Cognitive-behavioural processes during route previewing in bouldering.

INTRODUCTION: In the Olympic climbing discipline of bouldering, climbers can preview boulders before actually climbing them. Whilst such pre-climbing route previewing is considered as central to subsequent climbing performance, research on cognitive-behavioural processes during the preparatory phase in the modality of bouldering is lacking. The present study aimed at extending existing findings on neural efficiency processes associated with advanced skill level during motor activity preparation by examining cognitive-behavioural processes during the previewing of boulders. METHODS: Intermediate (n = 20), advanced (n = 20), and elite (n = 20) climbers were asked to preview first, and then attempt two boulders of different difficulty levels (boulder 1: advanced difficulty; boulder 2: elite difficulty). During previewing, climbers' gaze behaviour was gathered using a portable eye-tracker. RESULTS: Linear regression revealed for both boulders a significant relation between participants' skill levels and both preview duration and number of scans during previewing. Elite climbers more commonly used a superficial scan path than advanced and intermediate climbers. In the more difficult boulder, both elite and advanced climbers showed longer preview durations, performed more scans, and applied less often a superficial scan path than in the easier boulder. CONCLUSION: Findings revealed that cognitive-behavioural processes during route previewing are associated with climbing expertise and boulder difficulty. Superior domain-specific cognitive proficiency seems to account for the expertise-processing-paradigm in boulder previewing, contributing to faster and more conscious acquisition of perceptual cues, more efficient visual search strategies, and better identification of representative patterns among experts.

Overuse injury and affects in competitive sport: A prospective longitudinal study.

Overuse injuries, which have a high prevalence in sport, are suggested to result in different affective responses in comparison to traumatic injuries. Affects may also reciprocally act as risk factors for overuse injury. The aim of this study was to examine the associations between overuse injury and affects within a longitudinal follow-up design. Competitive athletes (N = 149) of various sports and levels of competition completed the Positive and Negative Affect Schedule (PANAS) and the Oslo Sports Trauma Research Centre Overuse injury questionnaire (OSTRC-O) once a week over 10 consecutive weeks. Bivariate unconditional latent curve model analyses with structured residuals were performed to evaluate the associations within and across weeks between OSTRC-O severity score and affects. Results indicated that OSTRC-O severity score and positive affects (PA) had a statistically significant negative within-week relation (r = -24.51, 95% CI = [-33.9, -15.1], p < 0.001). Higher scores of overuse injury were significantly related to lower levels of PA across weeks (ß = -0.02, 95% CI = [-0.04, -0.001], p = 0.044), while the reciprocal effect of PA on overuse injury was not significant (ß = -0.13, 95% CI = [-0.52, 0.26], p = 0.51). No statistically significant association was observed between OSTRC-O severity score and negative affects, neither within nor across weeks. Our findings suggest that overuse injury may have adverse psychological consequences on the long run through lessened PA and address the need for providing sustainable psychological support focusing upon such PA when working with athletes experiencing overuse injury.

Systematic documentation of the introduction of COVID-19 vaccines in Latin America and the Caribbean.

Objective: To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs. Methods: This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022. Results: The main strengths reported by countries were health workers' commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level. Conclusions: Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties' interests, the lack of information systems and difficulty in accessing vaccines and vaccine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes' strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises.

Systematic documentation of the introduction of COVID-19 vaccines in Latin America and the Caribbean / Documentación sistemática de la introducción de vacunas contra la COVID- 19 en América Latina y el Caribe / Documentação sistemática da introdução das vacinas contra a COVID-19 na América Latina e no Caribe

[ABSTRACT]. Objective. To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs. Methods. This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022. Results. The main strengths reported by countries were health workers’ commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level. Conclusions. Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties’ interests, the lack of information systems and difficulty in accessing vaccines and vac- cine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes’ strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises.

