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We use a background quasar to detect the presence of circumgalactic gas around a z = 0.91 low-mass star-forming galaxy. Data from the new Multi Unit Spectroscopic Explorer (MUSE) on the Very Large Telescope show that the galaxy has a dust-corrected star formation rate (SFR) of 4.7 ± 2.0 M⊙ yr-1, with no companion down to 0.22 M⊙ yr-1 (5σ) within 240 h-1 kpc ("30"). Using a high-resolution spectrum of the background quasar, which is fortuitously aligned with the galaxy major axis (with an azimuth angle α of only 15°), we find, in the gas kinematics traced by low-ionization lines, distinct signatures consistent with those expected for a "cold-flow disk" extending at least 12 kpc (3 × R1/2). We estimate the mass accretion rate Ṁin to be at least two to three times larger than the SFR, using the geometric constraints from the IFU data and the H I column density of log NH I/cm-2 ≃ 20.4 obtained from a Hubble Space Telescope/COS near-UV spectrum. From a detailed analysis of the lowionization lines (e.g., Zn II, Cr II, Ti II, Mn II, Si II), the accreting material appears to be enriched to about 0.4 Z⊙ (albeit with large uncertainties: log Z/Z⊙ = -0.4 ± 0.4), which is comparable to the galaxy metallicity (12 + log O/H = 8.7 ± 0.2), implying a large recycling fraction from past outflows. Blueshifted Mg II and Fe II absorptions in the galaxy spectrum from the MUSE data reveal the presence of an outflow. The Mg II and Fe II absorption line ratios indicate emission infilling due to scattering processes, but the MUSE data do not show any signs of fluorescent Fe II∗ emission.

We use a background quasar to detect the presence of circumgalactic gas around a z = 0.91 low-mass star-forming galaxy. Data from the new Multi Unit Spectroscopic Explorer (MUSE) on the Very Large Telescope show that the galaxy has a dust-corrected star formation rate (SFR) of 4.7 ± 2.0 M⊙ yr-1, with no companion down to 0.22 M⊙ yr-1 (5σ) within 240 h-1 kpc ("30"). Using a high-resolution spectrum of the background quasar, which is fortuitously aligned with the galaxy major axis (with an azimuth angle α of only 15°), we find, in the gas kinematics traced by low-ionization lines, distinct signatures consistent with those expected for a "cold-flow disk" extending at least 12 kpc (3 × R1/2). We estimate the mass accretion rate Ṁin to be at least two to three times larger than the SFR, using the geometric constraints from the IFU data and the H I column density of log NH I/cm-2 ≃ 20.4 obtained from a Hubble Space Telescope/COS near-UV spectrum. From a detailed analysis of the lowionization lines (e.g., Zn II, Cr II, Ti II, Mn II, Si II), the accreting material appears to be enriched to about 0.4 Z⊙ (albeit with large uncertainties: log Z/Z⊙ = -0.4 ± 0.4), which is comparable to the galaxy metallicity (12 + log O/H = 8.7 ± 0.2), implying a large recycling fraction from past outflows. Blueshifted Mg II and Fe II absorptions in the galaxy spectrum from the MUSE data reveal the presence of an outflow. The Mg II and Fe II absorption line ratios indicate emission infilling due to scattering processes, but the MUSE data do not show any signs of fluorescent Fe II∗ emission.

Summary: Adaptor chimeric antigen receptor (CAR) T‐cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T‐cell therapy in myeloid malignancies. The adaptor CAR T‐cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well‐tolerated, rapidly switchable, CD123‐directed UniCAR T‐cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti‐tumour responses, underlining the need to further design alternative AML‐specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS‐like tyrosine kinase 3 (FLT3)‐directed UniCAR T‐cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half‐life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3‐specific UniCAR T cells for the therapy of AML. [ABSTRACT FROM AUTHOR]

