Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients.

Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a+ T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration.

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity.

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.

Autosomal Recessive ADAMTSL4-Related Isolated Ectopia Lentis in the Ohio Old Order Amish and Mennonite Communities.

Purpose: To present a series of 4 patients from the Ohio Amish or Mennonite populations with isolated ectopia lentis. Methods: A case series was evaluated. Results: Four cases with bilateral lens subluxations were diagnosed with a homozygous c.767_786del pathogenic variant in ADAMTSL4. Their ages ranged from 2 to 22 years. Three cases were symptomatic and were managed surgically with lensectomy, vitrectomy, and endolaser photocoagulation with or without secondary intraocular lens (IOL) implantation. One asymptomatic patient was observed. The postoperative visual acuity ranged from 20/20 to 20/60 in nonamblyopic eyes. Conclusions: The pathogenic homozygous c.767_786del variant in ADAMTSL4 may be a cause of bilateral isolated ectopia lentis in the Ohio Amish and Mennonite populations, likely as a result of a founder effect. Vitrectomy and lens extraction with or without secondary IOL implantation may lead to good visual outcomes. There were no cases of retinal detachment.

COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Creutzfeldt-Jakob Disease and Fatal Familial Insomnia: Demographics and In-Hospital Mortality in Spain.

Background: Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI) are prion diseases characterized by severe neurodegenerative conditions and a short duration of illness. Methods: This study explores the characteristics of hospitalizations for CJD and FFI in Spain from 2016 to 2022 using the Spanish National Hospital Discharge Database (SNHDD). Results: We identified a total of 1063 hospital discharges, including 1020 for CJD and 43 for FFI. Notably, the number of hospitalized patients with FFI showed a significant peak in 2017. The average length of hospital stay (LOHS) was 13 days for CJD and 6 days for FFI, with in-hospital mortality rates (IHM) of 36.37% for CJD and 32.56% for FFI. Among CJD patients, the average LOHS was 14 days, with a significantly longer duration for those who experienced IHM. Conclusions: The presence of sepsis or pneumonia and older age were associated with a higher IHM rate among CJD patients. The total estimated cost for managing CJD and FFI patients over the study period was EUR 6,346,868. This study offers new insights into the epidemiology and healthcare resource utilization of CJD and FFI patients, which may inform future research directions and public health strategies.

Implications of Rebalancing Home-Based Care for Family Caregivers to Older Adults.

Over the last several decades, Medicaid has been "rebalancing" services from institutions to the community, increasing support of home- and community-based services (HCBS). These services could potentially substitute for care typically provided by family members, replacing or reducing care from kin. Leveraging one of the most recent Medicaid rebalancing programs, the Balancing Incentive Program (BIP), and using data from the 2008-2016 Health and Retirement Study on 953 Medicaid beneficiaries ages 65 and over with at least one functional limitation, we examined the relationship between exposure to BIP and family and professional caregiving. BIP exposure was not associated with receipt of care or total hours of care. It was, however, associated with more hours of professional care and fewer hours of family care from non-spouse kin. These findings suggest that recent Medicaid rebalancing programs, while intended to meet the desires of older adults, could have implications for their families.

An observational study of therapeutic procedures and in-hospital outcomes among patients admitted for acute myocardial infarction in Spain, 2016-2022: the role of diabetes mellitus.

