Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study.

Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1ß and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

BACKGROUND: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. MATERIALS AND METHODS: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. RESULTS: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. CONCLUSIONS: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case-Control Study.

This study was conducted to evaluate the role of methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism as a risk factor for endometriosis. A retrospective case-control study was conducted from January 2020 to December 2022 on all patients attending the gynecological outpatient clinic of our institution who had performed an MTHFR polymorphisms test. Patients with endometriosis were considered cases, while those without endometriosis were considered controls. The presence of an MTHFR C677T homozygous polymorphism was defined as exposure. Risk factors for endometriosis were considered confounders in a binomial logistic regression, with endometriosis diagnosis as the dependent variable. Among the 409 included patients, 106 (25.9%) cases and 303 (74.1%) controls were identified. A higher rate of MTHFR C677T homozygous polymorphism was found in patients with endometriosis (24.5% vs. 15.8%, p = 0.0453), with an adOR of 1.889 (95% CI 1.076-3.318, p = 0.0269) at the binomial logistic regression. A history of no previous pregnancy was associated with an endometriosis diagnosis (adOR 2.191, 95% CI 1.295-3.708, p = 0.0035). An MTHFR C677T homozygous polymorphism could be considered a risk factor for endometriosis. Epigenetic modifications may be the most important mechanism explaining the observed association through the processes of altered DNA methylation and reduced activity of antioxidant systems.

Multiple Sclerosis: Inflammatory and Neuroglial Aspects.

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease's natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells.

NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health.

Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous metabolite that takes part in many key redox reactions. NAD+ biosynthesis and NAD+-consuming enzymes have been attracting markedly increasing interest since they have been demonstrated to be involved in several crucial biological pathways, impacting genes transcription, cellular signaling, and cell cycle regulation. As a consequence, many pathological conditions are associated with an impairment of intracellular NAD+ levels, directly or indirectly, which include cardiovascular diseases, obesity, neurodegenerative diseases, cancer, and aging. In this review, we describe the general pathways involved in the NAD+ biosynthesis starting from the different precursors, analyzing the actual state-of-art of the administration of NAD+ precursors or blocking NAD+-dependent enzymes as strategies to increase the intracellular NAD+ levels or to counteract the decline in NAD+ levels associated with ageing. Subsequently, we focus on the disease-related and age-related alterations of NAD+ homeostasis and NAD+-dependent enzymes in endothelium and the consequent vascular dysfunction, which significantly contributes to a wide group of pathological disorders.

Microbiome Changes in Pregnancy Disorders.

The human microbiota comprises all microorganisms, such as bacteria, fungi, and viruses, found within a specific environment that live on our bodies and inside us. The last few years have witnessed an explosion of information related to the role of microbiota changes in health and disease. Even though the gut microbiota is considered the most important in maintaining our health, other regions of the human body, such as the oral cavity, lungs, vagina, and skin, possess their own microbiota. Recent work suggests a correlation between the microbiota present during pregnancy and pregnancy complications. The aim of our literature review was to provide a broad overview of this growing and important topic. We focused on the most significant changes in the microbiota in the four more common obstetric diseases affecting women's health. Thus, our attention will be focused on hypertensive disorders, gestational diabetes mellitus, preterm birth, and recurrent miscarriage. Pregnancy is a unique period in a woman's life since the body undergoes different adaptations to provide an optimal environment for fetal growth. Such changes also involve all the microorganisms, which vary in composition and quantity during the three trimesters of gestation. In addition, special attention will be devoted to the potential and fundamental advances in developing clinical applications to prevent and treat those disorders by modulating the microbiota to develop personalized therapies for disease prevention and tailored treatments.

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment.

TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects.

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.

Cerebrospinal Fluid α-Calcitonin Gene-Related Peptide: A Comparison between Alzheimer's Disease and Multiple Sclerosis.

