The use of new antibacterial drugs against infections caused by multidrug-resistant Gram-negative bacteria: an Italian real-world evidence study in a Lombardy hospital.

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects.

A Personalized Mediterranean Diet Improves Pain and Quality of Life in Patients with Fibromyalgia.

INTRODUCTION: Fibromyalgia is a form of chronic pain that affects a large number of women. It can start at any age and last a lifetime, with no cure. The Mediterranean diet is said to have an anti-inflammatory effect. Therefore, this study was conducted to investigate possible beneficial effects of a personalized Mediterranean diet in patients with fibromyalgia. METHODS: Outpatients with fibromyalgia were recruited and invited to participate in the study, including clinical, nutritional, and dietary assessments. Patients received a personalized Mediterranean diet (DIET group) or a general balanced diet (NODIET group) to be followed for 8 weeks. All tests were carried out at baseline and repeated after 4 and 8 weeks. RESULTS: In total, 100 subjects were included, 84 of whom completed the study. Most of the patients showed incorrect habits in terms of food choices, timing of meals and composition of nutrients. The DIET group showed an improvement in most of the fibromyalgia parameters, including the disability scores, fatigue, and anxiety. CONCLUSIONS: The habit of eating inflammatory foods and/or eating meals with the wrong nutritional content would increase the negative status of patients with fibromyalgia. With this study, we confirm that proper attention to feeding habits would improve the quality of life of such patients.

Real-World Effectiveness of Calcitonin Gene-Related Peptide-Binding Monoclonal Antibodies for Migraine Prevention: A Systematic Review.

Background: Migraine is a neurological disease with a high incidence. The new anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have demonstrated effectiveness in preventing episodic and chronic migraine. Objective: To collect evidence of the real-world effectiveness of anti-CGRP mAbs by assessing outcomes such as reduction in monthly migraine days (MMDs), reduction in monthly headache days (MHDs), and percentage of patients having a 50% reduction in MMDs. Data Sources: The PubMed database was searched for the period from inception to October 20, 2021. Study Selection and Data Extraction: Of interest for this review were studies that evaluated the real-world effectiveness of anti-CGRP mAbs in terms of MMDs and reduction in MHDs. The search terms included "migraine", "monthly migraine days", and various drug names. The data are reported in terms of patients' baseline characteristics and treatment effectiveness. Data Synthesis: A total of 46 studies were evaluated, of which 30 (enrolling a total of 4273 patients across 10 countries) were included in the systematic review. The greatest absolute reduction in MMD was from 20.4 at baseline to 10.7 after 3 months of treatment. After 6 months, the greatest absolute difference was 10, relative to baseline. The largest absolute reduction in MHD at 3 months was from 22 to 8, whereas at 6 months, the greatest absolute reduction in MHD was 13. The treatment could be considered clinically effective (≥ 50% reduction in MMDs) for 41% of patients at 3 months and about 44% of patients at 6 months. Conclusions: Despite substantial variability in baseline values, this review confirmed the effectiveness of anti-CGRP mAbs, which yielded important clinical reductions in both MMDs and MHDs.

