Immune profiling of dedifferentiated liposarcoma and identification of novel antigens for targeted immunotherapy.

Dedifferentiated liposarcoma (DDLS) is an aggressive, recurring sarcoma with limited treatments. T-cell immunotherapies selectively target malignant cells, holding promise against DDLS. The development of successful immunotherapy for DDLS requires a thorough evaluation of the tumor immune microenvironment and the identification and characterization of targetable immunogenic tumor antigens. To assess the complexity of the human DDLS tumor immune microenvironment and to identify target antigens, we used the nCounter NanoString platform, analyzing gene expression profiles across 29 DDLS and 10 healthy adipose tissue samples. Hierarchical clustering of tumors based on expression of tumor inflammation signature genes revealed two distinct groups, consisting of 15 inflamed tumors and 14 non-inflamed tumors, demonstrating tumor heterogeneity within this sarcoma subtype. Among the identified antigens, PBK and TTK exhibited substantial upregulation in mRNA expression compared to healthy adipose tissue controls, further corroborated by positive protein expression by IHC. This data shows considerable inter-tumoral heterogeneity of inflammation, which should be taken into consideration when designing an immunotherapy for DDLS, and provides a novel targetable antigen in DDLS. The results of this study lay the groundwork for the development of a novel immunotherapy for this highly aggressive sarcoma.

Pressurized pyrolysis of mattress residue: An alternative to landfill management.

Mattresses are a difficult waste to manage in landfills due to their large volume and low density. Pyrolysis treatment could reduce its volume while producing fuel or products valuable for the chemical industry. Pressurized pyrolysis at 400, 450, and 500 °C is carried out in a lab-scale autoclave at initial pressures 4.2, 8.4, and 16.8 bar. Product gas yield increases slightly along with elevated pressure as well as temperature. However, beyond 8.4 bar the initial pressure makes no discernible differences. CO and CO2 are the major gas species followed by CH4. CO contributes the most to the product gas energy content followed by C3 species, C2H6, and H2. Calculated energy content (heating value) is between 2 and 15 MJ·Nm-3. In terms of product gas energy content, low pressure pyrolysis is favorable over high pressure pyrolysis. According to integration areas of chromatographic measurements the liquid phase contains up to 25 % of N-compounds, with benzonitrile being the most abundant, followed by toluene, o-xylene, and ethylbenzene. The solid char maintains constant properties across operating conditions, with carbon and energy contents of approximately 75 wt% and 30 MJ·kg-1, respectively.

Financing for pandemic preparedness and response measures: a systematic scoping review.

Objective: To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and economic costs comparable to those of the coronavirus disease. Methods: We conducted a systematic scoping review using the databases ScienceDirect, Scopus, JSTOR, PubMed® and EconLit. We included articles published in any language until 1 August 2023, and excluded grey literature and publications on epidemics. We categorized eligible studies according to the elements of a framework proposed by the World Health Organization Council on the Economy of Health for All: (i) root/structural causes; (ii) social position/foundations; (iii) infrastructure and systems; and (iv) communities, households and individuals. Findings: Of the 188 initially identified articles, we included 60 in our review. Most (53/60) were published after 2020, when academic interest had shifted towards global financing mechanisms. Most (37/60) addressed two or more of the council framework elements. The most frequently addressed element was infrastructure and systems (54/60), discussing topics such as health systems, financial markets and innovation ecosystems. The roots/structural causes were discussed in 25 articles; communities, households and individuals in 22 articles; and social positions/foundations in 11. Conclusion: Our review identified three important gaps: a formal definition of pandemic preparedness and response, impeding the accurate quantification of the financing shortfall; research on the extent to which financing for pandemic preparedness and response has been targeted at the most vulnerable households; and an analysis of specific financial instruments and an evaluation of the feasibility of their implementation.

Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study.

