Cervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16 prevalence and vaccination impact.

INTRODUCTION: The etiology of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) can influence the efficacy of Public Health preventive strategies. This study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of bivalent vaccination, and the distribution of HPV 16 in squamous lesions. MATERIAL AND METHODS: Ninety-four histologically confirmed cases of CIN2+ (2009-2010) were retrospectively studied: 23 CIN2, 58 CIN3- squamous carcinoma in situ (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany) was performed on the cervical specimens. Bivalent vaccination impact was calculated, based on regional vaccination coverage data, local HR-HPV prevalence, and reported efficacy (direct and cross-protection) of the vaccine. RESULTS: HR-HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8-58.2%) and HPV 31 (9.3%-12.1%), considering single infections or single-multiple infections, respectively (hierarchical attribution). In squamous lesions, HPV 16 prevalence in women younger than 45 years of age increased in severe lesions (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or by 62.7% (direct and cross-protection). CONCLUSION: HPV vaccination could have a great impact in women younger than 45 years of age due to the high prevalence of HPV 16 in their lesions.

Open clinical trial evaluating the efficacy of a novel eyelash growth enhancer with peptides and glycosaminoglycans.

BACKGROUND: Eyelashes play a crucial role in self-image and ocular protection. Enhancements to their structure are of both cosmetic and clinical interest. AIMS: To assess the efficacy of a peptide and glycosaminoglycan-based eyelash enhancer serum in improving eyelash structure. PATIENTS/METHODS: This open-label clinical trial involved 30 females aged 25-65. Eyelashes were assessed at baseline (D0), 4 weeks (D28), and 12 weeks (D84) using specialized software and high-resolution imagery. Measurements included lash number, width, length, volume, arc, and angle. RESULTS: At 12 weeks, significant increases were observed in lash length (+8.3%), number (+5%), width (+10.1%), volume (+14.1%), arc (+13.4%), and angle (+28.3%) compared to baseline. Global Eyelash Assessment (GEA) scores significantly improved, and patient treatment satisfaction increased from 73.34% at D28 to 84.33% at D84. No adverse effects were reported. CONCLUSIONS: The eyelash growth enhancer serum demonstrated significant efficacy in improving eyelash structure by Week 12, with early signs of improvement evident by Week 4. The high patient satisfaction levels underscore the perceived effectiveness of the product.

Human papillomavirus (HPV) E6/E7 mRNA as a triage test after detection of HPV 16 and HPV 18 DNA.

High-risk human papillomavirus (HPV) DNA detection provides high sensitivity but low specificity for moderate-grade cervical intraepithelial neoplasia or worse histological identification. A prospective study evaluated mRNA testing efficacy for predicting this histological diagnosis in case of HPV 16 and/or 18 DNA detection. A total of 165 endocervical samples harboring HPV 16 and/or 18 DNA were tested with NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux, Marcy l´Etoile, France). Women with cytological alterations were referred to colposcopy (n = 111). Moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 25.8% of women presenting atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions and in 89.8% of women with high-grade squamous intraepithelial lesions. mRNA sensitivity was 81.3% and 84.1%, respectively. Specificity was 52.2%, and 80.0%, respectively. Negative predictive value (NPV) was 88.9% in undetermined or low-grade squamous lesions. Positive predictive value (PPV) was 97.4% in high-grade squamous lesions. mRNA reduced colposcopies by 44.3% in undetermined or low-grade squamous lesions. Direct treatment of mRNA-positive cases reduced 77.5% of colposcopies in high-grade squamous lesions. Women without cytological alterations were followed for 18 months (n = 35), and moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 34.3%; mRNA sensitivity and specificity were 83.3% and 86.9%, respectively. PPV and NPV were 76.9% and 90.9%, respectively for predicting moderate-grade cervical intraepithelial neoplasia or worse in 18 months. mRNA reduced the number of visits for follow-up in 62.2%. In conclusion, NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux) can serve as a triage test in case of HPV 16 and/or 18 DNA detection.