During the cutting process, it is crucial to replace cutting tools at the right time to meet machining accuracy requirements. However, determining tool life relies on the unsystematic tacit knowledge of skilled engineers. Moreover, the increasing variety of cutting tools needed to accommodate the trend towards small quantities of various products has made it even more challenging to determine tool life. This study aimed to address this issue by developing a system that could accurately determine when to replace ball end-mills without requiring the judgment of skilled engineers. The results of the study showed that anomaly detection methods can be applied to images of worn tools to determine tool life accurately. By converting current value data during cutting into images and using image classification methods, it is possible to classify tools according to their wear conditions, such as new, early wear, end stage of wear, and end of tool life. The study also showed that constructing a multimodal judgment system using both tool appearance image abnormality detection and current value data image classification resulted in a 98% judgment accuracy rate for tools that had reached the end of their service life, with a correct answer rate of over 90%.

Incorporation of Au° inside SiO2 was achieved by a solid-state method from the pyrolysis of the composites (Chitosan)•(AuCl3)n•(SiO2)m and (PS-co-4-PVP)•(AuCl3)n•(SiO2)m Similarly, the incorporation of Ag° inside SiO2 it was made from thermal treatment of the composites (Chitosan)•(AgNO3)n•(SiO2)m and (PS-co-4-PVP)•(AgNO3)n•(SiO2)m. The nature of the polymer controls the particle size for the Au/SiO2 composite, while that for the Ag/SiO2 both, polymer Chitosan and PS-co-4-PVP, produces similar particle size. In the case of the composite Ag/SiO2 the particle size as small as 5 nm were obtained. The 1:1 or 1:5 metal/polymer ratios, as well as the nature of the polymer in the macromolecular precursors (Chitosan)•(AuCl3)n•(SiO2)m and (PS-co-4-PVP)•(AuCl3)n•(SiO2)m influences the dispersion of the Au° nanostructures inside SiO2 matrix. The results are compared with those previously obtained for bimetallic composites Au/Ag//SiO2. A formation mechanism of the Au°/SiO2 and Ag°/SiO2 composites involving the combustion of the organic matter and the growth of the Au° and Ag° nanoparticles inside the holes, generated from the combustion process, is proposed. [ABSTRACT FROM AUTHOR]

Context. This paper presents the results obtained with the Multi Unit Spectroscopic Explorer (MUSE) for the core of the lensing cluster Abell 1689, as part of MUSE's commissioning at the ESO Very Large Telescope. Aims. Integral-field observations with MUSE provide a unique view of the central 1 × 1 arcmin2 region at intermediate spectral resolution in the visible domain, allowing us to conduct a complete census of both cluster galaxies and lensed background sources. Methods. We performed a spectroscopic analysis of all sources found in the MUSE data cube. Two hundred and eighty-two objects were systematically extracted from the cube based on a guided-and-manual approach. We also tested three different tools for the automated detection and extraction of line emitters. Cluster galaxies and lensed sources were identified based on their spectral features. We investigated the multiple-image configuration for all known sources in the field. Results. Previous to our survey, 28 di erent lensed galaxies displaying 46 multiple images were known in the MUSE field of view, most of them were detected through photometric redshifts and lensing considerations. Of these, we spectroscopically confirm 12 images based on their emission lines, corresponding to 7 different lensed galaxies between z = 0.95 and 5.0. In addition, 14 new galaxies have been spectroscopically identified in this area thanks to MUSE data, with redshifts ranging between 0.8 and 6.2. All background sources detected within the MUSE field of view correspond to multiple-imaged systems lensed by A1689. Seventeen sources in total are found at z ≥ 3 based on their Lyman-α emission, with Lyman-α luminosities ranging between 40:5 ≲ log(Lyα) ≲ 42:5 after correction for magnification. This sample is particularly sensitive to the slope of the luminosity function toward the faintest end. The density of sources obtained in this survey is consistent with a steep value of α ≤-1.5, although this result still needs further investigation. Conclusions. These results illustrate the effciency of MUSE in characterizing lensing clusters on one hand and in studying faint and distant populations of galaxies on the other hand. In particular, our current survey of lensing clusters is expected to provide a unique census of sources responsible for the reionization in a representative volume at z ~ 4-7. [ABSTRACT FROM AUTHOR]

