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The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRß and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRß clonality, lower TCRß evenness, higher TCRß Shannon diversity and lower TCRß convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs.

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Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.

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Cervical cancer is among the most frequently occurring neoplasms worldwide, and it particularly affects individuals in developing countries. Factors such as the low quality of screening tests, the high incidence of locally advanced cancer stages and the intrinsic resistance of certain tumors are the main causes of failure in the treatment of this neoplasm. Due to advances in the understanding of carcinogenic mechanisms and bioengineering research, advanced biological nanomaterials have been manufactured. The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including IGF receptor 1. These receptors are activated by binding to their respective growth factor ligands, IGF-1 and IGF-2, and insulin, and play an important role in the development, maintenance, progression, survival and treatment resistance of cervical cancer. In the present review, the role of the IGF system in cervical cancer and three nanotechnological applications that use elements of this system are described, namely Trap decoys, magnetic iron oxide nanoparticles and protein nanotubes. Their use in the treatment of resistant cervical cancer tumors is also discussed.

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(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3-CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3-CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56bright NK cell subpopulation (CD56+CD3-CD16-PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.

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INTRODUCTION: Drains for surgical wound management are frequently used in spine surgery. They are often used to decrease the incidence of postoperative hematoma and decrease wound tension. No conclusive evidence in the literature supports using drains to avoid complications in degenerative lumbar spine surgery. PURPOSE: We aimed to evaluate wound drains in patients with lumbar arthrodesis for degenerative disorders based on clinical outcomes, complications, hematocrit, and length of stay. STUDY DESIGN: A multicenter randomized prospective controlled clinical trial. PATIENT SAMPLE: We enrolled surgical candidates for posterior lumbar decompression and fusion surgery for degenerative disorders from October 2019 to August 2021. Patients were randomized into the drain or nondrain group at nine hospitals. The inclusion criteria were as follows: patients aged 40 to 80 years with lumbar and radicular pain, lumbar degenerative disorder, and primary surgery up to three levels. The exclusion criteria were bleeding abnormalities, bleeding >2,500 mL and dural tears. OUTCOME MEASURES: Preoperative data including Oswestry disability index (ODI), SF-36, lumbar and lower extremity visual analog scale (VAS), body mass index (BMI), hematocrit, and temperature were recorded. Surgical parameters, including surgical time, complications, estimated blood loss (EBL), postoperative temperature and hematocrit (days 1 and 4), dressing saturation, and length of hospital stay (LOS), were registered. METHODS: The two groups were assessed preoperatively, perioperatively and at the 1-month follow-up. A REDCap database was used for registration. Data analysis was performed using classical statistics. RESULTS: One hundred one patients were enrolled using the Redcap database, and 93 patients were evaluated at the final follow-up. Forty-five patients were randomized to the drain group, and 48 were randomized to the nondrain group. The preoperative characteristics were equivalent in both groups: demographic aspects, pain, ODI, SF-36, BMI, hematocrit, and spine pathology. Surgical time, EBL and complications were similar, with no difference between the groups. No difference was found between BMI and complications. No difference was observed in dressing saturation or postoperative temperature between the groups. The postoperative day 4 hematocrit was higher in the nondrain group [36.4% (32-39)] than in the drain group [34% (29.7-37.6)] without statistically differences (p=.054). The LOS was higher in the drain group [4 (3-5) days] than in the nondrain group [3 (2-4) days] (p=.007). The quality-of-life score, SF-36, was higher in the nondrain group [67.9 (53.6-79.2)] than in the drain group [56.7 (49.1-66)] (p=.043). CONCLUSIONS: Nondrain patients presented shorter LOS and better outcomes, with similar complication rates. No difference was found between BMI and complications. Based on this study, in patients undergoing primary posterior spinal decompression and fusion up to three levels for degenerative lumbar disorders, we do not recommend the use of postoperative drains.

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Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.