[Vaccination coverage, beliefs, and attitudes in transplanted children and adolescents: a mixed-methods systematic review.] / Cobertura vacunal, creencias y actitudes en niños y adolescentes trasplantados: una revisión sistemática de métodos mixtos.

OBJECTIVE: Vaccine-preventable infectious diseases are a cause of morbidity and mortality in transplanted children. The main objective of this study was to synthesize the available evidence of vaccination coverage in children and adolescents who are candidates or transplant recipients and to analyze beliefs, attitudes, and experiences about vaccination. METHODS: A mixed-methods systematic review was performed (Open Science Framework registration: https://osf.io/auqn3/). Searches were conducted in PubMed/MEDLINE, EMBASE, IBECS and LILACS (from January 2000 to August 2021) and in gray literature. Quantitative and qualitative studies reported information on coverage, beliefs, attitudes and/or experiences about recommended vaccines in children who are candidates or recipients of solid organ or hematopoietic progenitor transplantation. Quality assessment was undertaken using Mixed Methods Appraisal Tool (MMAT). A narrative synthesis of the studies was carried out. RESULTS: A total of thirty-two studies in thirty-five publications were included. The most studied interventions were vaccines against measles (n=21; 66%) and hepatitis B (n=20; 62%). Vaccination rates showed a high variability for the most represented vaccines (specifically, 2%-100% for measles, 0.4%-100% for hepatitis B, diphtheria-tetanus-pertussis and rubella), with coverages lower than 90% in at least 70% of the studies. The lowest rates were reported in post-transplantation and hematopoietic stem cell transplantation. Only one qualitative study was identified reporting information on beliefs and/or attitudes, although nine quantitative studies explored cognitive aspects. CONCLUSIONS: This review shows a high variability in vaccination coverage in children and adolescents who are transplant candidates or recipients, with rates lower than those recommended. Further studies would be needed to identify beliefs and attitudes about immunization in this context.

OBJETIVO: Las enfermedades infecciosas prevenibles mediante vacunación son una causa de morbilidad y mortalidad en niños trasplantados. El objetivo principal de este estudio fue sintetizar la evidencia disponible de la cobertura vacunal en niños y adolescentes candidatos o receptores de trasplante y analizar las creencias, actitudes y experiencias acerca de la vacunación. METODOS: Se realizó una revisión sistemática de métodos mixtos (registro Open Science Framework: https://osf.io/auqn3/). Se llevaron a cabo búsquedas en PubMed/MEDLINE, EMBASE, IBECS y LILACS (desde enero de 2000 hasta agosto de 2021) y en literatura gris. Los estudios cuantitativos y cualitativos informaron sobre cobertura, creencias, actitudes y/o experiencias con respecto a cualquier vacuna recomendada en niños candidatos o receptores de trasplante de órganos sólidos y/o progenitores hematopoyéticos. Se evaluó la calidad metodológica mediante la herramienta MMAT (Mixed Methods Appraisal Tool). Se llevó a cabo una síntesis narrativa de los estudios. RESULTADOS: Se incluyeron treinta y dos estudios disponibles en treinta y cinco publicaciones. Las intervenciones más estudiadas fueron las vacunas frente a sarampión (n=21; 66%) y hepatitis B (n=20; 62%). Las tasas de inmunización mostraron una alta variabilidad para las vacunas más representadas (concretamente, 2%-100% en sarampión, 0,4%-100% en hepatitis B, difteria-tétanos-tosferina y rubeola), con coberturas inferiores al 90% en al menos el 70% de los estudios. Los valores más bajos se registraron en situación postrasplante y trasplante de progenitores hematopoyéticos. Sólo se identificó un estudio cualitativo que incluyó información sobre creencias y/o actitudes, aunque nueve estudios cuantitativos exploraron aspectos cognitivos. CONCLUSIONES: Esta revisión muestra una elevada variabilidad en la cobertura vacunal de niños candidatos o receptores de trasplante, con cifras generalmente inferiores a las recomendadas. Sería necesario desarrollar más estudios que contribuyan a identificar creencias y actitudes sobre inmunización en este contexto.

