Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant.

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."

Altered exocrine function can drive adipose wasting in early pancreatic cancer.

Malignancy is accompanied by changes in the metabolism of both cells and the organism1,2. Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer3,4. Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic5,6. Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer. Using mouse models of PDAC, we show that tumour growth in the pancreas but not in other sites leads to adipose tissue wasting, suggesting that tumour growth within the pancreatic environment contributes to this wasting phenotype. We find that decreased exocrine pancreatic function is a driver of adipose tissue loss and that replacement of pancreatic enzymes attenuates PDAC-associated wasting of peripheral tissues. Paradoxically, reversal of adipose tissue loss impairs survival in mice with PDAC. When analysing patients with PDAC, we find that depletion of adipose and skeletal muscle tissues at the time of diagnosis is common, but is not associated with worse survival. Taken together, these results provide an explanation for wasting of adipose tissue in early PDAC and suggest that early loss of peripheral tissue associated with pancreatic cancer may not impair survival.

Exploring relationships with food after dietary intervention in patients with colorectal cancer: a qualitative analysis from the Protein Recommendations to Increase Muscle (PRIMe) trial.

PURPOSE: Patients with cancer often experience nutritional challenges and are vulnerable to muscle mass loss. While substantial research is directed towards understanding how nutritional interventions affect clinical outcomes, insights into patients' personal experiences during these trials remain limited. This qualitative study aimed to gain a deeper understanding of how participation in the Protein Recommendations to Increase Muscle (PRIMe) trial affected patients' relationships with food. METHODS: A subset of patients who completed a minimum of one follow-up visit in the PRIMe trial participated in a semi-structured interview about their experience implementing dietary modifications to increase protein intake. Data from 26 patients with a recent diagnosis of stage II-IV colorectal cancer (non-cachectic) were included. Interviews were audio recorded, transcribed verbatim, and qualitative content analysis was applied. RESULTS: Most patients were male (65.4%) with stage II or III (69.2%) colorectal cancer and were a mean age of 57 ± 10 years. Five key themes emerged to provide a deeper understanding of patients' relationship with food after the PRIMe trial: (1) new positive perspectives on nutrition and coping with a cancer diagnosis; (2) embracing a comprehensive approach to food and nutrition; (3) facilitators promoting adherence to the intervention; (4) barriers challenging adherence to the intervention; and (5) shaping future dietary intake. CONCLUSION: This qualitative study explored the emotional and psychological effects of a clinical nutrition trial on patients, focusing on their relationship with food. It underscored the trial's comprehensive intervention and its enduring influence on patients, extending beyond the immediate intervention phase. The role of current perspectives, motivation, and knowledge acquisition on ability to adhere to dietary changes to increase protein intake were emphasized by patients and are key considerations for both clinicians and researchers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02788955; registration posted on 2016-06-02.

Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines.

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h. CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2A13 were analyzed by RT-PCR and IL-10, IL-12p70, IL-18, IL-33, and thymic stromal lymphopoietin (TSLP) by Cytometric Bead Array (CBA). Through RT-PCR analysis, we observed that CA increased CYP1A2 and CYP1B1 expression in BEAS-2B, with a further increased in BEAS-2B-mDC co-culture. Additionally, exposure to CA increased IL-12p70 levels in mDC rather than in BEAS-2B-mDC co-culture. In regards to IL-18, level was higher in BEAS-2B than in BEAS-2B-mDC co-culture. A positive correlation between the levels of IL-10 and CYP1B1 was found in mDC-CA-exposed and between IL-12p70 and CYP1A1 was found in BEAS-2B after CA exposure. However, IL-12p70 and CYP1A2 as well as IL-18, IL-33, and CYP1A1 levels were negative, correlated mainly in co-culture control. These correlations highlight potential immunomodulatory interactions and complex regulatory relationships. Overall, exposure to CA enhances CYP450 expression, suggesting that CA can influence immune responses by degrading ligands on xenosensitive transcription factors.

