Geriatric Oncology: A 5-Year Strategic Plan.

The increasing rate of the older adult population across the world over the next 20 years along with significant developments in the treatment of oncology will require a more granular understanding of the older adult population with cancer. The ASCO Geriatric Oncology Community of Practice (COP) herein provides an outline for the field along three fundamental pillars: education, research, and implementation, inspired by ASCO's 5-Year Strategic Plan. Fundamental to improving the understanding of geriatric oncology is research that intentionally includes older adults with clinically meaningful data supported by grants across all career stages. The increased knowledge base that is developed should be conveyed among health care providers through core competencies for trainees and continuing education for practicing oncologists. ASCO's infrastructure can serve as a resource for fellowship programs interested in acquiring geriatric oncology content and provide recommendations on developing training pathways for fellows interested in pursuing formalized training in geriatrics. Incorporating geriatric oncology into everyday practice is challenging as each clinical setting has unique operational workflows with barriers that limit implementation of valuable geriatric tools such as Geriatric Assessment. Partnerships among experts in quality improvement from the ASCO Geriatric Oncology COP, the Cancer and Aging Research Group, and ASCO's Quality Training Program can provide one such venue for implementation of geriatric oncology through a structured support mechanism. The field of geriatric oncology must continue to find innovative strategies using existing resources and partnerships to address the pressing needs of the older adult population with cancer to improve patient outcomes.

Climate change consequences on the systemic heart of female Octopus maya: oxidative phosphorylation assessment and the antioxidant system.

There is evidence that indicates that temperature modulates the reproduction of the tropical species Octopus maya, through the over- or under-expression of many genes in the brain. If the oxygen supply to the brain depends on the circulatory system, how temperature affects different tissues will begin in the heart, responsible for pumping the oxygen to tissues. The present study examines the impact of heat stress on the mitochondrial function of the systemic heart of adult O. maya. The mitochondrial metabolism and antioxidant defense system were measured in the systemic heart tissue of female organisms acclimated to different temperatures (24, 26, and 30°C). The results show that acclimation temperature affects respiratory State 3 and State 4o (oligomycin-induced) with higher values observed in females acclimated at 26°C. The antioxidant defense system is also affected by acclimation temperature with significant differences observed in superoxide dismutase, glutathione S-transferase activities, and glutathione levels. The results suggest that high temperatures (30°C) could exert physical limitations on the circulatory system through the heart pumping, affecting nutrient and oxygen transport to other tissues, including the brain, which exerts control over the reproductive system. The role of the cardiovascular system in supporting aerobic metabolism in octopus females is discussed.

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis.

Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b+ LY6Chigh). Furthermore, both CD11b+ Ly6Clow F4/80high macrophages (MΦ) and recently differentiated CD11b+ Ly6Chigh F4/80high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206high) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.

Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species.

Social behaviour is essential for animal survival, and the hypothalamic neuropeptide oxytocin (OXT) critically impacts bonding, parenting, and decision-making. Dopamine (DA), is released by ventral tegmental area (VTA) dopaminergic neurons, regulating social cues in the mesolimbic system. Despite extensive exploration of OXT and DA roles in social behaviour independently, limited studies investigate their interplay. This narrative review integrates insights from human and animal studies, particularly rodents, emphasising recent research on pharmacological manipulations of OXT or DA systems in social behaviour. Additionally, we review studies correlating social behaviour with blood/cerebral OXT and DA levels. Behavioural facets include sociability, cooperation, pair bonding and parental care. In addition, we provide insights into OXT-DA interplay in animal models of social stress, autism, and schizophrenia. Emphasis is placed on the complex relationship between the OXT and DA systems and their collective influence on social behaviour across physiological and pathological conditions. Understanding OXT and DA imbalance is fundamental for unravelling the neurobiological underpinnings of social interaction and reward processing deficits observed in psychiatric conditions.

