Rocky Mountain spotted fever is a neglected tropical disease in Latin America.

Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, has emerged as a widespread public health crisis among predominantly vulnerable populations in several countries of Latin America, particularly evident in northern Mexico. Historically, RMSF has gained less attention than many other tropical infectious diseases, resulting in insufficient allocations of resources and development of capabilities for its prevention and control in endemic regions. We argue that RMSF fulfills accepted criteria for a neglected tropical disease (NTD). The relative neglect of RMSF in most Latin American countries contributes to disparities in morbidity and mortality witnessed in this region. By recognizing RMSF as an NTD, an increased public policy interest, equitable and more appropriate allocation of resources, scientific interest, and social participation can ameliorate the impact of this potentially treatable disease, particularly in vulnerable populations.

Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

IgE-Mediated Sensitization to Blo t 21 and Blo t 5 Is Associated With Asthma in the Tropics: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.

Association of vitamin D levels and oral lichen planus. Systematic review and meta-analysis.

BACKGROUND: Oral lichen planus (OLP) is an inmuno-mediated mucocutaneous chronical inflammatory disease. Multiple predisposing factors are considered, such as autoimmune response, microorganisms, medications, dental materials, psychological stress, genetic predisposition or nutritional deficiencies. The deficiency of vitamin D has been related to various autoimmune diseases like OLP. MATERIAL AND METHODS: The electronic search was conducted in the MEDLINE (Pubmed), Scopus, Cochrane Library and Web of Science databases. To assess any potential risk of bias, the authors critically appraised each study by the Newcastle-Ottawa Scale for cohort and case-control studies. Pooled analyses were performed using a random-effects model. Heterogeneity of the studies was assessed by the I2 statistics. Forest Plots were performed to graphically represent the difference between vitamin D concentrations in the OLP compared to healthy group, with a 95% confidence interval. RESULTS: After applying our inclusion and exclusion criteria, 7 articles were included in our review. The median concentration vitamin D in ng/ml found in serum for patients with OLP was of 26,6311,75ng/ml and for healthy patients was of 31,438,7ng/ml. Regarding the quantitative analysis, 7 studies were included. The difference in the concentration of vitamin D in healthy patients and patients with OLP statistically significant (Weighted Mean Difference (WMD): -6.20, 95% CI: -11.24 to -1.15, p=0.02 and I2 heterogeneity: 94%, p<0.00001). CONCLUSIONS: The patients with OLP have statistically lower vitamin D levels than healthy patients.

Translation, adaptation, and cross-cultural validation of the CDQ-24 scale in patients with primary blepharospasm under botulinum toxin treatment, pilot test.

BACKGROUND: Benign essential blepharospasm (BEB) is the most common adult-onset focal facial dystonia and its treatment of choice is periodic application of botulinum toxin (BtA). It has a higher incidence in middle and late adulthood, especially in women between 40 and 60 years of age. OBJECTIVE: To carry out the translation and cross-cultural adaptation of the CDQ24 questionnaire in its Spanish version in patients diagnosed with BEB who have been treated with BtA in an ophthalmologic center in Bogotá - Colombia. MATERIALS AND METHODS: Pilot test of validation study and adaptation of a scale assembled in a prospective cohort of the CDQ24 instrument to Spanish in adult patients with primary blepharospasm treated with botulinum toxin in Bogota, Colombia. RESULTS: We obtained a sample of 26 patients to whom the instrument was applied after translation and retranslation of the original document, composed of 19 (73%) women with a median age of 64.5 years; the average time to answer the survey was 4.93 min. The internal consistency of the scale evaluated by Cronbach's Alpha had a total score of 0.78. Criterion validity between the CDQ24 scale and the WHOQOL-BREF quality of life scale was determined by determining correlation between the Emotional Well-Being and Phsychological domains of both scales. CONCLUSIONS: The translation and cross-cultural adaptation of the CDQ-24 scale into Spanish allowed the applicability of the instrument to the Spanish-speaking population during the pilot test, which allows us to continue the relevant studies in the study population.

Rocky Mountain Spotted Fever Mimicking Multisystem Inflammatory Syndrome in Hospitalized Children, Sonora, Mexico.

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .

[Pressure digit sign in patients with knee osteoarthritis]. / Signo de digito-presión en pacientes con osteoartritis de rodilla.

INTRODUCTION: it is estimated that 302 million people worldwide are affected by osteoarthritis, corresponding to 60% osteoarthritis (OA) of the knee, which responsible 80% of disability in older adults, hence the importance of the association of the sign with the early inflammatory process in OA. OBJECTIVE: to determine the association of digital pressure sign in patients with and without osteoarthritis of the knee. MATERIAL AND METHODS: this was an observational, comparative cross-sectional study, carried out in patients with and without a diagnosis of knee OA, to whom the digital pressure sign was determined. The sample was calculated with the formula for two proportions, obtaining a total of 40 participants per group, obtained by non-probabilistic sampling for convenience. The statistical analysis included frequencies, percentages, 2 and OR. The bioethics regulations in force were respected. RESULTS: the study included 80 participants, with a median age of 48.9 years (RQI 46-53.7), 73.1% were predominantly female sex (38), and a statistically significant association was found between patients with OA and the presence of digital pressure sign, 2 4.62 and p value = 0.41, OR of 2.65. CONCLUSIONS: the presence of digital pressure sign increases the probability of having OA 2.65 times more.

INTRODUCCIÓN: se estima que 302 millones de personas en el mundo son afectadas por osteoartritis, correspondiendo 60% a osteoartritis (OA) de rodilla, causante de 80% de discapacidad en adultos mayores, de ahí la importancia de la asociación del signo de digito-presión con el proceso inflamatorio temprano en OA. OBJETIVO: determinar la asociación del signo de digito-presión en pacientes con y sin osteoartritis de rodilla. MATERIAL Y MÉTODOS: estudio observacional, transversal comparativo, realizado en pacientes con y sin diagnóstico de OA de rodilla, a quienes se les determinó el signo de digito-presión; la muestra se calculó con la fórmula para dos proporciones que determinó un total de 40 participantes por grupo, obtenidos por muestreo no probabilístico por conveniencia; el análisis estadístico incluyó frecuencias, porcentajes, 2 y OR. Se respetó la reglamentación de bioética vigente. RESULTADOS: el estudio incluyó a 80 participantes, con una mediana de edad de 48.9 años (RIQ 46-53.7), predominó el sexo femenino en 73.1% (38). Se encontró asociación estadísticamente significativa entre pacientes con OA y la presencia del signo de digito-presión, 2 4.62 y p = 0.41, OR de 2.65. CONCLUSIONES: la presencia del signo de digito-presión aumenta 2.65 veces más la probabilidad de tener OA.

Simulating drifting fish aggregating device trajectories to identify potential interactions with endangered sea turtles.

Purse-seine fishers using drifting fish aggregating devices (dFADs), mainly built with bamboo, plastic buoys, and plastic netting, to aggregate and catch tropical tuna, deploy 46,000-65,000 dFADs per year in the Pacific Ocean. Some of the major concerns associated with this widespread fishing device are potential entanglement of sea turtles and other marine fauna in dFAD netting; marine debris and pollution; and potential ecological damage via stranding on coral reefs, beaches, and other essential habitats for marine fauna. To assess and quantify the potential connectivity (number of dFADs deployed in an area and arriving in another area) between dFAD deployment areas and important oceanic or coastal habitat of critically endangered leatherback (Dermochelys coriacea) and hawksbill (Eretmochelys imbricata) sea turtles in the Pacific Ocean, we conducted passive-drift Lagrangian experiments with simulated dFAD drift profiles and compared them with known important sea turtle areas. Up to 60% of dFADs from equatorial areas were arriving in essential sea turtle habitats. Connectivity was less when only areas where dFADs are currently deployed were used. Our simulations identified potential regions of dFAD interactions with migration and feeding habitats of the east Pacific leatherback turtle in the tropical southeastern Pacific Ocean; coastal habitats of leatherback and hawksbill in the western Pacific (e.g., archipelagic zones of Indonesia, Papua New Guinea, and Solomon Islands); and foraging habitat of leatherback in a large equatorial area south of Hawaii. Additional research is needed to estimate entanglements of sea turtles with dFADs at sea and to quantify the likely changes in connectivity and distribution of dFADs under new management measures, such as use of alternative nonentangling dFAD designs that biodegrade, or changes in deployment strategies, such as shifting locations.