BACKGROUND: We used the Spanish national hospital discharge data from 2016 to 2022 to analyze procedures and hospital outcomes among patients aged ≥ 18 years admitted for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) according to diabetes mellitus (DM) status (non-diabetic, type 1-DM or type 2-DM). METHODS: We built logistic regression models for STEMI/NSTEMI stratified by DM status to identify variables associated with in-hospital mortality (IHM). We analyzed the effect of DM on IHM. RESULTS: Spanish hospitals reported 201,950 STEMIs (72.7% non-diabetic, 0.5% type 1-DM, and 26.8% type 2-DM; 26.3% female) and 167,285 NSTEMIs (61.6% non-diabetic, 0.6% type 1-DM, and 37.8% type 2-DM; 30.9% female). In STEMI, the frequency of percutaneous coronary intervention (PCI) increased among non-diabetic people (60.4% vs. 68.6%; p < 0.001) and people with type 2-DM (53.6% vs. 66.1%; p < 0.001). In NSTEMI, the frequency of PCI increased among non-diabetic people (43.7% vs. 45.7%; p < 0.001) and people with type 2-DM (39.1% vs. 42.8%; p < 0.001). In NSTEMI, the frequency of coronary artery by-pass grafting (CABG) increased among non-diabetic people (2.8% vs. 3.5%; p < 0.001) and people with type 2-DM (3.7% vs. 5.0%; p < 0.001). In the entire population, lower IHM was associated with undergoing PCI (odds ratio [OR] [95% confidence interval] = 0.34 [0.32-0.35] in STEMI; 0.24 [0.23-0.26] in NSTEMI) or CABG (0.33 [0.27-0.40] in STEMI; 0.45 [0.38-0.53] in NSTEMI). IHM decreased over time in STEMI (OR = 0.86 [0.80-0.93]). Type 2-DM was associated with higher IHM in STEMI (OR = 1.06 [1.01-1.11]). CONCLUSIONS: PCI and CABG were associated with lower IHM in people admitted for STEMI/NSTEMI. Type 2-DM was associated with IHM in STEMI.

Impact of genetic variants in the solute carrier (SLC) genes encoding drug uptake transporters on the response to anticancer chemotherapy.

Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients. This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemoresistance (MOC). These mechanisms are accounted for by the expression of a set of genes included in the so-called resistome, whose effectiveness often leads to a lack of response to pharmacological treatment. Additionally, genetic variants affecting these genes further increase the complexity of the question. This review focuses on a set of genes encoding members of the transportome involved in drug uptake, which have been classified into the MOC-1A subgroup of the resistome. These proteins belong to the solute carrier (SLC) superfamily. More precisely, we have considered here several members of families SLC2, SLC7, SLC19, SLC22, SLCO, SLC28, SLC29, SLC31, SLC46, and SLC47 due to the impact of their expression and genetic variants in anticancer drug uptake by tumor cells or, in some cases, general bioavailability. Changes in their expression levels and the appearance of genetic variants can contribute to the Darwinian selection of more resistant clones and, hence, to the development of a more malignant phenotype. Accordingly, to address this issue in future personalized medicine, it is necessary to characterize both changes in resistome genes that can affect their function. It is also essential to consider the time-dependent dimension of these features, as the genetic expression and the appearance of genetic variants can change during tumor progression and in response to treatment.

The Search for Risk, Diagnostic, and Prognostic Biomarkers of Cholangiocarcinoma and Their Biological and Clinicopathologic Significance.

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a dismal prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis, and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, and urine) and their potential usefulness in diagnosis, prognosis, and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments; however, challenges to its translation and clinical application for patients with CCA need to be resolved.

Fine-scale Dietary Polyphenol Intake is Associated with Systemic and Gastrointestinal Inflammation in Healthy Adults.

BACKGROUND: Polyphenols are dietary bioactive compounds, many of which have anti-inflammatory properties. However, information on the intake of dietary polyphenols at the class and compound level and their associations with gastrointestinal (GI) and systemic inflammation is lacking. OBJECTIVE: Estimate dietary polyphenol intake in healthy adults and examine its relationship with GI and systemic inflammation markers. METHODS: Healthy adults (n = 350) completed the USDA Nutritional Phenotyping Study, an observational, cross-sectional study balanced for age, sex, and body mass index. Dietary intake, assessed via multiple 24-hour recalls, was ingredientized and mapped to FooDB, a comprehensive food composition database. Dietary polyphenol intake (total, class, compound) was estimated and examined for its relationship to GI and systemic inflammation markers using linear models and random forest regressions. RESULTS: Mean total polyphenol intake was approximately 914 mg/1000 kcal per day with flavonoids as the greatest class contributor (495 mg/1000 kcal per day). Tea, coffee, and fruits were among the largest food contributors to polyphenol intake. Total polyphenol intake negatively associated with the GI inflammation marker, fecal calprotectin (ß=-0.004, p=0.04). At the class level, polyphenols categorized as prenol lipids (ß=-0.94, p<0.01) and phenylpropanoic acids (ß=-0.92, p<0.01) negatively associated with plasma lipopolysaccharide-binding protein, a proxy for GI permeability. Food sources of these two classes included mainly olive products. We further detected a positive association between C-Reactive protein and polyphenols in the "cinnamic acids and derivatives" class using hierarchical feature engineering and random forest modeling. CONCLUSION: Even in healthy adults, dietary polyphenol intake was negatively associated with GI inflammation and intake of prenol lipids and phenylpropanoic acids were negatively associated with GI permeability. Relationships between polyphenol intake and inflammatory outcomes varied with the resolution - total, class, compound - of polyphenol intake, suggesting a nuanced impact of polyphenols on GI and systemic inflammation. CLINICAL TRIAL REGISTRY: NCT02367287, ClinicalTrials.gov.

