Modulation of Vibrio cholerae gene expression through conjugative delivery of engineered regulatory small RNAs.

The increase in antibiotic resistance in bacteria has prompted the efforts in developing new alternative strategies for pathogenic bacteria. We explored the feasibility of targeting Vibrio cholerae by neutralizing bacterial cellular processes rather than outright killing the pathogen. We investigated the efficacy of delivering engineered regulatory small RNAs (sRNAs) to modulate gene expression through DNA conjugation. As a proof of concept, we engineered several sRNAs targeting the type VI secretion system (T6SS), several of which were able to successfully knockdown the T6SS activity at different degrees. Using the same strategy, we modulated exopolysaccharide production and motility. Lastly, we delivered an sRNA targeting T6SS into V. cholerae via conjugation and observed a rapid knockdown of the T6SS activity. Coupling conjugation with engineered sRNAs represents a novel way of modulating gene expression in V. cholerae opening the door for the development of novel prophylactic and therapeutic applications. IMPORTANCE: Given the prevalence of antibiotic resistance, there is an increasing need to develop alternative approaches to managing pathogenic bacteria. In this work, we explore the feasibility of modulating the expression of various cellular systems in Vibrio cholerae using engineered regulatory sRNAs delivered into cells via DNA conjugation. These sRNAs are based on regulatory sRNAs found in V. cholerae and exploit its native regulatory machinery. By delivering these sRNAs conjugatively along with a real-time marker for DNA transfer, we found that complete knockdown of a targeted cellular system could be achieved within one cell division cycle after sRNA gene delivery. These results indicate that conjugative delivery of engineered regulatory sRNAs is a rapid and robust way of precisely targeting V. cholerae.

Validation of ZIP4 as a tumor-associated antigen for nanotargeting.

Pancreatic ductal adenocarcinoma remains a highly aggressive and untreatable cancer. There is a need to develop a new PDAC-associated antigen-targeting drug delivery system to tackle this disease. We validated choosing ZIP4 as a putative target in PDAC theranostics. We developed a nanosystem composed of a fluorescent polystyrene core coated with gold nanoparticles onto which a ZIP4-specific polyclonal antibody is attached. The polystyrene core's fluorescence properties allow the nanosystem tracking by intravital imaging. We also developed two ZIP4-expressing cell lines by stably transfecting HEK293 and RWP1 cells with a ZIP4-coding plasmid that simultaneously provides cells with puromycin resistance. We studied the cell internalization of the as-synthesized nanoparticles and demonstrated that ZIP4-expressing HEK293 and ZIP4-expressing RWP1 cells tended to take up more ZIP4-targeting nanoparticles. Moreover, we observed that ZIP4-targeting nanoparticles accumulated more in ZIP4-expressing HEK293 and RWP1 tumors when injected intravenously in a subcutaneous xenograft and an orthotopic in vivo model, respectively. Furthermore, the administration of these nanoparticles did not induce any significant systemic toxicity as determined by histological analysis of all organs. Altogether, these results provide the first evidence of the feasibility of using a ZIP4-targeting nanosystem further to design efficient therapeutic and diagnostic tools for PDAC.

Implementing magnetically-active Sn-based nanocomposites in hexavalent chromium removal from drinking water.

A novel nanocomposite consisting of Fe3O4-loaded tin oxyhydroxy-chloride is demonstrated as an efficient adsorbent for the removal of hexavalent chromium in compliance to the new drinking water regulation. This study introduces a continuous-flow production of the nanocomposite through the separate synthesis of (i) 40 nm Fe3O4 nanoparticles and (ii) multilayered spherical arrangements of a tin hydroxy-chloride identified as abhurite, before the application of a wet-blending process. The homogeneous distribution of Fe3O4 nanoparticles on the abhurite's morphology, features nanocomposite with magnetic response whereas the 10 % loaded nanocomposite preserves a Cr(VI) uptake capacity of 7.2 mg/g for residual concentrations below 25 µg/L. Kinetic and thermodynamic examination of the uptake evolution indicates a relative rapid Cr(VI) capture dominated by interparticle diffusion and a spontaneous endothermic process mediated by reduction to Cr(III). The efficiency of the optimized nanocomposite was validated in a pilot unit operating in a sequence of a stirring reactor and a rotary magnetic separator showing an alternative and competitive application path than typical fixed-bed filtration, which is supported by the absence of any acute cellular toxicity according to human kidney cell viability tests.

Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Effects of Kinesiotape versus Low-Dye Tape on Pain and Comfort Measures in Patients with Plantar Fasciitis: A Randomized Clinical Trial.

BACKGROUND: Bandages are commonly used to relieve pain in patients with plantar fasciitis. The goal was to compare the effects of using kinesiotape versus low-dye tape in the acute phase of plantar fasciitis on pain and comfort measures. METHODS: Forty individuals with plantar fasciitis were allocated to the kinesiotape or low-dye tape interventions. The patients were assessed at baseline and every 24 h until the fifth day. The primary measure was a visual analog scale of pain. The other measures were comfort, mobility, durability, personal hygiene, sweating, and allergies. The effects were compared with an ANOVA test, 95% CI. RESULTS: Kinesiotape was more effective in reducing pain; the greater effect occurred during the first day, with a between-group difference of 2.0 (95% CI: 1.8 to 2.2). The pain differences between the treatments progressively reduced each day from the second day. Kinesiotape offered significantly higher performance than low-dye tape in mobility, comfort, and comfort in hygiene, sweating, and durability, with a large effect size d > 0.8. CONCLUSIONS: Kinesiotape could be more effective than low-dye tape in relieving pain in patients with plantar fasciitis, with a significant clinical impact on the first day of treatment. Kinesiotape can also provide higher performance in terms of comfort.

Real Time and Spatiotemporal Quantification of pH and H2O2 Imbalances with a Multiplex Surface-Enhanced Raman Spectroscopy Nanosensor.

Oxidative stress is involved in many aging-related pathological disorders and is the result of defective cellular management of redox reactions. Particularly, hydrogen peroxide (H2O2), is a major byproduct and a common oxidative stress biomarker. Monitoring its dynamics and a direct correlation to diseases remains a challenge due to the complexity of redox reactions. Sensitivity and specificity are major drawbacks for H2O2 sensors regardless of their readout. Luminiscent boronate-based probes such as 3-mercaptophenylboronic acid (3-MPBA) are emerging as the most effective quantitation tool due to their specificity and sensitivity. Problems associated with these probes are limited intracellular sensing, water solubility, selectivity, and quenching. We have synthesized a boronate-based nanosensor with a surface-enhanced Raman spectroscopy (SERS) readout to solve these challenges. Furthermore, we found out that environmental pH gradients, as found in biological samples, affect the sensitivity of boronate-based sensors. When the sensor is in an alkaline environment, the oxidation of 3-MPBA by H2O2 is more favored than in an acidic environment. This leads to different H2O2 measurements depending on pH. To solve this issue, we synthesized a multiplex nanosensor capable of concomitantly quantifying pH and H2O2. Our nanosensor first measures the local pH and based on this value, provides the amount of H2O2. It seems that this pH-dependent sensitivity effect applies to all boronic acid based probes. We tested the multiplexing ability by quantitatively measuring intra- and extracellular pH and H2O2 dynamics under physiological and pathological conditions on healthy cells and cells in which H+ and/or H2O2 homeostasis has been altered.

Influence of Sociodemographic Variables and Healthy Habits on the Values of Insulin Resistance Indicators in 386,924 Spanish Workers.

BACKGROUND: Insulin resistance (IR) is an alteration of the action of insulin in cells, which do not respond adequately to this action, leading to an increase in blood glucose levels. IR produces a very diverse clinical picture and increases the cardiometabolic risk of the population that suffers from it. Among the factors that influence IR are genetics, unhealthy lifestyle habits, overweight, and obesity. The objective of this work was to determine how different sociodemographic variables and healthy habits influence the values of different scales that assess the risk of presenting IR in a group of Spanish workers. METHODS: An observational, cross-sectional, descriptive study was carried out in 386,924 workers from different Spanish regions. Different sociodemographic variables and lifestyle habits were studied (age, social class, educational level, smoking, Mediterranean diet, physical exercise) along with their association with four scales to evaluate the risk of insulin resistance (TyG index, TyG-BMI, METS-IR, TG/HDL-c). To analyse the quantitative variables, Student's t test was used, while the Chi-squared test was used for the qualitative variables. A multinomial logistic regression analysis was performed, calculating the odds ratio with its 95% confidence intervals. The accepted level of statistical significance was set at p < 0.05. RESULTS: In the multivariate analysis, all variables, except educational level, increased the risk of presenting high values on the IR risk scales, especially a sedentary lifestyle and low adherence to the Mediterranean diet. CONCLUSIONS: Our results demonstrate an association between the practice of regular physical exercise and a reduction in the risk of IR; a strong role of the Mediterranean diet as a protective factor for IR; an association between aging and increased IR, which has also been suggested in other studies; and, finally, a relationship between a low socioeconomic level and an increase in IR.

