Diagnostic tests for progestogen hypersensitivity.

Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for in vivo or in vitro tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.

Sensitivity of Daphnia spinulata Birabén, 1917 to glyphosate at different salinity levels.

Daphnia spinulata Birabén, 1917 is an endemic cladoceran species, frequent in the zooplankton communities of the shallow lakes of the Pampean region of Argentina. These lakes have varying salinity levels and, being located in agricultural areas, are frequently subject to pesticide pollution. This study aimed to determine the effects of the herbicide glyphosate (Panzer Gold®) in combination with different salinity levels on the biological parameters of D. spinulata and its recovery ability after a short exposure. Three types of assays were performed: an acute toxicity test, a chronic assessment to determine survival, growth and reproduction, and recovery assays under optimal salinity conditions (1 g L-1). The LC50-48 h of glyphosate was 7.5 mg L-1 (CL 3.15 to 11.72). Longevity and the number of offspring and clutches were significantly reduced due to the combined exposure of glyphosate and increased salinity. The timing of the first offspring did not recover after glyphosate exposure. Our results reveal that D. spinulata is sensitive to the herbicide Panzer Gold® at concentrations well below those indicated in the safety data sheet of this commercial formulation, which causes stronger negative effects in conditions of higher salinity. Further research is needed to shed light on the sensitivity of this cladoceran to glyphosate and its variability under other interactive stress factors.

Sex Distributions in Non-ABCA4 Autosomal Macular Dystrophies.

Purpose: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies. Methods: We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2, only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored. Results: Of 325 patients included, numbers for BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease (n = 115), there were fewer females (38%; 95% confidence interval [CI], 29-48%; P = 0.015). For EFEMP1-associated disease (n = 35), there were significantly more females (77%; 95% CI, 60%-90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%-43%; P = 1.2 × 10-5). Pooling previously published EFEMP1-cases with ours yielded an overall female proportion of 62% (95% CI, 54%-69%; P = 0.0023). Conclusions: This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.

The proteasome inhibitor carfilzomib exerts anti-inflammatory and antithrombotic effects on the endothelium.

BACKGROUND: Carfilzomib (CFZ) is a second-generation proteasome inhibitor used to treat multiple myeloma. Potent inhibition of the proteasome results in chronic proteotoxic endoplasmic reticulum (ER) stress, leading to apoptosis. While CFZ has improved survival rates in multiple myeloma, it is associated with an increased risk of cardiovascular adverse effects. While this has been putatively linked to cardiotoxicity, CFZ could potentially also exhibit adverse effects on the endothelium. OBJECTIVES: To investigate the effects of CFZ on the endothelium. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with CFZ, and expression of relevant markers of ER stress, inflammation, and thrombosis was measured and functionally assessed. RESULTS: CFZ failed to induce ER stress in HUVECs but induced the expression of Kruppel-like factor 4, endothelial nitric oxide synthase, tissue plasminogen activator, and thrombomodulin and reduced tumor necrosis factor alpha (TNFα)-mediated intercellular adhesion molecule 1 and tissue factor expression, suggesting a potential protective effect on the endothelium. Consistent with these observations, CFZ reduced leukocyte adhesion under shear stress and reduced factor Xa generation and fibrin clot formation on the endothelium following TNFα treatment and inhibited von Willebrand factor (VWF) and angiopoietin-2 exocytosis from Weibel-Palade bodies. Subsequently, CFZ inhibited the formation of VWF-platelet strings, and moreover, media derived from myeloma cell lines induced VWF release, a process also inhibited by CFZ. CONCLUSION: These data demonstrate that CFZ is unable to induce ER stress in confluent resting endothelial cells and can conversely attenuate the prothrombotic effects of TNFα on the endothelium. This study suggests that CFZ does not negatively alter HUVECs, and proteasome inhibition of the endothelium may offer a potential way to prevent thrombosis.

Tocilizumab demonstrates superiority in decreasing C-reactive protein levels in hospitalized COVID-19 patients, compared to standard care treatment alone.

