Development of a novel clinimetric tool: PAtient Reported Disease Activity Index in Rheumatoid Arthritis (PARDAI-RA) by PANLAR, for the assessment of patients living with rheumatoid arthritis.

BACKGROUND: Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. METHODS: In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. RESULTS: We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. CONCLUSION: In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care.

Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's Disease.

Alzheimer's disease is the main cause of aging-associated dementia, for which there is no effective treatment. In this work, we reanalyze the information of a previous Genome Wide Association Study, using a new pipeline design to identify novel potential drugs. With this approach, ribonucleoside-diphosphate reductase gene (RRM2B) emerged as a candidate target and its inhibitor, 2', 2'-difluoro 2'deoxycytidine (Gemcitabine), as a potential pharmaceutical drug against Alzheimer's disease. We functionally verified the effect of inhibiting the RRM2B homologue, rnr-2, in an Alzheimer's model of Caenorhabditis elegans, which accumulates human Aß1-42 peptide to an irreversible paralysis. RNA interference against rnr-2 and also treatment with 200 ng/ml of Gemcitabine, showed animprovement of the phenotype. Gemcitabine treatment increased the intracellular ATP level 3.03 times, which may point to its mechanism of action. Gemcitabine has been extensively used in humans for cancer treatment but at higher concentration. The 200 ng/ml concentration did not exert a significant effect over cell cycle, or affected cell viability when assayed in microglia N13 cell line. Thus, inhibitory drug of the RRM2B activity could be of potential use to treat Alzheimer's disease and particularly Gemcitabine might be considered as a promising candidate to be repurposed for its treatment.

Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping.

The objective of this study was to develop a versatile lipid core for the 'brick-dust type of drugs' (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

Performance of ChatGPT, Bard, Claude, and Bing on the Peruvian National Licensing Medical Examination: a cross-sectional study.

PURPOSE: We aimed to describe the performance and evaluate the educational value of justifications provided by artificial intelligence chatbots, including GPT-3.5, GPT-4, Bard, Claude, and Bing, on the Peruvian National Medical Licensing Examination (P-NLME). METHODS: This was a cross-sectional analytical study. On July 25, 2023, each multiple-choice question (MCQ) from the P-NLME was entered into each chatbot (GPT-3, GPT-4, Bing, Bard, and Claude) 3 times. Then, 4 medical educators categorized the MCQs in terms of medical area, item type, and whether the MCQ required Peru-specific knowledge. They assessed the educational value of the justifications from the 2 top performers (GPT-4 and Bing). RESULTS: GPT-4 scored 86.7% and Bing scored 82.2%, followed by Bard and Claude, and the historical performance of Peruvian examinees was 55%. Among the factors associated with correct answers, only MCQs that required Peru-specific knowledge had lower odds (odds ratio, 0.23; 95% confidence interval, 0.09-0.61), whereas the remaining factors showed no associations. In assessing the educational value of justifications provided by GPT-4 and Bing, neither showed any significant differences in certainty, usefulness, or potential use in the classroom. CONCLUSION: Among chatbots, GPT-4 and Bing were the top performers, with Bing performing better at Peru-specific MCQs. Moreover, the educational value of justifications provided by the GPT-4 and Bing could be deemed appropriate. However, it is essential to start addressing the educational value of these chatbots, rather than merely their performance on examinations.

Determinants of genetic diversity in Neotropical salamanders (Plethodontidae: Bolitoglossini).

Genetic diversity is the raw material of evolution, yet the reasons why it varies among species remain poorly understood. While studies at deeper phylogenetic scales point to the influence of life history traits on genetic diversity, it appears to be more affected by population size but less predictable at shallower scales. We used proxies for population size, mutation rate, direct selection, and linked selection to test factors affecting genetic diversity within a diverse assemblage of Neotropical salamanders, which vary widely for these traits. We estimated genetic diversity of noncoding loci using ddRADseq and coding loci using RNAseq for an assemblage of Neotropical salamanders distributed from northern Mexico to Costa Rica. Using ddRADseq loci, we found no significant association with genetic diversity, while for RNAseq data we found that environmental heterogeneity and proxies of population size predict a substantial portion of the variance in genetic diversity across species. Our results indicate that diversity of coding loci may be more predictable than that of noncoding loci, which appears to be mostly unpredictable at shallower phylogenetic scales. Our results suggest that coding loci may be more appropriate for genetic diversity estimates used in conservation planning because of the lack of any association between the variables we used and genetic diversity of noncoding loci.

Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru.

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change in amino acid, leading to the non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014 and 2021. The criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi, and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced, and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of insecticide resistance mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

Time-Resolved Temperature Mapping Leveraging the Strong Thermo-Optic Effect in Phase-Change Materials.

Optical phase-change materials are highly promising for emerging applications such as tunable metasurfaces, reconfigurable photonic circuits, and non-von Neumann computing. However, these materials typically require both high melting temperatures and fast quenching rates to reversibly switch between their crystalline and amorphous phases: a significant challenge for large-scale integration. In this work, we use temperature-dependent ellipsometry to study the thermo-optic effect in GST and use these results to demonstrate an experimental technique that leverages the thermo-optic effect in GST to enable both spatial and temporal thermal measurements of two common electro-thermal microheater designs currently used by the phase-change community. Our approach shows excellent agreement between experimental results and numerical simulations and provides a noninvasive method for rapid characterization of electrically programmable phase-change devices.

