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OBJECTIVES: Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. METHODS: From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. RESULTS: Median follow up was 19.3 months (3.8 - 36.6). Median BOT was 4.6 min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. CONCLUSIONS: MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

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Introduction: Hearing health is a public health concern that affects the quality of life and can be disturbed by noise exposure, generating auditory and extra-auditory symptoms. Objective. To identify the hearing health status in adults living in Bogotá and its association with environmental noise exposure and individual and otological factors. Objective: To identify the hearing health status in adults living in Bogotá and its association with environmental noise exposure and individual and otological factors. Materials and methods: We conducted a cross-sectional study using a database with 10,311 records from 2014 to 2018, consigned in a structured survey of noise perception and hearing screening. We performed a descriptive, bivariate, and binary logistic regression analysis. Results: Of the included participants, 35.4% presented hearing impairment. In the perception component, 13.0 % reported not hearing well; 28.8 % had extra-auditory symptoms, 53.3 % informed otological antecedents and 69.0 % presented discomfort due to extramural noise. In the logistic regression, the variables with the highest association for hearing impairment were living in noisy areas (OR = 1.50) (95% CI: 1.34-1.69), being male (OR = 1.85) (95% CI: 1.64-2.09), increasing age (for each year of life, the risk of hearing impairment increased 6%), and having history of extra-auditory symptoms (OR = 1.86) (95% CI: 1.66-2.08). Conclusions: Hearing impairment is multi-causal in the studied population. The factors that promote its prevalence are increasing age, being male, smoking, ototoxic medications, living in areas with high noise exposure, and extra-auditory symptoms.

Introducción. La salud auditiva es un tema de interés en salud pública que afecta la calidad de vida y que puede afectarse por la exposición continua al ruido, un factor de riesgo que genera síntomas auditivos y extraauditivos. Objetivo. Identificar el estado de salud auditiva de adultos que viven en Bogotá, y su asociación con factores de exposición a ruido ambiental, individuales y otológicos. Materiales y métodos. Se realizó un estudio transversal mediante el análisis de una base de datos con 10.311 registros, obtenidos entre los años 2014 y 2018, producto de una encuesta estructurada de percepción de ruido y tamizaje auditivo. Se hizo un análisis descriptivo bivariado y una regresión logística binaria. Resultados. El 35,4 % de los participantes presentó disminución auditiva. En el componente de percepción: 13,0 % refirió no escuchar bien, 28,8 % informó síntomas extraauditivos, 53,3 % tenía antecedentes otológicos, y 69,0 % manifestó molestia por ruido extramural. En la regresión logística, las variables más asociadas con disminución auditiva fueron: de las ambientales, vivir en zonas de mayor ruido (OR = 1,50) (IC95%: 1,34-1,69); de las individuales, ser hombre (OR = 1,85) (IC95%: 1,64-2,09) y la edad (por cada año de vida, el riesgo de disminución auditiva aumentó 6 %); y de las otológicas, tener antecedente de síntomas otológicos (OR = 1,86) (IC95%: 1,66-2,08). Conclusiones. La disminución auditiva es multicausal en la población evaluada. Los factores que aumentan su prevalencia son incremento de la edad, ser hombre, tabaquismo, medicamentos ototóxicos, vivir en zonas de mayor exposición a ruido y presentar síntomas extraauditivos.

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Objective: SARS-CoV-2 infection induces an immune response that causes excessive inflammation damaging cardiac tissue and vascular endothelium. The objective of this study is to review a series of cases of hospitalized patients with pre-existing cardiac disease to describe the clinical behavior and highlight the low frequency of morbidity and mortality. Method: Retrospective study of 17 patients with a confirmed diagnosis of COVID-19 by polymerase chain reaction test or antigen test, a history of cardiovascular disease with or without comorbidities, and a history of at least one dose of the vaccine for COVID-19, during the period between December 30, 2021 and March 17, 2022 at the Ignacio Chávez National Institute of Cardiology in Mexico City. Results: The most frequent cardiac pathology was acute myocardial infarction (31.25%) and the most common arrhythmia was atrial fibrillation (25%). The median number of days of hospital stay was 10 days (interquartile range: 4-14). Regarding the outcomes, 94% of the patients were discharged due to clinical improvement, and only one patient died during his hospitalization. Conclusions: It is crucial to continue investigating SARS-CoV-2 effects in patients pre-existing heart disease and in those with persistent symptoms after infection. This will allow the development of more effective strategies for the treatment and prevention of cardiovascular complications associated with COVID-19.