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Theoretical approaches to dehumanization consider civility to be an attribute of human uniqueness (HU). However, studies that explore the links between civility and humanness are scarce. More precisely, the present research tests whether there is a consistent relationship between civility and HU. Method and results: The first study (N = 192; Mage = 19.91; SD = 2.70; 69% women) shows that individuals infer more HU traits in the agents of civil behaviors compared to agents of other positive behaviors that are not related to civility. The second study (N = 328; Mage = 19.69; SD = 3.65; 77% women) reveals that uncivil and immoral behaviors displayed a similar pattern of inference of HU traits; however, moral behaviors were more associated with human nature than civil behaviors. Conclusions: Overall, results confirmed that civil behaviors facilitate the inference of humanness, specifically of HU traits, and that civil and moral behaviors are not equivalent in terms of the human inferences to which they lead.

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Honduras' underdevelopment of the higher education system, national economic constraints, and low investment in science and technology (S&T) have created significant challenges in training, employing, and retaining its science workforce, resulting in what is known as "brain drain" in literature. There are no official statistics of Honduran scientists who have established their residency abroad, nor the Honduran scientific diasporas (HSD); however, various diaspora networks provide evidence of their existence and engagement in their home country. This study takes an empirical approach and explores experiences of networking and engagement of the HSD for the development of Honduras. Methodologically, a qualitative approach and a phenomenological design were used. The data were collected through documentary review and semi-structured interviews with 21 key respondents from three identified HSD networks: Honduras Global (HG), the Organization of Women in Science for the Developing World, Honduras National Chapter (OWSD Honduras), and the Alumni Association of the Zamorano Pan-American Agricultural School (AGEAP-Zamorano). The holistic analysis of HSD's engagement provides evidence of existing registry gaps. Neither the S&T agents nor the Honduras Foreign Policy have identified, mapped, and characterized Honduran scientists' emigration patterns. Evidence suggests the willingness of the HSD to transfer knowledge, build bridges, and facilitate access to world-class research practices to their peers residing in Honduras and interact with broader sectors of the Honduran society.

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BACKGROUND: Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard. RESULTS: MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12). CONCLUSIONS: Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations.

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BACKGROUND & AIMS: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. RESULTS: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m2 and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). CONCLUSIONS: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients.

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Guillain-Barré syndrome (GBS) is a well-established complication of infectious disease. So it is not surprising that several cases have been described during the actual SARS-CoV-2 infection pandemic. Most of the descriptions are patients suffering a severe GBS in the setting of a severe SARS-CoV-2 infection. We described five patients with mild forms of COVID-19. After 2-4 weeks, these patients develop mild neurological symptoms. The clinical and neurophysiological studies supported a diagnosis of an acute polyneuropathy. Symptoms resolved without specific treatment and primary care physicians managed all patients outpatiently. Mild SARS-CoV-2 infection could associate mild neurological complications too. So patients complaining about mild neurological symptoms, a SARS-CoV-2 infection may be excluded. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-021-00855-x.

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Immunotherapy has become a new paradigm in oncology, improving outcomes for several types of cancer. However, there are some aspects about its management that remain uncertain. One of the key points that needs better understanding is the interaction between immunotherapy and gut microbiome and how modulation of the microbiome might modify the efficacy of immunotherapy. Consequently, the negative impact of systemic antibiotics and corticosteroids on the efficacy of immunotherapy needs to be clarified.