Changes in Bone Mineral Density in Patients With Non-dialysis-Dependent Chronic Kidney Disease Are Associated With Body Composition.

OBJECTIVE: Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with nondialysis-dependent CKD (NDD-CKD). METHODS: Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry. The ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as T-score ≤ -1.0. RESULTS: The mean time between assessments was 2.8 ± 1.3 years; 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (P = .031), ALSTI (P = .021), a trend for BMD (P = .053), and an increase in percentage fat mass (P = .044) and LCI (P = .032). Females had a reduction in BMD (P = .034), ALST (P = .026), and ALSTI (P = .037). Patients with low BMD at baseline had lower LST (P = .013), ALST (P = .023), and percentage fat mass (P = .037) than those with normal BMD. Additionally, reductions in LST (P = .041), ALST (P = .006), and ALSTI (P = .008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (odds ratio [OR]: 0.899, 95% confidence interval [CI]: 0.829-0.976, P = .010), ALST (OR: 0.825, 95% CI: 0.704-0.967, P = .017), and ALSTI (OR: 0.586, 95% CI: 0.354-0.968, P = .037), independent of fat mass and LCI. CONCLUSIONS: Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.

Phase angle and cellular health: inflammation and oxidative damage.

Phase angle is a composite measure that combines two raw bioelectrical impedance analysis measures: resistance and reactance. Phase angle has been considered an indicator of cellular health, integrity, and hydration. As inflammation and oxidative stress can damage cellular structures, phase angle has potential utility in early detecting inflammatory and oxidative status. Herein, we aimed to critically review the current understanding on the determinants of phase angle and its relationship with markers of inflammation and oxidative stress. We also discussed the potential role of phase angle in detecting chronic inflammation and related adverse outcomes. Several factors have been identified as predictors of phase angle, including age, sex, extracellular to intracellular water ratio, and fat-free mass. In addition to these factors, body mass index (BMI) also seems to influence phase angle. Available data also show that lower phase angle values are correlated (negligible to high correlation coefficients) with higher c-reactive protein, tumour necrosis factor-α, interleukin-6, and interleukin-10 in studies involving the general and aging populations, as well as patients with chronic conditions. Although fewer studies have evaluated the relationship between phase angle and markers of oxidative stress, available data also suggest that phase angle has potential to be used as an indicator (for screening) of oxidative damage. Future studies including diverse populations and bioelectrical impedance devices are required to confirm the validity and accuracy of phase angle as a marker of inflammation and oxidative stress for clinical use.

Time-Restricted Eating in Breast Cancer Survivors: Effects on Body Composition and Nutritional Status.

In this secondary analysis of an 8-wk single-arm feasibility study of weekday time-restricted eating (TRE), we explored the effects of TRE on body composition. Women (n = 22; ≥60 yr) who had completed chemotherapy for early-stage breast cancer and had a body mass index ≥25 kg/m2 were enrolled. Bioelectrical impedance analysis was performed before and after 8 wk of TRE, and nutritional status was evaluated by bioelectrical impedance vector analysis (BIVA). Body weight (p = 0.01) and total fat mass (p = 0.04) decreased with TRE. Phase angle was low (defined as ≤5.6°) in 86% of participants at baseline and did not change. Four participants who initially presented with obesity (>95% ellipse, BIVA) had favorable body composition modifications after TRE. Our study highlighted a less favorable body composition profile, poorer cell integrity and overhydration in these patients. BIVA was a useful method to assess body composition and hydration. A short TRE intervention was associated with decreased estimated fat mass and a favorable change in nutritional status in those with obesity.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Personalized nutrition therapy in critical care: 10 expert recommendations.

Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.

Acceptability and preliminary effectiveness of a single-arm 12-week digital behavioral health intervention in patients with knee osteoarthritis.