Contexte: La migraine est une maladie neurologique à incidence élevée. Le nouvel anticorps monoclonal qui se lie au peptide lié au gène de la calcitonine (AcM anti-CGRP) a démontré son efficacité pour prévenir les migraines épisodiques et chroniques. Objectif: Recueillir des éléments probants concernant l'efficacité réelle des AcM anti-CGRP en évaluant des résultats comme la réduction du nombre de jours de migraine par mois (JMM), la réduction du nombre de jours de céphalées par mois (JCM) ainsi que le pourcentage de patients ayant une réduction de 50 % du nombre de JMM. Sources des données: La base de données PubMed a été utilisée pour mener une recherche pour la période allant du début jusqu'au 20 octobre 2021. Sélection des études et extraction des données: Les auteurs de la revue se sont intéressés aux études qui avaient évalué l'efficacité réelle des AcM anti-CGRP en termes de réduction du nombre de JMM et du nombre de JCM. Les termes de recherche comprenaient « migraine ¼, « jours de migraine par mois ¼ et divers noms de médicaments. Les données sont rapportées en termes de caractéristiques de base des patients et d'efficacité du traitement. Synthèse des données: Au total, 30 des 46 études répondant aux critères d'inclusion (comprenant un total de 4273 patients dans 10 pays) ont été retenues pour la revue systématique. La réduction absolue de JJM la plus importante était de 20,4 (la base de référence) à 10,7 après 3 mois de traitement. Après 6 mois, la différence absolue la plus importante était de 10 par rapport à la base de référence. La réduction absolue de JCM la plus importante à trois mois était de 22 à 8, alors qu'à 6 mois, la réduction absolue de JCM la plus importante était de 13. Le traitement pouvait être considéré comme cliniquement efficace (≥50 % de réduction de JMM) pour 41 % des patients à 3 mois et environ 44 % des patients à 6 mois. Conclusions: Malgré la variabilité importante des valeurs de la base de référence, cet examen confirme l'efficacité des AcM anti-CGRP, qui ont donné lieu à une réduction importante d'un point de vue clinique du nombre de JMM et de JCM.

Things Able to Treat Pain.

Chronic pain is a medical condition that affects a considerable number of people of all ages [...].

Serum Metabolomics and Proteomics to Study the Antihypertensive Effect of Protein Extracts from Tenebrio molitor.

Hypertension is the leading risk factor for premature death worldwide and significantly contributes to the development of all major cardiovascular disease events. The management of high blood pressure includes lifestyle changes and treatment with antihypertensive drugs. Recently, it was demonstrated that a diet supplemented with Tenebrio molitor (TM) extracts is useful in the management of numerous pathologies, including hypertension. This study is aimed at unveiling the underlying mechanism and the molecular targets of intervention of TM dietary supplementation in hypertension treatment by means of proteomics and metabolomics techniques based on liquid chromatography coupled with high-resolution mass spectrometry. We demonstrate that serum proteome and metabolome of spontaneously hypertensive rats are severely altered with respect to their normotensive counterparts. Additionally, our results reveal that a diet enriched with TM extracts restores the expression of 15 metabolites and 17 proteins mainly involved in biological pathways associated with blood pressure maintenance, such as the renin-angiotensin and kallikrein-kinin systems, serin protease inhibitors, reactive oxygen scavenging, and lipid peroxidation. This study provides novel insights into the molecular pathways that may underlie the beneficial effects of TM, thus corroborating that TM could be proposed as a helpful functional food supplement in the treatment of hypertension.

Food-Specific IgG4 Antibody-Guided Exclusion Diet Improves Conditions of Patients with Chronic Pain.

INTRODUCTION: Chronic pain is related to gastrointestinal (GI) functions because food components affect inflammation and pain through their action on the GI immune and/or neural system and because many analgesics interact with the gut to alter its structure and function. Immunoglobulin G4 (IgG4) are food-specific antibodies resulting from exposure of the gut immune system to nutrients. High IgG4 levels have been found to be associated with inflammation. METHODS: IgG4 were determined (both with the rapid test and enzyme-linked immunosorbent assay, ELISA) in men and women outpatients with chronic pain. All subjects were asked to exclude for 4 weeks all foods to which they had high blood levels of IgG4 antibodies. Pain and quality of life questionnaires were administered before (visit 1) and after (visit 2) the personalized exclusion diet period. Visual analogue scale (VAS), Italian Pain Questionnaire (QUID) and Margolis (MA) questionnaires were administered to determine pain intensity, pain features and pain extent, while Short Form Health Survey (SF-36) and Profile of Mood States (POMS) were used to test the quality of life and mood state. The nutritional status was evaluated in all subjects. Subject groups were women of reproductive age (pre-MW), women in menopause for at least 1 year (MW) and men. RESULTS: Fifty-four subjects with chronic pain (n = 12 neuropathic, n = 14 diffuse pain, n = 11 headache, n = 17 low back pain) completed the two visits and the 1-month exclusion diet. At visit 1, 47 (87%) subjects showed medium/high levels of IgG4 to at least one food. The foods showing the highest IgG4 values were eggs, dairy products, cereals and dried fruit. At visit 2, IgG4 levels were decreased, increased or unchanged. In all groups, the 4-week exclusion diet resulted in a significant reduction in all pain measures and an improvement of quality of life parameters. In particular, at visit 2, the VAS score determined in the morning decreased by more than 50%. CONCLUSIONS: A food elimination diet based on IgG4 antibody levels may be effective in reducing pain and improving quality of life in patients with chronic pain.