Objetivo: La infección por SARS-CoV-2 induce una respuesta inmunitaria que causa una inflamación excesiva dañando al tejido cardiaco y al endotelio vascular. El objetivo de este estudio es revisar una serie de casos de pacientes hospitalizados con patología cardiaca preexistente para describir el comportamiento clínico y resaltar la baja frecuencia de morbimortalidad. Método: Estudio retrospectivo de 17 pacientes con diagnóstico confirmado de COVID-19 mediante prueba de reacción en cadena de la polimerasa o prueba de antígenos, antecedente de enfermedad cardiovascular en presencia o no de comorbilidad, y antecedente de al menos una dosis de la vacuna para la COVID-19, durante el periodo entre el 30 de diciembre de 2021 y el 17 de marzo de 2022, en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México. Resultados: La patología cardiaca previa más frecuente fue el infarto agudo de miocardio (31.25%), y la arritmia más común fue la fibrilación auricular (25%). La mediana de días de estancia hospitalaria fue de 10 (rango intercuartílico: 4-14). En cuanto a los desenlaces, el 94% de los pacientes fueron dados de alta por mejoría clínica y solo un paciente falleció durante su internamiento. Conclusiones: Es crucial continuar investigando y monitoreando los efectos del SARS-CoV-2 en los pacientes con enfermedades cardiacas preexistentes y en aquellos con síntomas persistentes después de la infección. Esto permitirá desarrollar estrategias más efectivas para el tratamiento y la prevención de las complicaciones cardiovasculares asociadas a la COVID-19.

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This Systematic Review assesses the economic impact of Respiratory Syncytial Virus (RSV) in Latin America and the Caribbean (LAC) in relation to healthcare resource utilization and associated costs. We searched online databases from January 2012 to November 2022 to identify eligible publications. We identified 12 publications that reported direct costs, indirect costs, and resources associated with RSV and its complications. The primary direct medical resources reported were medical services, diagnostics tests and procedures, and length of stay (LOS). Direct total costs per patient ranged widely from $563 to $19,076. Direct costs are, on average, 98% higher than indirect costs. Brazil reported a higher total cost per patient than Colombia, El Salvador, México, Panamá, and Puerto Rico, while for indirect costs per patient, El Salvador and Panamá had higher costs than Brazil, Colombia, and Mexico. The mean LOS in the general ward due to RSV was 6.9 days (range 4 to 20 days) and the mean Intensive Care Unit LOS was 9.1 days (range 4 to 16 days). In many countries of the LAC region, RSV represents a considerable economic burden on health systems, but significant evidence gaps were identified in the region. More rigorous health economic studies are essential to better understand this burden and to promote effective healthcare through an informed decision-making process. Vaccination against RSV plays a critical role in mitigating this burden and should be a priority in public health strategies.

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Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective tissue disorder associated with mutations in the transforming growth factor ß receptor. It is characterized by distinctive craniofacial changes, skeletal features, and cardiovascular complications. We present a case of a 24-year-old male with development delay and a one-year history of progressively worsening dyspnea on moderate exertion and orthopnea. Echocardiography revealed right atrial and right ventricle dilation, right ventricle hypertrophy, atrial septal defect, and aneurysmal dilation of the pulmonary artery trunk. This case underscores the importance of early detection and comprehensive imaging in patients suspected of having LDS, particularly considering the potential for atypical vascular manifestations.

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BACKGROUND: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease. OBJECTIVES: To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC). METHODS: Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097). RESULTS: We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum. CONCLUSION: The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively.

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INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

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BACKGROUND: Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions. METHODS: We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data. RESULTS: Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities. CONCLUSIONS: SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) is a type of radiation therapy for cancer. With SMART, treatment can be adapted based on daily changes in the body seen via imaging. SMART can safely deliver radiation to lung tumors near the center of the body which are risky to treat, due to potential damage to nearby organs. We looked at 14 patients who received SMART to determine how much changing the radiation plan each day improved our ability to safely deliver high doses. We found that SMART not only improved our ability to cover the entirety of the tumor with the dose originally intended, but also reduced dose to nearby organs. Treatment resulted in excellent control of the tumor with few side effects. SMART shows promise for safer and more effective treatment for lung tumors in this part of the body.