Simulación de las trayectorias de dispositivos de concentración de peces a la deriva para identificar las interacciones potenciales con las tortugas marinas en peligro de extinción Resumen Los pescadores que usan redes de cerco con dispositivos de concentración de peces a la deriva (dFADs), hechos principalmente con bambú, boyas de plástico y redes de plástico, para concentrar y capturar atún, instalan entre 46,000 y 65,000 dFADs al año en el Océano Pacífico. Algunas de las problemáticas principales asociadas con este dispositivo de pesca de uso extenso son el enredamiento potencial de tortugas marinas y otras especies marinas en las redes de los dFADs; los desechos marinos y la contaminación; y el potencial daño ecológico por el varamiento en los arrecifes de coral, playas y otros hábitats esenciales para la fauna marina. Realizamos experimentos lagrangianos de deriva pasiva con la simulación de perfiles de deriva de los dFADs y los comparamos con áreas conocidas de importancia para las tortugas marinas. Esto fue con el objetivo de evaluar y cuantificar la conectividad potencial (número de dFADs instalados en un área que llegan a otra área) entre las áreas de instalación de dFADs y los hábitats oceánicos o costeros importantes para la tortuga laúd (Dermochelys coriacea) y la tortuga de carey (Eretmochelys imbricata), ambas en peligro crítico de extinción, en el Océano Pacífico. Hasta el 60% de los dFADs de las áreas ecuatoriales llegaron a los hábitats esenciales para las tortugas marinas. La conectividad fue menor sólo cuando se usaron áreas en donde actualmente hay dFADs instalados. Nuestras simulaciones identificaron regiones potenciales de interacción entre los dFADs y los hábitats de migración y alimentación de la tortuga laúd en el sureste tropical del Océano Pacífico; los hábitats costeros de ambas especies en el Pacífico occidental (p. ej.: zonas de archipiélagos en Indonesia, Papúa Nueva Guinea y en las Islas Salomón); y en el hábitat de forrajeo de la tortuga laúd en una gran área ecuatorial al sur de Hawái. Se requiere de mayor investigación para estimar el enredamiento de las tortugas marinas con los dFADs en el mar y para cuantificar los cambios probables en la conectividad y la distribución de los dFADs bajo nuevas medidas de manejo, como el uso alternativo de diseños que eviten el enredamiento y sean biodegradables, o cambios en las estrategias de instalación, como la reubicación.

Evaluation of enhanced nanofiltration membranes for improving magnesium recovery schemes from seawater/brine: Integrating experimental performing data with a techno-economic assessment.

The global demand for valuable metals and minerals necessitates the exploration of alternative, sustainable approaches to mineral recovery. Seawater mining has emerged as a promising option, offering a vast reserve of minerals and an environmentally friendly alternative to land-based mining. Among the various techniques, Nanofiltration (NF) has gained significant attention as a preliminary treatment step in Minimum Liquid Discharge (MLD) and Zero Liquid Discharge (ZLD) schemes. This study focused on the potential of two underexplored commercial polyamide based NF membranes, Synder NFX and Vontron VNF1, with enhanced divalent over monovalent separation factors, in optimizing the extraction of magnesium hydroxide (Mg(OH)2) from seawater and seawater reverse osmosis (SWRO) brines. The research encompassed a thorough characterization of the membranes utilizing advanced physic-chemical analytical techniques, followed by rigorous experimental assessments using synthetic seawater and SWRO brine in concentration configuration. The findings highlighted the superior selectivity of NFX for magnesium recovery from SWRO brine and the promising concentration factors of VNF1 for seawater treatment. Cross-validation of experimental data with a mathematical model demonstrated the model's reliability as a process design tool in predicting membrane performance. A comprehensive techno-economic evaluation demonstrates the potential of NFX, operating optimally at 23 bar pressure and 70% permeate recovery rate, to yield an estimated annual revenue of 5.683 M€/yr through Mg(OH)2 production from SWRO brine for a plant with a nominal capacity of 0.8 Mm3/y. This research shed light on the promising role of NF membranes in enhancing mineral recovery taking benefit of their separation factors and emphasizes the economic viability of leveraging NF technology for maximizing magnesium recovery from seawater and SWRO brines.

Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Biological and chemical characterization in relation to the yield of radish (Raphanus sativus L.) nourished with humus from plant residues.

The increase in prices of fertilizers, energy and other materials necessary for the industry triggered a global economic crisis. Reason that was investigated on the biological and chemical characteristics in relation to the yield of radish nourished with humus from plant residue. The objective was to determine the appropriate dose of humus to obtain greater yield and its relationship with the chemical and biological characteristics of the radish. It is based on applied methodology with an experimental approach; Therefore, the Completely Random Block Design model was used, which consisted of 3 blocks and 5 treatments that were T1 with 0, T2 with 4, T3 with 6, T4 with 8 and T5 with 10 t/ha of humus and They applied 15 days after sowing. The physical characteristics of the radish were evaluated and processed using analysis of variance and Duncan. Concentration of elements in leaves and stomatal density were also analyzed. It was determined that T5 stood out in total plant length with 28.95 cm, plant weight with 76.87 g, equatorial diameter with 4,404 cm and commercial yield with 20,296 t/ha. Nitrogen consumption in relation to yield with 247.44 kg/ha. Stomatal density 459 stomata/mm2 and profitability with 150% and nutrient concentration in leaves highlighted T4 with N, K, Ca, Mg, Mo and Zn. It concludes that T5 stood out with 20,296 t/ha, which differed by 26.04% in relation to the control (T1) with 15,011 t/ha. Therefore, this dose added nutrients to the soil that improved the availability for plant absorption and this influenced the concentration of nutrients in leaves such as N, P and Fe and stomatal density with 459 stomata/mm2, which had a response in good development, strengthening against environmental stress and therefore greater performance.

Assessing SARS-CoV-2 Testing Adherence in a University Town: Recurrent Event Modeling Analysis.

BACKGROUND: Healthy Davis Together was a program launched in September 2020 in the city of Davis, California, to mitigate the spread of COVID-19 and facilitate the return to normalcy. The program involved multiple interventions, including free saliva-based asymptomatic testing, targeted communication campaigns, education efforts, and distribution of personal protective equipment, community partnerships, and investments in the local economy. OBJECTIVE: This study identified demographic characteristics of individuals that underwent testing and assessed adherence to testing over time in a community pandemic-response program launched in a college town in California, United States. METHODS: This study outlines overall testing engagement, identifies demographic characteristics of participants, and evaluates testing participation changes over 4 periods of the COVID-19 pandemic, distinguished by the dominant variants Delta and Omicron. Additionally, a recurrent model is employed to explore testing patterns based on the participants' frequency, timing, and demographic characteristics. RESULTS: A total of 770,165 tests were performed between November 18, 2020, and June 30, 2022, among 89,924 (41.1% of total population) residents of Yolo County, with significant participation from racially or ethnically diverse participants and across age groups. Most positive cases (6351 of total) and highest daily participation (895 per 100,000 population) were during the Omicron period. There were some gender and age-related differences in the pattern of recurrent COVID-19 testing. Men were slightly less likely (hazard ratio [HR] 0.969, 95% CI 0.943-0.996) to be retested and more likely (HR 1.104, 95% CI 1.075-1.134) to stop testing altogether than women. People aged between 20 and 34 years were less likely to be retested (HR 0.861, 95% CI 0.828-0.895) and more likely to stop testing altogether (HR 2.617, 95% CI 2.538-2.699). However, older age groups were less likely to stop testing, especially those aged between 65-74 years and 75-84 years, than those aged between 0 and 19 years. The likelihood of stopping testing was lower (HR 0.93, 95% CI 0.889-0.976) for the Asian group and higher for the Hispanic or Latino (HR 1.185, 95% CI 1.148-1.223) and Black or African American (HR 1.198, 95% CI 1.054-1.350) groups than the White group. CONCLUSIONS: The unique features of a pandemic response program that supported community-wide access to free asymptomatic testing provide a unique opportunity to evaluate adherence to testing recommendations and testing trends over time. Identification of individual and group-level factors associated with testing behaviors can provide insights for identifying potential areas of improvement in future testing initiatives.