BACKGROUND: Digital health interventions may improve osteoarthritis (OA) management. This study evaluated the acceptability and preliminary effectiveness of a multimodal digital nutrition, exercise, and mindfulness intervention in adults with knee OA. METHODS: Adults with advanced knee OA and an orthopaedic referral were invited to self-enroll in a pragmatic 12-week single-arm intervention. OA-focused nutrition and exercise resources were delivered weekly by email, and secondary components accessed on-demand (web-platform, webinars, and nutrition consultation). Acceptability was assessed by qualitative interview data and completion rates. Preliminary effectiveness on clinical outcomes was assessed by change in health-related quality of life, well-being, mindfulness, self-efficacy, and interest in total knee arthroplasty (TKA) between baseline and 12-weeks. RESULTS: N = 102 patients self-enrolled (73.5% female, age 64 ± 7 years, body mass index 32.9 ± 7.3 kg/m2); n = 53 completed the 12-week intervention (71.7% female, age 65 ± 7 years, body mass index 33.4 ± 6.3 kg/m2). Acceptability was demonstrated by positive perceptions of tailored intervention resources. In study completers, health-related quality of life components of pain and physical functioning domains improved at 12-weeks [change in SF36 4.4 (95%CI 0.2-8.6), p = 0.016, and 6.7 (95%CI 2.7-10.7), p < 0.001, respectively]. Self-efficacy for managing daily activities improved [change in PROMIS T-score 4.4 (95%CI 2.8-6.0), p < 0.001]. CONCLUSION: A 12-week digital multimodal intervention for knee OA was acceptable to patients and shows preliminary effectiveness in improving self-efficacy, aspects of quality of life, and decreasing interest in TKA. Digital behavioral interventions for knee OA may be an acceptable approach to improve patient outcomes and OA self-management while potentially reducing utilization of costly health system resources.

Ability of Anthropometric Measurements to Predict Metabolic Health among Patients in Alberta: A Cross-sectional Study in Primary Care.

Purpose: This study compared anthropometric and body fat percent (BF%) equations in relation to measures of metabolic health.Methods: BF% calculations (Bergman, Fels, and Woolcott) and anthropometric measurements were used to determine obesity among a sample of patients attending primary care in Alberta, Canada. Anthropometric variables included body mass index (BMI), waist circumference, waist:hip ratio, waist:height ratio, and calculated BF%. Metabolic Z-score was computed as the average of the individual Z-scores of triglycerides, total cholesterol, and fasting glucose and the number of standard deviations from the sample mean.Results: Five hundred and fourteen individuals were included (41.2% male, age: 53 ± 16y, BMI: 27.4 ± 5.7 kg/m2). BMI ≥ 30 kg/m2 detected the smallest number of participants (n = 137) as having obesity, while Woolcott BF% equation categorized the largest number of participants as having obesity (n = 369). No anthropometric or BF% calculation predicted metabolic Z-score in males (all p ≥ 0.05). In females, age-adjusted waist:height ratio had the highest prediction power (R2 = 0.204, p < 0.001), followed by age-adjusted waist circumference (R2 = 0.200, p < 0.001) and age-adjusted BMI (R2 = 0.178, p < 0.001).Conclusions: This study did not find evidence that BF% equations more strongly predicted metabolic Z-scores than other anthropometric values. In fact, all anthropometric and BF% variables were weakly related to metabolic health parameters, with apparent sex differences.

Sarcopenic obesity is associated with telomere shortening: findings from the NHANES 1999-2002.

Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98-1.05) compared to 1.05 (95%CI: 1.01-1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres.

A high-protein total diet replacement alters the regulation of food intake and energy homeostasis in healthy, normal-weight adults.