Relationship between Abdominal Volume Index and Body Adiposity Index and Scales of Insulin Resistance and Metabolic Syndrome.

Introduction, objectives: Obesity is a global health problem with a great negative impact on health. Among the pathologies caused by obesity are insulin resistance and metabolic syndrome, which constitute an increasingly common health problem in both developed and developing countries. The aim of this study was to examine the relationship between two scales that assess obesity-based on hip circumference-and metabolic syndrome (MetS) and insulin resistance risk scales as predictors of these alterations. MATERIALS, METHODS: A descriptive, cross-sectional study was carried out on 193,462 workers from different Spanish regions and work groups between January 2019 and September 2021. Abdominal volume index (AVI) and body adiposity index (BAI) were evaluated to assess obesity and its association with insulin resistance using three risk scales (TyG index, Triglycerides/HDL, and METS-IR), while their association with metabolic syndrome was determined using the NCEP ATP III, IDF, and JIS models. RESULTS: The results of the ROC curves to determine the predictive value of BAI and AVI in relation to the three criteria evaluated to calculate MetS in all instances presented a higher area under the curve (AUC) for AVI. The high values of AVI stand out for predicting MetS when applying the IDF criteria. The cut-off point in women was 13.70 with a Youden index of 0.802, whereas in men, the cut-off point was set at 17.59 with a Youden index of 0.672. Regarding the relationship of BAI and AVI with insulin resistance risk scales for both sexes, the AUC only revealed high values when using the METS-IR formula for both AVI and BAI. The AVI cut-off points to predict high values of insulin resistance risk scales in women were established at 13.12 with a Youden index of 0.722. In men, the cut-off point was 17.59, with a Youden index of 0.626. The BAI cut-off points in women were set at 33.88 with a Youden index of 0.748. In men, the cut-off point was 27.91, with a Youden index of 0.598. CONCLUSIONS: AVI demonstrated its value as a predictor of metabolic syndrome while exclusively applying the IDF criteria. AVI and BAI demonstrated their value as predictors of high values of insulin resistance risk scales only in the case of METS-IR. This predictive value is also higher in women.

Determination of the Level of Cardiovascular Risk in 172,282 Spanish Working Women.

Introduction, objectives: Although cardiovascular events have been traditionally associated mainly with men, some data reflect an increase in women, which may even exceed their male counterparts, constituting the leading cause of death in working women in Spain. The objective of this present study was to analyze the level of cardiovascular risk in Spanish working women by assessing the influence of age, type of work, and tobacco consumption. MATERIAL, METHODS: A descriptive cross-sectional study was carried out in 172,282 working women from different Spanish geographical areas and from different companies between January 2018 and June 2020. A range of variables and risk factors were assessed and various cardiovascular risk scales were used to analyze the data. RESULTS: An increase in cardiovascular risk was observed in the least qualified work groups, mainly corresponding to blue-collar workers, when using the SCORE or REGICOR risk equation. The prevalence of altered values for all the parameters analyzed (overweight and obesity, hypertension, dyslipidemia, diabetes, fatty liver, hepatic fibrosis, atherogenic indexes, and cardiovascular risk scales) was higher among blue-collar women. Age was the only factor that influenced all the cardiovascular risk scales studied, increasing risk when comparing the group of women aged 50 years and older with the others. CONCLUSIONS: Aging and belonging to the blue-collar job category meant worse results in the cardiovascular risk scales and in all the parameters analyzed. This is in line with numerous studies that argue that age and zip code are more influential than genetic code.

Classification system for nanotechnology-enabled health products with both scientific and regulatory application.

