Near Infrared Biomimetic Hybrid Magnetic Nanocarrier for MRI-Guided Thermal Therapy.

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM-1s-1, decreasing respectively to 445 mM-1s-1 and 278 mM-1s-1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r2/r1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

Reflections on COVID-19 pandemic and waste management in developing countries: A case study in São Paulo city, Brazil.

COVID-19 pandemic has changed several aspects in human behaviour, whereas population mobility patterns have been strongly affected by social distancing. In parallel, changes in solid waste generation patterns have been reported worldwide. This work assessed the influence of the COVID-19 pandemic on waste generation and collection in São Paulo city, Brazil, the largest city of Latin America. Data on nine types of wastes collected between 2013 and 2021 were obtained, and the quantities of wastes collected before and during the pandemic were compared. These data were also discussed in light of data on COVID-19 cases and rates of social distancing and mobility. An increase in the amount of recyclables collected during the first wave of COVID-19 (March to September 2020) was observed. Decreases in the quantities of construction, demolition and bulky wastes (first wave of COVID-19) and farmers market wastes (second wave - October 2020 to February 2021) were also evidenced. The quantities of medical wastes collected during the pandemic significantly increased. The amount of residential wastes was lower than the mean for the pre-pandemic period during the first months of COVID-19. Thus, changes in lifestyle and consumption patterns of the population of São Paulo city seem to have affected solid waste generation during the pandemic, which reinforces the need of implementing solid waste management policies based on a diagnostic that characterise and consider these changes.

An emergent treat: Marine heatwaves - Implications for marine decapod crustacean species - An overview.

Anthropogenic-mediated climate change severely affects the oceans. The most common definition of a Marine heatwave (MHW) considers that water temperatures rise above the 90th percentile threshold values, based on the last 30 years' average of temperature records for a particular location, and remains this high for five or more days. The current review addresses the evolution of definitions used, as well as the current understanding of the driving mechanisms of MHWs. The collected information shows that the study of MHW is recent and there is a growing interest among the scientific community on this topic, motivated largely by the impacts that pose to marine ecosystems. Further, a more in-depth analysis was carried out, addressing the impacts of MHW events on marine decapod crustacean species. The investigation of such impacts has been carried out using three main methodological approaches: the analysis of in situ records, observed in 33 studies; simulating MHW events through mesocosm experiments, found in 6 studies; and using computational predictive models, detected in 1 study. From the literature available it has been demonstrated that consequences are serious for these species, from altered expansion ranges to alterations of assemblages' abundances. Still, studies addressing the impacts of these extreme events on the decapod communities are scarce, often only limited to adult life forms of commercially relevant species, neglecting non-commercial ones and meroplanktonic life stages. Despite the severe impacts on the health of ecosystems, repercussions on socioeconomic human activities, like fisheries and aquaculture, are also a reality. Overall, this review aims to raise scientific and public awareness of these marine events, which are projected to increase in intensity and frequency in the coming decades. Therefore, there is a growing need to better understand and predict the mechanisms responsible for these extreme events and the impacts on key species, like decapod crustaceans.

[Laboratories as predictors of length of hospital stay in patients with pneumonia]. / Laboratorios como predictores del tiempo de estancia hospitalaria en pacientes con neumonía.

Background: There are several factors that influence the length of hospital stay (LoHS) in patients with community-acquired pneumonia (CAP). There is currently no study in the literature that correlates laboratory parameters at hospital admittance with the LoHS. Objective: To find the association of laboratory parameters with the LoHS in patients with community-acquired pneumonia. Material and methods: An observational, prospective, longitudinal, and controlled study was conducted in the emergency room of a secondary level hospital. Results: The mean time of LoHS in patients with CAP was 6.6 ± 3.0 days. The parameters of laboratory of monocytes, basophils and segmented neutrophils presented a correlation (Spearman rho) of 0.363, 0.364 and 0.331; p =0.02, 0.02 and 0.04, respectively, with LoHS. Systemic arterial hypertension (SAH) presented a relative risk (RR) of 2.8 (95% confidence interval [95% CI]: 1.41-5.56; p < 0.001), and the chronic obstructive pulmonary disease (COPD) a RR 1.94, (95%CI: 1.31-2.88; p = 0.03) associated with prolonged LoHS. Conclusions: LoHS in patients with CAP is related to the counting of monocytes, basophils, and neutrophils at the time of the hospital admittance and it was increased in patients with SAH and patients with COPD.