[RESUMEN]. Objetivo. Documentar el proceso de introducción de las vacunas contra la COVID-19 en un algunos países de América Latina y el Caribe, incluidas las enseñanzas extraídas y sus puntos fuertes y débiles, así como las similitudes y diferencias entre los distintos programas. Métodos. Este estudio descriptivo se basa en una evaluación sistemática del proceso de introducción de las vacunas contra la COVID-19 en Argentina, Belice, Brasil, Costa Rica, Panamá y Perú. Los datos se recopilaron mediante un cuestionario distribuido a las principales partes interesadas. El estudio contó con la participación de un informante de cada uno de los seis países incluidos. El período de estudio fue de diciembre del 2021 a septiembre del 2022. Resultados. Los países indicaron como puntos fuertes principales el compromiso del personal de atención de salud con la vacunación, la toma de decisiones basada en la evidencia, la formulación de planes para la introducción de las vacunas, la participación de grupos técnicos asesores nacionales sobre inmunización, la disponibilidad de recursos económicos y las medidas favorables adoptadas por respectivos los Ministerios de Salud. Los retos más importantes fueron las acciones de los grupos contrarios a las vacunas, los problemas con los registros electrónicos de vacunación, la falta de vacunas, los retrasos en la entrega de vacunas y la escasez de personal de atención de salud a nivel local. Conclusiones. Se observó que el compromiso, la participación de múltiples sectores, la disponibilidad de recursos y la planificación de la preparación eran algunos de los puntos fuertes de los países que introdujeron las vacunas contra la COVID-19. Los puntos débiles fueron los intereses de terceros, la falta de sistemas de información y las dificultades para acceder a las vacunas y a los servicios de vacunación. Los países disponen ahora de una oportunidad para mantener las buenas prácticas que propiciaron los puntos fuertes de los procesos y evaluar los puntos débiles identificados a fin de fortalecer los programas de inmunización y prepararse para futuras crisis de salud.

[RESUMO]. Objetivo. Documentar o processo de introdução da vacina contra a COVID-19 em alguns países da América Latina e do Caribe, incluindo as lições aprendidas e os pontos fortes e fracos, bem como semelhanças e diferenças entre os programas. Métodos. Este estudo descritivo baseia-se em uma avaliação sistemática do processo de introdução das vacinas contra a COVID-19 na Argentina, em Belize, no Brasil, na Costa Rica, no Panamá e no Peru. Os dados foram coletados por meio de um questionário distribuído às principais partes interessadas. Seis informantes de cada um dos países incluídos participaram do estudo, que foi realizado entre dezembro de 2021 e setembro de 2022. Resultados. Os principais pontos fortes relatados pelos países foram o comprometimento dos profissionais de saúde com a vacinação, a tomada de decisões baseadas em evidências, o desenvolvimento de planos para a introdução de vacinas, a participação de grupos técnicos assessores nacionais sobre imunização, a disponibilidade de recursos econômicos e ações positivas dos respectivos ministérios da Saúde. Os principais desafios foram as ações de grupos antivacina, problemas com os registros eletrônicos de imunização, a falta de vacinas, atrasos na entrega das vacinas e a escassez de pessoal de saúde em nível local. Conclusões. O comprometimento, a participação de vários setores, a disponibilidade de recursos e o planejamento de preparação foram alguns dos muitos pontos fortes demonstrados pelos países ao introduzirem as vacinas contra a COVID-19. Entre os pontos fracos estavam os interesses de terceiros, a falta de sistemas de informação e a dificuldade de acesso às vacinas e aos serviços de vacinação. Há uma janela de oportunidade para que os países mantenham as boas práticas que viabilizaram os pontos fortes dos processos e avaliem os pontos fracos identificados a fim de revigorar os programas de imunização e preparar-se para futuras crises sanitárias.

Antibiotic prescription patterns in patients with suspected urinary tract infections in Ecuador.