The lack of specific regulatory guidelines for nanotechnology-enabled health products (NHPs) is hampering development and patient access to these innovative technologies. Namely, there is an urgent need for harmonized regulatory definitions and classification systems that allow establishing a standardized framework for NHPs regulatory assessment. In this work, a novel classification system for NHPs is proposed. This classification can be applied for sorting nano-based innovations and regulatory guidelines according to the type of NHPs they address. Said methodology combines scientific and regulatory principles and it is based on the following criteria: principal mode of action, chemical composition, medical purpose and nanomanufacturing approach. This classification system could serve as a useful tool to sensor the state of the art of NHPs which is particularly useful for regulators to support strategy development of regulatory guidelines. Additionally, this tool would also allow manufacturers of NHPs to align their development plans with their applicable guidelines and standards and thus fulfill regulators expectations.

Relationship between Atherogenic Dyslipidaemia and Lipid Triad and Scales That Assess Insulin Resistance.

BACKGROUND: Atherogenic dyslipidaemia (AD) and lipid triad (LT) are characterised by high triglyceride levels together with low HDL and normal or high LDL cholesterol and are favoured by a persistent state of insulin resistance (IR), which increases the release of free fatty acids from abdominal adipose tissue. This alteration in the lipid profile favours the accelerated development of atherosclerosis, which is the most important cause of morbidity and mortality in all countries in the developed and developing world. One of the elements that plays a major role in the genesis of AD is IR. The aim of this study was to determine the relationship between variables that assess atherogenic risk (AD and LT) and scales that assess the risk of presenting insulin resistance. METHODS: A descriptive cross-sectional study of 418,343 workers was conducted to evaluate atherogenic dyslipidaemia and lipid triad; a relationship with three insulin resistance risk scales (Triglycerides/HDL, TyG index, METS-IR) was established. The usefulness of IR risk scales for predicting AD and LT was calculated by applying ROC curves, obtaining the area under the curve (AUC) and cut-off points with their sensitivity, specificity, and Youden index. Multivariate analysis was performed by binary logistic regression. RESULTS: The prevalence of high-risk values for insulin resistance with all of the scales is much higher in people with AD and LT compared to those without. The ROC curves present us with an AUC with the three insulin resistance risk scales for the two dyslipidaemias studied with figures ranging between 0.856 and 0.991, which implies that the results are good/very good. CONCLUSIONS: A relationship between atherogenic dyslipidaemia and the three insulin resistance risk scales assessed is revealed, with higher IR mean values and prevalence in people with atherogenic dyslipidaemia and lipid triad. The three scales make it possible to adequately classify the presence of AD and LT. The highest AUC is presented by the triglycerides/HDL scale, with a result close to 1. METS-IR is the most recommended formula to estimate insulin resistance.

Risk factors and associated factors for calcaneal apophysitis (Sever's disease): a systematic review.

OBJECTIVES: The aim of this review was to identify the potential intrinsic and extrinsic risk factors (RFs), associated factors (AFs) and consequences of developing calcaneal apophysitis (CA). DESIGN: Systematic review. DATA SOURCES: Cochrane Library, Embase, Medline Ovid, PubMed, Web of Science and Evidence, searched from inception to April 2021. ELIGIBILITY CRITERIA: We included cohort, case-control and cross-sectional studies that were conducted in patients younger than 18 years who were exposed to RFs or who presented with factors associated with developing CA. Studies in languages other than English or Spanish were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers worked independently to evaluate the risk of bias of included studies. The Newcastle-Ottawa Scale (adapted version) was used. RESULTS: A total of 736 studies were identified and 11 observational studies fully met the inclusion criteria, including 1265 participants with a mean age of 10.72 years. Four studies identified extrinsic factors, 10 identified intrinsic factors and three identified both. The extrinsic and intrinsic RFs, AFs and consequences of CA include limitation of ankle dorsiflexion, foot alignment, stiffness and mobility of the midfoot, plantar pressures and ground reaction force, body mass index, age, gender, presence of other osteochondroses and practice of sport. The risk of bias varied, being either moderate or low. CONCLUSIONS: Regarding the factors and consequences associated with CA (Sever's disease), ankle dorsiflexion limitation is the most frequent intrinsic factor studied, followed by peak plantar pressures and foot malalignment. However, disagreements between the investigators of the included studies were found; in some cases, there is a lack of unanimity between different studies as to which factors are considered to be RFs, AFs and consequences. PROSPERO REGISTRATION NUMBER: CRD42021246366.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Dietary Intervention on Overweight and Obesity after Confinement by COVID-19.

