU. However, these national averages masked substantial variation within sub-populations. For example, shifting to healthy diets among those with dietary energy intake below recommended guidelines would result in increases of 28% in GHG emissions, 18 and 34% in blue and green WFs, respectively, and 41% in LU. Decreased environmental impacts were seen among those who currently consume above recommended dietary energy (-6 to -16% across footprints). Adoption of affluent diets by the whole population would result in increases of 19-36% across the environmental indicators. Specific food groups contributing to these shifts varied by scenario. Environmental impacts also varied markedly between six major Indian sub-regions. In India, where undernutrition is prevalent, widespread adoption of healthy diets may lead to small increases in the environmental footprints of the food system relative to the status quo, although much larger increases would occur if there was widespread adoption of diets currently consumed by the wealthiest quartile of the population. To achieve lower diet-related disease burdens and reduced environmental footprints of the food system, greater efficiency of food production and reductions in food waste are likely to be required alongside promotion of healthy diets.

Climate change and human health: impacts, vulnerability, and mitigation.

It is now widely accepted that climate change is occurring as a result of the accumulation of greenhouse gases in the atmosphere arising from the combustion of fossil fuels. Climate change may affect health through a range of pathways--eg, as a result of increased frequency and intensity of heat waves, reduction in cold-related deaths, increased floods and droughts, changes in the distribution of vector-borne diseases, and effects on the risk of disasters and malnutrition. The overall balance of effects on health is likely to be negative and populations in low-income countries are likely to be particularly vulnerable to the adverse effects. The experience of the 2003 heat wave in Europe shows that high-income countries might also be adversely affected. Adaptation to climate change requires public-health strategies and improved surveillance. Mitigation of climate change by reducing the use of fossil fuels and increasing the use of a number of renewable energy technologies should improve health in the near term by reducing exposure to air pollution.

Efficient nonviral transfection of dendritic cells and their use for in vivo immunization.

Immunization with dendritic cells (DCs) transfected with genes encoding tumor-associated antigens (TAAs) is a highly promising approach to cancer immunotherapy. We have developed a system, using complexes of plasmid DNA expression constructs with the cationic peptide CL22, that transfects human monocyte-derived DCs much more efficiently than alternative nonviral agents. After CL22 transfection, DCs expressing antigens stimulated autologous T cells in vitro and elicited primary immune responses in syngeneic mice, in an antigen-specific manner. Injection of CL22-transfected DCs expressing a TAA, but not DCs pulsed with a TAA-derived peptide, protected mice from lethal challenge with tumor cells in an aggressive model of melanoma. The CL22 system is a fast and efficient alternative to viral vectors for engineering DCs for use in immunotherapy and research.

Simulating Moral Actions: An Investigation of Personal Force in Virtual Moral Dilemmas.

Advances in Virtual Reality (VR) technologies allow the investigation of simulated moral actions in visually immersive environments. Using a robotic manipulandum and an interactive sculpture, we now also incorporate realistic haptic feedback into virtual moral simulations. In two experiments, we found that participants responded with greater utilitarian actions in virtual and haptic environments when compared to traditional questionnaire assessments of moral judgments. In experiment one, when incorporating a robotic manipulandum, we found that the physical power of simulated utilitarian responses (calculated as the product of force and speed) was predicted by individual levels of psychopathy. In experiment two, which integrated an interactive and life-like sculpture of a human into a VR simulation, greater utilitarian actions continued to be observed. Together, these results support a disparity between simulated moral action and moral judgment. Overall this research combines state-of-the-art virtual reality, robotic movement simulations, and realistic human sculptures, to enhance moral paradigms that are often contextually impoverished. As such, this combination provides a better assessment of simulated moral action, and illustrates the embodied nature of morally-relevant actions.

Immunohistochemical expression of MDR1-Pgp 170 in canine cutaneous and oral melanomas: pattern of expression and association with tumour location and phenotype.

Canine melanoma (CMM) more commonly affects the oral mucosa and the cutis. CMM shares several features with human melanomas (HMM), included resistance to a broad variety of antineoplastic chemotherapy agents. P-glycoprotein 1 (Pgp) expression is a well-recognized feature of multi-drug resistance and the purpose of this study was to investigate its expression in treatment naïve CMM. We also investigated Pgp association with tumour location and histological features. Histology records of CMM were retrieved, including patients from 2012-2014. Twenty-five cases of CMM were included in this study. Results revealed that Pgp is expressed in CMM and oral tumours were more likely to have a membranous Pgp expression (100%) than cutaneous tumours (66.6%) (P = 0.010). Cytoplasmic and nuclear Pgp expression could also be identified. Results of this study bring useful data that help in understanding one of the possible mechanisms responsible of intrinsic chemotherapy resistance in canine CMM.