BACKGROUND: Urinary tract infections (UTI) are among the most common cause to prescribe antibiotics in primary care. Diagnosis is based on the presence of clinical symptoms in combination with the results of laboratory tests. Antibiotic therapy is the primary approach to the treatment of UTIs; however, some studies indicate that therapeutics in UTIs may be suboptimal, potentially leading to therapeutic failure and increased bacterial resistance. METHODS: This study aimed to analyze the antibiotic prescription patterns in adult patients with suspected UTIs and to evaluate the appropriateness of the antibiotic prescription. This is a cross-sectional study of patients treated in outpatient centers and in a second-level hospital of the Ministry of Public Health (MOPH) in a city in Ecuador during 2019. The International Classification of Disease Tenth Revision (ICD-10) was used for the selection of the acute UTI cases. The patients included in this study were those treated by family, emergency, and internal medicine physicians. RESULTS: We included a total of 507 patients in the analysis and 502 were prescribed antibiotics at first contact, constituting an immediate antibiotic prescription rate of 99.01%. Appropriate criteria for antibiotic prescription were met in 284 patients, representing an appropriate prescription rate of 56.02%. Less than 10% of patients with UTI had a urine culture. The most frequently prescribed antibiotics were alternative antibiotics (also known as second-line antibiotics), such as ciprofloxacin (50.39%) and cephalexin (23.55%). Factors associated with inappropriate antibiotic prescribing for UTIs were physician age over forty years, OR: 2.87 (95% CI, 1.65-5.12) p<0.0001, medical care by a general practitioner, OR: 1.89 (95% CI, 1.20-2.99) p = 0.006, not using point-of-care testing, OR: 1.96 (95% CI, 1.23-3.15) p = 0.005, and care at the first level of health, OR: 15.72 (95% CI, 8.57-30.88) p<0.0001. CONCLUSIONS: The results of our study indicate an appropriate prescription rate of 56.02%. Recommended antibiotics such as nitrofurantoin and fosfomycin for UTIs are underutilized. The odds for inappropriate antibiotic prescription were 15.72 times higher at the first level of care compared to the second. Effective strategies are needed to improve the diagnosis and treatment of UTIs.

Effectiveness of COVID-19 vaccines in Ecuador: A test-negative design.

Background: The COVID-19 pandemic poses a significant global health threat, characterized by high morbidity, severity, and the emergence of concerning variants. Latin America has been greatly affected, with high infection and mortality rates. Vaccination plays a crucial role in mitigating severe disease and controlling the pandemic. This study aims to assess the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 severe acute respiratory infections (SARI) in hospitalized vaccination target groups in Ecuador. Methods: This is a test-negative design study. We used data reported through sentinel surveillance of SARI between May 2021 and March 2022 in Ecuador. Patients with case criteria of SARI and hospitalized for a minimum of 24 hours were included in the study. Cases were defined as patients with SARI with a positive RT-qPCR test for SARS-CoV-2 and controls were those with a negative result. Information on vaccination status was obtained from the national vaccination registry, a valid dose of vaccination was considered when it was administered at least 14 days prior to symptom onset. Vaccine effectiveness (VE) (1-OR/OR) was calculated using a logistic regression. Results: A total of 1,277 patients were included in the analysis of VE. The adjusted vaccine effectiveness (aVE) in preventing hospitalization, adjusted for sex, age group, presence of one or more comorbidities, and period of the predominance of the omicron variant, was 44.5% for the partial primary schedule, 74.7% for the complete primary schedule, and 79.9% for the complete primary schedule plus booster doses. The aVE in avoiding ICU admissions was close to 80% with both the complete primary schedule and the booster doses, and in avoiding deaths, the aVE was 89% and 98%, respectively. Conclusions: In Ecuador, COVID-19 vaccination prevents hospitalizations, ICU admissions, and deaths. The effectiveness of the vaccines improves with more doses, offering increased protection across all age groups.

Antibiotic Prescription Patterns in Children Under 5 Years of Age With Acute Diarrhea in Quito-Ecuador.

