Clinical and Epidemiological Characteristics of Patients Being Treated for Scabies in Spain: Opportunities for Improvement - A Multicenter Cross-Sectional CLINI-AEDV Study. / Características clínicas y epidemiológicas de pacientes diagnosticados de escabiosis en España: oportunidades de mejora. Estudio transversal multicéntrico CLINI-AEDV.

BACKGROUND: Several studies support the hypothesis that scabies is on the rise in Spain. There are also concerns about the possible development of resistance to treatment and an increase in atypical presentations. The aims of this study were to describe the demographic and clinical characteristics of patients with scabies seen by dermatologists in Spain, to identify the possible emergence of atypical forms of scabies, and to explore the frequency of treatment failures and associated risk factors. METHODS: We conducted an observational, cross-sectional, multicenter study of data collected prospectively in April and May 2023 using the CLINI-AEDVp platform created by the Spanish Academy of Dermatology and Venereology (AEDV). RESULTS: Participating dermatologists from 31 hospitals in 15 of Spain's autonomous communities recorded 186 cases of active scabies (51% in women) during the study period. A diagnostic certainty level of A, B or C as per the International Alliance for the Control of Scabies Consensus Criteria was required for diagnosis. Overall, 92% of patients had typical scabies and 66% had already been treated with a scabicide for the current episode. Of the treated patients, only 36% had received and completed adequate treatment (including the simultaneous treatment of all household members) and 50% had not received clear written recommendations. CONCLUSIONS: In a high proportion of the cases of scabies studied, the patient had already received treatment. In those cases, we observed several remediable shortcomings that could explain why some of these treatments had failed. Remedying these deficiencies should lead to better control of scabies and an improved assessment of the actual effectiveness of currently available scabicides.

[Translated article] Clinical and Epidemiological Characteristics of Patients Being Treated for Scabies in Spain: Opportunities for Improvement - A Multicenter Cross-Sectional CLINI-AEDV Study.

BACKGROUND: Several studies support the hypothesis that scabies is on the rise in Spain. There are also concerns about the possible development of resistance to treatment and an increase in atypical presentations. The aims of this study were to describe the demographic and clinical characteristics of patients with scabies seen by dermatologists in Spain, to identify the possible emergence of atypical forms of scabies, and to explore the frequency of treatment failures and associated risk factors. METHODS: We conducted an observational, cross-sectional, multicenter study of data collected prospectively in April and May 2023 using the CLINI-AEDVp platform created by the Spanish Academy of Dermatology and Venereology (AEDV). RESULTS: Participating dermatologists from 31 hospitals in 15 of Spain's autonomous communities recorded 186 cases of active scabies (51% in women) during the study period. A diagnostic certainty level of A, B or C as per the International Alliance for the Control of Scabies Consensus Criteria was required for diagnosis. Overall, 92% of patients had clinical features of classic scabies and 66% had already been treated with a scabicide for the current episode. Of the treated patients, only 36% had received and completed adequate treatment (including the simultaneous treatment of all household members) and 50% had not received clear written recommendations. CONCLUSIONS: In a high proportion of scabies cases, the patient has already received treatment. In those cases, we observe several remediable shortcomings that could explain why some of these treatments fail. Remedying these deficiencies should lead to better control of scabies and an improved assessment of the actual effectiveness of currently available scabicides.

Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Prussian Blue: A Nanozyme with Versatile Catalytic Properties.

Nanozymes, nanomaterials with enzyme-like activities, are becoming powerful competitors and potential substitutes for natural enzymes because of their excellent performance. Nanozymes offer better structural stability over their respective natural enzymes. In consequence, nanozymes exhibit promising applications in different fields such as the biomedical sector (in vivo diagnostics/and therapeutics) and the environmental sector (detection and remediation of inorganic and organic pollutants). Prussian blue nanoparticles and their analogues are metal-organic frameworks (MOF) composed of alternating ferric and ferrous irons coordinated with cyanides. Such nanoparticles benefit from excellent biocompatibility and biosafety. Besides other important properties, such as a highly porous structure, Prussian blue nanoparticles show catalytic activities due to the iron atom that acts as metal sites for the catalysis. The different states of oxidation are responsible for the multicatalytic activities of such nanoparticles, namely peroxidase-like, catalase-like, and superoxide dismutase-like activities. Depending on the catalytic performance, these nanoparticles can generate or scavenge reactive oxygen species (ROS).