Recent experimental findings in animals and humans indicate adverse respiratory effects from short-term exposures to particulate air pollutants, especially in sensitive subpopulations such as asthmatics. The relationship between air pollution and asthma has mainly been determined using particulate matter (PM) measurements from central sites. Validated tools are needed to assess exposures most relevant to health effects. Recently; a personal passive particulate sampler (personal Data-RAM, pDR, MIE Inc., Bedford, MA) has become available for studying personal exposures to PM with time resolution at 1 min. The pDR measures light scatter from PM in the 0.1-10 μM range, the significant range for health effects. In order to assess the ability of the pDR in predicting gravimetric mass, pDRs were collocated with PM[SUB2.5] and PM[SUB10] Harvard Impactors (HI) inside and outside nine homes of asthmatic children and at an outdoor central Air Pollution Control District site. Results are presented of comparisons between the HI samplers and the pDR in various modes of operation: passive, active, and active with a heated inlet. When used outdoors at fixed sites the pDR readings exhibit interference from high relative humidity (RH) unless operated with a method for drying inlet air such as a heater, or if readings at times of high RH are adjusted. The pDR correlates more highly with the HI PM[SUB2.5] than with the HI PM[SUB10] (r[SUP2]=0.66 vs. 0.13 for outdoors, r[SUP2] = 0.42 vs. 0.20 for indoors). The pDR appears to be a useful tool for an epidemiologic study that aims to examine the relationship between health outcomes and personal exposure to peaks in PM. [ABSTRACT FROM AUTHOR]

The stability of Interleukin 2 (IL-2) is an essential characteristic for the development of a stable formulation. Thus, this function should be preserved during purification, formulation and long-term storage. For IL-2 the major degradation routes are oxidation and aggregation, so formulations avoiding this kind of modifications must be carefully design. In this work we developed two formulations of IL-2 which efficiently retained the stability of this cytokine. IL-2 was obtained from the Center for Genetic Engineering and Biotechnology (Havana, Cuba). All reagents used to prepared each formulation were of analytical grade and purchased by different commercial sources. IL-2 was prepared in different formulations by adding the additives (aminoacids, polymers and quelators) diluted into the formulation buffer to a convenient concentration. Formulations were filtered, and 1.0 mL volumes were aliquoted into 3 c.c. type 1 glass vials. Afterward vials were sealed with bromobutyl stoppers and aluminum seals. When lyophilization took place vials were sealed after the process. All steps were under laminar flow conditions. Samples were analyzed through the Quality Control System of CIGB. Results obtained by different techniques pointed to that additives used here (dextrane/glycine for the freeze-dried formulation, and EDTA/glycine for liquid formulation) efficiently preserved IL-2 stability. Although this is not an unexpected result because of the preferential exclusion mechanism by which solutes stabilized proteins, this is an essential verification to develop a stable formulation. As judged by different assays, the use of aminoacids and polymers may decrease IL-2 degradation in formulations developed in this work. [ABSTRACT FROM AUTHOR]

Objective: This study aims to identify factors associated with excessive screen time among preschoolers in Lima, Peru., Methods: Cross-sectional analysis from a 2019 panel study in Lima, Peru, was conducted focusing on women, aged 18 and above, who are mothers of 3- to 5-year-olds in mid-high and mid-low districts. There were two outcome variables: excessive TV and excessive electronic devices screen time, defined as ≥ 1 h of screen exposure for each one. Explored factors included the mother's age, education and wealth index and the children's age, sex, physical activity, day care attendance and ultra-processed food consumption. Crude (cPR) and adjusted prevalence ratios (aPR) were estimated for the association between associated factors and excessive screen time using the GLM Poisson of with a logarithmic link., Results: Excessive TV screen time and electronic devices prevalence was 74% and 36.9%, respectively. For TV screen time, a high wealth index (aPR 1.13; 95%CI: 1.03-1.23) and children's age (aPR 1.18; 95%CI: 1.08-1.29 for 4 years, PR = 1.17; 95%CI: 1.07-1.28 for 5 years) were significant. For electronic devices, significant associations included mothers with more than 3 children (aPR 0.77; 95%CI: 0.62-0.96), being single (aPR 1.27; 95%CI: 1.01-1.58) and a high wealth index (aPR 1.38; 95%CI: 1.13-1.68). Furthermore, significant associations were found between excessive electronic device screen time and consumption of candies and chocolates (aPR 1.38; 95%CI: 1.08-1.77)., Conclusions: Seven out of 10 preschool children exceeded the recommended television screen time. Certain characteristics of the children, their mothers and the family's socio-economic situation are related to excessive television screen time and excessive electronic device screen time., (© 2024 John Wiley & Sons Ltd.)

