Car T Cells in Solid Tumors: Overcoming Obstacles.

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.

Antioxidants in Photoaging: From Molecular Insights to Clinical Applications.

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.

Pancreatic and Hepatic Injury in COVID-19: A Worse Prognosis in NAFLD Patients?

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient's clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

Weight Regain after Metabolic Surgery: Beyond the Surgical Failure.

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients. Even metabolic surgery has proven to be effective in reducing excess weight in patients with obesity; some of them regain weight after this intervention. In this vein, several studies have been conducted to search factors and mechanisms involved in weight regain, to stablish strategies to manage this complication by combining metabolic surgery with either lifestyle changes, behavioral therapies, pharmacotherapy, endoscopic interventions, or finally, surgical revision. The aim of this revision is to describe certain aspects and mechanisms behind weight regain after metabolic surgery, along with preventive and therapeutic strategies for this complication.

Psychometric properties of the self-efficacy scale for chronic disease management (SEMCD-S) in older Colombian adults.

BACKGROUND: Self-efficacy alludes to personal competence in an individual's effectiveness when facing stressful situations. This construct has been related to different domains of the health field, finding that high levels of self-efficacy benefit human functioning and enhance well-being. METHODS: The present study aimed to determine the psychometric properties of the self-efficacy scale for managing chronic diseases (SEMCD-S) by assessing factorial, convergent and divergent validity, reliability, and measurement invariance. Likewise, the comparison of self-efficacy according to socio-demographic characteristics was proposed by contrasting latent factors. An instrumental, transactional, descriptive, and non-experimental design study was carried out with the participation of 325 Colombian senior citizens. RESULTS: The findings suggest that the scale has appropriate psychometric properties. The one-factor structure exhibited a satisfactory fit, the mean-variance extracted reported acceptable figures and the correlation analysis with other constructs supported this instrument's convergent and discriminant validity. Likewise, it was invariant to the different socio-demographic aspects examined, while the internal consistency figures were high. Differences in the means of the latent factors were only detected in the academic grade. In this case, older adults with a primary school level attained higher self-efficacy values than those who had completed high school or university studies. CONCLUSIONS: It is concluded that the self-efficacy scale for chronic disease management is a valid and reliable instrument that can be used in the Colombian context to measure and compare this construct.

The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Intrinsic and environmental basis of aging: A narrative review.

Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

Metabolic Adverse Effects of Psychotropic Drug Therapy: A Systematic Review.

This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.

Low Doses of Melatonin to Improve Sleep in Children with ADHD: An Open-Label Trial.

OBJECTIVE: Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH). METHODS: Children and adolescents (7-15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment. RESULTS: Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported. CONCLUSION: Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients.

A bibliometric analysis and literature review on emotional skills.

The content, management, and implementation of social skills have been developed since the end of the 20th century as a model of capabilities. Thus, as human beings develop and train their basic cognitive and perceptual-motor functions, they increase their ability to solve and cope with difficulties. This article aims to present a bibliometric and systematic review of social skills, using query sources in databases such as Web of Science (WoS) and Scopus between the years 2000 and 2022, with platforms such as Bibliometrix and Gephi. This search yielded a total of 233 records in WoS and 250 records in Scopus that were merged and, after eliminating 143 duplicate data, were consolidated into 340 records that enclose the academic production of 20 years. Through scientific mapping, the main authors, journals, and countries in this field were determined; similarly, the most relevant studies were classified into three categories, namely, classic, structural, and perspectives, which were represented by means of the metaphor of the tree of science. In addition, a program for further studies was planned, such as in-depth qualitative research measuring observationally and directly taking into account emotional expressiveness, emotional understanding, emotion regulation, and behavior, and the impact of social skills training on social problem-solving. Finally, another important aspect to mention is that this research work is useful for the scientific academic community in many areas of knowledge such as psychology, education, and managers of educational institutions.

Exploring the Relationship between the Gut Microbiota and Ageing: A Possible Age Modulator.