Severe hidradenitis suppurativa complicated by renal AA amyloidosis.

Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease affecting the skin folds. Multiple therapeutic options have been proposed for severe cases, but persistent responses are rarely seen. Important complications of HS are uncommon, and usually seen only in severe and unresponsive disease. Amyloid A (AA) amyloidosis is secondary to inflammatory chronic diseases, and is an uncommon complication of dermatological diseases. Only a few cases related with HS have been reported. We report the case of a 37-year-old patient who developed AA amyloidosis secondary to severe HS.

Modification of FP-HIV activity by peptide sequences of GB virus C: a biophysical approach.

Three synthetic peptide sequences of 18 amino acid each, corresponding to different fragments of the E2 capsid protein of GB virus C (GBV-C): SDRDTVVELSEWGVPCAT (P45), GSVRFPFHRCGAGPKLTK (P58) and RFPFHRCGAGPKLTKDLE (P59) have been characterized in order to find a relationship between their physicochemical properties and the results obtained in cellular models. Experiments were performed in presence and absence of the HIV fusion peptide (FP-HIV) due to the evidences that GBV-C inhibits AIDS progression. P45 peptide showed lower surface activity and less extent of penetration into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) (3:2, mol/mol) lipid monolayers than P58 and P59. However, P45 peptide presented higher capacity to inhibit FP-HIV induced cell-cell fusion than the other two sequences. These results were supported by fluorescence anisotropy measurements which indicated that P45 had a significant effect on the inhibition of FP-HIV perturbation of liposomes of the same lipid composition. Finally, atomic force microscopy (AFM) studies have evidenced the modification of the changes induced by the FP-HIV in the morphology of lipid bilayers when P45 was present in the medium.

Miscibility and Langmuir Studies of the Interaction of E2 (279-298) Peptide Sequence of Hepatitis G Virus/GB Virus-C with Dipalmitoylphosphatidyl Choline and Dimiristoylphosphatidyl Choline Phospholipids.

Mixed monolayers of E2(279-298), a synthetic peptide belonging to the structural protein E2 of the GB virus C (GBV-C), formerly know as hepatitis G virus (HGV), and the phospholipids dipalmitoylphosphatidyl choline (DPPC) and dimiristoylphosphatidyl choline (DMPC),which differ in acyl chains length, were obtained at the A/W interface (monolayers of extension) in order to provide new insights on E2/phospholipids interaction. Analysis of the surface pressure-area isotherms, Brewster angle microscopy images, relative thickness, and mean areas per molecule has allowed us to establish the conditions under which the mixed components of the monolayer are miscible or immiscible and know how the level of the E2/phospholipid interaction varies with the composition of the mixed films, the surface pressure, and the hydrocarbon chains length of the phospholipids. The steric hindrance caused by the penetration of the polymer strands into the more or less ordered hydrocarbon chains of the phospholipids was suggested to explain the differences in the peptide interaction with the phospholipids studied. Therefore, the novelty of results obtained with the Langmuir film balance technique, supplemented with BAM images allow us to achieve a deeper understanding of the interaction.

Retrospective study of pilomatricoma: 261 tumors in 239 patients.