Background: A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer's disease (AD) in which a given outcome is most relevant (i.e., has the greatest risk of degradation). The framework guides the selection of endpoints measuring outcomes relevant within a target AD population. Here, a proof of concept is presented via post-hoc analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012). Objective: To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized 'target' stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS). Methods: Three endpoints were tested: ADAS-Cog 12, ADCS-ADL, and QoL-AD. The magnitude of treatment efficacy was hypothesized to be maximized in the target stages of mild, mild-to-moderate, and very mild AD, respectively, compared to the full analysis set (FAS) and non-target stages. Results: For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (-4.0, p = 0.0760) compared to target stage and FAS. For ADCS-ADL and QoL-AD, the magnitude of treatment efficacy was largest in the target stage (14.2, p = 0.0003; 2.4, p < 0.0001, respectively) compared to non-target stage and FAS. Conclusions: Findings indicated that evaluating endpoints in the most relevant AD stage can increase the magnitude of the observed treatment efficacy. Evidence provides preliminary proof of concept for the endpoint staging framework.

Remote Sensing Evaluation Drone Herbicide Application Effectiveness for Controlling Echinochloa spp. in Rice Crop in Valencia (Spain).

Rice (Oryza sativa L.) is a staple cereal in the diet of more than half of the world's population. Within the European Union, Spain is a leader in rice production due to its climate and tradition, accounting for 26% of total EU production in 2020. The Valencian rice area covers around 15,000 hectares and is strongly influenced by biotic and abiotic factors. An important biotic factor affecting rice production is weeds, which compete with rice for sunlight, water and nutrients. The dominant weed in Spain is Echinochloa spp., although wild rice is becoming increasingly important. Rice cultivation in Valencia takes place in the area of L'Albufera de Valencia, which is a natural park, i.e., a special protection area. In this natural area, the use of phytosanitary products is limited, so it is necessary to use the minimum amount possible. Therefore, the objective of this work is to evaluate the possibility of using remote sensing effectively to determine the effectiveness of the application of the herbicide cyhalofop-butyl by drone for the control of Echinochloa spp. in rice crops in Valencia. The results will be compared with those obtained by using sterilisation machines (electric backpack sprayers) to apply the herbicide. To evaluate the effectiveness of the application, the reflectance obtained by the satellite sensors in the red and near infrared (NIR) wavelengths, as well as the normalised difference vegetation index (NDVI), were used. The remote sensing results were analysed and complemented by the number of rice plants and weeds per area, plant dry weight, leaf area, BBCH phenological state, SPAD index values, chlorophyll content and relative growth rate. Remote sensing is validated as an effective tool for determining the efficacy of an herbicide in controlling weeds applied by both the drone and the electric backpack sprayer. The weeds slowed down their development after the treatment. Depending on the phenological state of the crop and the active ingredient of the herbicide, these results are applicable to other areas with different climatic and environmental conditions.

Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

Real-World Use of Ubrogepant as Acute Treatment for Migraine with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody: Results from COURAGE.

INTRODUCTION: Although acute and preventive treatments for migraine are commonly given in combination, data on the real-world effectiveness of ubrogepant as an acute treatment when used with an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (with or without onabotulinumtoxinA) are limited. This analysis sought to evaluate the real-world effectiveness, treatment satisfaction, and optimization of ubrogepant for the acute treatment of migraine when used in combination with an anti-CGRP monoclonal antibody, with or without concomitant onabotulinumtoxinA. METHODS: This prospective, multiple-attack, open-label, observational study (COURAGE) assessed meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization of ubrogepant (50 or 100 mg) when combined with an anti-CGRP monoclonal antibody, onabotulinumtoxinA, or both in adult users of Migraine Buddy, a migraine tracking application. RESULTS: In the ubrogepant and anti-CGRP monoclonal antibody arm (n = 245), following the first ubrogepant-treated attack, 61.6% (151/245) and 80.4% (197/245) of ubrogepant-treated participants achieved MPR at 2 and 4 h post-dose, respectively, and 34.7% (85/245) and 55.5% (136/245) achieved RNF at 2 and 4 h post-dose, respectively. Across up to 10 ubrogepant-treated attacks (N = 1153), MPR was achieved in 51.3% (592/1153) and 73.5% (847/1153) at 2 and 4 h post-dose, respectively. RNF was achieved by 32.2% (371/1153) and 53.2% (613/1153) at 2 and 4 h post-dose. After 30 days, 72.7% (168/231) of participants reported satisfaction (using a 7-point scale) with ubrogepant when used in combination with an anti-CGRP monoclonal antibody, and 79.7% (184/231) of participants achieved acute treatment optimization (defined as moderate-maximum treatment efficacy using the Migraine Treatment Optimization Questionnaire-4). CONCLUSION: Real-world ubrogepant use with an anti-CGRP monoclonal antibody was associated with MPR, RNF, satisfaction, and acute treatment optimization.