BACKGROUND: Diarrheal disease remains a significant cause of child mortality, particularly in regions with limited access to healthcare and sanitation. Inappropriate practices, including unjustified medication prescriptions, pose challenges in the management of acute diarrhea (AD), especially in low- and middle-income countries. OBJECTIVE: This study analyzed antibiotic prescription patterns and assessed compliance with Integrated Management of Childhood Illness (IMCI) guidelines in children under 5 with AD in the Ministry of Public Health (MOPH) Ambulatory Care Centers of Quito city, Ecuador. METHODS: A cross-sectional design was used, collecting electronic health records (EHR) of patients diagnosed with AD from 21 health facilities in District 17D03. A probabilistic and stratified sampling approach was applied. Patient characteristics, prescriber characteristics, treatments, and compliance of IMCI guideline recommendations were evaluated. A stepwise logistic regression analysis examined the association between antibiotic prescription and patient and physician characteristics. RESULTS: A total of 359 children under 5 years of age were included, with 58.77% being girls. 85.24% of the cases of AD were attributed to gastroenteritis and colitis of infectious and unspecified origin. Amebiasis and other protozoal intestinal diseases accounted for 13.37% and 1.11% of the cases, respectively. The completion rates of recording various IMCI parameters varied; parameters such as duration of diarrhea, presence of blood in stool, and evidence of sunken eyes had high completion rates (100%, 100%, and 87.47%, respectively), while parameters like state of consciousness, presence of thirst, and type of diarrhea had low completion rates (0.28%, 0.28%, and 0.84%, respectively). None of the cases had all parameters fully recorded. Antimicrobials were prescribed in 38.72% of the cases. Children aged 3 to 5 years had higher odds of receiving antimicrobial prescription for AD (aOR: 4.42, 95% CI 2.13-9.18, P < .0001) compared to those under 1 year, after adjusting for the number of loose stools per day, gender, and age of the health professional. CONCLUSION: Variations in IMCI guideline compliance were observed, with no cases fully adhering to the guidelines. Antimicrobial prescription rates were notably high, especially among older children. Further research and specialized interventions are necessary to gain comprehensive insight into the factors underlying non-compliance with the IMCI guidelines.

Distribution of Escherichia coli Pathotypes along an Urban-Rural Gradient in Ecuador.

Diarrheal diseases are a leading cause of mortality and morbidity in low- and middle-income countries. Diarrhea is associated with a wide array of etiological agents including bacterial, viral, and parasitic enteropathogens. Previous studies have captured between- but not within-country heterogeneities in enteropathogen prevalence and severity. We conducted a case-control study of diarrhea to understand how rates and outcomes of infection with diarrheagenic pathotypes of Escherichia coli vary across an urban-rural gradient in four sites in Ecuador. We found variability by site in enteropathogen prevalence and infection outcomes. Any pathogenic E. coli infection, coinfections, diffuse adherent E. coli (DAEC), enteroinvasive E. coli (EIEC), and rotavirus were significantly associated with acute diarrhea. DAEC was the most common pathotype overall and was more frequently associated with disease in urban areas. Enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) were more common in rural areas. ETEC was only associated with diarrhea in one site. Phylogenetic analysis revealed that associations with disease were not driven by any single clonal complex. Higher levels of antibiotic resistance were detected in rural areas. Enteropathogen prevalence, virulence, and antibiotic resistance patterns vary substantially by site within Ecuador. The variations in E. coli pathotype prevalence and virulence in this study have important implications for control strategies by context and demonstrate the importance of capturing within-country differences in enteropathogen disease dynamics.

Medical cost of acute diarrhea in children in ambulatory care.

OBJECTIVE: The aim of this study was to estimate the direct medical cost per episode and the annual cost for acute diarrhea (AD) in children under five years of age in Ambulatory Care Centers of the Ministry of Public Health (MOPH) of Ecuador. METHODS: A cost of illness study with a provider perspective was carried out through a micro-costing of health resources and valuated in international dollars. Medical consultations and laboratory tests were valued using the tariff framework of services for the National Health System and for the prescribed medications, a reported cost registry of pharmacy purchases made in the year of study was used. RESULTS: A total of 332 electronic health records of children under five years of age were included in the analysis. Laboratory tests were performed on 37.95% (126/332), medications were prescribed to 93.67% (311/332) of the children, and antimicrobials were prescribed to 37.35% (124/332) of the children, representing an antibiotic prescription rate of 26.51% (88/332) and an antiparasitic prescription rate of 10.84% (36/332). The mean cost of the MOPH per child per episode of AD was US$45.24 (2019 dollars) (95% CI:43.71 to 46.76). CONCLUSION: The total estimated cost of AD in children under five years of age for the MOPH in 2019 was about US$6,645,167.88 million (2019 dollars) (95% CI: 6,420,430.77 to 6,868,436.12). A high proportion of the direct medical cost of AD in children under five years of age in outpatient settings is due to unnecessary laboratory tests.

