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Diabetic foot (DF) is a leading cause of nontraumatic lower-extremity amputations, premature death, and a sign of social inequality in diabetes treatment. In Mexico, the incidence of DF is on the rise yet little is known about its impact among indigenous people, a disadvantaged group. Based on ethnographic research conducted in Oaxaca and analysis of institutional health-data, in this article we show the health care delays that rural indigenous people face when dealing with DF. Indigenous people's uncertainty regarding their right to health and the structural barriers to medical care favor DF complications, a phenomenon that should be read as social suffering. Since health data concerning indigenous health care service users is patchy and imprecise, indigenous people's social suffering is invisibilized. This omission or partiality in the official records limits public health decision-making and undermines the human rights of the population.

Background: The pathophysiology of sensitive skin is largely unknown and no univocal data on the role of the epidermal barrier impairment have been identified. The aim of this study was to assess whether subjects with or without sensitive skin differ for some biophysical skin parameters, which reflect skin barrier integrity or skin hyperactivity., Methods: This observational, cross-sectional study included adult volunteers not affected with chronic inflammatory skin diseases who attended the Unit of Dermatology and the Center of Cosmetology of the University of Ferrara, Ferrara, Italy, between March 2021 and November 2022. All subjects, subdivided into those with or without sensitive skin, based on either Lactic Acid Stinging Test (LAST) result or a questionnaire-based skin sensitivity score ≥4, were tested for transepidermal water loss (TEWL), skin elasticity and hydrations and dermographism., Results: One hundred and eighty-seven subjects were included. No significant differences in terms of TEWL, elasticity and hydration levels were recorded between subjects with sensitive skin and those without, subdivided according to both the LAST result and the questionnaire score. Dermographism was elicited more in subjects with sensitive skin than in the others, although without statistical significance., Conclusions: The study failed to find significant biophysical differences between sensitive and non-sensitive skin. Therefore, the role of skin barrier impairment does not appear to be a necessary condition in determining an abnormal skin sensitivity to potentially unpleasant and irritating stimuli. These findings indirectly support the relevance of a peripheral sensory neural hyperactivity in the pathophysiology of sensitive skin.

Luca Montesi,1 Marwan El Ghoch,2 Lucia Brodosi,1 Simona Calugi,2 Giulio Marchesini,1 Riccardo Dalle Grave2 1Unit of Metabolic Diseases, S Orsola-Malpighi Hospital, “Alma Mater Studiorum” University, Bologna, Italy; 2Department of Eating and Weight Disorders, Villa Garda Hospital, Verona, Italy Abstract: The long-term weight management of obesity remains a very difficult task, associated with a high risk of failure and weight regain. However, many people report that they have successfully managed weight loss maintenance in the long term. Several factors have been associated with better weight loss maintenance in long-term observational and randomized studies. A few pertain to the behavioral area (eg, high levels of physical activity, eating a low-calorie, low-fat diet; frequent self-monitoring of weight), a few to the cognitive component (eg, reduced disinhibition, satisfaction with results achieved, confidence in being able to lose weight without professional help), and a few to personality traits (eg, low novelty seeking) and patient–therapist interaction. Trials based on the most recent protocols of lifestyle modification, with a prolonged extended treatment after the weight loss phase, have also shown promising long-term weight loss results. These data should stimulate the adoption of a lifestyle modification-based approach for the management of obesity, featuring a nonphysician lifestyle counselor (also called “lifestyle trainer” or “healthy lifestyle practitioner”) as a pivotal component of the multidisciplinary team. The obesity physicians maintain a primary role in engaging patients, in team coordination and supervision, in managing the complications associated with obesity and, in selected cases, in the decision for drug treatment or bariatric surgery, as possible more intensive, add-on interventions to lifestyle treatment. Keywords: obesity, lifestyle modification, cognitive behavior therapy, multidisciplinary treatment

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.

Objective: A recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result., Methods: Adult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items., Results: Three hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor., Conclusion: With small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice., (© 2022 The Authors. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Francesco Di Pierro,1 Pietro Putignano,2 Nicola Villanova,3 Luca Montesi,3 Simona Moscatiello,3 Giulio Marchesini3 1Scientific Department, Velleja Research, Milano, Italy; 2Outpatient Diabetic Clinic, University Hospital San Gerardo, Monza, Italy; 3Diseases of Metabolism, S Orsola Malpighi Hospital, Bologna, Italy Background: Berberine is an isoquinoline alkaloid widely used to improve the glucidic and lipidic profiles of patients with hypercholesterolemia, metabolic syndrome, and type 2 diabetes. The limitation of berberine seems to be its poor oral bioavailability, which is affected by the presence, in enterocytes, of P-glycoprotein – an active adenosine triphosphate (ATP)-consuming efflux protein that extrudes berberine into the intestinal lumen, thus limiting its absorption. According to some authors, silymarin, derived from Silybum marianum, could be considered a P-glycoprotein antagonist. Aim: The study aimed to evaluate the role played by a possible P-glycoprotein antagonist (silymarin), when added to a product containing Berberis aristata extract, in terms of benefits to patients with type 2 diabetes. Methods: The study enrolled 69 patients with type 2 diabetes in suboptimal glycemic control who were treated with diet, hypoglycemic drugs, and in cases of concomitant alterations of the lipid profile, hypolipidemic agents. The patients received an add-on therapy consisting of either a standardized extract of Berberis aristata (titrated in 85% berberine) corresponding to 1,000 mg/day of berberine, or Berberol®, a fixed combination containing the same standardized extract of Berberis aristata plus a standardized extract of Silybum marianum (titrated as .60% in silymarin), for a total intake of 1,000 mg/day of berberine and 210 mg/day of silymarin. Results: Both treatments similarly improved fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, and liver enzyme levels, whereas glycosylated hemoglobin (HbA1c) values were reduced to a greater extent by the fixed combination. Conclusion: The association of berberine and silymarin demonstrated to be more effective than berberine alone in reducing HbA1c, when administered at the same dose and in the form of standardized extracts in type 2 diabetic patients. Keywords: Berberol®, P-glycoprotein, cholesterol, triglycerides, glycosylated hemoglobin