Background: ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR., Objectives: To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients., Methods: Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0-II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment., Results: At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) -9.3 versus -4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS-6) questionnaire, (2) -2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus -0.6 (p = .01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis-treated patients, whereas it rose across all the biopsies in the control group. At the 4-year follow-up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of -3.0 vs. -9.3 fibers/mm) and the distal leg (mean difference [MD] -4.9 vs. -8.6 fibers/mm). ADI in tafamidis-treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm 2 ) and the distal leg (23 vs. 40 amyloid/mm 2 ) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years., Conclusions: Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes., (© 2024 Peripheral Nerve Society.)

Zika virus (ZIKV) is a mostly non-lethal disease in humans transmitted by mosquitoes or humans that can produce severe brain defects such as microcephaly in babies and Guillain-Barré syndrome in elderly adults. The use of optimal control strategies involving information campaigns about insect repellents and condoms alongside an available safe and effective vaccine can prevent the number of infected humans with ZIKV. A system of nonlinear ordinary differential equations is formulated for the transmission dynamics of ZIKV in the presence of three control strategies to evaluate the impact of various scenarios during a ZIKV epidemic. In addition, we estimate parameters using weekly incidence data from previous ZIKV outbreaks in Colombia and Puerto Rico to capture the dynamics of an epidemic in each country when control measures are available. The basic reproduction number, R 0 , of each country is calculated using estimated parameters (without the controls). The vector-borne transmission threshold (R v ) is dominant in both countries , but the sexual transmission threshold (R d ) in Colombia is considerably higher than in Puerto Rico. Numerical simulations for Colombia show that the most effective strategies are to use three controls since the start of the outbreak. However, for Puerto Rico only information campaigns about mosquito repellents and vaccination are the most effective ways to mitigate the epidemic., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The use of pesticides can result in harm to both the environment and human health. There is a growing concern in the field of occupational health about the impact on the mental health of agricultural workers., Objectives: The objective of this review was to systematize scientific evidence from the last ten years on the impact of occupational exposure to pesticides on the development of depression symptoms in agricultural workers., Methods: We conducted a comprehensive search in the PubMed and Scopus databases from 2011 to September 2022. Our search included studies in English, Spanish, and Portuguese that examined the association between occupational exposure to pesticides and symptoms of depression in agricultural workers, following the guidelines recommended by the PRISMA statement and the PECO strategy (Population, Exposure, Comparison, and Outcomes)., Results: Among the 27 articles reviewed, 78% of them indicated a link between exposure to pesticides and the incidence of depression symptoms. The pesticides most frequently reported in the studies were organophosphates (17 studies), herbicides (12 studies), and pyrethroids (11 studies). The majority of the studies were rated as having intermediate to intermediate-high quality, with the use of standardized measures to assess both exposure and effect., Conclusion: The updated evidence presented in our review indicates a clear association between pesticide exposure and the development of depressive symptoms. However, more high-quality longitudinal studies are necessary to control for sociocultural variables and utilize pesticide-specific biomarkers and biomarkers of depression. Given the increased use of these chemicals and the health risks associated with depression, it is crucial to implement more stringent measures to monitor the mental health of agricultural workers regularly exposed to pesticides and to enhance surveillance of companies that apply these chemicals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Boris Lucero reports financial support was provided by The National Fund for Scientific and Technological Development FONDECYT, Chile., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC)., Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes., Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants . COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes., Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients., Competing Interests: The authors declare that there are no conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Mouse models are useful for the early down-selection of malaria vaccine candidates. The Walter Reed Army Institute of Research has optimized a transgenic Plasmodium berghei sporozoite challenge model to compare the efficacy of Plasmodium falciparum circumsporozoite protein (CSP) vaccines. GSK's RTS,S vaccine formulated in the adjuvant AS01 can protect malaria-naïve individuals against malaria. We report that the RTS,S/AS01 vaccine induces high level sterile protection in our mouse model. Down titration of the antigen at a constant AS01 dose revealed a potent antigen dose-sparing effect and the superiority of RTS,S/AS01 over a soluble CSP antigen. RTS,S-mediated protective immunity was associated with a threshold of major repeat antibody titer. Combined titration of the antigen and adjuvant showed that reducing the adjuvant could improve antibody boosting post-3rd vaccination and reduce the threshold antibody concentration required for protection. Mouse models can provide a pathway for preclinical assessment of strategies to improve CSP vaccines against malaria., (© 2023. Springer Nature Limited.)