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Abstract The aims of this study were to update the prevalence of vaginal dysfunction (VD) in non-pregnant women of childbearing age, pregnant women and menopausal women, to analyse microbiological aspects, to evaluate the influence of parity and contraception in the vaginal microenvironment, to analyse case studies, and to compare the prevalence in the five regions of Argentina: Northeast, Northwest, Centre, Cuyo and South. Eight thousand three hundred twenty-four (8324) vaginal content samples of patients from 39 institutions, examined between May 2019 and June 2020, were prospectively and consecutively studied. The samples were analysed applying the standardized BAVACO-VIR methodology (study of the balance of vaginal content and genital inflammatory response). Of the 8324 samples, 5947 (71.5%) corresponded to women of childbearing age; 1627 (19.5%) to pregnant women and 750 (9.0%) to menopausal women. The most frequent basic vaginal state (BVS) in the three groups was BVS I with normal microbiota, accounting for 33.5% of the entire studied population. Moreover, 66.5% of vaginal dysfunction states were detected. In the pregnant women and menopausal women group there was a significant increase in the frequency of normal BVS I, in contrast with the group of women of childbearing age, where a significant increase of vaginosis and vaginitis was observed. In asymptomatic women, a predominance of BVS I was detected in the three groups. In symptomatic women, there was a predominance of BVS II and V in pregnant women, of BVS II, IV and V in women of childbearing age, and of BVS III and V in menopausal women. Asymptomatic VD was detected in 56.6% of pregnant women, 62.8% of women of childbearing age and 50.9% of menopausal women. A significantly positive association was detected between the presence of yeasts and BVS II and V and the presence of trichomonas and BVS V. The multiparity history variable showed a statistically significant positive association with BVS V and a negative association with BVS I. With regard to contraception, in women who used hormonal contraceptives it was observed that oral contraceptives increased the frequency of BVS I and II and decreased the frequency of BVS III, IV and V of VD; in those who used an intradermal device, there was a decrease in the frequency of BVS I, II and III and an increase in the frequency of BVS IV and V, whereas in women using injectable contraceptives, there was no association. The intrauterine device decreased the frequency of BVS I and II and increased the frequency of BVS V; the condom increased the frequency of BVS IV and the rhythm method decreased the frequency of BVS II. In BVS I, a decrease in the frequency of signs and symptoms was detected. The prevalence of VD in some regions accounted for values over 80%, a higher figure than that described at the national and international levels, which reflects the poor and insufficient action in Sexual and Reproductive Health. The high percentage of asymptomatic women with VD highlights the importance of studying the vaginal content, even in the absence of symptoms. A history of multiparity and contraception showed a link with vaginal function, reflecting the importance of considering this fact in a gynecological evaluation. Although the relationship of BVS with signs and symptoms does not constitute a diagnostic tool, it contributes to the understanding of pathogenic mechanisms.

Resumo Os objetivos deste estudo foram: atualizar a prevalência de disfunção vaginal (DV) em mulheres não grávidas em idade fértil (MEF), mulheres grávidas (EMB) e mulheres menopausadas (MPN), analisar aspectos microbiológicos, avaliar a influência da paridade e contracepção no microambiente vaginal, analisar quadros clínicos e comparar as prevalências das 5 regiões do nosso país: Nordeste, Noroeste, Centro, Cuyo e Sur. 8324 conteúdos vaginais de pacientes de 39 instituições, que compareceram entre maio de 2019 e junho de 2020, foram estudados prospectiva e facilitadoconsecutivamente. As amostras foram analisadas aplicando-se a metodologia padronizada BACOVA-ERIGE (estudo do equilíbrio do conteúdo vaginal e resposta inflamatória genital). Das 8324 amostras de conteúdo vaginal, 5947 (71,5%) corresponderam às MEF; 1627 (19,5%) às EMB e 750 (9,0%) às MNP. O estado vaginal básico (EVB) mais frequente nos três grupos foi EVB I de microbiota normal e representou 33,5% de toda a população global. Foram detectados 66,5% dos estados de disfunção vaginal. No grupo EMB e MNP, um aumento significativo na frequência de EVB I normal foi registrado, em contraste com o grupo MEF, onde foi reconhecido um aumento significativo de EVB de vaginose e vaginite. Em mulheres assintomáticas, foi detectado predomínio de EVB I nos três grupos. Em mulheres sintomáticas foi detetado: nas EMB, predomínio de EVB II e V; nas MEF, predominância de EVB II, IV e V, e nas MNP, predominância de EVB III e V. 56,6% das EMB, 62,8% das MEF e 50,9% das MNP apresentaram DV na ausência de sintomas. Foi detectada associação significativamente positiva entre a presença de leveduras e EVB II e V e a presença de tricomonas e EVB V. A variável antecedente de multiparidade apresentou associação positiva estatisticamente significativa com EVB V e associação negativa com EVB I. Em relação à contracepção, observou-se em mulheres que usavam anticoncepcionais hormonais, que os anticoncepcionais orais aumentaram a frequência de EVB I e II e diminuíram a frequência de EVB III, IV e V de DV; Em mulheres com dispositivo intradérmico, foi observada uma diminuição na frequência de EVB I, II e III e um aumento na frequência de EVB IV e V, e finalmente em mulheres com anticoncepcionais injetáveis, nenhuma associação foi demonstrada. O dispositivo intrauterino diminuiu a frequência de EVB I e II e aumentou a frequência de EVB V; o preservativo aumentou a frequência de EVB IV e o método do ritmo diminuiu a frequência de EVB II. Na EVB I, foi detectada diminuição da frequência de sinais e sintomas. A prevalência de DV em algumas regiões ultrapassou valores de 80%, valor superior ao descrito a nível nacional e internacional, o que reflete a atuação precária e insuficiente em Saúde Sexual e Reprodutiva. O alto percentual de mulheres assintomáticas com DV demonstra a importância da realização do estudo do conteúdo vaginal, mesmo na ausência de sintomas. A história de multiparidade e contracepção mostrou ligação com a função vaginal, refletindo a importância da sua consideração na avaliação ginecológica. Embora a relação da EVB com os sinais e sintomas não constitua uma ferramenta diagnóstica, ela contribui para o entendimento dos mecanismos patogênicos.