The gut microbiota (GM) has been the subject of intense research in recent years. Therefore, numerous factors affecting its composition have been thoroughly examined, and with them, their function and role in the individual's systems. The gut microbiota's taxonomical composition dramatically impacts older adults' health status. In this regard, it could either extend their life expectancy via the modulation of metabolic processes and the immune system or, in the case of dysbiosis, predispose them to age-related diseases, including bowel inflammatory and musculoskeletal diseases and metabolic and neurological disorders. In general, the microbiome of the elderly tends to present taxonomic and functional changes, which can function as a target to modulate the microbiota and improve the health of this population. The GM of centenarians is unique, with the faculty-promoting metabolic pathways capable of preventing and counteracting the different processes associated with age-related diseases. The molecular mechanisms by which the microbiota can exhibit anti-ageing properties are mainly based on anti-inflammatory and antioxidant actions. This review focuses on analysing the current knowledge of gut microbiota characteristics and modifiers, its relationship with ageing, and the GM-modulating approaches to increase life expectancy.

New Evidence on BPA's Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity.

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1ß, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.

Quality of life in the older adults: The protective role of self-efficacy in adequate coping in patients with chronic diseases.

The purpose of the present study was to establish the association between self-efficacy, perception of disease, emotional regulation, and fatigue and the health-related quality of life in older adults living in the departments of Cesar and Atlántico in Colombia and who have been diagnosed with a chronic disease. The participants were 325 older adults of both sexes, with literacy and no presence of cognitive impairment in the Mini-Mental State Examination (MMSE); A non-probabilistic sampling was carried out. We used the MOS-SF-36 questionnaire, the Brief Illness Perception Questionnaire scale for measuring the perception of disease, the Stanford Patient Education Research Center's Chronic Disease Self self-efficacy questionnaire for chronic patients, the Difficulties in Emotional Regulation Scale, and the Fatigue Severity Questionnaire as measurement instruments. The design was non-experimental cross-sectional with a correlational scope. The results indicate that self-efficacy, disease perception, emotional regulation and severity of fatigue are variables that could impact the physical function of quality of life, confirming that self-efficacy would work as a factor that decreases the probability that a participant score low on this dimension of quality of life. On the other hand, both the perception of the disease and the severity of fatigue were identified as factors that probably negatively influence quality of life.

NHANES 2011-2014 Reveals Decreased Cognitive Performance in U.S. Older Adults with Metabolic Syndrome Combinations.

A relationship between metabolic syndrome and cognitive impairment has been evidenced across research; however, conflicting results have been observed. A cross-sectional study was conducted on 3179 adults older than 60 from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) to analyze the relationship between metabolic syndrome and cognitive impairment. In our results, we found that adults with abdominal obesity, high triglycerides, and low HDL cholesterol had 4.39 fewer points in the CERAD immediate recall test than adults without any metabolic syndrome factors [Beta = -4.39, SE = 1.32, 17.75 (1.36) vs. 22.14 (0.76)]. In addition, people with this metabolic syndrome combination exhibited 2.39 fewer points in the CERAD delayed recall test than those without metabolic syndrome criteria [Beta = -2.39, SE = 0.46, 4.32 (0.49) vs. 6.71 (0.30)]. It was also found that persons with high blood pressure, hyperglycemia, and low HDL-cholesterol levels reached 4.11 points less in the animal fluency test than people with no factors [Beta = -4.11, SE = 1.55, 12.67 (2.12) vs. 16.79 (1.35)]. These findings suggest that specific metabolic syndrome combinations are essential predictors of cognitive impairment. In this study, metabolic syndrome combinations that included obesity, fasting hyperglycemia, high triglycerides, and low HDL-cholesterol were among the most frequent criteria observed.

Role of Gut Microbiome in Atherosclerosis: Molecular and Therapeutic Aspects.

Atherosclerosis is one of the most relevant and prevalent cardiovascular diseases of our time. It is one of the pathological entities that increases the morbidity and mortality index in the adult population. Pathophysiological connections have been observed between atherosclerosis and the gut microbiome (GM), represented by a group of microorganisms that are present in the gut. These microorganisms are vital for metabolic homeostasis in humans. Recently, direct and indirect mechanisms through which GM can affect the development of atherosclerosis have been studied. This has led to research into the possible modulation of GM and metabolites as a new target in the prevention and treatment of atherosclerosis. The goal of this review is to analyze the physiopathological mechanisms linking GM and atherosclerosis that have been described so far. We also aim to summarize the recent studies that propose GM as a potential target in atherosclerosis management.

Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson's disease psychosis (PDP) occurs in 18-50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the disease's motor symptoms. OBJECTIVE: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP and recent innovative alternatives for its treatment. METHODS: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases from inception to August 2021. The terms "Parkinson's disease psychosis", "Parkinson psychosis," "neurodegenerative psychosis", and "dopamine psychosis" were among the keywords used in the search. RESULTS: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity dependent on extrinsic and novel intrinsic mechanisms, including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval to treat PDP-associated hallucinations and illusions. CONCLUSION: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.