Co-morbid sarcopenia and low bone mineral density in young paediatric cancer survivors.

BACKGROUND: Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z-score in young paediatric cancer survivors with sarcopenia confirmed/probable. METHODS: This cross-sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). 'No sarcopenia' was defined when muscle strength was >decile 2. 'Sarcopenia probable' was defined when muscle strength was ≤ decile 2 and ALMI Z-score was > -1.5 standard deviation (SD). 'Sarcopenia confirmed' was defined when muscle strength was ≤ decile 2 and ALMI Z-score ≤ -1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z-score < -1.0). RESULTS: Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (-1.2 [95% CI: -1.5 to -0.8] vs. 0.2 [-0.2 to 0.6], P < 0.001), lumbar spine (-0.7 [-1.1 to -0.3] vs. 0.4 [0.0 to 0.8], P < 0.001), total hip (-0.5 [-0.9 to -0.2] vs. 0.4 [0.1 to 0.8], P < 0.001), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.3 to 0.4], P = 0.001). Compared with survivors with sarcopenia probable, survivors with sarcopenia confirmed had significantly lower aBMD Z-score at total body (-1.2 [-1.5 to -0.8] vs. -0.2 [-0.7 to 0.4], P = 0.009), total hip (-0.5 [-0.9 to -0.2] vs. 0.5 [-0.1 to 1.0], P = 0.010), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.5 to 0.7], P = 0.014). Survivors with sarcopenia confirmed were at higher risk of low aBMD Z-score at the total body (OR: 6.91, 95% CI: 2.31-24.15), total hip (OR: 2.98, 1.02-9.54), and femoral neck (OR: 4.72, 1.72-14.19), than those without sarcopenia. Survivors with sarcopenia probable were at higher risk of low aBMD Z-score at the total body (OR: 4.13, 1.04-17.60) than those without sarcopenia. CONCLUSIONS: Young paediatric cancer survivors with sarcopenia present higher risk of low aBMD. Resistance training-based interventions designed to mitigate osteosarcopenia in this population should be implemented at early stages.

Effects of combined aerobic and resistance training on the inflammatory profile of children with overweight/obesity: A randomized clinical trial.

BACKGROUND: We assessed the effects of a 20-week combined (aerobic and resistance) exercise training programme on the inflammatory profile of prepubertal children with overweight or obesity. METHODS: Totally 109 participants (10.1 ± 1.1 years, 41% girls) were randomly allocated to an exercise or control group. Adiponectin, C-reactive protein, epidermal growth factor, insulin-like growth factor-1, interleukin (IL)-1ß, IL-6, leptin, tumour necrosis factor-α and vascular endothelial growth factor A (VEGFA) were analysed in plasma. Total white blood cell (WBC) count and immune subpopulations (eosinophils, basophils, neutrophils, lymphocytes and monocytes) were also determined. RESULTS: No intervention effect was found for any of the analysed biomarkers (all p ≥ 0.05). We observed a significant sex by intervention interaction for IL-1ß (p = 0.03). When stratifying the sample by sex, the exercise programme induced a significant effect on IL-1ß levels (mean Z-score difference, 0.66 [95% confidence interval 0.32-1.01]) in girls, but not in boys. A lower number of girls in the exercise group showed a meaningful reduction in IL-1ß (i.e., ≥0.2 standard deviations) than in the control group (15% vs. 85%, p = 0.01). CONCLUSIONS: This exercise programme failed to improve the inflammatory profile in prepubertal children with overweight/obesity. Future studies should explore the effect of longer exercise interventions and in combination with diet.

Cross-sex hormonal replacement: Some effects over mitochondria.