Severe acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crisis. The virus triggers the activation of inflammatory reactants including interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP), causing multiorgan damage, particularly affecting the lungs. Tocilizumab, an IL-6 receptor blocker, has the potential to diminish the progression of the disease and reduce organ damage and long-term complications. The aim of this observational retrospective cohort study was to evaluate the efficacy of tocilizumab in decreasing CRP levels in hospitalized coronavirus disease 2019 (COVID-19) patients compared to standard care without the drug. The study included 141 patients during their Hospital Stay (HS), with 100 in the Tocilizumab group and 41 in the non-Tocilizumab group. Clinical information was collected from the electronic clinical record, analyzed using statistical software, and homogenized the CRP levels from the severe group to the levels of the less complicated group at 48 h of hospitalization. The results showed a statistically significant greater decrease in CRP levels in the Tocilizumab group at 48 h after the use of the treatment, with no differences in mortality or length of stay between the groups. In conclusion, tocilizumab accelerates the diminishing of CRP levels compared to standard treatment alone, and its use may have potential benefits in the management of severe COVID-19 patients when used alongside with follow-up quantification of CRP levels reduction.IMPORTANCESevere acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crises. International guidelines for managing coronavirus disease 2019 (COVID-19) give recommendations according to the severity of the disease and the level of oxygen therapy needed. Tocilizumab is an option for the therapeutic management of hospitalized patients with any level of oxygen therapy; IL-6 serum level is the parameter for the follow-up on the efficacy, but it is not available at many hospitals. In this study, we demonstrate that C-reactive protein determination can predict the response to tocilizumab in severe COVID-19, the target patients for treatment with this drug. The use of this affordable and extensively available biomarker supports clinical decisions for the early escalation of the therapy and for the rational use of this drug on those prone to improve with the use of it.

Experiencias de las enfermeras en primera línea contagiadas con COVID-19 que recibieron atención domiciliaria / Experiências de enfermeiros da linha de frente infectados com COVID-19 que receberam atendimento domiciliar / Experiences of frontline nurses infected with COVID-19 who received home care

Introducción: Las enfermeras han brindado cuidados a lospacientes con COVID-19, y muchas tuvieron que lidiar coneste virus al ser infectadas.Objetivo: Describir las experiencias de las enfermeras enprimera línea contagiadas con COVID-19 que recibieronatención domiciliaria.Método: Investigación cualitativa descriptiva, el tamaño dela muestra fue con 12 enfermeras infectadas con COVID-19que recibieron tratamiento domiciliario en Chiclayo, Perú. Elmuestreo fue por la técnica de bola de nieve. Para recolectarlos datos se utilizó la entrevista semiestructurada a travésde los medios virtuales previo consentimiento informado.Resultados: Surgieron tres categorías: a) Incertidumbre antemodo de contagio, medios de diagnóstico, sintomatología yevolución por la COVID-19, b) Cuidados recuperativos enel hogar: tratamiento médico, uso de medicina tradicional ymedidas de bioseguridad, y c) Impacto en la vida familiar,laboral, social, emocional y espiritual al sufrir de la COVID-19.Conclusiones: Las enfermeras presentaron síntomas leves dela COVID-19 y se recuperaron en su domicilio, cumplieroncon el tratamiento médico, algunas usaron remedios caseros.Practicaron estrictamente las medidas de bioseguridad paraevitar que su familia se contagie. Utilizaron la tecnologíadigital y reforzaron su fe para afrontar el impacto familiar,emocional y social.(AU)

Introduction: Nurses have provided care to patients with COVID-19,and many have had to deal with this virus when infected.Objective: To describe the experiences of frontline nursesinfected with COVID-19 who received home care.Method: Descriptive qualitative research, the sample sizewas 12 nurses infected with COVID-19 who received hometreatment in Chiclayo, Peru. Sampling was by snowballtechnique. To collect the data, the semi-structured interviewwas used through virtual media with prior informed consent.Results: Three categories emerged: a) Uncertainty regardingthe mode of transmission, means of diagnosis, symptomatologyand evolution due to COVID-19, b) Recuperative care athome: medical treatment, use of traditional medicine andbiosafety measures, and c) Impact on the family, work, social,emotional and spiritual life when suffering from COVID-19.Conclusions: The nurses presented mild symptoms ofCOVID-19 and recovered at home, complied with medicaltreatment, some used home remedies. They strictly practicedbiosecurity measures to prevent their family from gettinginfected. They used digital technology and strengthened theirfaith to cope with the family, emotional and social impact.(AU)