Stomatognathic System Changes in Obese Patients Undergoing Bariatric Surgery: A Systematic Review.

BACKGROUND: Obesity is a multifactorial chronic disease involving multiple organs, devices, and systems involving important changes in the stomatognathic system, such as in the orofacial muscles, temporomandibular joint, cheeks, nose, jaw, maxilla, oral cavity, lips, teeth, tongue, hard/soft palate, larynx, and pharynx. Patients with obesity indicated for bariatric surgery reportedly presented with abnormalities in the structures and function of the stomatognathic apparatus. This occurs through the accumulation of adipose tissue in the oral cavity and pharyngeal and laryngeal regions. Therefore, this systematic review aimed to elucidate the changes occurring in the stomatognathic system of patients with obesity after undergoing bariatric surgery. METHOD: Information was searched based on the equations developed with the descriptors obtained in DECS and MESH using the PRISMA methodology. Studies published between 2010 and October 2021 in databases including PubMed, ProQuest, Scielo, Dialnet, EBSCO, and Springer Link were considered. RESULTS: Eighty articles met the inclusion criteria after evaluating the articles, thereby allowing for the determination of the morphophysiological correlation of the stomatognathic system with the population studied. At the morphological or structural level, changes were observed in the face, nose, cheeks, maxilla, jaw, lips, oral cavity, teeth, tongue, palate, temporomandibular joint, neck, muscles, head, shoulders, larynx, and pharynx. At the morphological level, the main changes occurred in, and the most information was obtained from, the labial structures, teeth, muscles, pharynx, and larynx. Physiological changes were in breathing, phonation, chewing, and swallowing, thereby revealing the imbalance in basic and vital functions. CONCLUSIONS: Analyzing the changes and structures of obese patients and candidates for bariatric surgery revealed that, in the preoperative period, the evidence is clear owing to the presence of a wide range of information. However, the information is more limited regarding the postoperative period; thus, further research focusing on characterization of the system postoperatively is warranted.

Probiotics and Gut Microbiota in Obesity: Myths and Realities of a New Health Revolution.

Obesity and its comorbidities are humans' most prevalent cardio-metabolic diseases worldwide. Recent evidence has shown that chronic low-grade inflammation is a common feature in all highly prevalent chronic degenerative diseases. In this sense, the gut microbiota is a complete ecosystem involved in different processes like vitamin synthesis, metabolism regulation, and both appetite and immune system control. Thus, dysbiosis has been recognised as one of the many factors associated with obesity due to a predominance of Firmicutes, a decrease in Bifidobacterium in the gut, and a consequent short-chain fatty acids (SCFA) synthesis reduction leading to a reduction in incretins action and intestinal permeability increase. In this context, bacteria, bacterial endotoxins, and toxic bacterial by-products are translocated to the bloodstream, leading to systemic inflammation. This review focuses on gut microbiota composition and its role in obesity, as well as probiotics and prebiotics benefits in obesity.

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine-Immune Therapeutic Mechanisms and Clinical Implications.

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms "electroconvulsive therapy", "neurobiological effects of electroconvulsive therapy", "molecular mechanisms in electroconvulsive therapy", and "psychiatric disorders" were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus-hypophysis-adrenal and hypothalamus-hypophysis-thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson's disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive-compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.

Exploring the Links between Obesity and Psoriasis: A Comprehensive Review.

Obesity is a major public health issue worldwide since it is associated with the development of chronic comorbidities such as type 2 diabetes, dyslipidemias, atherosclerosis, some cancer forms and skin diseases, including psoriasis. Scientific evidence has indicated that the possible link between obesity and psoriasis may be multifactorial, highlighting dietary habits, lifestyle, certain genetic factors and the microbiome as leading factors in the progress of both pathologies because they are associated with a chronic pro-inflammatory state. Thus, inflammation management in obesity is a plausible target for psoriasis, not only because of the sick adipose tissue secretome profile but also due to the relationship of obesity with the rest of the immune derangements associated with psoriasis initiation and maintenance. Hence, this review will provide a general and molecular overview of the relationship between both pathologies and present recent therapeutic advances in treating this problem.