Clearance rates of sand-burrowed and laterally pressed unburrowed Pismo clam Tivela stultorum (Mawe 1823) in a laboratory open-flow system.

Pismo clam extraction is currently banned in Mexico to help the recovery of natural populations. Thus, the primary objective of this study was to gain insight on its basic biology and husbandry protocols. Growth and clearance rate (CR) of sand-burrowed and sediment-free, laterally pressed adult Pismo clams were quantified in the laboratory as a function of burrowing condition, flow, temperature, and microalgal concentration using open-flow chambers. After 40 days, clams remained healthy regardless of burrowing condition and showed a hyperbolic CR response pattern to increased flow, with CR directly proportional to flows lower than 1000 ml min-1. Maximal asymptotic CR values (300 to 400 ml min-1 org-1) were observed from 1000 to 2000 ml min-1. No significant CR differences were observed between burrowed and laterally pressed clams, yet microalgal concentration effects were detected, with constant maximal CRs of ∼250 ml min-1 in the range of 50 to 200 cells µl-1 and decline at higher concentrations. Maintenance protocols of laterally pressed organisms were validated in the laboratory with both weight and CR data. To our knowledge, this is the first study providing whole-body physiological data translated into effective husbandry protocols for Pismo clams. This approach represents a fresh perspective to traditional research areas, opening the possibility for continued experimentation under controlled conditions.

Electrochemical synthesis of 2D-silver nanodendrites functionalized with cyclodextrin for SERS-based detection of herbicide MCPA.

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has found application in the trace detection of a wide range of contaminants. In this paper, we report on the fabrication of 2D silver nanodendrites, on silicon chips, synthesized by electrochemical reduction of AgNO3at microelectrodes. The formation of nanodendrites is tentatively explained in terms of electromigration and diffusion of silver ions. Electrochemical characterization suggests that the nanodendrites do not stay electrically connected to the microelectrode. The substrates show SERS activity with an enhancement factor on the order of 106. Density functional theory simulations were carried out to investigate the suitability of the fabricated substrate for pesticide monitoring. These substrates can be functionalized with cyclodextrin macro molecules to help with the detection of molecules with low affinity with silver surfaces. A proof of concept is demonstrated with the detection of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

Frequency and Focus of in Vitro Studies of Microglia-Expressed Cytokines in Response to Viral Infection: A Systematic Review.

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.

The Use of CAD-CAM Templates in Lateral Sinus Floor Augmentation Procedure: A Systematic Review.

INTRODUCTION: Maxillary sinus floor augmentation is a procedure known for its long-term success and predictable outcomes. However, the perforation of the Schneiderian membrane remains the most common complication associated with this procedure. OBJECTIVE: This systematic review aims to determine the presence of complications during maxillary sinus floor augmentation procedures using CAD-CAM surgical templates. MATERIAL AND METHODS: An electronic search was carried out in MEDLINE (via PubMed), Web of Science, and Scopus. A descriptive analysis of the data was performed. Studies that have performed lateral sinus floor augmentation were included in the inclusion criteria. The CAD-CAM surgical template design and the intraoperative complications were registered. RESULTS: A total of 13 studies were included. Seven were case reports, four were case series, and two were randomized clinical trials. A total of 94 lateral SFA procedures were included (84 using CADCAM templates and 10 without using templates). Three of the 84 maxillary sinus floor augmentation procedures using a CAD-CAM template presented intraoperative complications. CONCLUSIONS: Maxillary sinus floor augmentation performed by using CAD-CAM surgical templates could be related to low rates of complications, however, due to the heterogeneity of the articles included, more standardized studies are needed to confirm these outcomes.

Brief exposure to enriched environment rapidly shapes the glutamate synapses in the rat brain: A metaplastic fingerprint.

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward-seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area-specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate rewarding and memory processes.

Major and durable responses to photon and electron-beam palliative radiotherapies after immune-checkpoint inhibitors in head and neck cancer.