Introdução: Enfermeiras têm prestado atendimento a pacientescom COVID-19, e muitos tiveram que lidar com esse vírusquando infectados.Objetivo: Descrever as experiências de enfermeiros dalinha de frente infectados com COVID-19 que receberamatendimento domiciliar.Método: Emergiram três categorias: a) Incerteza quanto aomodo de contágio, meios de diagnóstico, sintomatologiae evolução da COVID-19, b) Cuidados de recuperação nodomicílio: tratamento médico, uso da medicina tradicional emedidas de biossegurança, e c) Impacto na saúde vida familiar,laboral, social, emocional e espiritual ao sofrer de COVID-19. Resultados: a) Participação do pessoal de saúde na atenção domiciliar: Consulta médica,administração de medicamentos e educação em saúde, b) Participação da família na atençãodomiciliar: Satisfação das necessidades básicas, apoio emocional e espiritual, c) Anedotas familiaressobre oferta de oxigênio, cuidados com oxigenoterapia e pós -Terapia respiratória COVID-19, d)Controvérsias para aplicação de protocolos de biossegurança durante o atendimento domiciliar.Conclusões: As enfermeiras apresentaram sintomas leves de COVID-19 e se recuperaram em casa,cumpriram tratamento médico, alguns usaram remédios caseiros. Eles praticavam rigorosamenteas medidas de biossegurança para evitar que sua família fosse infectada. Eles usaram a tecnologiadigital e fortaleceram sua fé para lidar com o impacto familiar, emocional e social.(AU)

Evaluation of the environmental impacts of the smallholder milk-production system in Central Mexico.

In order to analyze the environmental performance of Smallholder Dairy Farms (SHDFs) located in the State of Mexico, a Life Cycle Analysis (LCA) was carried out using two methodological approaches (A1 and A2) to estimate and interpret environmental impacts. A1 consisted in obtaining the average inputs and outputs of 15 SHDFs to generate a representative farm life cycle inventory, while A2 included an individual environmental impact analysis per SHDF to obtain average values of the contributions per analyzed midpoint impact category. The feed production subsystem generated the highest contributions to environmental impacts per liter of raw milk produced. Estimated emissions based on A2 approach, resulted in higher environmental impacts compared to results obtained with A1. The estimated values for the midpoint impact categories obtained with A2: Climate change, Fossil depletion, Terrestrial acidification, and Agricultural land occupation, were 8.73%, 30.77%, 100%, and 20.49% higher compared to A1 approach, respectively. While A2 provides more accurate results, it requires more time and resources compared to the integration of a panel of representative dairy farms.

Evaluation of acetanilide and antipyrine adsorption on lignin-derived activated carbons.

In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of Organosolv lignin with H3PO4 were evaluated. ACs with different pore size distribution were obtained at different impregnation ratios (H3PO4/lignin, 0.5-3.0 w/w) and activating temperatures (500-900 °C). The porosity and surface chemistry of the ACs were determined, and a bimodal size distribution of micropores and narrow mesopores was observed for the different ACs. These ACs were tested for antipyrine and acetanilide adsorption in aqueous solutions in a batch system at 20 °C and low concentration levels (0.5-10 ppm). In general, the ACs exhibited higher adsorption affinity to acetanilide than to antipyrine due to its smaller molecular size. Langmuir adsorption isotherm was able to describe the adsorption equilibrium data. A new Linear Driving Force (2-LDF) kinetic model, based on the bimodal size distribution of micropores and narrow mesopores observed for the ACs has been developed. The new model provided a more accurate description of the batch adsorption rates than that obtained from conventional kinetic models, and also enabled to relate the pore size distribution of the adsorbent with the adsorption kinetics. The validity of this model was checked in small-scale column fixed bed adsorption for the AC showing the highest affinity for both EP. The kinetic model and equilibrium adsorption isotherm obtained from the batch experiments were successfully used to provide an accurate description of the bed service time and the full breakthrough profile of acetanilide and antipyrine.

Cytokine Storm Syndrome Responsive to IL-1 Inhibition in Trisomy 21.