Introducción: son diversos los factores que influyen en el tiempo de estancia intrahospitalaria (TEIH) en pacientes con neumonía adquirida en la comunidad (NAC). Actualmente no existen estudios que relacionen los parámetros de laboratorio con la duración de la TEIH. Objetivo: analizar la asociación de los laboratorios con el TEIH en pacientes con NAC. Material y métodos: se hizo un estudio prospectivo, longitudinal en el área de urgencias de un hospital de segundo nivel de atención. Resultados: el tiempo promedio de TEIH en pacientes con NAC en la comunidad fue de 6.6 ± 3.0 días. Los parámetros de laboratorio de monocitos, basófilos y neutrófilos segmentados presentaron una correlación (rho de Spearman) de 0.363, 0.364 y 0.331, p =0.02, 0.02 y 0.04, respectivamente con el TEIH. La hipertensión arterial sistémica (HAS) presentó un riesgo relativo (RR) de 2.8 (intervalo de confianza del 95% [IC 95%]: 1.41-5.56; p < 0.001), y la enfermedad pulmonar obstructiva crónica (EPOC) un RR 1.94 (IC 95%: 1.31-2.88; p = 0.03) asociada a TEIH prolongado. Conclusiones: la duración del TEIH en pacientes con NAC se relaciona con el recuento de monocitos, basófilos y neutrófilos en el momento del ingreso hospitalario y se incrementó en pacientes con HAS y pacientes con EPOC.

Upper Extremity Trauma in Costa Rica - Evaluating Epidemiology and Identifying Opportunities.

Background: Traffic accidents and musculoskeletal injuries represent a major cause of morbidity and mortality in Costa Rica. To inform capacity building efforts, we conducted a survey study of hand and upper extremity (UE) fellowship-trained surgeons in Costa Rica to evaluate the epidemiology, complications, and challenges in care of UE trauma. Methods: Aiming to capture all hand and UE trained surgeons in Costa Rica, we compiled a list of nine surgeons and sent a survey in Spanish using Qualtrics. Assessment questions were developed to understand the burden, complications, practice patterns, challenges, and capacity associated with care of UE trauma. Questions were designed to focus on opportunities for future investigation. Questions were translated and adapted by two bilingual speakers. Data were reported descriptively and open-ended responses were analyzed using content analysis. Results: Nine (100%) surgeons completed the survey. Distal radius fractures, hand and finger fractures, and tendon injuries are the most frequently noted conditions. Stiffness and infection are the most common complications. About 29% of patients are unable to get necessary therapy and 13% do not return for follow-up care with monetary, distance, and transportation limitations being the greatest challenges. Conclusions: The burden of UE trauma in Costa Rica is high. Identifying common conditions, complications, challenges, and capacity allows for a tailored approach to partnership and capacity building (e.g. directing capacity building and/or research infrastructure toward distal radius fractures). These insights represent opportunities to inform community-driven care improvement and research initiatives, such as Delphi consensus approaches to identify priorities or the development of outcome measurement systems.

Do biofertilizers affect nodulation ability and pod production in peanut genotypes?

Peanuts are an important legume for the Northeastern Brazilian market, but their production in this region is low. The present study aimed to evaluate the effect of biofertilizer doses on peanut nodulation and production components, to define the best dose and genotype. The experiment was conducted in a completely randomized block design (DBC) in a 3 x 3 factorial arrangement, with three replications. The treatments consisted of two evaluation factors: 1) Fertilization via different doses of organic fertilizer applied to the substrate (D1 = 0mL; D2 = 500mL; and D3 = 1000mL); and 2) Peanut genotypes (BR-1, UNI43 and UNI08). The following traits were assessed: number of nodules per plant (NNP), number of mature pods (NVM), pod mass per plant (MVP), seed mass per plant (MSP) and root length (CR). Peanut production is affected by fertilization via bovine biofertilizer, mainly for the components NVM, MVP and MSP. Besides, nodulation is a likely conditioner. The 1000mL dose proved to be the best treatment for the traits analyzed, and UNI08 accession, the most responsive material.