[Impact of vaccination against SARS-CoV-2 on the incidence of infection in school settings]. / Impacto de la vacunación contra SARS-CoV-2 en la incidencia de infección en ámbito escolar.

Background: The SARS-CoV-2 pandemic affected the school-aged population because of the disease itself and due to the measures applied for prevention and control of the infection. The aim of the study was to evaluate the effect of population-based vaccination against COVID-19 on the incidence of infection in school settings. Material and Methods: A retrospective descriptive study of COVID-19 cases and school outbreaks was carried out at the province level. Students, teachers and staff from different educational stages of the schools were included. The outcome measure was the incidence according to educational stage, case profile and clinic during the first of the academic year 2020/2021 versus the same period 2021/2022. Results: The total incidence of SARS-CoV-2 in classrooms was 2,470 cases per 100,000 population in the first trimester of the academic year 2020/2021 and 2,720 cases per 100,000 population in the same period 2021/2022. The number of reported school outbreaks was 7 times higher in this second period; and the risk of infection in classrooms over 12 years of age (students and teachers) was reduced by 43.1% (vaccinated in high percentage). Conclusions: This study shows a reduction in transmission of SARS-CoV-2 infection in students of higher educational stages (secondary and high school) during the first of the academic year 2021/2022 (group with high vaccination coverage at the beginning of the period) compared to the previous school year (without vaccination).

Histopathology and immunohistochemistry of cutaneous lupus erythematosus after pulsed dye laser treatment.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disorder with a wide range of skin manifestations. Current treatment options include topical and systemic approaches. Few controlled prospective studies have been performed using the pulsed dye laser (PDL). Based on previous experience that supported the efficacy of PDL treatment of CLE, we decided to study the histological changes induced by PDL. OBSERVATIONS: A prospective study was performed on nine patients with histologically confirmed CLE treated with PDL. Biopsies were taken before, immediately after, and 4 weeks after treatment and stained with hematoxylin and eosin and with commercially available antibodies to intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1. Evaluation after PDL treatment showed a significant reduction of the dermal lymphocytic infiltrate in six of nine patients (66.7%) and an important reduction of the basal damage in six of seven patients (85.7%). Other epidermal changes improved in four of six patients (66.7%). Mucin deposition persisted in two patients. ICAM and VCAM expression was reduced in seven of seven patients (100%) and five of six patients (83.3%) (p<.05). Clinical improvement was present in eight of nine patients (88.9%), without side effects. CONCLUSIONS: PDL therapy is an effective treatment for CLE. Immunohistologic improvement has been confirmed in this study.

Angiolymphoid hyperplasia with eosinophilia treated with vascular laser.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia is a rare, benign disorder characterized by reddish-brown nodules and plaques in the dermis and the subcutaneous tissues, typically occurring on the neck and head. Surgical excision, corticosteroids, radiotherapy, and other therapies have been used, however, recurrences are common. Treatment with vascular lasers such as pulsed dye laser (PDL) or Nd:YAG seems to be a promising therapeutic option. OBJECTIVE: To assess the efficacy and safety of PDL and combined sequential PDL-Nd:YAG laser in patients with ALHE. METHODS: Three patients with ALHE were treated with PDL at 595-nm wavelength or with a combined sequential application of 595-nm PDL and 1,064-nm Nd:YAG wavelengths. Topical anesthetic was applied before laser treatment. RESULTS: Complete resolution of the lesions was achieved in two patients with ALHE; a partial response was seen in one patient. No significant side-effects were reported. CONCLUSIONS: We consider that PDL should be a first-line therapy for AHLE. Sequential application of PDL and Nd:YAG laser seems to show promising results, so it could be an interesting new treatment option.

Letter: Cerebriform intradermal nevus presenting as secondary cutis verticis gyrata.

Cutis verticis gyrata is a rare skin condition characterized by ridges and furrows resembling the surface of the brain. It can be considered as a manifestation of a variety of diverse causes such as cerebriform intradermal nevus. We report a 48-year-old man with cerebriform and soft folds on the left parietal and temporal areas. Histology showed solitary or clusters of nevus cells in the dermis. The diagnosis of cerebriform intradermal nevus was confirmed.