Is Oral Vaccination against Escherichia coli Influenced by Zinc Oxide?

BACKGROUND: Although zinc oxide has been banned at therapeutic doses in the EU, its use is still legal in most countries with industrial pig farming. This compound has been shown to be very effective in preventing E. coli-related diseases. However, another strategy used to control this pathogen is vaccination, administered parenterally or orally. Oral vaccines contain live strains, with F4 and F18 binding factors. Since zinc oxide prevents E. coli adhesion, it is hypothesised that its presence at therapeutic doses (2500 ppm) may alter the immune response and the protection of intestinal integrity derived from the vaccination of animals. METHODS: A group of piglets were orally vaccinated at weaning and divided into two subgroups; one group was fed a feed containing 2500 ppm zinc oxide (V + ZnO) for the first 15 days post-vaccination (dpv) and the other was not (V). Faeces were sampled from the animals at 6, 8, 11, 13, and 15 dpv. Unvaccinated animals without ZnO in their feed (Neg) were sampled simultaneously and, on day 15 post-vaccination, were also compared with a group of unvaccinated animals with ZnO in their feed (ZnO). RESULTS: Differences were found in E. coli excretion, with less quantification in the V + ZnO group, and a significant increase in secretory IgA in the V group at 8 dpv, which later equalised with that of the V + ZnO group. There was also some difference in IFNα, IFNγ, IL1α, ILß, and TNFα gene expression when comparing both vaccinated groups (p < 0.05). However, there was no difference in gene expression for the tight junction (TJ) proteins responsible for intestinal integrity. CONCLUSIONS: Although some differences in the excretion of the vaccine strain were found when comparing both vaccinated groups, there are no remarkable differences in immune stimulation or soluble IgA production when comparing animals orally vaccinated against E. coli in combination with the presence or absence of ZnO in their feed. We can conclude that the immune response produced is very similar in both groups.

Evaluating therapeutic benefits of ubrogepant via latent class models: A post hoc exploratory analysis of the ACHIEVE I and ACHIEVE II trials.

OBJECTIVE: To evaluate an alternative method of defining acute treatment success in migraine by combining multiple indicators into a single dichotomous measure of success. BACKGROUND: Migraine is characterized by a symptom complex; combining these features as a single endpoint may improve the measurement of treatment effects and better predict patient satisfaction with treatment. METHODS: We used a confirmatory latent class model (LCM) with two latent classes interpreted as treatment success and treatment failure. Pooled data for placebo and ubrogepant 50 mg from the ACHIEVE I and ACHIEVE II trials and data for ubrogepant 100 mg from ACHIEVE I were used. LCM inputs included pre-dose and 2-h post-dose measures of pain severity (0-3), the presence/absence of associated symptoms (nausea, photophobia, and phonophobia [0 or 1]), and functional disability (0-3). All definitions were validated against satisfaction with study medication (SWSM) at 24 h post-dose; results were compared with 2-hour pain freedom (2hPF). RESULTS: This pooled analysis included 2247 participants. At 2 h post-dose in the ubrogepant 50 and 100 mg dose groups, 53.2% (472/887) and 54.9% (246/448) of participants, respectively, were classified as achieving treatment success using the LCM-based approach, compared to 39.0% (356/912) of participants in the placebo group. The results for treatment success using the 2hPF endpoint were 20.7% (184/887) and 21.5% (96/447) in the ubrogepant 50 and 100 mg dose groups, respectively, compared to 12.7% (116/912) for placebo. Using 24-h SWSM as an external validator, the LCM approach sensitivity and correct classification rates were higher than for 2hPF. CONCLUSION: The LCM approach led to higher rates of treatment success and greater separation between ubrogepant and placebo and was a more sensitive predictor of treatment satisfaction than the regulatory endpoint of 2hPF.

Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVΔ51 oncolytic virotherapy.