Patient Follow-up After Orthopaedic Outreach Trips - Do We Know Whether Patients are Improving?

BACKGROUND: The burden of traumatic musculoskeletal injuries falls greatest on low- and middle-income countries (LMICs). To help address this burden, organizations host over 6,000 outreach trips annually, 20% of which are orthopaedic. Monitoring post-surgical outcomes is critical to ensuring care quality; however, the implementation of such monitoring is unknown. The purpose of this review is to identify published follow-up practices of short-term orthopaedic surgery outreach trips to LMICs. METHODS: We completed a systematic review of Pubmed, Web of Science, EMBASE, and ProQuest following PRISMA guidelines. Follow-up method, rate, duration, and types of outcomes measured along with barriers to follow-up were collected and reported. RESULTS: The initial search yielded 1,452 articles, 18 of which were eligible. The mean follow-up time was 5.4 months (range: 15 days-7 years). The mean follow-up rate was 65.8% (range: 22%-100%), the weighted rate was 57.5%. Fifteen studies reported follow-up at or after 3 months while eight studies reported follow-up at or after 9 months. Fifteen studies reported follow-up in person, three reported follow-up via phone call or SMS. Outcome reporting varied among mortality, complications, and patient-reported outcomes. The majority (75%) outlined barriers to follow-up, most commonly noting transportation and costs of follow-up to the patient. CONCLUSIONS: There is minimal and heterogeneous public reporting of patient outcomes and follow-up after outreach trips to LMICs, limiting quality assessment and improvement. Future work should address the design and implementation of tools and guidelines to improve follow-up as well as outcome measurement to ensure provision of high-quality care.

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution.

Exposures to fine particulate matter PM2.5 are associated with Alzheimer's, Parkinson's (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.0 years old. We used multivariate linear regressions to examine cortical surface area and thickness, subcortical and cerebellar volumes and MoCA in ≤30 vs. ≥31 years old. MMC residents were exposed to PM2.5 ~ 30.9 µg/m3. Robust hemispheric differences in frontal and temporal lobes, caudate and cerebellar gray and white matter and strong associations between MoCA total and index scores and caudate bilateral volumes, frontotemporal and cerebellar volumetric changes were documented. MoCA LIS scores are affected early and low pollution controls ≥ 31 years old have higher MoCA vs. MMC counterparts (p ≤ 0.0001). Residency in MMC is associated with cognitive impairment and overlapping targeted patterns of brain atrophy described for AD, PD and Fronto-Temporal Dementia (FTD). MMC children and young adult longitudinal studies are urgently needed to define brain development impact, cognitive impairment and brain atrophy related to air pollution. Identification of early AD, PD and FTD biomarkers and reductions on PM2.5 emissions, including poorly regulated heavy-duty diesel vehicles, should be prioritized to protect 21.8 million highly exposed MMC urbanites.

A Lung Cancer Screening Education Program Impacts both Referral Rates and Provider and Medical Assistant Knowledge at Two Federally Qualified Health Centers.

BACKGROUND: Federally Qualified Health Centers (FQHCs) serve minority and low-socioeconomic populations and provide care to high-risk smokers. These centers frequently experience barriers, including low provider and medical assistant (MA) knowledge around lung cancer screening (LCS). Subsequent low LCS referral rates by providers at FQHCs limit utilization of LCS in eligible, high-risk, underserved patients. METHODS: Providers and MAs from two FQHCs participated in a LCS educational session. A pre-educational survey was administered at the start of the session and a post-educational survey at the end. The intervention included a presentation with education around non-small cell lung cancer, LCS, tobacco cessation, and shared-decision making. Both surveys were used to evaluate changes in provider and MA ability to determine eligible patients for LCS. The Pearson's Chi-squared test with Yates' continuity correction was used to measure the impact. RESULTS: A total of 29 providers and 28 MAs enrolled in the study from two FQHCs. There was an improvement, P < .009 and P < .015 respectively, in provider and MA confidence in identifying patients for LCS. Additionally, one year prior to the program, 9 low-dose computed tomography (LDCTs) were ordered at one of the FQHCs and 0 at the other. After the program, over 100 LDCTs were ordered at each FQHC. CONCLUSIONS: A targeted LCS educational program improves provider and MAs' ability to identify eligible LCS patients and is associated with an increase in the number of patients referred to LDCT at FQHCs.