Water Ultrasound-Assisted Extraction of Polyphenol Compounds from Brewer's Spent Grain: Kinetic Study, Extract Characterization, and Concentration.

Brewer's spent grain (BSG) was chemically characterized obtaining 52.1% of carbohydrates, 17.8% protein, 5.9% lipids, 13.5% insoluble lignin and 24.3% of water-soluble extractives. This work has been focused on the study of polyphenol extraction of the extractive fraction by water ultrasound-assisted extraction. Selected extraction conditions were 47 °C and 21.7 mL water/gdry-BSG. The effect of solvent polarity on polyphenol extraction was studied by using ethanol aqueous mixtures, from 20% to 100% ethanol. The kinetics of polyphenol extraction have been fitted to the power law and the Weibull models yielding mean values of the root mean square deviation lower than 7.5%. Extracts have been characterized in terms of quantification of individual phenolic compounds by HPLC-DAD and protein and sugar soluble fractions (glucose, xylose, and arabinose). Polyphenol profile has been compared with other hydrolytic techniques, such as acid, basic and enzymatic hydrolysis, showing that ultrasound was not as effective as basic hydrolysis to release the phenolic acids esterified to the cell wall. A further centrifuge ultrafiltration concentration step was able to yield a retentate enriched in the protein fraction while individual phenolic compounds where mainly transferred to the permeate.

PAP inhibitor with in vivo efficacy identified by Candida albicans genetic profiling of natural products.

Natural products provide an unparalleled source of chemical scaffolds with diverse biological activities and have profoundly impacted antimicrobial drug discovery. To further explore the full potential of their chemical diversity, we survey natural products for antifungal, target-specific inhibitors by using a chemical-genetic approach adapted to the human fungal pathogen Candida albicans and demonstrate that natural-product fermentation extracts can be mechanistically annotated according to heterozygote strain responses. Applying this approach, we report the discovery and characterization of a natural product, parnafungin, which we demonstrate, by both biochemical and genetic means, to inhibit poly(A) polymerase. Parnafungin displays potent and broad spectrum activity against diverse, clinically relevant fungal pathogens and reduces fungal burden in a murine model of disseminated candidiasis. Thus, mechanism-of-action determination of crude fermentation extracts by chemical-genetic profiling brings a powerful strategy to natural-product-based drug discovery.

Antisense-guided isolation and structure elucidation of pannomycin, a substituted cis-decalin from Geomyces pannorum.

Antisense-based screening strategies can be used to sensitize a microorganism and selectively detect inhibitors against a particular cellular target of interest. A strain of Staphylococcus aureus that generates an antisense RNA against SecA,a central member of the protein secretion machinery, has been used to screen for novel antibacterials. Possible inhibitors of the SecA ATP-ase were selected with a high-throughput, two-plate agar-based whole cell differential sensitivity screen. After screening a library of over 115 000 natural products extracts with the SecA antisense strain, an extract of Geomyces pannorum was identified as providing increased activity against the sensitized strain as compared with the wild-type control. Bioassay-guided isolation of the active component from this fungal extract provided a new cis-decalin secondary metabolite, which we have named pannomycin.

Isolation and structure elucidation of parnafungins, antifungal natural products that inhibit mRNA polyadenylation.

The Candida albicans Fitness Test, a whole-cell screening platform, was used to profile crude fermentation extracts for novel antifungal natural products with interesting mechanisms of action. An extract with intrinsic antifungal activity from the fungus Fusarium larvarum displayed a Fitness Test profile that strongly implicated mRNA processing as the molecular target responsible for inhibition of fungal growth. Isolation of the active components from this sample identified a novel class of isoxazolidinone-containing natural products, which we have named parnafungins. These natural products were isolated as an interconverting mixture of four structural- and stereoisomers. The isomerization of the parnafungins was due to a retro-Michael ring-opening and subsequent reformation of a xanthone ring system. This interconversion was blocked by methylation of an enol moiety. Structure elucidation of purified parnafungin derivatives was accomplished by X-ray crystallography and NMR analysis. The biochemical target of these natural products has been identified as the fungal polyadenosine polymerase. Parnafungins demonstrated broad spectrum antifungal activity with no observed activity against gram-positive or gram-negative bacteria. The intact isoxazolidinone ring was required for antifungal activity. In addition, the natural products were efficacious in a mouse model of disseminated candidiasis.

