Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Lyophilized Avocado Paste Improves Corn Chips' Nutritional Properties and Sensory Acceptability.

Avocado paste (AP) is an industrial byproduct and a potential source of bioactive compounds, so there is great interest in its valorization. The objective of the present study was to evaluate the effects of adding AP to corn chips regarding their nutritional profile and sensory acceptability. Three AP-supplemented corn chip samples were prepared (C-2%, C-6%, and C-10%), along with a control chip (C), whose total phenolics, flavonoids, antioxidant capacity, proximate composition, minerals, fatty acids, and sensory acceptability were evaluated. Regarding the content of phenolic compounds and flavonoids, significant increases were found between all samples (p < 0.05), particularly between C and C-10% (from 0.93 to 3.56 mg GAE/g dw and 1.17 to 6.61 mg QE/g dw, respectively). Their antioxidant capacity also increased significantly (p < 0.05) with all methods used (FRAP, DPPH, ORAC, and TEAC). Regarding the sensory analysis, no significant differences were found (p > 0.05) between C and C-2% in the parameters of smell, color, flavor, and overall acceptability; however, the texture of C-2% was better evaluated. The C-2% sample also had the highest acceptability; 82% of the participants mentioned that they would buy the C-2%, higher than the rest of the samples. These results suggest the feasibility of adding 2% AP as a strategy to improve the nutritional properties of corn chips without compromising their sensory acceptability; therefore, AP may be used as a food ingredient.

Photoprotection Knowledge, Habits, and Attitudes Among Spanish and Italian Medical Students. / Conocimientos y hábitos sobre fotoprotección en estudiantes de Medicina españoles e italianos.

Exposure to UV radiation is a major risk factor for the development of malignant skin neoplasms. Currently, there are no studies available on sun-exposure habits among different countries. We conducted a cross-sectional survey among medical students from the University of Rome, Italy and the University of Granada, Spain to compare their photoprotection knowledge, habits, and attitudes. A total of 215 medical students (114 Spanish, and 101 Italian) were included. Spanish students considered the Sun to be the main cause of skin cancer (83.3% vs 61.4%, P=.003) and they looked at their skin more often than Italian students did (32.5% vs 9.9%, P <.001). The latter received information on photoprotection mainly from their dermatologist (34.7%, 35/101) vs Spaniards who received such information from their university (39.5%, 45/114; P <.001). After studying dermatology, Spaniards used sunscreen more frequently than Italians did (76.8% before vs 88.1% after; P=.007), and recognised the need to implement other measures as well (44.9% vs 67.2%; P=.025).

Avocado Paste Phenolics Mitigate a High-Fat Diet-Induced Plasma HDL Decrease in Male Wistar Rats, by Altering the mRNA Expression of Hepatic SCARB1.

Avocado paste (AP) is the main industrial byproduct of its processing, and retains various phenolic compounds (PCs). PCs are known to normalize the plasma lipid profile, but those from avocado byproducts have been minimally studied. We report the normalizing effects of an AP-derived phenolic extract (PE) on the plasma lipid profile of male Wistar rats. A standard (SD) and high-fat diet (HFD) were formulated, and the same diets were supplemented with 1 g/kg of diet of PE (SD + PE and HFD + PE). Rats were fed these diets during an 8-week period. The HFD induced signs of dyslipidemia, but PE treatment countered the decrease in HDL. Relative mRNA expression (real-time PCR) of the hepatic HDL receptor (SCARB1) increased in both groups (SD + PE and HFD + PE), while the LDR receptor (LDLR) increased in SD + PE group. The mRNA expression of apolipoproteins APOA1 and APOB was unaffected. We conclude that PCs from AP can counter a diet-induced decrease in plasma HDL by acting on the mRNA expression of its hepatic receptor.

The Role of Lipid-Lowering Therapy in Post-Stroke Patients: Update and Recommendations.

PURPOSE OF REVIEW: Stroke is the second leading cause of death and disability-adjusted life years worldwide, and the global lifetime risk of stroke is rising. Moreover, patients with a prior stroke are at high risk of recurrent events. We aimed at reviewing the evidence supporting aggressive secondary prevention strategies for lipid-lowering treatment in this population. RECENT FINDINGS: Statins are the key players in such aggressive management; however, stroke survivors remain at significant residual risk suggesting the need for both better implementation of statin use as well as additional lipid lowering therapies. Newer drugs have become available and represent important tools in the management of patients with prior ischemic stroke. The role of lipid lowering treatment in hemorrhagic stroke is more controversial, given epidemiological data linking low lipid levels with increased risk of first and recurrent events. Aggressive secondary prevention strategies, including lipid lowering treatments, have proven to mitigate the risk of recurrent events in post-stroke patients. The tools available for treating such high-risk population have expanded beyond statins, and clinicians should familiarize themselves with them.