The impact of income and education on lung cancer screening utilization, eligibility, and outcomes: a narrative review of socioeconomic disparities in lung cancer screening.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the US and worldwide. In particular, vulnerable populations such as those of low socioeconomic status (SES) are at the highest risk for and suffer the highest mortality from NSCLC. Although lung cancer screening (LCS) has been demonstrated to be a powerful tool to lower NSCLC mortality, it is underutilized by eligible smokers, and disparities in screening are likely to contribute to inequities in NSCLC outcomes. It is imperative that we collect and analyze LCS data focused on individuals of low socioeconomic position to identify and address barriers to LCS utilization and help close the gaps in NSCLC mortality along socioeconomic lines. Toward this end, this review aims to examine published studies that have evaluated the impact of income and education on LCS utilization, eligibility, and outcomes. We searched the PubMed, Ovid MEDLINE, and CINAHL Plus databases for all studies published from January 1, 2010, to October 21, 2020, that discussed socioeconomic-based LCS outcomes. The review reveals that income and education have impact on LCS utilization, eligibility, false positive rates and smoking cessation attempts; however, there is a lack of studies evaluating the impact of SES on LCS follow-up, stage at diagnosis, and treatment. We recommend the intentional inclusion of lower SES participants in LCS studies in order to clarify appropriate eligibility criteria, risk-based metrics and outcomes in this high-risk group. We also anticipate that low SES smokers and their providers will require increased support and education regarding smoking cessation and shared decision-making efforts.

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders.

Quadruple aberrant hyperphosphorylated tau (p-τ), amyloid-ß peptide, alpha-synuclein and TDP-43 brainstem and supratentorial pathology are documented in forensic ≤40y autopsies in Metropolitan Mexico City (MMC), and p-τ is the major aberrant protein. Post-traumatic stress disorder (PTSD) is associated with an elevated risk of subsequent dementia, and rapid eye movement sleep behavior disorder (RBD) is documented in PD, AD, Lewy body dementia and ALS. This study aimed to identify an association between PTSD and potential pRBD in Mexico. An anonymous online survey of 4502 urban college-educated adults, 29.3 ± 10.3 years; MMC, n = 1865; non-MMC, n = 2637, measured PTSD symptoms using the Impact of Event Scale-Revised (IES-R) and pRBD symptoms using the RBD Single-Question. Over 50% of the participants had IES-R scores ≥33 indicating probable PTSD. pRBD was identified in 22.6% of the participants across Mexico and 32.7% in MMC residents with PTSD. MMC subjects with PTSD had an OR 2.6218 [2.5348, 2.7117] of answering yes to the pRBD. PTSD and pRBD were more common in women. This study showed an association between PTSD and pRBD, strengthening the possibility of a connection with misfolded proteinopathies in young urbanites. We need to confirm the RBD diagnosis using an overnight polysomnogram. Mexican women are at high risk for stress and sleep disorders.

Metals, Nanoparticles, Particulate Matter, and Cognitive Decline.