Alzheimer's disease (AD) and Multiple Sclerosis (MS) represent an emerging health problem on a global scale, as they are responsible for a significant contribution to the burden of disability in Western countries. Limited numbers of cerebrospinal fluid (CSF) diagnostic markers are available for each disease (amyloid and tau deposition markers for AD and oligoclonal bands for MS) representing mostly state markers that provide few, if any, clues about the severity of the clinical phenotype. α-CGRP is a neuropeptide implied in nociception, vasodilation, synaptic plasticity and immune functions. This neuropeptide is expressed in encephalic regions connected to memory, attention, autonomic and behavioral functions and is also expressed by spinal motor neurons. The present work confronted α-CGRP levels between 19 AD, 27 MS and 17 control subjects using an ELISA/EIA assay. We measured higher CSF α-CGRP contents in control subjects with respect to AD, as shown in previous studies, as well as in MS patients in comparison to AD. The control subjects and MS patients did not significantly differ between each other. We did not observe a relationship between CSF protein content, albumin quotient and α-CGRP. We also describe, retrospectively, an association between higher CSF CGRP content and higher MRI overall lesion count in MS and between lower α-CGRP and worse attention and visuo-perceptual skills in AD. We speculate that α-CGRP could be differentially involved in both disabling diseases.

The ALA5/ALA6/ALA7 repeat polymorphisms of the glutathione peroxidase-1 (GPx1) gene and autism spectrum disorder.

Autism is a severe neurodevelopmental disorder leading to deficits in social interaction, communication, and several activities. An increasing number of evidence suggests a role of oxidative stress in the etiology of autism spectrum disorder (ASD). Indeed, impaired antioxidant mechanisms may lead to the inadequate removal of H2 O2 with a consequent increase in highly active hydroxyl radicals and other reactive oxygen species causing cellular damages. The GPx1 is one of the most important enzymes counteracting oxidative stress. In this work, we investigated a possible correlation between the GCG repeat polymorphism present in the first exon of GPx1 gene encoding a tract of five to seven alanine residues (ALA5, ALA6, and ALA7) and ASD. Our findings highlighted a high frequency of ALA5 allele in ASD subjects. Moreover, proteins corresponding to the three GPx1 variants were produced in vitro, and the evaluation of their activity showed a lower values for GPx1 having ALA5 polymorphism. The comparison of the secondary and tertiary structure predictions revealed an alpha-helix in correspondence of alanine stretch only in the case of GPx1-ALA7 variant. Finally, to better investigate protein structure, steady-state fluorescence measurements of GPx1 intrinsic tryptophan were carried out and the three tested proteins exhibited a different stability under denaturing conditions. This work demonstrates the importance in adopting a multidisciplinary strategy to comprehend the role of GPx1 in ASD. LAY SUMMARY: Results here obtained suggest a possible role of ALA5 GPx1 variant in ASD. However, given the multifactorial nature of autism, this evidence might be a piece of a more complex puzzle being the GPx1 enzyme part of a complex pathway in which several proteins are involved.

Senatore cappelli (Triticum turgidum ssp. durum) pasta: a study on the nutritional quality of whole grains and its physical form.

Pasta is one of the components of the Mediterranean Diet, despite considerable attention given, its use is still debated. Several studies encouraged the consumption of whole grain because of its many properties and the positive association between refined carbohydrates and insulin resistance, by measuring the Glycaemic Index (GI), an indicator of the physiological effects of a carbohydrate meal. In this study, the GI and polyphenol content of Senatore Cappelli (Triticum turgidum ssp. durum) pasta were evaluated. Using spectrophotometric methods, total polyphenols and flavonoids were found to be 113.5 mg/100 g and 52.96 mg/100 g, respectively. To measure the GI, a standard assay was performed, and values of 47.9 ± 5.2 for long format pasta and 68.5 ± 4.6 for short format pasta were obtained. The present study confirms the presence of polyphenols and flavonoids in pasta Senatore Cappelli. The value of GI is influenced by the pasta shape. These informations could provide valuable data for practitioners preparing personalised diets.

A Pilot Cross-Sectional Study on Oral Health and Nutritional Status of Institutionalized Older Adults: A Focus on Sarcopenia.

The global population aged over 60 will double by 2050. This pilot cross-sectional study aims at evaluating nutritional and oral health status and the prevalence of sarcopenia in older adults living in an Italian residential aged care facility. Thirty-two adults aged ≥65 years were included. Individual sociodemographic data and nutritional and oral health data were collected. For sarcopenia diagnosis, muscle mass, physical performance, muscle strength and anthropometric parameters were recorded. Participants underwent a nutritional screening and a dental examination. Mini Nutritional Assessment and masticatory mixing ability test were performed. The results showed that men recorded a hand strength significantly higher than that of women, 25.5 ± 7.2 Kg vs. 12.8 ± 5.9 Kg (p < 0.01), respectively. Gait speed test showed that only 20.8% of the participants had a speed of more than 0.8 m/s. A strong negative correlation between masticatory performance and the number of missing teeth was detected (r = -0.84, 95% C.I. [-0.92; -0.69], p < 0.01). Overall, a high percentage of institutionalized older adults were diagnosed as being sarcopenic. Poor oral health in older adults is a major general health problem as it may restrict both food selection and nutrient intake, representing a risk factor for sarcopenia, although longitudinal studies are needed to confirm this relationship.