BACKGROUND: The immuno-modulatory effects of ionizing radiation are well-known and preclinical studies suggest a synergistic effect of combining radiotherapy (RT) and IO. However, data regarding the clinical activity and safety of this approach are limited. METHODS: We present the cases of two patients with SCCHN primary progressing to PDL1-based IO within a clinical trial (NCT03383094), that received subsequent but not concurrent palliative RT using two different modalities (electron beam and photon beam therapies). RESULTS: Both patients achieved major and durable responses at 4 irradiated sites, with excellent tolerance and no grade ≥ 3 toxicities. Complete response occurred in 3 of the disease areas (all locoregional) and partial response in 1 metastatic lesion. CONCLUSION: Palliative radiotherapy after progression to IO was safe and demonstrated profound and durable responses in the cases presented.

Using LEGO® Serious Play for students' Critical-Reflective Reasoning development in the construction of the nursing metaparadigm.

INTRODUCTION: In a nursing degree critical reasoning competency includes reasoning both inside and outside the clinical setting. One of the major challenges for nursing students is learning concepts at a high abstract level. In this sense, the LEGO® Serious Play method has the potential to improve thinking skills. AIMS: To describe a) which elements of thinking link to the learning of the nursing metaparadigm through the use of the LEGO® Serious Play "four Cs" method b) analyse how this method helps to generate critical reflective thinking in nursing students during the process of application of theoretical knowledge about the nursing metaparadigm in a new situation. METHODS: An interpretive phenomenological analysis, integrating qualitative research methods was implemented as a means of undertaking research facilitated using LEGO® Serious Play method as an innovative method of data collection. RESULTS: 280 participants were recruited. From the analysis of the contributions made to the students' forum, six categories emerged: Starting point, Consciousness, Process, Teamwork, Capacities and Limitations. CONCLUSION: LEGO® Serious Play is an effective method for teaching nursing metaparadigms and helps students acquire and generate new knowledge.

Evaluation of the osmoregulatory capacity and three stress biomarkers in white shrimp Penaeus vannamei exposed to different temperature and salinity conditions: Na+/K+ ATPase, Heat Shock Proteins (HSP), and Crustacean Hyperglycemic Hormones (CHHs).

Salinity and temperature influence growth, survival, and reproduction of crustacean species such as Penaeus vannamei where Na +/K+-ATPase plays a key role in maintaining osmotic homeostasis in different salinity conditions. This ability is suggested to be mediated by other proteins including neuropeptides such as the crustacean hyperglycemic hormones (CHHs), and heat shock proteins (HSPs). The mRNA expression of Na+/K+-ATPase, HSP60, HSP70, CHH-A, and CHH-B1, was analyzed by qPCR in shrimp acclimated to different salinities (10, 26, and 40 PSU) and temperature conditions (20, 23, 26, 29, and 32 °C) to evaluate their uses as molecular stress biomarkers. The results showed that the hemolymph osmoregulatory capacity in shrimp changed with exposure to the different salinities. From 26 to 32 °C the Na+/K+-ATPase expression increased significantly at 10 PSU relative to shrimp acclimated at 26 PSU and at 20 °C increased at similar values independently of salinity. The highest HSP expression levels were obtained by HSP70 at 20 °C, suggesting a role in protecting proteins such as Na+/K+ -ATPase under low-temperature and salinity conditions. CHH-A was not expressed in the gill under any condition, but CHH-B1 showed the highest expression at the lowest temperatures and salinities, suggesting its participation in the Na+/K+-ATPase induction. Since Na+/K+-ATPase, HSPs, and CHHs seem to participate in maintaining the osmo-ionic balance and homeostasis in P. vannamei, their expression levels may be used as a stress biomarkers to monitor marine crustacean health status when acclimated in low salinity and temperature conditions.

Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults.

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.

Clusterin protects mature dendritic cells from reactive oxygen species mediated cell death.