Exposure to metals is ubiquitous and emission sources include gasoline, diesel, smoke from wildfires, contaminated soil, water and food, medical implants, waste recycling facilities, subway exposures, and occupational environments. PM2.5 exposure is associated with impaired cognitive performance, neurobehavioral alterations, incidence of dementia, and Alzheimer's disease (AD) risk. Heavy-duty diesel vehicles are major emitters of metal-rich PM2.5 and nanoparticles in Metropolitan Mexico City (MMC). Cognitive impairment was investigated in 336 clinically healthy, middle-class, Mexican volunteers, age 29.2 ± 13.3 years with 13.7 ± 2.4 years of education using the Montreal Cognitive Assessment (MoCA). MoCA scores varied with age and residency in three Mexican cities with cognition deficits impacting ~74% of the young middle-class population (MoCA ≤ 25). MMC residents ≥31 years ( x ¯ 46.2 ± 11.8 y) had MoCA x ¯ 20.4 ± 3.4 vs. low pollution controls 25.2 ± 2.4 (p < 0.0001). Formal education years positively impacted MoCA total scores across all participants (p < 0.0001). Residency in PM2.5 polluted cities impacts multi-domain cognitive performance. Identifying and making every effort to lower key pollutants impacting neural risk trajectories and monitoring cognitive longitudinal performance are urgent. PM2.5 emission control should be prioritized, metal emissions targeted, and neuroprevention interventions implemented early.

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young.

To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg tests in 575 clinically healthy subjects, age 21.0 ±â€¯5.7 y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3 ±â€¯9.1 y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.

Antimicrobials Used in Backyard and Commercial Poultry and Swine Farms in the Philippines: A Qualitative Pilot Study.

Chicken and pork are the most frequently consumed meat products in the Philippines. Swine and poultry are reared in either commercial farms (CMf) or backyard farms (BYf); the latter production system is relatively common and essential to food security in low- and middle-income countries (LMICs) such as the Philippines. Similar to resource-limited LMICs, antimicrobial use (AMU) surveillance has not yet been established; thus, AMU in food animals is a knowledge gap in understanding the emergence of antimicrobial resistance (AMR) in zoonotic foodborne bacteria in the country. This qualitative AMU pilot study aims to describe the antimicrobial active ingredients (AAIs) used and associated AMU practices (e.g., source of AAIs and informed AMU decisions) by poultry and swine CMf and BYf in the Philippines. Ninety-three farms across four regions in the Philippines voluntarily provided AMU information as part of a larger biosecurity and good practices study. The percentage of farms using AAI over the total number of farms was the metric used to describe AMU. In total, there were 30 AAIs used (CMf: n =27 and BYf: n = 13); per farm, the number of AAIs used ranged from 1 to 7. The spectrum of AAIs was more diverse in swine (n = 24) compared to poultry (n = 18). Enrofloxacin was the most frequently reported AAI in poultry (33%) and swine (36%) farms. Respiratory diseases were the most frequently reported reason for AMU in both species. Between production systems, significant differences were observed in the percentage of farms using amoxicillin (27% CMf vs. 3% BYf), colistin (17% CMf vs. 3% BYf), and oxytetracycline (12% CMf vs. 39% BYf). In terms of AMU practices, of important concern was the over-the-counter access of AAIs at retail outlets and the limited veterinary oversight in BYf. Our data indicated that antimicrobials critically important for human medicine are frequently used in poultry and swine farms in the Philippines. This study can inform the development of guidelines for curbing AMR through prudent AMU and serves as a reference point for AMU surveillance capacity development in the Philippines.

Thermal Conductivity Performance of 2D hBN/MoS2/Hybrid Nanostructures Used on Natural and Synthetic Esters.

In this paper, the thermal conductivity behavior of synthetic and natural esters reinforced with 2D nanostructures-single hexagonal boron nitride (h-BN), single molybdenum disulfide (MoS2), and hybrid h-BN/MOS2-were studied and compared to each other. As a basis for the synthesis of nanofluids, three biodegradable insulating lubricants were used: FR3TM and VG-100 were used as natural esters and MIDEL 7131 as a synthetic ester. Two-dimensional nanosheets of h-BN, MoS2, and their hybrid nanofillers (50/50 ratio percent) were incorporated into matrix lubricants without surfactants or additives. Nanofluids were prepared at 0.01, 0.05, 0.10, 0.15, and 0.25 weight percent of filler fraction. The experimental results revealed improvements in thermal conductivity in the range of 20-32% at 323 K with the addition of 2D nanostructures, and a synergistic behavior was observed for the hybrid h-BN/MoS2 nanostructures.