Background: Cytokine storm syndromes (CSS) are life-threatening systemic inflammatory disorders caused by immune system dysregulation. They can lead to organ failure and are triggered by various factors, including infections, malignancy, inborn errors of immunity, and autoimmune conditions. Trisomy 21 (TS21), also known as Down syndrome, is a genetic disorder associated with immune dysfunction, increased infection susceptibility, and inflammation. While TS21 has been linked to infectious-triggered hyperinflammation, its role as a primary cause of CSS has not been confirmed. Case Presentation. We present a case of a 16-year-old male with TS21 with fever, rash, joint pain, and abdominal symptoms. Extensive investigations ruled out infections, autoimmune conditions, malignancies, and inborn errors of immunity as triggers for a CSS. The patient's symptoms improved with treatment using IL-1 inhibition and corticosteroids. Conclusions: This case reinforces that TS21 is an immune dysregulation disorder and highlights the importance of considering CSS in TS21 patients, even when triggers are unclear. The positive response to IL-1 inhibition in this patient suggests that dysregulation of the IL-1 superfamily and the NLRP3 inflammasome may contribute to CSS in TS21. This finding raises the possibility of using IL-1 inhibition as a treatment approach for CSS in TS21 patients.

Addressing Challenges in Wildlife Rehabilitation: Antimicrobial-Resistant Bacteria from Wounds and Fractures in Wild Birds.

Injuries and bone fractures are the most frequent causes of admission at wildlife rescue centers. Wild birds are more susceptible to open fractures due to their anatomical structure, which can lead to osteomyelitis and necrosis. Antibiotic therapy in these cases is indispensable, but the increase of antimicrobial-resistant isolates in wildlife has become a significant concern in recent years. In this context, the likelihood of antibiotic failure and death of animals with infectious issues is high. This study aimed to isolate, identify, and assess the antimicrobial resistance pattern of bacteria in wounds and open fractures in wild birds. To this end, injured birds admitted to a wildlife rescue center were sampled, and bacterial isolation and identification were performed. Then, antimicrobial susceptibility testing was assessed according to the disk diffusion method. In total, 36 isolates were obtained from 26 different birds. The genera detected were Staphylococcus spp. (63.8%), Escherichia (13.9%), Bacillus (11.1%), Streptococcus (8.3%), and Micrococcus (2.8%). Among Staphylococcus isolates, S. lentus and S. aureus were the most frequent species. Antimicrobial resistance was detected in 82.6% of the isolates, among which clindamycin resistance stood out, and 31.6% of resistant isolates were considered multidrug-resistant. Results from this study highlight the escalating scope of antimicrobial resistance in wildlife. This level of resistance poses a dual concern for wildlife: firstly, the risk of therapeutic failure in species of significant environmental value, and, secondly, the circulation of resistant bacteria in ecosystems.

From Knee Pain Consultation to Pituitary Surgery: The Challenge of Cushing Disease Diagnosis.

Cushing syndrome (CS) is a rare endocrinological disorder resulting from chronic exposure to excessive cortisol. The term Cushing disease is used specifically when this is caused by excessive secretion of adrenocorticotropic hormone (ACTH) by a pituitary tumor, usually an adenoma. This disease is associated with a poor prognosis, and if left untreated, it has an estimated 5-year survival rate of 50%. We present the case of a 66-year-old female patient who received a referral to endocrinology for an evaluation of obesity due to right knee arthropathy. Taking into consideration her age, she was screened for osteoporosis, with results that showed diminished bone density. Considering this, combined with other clinical features of the patient, suspicion turned toward hypercortisolism. Laboratory findings suggested that the CS was ACTH-dependent and originated in the pituitary gland. After a second look at the magnetic resonance imaging results, a 4-mm lesion was identified on the pituitary gland, prompting a transsphenoidal resection of the pituitary adenoma.