Flat Γ Moiré Bands in Twisted Bilayer WSe_{2}.

The recent observation of correlated phases in transition metal dichalcogenide moiré systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moiré superlattice effects in 57.4° twisted WSe_{2} (tWSe_{2}). Our data reveal a split-off flat band that derives from the monolayer Γ states. Using advanced data analysis, we directly quantify the moiré potential from our data. We further demonstrate that the global valence band maximum in tWSe_{2} is close in energy to this flat band but derives from the monolayer K states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that Γ-valley flat bands might be involved in the correlated physics of twisted WSe_{2}.

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment.

BACKGROUND: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´-deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. MATERIAL AND METHODS: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of follow-up. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. RESULTS: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). CONCLUSIONS: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death.

Alkylphosphonium carboxylate ionic liquids with tuned microscopic structures and properties.

Eleven pure alkylphosphonium carboxylate ionic liquids (ILs) were synthesised following a reliable and accessible route. Tetrabutylphosphonium and tetradecyltrihexylphosphonium cations were associated to a variety of [R-COO]- anions with R varying from shorter to longer linear alkyl chains; smaller to bulkier branched alkyl chains; cyclic saturated aliphatic and aromatic moieties; and one heterocyclic aromatic ring containing nitrogen. A combined experimental and molecular simulation study allowed the full characterization of the physico-chemical properties, the structure and the thermal stability of the synthesized ILs. Although slightly more viscous than their imidazolium counterparts, the viscosities of the prepared salts decrease dramatically with temperature and are comparable to other ILs above 50 °C, a manageable temperature as they are thermally stable up to temperatures above 250 °C, even under an oxidizing atmosphere. The microscopic structure of the phophonium ILs is rich and has been studied both experimentally using SAXS and by molecular dynamics simulation using state of the art polarizable force fields whose parameters were determined when necessary. Unique and surprising anion-anion correlations were found for the tetrazolate-based IL allowing to explain some of the unique physical-chemical properties of this phosphonium salt.

Could Naringenin Participate as a Regulator of Obesity and Satiety?

Obesity is a serious health problem worldwide, since it is associated with multiple metabolic disorders and complications such as cardiovascular disease, type 2 diabetes, fatty liver disease and overall metabolic dysfunction. Dysregulation of the hunger-satiety pathway, which includes alterations of central and peripheral signaling, explains some forms of obesity by favoring hyperphagia and weight gain. The present work comprehensively summarizes the mechanisms by which naringenin (NAR), a predominant flavanone in citrus fruits, could modulate the main pathways associated with the development of obesity and some of its comorbidities, such as oxidative stress (OS), inflammation, insulin resistance (IR) and dyslipidemia, as well as the role of NAR in modulating the secretion of enterohormones of the satiety pathway and its possible antiobesogenic effect. The results of multiple in vitro and in vivo studies have shown that NAR has various potentially modulatory biological effects against obesity by countering IR, inflammation, OS, macrophage infiltration, dyslipidemia, hepatic steatosis, and adipose deposition. Likewise, NAR is capable of modulating peptides or peripheral hormones directly associated with the hunger-satiety pathway, such as ghrelin, cholecystokinin, insulin, adiponectin and leptin. The evidence supports the use of NAR as a promising alternative to prevent overweight and obesity.

The CLEAR X-ray emission spectrometer available at the CLAESS beamline of ALBA synchrotron.