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O 3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O 3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O 3 exposure.Inizio modulo.

Objective: Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy., Methods and Materials: We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test., Results: Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months., Conclusions: Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w / w , suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin.

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application.

In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate's chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w / w led to multivesicular vesicles with 344 nm mean size, controlling the drug's chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w / w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases.

Background: Sensitive skin is very common and distressing. Its diagnosis may be difficult with the tools/methods available at the moment., Aims: To assess the reliability of a self-assessment questionnaire for the diagnosis of sensitive skin, using the results of lactic acid stinging test (LAST) as a reference for the identification of subjects suffering from this condition. A further objective was to identify the questionnaire cutoff score that better discriminates between subjects with or without sensitive skin., Patients/methods: Among the adult volunteers included in this observational, cross-sectional study, both LAST-positive subjects, who were considered as having sensitive skin ("patients"), and negative ones ("controls") completed the questionnaire. It consisted of a part for self-assessing and quantifying (0-10) sensitive skin and another one that included 10 items, each referring to a specific, potentially triggering stimulus. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items considered capable of triggering unpleasant skin sensations in real-life experience., Results: One hundred and sixty-two subjects were enrolled, 102 patients and 60 controls; 98 subjects thought they had sensitive skin. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls and correlated with skin sensitivity self-assessments. A cutoff value of 3 was set for the identification of LAST-positive subjects, with 79% accuracy., Conclusions: The study self-assessment questionnaire seems to be a reliable tool for diagnosing sensitive skin in clinical practice. These results led us to identify a numerical cutoff for detecting propensity to experience sensitive skin., (© 2021 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objectives: Retrograde intrarenal surgery (RIRS) is commonly performed under general anesthesia (GA) because renal mobility during breathing may affect lithotripsy. However, spinal anesthesia (SA) is adopted in clinical practice due to clinical conditions that contraindicate GA. We aimed to compare results of RIRS for stones performed under GA compared to SA regarding stone-free rate (SFR) status and postoperative complications in a consecutive single-center series., Methods: We retrospectively reviewed all patients who underwent RIRS for stones between 2017 and 2020., Inclusion Criteria: age ≥ 18 years, renal stone burden deemed suitable for RIRS with a stone diameter ≤ 20 mm., Exclusion Criteria: stones >20 mm, urinary tract infection, bilateral surgery, second-look procedures, unmodifiable bleeding diathesis, <5mm asymptomatic lower calyx stones. SFR was defined as no residual fragment >3 mm at 6-12 weeks follow-up. The choice of anesthesia was a shared decision between anesthesiologists and patient preference., Results: 230 patients were included in the analysis. Mean age was 57.50±13.73 years. 33% of stones were located in the pelvis. 28.7% of patients had multiple stones. Mean cumulative stone diameter was 16.60±6.54 mm. 63% of patients underwent RIRS under SA. There were no significant differences between the two groups in terms of preoperative characteristics, except for comor-bidity, significantly higher in the GA group. Mean time of operating room occupation was longer in the GA group (81.58±35.37 minutes) than in the SA group (72.85±25.91 minutes,p=0.033). Length of stay was shorter in the SA group (mean 2.2±1.66 days vs 3.46±5.88 in GA,p=0.019). Logistic regression showed that multiple stones in the collecting system were associated with residual fragments (HR 0.386, 95%CI 0.151-0.991,p=0.04). There were no statistically significant differences in overall and high-grade complications, and in SFR between SA (75.9%) and GA groups (70.6%,p=0.317)., Conclusion: SA does not affect SFR and postoperative complications in patients who underwent RIRS in daily practice.

Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.

The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O 2 concentration changes in the membrane induced by polyphenols and H 2 O 2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.

Based on seven months of ethnographic fieldwork in two urban health centres in Oaxaca City, Mexico, this paper analyses the ways in which underprivileged middle-aged and older female patients experience and transform grupos de ayuda mutua (GAMs), or mutual-aid groups, a public health programme aimed at improving chronic patients' adherence to their biomedical treatments. GAMs work as 'technologies of the self' within the context of the Mexican neoliberal regime and patients are urged to be self-responsible. GAM members regard such urging favourably and act according to their broader understandings of life, which they see as a lucha (struggle) that requires cuidarse (a polysemic verb alluding to self-care for self-preservation) and hard work in a structurally unequal place characterised by precarity and social unrest. This seemingly rugged individualism is converted into microlevel collaboration through culturally distinctive Oaxacan practices of mutual help. By exploring the playful ways these women participate in GAMs, this paper shows how biomedical settings can be repurposed as spaces of socialisation and wellbeing for older women living in vulnerable conditions.