New Insights on Formyl Peptide Receptor Type 2 Involvement in Nociceptive Processes in the Spinal Cord.

Formyl peptide receptor type 2 (FPR2/ALX) belongs to the formyl peptide receptors (FPRs) family clustered on chromosome 19 and encodes a family of three Class A of G protein-coupled receptors (GPCRs). A short N-terminal region, an NPXXY motif in transmembrane (TM) region 7 and an E/DRY motif that bridges TM3 and TM6 stabilizing inactive receptor conformations characterize this class of receptors. In recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), FPRs play a crucial role in innate immune responses. FPR2/ALX is highly expressed in myeloid cells, as well as in chondrocytes, fibroblasts, endothelial, epithelial and smooth muscle cells. FPR2/ALX mRNA expression was recently reported in the rat brainstem, spinal cord, thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum. The central nervous system (CNS) distribution of FPR2/ALX suggests important functions in nociception. Thus, the present study was carried out to investigate the possible role of FPR2/ALX in nociception in mice. Intrathecal administration of the formyl peptide receptor type 1 (FPR1) agonist fMLF and the FPR2/ALX agonist BML-111 relieved nociception and these effects were reduced by contemporary administration of the FPR2/ALX antagonist WRW4. Furthermore, measurement of cytokines and brain-derived neurotrophic factor (BDNF) in the spinal cord of neuropathic mice demonstrated that the antinociceptive effects of BML-111 might depend on the reduction in cytokine release and BDNF in the spinal cord. These results suggest a possible role of FPR2/ALX for pain control in the spinal cord.

Calceolarioside A, a Phenylpropanoid Glycoside from Calceolaria spp., Displays Antinociceptive and Anti-Inflammatory Properties.

Phenylpropanoid glycosides are a class of natural substances of plant origin with interesting biological activities and pharmacological properties. This study reports the antinociceptive and anti-inflammatory effects of calceolarioside A, a phenylpropanoid glycoside previously isolated from various Calceolaria species. In models of acute nociception induced by thermal stimuli, such as the hot plate and tail flick test, calceolarioside administered at doses of 1, 5, and 10 µg in the left cerebral ventricles did not modify the behavioral response of mice. In an inflammatory based persistent pain model as the formalin test, calceolarioside A at the high dose tested (100 µg/paw) reduced the licking activity induced by formalin by 35% in the first phase and by 75% in the second phase of the test. In carrageenan-induced thermal hyperalgesia, calceolarioside A (50 and 100 µg/paw) was able to significantly reverse thermal hyperalgesia induced by carrageenan. The anti-inflammatory activity of calceolarioside A was then assessed using the zymosan-induced paw edema model. Calceolarioside A (50 and 100 µg/paw) induced a significant reduction in the edema from 1 to 4 h after zymosan administration. Measuring IL-6, TNFα, and IL-1ß pro-inflammatory cytokines released from LPS-stimulated THP-1 cells, calceolarioside A in a concentration-dependent manner reduced the release of these cytokines from THP-1 cells. Taken together, our results highlight, for the first time, the potential and selective anti-inflammatory properties of this natural-derived compound, prompting its rationale use for further investigations.

Age and training intensity differently affect male runners' endocrine and sexual parameters.