The Influence of Age and Oral Health on Taste Perception in Older Adults: A Case-Control Study.

Declining gustatory function, nutrition, and oral health are important elements of health in older adults that can affect the aging process. The aim of the present work was to investigate the effect of age and oral status on taste discrimination in two different groups of elderly subjects living either in an Italian residential institution (TG) or in the community (CG). A total of 90 subjects were enrolled in the study (58 CG vs. 32 TG). Masticatory performance (MP) was assessed using the two-color mixing ability test. Taste function was evaluated using cotton pads soaked with six taste stimuli (salty, acid, sweet, bitter, fat and water). A positive correlation between age and missing teeth (r = 0.51, C.I. [0.33; 0.65], p < 0.0001), and a negative correlation between age and MP (r = -0.39, C.I. [-0.56; -0.20], p < 0.001) were found. Moreover, significant differences for salty taste, between TG and CG were detected (p < 0.05). Significant differences in bitter taste sensitivity between subjects wearing removable and non-removable prosthesis were also determined (p < 0.05). In addition, significant gender differences and between males in TG and CG were identified (p < 0.05). The best understanding of the relationship between MP, taste sensitivity, and nutritional factors is a necessary criterion for the development of new therapeutic strategies to address more effectively the problems associated with malnutrition in elderly subjects.

Vasoactive neuropeptides and Alzheimer's disease: a systematic review focusing on calcitonin gene-related peptide.

Vasoactive peptides constitute a heterogenous family of mediators exerting various physiological functions, mostly studied for their vasotropic effects and role as peripheral neurotransmitters/neuromodulators, mainly involved in nociceptive transmission modulation. They have been divided into vasodilatory or vasoconstrictive peptides, according to their predominant effects on vascular tone. Recent research has shown in the Central Nervous System effects as transmitters and "growth factor-like" signals. Therefore, deregulation of their signaling systems has been thought to play a role in neural cell death and in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease, since these peptides can regulate neuronal stress signaling, survival cascades, synaptic plasticity. This review considers evidence about the implication of neuropeptide systems in Alzheimer's disease while focusing mainly on calcitonin gene-related peptide-alpha. In vitro and in vivo studies have shown potential implications in its pathogenesis. It has been possibly proposed as a neuroprotective agent, considering not only its pleiotropic actions on blood vessels, neurovascular coupling, energy metabolism, but also its potential actions on neuronal, glial, and immune system stress signaling, which might also derive from its structural homology to amylin. Amylin signaling is thought to be disrupted in Alzheimer's disease, and amylin itself takes part in the composition of senile plaques. Calcitonin gene-related peptide-containing systems seem more closely related to Alzheimer's disease pathogenesis than other neuropeptidergic systems, and their regulation might represent an interesting mechanism in developing novel therapeutic approaches.

Prospective observational study of taste assay in patients with solid tumors treated with standard chemotherapy (POTATO).

PURPOSE: The aim of our study is to evaluate taste changes in patients affected by solid tumors not involving oral cavity within the first month of standard chemotherapy. METHODS: In this monocentric, prospective, cohort study, we enrolled patients treated at our institution for different types of solid tumors between February and July 2019. Taste cotton swabs assay was used to assess taste changes. RESULTS: Thirty-one patients were enrolled and most of them had at least one change in taste. The taste that changed less was acid (42% of the population) whereas the one that changed the most was the perception of sweet (reduced in 35% of the population and increased in 45% of the population) and sour (reduced in 35% of the population). We did not find any statistical significant difference in terms of changes of taste and type of chemotherapy (emetogenic vs not, p > 0.05 for salty, sweet, bitter, and acid tastes). The type of primary tumor (breast vs GI-related) had a significant impact on perception of both salty (p = 0.0163) and acid (p = 0.0312) flavor. Furthermore, body mass composition assessed by BIA showed that obese patients had different changes in acid flavor vs non-obese patients (p = 0.04). This could not be proven when the assessment was made using BMI calculation. CONCLUSIONS: Our study suggests that type of primary tumor (GI vs breast) more than type of chemotherapy used could be relevant in determining changes in taste during chemotherapy. Individualized dietary strategies based on these reported data are suggested, as to optimize patients' management.