Ecological risk assessment of glyphosate in surface water when it is used to control floating aquatic macrophytes.

The present work evaluated the ecological risk of glyphosate by its commercial formulation (Roundup Original®) used to control floating aquatic macrophytes. Exposure analysis and ecological effects were performed from microcosm studies. The risk characterization was performed based on the calculation of the risk quotient. The commercial formulation of glyphosate had high toxicity when it was assessed separately. On the other hand, ecotoxicological evaluation of water samples from microcosms did not present toxicity to any tested organisms, however, glyphosate application is recommended exclusively to water bodies that have the surface completely covered by macrophytes.

Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies.

Checkpoint inhibitors have revolutionized cancer therapy but only work in a subset of patients and can lead to a multitude of toxicities, suggesting the need for more targeted delivery systems. Because of their preferential colonization of tumors, microbes are a natural platform for the local delivery of cancer therapeutics. Here, we engineer a probiotic bacteria system for the controlled production and intratumoral release of nanobodies targeting programmed cell death-ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) using a stabilized lysing release mechanism. We used computational modeling coupled with experimental validation of lysis circuit dynamics to determine the optimal genetic circuit parameters for maximal therapeutic efficacy. A single injection of this engineered system demonstrated an enhanced therapeutic response compared to analogous clinically relevant antibodies, resulting in tumor regression in syngeneic mouse models. Supporting the potentiation of a systemic immune response, we observed a relative increase in activated T cells, an abscopal effect, and corresponding increases in systemic T cell memory populations in mice treated with probiotically delivered checkpoint inhibitors. Last, we leveraged the modularity of our platform to achieve enhanced therapeutic efficacy in a poorly immunogenic syngeneic mouse model through effective combinations with a probiotically produced cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). Together, these results demonstrate that our engineered probiotic system bridges synthetic biology and immunology to improve upon checkpoint blockade delivery.

Programmable bacteria induce durable tumor regression and systemic antitumor immunity.

Synthetic biology is driving a new era of medicine through the genetic programming of living cells1,2. This transformative approach allows for the creation of engineered systems that intelligently sense and respond to diverse environments, ultimately adding specificity and efficacy that extends beyond the capabilities of molecular-based therapeutics3-6. One particular area of focus has been the engineering of bacteria as therapeutic delivery systems to selectively release therapeutic payloads in vivo7-11. Here we engineered a non-pathogenic Escherichia coli strain to specifically lyse within the tumor microenvironment and release an encoded nanobody antagonist of CD47 (CD47nb)12, an anti-phagocytic receptor that is commonly overexpressed in several human cancer types13,14. We show that delivery of CD47nb by tumor-colonizing bacteria increases activation of tumor-infiltrating T cells, stimulates rapid tumor regression, prevents metastasis and leads to long-term survival in a syngeneic tumor model in mice. Moreover, we report that local injection of CD47nb-expressing bacteria stimulates systemic tumor-antigen-specific immune responses that reduce the growth of untreated tumors, providing proof-of-concept for an abscopal effect induced by an engineered bacterial immunotherapy. Thus, engineered bacteria may be used for safe and local delivery of immunotherapeutic payloads leading to systemic antitumor immunity.

Rapid screening of engineered microbial therapies in a 3D multicellular model.

Synthetic biology is transforming therapeutic paradigms by engineering living cells and microbes to intelligently sense and respond to diseases including inflammation, infections, metabolic disorders, and cancer. However, the ability to rapidly engineer new therapies far outpaces the throughput of animal-based testing regimes, creating a major bottleneck for clinical translation. In vitro approaches to address this challenge have been limited in scalability and broad applicability. Here, we present a bacteria-in-spheroid coculture (BSCC) platform that simultaneously tests host species, therapeutic payloads, and synthetic gene circuits of engineered bacteria within multicellular spheroids over a timescale of weeks. Long-term monitoring of bacterial dynamics and disease progression enables quantitative comparison of critical therapeutic parameters such as efficacy and biocontainment. Specifically, we screen Salmonella typhimurium strains expressing and delivering a library of antitumor therapeutic molecules via several synthetic gene circuits. We identify candidates exhibiting significant tumor reduction and demonstrate high similarity in their efficacies, using a syngeneic mouse model. Last, we show that our platform can be expanded to dynamically profile diverse microbial species including Listeria monocytogenes, Proteus mirabilis, and Escherichia coli in various host cell types. This high-throughput framework may serve to accelerate synthetic biology for clinical applications and for understanding the host-microbe interactions in disease sites.