Physical activity is widely recognized to improve health and its inclusion in daily life at all ages is highly recommended. Gonadal hormones are known to be affected by physical activity. The exercise-induced effects on male runners of different ages were investigated by dividing 31 runners by age (Young, Y, 30-55 years; Old, O, 56-70 years) and amount of training (Light, L, <50 km/week; Heavy, H, 50 or more km/week). To test the somatic, sexual, and psychological health aspects, the Aging Male's Symptoms Scale (AMS) and the International Index of Erectile Function-6 (IIEF-6) questionnaires were administered and blood samples were drawn for adrenocorticotropic hormone, testosterone (Total-TT), free testosterone (Free-T), cortisol (C), dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin determinations. Clinical evaluations and questionnaire results showed the presence in all groups of some subclinical symptoms and "Light" dysfunctions. TT in the old-heavy (OH) group was significantly lower than in the OL group (2.38 ± 0.18 ng/mL vs. 3.36 ± 0.44 ng/ml, P = 0.05). The TT/DHT ratio was significantly higher in YH than in OH (3.64 ± 0.16 vs. 2.92 ± 0.23, P < 0.05). TT was positively correlated with AMS sexual subscale and negatively correlated with IIEF-6. Physical activity can significantly affect andrological health and testosterone levels in runners at all ages. Thus, due to the important testosterone-mediated vital functions in men, the evaluation of these parameters would be indicated in old as well as in young subjects.

Trop-2, Na+/K+ ATPase, CD9, PKCα, cofilin assemble a membrane signaling super-complex that drives colorectal cancer growth and invasion.

Trop-2 is a transmembrane signal transducer that is overexpressed in most human cancers, and drives malignant progression. To gain knowledge on the higher-order molecular mechanisms that drive Trop-2 signaling, we applied next-generation sequencing, proteomics, and high-resolution microscopy to models and primary cases of human colorectal cancer (CRC). We had previously shown that Trop-2 induces a Ca2+ signal. We reveal here that Trop-2 binds the cell membrane Na+/K+-ATPase, and that clustering of Trop-2 induces an intracellular Ca2+ rise followed by membrane translocation of PKCα, which in turn phosphorylates the Trop-2 cytoplasmic tail. This feed-forward signaling is promoted by the binding of Trop-2 to the PKCα membrane-anchor CD9. CRISPR-based inactivation of CD9 in CRC cells shows that CD9 is required by Trop-2 for recruiting PKCα and cofilin-1 to the cell membrane. This induces malignant progression through proteolytic cleavage of E-cadherin, remodeling of the ß-actin cytoskeleton, and activation of Akt and ERK. The interaction between Trop-2 and CD9 was validated in vivo in murine models of CRC growth and invasion. Overexpression of the components of this Trop-2-driven super-complex significantly worsened disease-free and overall survival of CRC patients, supporting a pivotal relevance in CRC malignant progression. Our findings demonstrate a previously unsuspected layer of cancer growth regulation, which is dormant in normal tissues, and is activated by Trop-2 in cancer cells.

Food addiction assessment in a nonclinical sample of the Italian population.

OBJECTIVE: Discussion about the potential addictive role of certain types of food and their link with obesity has recently increased. Researchers have developed instruments to specifically assess food addiction (FA). The aim of this pilot study was to investigate the prevalence of food addiction in a nonclinical sample of the Italian population. METHODS: All participants (n = 148: 46 males, 102 females) completed the Yale Food Addiction Scale 2.0 (YFAS 2.0) and provided self-reported measures and demographic information. They were divided into three age groups. RESULTS: The prevalence of FA was 15.5% of our sample (82.6% of the subjects diagnosed with FA were female). The FA symptoms mean was 1.90 (SD = 2.87). In both sexes, participants aged 18-30 had the highest diagnosis of FA, with 52.1% of all FA subjects being females aged 18-30. According to the Body Mass Index (BMI), all the males diagnosed with FA were overweight or obese, as were most (63.2%) of the FA females. CONCLUSIONS: Future food education policies could consider FA assessment together with that of other eating disorders, even among nonclinical subjects in order to anticipate diagnosis and improve treatment.