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Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRß (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs.

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Tomato (Solanum lycopersicum) is a widely consumed fruit all around the world. The industrial exploitation of tomato generates a lot of waste. Most of the utilization of tomato seeds waste is focused on animal feeding, as well as a food ingredient aimed to increase the protein content, and raw material for some organic bioactive component extraction. The aim of this work was to evaluate the techno-functional properties of tomato seed meal (TSM) and its nutraceutical properties after applying defatting processing (TSMD), and to evaluate the nutraceutical properties after a fermentation processing (TSMDF) by Lactobacillus sp. The results showed that, at alkaline conditions (pH 8-9), the techno-functional properties for TSM and TSMD improved. In comparison with TSM, TSMD showed higher water holding capacity (WHC ≈32%), higher oil holding capacity (OHC ≈13%), higher protein solubility (49-58%), more than 10 times foaming activity (FA), more than 50 times foam stability (Fst), as well as an improved emulsifying activity (EA) and emulsion stability (Est) wich were better at pH 9. Regarding the nutraceutical properties, after 48 h of fermentation (TSMDF), the antioxidant activity was doubled and a significant increase in the iron chelating activity was also observed. During the same fermentation time, the highest angiotensin-converting enzyme inhibition (ACEI) was achieved (IC50 73.6 µg/mL), more than 10 times higher than TSMD, which leads to suggest that this fermented medium may be a powerful antihypertensive. Therefore, the strategy proposed in this study could be an option for the exploitation of tomato wastes.

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The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.

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Endoreplication is a cell cycle program in which cells replicate their genomes without undergoing mitosis and cytokinesis. For the normal development of many organisms (from fungi to humans) and the formation of their organs, endoreplication is indispensable. The aim of the present study was to explore whether endoreplication and DNA synthesis are relevant processes during the induction of trained innate immunity in human monocytes and in the Anopheles albimanus mosquito cell line. During the induction of trained immunity in both models, endoreplication markers were overexpressed and we observed an increase in DNA synthesis with an augmented copy number of genes essential for trained immunity. Blocking DNA synthesis prevented trained immunity from being established. Overall, these findings suggest that DNA synthesis and endoreplication are important mechanisms involved in inducing innate immune memory. They have probably been conserved throughout evolution from invertebrates to humans.

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Background: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. Aim: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. Patients and Methods: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. Results: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. Conclusions: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.

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A novel catalytic enantioselective methodology based on synergistic catalysis for the synthesis of chiral 2-acyl pyridines and pyrazines is reported. The strategy involves the metal-Lewis acid activation of acetyl aza-arenes and the secondary-amine activation of enals. The proposed mechanism is supported by DFT calculations.

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BACKGROUND: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. AIM: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. PATIENTS AND METHODS: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. RESULTS: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. CONCLUSIONS: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.

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