BACKGROUND: Obesity has become a public health problem in our society and is associated with many diseases, including type 2 diabetes mellitus, cardiovascular diseases, dyslipidemia, respiratory diseases, and cancer. Several studies relate weight loss in obese patients to improved anthropometric measurements and cardiometabolic risk. The objective of our study was to evaluate anthropometric changes, analytical parameters, insulin resistance, fatty liver, and metabolic scales, after a personalized weight loss program, through dietary advice to increase adherence to the Mediterranean diet and a motivational booster via mobile SMS messaging. METHODS: Intervention study on a sample of 1964 workers, in which different anthropometric parameters were evaluated before and after dietary intervention: the metabolic score of insulin resistance; non-alcoholic fatty liver disease using different scales; metabolic syndrome; atherogenic dyslipidemia; and the cardiometabolic index. A descriptive analysis of the categorical variables was performed, by calculating the frequency and distribution of the responses for each one. For quantitative variables, the mean and standard deviation were calculated, since they followed a normal distribution. Bivariate association analysis was performed by applying the chi-squared test (corrected by Fisher's exact statistic when conditions required it) and Student's t-test for independent samples (for comparison of means). RESULTS: The population subjected to the Mediterranean diet improved in all the variables evaluated at 12 months of follow-up and compliance with the diet. CONCLUSIONS: Dietary advice on a Mediterranean diet and its reinforcement with reminder messages through the use of mobile phones may be useful to improve the parameters evaluated in this study and reduce the cardiometabolic risk of patients.

Waist Circumference Is an Essential Factor in Predicting Insulin Resistance and Early Detection of Metabolic Syndrome in Adults.

BACKGROUND: Metabolic syndrome (Met-S) is considered one of the most important health problems of the 21st century. It includes a group of metabolic disorders that increase the risk of cardiovascular diseases such as overweight and obesity, elevated lipid profile and blood pressure and insulin resistance (IR). Based on the information mentioned above in which there seems to be a relationship between IR and Met-S, the objective of this work was twofold: on the one hand, to assess the relationship between the values of different insulin resistance risk scales and Met-S determined with three different scales, and on the other, to determine whether any of the components of Met-S predispose more to the appearance of IR. METHODS: A descriptive cross-sectional study of 418,343 workers. Waist circumference was measured and evaluated together with six formulas to assess the insulin resistance index. Categorical variables were evaluated by calculating the frequency and distribution of each one. For quantitative variables, mean and standard deviation were determined, and Student's t-test was applied, while for qualitative variables, the chi-square test was performed. The usefulness of the different risk scales for insulin resistance for predicting metabolic syndrome was evaluated using ROC curves, the area under the curve (AUC), as well as their cut-off points for sensitivity, specificity, and the Youden index. RESULTS: People with metabolic syndrome applying any criteria had higher values in the IR risk scales. The different IR scales made it possible to adequately classify people with metabolic syndrome. Of the three definitions of Met-S, the one that showed the greatest relationship with IR was IDF. CONCLUSIONS: Most risk scales for insulin resistance enable the presence of metabolic syndrome to be adequately classified, finding the best ones if the International Diabetes Federation (IDF) criteria are applied. Of the elements included in the Met-S, the one that seems to increase the risk of presenting IR the most is waist circumference; hence, the Met-S definition that is most related to IR is that of the IDF, which is the only one of the three in which a high value of waist circumference is necessary to be able to diagnose Met-S. Waist circumference can be considered the central essential component for detecting insulin resistance and, therefore, the early detection of metabolic syndrome.

Comparative study between nail retraining with gauze bandaging and the nail remodeling with acrylics as a conservative treatment for stage I and IIa onychocryptosis.