Dendritic cells (DCs) play a key role in the induction of the adaptive immune response. They capture antigens in peripheral tissues and prime naïve T lymphocytes, triggering the adaptive immune response. In the course of inflammatory processes DCs face stressful conditions including hypoxia, low pH and high concentrations of reactive oxygen species (ROS), among others. How DCs survive under these adverse conditions remain poorly understood. Clusterin is a protein highly expressed by tumors and usually associated with bad prognosis. It promotes cancer cell survival by different mechanisms such as apoptosis inhibition and promotion of autophagy. Here, we show that, upon maturation, human monocyte-derived DCs (MoDCs) up-regulate clusterin expression. Clusterin protects MoDCs from ROS-mediated toxicity, enhancing DC survival and promoting their ability to induce T cell activation. In line with these results, we found that clusterin is expressed by a population of mature LAMP3+ DCs, called mregDCs, but not by immature DCs in human cancer. The expression of clusterin by intratumoral DCs was shown to be associated with a transcriptomic profile indicative of cellular response to stress. These results uncover an important role for clusterin in DC physiology.

The future of vaccination in Latin America: learning from the COVID-19 pandemic.

The SARS-CoV-2 pandemic caused millions of deaths around the world. This dramatic balance requires governments, international organizations, vaccine manufacturers, and the scientific community itself to take stock of what has been done and what could have been done better. In this sense, the tremendous inequity in access to vaccines, the main tool to deal with the pandemic, deserves deep reflection and a set of actions to be carried out by low- and middle-income countries. Among them, the construction of a joint effort to produce their own vaccines and the reconsideration of the bases that govern the intellectual property rights of vaccines and medicines, which harmed equitable access to health, with the consequent loss of many lives that could have been saved.

Females translate male mRNA transferred during mating.

Although RNA is found in the seminal fluid of diverse organisms, it is unknown whether this RNA is functional within females. Here, we develop an experimental proteomic method called VESPA (Variant Enabled SILAC Proteomic Analysis) to test the hypothesis that Drosophila male seminal fluid RNA is translated by females. We find strong evidence for 67 male-derived, female-translated proteins (mdFTPs) in female lower reproductive tracts at six hours postmating, many with predicted functions relevant to reproduction. Gene knockout experiments indicate that genes coding for mdFTPs play diverse roles in postmating interactions, with effects on fertilization efficiency, and the formation and persistence of the insemination reaction mass, a trait hypothesized to be involved in sexual conflict. These findings advance our understanding of reproduction by revealing a novel mechanism of postmating molecular interactions between the sexes that strengthens and extends male influences on reproductive outcomes in previously unrecognized ways. Given the diverse species known to carry RNA in seminal fluid, this discovery has broad significance for understanding molecular mechanisms of cooperation and conflict during reproduction.

Cross-border utilization of cancer care by patients in the US and Mexico - a survey of Mexican oncologists.

BACKGROUND: The US-Mexico border is the busiest in the world, with millions of people crossing it daily. However, little is known about cross-border utilization of cancer care, or about the reasons driving it. We designed a cross sectional online survey to understand the type of care patients with cancer who live in the US and Mexico seek outside their home country, the reasons why patients traveled across the border to receive care, and the barriers faced when seeking cross-border care. RESULTS: The online survey was sent to the 248 cancer care providers working in the six Mexican border states who were registered members of the Mexican Society of Oncology. Responses were collected between September-November 2022. Sixty-six providers (response rate 26%) completed the survey. Fifty-nine (89%) reported interacting with US-based patients traveling to Mexico to receive various treatment modalities, with curative surgery (n = 38) and adjuvant chemotherapy (n = 31) being the most common. Forty-nine (74%) reported interacting with Mexico-based patients traveling to the US to receive various treatment modalities, with immunotherapy (n = 29) and curative surgery (n = 27) being the most common. The most frequently reported reason US-based patients sought care in Mexico was inadequate health insurance (n = 45). The most frequently reported reason Mexico-based patients sought care in the US was patients' perception of superior healthcare (n = 38). CONCLUSIONS: Most Mexican oncologists working along the Mexico-US border have interacted with patients seeking or receiving binational cancer care. The type of care sought, as well as the reasons for seeking it, differ between US and Mexico-based patients. These patterns of cross-border healthcare utilization highlight unmet needs for patients with cancer in both countries and call for policy changes to improve outcomes in border regions.