INTRODUCTION AND OBJECTIVES: Pilomatricoma is the second most common skin tumor in childhood and youth and it has a broad differential diagnosis. The main objective of the present study was to determine the incidence of pilomatricomas in our hospital and to analyze the following variables: patient age and sex, tumor site, symptoms, previous trauma, clinical diagnosis, associated diseases, number of cases of multiple tumors, ultrasound findings, anesthetic and surgical techniques, and postoperative complications. MATERIAL AND METHOD: This was a retrospective study of the pilomatricomas surgically excised between January 2004 and December 2012 and registered in the database of the pathology department of our hospital. RESULTS: We found 261 pilomatricomas in 239 patients (120 female and 119 male) between 1 and 83 years of age (mean age, 26.4 years). The most common presentation was as a firm subcutaneous nodule, which was asymptomatic in 82% of cases. Tumors most commonly affected the head and neck (49.81%). Preoperative diagnosis was correct in 54.4% of cases, concomitant diseases were present in 59 cases, and 7 patients reported a history of trauma in the area of the tumor. There were 17 cases of multiple tumors, 1 case in a patient with familial disease and 2 in patients with Steinert disease. Soft-tissue ultrasound was performed on 57 lesions; images were compatible with pilomatricoma in 48 cases. Tumor excision was performed under local anesthesia in 185 cases and under local and general anesthesia in 76. The postoperative complications were hypertrophic scarring and wound dehiscence (1 case each). CONCLUSIONS: This was a retrospective study with the largest series recorded in Spain and with one of the highest incidences. In addition, we report on variables not described in other studies.

Effect of E1(64-81) hepatitis G peptide on the in vitro interaction of HIV-1 fusion peptide with membrane models.

One way to gain information about the fusogenic potential of virus-derived synthetic peptides is to examine their interfacial properties and subsequently to study them in monolayers and bilayers. Here, we characterize the physicochemical surface properties of the peptide E1(64-81), whose sequence is AQLVGELGSLYGPLSVSA. This peptide is derived from the E1 structural protein of GBV-C/HGV which was previously shown to inhibit leakage of vesicular contents caused by the HIV-1 fusion peptide (HIV-1 FP). Mixed isotherms of E1(64-81) and HIV-1 FP were obtained and their Brewster angle microscopy (BAM) and atomic force microscopy (AFM) images showed that the peptide mixture forms a different structure that is not present in the pure peptide images. Studies with lipid monolayers (1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG)) show that both peptides interact with all the lipids assayed but the effect that HIV-1 FP has on the monolayers is reduced in the presence of E1(64-81). Moreover, differential scanning calorimetry (DSC) experiments show the capacity of HIV-1 FP to modify the properties of the bilayer structure and the capacity of E1(64-81) to inhibit these modifications. Our results indicate that E1(64-81) interacts with HIV-1 FP to form a new structure, and that this may be the cause of the previously observed inhibition of the activity of HIV-1 FP by E1(64-81).

Study of the inhibition capacity of an 18-mer peptide domain of GBV-C virus on gp41-FP HIV-1 activity.

The peptide sequence (175-192) RFPFHRCGAGPKLTKDLE (P59) of the E2 envelope protein of GB virus C (GBV-C) has been proved to decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner. Based on these previous results, the main objective of this study was to deepen in the physicochemical aspects involved in this interaction. First, we analyzed the surface activity of P59 at the air-water interface as well as its interaction with zwitterionic or negatively charged lipid monolayers. Then we performed the same experiments with mixtures of P59/gp41-FP. Studies on lipid monolayers helped us to understand the lipid-peptide interaction and the influence of phospholipids on peptide penetration into lipid media. On another hand, studies with lipid bilayers showed that P59 decreased gp41-FP binding to anionic Large Unilamellar Vesicles. Results can be attributed to the differences in morphology of the peptides, as observed by Atomic Force Microscopy. When P59 and gp41-FP were incubated together, annular structures of about 200 nm in diameter appeared on the mica surface, thus indicating a peptide-peptide interaction. All these results confirm the gp41-FP-P59 interaction and thus support the hypothesis that gp41-FP is inhibited by P59.

Phospholipid bilayer-perturbing properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes.