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Weeds are attractive models for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Currently, a lack of genomic information precludes research to elucidate the genetic basis of rapid adaptation for important traits like herbicide resistance and stress tolerance and the effect of evolutionary mechanisms on wild populations. The International Weed Genomics Consortium is a collaborative group of scientists focused on developing genomic resources to impact research into sustainable, effective weed control methods and to provide insights about stress tolerance and adaptation to assist crop breeding.

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Background: Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed. Methods: We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097). Results: From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I2: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I2: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I2: 87.7], and 9.7% [95%IC 5.9-15.6, I2: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime. Conclusion: Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.

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Purpose: Bladder preservation with trimodal therapy (TMT; maximal tumor resection followed by chemoradiation) is an effective paradigm for select patients with muscle invasive bladder cancer. We report our institutional experience of a TMT protocol using nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB). Methods and Materials: A retrospective analysis was performed on consecutive patients with nonmetastatic muscle invasive bladder cancer who were treated with TMT using MRgRT between 2019 and 2022. Patients underwent intensity modulated RT-based nonadaptive MRgRT PBB contoured on True fast imaging with steady state precession (FISP) images (full bladder) followed sequentially by computed tomography-based RT to the whole empty bladder and pelvic lymph nodes with concurrent chemotherapy. MRgRT treatment time, table shifts, and dosimetric parameters of target coverage and normal tissue exposure were described. Prospectively assessed acute and late genitourinary and gastrointestinal (GI) toxicity were reported. Two-year local control was assessed with Kaplan-Meier methods. Results: Seventeen patients were identified for analysis. PBB planning target volume margins were ≤8 mm in 94% (n = 16) of cases. Dosimetric target coverage parameters were favorable and all normal tissue dose constraints were met. For MRgRT PBB fractions, median table shifts were 0.4 cm (range, 0-3.15), 0.45 cm (0-2.65), and 0.75 cm (0-4.8) in the X, Y, and Z planes, respectively. Median treatment time for MRgRT PBB fractions was 9 minutes (range, 6.9-17.4). We identified 32 out of 100 total MRgRT fractions that may have benefitted from online adaptation based on changes in organ position relative to planning target volume, predominantly because of small bowel (13/32, 41%) or rectum (8/32, 25%). Two patients discontinued RT prematurely. The incidence of highest-grade acute genitourinary toxicity was 1 to 2 (69%) and 3 (6%), whereas the incidence of acute GI toxicity was 1 to 2 (81%) and 3 (6%). There were no late grade 3 events; 17.6% had late grade 2 cystitis and none had late GI toxicity. With median follow-up of 18.2 months (95% CI, 12.4-22.5), the local control rate was 92%, and no patient has required salvage cystectomy. Conclusions: Nonadaptive MRgRT PBB is feasible with favorable dosimetry and low resource utilization. Larger studies are needed to evaluate for potential benefits in toxicity and local control associated with this approach in comparison to standard treatment techniques.

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INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. METHODS: We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. RESULTS: From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. CONCLUSION: There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

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Antimicrobial resistance is a pressing global health concern, leading to 4.95 million deaths in 2019. We conducted a systematic review and meta-analysis to assess the lethality attributed to infections caused by multidrug-resistant organisms (MDROs) in Latin America and the Caribbean. A comprehensive search of major databases retrieved relevant studies from 2000-2022. We included 54 observational studies, primarily from Brazil, Argentina, and Colombia. The most commonly studied organism was methicillin-resistant Staphylococcus aureus. The overall unadjusted case fatality rate related to MDROs was 45.0%; higher adjusted lethality was observed in persons infected with MDROs than in those infected with other pathogens (adjusted odds ratio 1.93, 95% CI 1.58-2.37). A higher lethality rate was seen in patients who did not receive appropriate empirical treatment (odds ratio 2.27, 95% CI 1.44-3.56). These findings underscore the increased lethality associated with antimicrobial resistance in Latin America and the Caribbean.

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Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris' water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [ 3 H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (K D ) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (B max ) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M 1 subtype of MSG when compared with control rats (M 2 to M 5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M 1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M 1 mAChR subtype protein expression is a potential therapeutic target.