PURPOSE: Dietary intake can affect energy homeostasis and influence body weight control. The aim of this study was to compare the impact of high-protein total diet replacement (HP-TDR) versus a control (CON) diet in the regulation of food intake and energy homeostasis in healthy, normal-weight adults. METHODS: In this acute randomized controlled, cross-over study, participants completed two isocaloric arms: a) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat; b) CON: 55% carbohydrate, 15% protein, and 30% fat. The diets were provided for 32 h while inside a whole-body calorimetry unit. Appetite sensations, appetite-related hormones, and energy metabolism were assessed. RESULTS: Forty-three healthy, normal-weight adults (19 females) participated. Appetite sensations did not differ between diets (all p > 0.05). Compared to the CON diet, the change in fasting blood markers during the HP-TDR intervention was smaller for peptide tyrosine-tyrosine (PYY; - 18.9 ± 7.9 pg/mL, p = 0.02) and greater for leptin (1859 ± 652 pg/mL, p = 0.007). Moreover, postprandial levels of glucagon-like peptide 1 (1.62 ± 0.36 pM, p < 0.001) and PYY (31.37 ± 8.05 pg/mL, p < 0.001) were higher in the HP-TDR. Significant correlations were observed between energy balance and satiety (r = - 0.41, p = 0.007), and energy balance and PFC (r = 0.33, p = 0.033) in the HP-TDR. CONCLUSION: Compared to the CON diet, the HP-TDR increased blood levels of anorexigenic hormones. Moreover, females and males responded differently to the intervention in terms of appetite sensations and appetite-related hormones. TRIAL REGISTRATION: NCT02811276 (retrospectively registered on 16 June 2016) and NCT03565510 (retrospectively registered on 11 June 2018).

Examining guidelines and new evidence in oncology nutrition: a position paper on gaps and opportunities in multimodal approaches to improve patient care.

Malnutrition, muscle loss, and cachexia are prevalent in cancer and remain key challenges in oncology today. These conditions are frequently underrecognized and undertreated and have devastating consequences for patients. Early nutrition screening/assessment and intervention are associated with improved patient outcomes. As a multifaceted disease, cancer requires multimodal care that integrates supportive interventions, specifically nutrition and exercise, to improve nutrient intake, muscle mass, physical functioning, quality of life, and treatment outcomes. An integrated team of healthcare providers that incorporates societies' recommendations into clinical practice can help achieve the best possible outcomes. A multidisciplinary panel of experts in oncology, nutrition, exercise, and medicine participated in a 2-day virtual roundtable in October 2020 to discuss gaps and opportunities in oncology nutrition, alone and in combination with exercise, relative to current evidence and international societies' recommendations. The panel recommended five principles to optimize clinical oncology practice: (1) position oncology nutrition at the center of multidisciplinary care; (2) partner with colleagues and administrators to integrate a nutrition care process into the multidisciplinary cancer care approach; (3) screen all patients for malnutrition risk at diagnosis and regularly throughout treatment; (4) combine exercise and nutrition interventions before (e.g., prehabilitation), during, and after treatment as oncology standard of care to optimize nutrition status and muscle mass; and (5) incorporate a patient-centered approach into multidisciplinary care.

Does obesity affect patient-reported outcomes following total knee arthroplasty?

BACKGROUND: There is an existing perception that obesity has a negative impact on complications following total knee arthroplasty (TKA). However, data on the impact of obesity levels on patient-reported outcomes (PROMs) is sparse. We investigated the association between different obesity classes with PROMs among patients who underwent TKA. METHODS: We performed retrospective secondary analyses on data extracted from the total joint replacement data repository (Alberta, Canada) managed by the Alberta Bone and Joint Health Institute (ABJHI). Patients had WOMAC and EQ5D scores measured at baseline in addition to 3 and/or 12 months following TKA. Patients were stratified according to the World Health Organization (WHO) classification, into five body mass index (BMI) groups of normal, overweight, BMI class I, BMI class II, and BMI class III. The association between BMI and mean changes in WOMAC subscales (pain, function, and stiffness) and EQ-5D-5L index over the time intervals of baseline to 3 months and 3 to 12 months following TKA was assessed. Linear mixed-effects models were used, and the models were adjusted for age, sex, length of surgery, comorbidities, year of surgery, and geographical zone where the surgery was performed. RESULTS: Mean age was 65.5 years (SD = 8.7). Postoperatively, there was a significant improvement (p < 0.001) in WOMAC subscales of patient-reported pain, function, and stiffness, as well as EQ-5D-5L regardless of BMI group. Although, patients in BMI class II and class III reported significantly improved pain 3 months after TKA compared to those with normal BMI, all BMI groups attained similar level of pain reduction at 12 months after TKA. The greatest improvement in all WOMAC subscales, as well as EQ5D index, occurred between baseline and 3 months (adjusted p < 0.0001). CONCLUSION: The findings indicate that patients reported improved pain, function, and stiffness across all BMI groups following TKA. Patients with BMI classified as obese reported similar benefits to those with BMI classified as normal weight. These results may help health care providers to discuss expectations regarding the TKA recovery in terms of pain, function, and quality of life improvements with their TKA candidates.