Transgender is a term for people whose gender identity or expression differs from their natal sex. These individuals often seek cross-hormonal therapy to simulate the individual´s desired gender. However, the use of estrogens and testosterone has side effects such as a higher propensity to cancer, weight changes and cardiovascular diseases. Testosterone has also been linked with hypertension. Still, little is known about the outcomes and prevalence of metabolic perturbations in the trans community. Here we aim to analyze if cross-administering sexual hormones affects heart mitochondrial function. Mitochondria produces the ATP needed for heart function. In fact, different studies show that mitochondrial dysfunction precedes cardiac damage. In this work we used either female rats castrated and injected with testosterone or male rats castrated and injected with estrogens for 4 months. We performed an electrocardiogram, and then we isolated heart mitochondria to measure the rate of oxygen consumption, calcium fluxes, membrane potential, superoxide dismutase activity, lipoperoxidation and cytokines. We detected wide modifications in all parameters associated to cross-hormonal administration.

Interventional solutions for post-surgical problems: a lymphatic leaks review.

The lymphatic circulation plays a crucial role in maintaining fluid balance and supporting immune responses by returning serum proteins and lipids to the systemic circulation. Lymphatic leaks, though rare, pose significant challenges post-radical neck surgery, oesophagectomy, and thoracic or retroperitoneal oncological resections, leading to heightened morbidity and mortality. Managing lymphatic leaks necessitates consideration of aetiology, severity, and volume of leakage. Traditionally, treatment involved conservative measures such as dietary restrictions, drainage, and medical management, with surgical intervention reserved for severe cases, albeit with variable outcomes and extended recovery periods. Lymphography, introduced in the 1950s, initially served as a diagnostic tool for lymphoedema, lymphoma, tumour staging, and monitoring chemotherapy response. However, its widespread adoption was impeded by alternative techniques like Computed Tomography, learning curves, and its associated complications. Contemporary lymphatic interventions have evolved, favouring nodal lymphangiography over pedal lymphangiography for its technical simplicity and reduced complexity. Effective management of chylous leaks mandates a multimodal approach encompassing clinical evaluation and imaging techniques. In cases where conservative management proves ineffective, embolization through conventional lymphangiography by bipedal dissection or intranodal injection emerges as a viable option. This review underscores the importance of a comprehensive approach to diagnosing and treating lymphatic leaks, highlighting advancements in imaging and therapeutic interventions that enhance patient outcomes.

Punicalagin increases follicular activation, development and activity of superoxide dismutase 1, catalase, and glutathione peroxidase 1 in cultured bovine ovarian tissues.

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2 ), superoxide dismutase 1 (SOD1 ), catalase (CAT ), glutathione peroxidase 1 (GPX1 ) and perirredoxin 6 (PRDX6 ), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6days in α-MEM+ alone or with 1.0, 10.0, or 100.0µM punicalagin at 38.5°C with 5% CO2 . Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT , but did not influence stromal cells or collagen fibres. Punicalagin (10.0µM) increased the levels of thiol and activity of SOD1, CAT , and GPX1 enzymes. Conclusions Punicalagin (10.0µM) promotes follicle survival and development and activates SOD1, CAT , and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.

Changes at small intestine induced by food-fish contaminated with ciguatoxins.

Ciguateric syndrome is a food poisoning associated with the consumption of some species of fish that have accumulated ciguatoxins (CTXs) in their tissues. The effects of the syndrome occur with nervous imbalances which have been described for quite some time, and mentioned in sailing literature for centuries. In the last decade, research has been focused on the implementation of analytical methods for toxin identification and the study of action modes of CTXs to design effective treatments. However, an important aspect is to determine the damage that CTXs caused in the organs of affected individuals. In this work, the damages observed in tissues of mice, mainly in the small intestine, were analyzed. The animals were fed with CTX-contaminated fish muscle at concentrations 10-times below the median lethal dose (LD50) for 10 weeks. The analysis of tissues derived from the oral treatment resulted in an increased occurrence of Paneth cells, presence of lymphoid tissue infiltrating the mucosa and fibrous lesions in the mucosal layer of the small intestine. A decreasing weight in animals fed with toxic muscle was observed.

Photocatalytic Synthesis and Functionalization of Sulfones, Sulfonamides and Sulfoximines.