Histology and immunology of the placenta in the Atlantic sharpnose shark, Rhizoprionodon terraenovae.

The Atlantic sharpnose shark, Rhizoprionodon terraenovae, is viviparous species that forms a yolk sac placenta to facilitate exchange between mother and embryo. However, very little is known about the immunological aspects of this organ in sharks. To begin to understand this, we used histology, histochemistry and immunohistochemistry to investigate the sharpnose shark placenta throughout gestation. We report the presence of lymphoid aggregates in the maternal portion of the placenta during all stages of gestation, and their increasing size and vascularity near term. Immunoglobulin is found in the maternal tissues of the placenta, but its presence in embryonic tissue and potential transfer from maternal circulation remains unclear. Placental cells resembling mammalian uterine NK cells and melanomacrophages of lower vertebrates are described for the first time. Similarities with mammalian placentae point to shared aspects in the co-evolution of reproductive and immune systems, even between two phylogenetically diverse groups in which placentation arose by convergent evolution.

Carriage of group B streptococcus in pregnant women from Oxford, UK.

OBJECTIVE: To investigate asymptomatic vagino-rectal carriage of group B streptococcus (GBS) in pregnant women. METHODS: Women in the final trimester of pregnancy were recruited. A single vagino-rectal swab was taken, with consent, for culture of GBS. Two microbiological methods for isolation of GBS from vagino-rectal swabs were compared. The distribution of capsular serotypes of the GBS identified was determined. Epidemiological data for a subset (n = 167) of the pregnant women participating were examined. RESULTS: 21.3% were colonised vagino-rectally with GBS. Risk factors for neonatal GBS disease (maternal fever, prolonged rupture of membranes, and preterm delivery) were present in 34 of 167 women (20.4%), and the presence of these factors correlated poorly with GBS carriage. Capsular serotypes III (26.4%), IA (25.8%), V (18.9%), and IB (15.7%) were prevalent in the GBS isolates. Selective broth culture of vagino-rectal swabs was superior to selective plate culture, but the combination of both methods was associated with increased detection of GBS (7.5%). An algorithm for the identification of GBS from vagino-rectal swabs was developed. CONCLUSIONS: GBS carriage is prevalent in pregnant women in Oxfordshire, UK. The poor correlation between risk factors and GBS carriage requires further investigation in larger groups, given that the identification of these surrogate markers is recommended to guide administration of intrapartum antibiotic prophylaxis by the Royal College of Obstetricians of the UK. A selective broth culture detected more GBS carriers than a selective plate culture.

Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells.

Radiolabeled antibodies have produced encouraging remissions in patients with chemotherapy-resistant hematological malignancies; however, the selection of therapeutic radionuclides for clinical trials remains controversial. In this study, we compared the internalization, lysosomal targeting, metabolism, and cellular retention of radiolabeled murine and humanized monoclonal antibodies targeting the CD33 antigen (monoclonal antibodies mP67 and hP67, respectively) on myeloid leukemia cell lines (HEL and HL-60) and of anti-carcinoma antibodies (monoclonal antibodies hCTM01 and hA33) targeting breast cancer and colorectal carcinoma cell lines (MCF7 and Colo 205, respectively). Each antibody was labeled with 125I (by the IodoGen method) and with 111In and 90Y using macrocyclic chelation technology. Targeted tumor cells were analyzed for retention and metabolism of radioimmunoconjugates using cellular-radioimmunoassays, Percoll gradient fractionation of cell organelles, SDS-PAGE, and TLC of cell lysates and culture supernatants. Our results suggest that antibodies are routed to lysosomes after endocytosis, where they are proteolytically degraded. [125I]monoiodotyrosine is rapidly excreted from cells after lysosomal catabolism of antibodies radioiodinated by conventional methods, whereas small molecular weight 111In and 90Y catabolites remain trapped in lysosomes. As a consequence of the differential disposition of small molecular weight catabolites, 111In and 90Y conjugates displayed superior retention of radioactivity compared with 125I conjugates when tumor cells were targeted using rapidly internalizing antibody-antigen systems (e.g., hP67 with HEL cells and hCTM01 with MCF7 cells). When tumor cells were targeted using antibody-antigen systems exhibiting slow rates of endocytosis (e.g., hP67 on HL-60 cells and hA33 on Colo 205 cells), little differences in cellular retention of radioactivity was observed, regardless of whether 125I, 111In, or 90Y was used.