The CLEAR X-ray emission spectrometer installed at the CLAESS beamline of the ALBA synchrotron is described. It is an energy-dispersive spectrometer based on Rowland circle geometry with 1 m-diameter circle. The energy dispersion is achieved by the combination of a diced analyzer crystal and a unidimensional detector. A single unconventional dynamically bent analyzer crystal (Si 111) permits a wide energy range to be covered, just by exploiting its different reflections (333, 444, 555, 777, 888): 6-22 keV, with a spectrometer efficiency that decreases above 11 keV because of the Si detector thickness (Mythen, 350 µm), while the relative scattering intensities for the Si 333, 444, 555, 777 and 888 reflections correspond to 36, 40, 21, 13 and 15, respectively. The provided energy resolution is typically below 1-2 eV and depends on the beam size, working Bragg angle and reflection exploited. In most cases the energy dispersion ranges from 10 to 20 eV and can be enlarged by working in the out-of-Rowland geometry up to 40 eV. The spectrometer works in full backscattering geometry with the beam passing through the two halves of the analyzer. The vacuum beam path and the particular geometry allow a typical average noise of only 0.5 counts per second per pixel. The spectrometer is mainly used for measuring emission lines and high-resolution absorption spectra, with a typical scanning time for highly concentrated systems of around half an hour, including several repeats. The intrinsic energy dispersion allows systematic collection of resonant X-ray emission maps by measuring high-resolution absorption spectra. Moreover, it allows spectra to be measured on a single-shot basis. Resonant inelastic X-ray scattering experiments to probe electronic excitations are feasible, although the spectrometer is not optimized for this purpose due to the limited energy resolution and scattering geometry provided. In that case, to minimize the quasi-elastic line, the spectrometer is able to rotate along the beam path. Advantages and disadvantages with respect to other existing spectrometers are highlighted.

Revisiting the high-fat diet/low streptozotocin prediabetic rat model: A bioanalytical adjustment.

Insulin resistance (IR) is the main feature of prediabetes (PD), which ultimately leads to diabetes. High-dose streptozotocin-treated rodents often show irreversible ß-cell mass loss and function, leaving the premorbid diabetic state (PD/IR) unnoticed. This study aimed to re-evaluate the synergistic/independent effect of a sub-chronic consumption (1-5 weeks) of a high-fat diet (60% gross energy from fat, 3.8 kcal.g-1) with [PD/IR-2 (week 2) to PD/IR-5 week five)] or without [HFD-5 (week five)] a single intraperitoneal dose (35 mg.kg-1) of streptozotocin in Wistar rats. Bioassay performance and clinical/histological features suggesting PD/IR or diabetes, were documented weekly and compared to standard chow-fed (3.5 kcal.g-1) rats (healthy controls, HC). PD/IR1-5 (fed with HFD for 1 to 5 weeks plus a single dose of streptozotocin) and HFD-5 (just fed with HFD for 5 weeks) groups reduced their food intake yet gained more body weight than HC. Groups exhibited hyperglycemia, dyslipidemia, and impaired glucose tolerance in decreasing order as follows: PD/IR-5, PD/IR-4, HFD-5, PD/IR-2-3, and HC. Histological disturbances in the pancreas, Soleus muscle, and liver were mostly observed in HFD-5 and PD/IR4-5 groups. HFD administration for 4 weeks white a single moderate dose of streptozotocin four days before sacrifice, leads to a convenient PD/IR rat model.

Caesalpinia palmeri: First Report on the Phenolic Compounds Profile, Antioxidant and Cytotoxicity Effect.

This study aimed to determine the phenolic compounds profile, antioxidant potential and cytotoxicity of extracts and fractions of Caesalpinia palmeri. Methanolic extracts were generated from C. palmeri berries, stems and flowers. The latter was subjected to liquid-liquid partition, obtaining hexane, ethyl acetate and residues fractions. Results showed that the flower extract and ethyl acetate fraction had a larger concentration of phenolic compounds (148.9 and 307.9 mg GAE/g, respectively), being ellagic acid (6233.57 and 19550.08 µg/g, respectively), quercetin-3-ß-glycoside (3023.85 and 8952.55 µg/g, respectively) and gallic acid (2212.98 and 8422.34 µg/g, respectively) the most abundant compounds. Flower extract and ethyl acetate fraction also presented the highest antioxidant capacity on all tested methods (DPPH, ABTS, ORAC and FRAP) and low cytotoxicity against ARPE-19 cells (IC50 >170 µg/mL). C. palmeri possessed high antioxidant potential, associated with the presence of phenolic compounds and low cytotoxicity, suggesting that they could represent an option to counter oxidative stress.

Optimization and In Vitro Digestion of a Guava (Psidium guajava), Mamey (Pouteria sapota) and Stevia (Stevia rebaudiana) Functional Beverage.