Self-regulation and healthy lifestyles: considering the future may increase current physical activity levels.

The present study examined whether people's consideration of consequences (future vs. immediate consequences; CFC) can predict physical activity behaviour (PAB) and, to explore key mechanisms that may underline such association. To that end, participants (N = 128) filled in standardised measures of CFC and PAB, and questionnaires of health regulatory focus, attitude and intention as mediators of the CFC-PAB association. Regression analysis revealed that CFC-immediate was negatively associated with PAB, and that health regulatory promotion focus and intention were both positively associated with PAB. Mediation analysis revealed a significant effect of CFC-future via health promotion focus, attitude, and intention on PAB. Findings are discussed considering both susceptibility and buffering hypotheses. CFC-future buffers against self-control failure because it is associated with a promotion focus and with both more positive attitudes and stronger intentions towards PAB. Interventions promoting a physically active lifestyle should foster people to value and become aware of the future consequences of their actual PAB.

Visual Perception in Expert Athletes: The Case of Rock Climbers.

The purpose of the present study was to examine the visual perception system in expert climbers through a psychophysical optical test in a cross-sectional study. Twenty-seven male participants with an International Rock Climbing Research Association (IRCRA) best on-sight lead skill level ranging between 18 and 27 and a best red-point level ranging between 18 and 29 completed a series of psychophysical optic tests assessing their visual field, visual acuity, and contrast sensitivity. Climbers were divided by their best red-pointed lead level, and, following IRCRA recommendations, two groups were created: an advanced group (IRCRA redpoint level between 18 and 23), and an elite-high elite group (IRCRA redpoint level between 24 and 29). The elite group presented more training days per week (5.25 ± 1.28), best on-sighted lead level (24.63 ± 1.92 IRCRA), and best red-pointed lead level (26.63 ± 2.56 IRCRA) than the advanced group (3.67 ± 0.91 training days per week, 19.50 ± 1.04 IRCRA on-sighted level and 20.67 ± 1.57 IRCRA red-pointed level). Better visual perception outputs were produced by the group of elite climbers in visual field tests; no differences were observed between the two groups for visual acuity and contrast sensitivity tests. Overall, findings indicate that best climbers performed better at the visual perception tasks that tested their visual field. Such better perception from best climbers is discussed given (1) the greater time they spend coercing the visual system during practicing climbing and (2) the specific complexity of the stimuli as they are confronted to harder routes where holds are less perceptible and the time to find best hold sequences is constrained.

Return on Investment of 10-Valent Pneumococcal Conjugate Vaccine in Ecuador From 2010 to 2030.

OBJECTIVES: Ecuador introduced the pneumococcal conjugate vaccine in 2010. A recent time series analysis has demonstrated the impact of 10-valent pneumococcal conjugate vaccine (PCV10) on hospitalized pneumococcal disease in children. We leveraged these estimates to calculate the return on investment (ROI) of PCV10 in Ecuador from 2010 to 2030 at the national and regional levels. METHODS: We used 2 approaches to estimate the economic benefits: (1) cost of illness, which includes treatment, transportation, and productivity loss averted, (2) and the value of statistical life, which reflects society's average willingness to pay to save one life. Costs of the immunization program include vaccine costs (doses, syringes, injection supplies) and immunization delivery costs (personnel, cold chain equipment and maintenance, transportation, distribution services, and other recurrent costs). We estimated the ROI by dividing the net benefits by costs. RESULTS: The ROI using the cost-of-illness approach was slightly negative in the introduction year. From 2011 to 2020, we estimated the ROI to be 0.45 (0.15-0.73). For the future decade, the ROI is estimated at 0.37 (-0.03 to 1.03). Using the value-of-statistical-life approach, the ROI was 1.46 (0.82-2.17) in the introduction year. In the first decade, the ROI was 1.01 (0.49-1.60); in the second decade, the ROI fell to 0.83 (0.23-1.78). CONCLUSIONS: The results of this study demonstrate the total economic benefits of PCV10 in Ecuador exceed immunization program costs after the introduction year. Estimates from this study will inform country policy makers and will contribute to efforts to mobilize resources for immunization.