Estrogens and phytoestrogens in body functions.

Estrogens are the hormones of reproduction in women as well as of many other important functions in the male and female body. They undergo significant changes in the different phases of life, e.g. during puberty, pregnancy or at menopause/andropause. Phytoestrogens are natural non-steroidal phenolic plant compounds that can mimic the activity of estrogens and their beneficial effects in women and in men. This narrative review summarizes the literature on the physiological role of estrogens and the several potential health benefits of phytoestrogens, with particular attention given to the possible role of phytoestrogens in aging.

Very-Low-Calorie Ketogenic Diet: A Potential Treatment for Binge Eating and Food Addiction Symptoms in Women. A Pilot Study.

BACKGROUND: many patients who struggle to lose weight are unable to cut down certain ultra-processed, refined types of food with a high glycemic index. This condition is linked to responses similar to addiction that lead to overeating. A very-low-calorie ketogenic diet (VLCKD) with adequate protein intake could be considered a valid dietary approach. The aim of the present study was to evaluate the feasibility of a VLCKD in women with binge eating and/or food addiction symptoms. METHODS: subjects diagnosed with binge eating and/or food addiction symptoms (measured with the Binge Eating Scale and the Yale Food Addiction Scale 2.0) were asked to follow a VLCKD with protein replacement for 5-7 weeks (T1) and a low-calorie diet for 11-21 weeks (T2). Self-reported food addiction and binge eating symptoms and body composition were tested at T0 (baseline) and at the end of each diet (T1 and T2 respectively); Results: five women were included in the study. Mean age was 36.4 years (SEM = 4.95) and mean BMI was 31.16 (SEM = 0.91). At T0, two cases of severe food addiction, one case of mild food addiction, one case of binge eating with severe food addiction, and one case of binge eating were recorded. Weight loss was recorded at both T1 and T2 (ranging from 4.8% to 11.6% of the initial body weight at T1 and from 7.3% to 12.8% at T2). No case of food addiction and/or binge eating symptoms was recorded at T2. Muscle mass was preserved. CONCLUSIONS: recent findings have highlighted the potential therapeutic role of ketogenic diets for the treatment of addiction to high-calorie, ultra-processed and high-glycemic food. Our pilot study demonstrates the feasibility of a ketogenic diet in women with addictive-like eating disorders seeking to lose weight.

Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.

Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. No Trop-2 cleavage was detected in normal human tissues, whereas most tumors showed Trop-2 cleavage, including skin, ovary, colon, and breast cancers. Coimmunoprecipitation and mass spectrometry analysis revealed that ADAM10 physically interacts with Trop-2. Immunofluorescence/confocal time-lapse microscopy revealed that the two molecules broadly colocalize at the cell membrane. We show that ADAM10 inhibitors, siRNAs and shRNAs abolish the processing of Trop-2, which indicates that ADAM10 is an effector protease. Proteolysis of Trop-2 at R87-T88 triggered cancer cell growth both in vitro and in vivo. A corresponding role was shown for metastatic spreading of colon cancer, as the R87A-T88A Trop-2 mutant abolished xenotransplant metastatic dissemination. Activatory proteolysis of Trop-2 was recapitulated in primary human breast cancers. Together with the prognostic impact of Trop-2 and ADAM10 on cancers of the skin, ovary, colon, lung, and pancreas, these data indicate a driving role of this activatory cleavage of Trop-2 on malignant progression of tumors.

Pain Study in X-Linked Adrenoleukodystrophy in Males and Females.