The clinical efficacy of VSVΔ51 oncolytic virotherapy has been limited by tumor resistance to viral infection, so strategies to transiently repress antiviral defenses are warranted. Pevonedistat is a first-in-class NEDD8-activating enzyme (NAE) inhibitor currently being tested in clinical trials for its antitumor potential. In this study, we demonstrate that pevonedistat sensitizes human and murine cancer cells to increase oncolytic VSVΔ51 infection, increase tumor cell death, and improve therapeutic outcomes in resistant syngeneic murine cancer models. Increased VSVΔ51 infectivity was also observed in clinical human tumor samples. We further identify the mechanism of this effect to operate via blockade of the type 1 interferon (IFN-1) response through neddylation-dependent interferon-stimulated growth factor 3 (ISGF3) repression and neddylation-independent inhibition of NF-κB nuclear translocation. Together, our results identify a role for neddylation in regulating the innate immune response and demonstrate that pevonedistat can improve the therapeutic outcomes of strategies using oncolytic virotherapy.

Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: results from the COURAGE Study.

BACKGROUND: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. METHODS: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). RESULTS: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. CONCLUSIONS: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments.

Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

The effect of public policy on high BMI trends of Mexican children: an interrupted time series analysis.

BACKGROUND: Mexico declared an obesity epidemic in 2000, and in response, became an early adopter of public policies in the form of natural experiments, which have not been evaluated for their effect on high BMI. We focus on children younger than 5 years due to the long-term outcomes of childhood obesity. METHODS: We used the Global Burden of Disease data to evaluate time trends in high BMI, defined as being overweight or obese based on the International Obesity Task Force standards, between 1990 and 2019. Marginalisation and poverty estimates from Mexico's Government were used to identify differences in socioeconomic groups. The time variable reflects the introduction of policies between 2006 and 2011. Our hypothesis was that poverty and marginalisation modify the effects of public policies. We tested for the change in prevalence of high BMI over time using Wald-type tests, correcting for the effect of repeated measures. We stratified the sample by gender, marginalisation index, and households under the poverty line. Ethics approval was not required. FINDINGS: Between 1990 and 2019, high BMI in children younger than 5 years increased from 23·5% (95% uncertainty interval 38·6-14·3) to 30·2% (46·0-20·4). After a period of sustained increase to 28·7% (44·8-18·6) in 2005, high BMI decreased to 27·3% (42·4-17·4; p<0·001) in 2011. Afterwards, high BMI increased constantly. We found an average gender gap of 12·2%, with a higher rate in males, in 2006, which remained constant. With respect to marginalisation and poverty, we observed a reduction in high BMI across all strata, except for the uppermost quintile of marginalisation in which high BMI remained flat. INTERPRETATION: The epidemic affected groups across different socioeconomic levels, thus weakening economic explanations for the decrease in high BMI, while gender gaps point to behavioural explanations of consumption. The observed patterns warrant investigation through more granular data and structural models to isolate the effect of the policy from secular trends in the population, including other age groups. FUNDING: Tecnológico de Monterrey Challenge-Based Research Funding Program.

Functional results and return to sports on recurrent anterior glenohumeral instability. Influence of the COVID-19 pandemic; Comparative retrospective study and short-term results.

AIMS: Our objective is to compare the functional results in patients that underwent surgery for recurrent anterior shoulder instability (RAGHI) during the COVID-19 pandemic with remotely-based rehabilitation, to those who had surgery before the pandemic and had in-person rehabilitation therapy. METHODS: A retrospective case series of 68 patients were included and divided into two groups: In person-group and Home-based group. Western Ontario Shoulder Instability Index (WOSI) and Subjective Shoulder Value (SSV) scores were used to evaluate objective and subjective clinical parameters. Time and level of return to sports was studied by the Subjective Patient Outcome for Return to Sports (SPORTS) score. RESULTS: The mean SSV score was 82% (40-100) on the In-Person group compared with 87% (65-100) for the Home-Based group. Results for WOSI score were similar, with an average of 210.42 (90%) for In-Person and 261.45 (88%) for the Home-Based group (p 0.12). Return to sports was carried out in an average of 6.6 (4-16) months for In-Person group, compared to 6.5 (5-8) months for Home-Based. CONCLUSION: Follow-up and rehabilitation methods for patients who underwent surgery for RAGHI, during COVID-19 lockdown, were not significantly (p 0.12) affected on functional and athletic return in comparison to traditional methods according to WOSI scale. LEVEL OF EVIDENCE: IV Retrospective series of cases.

Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol.

Introduction: Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. Methods: The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. Results: The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Discussion: Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.

Burden of overweight and obesity in Mexico from 1990 to 2021.