Necesidades de Intervención en Prisión con Internos con Pedofilia / Intervention Needs in Prison With Pedophile Inmates

En prisión existen programas específicos de tratamiento para condenados por agresión sexual a menores; sin embargo, quienes además tienen pedofilia, requieren una atención específica. El objetivo del presente estudio es doble: primero, ofrecer una propuesta de intervención específica para pedofilia en el entorno penitenciario basada en la evidencia científica disponible y complementaria al Programa de Control de la Agresión Sexual y después, justificar dicha propuesta a través del caso de un interno con pedofilia. En concreto, proponemos una intervención individual y centrada en personas con pedofilia; trabajando la baja autoestima, evaluando la ideación suicida y reestructurando las distorsiones cognitivas con menores, facilitando la creación de relaciones personales funcionales con adultos, evaluando la polivictimización pasada y su posible influencia sobre la conducta sexual posterior, proporcionar a los internos psicoeducación sobre pedofilia; atender de forma específica las fantasías sexuales con menores, evitando las conductas disexuales y la eliminación del consumo de material abusivo.(AU)

There are specific treatment programs in prisons for those convicted of sexually assaulting minors; however, those who also have pedophilia require specific attention. The aim of this study is twofold: first, to offer a specific intervention proposal for pedophilia in the prison setting based on the available scientific evidence, and complementary to the Sexual Assault Control Program, and second, to justify this proposal through the case of an inmate with pedophilia. Specifically, we propose an individual intervention focused on people with pedophilia; working on low self-esteem, assessing suicidal ideation and restructuring cognitive distortions with minors, facilitating the creation of functional personal relationships with adults, assessing past polyvictimization and its possible influence on subsequent sexual behavior, providing inmates with psychoeducation on pedophilia; specifically addressing sexual fantasies with minors, avoiding dyssexual behavior, and eliminating the consumption of abusive material.(AU)

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019–2021 / Prevalencia del tracoma en zonas de población indígena y no indígena del nordeste de Brasil, 2019-2021 / Prevalência de tracoma em áreas indígenas e não indígenas, Nordeste do Brasil, 2019-2021

[ABSTRACT]. Objective. To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods. This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation – follicular (TF) in children aged 1–9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results. The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions. The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

[RESUMEN]. Objetivo. Estimar la prevalencia del tracoma en poblaciones indígenas y no indígenas en determinadas zonas del estado de Maranhão, en el nordeste de Brasil. Métodos. Se trató de una encuesta de ámbito poblacional con muestreo probabilístico. Para el diagnóstico del tracoma, se realizó un examen ocular externo con una lupa frontal de 2,5X aumentos. Se estimó la prevalencia de la inflamación tracomatosa folicular (TF) en la población infantil de 1 a 9 años y la prevalencia de la triquiasis tracomatosa (TT) en la población de 15 años o más. Se obtuvieron las frecuencias relativas de las características sociodemográficas y ambientales. Resultados. En el estudio participaron 7 971 personas, 3 429 de poblaciones no indígenas y 4 542 de poblaciones indígenas. La prevalencia de la TF en las poblaciones no indígenas e indígenas fue de 0,1% y 2,9%, respectivamente, en tanto que la de la TT en las poblaciones indígenas fue de 0,1%. Conclusiones. La prevalencia de la TF y la TT en las dos unidades de evaluación del estado de Maranhão estuvo dentro de los límites recomendados para la eliminación del tracoma como problema de salud pública. Sin embargo, la prevalencia de la TF fue mayor en la unidad de evaluación indígena, lo que indica una mayor vulnerabilidad de esta población a la enfermedad. La prevalencia de la TF inferior al 5,0% implica una reducción de la transmisión, que puede haber sido consecuencia tanto de la mejora de las condiciones socioeconómicas como de la aplicación de la estrategia SAFE de la Organización Mundial de la Salud.

[RESUMO]. Objetivo. Estimar a prevalência do tracoma em populações indígenas e não indígenas em áreas selecionadas do estado do Maranhão, na região Nordeste do Brasil. Métodos. Inquérito de base populacional com amostragem probabilística. Para o diagnóstico de tracoma, foi realizado exame ocular externo com o auxílio de lupas binoculares com ampliação de 2,5×. Foram estimadas a prevalência de inflamação tracomatosa folicular (TF) em crianças de 1 a 9 anos de idade e a prevalência de triquíase tracomatosa (TT) na população com idade ≥15 anos. Foram obtidas as frequências relativas das características sociodemográficas e ambientais. Resultados. O estudo incluiu 7 971 indivíduos (3 429 de populações não indígenas e 4 542 de populações indígenas). A prevalência de TF nas populações não indígenas e indígenas foi de 0,1% e 2,9%, respectiva- mente, e a prevalência de TT entre as populações indígenas foi de 0,1%. Conclusões. A prevalência de TF e TT nas duas unidades de avaliação no estado do Maranhão ficou dentro dos limites recomendados para a eliminação do tracoma como problema de saúde pública. No entanto, a prevalência de TF foi maior na unidade de avaliação indígena, indicando uma maior vulnerabilidade dessa população à doença. A prevalência de TF abaixo de 5,0% implica uma redução na transmissão, que pode ter sido resultado de melhores condições socioeconômicas e da implementação da estratégia SAFE da Organização Mundial da Saúde.