INTRODUCTION: X-linked adrenoleukodystrophy (ALD) is a metabolic disorder in which very long chain fatty acids (VLCFAs) are accumulated in the nervous system and adrenal cortex, impairing their functions. Three main variants are described in males: adrenomyeloneuropathy (AMN), a cerebral form (cALD or cAMN) and Addison's disease only (AD), while for females no classification is used. To evaluate pain and the functional state of afferent fibers, a series of tests was carried out in male and female patients. METHODS: Chronic pain occurrence and sensory phenotype profile were assessed in 30 patients (20 male: 10 AMN, 1 cAMN, 1 cALD, 8 AD; and 10 female). A set of instruments assessed the intensity, quality and extent of pain, while a battery of quantitative sensory testing (QST) procedures examined the functional status of Aß and Aδ fibers. Principal component analysis and hierarchical clustering with sensory responses input were used to identify distinct clusters. RESULTS: Nearly half of the subjects reported pain, with a high prevalence in females and male AMN patients. No sex differences in pain dimensions were found. The sensory responses were heterogeneous, differing among the clinical variants and between genders. Male AMN/cAMN/cALD patients showed the worst impairment. Aß and Aδ fibers were affected in males and females, but Aß fibers appeared undamaged in females when tactile sensitivity was tested. Abnormal responses were localized in the lower body district, according to the dying-back pattern of the neuropathy. Cluster analysis showed discrete clusters for each function examined, with well-interpretable sensory and clinical phenotypes. CONCLUSION: The study of pain and of the sensory profile appears to indicate a difference in the mechanisms underlying the AMN/cAMN/cALD and AD clinical forms and in the treatment of the respective generated pain types.

Feeding Your Himalayan Expedition: Nutritional Signatures and Body Composition Adaptations of Trekkers and Porters.

High-altitude exposure leads to many physiological challenges, such as weight loss and dehydration. However, little attention has been posed to the role of nutrition and ethnic differences. Aiming to fulfill this gap, five Italian trekkers and seven Nepalese porters, all males, recorded their diet in diaries during a Himalayan expedition (19 days), and the average daily intake of micro and macro-nutrients were calculated. Bioimpedance analysis was performed five times during the trek; muscle ultrasound was performed before and after the expedition, only for the Italians. The Nepalese group consumed a lot of rice and only Italians consumed cheese. Water intake was slightly over 3000 g/d for both groups. Nepalese diet had a higher density of dietary fibre and lower density of riboflavin, vitamins A, K, and B12. Intake of calcium was lower than recommended levels. Body mass index, waist circumference, fat-free mass, and total body water decreased in both groups, whereas resistance (Rz) increased. Italians reactance (Xc) increased at day 9, whereas that of Nepalese occurred at days 5, 9, and 16. The cross-sectional area of the Vastus lateralis was reduced after the expedition. Specific nutritional and food-related risk factors guidance is needed for diverse expedition groups. Loss of muscle mass and balance of fluids both deserve a particular focus as concerns altitude expeditions.

Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage.

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats' eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.

Infrared Thermography Images Acquisition for a Technical Perspective in Screening and Diagnostic Processes: Protocol Standardized Acquisition.

In this technical report we describe the thermographic setting protocol suitable for the FLIR T650SC thermal imager (FLIR Systems, Inc., Wilsonville, OR), an instrument that detects electromagnetic radiation in the infrared field which is physiologically emitted from the human body. FLIR T650SC thermal imager processes infrared radiations graphically and analyzes them through a specific software. In biomedicine, infrared thermography is a promising technique amongst other conventional methods used for detecting skin temperature differences considered as a possible sign of disturbances in the human body. Currently, automatic screening of temperature from a safe distance is an instrument utilized in the front line of the SARS CoV2 emergency. The processing method of the thermogram considers an initial setting of constant parameters that cannot be subsequently modified such as temperature range, focusing and image composition. After the acquisition variable values important in the processing and analysis of the thermogram, such as detection of environment temperature, reflected temperature, emissivity, relative humidity and contrast palette, are set in the software. The analysis is performed using the FLIR Tools software. In the biomedical field standardized acquisition of thermograms facilitates the identification of trigger points and areas of hyper- and hypothermia distributed on the skin surface and muscle bundles. The protocol made it possible to create images with the same acquisition method for all patients. The thermal imaging camera is a valid screening tool because its execution is rapid, it is non-invasive, well-tolerated, and at a low cost for patients.