Sulfur(VI)-based functional groups are popular scaffolds in a wide variety of research fields including synthetic and medicinal chemistry, as well as chemical biology. The growing interest in sulfur(VI)-containing molecules has motivated the scientific community to explore new methods to synthesize and modify them. Here, photocatalysis plays a key role granting access to new types of reactivity under mild reaction conditions. In this Perspective, we present a selection of works reported in the last six years focused on the photocatalytic assembly and reactivity of sulfones, sulfonamides, and sulfoximines. We addressed the key synthetic intermediates for each transformation, while discussing limitations and strength points of the protocols. Future directions of the field are finally presented.

Optogenetic modulation of cardiac autonomic nervous system.

The following is a narrative review of the fundamentals of optogenetics. It focuses on the advantages and constraints of manipulating the autonomic nervous system by modifying the pathophysiological characteristics that arise in different diseases. Although the use of this technique is currently experimental, we will discuss improvements that have been implemented and identify the necessary measures for potential preclinical translation in the control of the cardiac autonomic nervous system.

Findings on Age at Onset of Cancer in Diabetic and Non-diabetic Populations.

Background Diabetes mellitus and cancer are two associated chronic diseases. Despite being a widely researched topic, the underlying mechanisms of this association remain unclear. One of the poorly explored topics regarding diabetes and cancer is the relation between the age of cancer onset and diabetes mellitus status; therefore, this research exposes the difference in the age of cancer diagnosis in both groups. Methods We conducted a retrospective study by reviewing the clinical files on a secondary care hospital's database. Files from first-time consultations of patients over 18 diagnosed using a histopathological report were included. The present study aimed to determine whether there is a difference in age at the onset of cancer in diabetic and non-diabetic individuals. Moreover, we calculated the average BMI at the onset for both populations. Results Our study included 8,741 patients; 1,551 (17.8%) were diabetic, and 7,190 (82.2%) were non-diabetic. From 28 types of cancer, 27 showed a difference in the age at the onset of cancer when diabetic and non-diabetic subjects were compared. This difference is significant as it suggests a potential link between diabetes and cancer, which could have implications for early detection and prevention strategies. Out of the 27 types, 17 showed statistical significance with p-values ranging from 0.048 to <0.0001 considering a 95% CI. Among those, the most significant types of cancer were breast, cervical, lung, ovarian, rectal, thyroid, and sarcoma, reporting p-values <0.0001. The mean age at onset of cancer in diabetic and non-diabetic populations was 62.7 years (SD ± 3.9) and 55.3 years (SD ± 7.9), respectively, showing a difference of 7.4 years in both groups. The BMI was statistically significant in patients with breast (p = 0.006), endometrial (p = 0.007), head and neck (p=0.014), and thyroid (p = 0.022) cancer types. Conclusion  The data offer a critical view of the relationship between cancer and diabetes. Since virtually no one has produced a similar report, there is a broad field for researching the causal factors implicated in the pathway of diabetic and non-diabetic individuals who develop cancer. Research regarding metformin, diabetic neuropathy, and other possible causes must be addressed to determine whether they are involved in this process.

Differential impacts of furfural and acetic acid on the bioenergetics and fermentation performance of Scheffersomyces stipitis.

Lignocellulosic material is a leading carbon source for economically viable biotechnological processes; however, compounds such furfural and acetic acid exhibit toxicity to yeasts. Nonetheless, research about the molecular mechanism of furfural and acetic acid toxicity is still scarce in yeasts like Scheffersomyces stipitis. Thus, this study aims to elucidate the impact of furfural and acetic acid on S. stipitis regarding bioenergetic and fermentation parameters. Here, we provide evidence that furfural and acetic acid induce a delay in cell growth and extend the lag phase. The mitochondrial membrane potential decreased in all treatments with no significant differences between inhibitors or concentrations. Interestingly, reactive oxygen species increased when the inhibitor concentrations were from 0.1 to 0.3 % (v/v). The glycolytic flux was not significantly (p > 0.05) altered by acetic acid, but furfural caused different effects. Ethanol production decreased significantly (4.32 g·L-1 in furfural and 5.06 g·L-1 in acetic acid) compared to the control (26.3 g·L-1). In contrast, biomass levels were not significantly different in most treatments compared to the control. This study enhances our understanding of the effects of furfural and acetic acid at the mitochondrial level in a pentose-fermenting yeast like S. stipitis.