Analysis of births, abortions and maternal mortality in adolescents in Ecuador from 2013 to 2016.

Introduction: Adolescent pregnancy is associated to school desertion, violence, termination of pregnancy under suboptimal conditions, obstetric complications and other consequences that can put the woman's quality of life at risk and of those that surround her. The purpose of this study is to describe the situation and tendencies of adolescent pregnancies, abortions and maternal deaths between 2013 and 2016 in Ecuador. Methods: This cross-sectional study uses secondary data from national Ecuadorian vital statistics reports of adolescents between 10 and 19 years old. The data sources used register all the births, deaths and hospital discharges in the country at both public and private health establishments. We performed a descriptive analysis of qualitative and quantitative variables. Results: Ecuador has approximately 1.5 million female adolescents that gave birth to 256,561 newborns between 2013 and 2016, resulting in an average annual birth rate in early adolescence of 13.9 live births per 1000 and in late adolescence of 86.6 per 1000 live births.The number of registered abortions among adolescents between 2013 and 2016 was of 19,214. The estimated annual abortion rate in late stage adolescents is 6.3 abortions per 1000 women between 15 and 19. The estimated abortion ratio for this same age group is 72.9 per 1000 live births.Of all the adolescents that gave birth, 84.9% self-identified as mestiza, while 71.9% of Ecuador's general population identifies as such. Only 7% of the general population in Ecuador self-identifies as indigenous, while 21.6% of pregnancies come from this population. Out of all adolescents that gave birth, 57.4% of those aged 17 and over; 43% of those between 14 and 16 and 96.7% of adolescents from 10 to 13, completed the level of education for their age. There were 81 maternal deaths among this group. The maternal mortality rate for late stage adolescents is of 7.72 per 100,000.

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche.

Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but patients relapse, highlighting the need to understand the mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent. Quiescent cancer cells (QCCs) form clusters with reduced immune infiltration. They also display superior tumorigenic capacity and higher expression of chemotherapy resistance and stemness genes. We adapted single-cell RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside the QCC niche. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T cell function. Eliminating QCCs holds the promise to counteract immunotherapy resistance and prevent disease recurrence in TNBC.

Soft-Tissue Sarcomas in Adults in Ecuador in the Period 2010-2020.

Background: Soft-tissue sarcomas (STSs) are rare tumors; they represent 1% of all tumors in adults. There are new diagnostic techniques to differentiate tumor types, and surgery continues to be the most important treatment for STS. Methods: This cross-sectional study analyzed the morbidity and mortality caused by STS in adults between 2010 and 2020 using national databases. Results: A total of 8,393 patients hospitalized due to STS were reported. The total number of deaths in Ecuador due to STS was 7,088 over the last decade, the provinces of Pichincha and Guayas registered the highest number of cases, and the mortality rate was 1.2 to 2.0 per 100,000 people. It is noteworthy that the lowest point of registered cases was in 2012. Conclusion: Soft-tissue sarcomas are rare tumors in Ecuador. The morbidity and mortality caused by these tumors have not changed in the last decade. National studies are needed to determine the prevalence of this illness and study intervention to lower mortality.

Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 1013 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.

Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy.

Mucopolysaccharidosis type IVA (MPSIVA) or Morquio A disease, a lysosomal storage disorder, is caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, resulting in keratan sulfate (KS) and chondroitin-6-sulfate accumulation. Patients develop severe skeletal dysplasia, early cartilage deterioration and life-threatening heart and tracheal complications. There is no cure and enzyme replacement therapy cannot correct skeletal abnormalities. Here, using CRISPR/Cas9 technology, we generate the first MPSIVA rat model recapitulating all skeletal and non-skeletal alterations experienced by patients. Treatment of MPSIVA rats with adeno-associated viral vector serotype 9 encoding Galns (AAV9-Galns) results in widespread transduction of bones, cartilage and peripheral tissues. This led to long-term (1 year) increase of GALNS activity and whole-body correction of KS levels, thus preventing body size reduction and severe alterations of bones, teeth, joints, trachea and heart. This study demonstrates the potential of AAV9-Galns gene therapy to correct the disabling MPSIVA pathology, providing strong rationale for future clinical translation to MPSIVA patients.