Guava and mamey are phenolic- and carotenoid-rich fruits with potential health benefits, but are minimally used as ingredients in functional beverages. The objectives of the present work are to optimize the content of guava and mamey pulps and a stevia solution in the formulation of a functional beverage with high content of bioactive compounds and sensory acceptability using a mixture design analysis, and to analyze its composition after in vitro digestion. The optimized formulation (17.77 and 19.23 g of guava and mamey pulps, respectively; 1% stevia solution) yielded a beverage with 418.21 mg gallic acid equivalents (GAE)/100 mL and 0.20 mg ß-carotene/100 mL, and an antioxidant capacity of 213.58, 78.90 and 234.03 mg Trolox equivalents (TE)/100 mL using three methodologies. The mathematical model developed was significant (p < 0.05), according to R2 values between 0.70 and 0.75. α- and ß-carotene were quantified during the oral phase of in vitro digestion. Gallic, p-coumaric, ferulic and chlorogenic acids were also identified. The beverage had a general acceptability of 6.72. We conclude that the mathematical model developed was a good predictor of the experimental data and that the optimized beverage contained high bioactive concentrations (phenolics and carotenoids) and was well-accepted by potential consumers.

Dietary Phenolic Compounds Exert Some of Their Health-Promoting Bioactivities by Targeting Liver X Receptor (LXR) and Retinoid X Receptor (RXR).

Consuming foods of vegetable origin has been shown to exert multiple health-related effects, many of them attributed to their phenolic compounds. These molecules are known for being bioactive across multiple cells and organs, with documented changes in gene expression being commonly reported. Nuclear receptors are signal transducers capable of regulating gene expression in response to endogenous and/or exogenous ligands. Liver X receptor (LXR) and retinoid X receptor (RXR) are two important nuclear receptors that can be acted on by phenolic compounds, thereby modifying gene expression and potentially exerting numerous subsequent bioactivities. The present work summarizes recent evidence of the effects of the phenolic compounds that are exerted by targeting LXR and/or RXR. The data show that, when LXR is being targeted, changes in lipid metabolism are commonly observed, due to its ability to regulate genes relevant to this process. The effects vary widely when RXR is the target since it is involved in processes like cell proliferation, vitamin D metabolism, and multiple others by forming heterodimers with other transcription factors that regulate said processes. The evidence therefore shows that phenolic compounds can exert multiple bioactivities, with a mechanism of action based, at least in part, on their ability to modulate the cell at the molecular level by acting on nuclear receptors. The data point to a promising and novel area of study that links diet and health, although various unknowns justify further experimentation to reveal the precise way in which a given phenolic can interact with a nuclear receptor.

Female sex workers and police violence during the Covid-19 health crisis in 2020-2021: results from the EPIC multi-country community-based research program in Argentina.

BACKGROUND: Female sex workers (FSW) have been disproportionately impacted by the Covid-19 crisis. Data show increases of police violence toward key populations (KP), likely a consequence of their role in enforcing health government measures. This study aimed to identify factors associated with police violence experienced by FSW during the Covid-19 crisis in Argentina. METHODS: EPIC is a multi-country, cross-sectional, community-based research program evaluating the impact of Covid-19 among KP. In Argentina, the study was conducted in collaboration with FSW community-based organizations (CBO). Participants completed an online survey (October 2020-April 2021). Police violence was measured as having experienced episodes of violence (physical, verbal, psychological or sexual) by security forces since the start of the health crisis. Factors associated with police violence were assessed in logistic regression models. RESULTS: Among 173 respondents, median age was 34 [IQR 27-42], 39.3% were transgender women (TW), 78.1% declared sex work as their only income and 71.7% mentioned their financial situation has deteriorated with the health crisis. Nearly half of FSW (44.5%) reported experiencing police violence within the first year of the Covid-19 pandemic, and among them, 76.6% declared more frequent violence episodes since the beginning of the health crisis. After adjustment for age, being a TW (aOR [95% CI] = 2.71 [1.21;6.05]), reporting non-injection drug use (2.92 [1.02;8.36]), having a considerably deteriorated financial situation (3.67 [1.47;9.21]), having had a consultation with a CBO worker for medical care/treatments (5.56 [2.15;14.37]) and declaring fear or experiences of discrimination by physicians/other health workers (2.97 [1.21;7.29]), since the beginning of the Covid-19 health crisis, were independently associated with police violence. CONCLUSIONS: FSW in Argentina have experienced an increase in police violence since the beginning of the health crisis. Belonging to multiple KP (FSW, TW, people who use drugs) increases the likelihood of experiencing police violence, highlighting the need of an intersectional approach to develop interventions to reduce stigma and violence against FSW. CBOs have provided essential support and services during the crisis to FSWs, and other KPs, who may have avoided traditional healthcare structures due to fear or experiences of discrimination.