Proinflammatory State in the Odontogenesis of Fetuses Exposed to Different Types of Fatty Acids during Pregnancy.

OBJECTIVES: The aim of the present study was to analyze the possible changes caused by the maternal ingestion of different types of fatty acids during pregnancy in the proinflammatory state in the odontogenesis of the fetuses. SUBJECT AND METHODS: Twenty-four jaws (n = 6 per group) of Wistar rats were collected on the 20th day of intrauterine life. Mothers were separated on the first day of pregnancy into 4 groups according to diet, as described below: control group (C) - diet with soy oil as a source of fat; saturated fatty acid group (S) - diet with lard in saturated fatty acids; trans-fatty acid group (T) - diet with vegetable fat, rich in trans-saturated fatty acids; and polyunsaturated fatty acid (PUFA) group - diet with fish oil, rich in PUFAs. RESULTS: Microscopic analysis showed no alterations in tissue development of the teeth between the groups with different lipid diets (T, S, and PUFA) when compared to the control group (C); immunohistochemical analysis for the expression of JAK2, STAT3, P-STAT3, SOCS3, and IL-6 showed no statistically significant difference (p > 0.05) compared to the control group. However, there were changes (p < 0.05) between the T group and the PUFA group in the expression of JAK2. CONCLUSION: Thus, lipid consumption in the maternal diet remains a topic to be explored in embryonic development, despite not causing morphological changes to the tooth germ of rats.

Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice.

Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-ß, tumor necrosis factor-α, neutrophils, IL-1ß, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.

Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care.

BACKGROUND: An underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life. METHODS: Fifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48-72 h prior to each chemotherapy treatment and will perform 30-60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival. DISCUSSION: The DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03795493 , registered 7 January, 2019.

SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue.

Effects of Eugenol and Dehydrodieugenol B from Nectandra leucantha against Lipopolysaccharide (LPS)-Induced Experimental Acute Lung Inflammation.

Acute lung injury (ALI) is an important public health problem. The present work investigated whether dehydrodieugenol B treatment, a compound isolated from Brazilian plant Nectandra leucantha (Lauraceae), modulates experimental ALI and compared the observed effects to eugenol. Effects of dehydrodieugenol B in vitro in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were evaluated. The lung and systemic inflammatory profile, lung function, and possible mechanisms involved in BALB/C male mice (6-8 weeks) with ALI induced by LPS instillation (5 mg/kg) was assayed. Dehydrodieugenol B did not affect the cell viability and inhibited the increase in NO release and IL-1ß and IL-6 gene expression induced by LPS. In vivo, both compounds reduced lung edema, inflammatory cells, and the IL-6 and IL-1 ß levels in bronchoalveolar lavage fluid, as well as reduced inflammatory cell infiltration and those positive to iNOS, MMP-9, and TIMP-1, and reduced the collagen content and the 8-isoprostane expression in lung tissue. Eugenol and dehydrodieugenol B also inhibited the phosphorylation of Jc-Jun-NH2 terminal Kinase (JNK), a signaling protein involved in the MAPKinase pathway. There was no effect of these compounds in lung function. Therefore, eugenol and dehydrodieugenol B ameliorates several features of experimental ALI and could be considered as a pharmacological tool to ameliorate acute lung inflammation.