Study of Viscoelastic Rubber Mounts on Vehicle Suspensions with In-Wheel Electric Motors.

Rubber bushings and mounts are vastly used in automotive applications as support and interface elements. In suspension systems, they are commonly employed to interconnect the damping structure to the chassis. Therein, the viscoelastic nature of the material introduces a desirable filtering effect to reduce mechanical vibrations. When designing a suspension system, available literature often deals with viscoelastic mounts by introducing a linear or nonlinear stiffness behavior. In this context, the present paper aims at representing the rubber material using a proper viscoelastic model with the selection of different in-wheels motors. Thus, the mount dynamic behavior's influence in a suspension is studied and discussed thoroughly through numerical simulations and sensitivity analyses. Furthermore, guidelines are proposed to orient the designer when selecting these elements.

Reducing unnecessary antibiotic prescription through implementation of a clinical guideline on self-limiting respiratory tract infections.

BACKGROUND: Clinical guidelines (CG) are used to reduce variability in practice when the scientific evidence is sparse or when multiple therapies are available. The development and implementation of evidence-based CG is intended to organize and provide the best available evidence to support clinical decision making in order to improve quality of care. Upper respiratory tract infections (URTI) are the leading cause of misuse of antibiotics and a CG may reduce the unnecessary antibiotic prescription. METHODS: The aim of this quasi-experimental, before-after study was to analyze the short- and long-term effects of the implementation of a CG to decrease the rate of antibiotic prescription in URTI cases in the emergency department of a third level private hospital in Quito, Ecuador. The study included 444 patients with a main diagnosis of URTI. They were distributed in three groups: a baseline cohort 2011 (n = 114), a first post-implementation cohort 2011 (n = 114), and a later post-implementation cohort 2018 (n = 216). The implementation strategy consisted of five key steps: acceptance of the need for implementation of the CG, dissemination of the CG, an educational campaign, constant feedback, and sustainability of the strategy through continuous training. RESULTS: The results of this study show a 42.90% of antibiotic prescription rate before the CG implementation. After the implementation of the CG, the prescription rate of antibiotics was significantly reduced by 24.5% (42.9% vs 18.4%, p<0.0001) and the appropriate antibiotic prescription rate was significantly increased by 44.2% (22.4% vs 66.6%, p<0.0001) in the first post-implementation cohort 2011. There was not a significant difference in antibiotic prescription rate and appropriate antibiotic prescription rate between two post-implementation cohorts: 18.4% vs 25.9% (p = 0.125) and 66.6% vs 50% (p = 0.191), respectively. CONCLUSIONS: The implementation of CGs decreases the rate of antibiotic prescription in URTI cases. The results are remarkable after early implementation, but the effect persists over time. The emphasis must shift from guideline development to strategy implementation.

Knowledge, Attitudes and Practices in Antibiotic Use in Family Medicine Students.

BACKGROUND: Inappropriate prescriptions of antibiotics lead to ineffective and unsafe treatments and worsening of diseases. Medical students may have deficiencies in their prescription skills and they may need further training in the use of antibiotics for their practice. Medical skills in prescribing antibiotics can be improved through continuous medical education. The aim of this study was to assess the current levels of knowledge, attitudes, and practices (KAP) in antibiotic prescription in upper respiratory tract infections (URTI) among postgraduate family medicine students in Ecuador. METHODS: A cross-sectional study with an on-line survey, based on micro-curricular contents, to evaluate KAPs regarding antibiotic prescription in URTI among postgraduate family medicine students in 5 provinces of Ecuador. RESULTS: Two hundred and seventy-three physicians responded (94.1%). Most physicians treated between 1 and 5 URTI cases per day. The odds for inadequate knowledge and inappropriate practices in URTI among postgraduate family medicine students were 8.74 (95%CI, 4.94-15.46, P < .001) and 5.99, (IC95%, 2.66-13.50, P < .001) in physicians who were students of the first half of the study program. CONCLUSION: The knowledge in URTI was limited among physicians. Nonetheless, they expressed a positive attitude toward not using antibiotics in URTI. A postgraduate program can significantly improve the knowledge and practices related to antibiotic prescriptions in URTI.