Single-Cell Protein Production as a Strategy to Reincorporate Food Waste and Agro By-Products Back into the Processing Chain.

Food waste is a serious problem with negative environmental and economic consequences. Unused food (either as waste or by-products and referred to as food residues in the present work) is a source of carbohydrates, lipids, proteins, vitamins, minerals and bioactive compounds that could be used in an alternate or secondary life cycle to avoid discarding it. The present work reviews the potential use of food residues for the bioengineering of single-cell protein (SCP), addressing aspects of production, nutrition and safety, as well as the main challenges and perspectives. SCP is obtained from various microorganisms, including fungi, bacteria, yeasts and algae, in pure or mixed form. SCP generally contains a higher percentage of protein (30-80%) compared to soy (38.6%), fish (17.8%), meat (21.2%) and whole milk (3.28%). SCP is a source of essential amino acids, including methionine, threonine and lysine. The use of food residues as substrates for the production of SCP would reduce production costs (35-75%); however, optimization and industrial scaling are some of the main challenges to its sustainable production. The use food waste and agro by-products from the food industry could be a promising alternative to obtain protein according to a circular production scheme.

Lesser-Consumed Tropical Fruits and Their by-Products: Phytochemical Content and Their Antioxidant and Anti-Inflammatory Potential.

Açaí, lychee, mamey, passion fruit and jackfruit are some lesser-consumed tropical fruits due to their low commercial production. In 2018, approximately 6.8 million tons of these fruits were harvested, representing about 6.35% of the total world production of tropical fruits. The present work reviews the nutritional content, profile of bioactive compounds, antioxidant and anti-inflammatory capacity of these fruits and their by-products, and their ability to modulate oxidative stress due to the content of phenolic compounds, carotenoids and dietary fiber. Açaí pulp is an excellent source of anthocyanins (587 mg cyanidin-3-glucoside equivalents/100 g dry weight, dw), mamey pulp is rich in carotenoids (36.12 mg ß-carotene/100 g fresh weight, fw), passion fruit peel is rich in dietary fiber (61.16 g/100 dw). At the same time, jackfruit contains unique compounds such as moracin C, artocarpesin, norartocarpetin and oxyresveratrol. These molecules play an important role in the regulation of inflammation via activation of mitogen-activated protein kinases (including p38, ERK and JNK) and nuclear factor κB pathways. The properties of the bioactive compounds found in these fruits make them a good source for use as food ingredients for nutritional purposes or alternative therapies. Research is needed to confirm their health benefits that can increase their marketability, which can benefit the primary producers, processing industries (particularly smaller ones) and the final consumer, while an integral use of their by-products will allow their incorporation into the circular bioeconomy.

The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Phenolic compounds can induce systemic and central immunomodulation, which result in a neuroprotective effect.

Inflammation may negatively impact health, particularly that of the central nervous system. Phenolic compounds are bioactive molecules present in fruits and vegetables with potential anti-inflammatory effects. The purpose of the present work is to review the immunomodulatory bioactivities of phenolic compounds in the periphery and in the central nervous system. Results show that various types of phenolics are able to counter diet- or pathogen-induced systemic inflammation (among others) in various models. In vitro data show significant effects of flavonoids and phenolic acids in particular; similar bioactivities were reported in vivo, when administering them as pure compounds or from fruit and vegetable extracts that contain them. In the central nervous system, phenolics counter chronic inflammation and aggressive acute inflammatory processes, such as ischemic events, when administered preemptively and even therapeutically. We therefore conclude that the immunomodulatory potential of phenolic compounds can maintain an adequate immune response; their regular consumption should therefore be prioritized in order to maintain health. PRACTICAL APPLICATIONS: The immune response must be carefully regulated in order to avoid its deleterious effects. The present work highlights how phenolic compounds, dietary components ubiquitous in everyday diet, are able to maintain it within an adequate range. As humans are exposed to more proinflammatory stimuli (inadequate dietary pattern, mental stress, environmental pollution, chronic diseases, etc.), it becomes necessary to counter them, and consuming adequate amounts of foods that contain compounds with this ability is a rather simple strategy. Thus, the present work highlights how fruits and vegetables can help to maintain an adequate immune response that can preserve systemic health and that of the central nervous system. Furthermore, specific compounds contained in them can also be ideal candidates for additional in-depth studies, which can potentially lead to the development of potent, targeted, and safe anti-inflammatory molecules.