OBJECTIVE: Onychocryptosis is one of the most prevalent onychopathies, being a frequent reason for consultation in podiatric clinical practice. Conservative treatments are the first therapeutic choice, with nail remodeling using clotrimazole gel emerging as an alternative, although its medium-term effectiveness is unknown. The objective of this study was therefore to compare the efficacy of the technique of nail retraining using gauze bandaging with that of nail remodeling for the conservative treatment of stage I and IIA onychocryptosis. METHODS: An analytical, randomized clinical trial study was performed following a longitudinal and prospective design. A sample was selected of 20 subjects presenting stage I and IIA onychocryptosis. Of these, 10 cases formed the group of nail retraining using gauze bandaging, and the other 10 the nail remodeling group. The presence of recurrence in a 3-month period was evaluated. RESULTS: Before the intervention, the patients in the retraining group presented pain of 6.7 ± 1.9 vs. 6.8 ± 1.6 in the remodeling group, with no significant difference between the two (p = 0.900). After the 3-month follow-up period, seven of the retraining group patients presented recurrence of onychocryptosis vs. only one in the remodeling group. CONCLUSION: The technique of nail remodeling has a lower recurrence rate than that of nail retraining with gauze bandaging, with the pain, inflammation, and infection reported being less, and with greater patient satisfaction.

Implementing Horizon Scanning as a tool for the strategic development of regulatory guidelines for nanotechnology-enabled health products.

Strategic regulatory development is essential to ensure that new innovations in nanotechnology-enabled health products (NHPs) successfully reach the market and benefit patients. Currently, the lack of specific regulatory guidelines for NHPs is considered one of the primary causes of the so-called "valley of death" in these products, impacting both current and future advancements. In this study, we have implemented a methodology to anticipate key trends in NHP development and compare them with the current regulatory landscape applicable to NHPs. This methodology relies on Horizon Scanning, a tool commonly used by policymakers to foresee future needs and proactively shape a regulatory framework tailored to those needs. Through the application of this methodology, different trends in NHP have been identified, notably NHPs for drug delivery and dental applications. Furthermore, the most disruptive elements involve NHPs that are multicomposite and multifunctional, harnessing nano-scale properties to combine therapeutic and diagnostic purposes within a single product. When compared with the regulatory landscape, current regulations are gradually adapting to accommodate emerging trends, with specific guidelines being developed. However, for the most disruptive elements, multicomposite and multifunctional NHPs, their novelty still poses significant regulatory challenges, requiring a strategic development of guidelines by regulatory agencies to ensure their safe and effective integration into healthcare practices. This study underscores the importance of proactive regulatory planning to bridge the gap between NHP innovation and market implementation.

Quantification of glycated hemoglobin and glucose in vivo using Raman spectroscopy and artificial neural networks.

Undiagnosed type 2 diabetes (T2D) remains a major public health concern. The global estimation of undiagnosed diabetes is about 46%, being this situation more critical in developing countries. Therefore, we proposed a non-invasive method to quantify glycated hemoglobin (HbA1c) and glucose in vivo. We developed a technique based on Raman spectroscopy, RReliefF as a feature selection method, and regression based on feed-forward artificial neural networks (FFNN). The spectra were obtained from the forearm, wrist, and index finger of 46 individuals. The use of FFNN allowed us to achieve an error in the predictive model of 0.69% for HbA1c and 30.12 mg/dL for glucose. Patients were classified according to HbA1c values into three categories: healthy, prediabetes, and T2D. The proposed method obtained a specificity and sensitivity of 87.50% and 80.77%, respectively. This work demonstrates the benefit of using artificial neural networks and feature selection techniques to enhance Raman spectra processing to determine glycated hemoglobin and glucose in patients with undiagnosed T2D.

Controlled nano-agglomerates as stabile SERS reporters for unequivocal labelling.

Biosensors, especially those with a SERS readout, are required for an early and precise healthcare diagnosis. Unreproducible SERS platforms hamper clinical SERS. Here we report a synthetic procedure to obtain stabile, reproducible and robust highly-SERS performing nanocomposites for labelling. We controlled the NPs agglomeration and codification which resulted in an increased number of hot spots, thus exhibiting reproducible and superior Raman enhancement. We studied fundamental aspects affecting the plasmonic thiol bond resulting in pH exhibiting a determining role. We validated their biosensing performance by designing a SERS-based detection assay model for SARS-CoV-2. The limit of detection of our assay detecting the spike RBD was below 10 ng/mL.