Síndrome de Alicia en el País de las Maravillas secundario a infección por SARS-CoV-2 / Alice in Wonderland syndrome in SARS-CoV-2 infection

El síndrome de Alicia en el País de las Maravillas es un conjunto de trastornos complejos de la percepción visual con múltiples etiologías, siendo las infecciones las más frecuentes en Pediatría. Es un cuadro poco frecuente, pero es importante conocerlo por su carácter generalmente autolimitado. Presentamos el caso de un niño de 11 años que, a las 48 horas de infección por SARS-CoV-2, inició distorsión visual de la forma corporal, micropsias y macropsias. Se descartaron otras causas orgánicas, manteniéndose actitud expectante dada su evolución benigna. Se destaca la aparición de este síndrome en contexto clínico de infección por SARS-CoV-2, no habiendo sido descrita hasta ahora su asociación en la literatura. (AU)

The Alice in Wonderland syndrome is defined by the presence of visual perception disorders with several etiologies, being infectious the most frequent in pediatrics. It is a rare clinical condition, but it is important to recognize it because of the generally self-limited nature. We present an 11 years old child who presented visual body distortions, micropsia and macropsia 48 after SARS-CoV-2 infection. Other organic causes were discarded, maintaining an expectant treatment because of its benign evolution. It is noteworthy that this syndrome associated with SARS-CoV-2 infection has not yet been published. (AU)

Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) liver stiffness measurement (LSM)-decrease in cACLD by ≥20% associated with a final LSM<20 kPa, or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed cACLD patients (LSM≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV-cure by interferon-free therapies from 15 European centers. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: 2335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV-cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM-change of -5.3 (-8.8-[-2.4])kPa corresponding to -33.9 (-48.0-[-15.9])%. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio [SHR]: 0.12 [95%CI: 0.04-0.35], p<0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5y-cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5y-cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM-decrease ≥20% (p=0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV-cure and should guide clinical decision-making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV-cure.

PRPH2-Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort.

PRPH2, one of the most frequently inherited retinal dystrophy (IRD)-causing genes, implies a high phenotypic variability. This study aims to analyze the PRPH2 mutational spectrum in one of the largest cohorts worldwide, and to describe novel pathogenic variants and genotype-phenotype correlations. A study of 220 patients from 103 families recruited from a database of 5000 families. A molecular diagnosis was performed using classical molecular approaches and next-generation sequencing. Common haplotypes were ascertained by analyzing single-nucleotide polymorphisms. We identified 56 variants, including 11 novel variants. Most of them were missense variants (64%) and were located in the D2-loop protein domain (77%). The most frequently occurring variants were p.Gly167Ser, p.Gly208Asp and p.Pro221_Cys222del. Haplotype analysis revealed a shared region in families carrying p.Leu41Pro or p.Pro221_Cys222del. Patients with retinitis pigmentosa presented an earlier disease onset. We describe the largest cohort of IRD families associated with PRPH2 from a single center. Most variants were located in the D2-loop domain, highlighting its importance in interacting with other proteins. Our work suggests a likely founder effect for the variants p.Leu41Pro and p.Pro221_Cys222del in our Spanish cohort. Phenotypes with a primary rod alteration presented more severe affectation. Finally, the high phenotypic variability in PRPH2 hinders the possibility of drawing genotype-phenotype correlations.

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019-2021.

Objective: To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods: This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results: The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions: The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy.

Background: Lower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis. Methods: This study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns. Results: We identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk. Conclusion: This study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying disease risk at birth. Moreover, our results prompt further study on PDP enzymes as pharmacological targets to decrease LRTI morbidity and mortality for at-risk newborns.

Understanding the Biological Relationship between Migraine and Depression.

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.