Amino acid-based surfactants constitute an important class of natural surface-active biomolecules with an unpredictable number of industrial applications. To gain a better mechanistic understanding of surfactant-induced membrane destabilization, we assessed the phospholipid bilayer-perturbing properties of new cationic lysine-based surfactants. We used erythrocytes as biomembrane models to study the hemolytic activity of surfactants and their effects on cells' osmotic resistance and morphology, as well as on membrane fluidity and membrane protein profile with varying pH. The antihemolytic capacity of amphiphiles correlated negatively with the length of the alkyl chain. Anisotropy measurements showed that the pH-sensitive surfactants, with the positive charge on the α-amino group of lysine, significantly increased membrane fluidity at acidic conditions. SDS-PAGE analysis revealed that surfactants induced significant degradation of membrane proteins in hypo-osmotic medium and at pH 5.4. By scanning electron microscopy examinations, we corroborated the interaction of surfactants with lipid bilayer. We found that varying the surfactant chemical structure is a way to modulate the positioning of the molecule inside bilayer and, thus, the overall effect on the membrane. Our work showed that pH-sensitive lysine-based surfactants significantly disturb the lipid bilayer of biomembranes especially at acidic conditions, which suggests that these compounds are promising as a new class of multifunctional bioactive excipients for active intracellular drug delivery.

Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide.

Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research.

[Impact of hygienic and social distancing measures against SARS-CoV-2 on respiratory infections caused by other viruses]. / Impacto de las medidas higiénicas y de distanciamiento social frente al SARS-CoV-2 sobre las infecciones respiratorias causadas por otros virus.

OBJECTIVE: To control the pandemic caused by SARS-CoV-2, the implementation of social and hygienic confinement measures was determined in all countries. These measures reduce the circulation of most respiratory viruses that are transmitted preferentially by air and contact. METHODS: The impact of these measures on non-Covid respiratory viruses during the period August-December 2020 and 2019 has been comparatively analyzed. To all nasopharyngeal aspirates that were negative against SARS-CoV-2 by RT-PCR and the suspicion of acute respiratory infection persisted, were subjected to a new RT-PCR that simultaneously and differentially amplifies 21 different respiratory viruses. RESULTS: In the year of the pandemic, a 36.6% decrease was detected in the number of respiratory samples studied and 66% in their positivity in relation to 2019. All viruses showed reduction percentages of between 40-100%. The only viruses that circulated during and after national lockdown were rhinovirus (74.1%), adenovirus (10.1%), and enterovirus (9.6%). CONCLUSIONS: The measures used to control the SARS-CoV-2 infection have also affected the community circulation of most respiratory viruses including influenza and respiratory syncytial virus.

Granulosa cell tumor and endometrial cancer: a case report and review of the literature.

Granulosa cell tumors (GCTs) of the ovary are an uncommon type of ovarian cancer, representing only 2-5%. Frequently, their tumoral cells present some features of normal granulosa cells, like hormonal production. As a consequence, this neoplasia can be diagnosed either by common ovarian cancer symptoms or endometrial pathologies due to an estrogenic effect. Symptoms caused by estrogen production can also give rise to different clinical manifestations depending on whether they appear in postmenopausal or young women. In the case we present below, a patient was referred for presenting postmenopausal bleeding of one year's duration. Once endometrial cancer was diagnosed and subsequently staged, an ovarian mass was detected. We report an atypical case of ovarian cancer with the aim of reviewing the clinical features of GCT, as well as its prognosis, treatment and follow-up recommendations, according to the available literature.

Fluorescence study of the dynamic interaction between E1(145-162) sequence of hepatitis GB virus C and liposomes.

The physicochemical characterization of the peptide sequence E1(145-162) corresponding to the structural protein E1 of the hepatitis G virus was done by studying its interaction with model membranes. Small unilamellar vesicles (SUVs) of dimyristoylphosphatidylglycerol or dimyristoylphosphatidylcholine were chosen as mimetic membranes. Peptide incorporation and location in the phospholipid bilayer was investigated by fluorescence anisotropy with SUVs labeled with diphenylhexatriene (DPH) or trimethylammonium-DPH. The addition of the peptide E1(145-162) showed significant changes in the anisotropy values of the probe located at the air/water interface. These results indicate that the peptide E1(145-162) preferably interacts with the lipid surface without penetrating inside the bilayer. A series of fluorescence experiments based on tryptophan peptide fluorescence were modeled by means of multivariate curve resolution-alternating least squares (MCR-ALS) algorithm to further study the peptide interaction with bilayers at different temperatures. The preliminary results obtained with MCR-ALS showed how the peptide concentration decay is directly linked to the appearance of a new specie, which corresponds to the lipid-peptide binding. These results provide useful information for the design of synthetic immunopeptides that can be incorporated into a liposomal system with potential to promote a direct delivery of the membrane-incorporated immunogen to the immunocompetent cells, thus increasing the immuno response from the host.