Determination of phenolic compounds derived from hydrolysable tannins in biological matrices by RP-HPLC.

An RP-HPLC method for the determination of four phenolic compounds: gallic acid (GA), pyrogallol (PY), resorcinol (RE) and ellagic acid (EA), derived from hydrolysable tannins is reported. Separation was achieved on a SunFire C18 (250 x 4.6 mm id, 5 microm) column at 40 degrees C with gradient elution. UV detection at 280 nm was applied. The developed method was validated in terms of linearity, accuracy and precision. Satisfactory repeatability and between day precision were noticed with RSD values lower than 3%. Recoveries from different biological samples ranged from 91.50 to 105.25%. The LODs were estimated as 1.70 mg/L for PY, 1.68 mg/L for GA, 1.52 mg/L for RE and 0.98 mg/L for EA with a 20 microL injection volume. The method was applied for the determination of these compounds in oak leaves and in ruminal fluid and urine samples taken from beef cattle fed with oak leaves. The proposed method could be used in ruminant nutrition studies to verify the effect that a diet rich in tannins have on ruminal fermentation and to determine the toxicity of these compounds.

Simultaneous determination of adenine and guanine in ruminant bacterial pellets by ion-pair HPLC.

An ion-pair reversed-phase high-performance liquid chromatography with gradient elution and UV detection was used to measure adenine (A) and guanine (G) in lyophilized bacterial pellets from ruminants using allopurinol as internal standard. The separation was performed on a Symmetry C18 column and the detection was monitored at 280 nm. Calibration curves were found to be linear in the concentration range from 5 to 50 mg/l with correlation coefficients (r2)>0.999. Mean recoveries of A and G standards added to bacterial samples were 102.2 and 98.2, respectively. The method proposed yielded sharp, well-resolved peaks within 25 min and was successfully applied for the determination of A and G in bacterial pellets.

[Trends in the utilization of antidepressant drugs in the Rioja and Zamora health districts throughout the 1997-2001 period]. / Evolución del consumo de fármacos antidepresivos en las áreas sanitarias de La Rioja y Zamora durante el periodo 1997-2001.

BACKGROUND: Due to the high increase in the utilization of antidepressant drugs and the change in the prescription profile within this group, this study is aimed at discovering the evolution of the utilization of antidepressant drugs (NO6A subgroup) outside of the hospital setting in the Rioja and Zamora health districts throughout the 1997-2001 period and to evaluate the impact of the new drugs. METHODS: A study was made of the utilization of drugs included in the NO6A treatment subgroup under the Anatomical Therapeutic Chemical (ATC) classification. The data on the utilization of each specialty was taken from the pharmacy management (SIFAR) software applications and has been stated for each active ingredient in Daily Dose per Inhabitant (DDI). RESULTS: In the period under study, there was an increase in the total utilization of antidepressants in the two areas (Zamora 55% and Rioja 93%) due mainly to the increase in selective serotonin reuptake inhibitors (SSRI) (Zamora 80% and Rioja 143%) and in the new heterocyclic antidepressants (Zamora 82% and Rioja 78%). CONCLUSIONS: There has been an increase in the utilization of antidepressants, all of which has taken place in conjunction with a change in the prescription profile. There is a clear shift toward the utilization of the SSRI's and some heterocyclic antidepressants (venlafaxine, trazodone, reboxetine), the utilization of tricyclic antidepressants and IMAO's having decreased.