BACKGROUND: Overweight and obesity (OW/OB) represent a serious challenge in Mexico, with effects on health, society and economy. Demographic, epidemiological, nutritional, social and economic factors have exacerbated this problem. OBJECTIVE: To analyze mortality and years of healthy life lost in Mexico due to OW/OB in the 1990-2021 period. MATERIAL AND METHODS: The Global Burden of Disease and Risk Factors 2021 study was used to analyze data on elevated body mass index (BMI) as a risk factor and its evolution in Mexico. RESULTS: In 2021, 118 thousand deaths attributable to high BMI were recorded, which accounted for 10.6% of total deaths and more than 4.2 million disability-adjusted life years lost. CONCLUSIONS: The obesogenic environment, influenced by social determinants of health, has had a significant impact on mortality, burden of disease, and economic costs. Addressing OW/OB requires multisector interventions to strengthen the Mexican health system.

ANTECEDENTES: El sobrepeso y la obesidad constituyen un grave desafío en México, con efectos en la salud, sociedad y economía. Factores demográficos, epidemiológicos, nutricionales, sociales y económicos han agravado esta problemática. OBJETIVO: Analizar la mortalidad y los años de vida saludable perdidos en México por sobrepeso y obesidad en el período de 1990 a 2021. MATERIAL Y MÉTODOS: Se utilizó el Global Burden of Disease 2021 para analizar los datos sobre índice de masa corporal elevado como factor de riesgo y su evolución en México. RESULTADOS: En 2021 se registraron 118 mil muertes atribuibles a índice de masa corporal elevado, que representaron 10.6 % del total de muertes y más de 4.2 millones de años de vida perdidos ajustados por discapacidad. CONCLUSIONES: El ambiente obesogénico, influido por determinantes sociales, ha tenido un impacto significativo en la mortalidad, la carga de enfermedad y los costos económicos. Abordar el sobrepeso y la obesidad requiere intervenciones multisectoriales para fortalecer el sistema de salud mexicano.

Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines.

Oncolytic viruses (OVs) are promising anticancer treatments that specifically replicate in and kill cancer cells and have profound immunostimulatory effects. We previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) as immunostimulatory enhancers of OV immunotherapy. These compounds, in conjunction with RNA-based OVs such as oncolytic vesicular stomatitis virus (VSVΔ51), improve viral spread and oncolysis, leading to long-term antitumor immunity and prolonged survival in resistant tumor models. This effect is associated with a virus-induced antiviral type I IFN response shifting towards a type II IFN response in the presence of vanadium. Here, we investigated the systemic impact of VS+VSVΔ51 combination therapy to understand the immunological mechanism of action leading to improved antitumor responses. VS+VSVΔ51 combination therapy significantly increased the levels of IFN-γ and IL-6, and improved tumor antigen-specific T-cell responses. Supported by immunological profiling and as a proof of concept for the design of more effective therapeutic regimens, we found that local delivery of IL-12 using VSVΔ51 in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model.

Spontaneous Osteonecrosis of the Knee: State of the Art.

Osteonecrosis is a terrible condition that can cause advanced arthritis in a number of joints, including the knee. The three types of osteonecrosis that can affect the knee are secondary, post-arthroscopic, and spontaneous osteonecrosis of the knee (SPONK). Regardless of osteonecrosis classification, treatment for this condition seeks to prevent further development or postpone the onset of knee end-stage arthritis. Joint arthroplasty is the best course of action whenever there is significant joint surface collapse or there are signs of degenerative arthritis. The non-operative options for treatment at the moment include observation, nonsteroidal anti-inflammatory medications (NSAIDs), protective weight bearing, and analgesia if needed. Depending on the severity and type of the condition, operational procedures may include unilateral knee arthroplasty (UKA), total knee arthroplasty (TKA), or joint preservation surgery. Joint preservation techniques, such as arthroscopy, core decompression, osteochondral autograft, and bone grafting, are frequently used in precollapse and some postcollapse lesions, when the articular cartilage is typically unaffected and only the underlying subchondral bone is affected. In contrast, operations that try to save the joint following significant subchondral collapse are rarely successful and joint replacement is required to ease discomfort. This article's goal is to summarise the most recent research on evaluations, clinical examinations, imaging and various therapeutic strategies for osteonecrosis of the knee, including lesion surveillance, medicines, joint preservation methods, and total joint arthroplasty.