Prognostic factors for the development of vaginal intraepithelial neoplasia.

OBJECTIVE: To identify risk factors for the appearance of vaginal intraepithelial neoplasia (VAIN). MATERIAL AND METHODS: A total of 485 women with abnormal cytologies were followed over three years (2003-2006). They underwent cytolology and colposcopy, and testing for human papillomavirus virus (HPV) infection. If the colposcopy was atypical, a biopsy was performed. RESULTS: A total of 256 women were treated: 161 by cone biopsy, 103 by LLETZ, 12 by repeat conization, and 44 by total hysterectomy. In eight cases VAIN was diagnosed following hysterectomy. The average age at which VAIN appeared was 49.8 years (age range 39-61). Hysterectomy was indicated in two cases of cervical cancer, four cases of persistent high-grade cervical SIL, and two cases of recurrent high-grade cervical SIL. The mean time for the appearance of VAIN following hysterectomy was 3.8 years (range 1-9 years). Of these eight women, seven had HPV infections at high risk for carcinogenesis. CONCLUSIONS: Long-term follow-up cytology is necessary for women treated for high-grade SIL, even after hysterectomy, because of the increased risk of a primary vaginal VAIN lesion, especially in women with high-risk HPV infection.

Dual responsive gelatin-based nanoparticles for enhanced 5-fluorouracil efficiency.

The very slow progress in the therapeutic efficacy of the treatment of severe diseases has suggested the use of a growing need for a multidisciplinary approach to the delivery of therapeutics to targets tissues. There has been increasing effort in the design of stimuli-responsive nanomaterials that they will be developed into effective drug delivery vehicles. Most commonly, effective drug delivery is associated with nanomaterial-facilitated accumulation and/or cellular internalization. Recent studies in our lab have demonstrated that gelatin-based NPs can be considered suitable pH responsive devices for the effective intracellular delivery of drugs. Concerning cancer treatment, ligands recognizing tumour-associated antigens expressed on the surface of the tumour cells have been employed. Some of the target structures suitable for tumour targeting belong to integrins which mediate cell adhesion to extracellular matrix and other cells. Interestingly, gelatin chains contain motifs such as RGD sequences that can be recognised by integrins. In this work the inclusion of the anticancer drug 5-fluorouracil (5-FU) on these gelatin-based NPs has been projected. These NPs may provide an opportunity to increase the therapeutic effect using a dual approach by: i) targeting the therapeutic drug to the tumour cells by the action of the naturally occurring RGD-motif on gelatin and ii) minimizing the non-productive trafficking from endosomes to lysosomes by releasing the cargo using the charge reversal approach after cellular internalization. In vitro cytotoxicity experiments of NPs on tumoral and non-tumoral cell lines have reported selectivity indexes higher than 30 demonstrating a great selectivity on the mode of action as a function of the cell line and the imposed compositions.

Disturbance of erythrocyte lipid bilayer by amino acid-based surfactants.

In an attempt to increase our knowledge regarding the mechanisms of surfactant membrane interaction, we studied the action of several anionic and cationic amino acid-based surfactants on membrane fluidity using fluorescence anisotropy. Anisotropy measurements demonstrated that almost all of the surfactants studied disturbed the external region of the erythrocyte membrane without affecting the core of the bilayer. How the physico-chemical properties and structure of these compounds affect dynamics of the lipid bilayer is discussed in detail.