Objectives.: Motivation for the study. Peruvian Law No. 30021 establishes the use of warning octagons for foods with high content of critical nutrients (sugar, sodium, saturated and trans fats); however, the declaration of nutritional information is not mandatory. Main findings. Of a total of 4404 processed and ultra-processed foods marketed in supermarkets in Lima, only 71.4% declared some type of nutritional information. In addition, only 46.0% declared information on the content of critical nutrients regulated by Law No. 30021. Implications. There is a need for a mandatory and standardized declaration of nutritional information on packaged foods marketed in Peru, in order to allow the population to make healthy decisions when choosing their food and to monitor the correct use of warning octagons. . To estimate the number of processed and ultra-processed beverages and foods that provide nutritional information on their packaging, and to describe the characteristics of this information, as well as to determine the presence of nutritional information on products with octagons., Materials and Methods.: Photographs were taken of the labels of 4404 processed and ultra-processed beverages and foods marketed in supermarkets in Metropolitan Lima. The information on the label was collected and registered in the mobile and web version of the Food Label Information Program (FLIP). We analyzed variables related to the nutritional information, the way in which such information is declared and the information in beverages and foods with octagons., Results.: Only 71.4% of the products had some type of nutritional information. Of these, 13.8% provided the nutritional information as a text and not in a table, and only 56.3% declared it per 100 grams or milliliters. Of the total number of foods with the octagon "Contains trans fats", only 19.2% declared their content., Conclusions.: More than a quarter of the beverages and packaged foods in the Peruvian market did not provide nutritional information of any kind, and of those that did, only one did so in different formats and units. In addition, we found that a proportion of beverages and foods for each type of octagon did not declare information of the nutrient that is mentioned in the octagon.

Fleas and ticks represent the two main groups of ectoparasites that infest companion animals. In particular, the flea Ctenocephalides felis felis and several members of the Rhipicephalus sanguineus complex are the main vectors of a wide range of pathogens on the American continent. They are competent vectors for several members of the genus Rickettsia, which encompass at least 15 pathogenic obligate intracellular bacteria that colonize the endothelial cells of vertebrates. In Mexico, 10 species of Rickettsia belonging to three groups have been detected in six species of ectoparasites from dogs in 9 of the 32 states of the country. However, in some larger regions of the country, active epidemiological surveillance has not been carried out. For this reason, the aim of this study was to identify the presence of members of the genus Rickettsia in fleas and ticks of dogs and cats in the state of Puebla, Mexico. A cross-sectional study was carried out to collect ectoparasites of dogs and cats during August to November 2019. Samples were fixed in 70% ethanol and examined to identify the presence of Rickettsia DNA by the amplification and sequencing of specific fragments of the gltA and ompB genes using conventional PCR. The recovered sequences were compared with those deposited in GenBank, and phylogenetic analyses were carried out to identify the position of the pathogens detected with respect to the valid species previously reported worldwide. Additionally, ecological parameters of the ectoparasite infestations were also calculated. We recovered 196 ectoparasites belonging to two species, 33 C. felis felis and 163 R. sanguineus s.l. (Rhipicephalus linnaei), parasitizing 46 hosts (42 dogs and 4 cats) in 11 localities of the state of Puebla. We detected the presence of Rickettsia felis in three pools of C. felis felis, and five from R. sanguineus s.l. Our work provides the first record of R. felis in hard ticks of Mexico and Central America, with new collection localities for this pathogen in central Mexico., (© 2022 Wiley-VCH GmbH.)