Morphological and clinical findings in placentas and newborns with a history of tobacco, alcohol, and other substance abuse during pregnancy.

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.

Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit?

Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP ''per se'' and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin-angiotensin-aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide-like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.

Bilateral macular edema in sistemic sclerosis.

Systemic sclerosis is a chronic, autoimmune, multisystem disease characterized by vascular dysfunction, chronic inflammation and widespread fibrosis. Although vascular involvement commonly manifests in the skin, it can also affect other organs, including the eyes. The characteristic vascular alteration is an obliterative fibroproliferative vasculopathy leading to hypoxia and tissue ischemia. We present a case of bilateral macular edema in a patient diagnosed with systemic sclerosis, as a consequence of retinal and choroidal vascular changes.

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-ß1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics.

BACKGROUND: Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers. METHODS: Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-ß1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves. RESULTS: Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-ß1 (p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A (p = 0.016), TGF-ß1 (p = 0.009), and Dkk1 (p = 0.042). ROC curve analysis of IHC reactivity for TGF-ß1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; p 0.005) S 75% E 84.4%. CONCLUSIONS: Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-ß1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

Wildfires and social media discourse: exploring mental health and emotional wellbeing through Twitter.

Introduction: The rise in global temperatures due to climate change has escalated the frequency and intensity of wildfires worldwide. Beyond their direct impact on physical health, these wildfires can significantly impact mental health. Conventional mental health studies predominantly rely on surveys, often constrained by limited sample sizes, high costs, and time constraints. As a result, there is an increasing interest in accessing social media data to study the effects of wildfires on mental health. Methods: In this study, we focused on Twitter users affected by the California Tubbs Fire in 2017 to extract data signals related to emotional well-being and mental health. Our analysis aimed to investigate tweets posted during the Tubbs Fire disaster to gain deeper insights into their impact on individuals. Data were collected from October 8 to October 31, 2017, encompassing the peak activity period. Various analytical methods were employed to explore word usage, sentiment, temporal patterns of word occurrence, and emerging topics associated with the unfolding crisis. Results: The findings show increased user engagement on wildfire-related Tweets, particularly during nighttime and early morning, especially at the onset of wildfire incidents. Subsequent exploration of emotional categories using Linguistic Inquiry and Word Count (LIWC) revealed a substantial presence of negative emotions at 43.0%, juxtaposed with simultaneous positivity in 23.1% of tweets. This dual emotional expression suggests a nuanced and complex landscape, unveiling concerns and community support within conversations. Stress concerns were notably expressed in 36.3% of the tweets. The main discussion topics were air quality, emotional exhaustion, and criticism of the president's response to the wildfire emergency. Discussion: Social media data, particularly the data collected from Twitter during wildfires, provides an opportunity to evaluate the psychological impact on affected communities immediately. This data can be used by public health authorities to launch targeted media campaigns in areas and hours where users are more active. Such campaigns can raise awareness about mental health during disasters and connect individuals with relevant resources. The effectiveness of these campaigns can be enhanced by tailoring outreach efforts based on prevalent issues highlighted by users. This ensures that individuals receive prompt support and mitigates the psychological impacts of wildfire disasters.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Proteasome-dependent degradation of histone H1 subtypes is mediated by its C-terminal domain.

Histone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1.0-H1.5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib. H1 subtypes accumulate upon treatment with both drugs, indicating that the proteasome is involved in the regulation of H1 protein levels. Proteasome inhibition caused a global increase in cytoplasmatic H1, with slight changes in the composition of H1 bound to chromatin and chromatin accessibility and no alterations in the nucleosome repeat length. The analysis of the proteasome degradation pathway showed that H1 degradation is ubiquitin-independent. The whole protein and its C-terminal domain can be degraded directly by the 20S proteasome in vitro. Partial depletion of PA28γ revealed that this regulatory subunit contributes to H1 degradation within the cell. Our study shows that histone H1 protein levels are under tight regulation to prevent its accumulation in the nucleus. We revealed a new regulatory mechanism for histone H1 degradation, where the C-terminal disordered domain is responsible for its targeting and degradation by the 20S proteasome, a process enhanced by the regulatory subunit PA28γ.