Eficacia de un plan de cuidados de enfermería específico para el paciente con delirio / Effectiveness of a Specific Nursing Care Plan for the Patient with Delirium

RESUMEN Introducción: El síndrome confusional agudo o delirio es un trastorno psiquiátrico severo frecuente en pacientes mayores ingresados, tiende a agravarse en las horas del final de la tarde y nocturnas, con un gran impacto en los cuidados nocturnos. Objetivos: Evaluar la eficacia de los cuidados de enfermería específicos ante el delirio nocturno en pacientes hospitalizados. Métodos: Ensayo clínico cuasi-experimental en dos unidades de hospitalización de Medicina Interna de un hospital de alta complejidad. Se identificaron un grupo control y un grupo experimental, mediante muestreo de conveniencia. En ambos grupos, se seleccionaron pacientes con delirio, mediante la escala validada Intensive Care Delirium Screening Checklist. Se expuso al grupo experimental a plan de cuidados específico basado en bibliografía y plan de cuidados estándar al grupo control. Sobre resultados de indicadores de delirio, pre y posaplicación de planes de cuidados en ambos grupos, se realizaron pruebas de contraste (ANOVA, t-Student y Chi2-test de Fisher). Resultados: Con incidencia de 12-15 por ciento, los grupos control y experimental mostraron resultados homogéneos en el test del delirio PRE (p > 0,05). La edad, motivo de ingreso, género, y número de interrupciones durante el sueño, no mostraron repercusión sobre los resultados de delirio. Tras la aplicación de los planes de cuidados, el grupo experimental mostró reducción significativa de los índices de delirio (p < 0,05), y no se obtuvieron cambios significativos en el grupo control (p > 0,05). Conclusiones: El plan de cuidados específico a pacientes con delirio demostró ser eficaz al mejorar los indicadores del test de delirio y evitar el empeoramiento del cuadro(AU)

ABSTRACT Introduction: Acute confusional syndrome or delirium is a severe psychiatric disorder of frequent presentation in hospitalized elderly patients. It worsens likely in the late afternoon and evening hours, with a great impact on night care. Objectives: To evaluate the effectiveness of specific nursing care for sundown delirium in hospitalized patients. Methods: Quasi-experimental clinical trial in two hospitalization units of internal medicine of a high-complexity hospital. A control group and an experimental group were identified by convenience sampling. In both groups, patients with delirium were selected, using the validated scale Intensive Care Delirium Screening Checklist. The experimental group was exposed to a specific care plan, considering the bibliography; and the control group was exposed to a standard care plan. Regarding the results of delirium indicators, before and after the application of the care plans in both groups, contrast tests were performed (ANOVA, t-Student and Fisher's Chi-square test). Results: With an incidence of 12-15 percent, the control and experimental groups showed homogeneous results in the delirium test PRE (p >0.05). Age, reason for admission, gender, and number of interruptions during sleep did not show repercussion on delirium results. After the application of the care plans, the experimental group showed a significant reduction in delirium rates (p < 0.05), and no significant changes were obtained in the control group (p >0.05). Conclusions: The specific care plan for patients with delirium was shown to be effective in improving the indicators of the delirium test and avoiding the worsening of the health status(AU)

Coniothyrione, a chlorocyclopentandienylbenzopyrone as a bacterial protein synthesis inhibitor discovered by antisense technology.

Bacterial protein synthesis inhibitors interact mainly with rRNA and to some extent ribosomal proteins, which are potential targets for developing new antibacterial agents. Specifically, the ribosomal protein S4 of the 30s ribosomal subunit known as ribosomal protein small-subunit D (rpsD) may be useful as a target. The antisense-rpsD gene-sensitized two-plate assay led to the discovery of a novel chlorinated cyclopentandienylbenzopyrone antibiotic, coniothyrione, C14H9ClO6, isolated from Coniothyrium cerealis MF7209. It exhibited liquid MICs of 16-32 microg/mL against Staphylococcus aureus, Bacillus subtilis, Haemophilus influenzae, Streptococcus pneumoniae, and Enterococcus faecalis and >64 microg/mL against Escherichia coli. Isolation, structure elucidation, and antibacterial activity of coniothyrione are described.