Context: The COVID-19 pandemic has disproportionately impacted vulnerable populations, including those who are non-English-speaking and those with lower socioeconomic status; yet, participation of these groups in contact tracing was initially low. Distrust of government agencies, anticipated COVID-19-related stigma, and language and cultural barriers between contact tracers and communities are common challenges., Program: The Community Outreach Specialist (COS) program was established within the Connecticut Department of Public Health (DPH) COVID-19 contact tracing program to encourage participation in contact tracing and address a need for culturally competent care and social and material support among socially vulnerable and non-English-speaking populations in 11 high-burden jurisdictions in Connecticut., Implementation: In partnership with state and local health departments, we recruited 25 COS workers with relevant language skills from target communities and trained them to deliver contact tracing services to vulnerable and non-English speaking populations., Evaluation: We conducted a cross-sectional analysis using data from ContaCT, DPH's enterprise contact tracing system. Overall, the COS program enrolled 1938 cases and 492 contacts. The proportion of residents reached (ie, called and interviewed) in the COS program was higher than that in the regular contact tracing program for both cases (70% vs 57%, P < .001) and contacts (84% vs 64%, P < .001). After adjusting for client age, sex, race and ethnicity, language, and jurisdiction, we found that the COS program was associated with increased reach for contacts (odds ratio [OR] = 1.52; 95% confidence interval [95% CI], 1.17-1.99) but not for cases (OR = 0.78; 95% CI, 0.70-0.88). Rapid qualitative analysis of programmatic field notes and meeting reports provided evidence that the COS program was feasible and acceptable to clients and contributed to COVID-19 education and communication efforts., Conclusion: A COS program employing a client-centered, community-engaged strategy for reaching vulnerable and non-English-speaking populations was feasible and more effective at reaching contacts than standard COVID-19 contact tracing., Competing Interests: The authors have indicated that they have no potential conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The effects of diabetes on the cardiovascular system as well as in the kidney are profound, which include hypertrophy and fibrosis. Diabetes also induces oxidative stress, at least in part due to the uncoupling of nitric oxide synthase (NOS); this is a shift in NO production toward superoxide production due to reduced levels of the NOS cofactor tetrahydrobiopterin (BH4). With this in mind, we tested the hypothesis that BH4 supplementation may prevent the development of diabetic cardiomyopathy and nephropathy. Methods: Diabetes was induced in Balb/c mice with streptozotocin. Then, diabetic mice were divided into two groups: one group provided with BH4 (sapropterin) in drinking water (daily doses of 15 mg/kg/day, during eight weeks) and the other that received only water. A third group of normoglycemic mice that received only water were used as the control. Results: Cardiac levels of BH4 were increased in mice treated with BH4 (p = 0.0019). Diabetes induced cardiac hypertrophy, which was prevented in the group that received BH4 (p < 0.05). In addition, hypertrophy was evaluated as cardiomyocyte cross-sectional area. This was reduced in diabetic mice that received BH4 (p = 0.0012). Diabetes induced cardiac interstitial fibrosis that was reduced in mice that received BH4 treatment (p < 0.05). We also evaluated in the kidney the impact of BH4 treatment on glomerular morphology. Diabetes induced glomerular hypertrophy compared with normoglycemic mice and was prevented by BH4 treatment. In addition, diabetic mice presented glomerular fibrosis, which was prevented in mice that received BH4. Conclusions: These results suggest that chronic treatment with BH4 in mice ameliorates the cardiorenal effects of diabetes,, probably by restoring the nitroso−redox balance. This offers a possible new alternative to explore a BH4-based treatment for the organ damage caused by diabetes., Competing Interests: The authors declare no conflict of interest.