Geriatric Assessments in Older Adults With Cancer.

This JAMA Oncology Patient Page describes the geriatric assessment used by clinicians to evaluate the health of older adults with cancer.

Lactate and pH values in newborns with a history of acute fetal distress.

BACKGROUND: Acute fetal distress (AFD) is a condition that requires timely diagnosis because it generates hypoxia, acidosis, and even intrauterine death. This study aimed to determine lactate and pH values in the umbilical cord in full-term newborns (NBs) with a history of AFD. METHODS: We conducted a cross-sectional study in full-term NBs of mothers with at least one perinatal, neonatal, or gasometric AFD antecedent. Neonatal morbidity was considered: if 1-min Apgar ≤ 6, or advanced neonatal maneuvers, or neonatal intensive care unit (NICU) admissions were necessary. The cutoff points were lactate > 4mmol/L and pH < 7.2. RESULTS: Of 66 NBs, 33.3% of mothers presented at least one antecedent for developing AFD; 22.7% presented hypertensive pregnancy disease, 13.6% oligohydramnios, and 63.6% other factors. Perinatally, 28.7% required advanced neonatal resuscitation maneuvers and 7.5% admission to the NICU. In the gasometry, the lactate and pH values for the neonatal morbidity of the NBs' group were 4.726 ± 1.401 and 7.293 ± 0.056, respectively, versus 2.240 ± 0.318 and 7.359 ± 0.022 (p < 0.05) for the group without associated neonatal morbidity. CONCLUSIONS: Lactate values in the umbilical cord increased by 25%, and pH decreased by one percent in NBs with a history of AFD and associated morbidity.

INTRODUCCIÓN: El sufrimiento fetal agudo (SFA) es una condición que amerita un diagnóstico oportuno debido a que genera hipoxia, acidosis e incluso la muerte intrauterina. El objetivo de este estudio fue determinar los valores de lactato y pH en cordón umbilical en recién nacidos de término con antecedente SFA. MÉTODOS: Se llevó a cabo un estudio transversal, en recién nacidos a término, de madres que tuvieron al menos un antecedente para SFA de tipo perinatal, neonatal o gasométrico. Se consideró morbilidad neonatal cuando presentaron Apgar al minuto ≤ 6, o requirieron maniobras avanzadas de reanimación neonatal, o ingreso a Unidad de Cuidados Intensivos Neonatales (UCIN). El punto de corte fue > 4 mmol/L para los valores de lactato y pH < 7.2. RESULTADOS: De un total de 66 recién nacidos, el 33.3% de las madres presentaron al menos un antecedente para desarrollar SFA; el 22.7% presentó enfermedad hipertensiva del embarazo, el 13.6%, oligohidramnios, y el 63.6%, otros factores. El 28.7% requirieron maniobras avanzadas de la reanimación neonatal y el 7.5%, el ingreso a la UCIN. En la gasometría, el valor de lactato y pH para el grupo de recién nacidos con morbilidad neonatal fue de 4.726 ± 1.401 y 7.293 ± 0.056 respectivamente, versus 2.240 ± 0.318 y 7.359 ± 0.022 (p < 0.05) para el grupo sin morbilidad neonatal asociada. CONCLUSIONES: Se observó un incremento del 25% de los valores de lactato en cordón umbilical y una disminución del 1% del pH en los recién nacidos con antecedente de SFA y morbilidad asociada.