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Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

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INTRODUCTION: Neisseria gonorrhoeae causes gonorrhoea, a globally neglected but increasing disease. This systematic review and meta-analysis reviewed the epidemiology and economic burden of gonorrhoea in Latin America and the Caribbean (LAC). METHODS: We searched PubMed, EMBase, Cochrane Library, EconLIT, CINAHL, CRD, LILACS, Global Health, Global Dissertations and Theses, SciELO, Web of Science databases, countries' ministries of health, and the IHME's Global Burden of Disease databases. Studies published in the last 10 years (20 years for economic studies) were included if conducted in any LAC country, without language restrictions. The main outcome measures were incidence/prevalence, proportion of co-infections, case fatality rates, specific mortality/hospitalisation rates, direct/indirect costs, and impact of gonorrhoea on quality of life. To assess evidence quality, we used a checklist developed by the US National Heart, Lung, and Blood Institute for observational studies and trial control arms, the Cochrane Effective Practice Organization of Care Group tool for randomised controlled trials, and the CICERO checklist for economic studies. RESULTS: We identified 1290 articles; 115 included epidemiological studies and one included an economic study. Ministry of health data from Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay were identified. Gonorrhoea prevalence was 1.46% (95% confidence interval [CI] 1.00-2.00%) from 48 studies and 5.68% (95% CI 4.23-7.32%) from 58 studies for non-high-risk and high-risk populations, respectively. Cumulative incidence for the high-risk population was 2.05 cases per 100 persons/year. Few published studies were rated as "good" in the risk of bias assessments. Variations in the methodology of the sources and limited information found in the countries' surveillance systems hinder the comparison of data. CONCLUSION: The burden of gonorrhoea in LAC is not negligible. Our results provide public health and clinical decision support to assess potential interventions to prevent gonorrhoea. TRIAL REGISTRATION: The protocol is registered on PROSPERO (CRD42021253342). The study was funded by GlaxoSmithKline Biologicals SA (GSK study identifier VEO-000025).

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BACKGROUND: Detailed information is needed on the dynamic pattern of antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Latin America and the Caribbean (LAC). OBJECTIVES: To conduct a systematic review of AMR in N. gonorrhoeae in LAC. METHODS: Electronic searches without language restrictions were conducted in PubMed, Embase, Cochrane Library, EconLIT, Cumulative Index of Nursing and Allied Health Literature, Centre for Reviews and Dissemination, and Latin American and Caribbean Literature in Health Sciences. Studies were eligible if published between 1 January 2011 and 13 February 2021, conducted in any LAC country (regardless of age, sex and population) and measured frequency and/or patterns of AMR to any antimicrobial in N. gonorrhoeae. The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO-GASP) for LAC countries and Latin American AMR SurveillanceNetwork databases were searched. AMR study quality was evaluated according to WHO recommendations. RESULTS: AMR data for 38, 417 isolates collected in 1990-2018 were included from 31 publications, reporting data from Argentina, Brazil, Colombia, Peru, Uruguay, Venezuela and WHO-GASP. Resistance to extended-spectrum cephalosporins was infrequent (0.09%-8.5%). Resistance to azithromycin was up to 32% in the published studies and up to 61% in WHO-GASP. Resistance to penicillin, tetracycline and ciprofloxacin was high (17.6%-98%, 20.7%-90% and 5.9%-89%, respectively). Resistance to gentamicin was not reported, and resistance to spectinomycin was reported in one study. CONCLUSIONS: This review provides data on resistance to azithromycin, potentially important given its use as first-line empirical treatment, and indicates the need for improved surveillance of gonococcal AMR in LAC. Trial registration: Registered in PROSPERO, CRD42021253342.

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Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions. Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney U test and Fisher's exact test. Results: A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/ß = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen. Conclusions: Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.

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Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care.

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A solid-phase dispersive microextraction procedure has been developed using ferrite (Fe3O4), an inexpensive magnetic material, as an adsorbent for the separation and subsequent determination of Ga(III) and In(III). The ions were removed from an aqueous solution by adsorption on Fe3O4, which was next easily collected from the medium by the action of a magnet. The analytes were then desorbed using 50 µL of 2 M NaOH or 50 µL of a 4:1 mixture of 0.1 M EDTA and 2 M HNO3 for the determination of Ga(III) or In(III), respectively. The level of the elements in the desorption phase was measured by electrothermal atomic absorption spectrometry (ETAAS) by injecting 10 µL of this phase into the atomizer. The enrichment factor was 163, and detection limits of 0.02 and 0.01 µg L-1 were achieved for Ga(III) and In(III), respectively. The reliability of the procedure has been verified by means of standard reference materials and by means of standard additions. Results are given for waters, soils and samples obtained from various electronic devices. It is of note that the procedure could be the basis for a useful way of recovering these valuable elements from different matrices for reuse.