In 2019, Connecticut launched an opioid overdose-monitoring program to provide rapid intervention and limit opioid overdose-related harms. The Connecticut Statewide Opioid Response Directive (SWORD)-a collaboration among the Connecticut State Department of Public Health, Connecticut Poison Control Center (CPCC), emergency medical services (EMS), New England High Intensity Drug Trafficking Area (HIDTA), and local harm reduction groups-required EMS providers to call in all suspected opioid overdoses to the CPCC. A centralized data collection system and the HIDTA overdose mapping tool were used to identify outbreaks and direct interventions. We describe the successful identification of a cluster of fentanyl-contaminated crack cocaine overdoses leading to a rapid public health response. On June 1, 2019, paramedics called in to the CPCC 2 people with suspected opioid overdose who reported exclusive use of crack cocaine after being resuscitated with naloxone. When CPCC specialists in poison information followed up on the patients' status with the emergency department, they learned of 2 similar cases, raising suspicion that a batch of crack cocaine was mixed with an opioid, possibly fentanyl. The overdose mapping tool pinpointed the overdose nexus to a neighborhood in Hartford, Connecticut; the CPCC supervisor alerted the Connecticut State Department of Public Health, which in turn notified local health departments, public safety officials, and harm reduction groups. Harm reduction groups distributed fentanyl test strips and naloxone to crack cocaine users and warned them of the dangers of using alone. The outbreak lasted 5 days and tallied at least 22 overdoses, including 6 deaths. SWORD's near-real-time EMS reporting combined with the overdose mapping tool enabled rapid recognition of this overdose cluster, and the public health response likely prevented additional overdoses and loss of life.

Prions are proteins that cause fatal neurodegenerative diseases. The misfolded conformation adopted by prions can be transmitted to other normally folded proteins. Therapeutics to stop prion proliferation have been studied experimentally; however, it is not clear how the combination of different types of treatments can decrease the growth rate of prions in the brain. In this article, we combine the implementation of pharmacological chaperones and interferons to develop a novel model using a non-linear system of ordinary differential equations and study the quantitative effects of these two treatments on the growth rate of prions. This study aims to identify how the two treatments affect prion proliferation, both individually and in tandem. We analyze the model, and qualitative global results on the disease-free and disease equilibria are proved analytically. Numerical simulations, using parameter values from in vivo experiments that provide a pharmaceutically important demonstration of the effects of these two treatments, are presented here. This mathematical model can be used to identify and optimize the best combination of the treatments within their safe ranges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Graft-versus-host disease (GVHD) is a serious complication in allogeneic transplantation. The first-line treatment is high doses of corticosteroids. In the absence of response to corticosteroids, several immunosuppressive drugs can be used, but they entail an elevated risk of severe infections. Added to this, there are patients who do not improve on any immunosuppressive treatment, with subsequent deteriorated quality of life and high mortality. Ruxolitinib has been shown to induce responses in refractory patients. In this study we have presented our real-life experience., Methods: A retrospective analysis was performed on patients with severe GVHD refractory to corticosteroids. Demographic, previous treatment, response and mortality data were collected., Results: Since 2014, seventeen patients with GVHD were treated with ruxolitinib due to refractoriness to corticosteroids and immunosuppressants and a few to extracorporeal photopheresis, 8 with acute GVHD (1 pulmonary, 4 cutaneous grade IV and 3 digestive grade IV) and 9 with chronic GHVD (5 cutaneous sclerodermiform, 2 pulmonary and 1 multisystemic). The overall response to ruxolitinib treatment for acute GVHD was 80%, 40% with partial response and 40% with complete remission. Global response in chronic GVHD was 79%. The GVHD mortality was only seen in acute disease and was 40%. Causes of mortality in those patients were severe viral pneumonia, post-transplantation hemophagocytic syndrome and meningeal GVHD refractory to ruxolitinib., Conclusions: In our series, the use of ruxolitinib as a rescue strategy in acute or chronic GVHD was satisfactory. Ruxolitinib treatment in patients with a very poor prognosis showed encouraging results. However, the GVHD mortality remains high in refractory patients, showing that better therapeutic strategies are needed., (Copyright © 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.