Análise estatística da caracterização gravimétrica de resíduos sólidos domiciliares: estudo de caso do município de Juiz de Fora, Minas Gerais / Statistical analysis of the gravimetric characterization of household solid waste: a case study from the city of Juiz de Fora, Minas Gerais, Brazil

RESUMO Parte dos resíduos coletados nos municípios brasileiros ainda são destinados de forma inadequada, resultando em transtornos à qualidade de vida e à saúde pública. Assim, a caracterização gravimétrica dos resíduos é um importante instrumento de gestão integrada, uma vez que permite conhecer quantitativamente as frações geradas. Nesse sentido, o presente estudo teve por objetivo analisar estatisticamente a composição gravimétrica dos resíduos sólidos domésticos de Juiz de Fora, Minas Gerais, em função das sete regiões urbanas do município e da renda domiciliar da população. Cerca de 140.500 toneladas de resíduos sólidos domésticos foram coletadas no município em 2015, representando uma geração per capita de 0,7 kg/hab./dia. Foram feitos testes estatísticos de hipóteses a 5% de significância em avaliações comparativas, além de testes de correlação para as frações majoritárias (orgânicos e recicláveis) e as respectivas rendas domiciliares. Os resultados indicaram que a fração de orgânicos corresponde a 43,81% dos resíduos gerados no município, 31,74% são passíveis de reciclagem, 14,36% são resíduos potencialmente contaminantes e 10,10% são rejeitos diversos. Observou-se que o resíduo gerado por famílias de alto poder aquisitivo tende a conter maiores percentuais de recicláveis, enquanto em famílias de menor poder aquisitivo os maiores percentuais tendem a ser de orgânicos. A grande incidência de orgânicos e recicláveis evidencia um potencial a ser explorado, apontando a necessidade de reavaliação da estrutura da coleta seletiva e possível instalação da usina de compostagem, mediante estudo de viabilidade técnica e econômica. Por fim, espera-se que o estudo auxilie o poder público local, norteando o planejamento e o dimensionamento de sistemas de coleta, tratamento e destinação de resíduos, além de projetos de educação ambiental, servindo de modelo para outras municipalidades.

ABSTRACT Much of the solid waste collected in Brazilian municipalities is still inappropriately destined, resulting in disorders related to quality of life and public health. Thus, the gravimetric characterization of household solid wastes is an important instrument of integrated management, since it quantitatively indicates the fractions generated. In this sense, the present study aims to analyse statistically the gravimetric composition of solid household waste from Juiz de Fora, Minas Gerais, Brazil, generated in 2015 regarding the seven urban regions of the city and the domestic income of the population. Statistical tests of hypothesis were carried out at 5% significance in comparative assessments, as well as correlation tests for organic and recyclable fractions and their respective domestic incomes. The results indicated that the organic fraction corresponds to 43.81% of the solid waste generated in the municipality, 31.74% is the recyclable fraction, 14.36% to potentially contaminant wastes and 10.10% of others. It was observed a trend of greater generation of recyclables in regions with higher socioeconomic status; on the other hand, regions with a predominance of families with lower incomes there was an increase in organic fraction. The high incidence of organic and recyclable materials indicates a potential to be explored, pointing out the need of re-evaluating the structure of the selective collection and the possible installation of a composting plant by a technical and economical feasibility study. Therefore, it is expected that the study supports the local public power, guiding the plan and design of solid waste collection, treatment and disposal systems, as well as environmental education projects and serving as a model for other municipalities.