A Study on the Relationship between Type 2 Diabetes and Taste Function in Patients with Good Glycemic Control.

Type 2 diabetes mellitus (T2DM) has a very high impact on quality of life as it is characterized by disabling complications. There is little evidence about taste alterations in diabetes. Since many individual factors are involved in the onset of diabetes, the purpose of our study is to search a possible link between diabetes and individual taste function. Thirty-two participants with T2DM and 32 volunteers without T2DM (healthy controls) were recruited. Four concentrations of each of the four basic tastes (sweet, sour, salty, bitter), and pure rapeseed oil and water, were applied with cotton pads to the protruded tongue, immediately posterior to its first third, either to the left or right side. The results showed significant differences between groups in the ability to recognize sour, bitter, sweet, and water. Taste scores were lower in subjects with T2DM than in healthy controls, and an age-related decline in taste function was found. The taste function reduction associated with T2DM was not related to gender, disease duration, and glycemic control. In conclusion, it can be hypothesized that a general alteration of taste function can lead patients with type 2 diabetes to search for foods richer in sugars, as in a vicious circle, thus decreasing the likelihood of remission of diabetes mellitus.

Impact of Elderly Masticatory Performance on Nutritional Status: An Observational Study.

Background and Objectives: Masticatory limitations on the dietary habits of edentulous subjects restrict their access to adequate nutrition, exposing them to a greater risk of protein energy malnutrition. The aim of this study is to verify the existence of an association between Masticatory Performance (MP) and nutritional changes in the elderly. Materials and Methods: 76 participants were enrolled. MP testing was performed using the two-color chewing gum mixing test. The system used reveals the extent to which the two differently colored chewing gums mix, and allows discrimination between different MPs. The assessment of the participants' nutritional statuses was carried out through a food interview. Anthropometric parameters were collected, and bioimpedance analysis was performed. Results: Mean MP was 0.448 ± 0.188. No statistically significant differences were detected between male and female subjects (p > 0.05). According to the Body Mass Index (BMI), obese patients had a lower MP than overweight and normal weight subjects (0.408 ± 0.225, 0.453 ± 0.169 and 0.486 ± 0.181, respectively). MP values were lower both in male and female subjects with a waist circumference above the threshold than those below it (0.455 ± 0.205 vs. 0.476 ± 0.110, respectively, in males and 0.447 ± 0.171 vs. 0.501 ± 0.138, respectively, in females). No relationship was noticed between MP and bioimpedance parameters (p > 0.05). Conclusions: A statistically significant relation was observed between MP and the number of missing teeth. A reduced MP could worsen nutritional parameters. A reduced MP did not seem to negatively affect bioimpedance parameters.

Modifications of taste sensitivity in cancer patients: a method for the evaluations of dysgeusia.

PURPOSE: Taste changes due to chemotherapy may contribute to the high prevalence of malnutrition in cancer patients. It is believed that 50-70% of patients with cancer suffer from taste disorders. The aim of the present study was to analyze the taste alterations in patient population compared with that in controls, also in relation to gender. In this way, it could open to a new approach for a personalized diet to prevent and/or reduce taste alterations and malnutrition in cancer patients. METHODS: Forty-five cancer patients undergoing chemotherapy were compared with healthy controls (n = 32). Taste function test was used to determine taste sensitivity. Different concentrations for each of the four basic tastes (salty, sweet, sour, bitter) and also fat and water tastes were evaluated. RESULTS: A significant difference in taste sensitivity between patients and control group was found, in line with previous similar studies. As in the control group, taste perception in patients was better in females than in males, suggesting interaction effect between group and gender. CONCLUSIONS: Coping strategies regarding subjective taste impairment should be provided since alterations in taste sensitivity influence food preferences and appetite. Clinicians could thus have the potential to underpin changes in dietary intake and consequently in nutritional status; understanding the extent of the contribution of each taste would help in the development of effective interventions in future. Consequently, patients can adopt appropriate appetizing strategies and, based on that, change their feeding habits.