[Kawasaki disease and multisystem inflammatory syndrome in children. Differences, and similarities in a pediatric center in Mexico]. / Enfermedad de Kawasaki y síndrome inflamatorio multisistémico en niños. Diferencias y similitudes en un centro pediátrico de México.

OBJECTIVE: To evaluate the differences and similarities in clinical picture, laboratory findings and outcomes between children's with Kawasaki Disease (KD) versus multisystem inflammatory syndrome (MIS-C). METHODS: We conducted a retrospective, comparative study from children with Kawasaki Disease (KD) hospi-talized in Sinaloa Pediatric Hospital from January 1, 2004, to March 31, 2020, and patients with multisystem inflammatory syndrome (MIS-C) according with World Health Organization (WHO) case definition criteria be-tween May 1, 2020 and May 31, 2021. Demographic characteristics, epidemiological data, clinical features, laboratory findings, type of treatment and clinical outcomes were compared among both groups. RESULTS: Eighty-one patients were included (62 patients with KD and 19 with MIS-C). several clinical and lab-oratory differences were found among these two entities. Median age was lower in KD vs. MIS-C (25 vs 79 months). Those finding more frequent in KD were male gender (64.5 vs. 47.4%), Mucocutaneous features (93.5 vs. 63.2%): Oral changes (83.9 vs. 63.2%) and extremity changes (77.4 vs. 57.9%); complete form of KD was (75.8 vs. 47.4%), Coronary artery aneurysm (16.1 vs. 11.8%). Secondly, findings that were more frequent in MIS-C than KD were Gastrointestinal involvement (89.4 vs. 9.6%), shock (57.9 vs. 3.2%), neurological symp-toms (63.1 vs. 11.2%), kidney involvement (52.6 vs. 16.1%), heart disease in general (52.9% vs 29%): Myocardial dysfunction (23.5 vs. 11.3%) and pericardial effusion (17.6 vs. 2.9%). Lymphocyte count (2.07 + 2.03 vs. 4.28 + 3.01/mm3), platelet count (197.89 + 187.51 vs. 420.37 + 200.08/mm3); serum albumin (2.29 + 0.65 vs. 3.33 + 0.06g/dL), and CPR (21.4 + 11.23 vs. 14.26 + 12.37 mg/dL). KD vs. MIS-C types of Treatment: IVIG (96.8 vs. 94.7%), systemic steroids (4.82 vs. 94.7%), IVIG resistance (19.4 vs. 15.8). Finally, mortality in KD was 0% and 5.3% in MIS-C. CONCLUSIONS: Similarities were found in both groups such as fever, rash, and conjunctivitis. Nevertheless, signifi-cant differences such as severity of clinical presentation with multi-organ involvement and worst inflammato-ry response were found more frequently in MIS-C group than KD group, requiring more fluid replacement, use of inotropic agents and higher steroids dosages. Also, mortality rate was higher in patients with MIS-C thanpatients with KD. Similar results have been observed in other studies where both disorders were compared.

OBJECTIVO: Evaluar las diferencias y similitudes en el cuadro clínico, los hallazgos de laboratorio y desenlaces médicos de pacientes pediátricos con enfermedad de Kawasaki versus síndrome inflamatorio multisistémico. MÉTODOS: Estudio comparativo y retrospectivo, efectuado en niños con enfermedad de Kawasaki, atendidos en el Hospital Pediátrico de Sinaloa, entre el 1 de enero de 2004 al 31 de marzo de 2020, y pacientes con sín-drome inflamatorio multisistémico (según los criterios de la Organización Mundial de la Salud), del 1 de mayo de 2020 al 31 de mayo de 2021. Se evaluaron las características demográficas, epidemiológicos y clínicas, además de los hallazgos de laboratorio, tipo de tratamiento y desenlaces clínicos en ambos grupos. RESULTADOS: Se incluyeron 81 pacientes: 62 con enfermedad de Kawasaki y 19 con síndrome inflamatorio mul-tisistémico. Se encontraron varias diferencias clínicas y de laboratorio en ambas alteraciones. La mediana de edad fue menor en pacientes con enfermedad de Kawasaki versus síndrome inflamatorio multisistémico (25 vs 79 meses). La mayoría de los pacientes con enfermedad de Kawasaki fueron hombres (64.5 vs 47.4%), con características mucocutáneas (93.5 vs 63.2%): cambios orales (83.9 vs 63.2%) y cambios en las extremidades (77.4 vs 57.9%); la forma completa de enfermedad de Kawasaki fue 75.8 vs 47.4%, concomitante con aneuris-ma de la arteria coronaria (16.1 vs 11.8%). Los hallazgos más frecuentes en sujetos con síndrome inflamatorio multisistémico fueron: afectación gastrointestinal (89.4 vs 9.6 %), choque (57.9 vs 3.2%), síntomas neurológicos (63.1 vs 11.2%), afectación renal (52.6 vs 16.1%) y cardiopatías en general (52.9 vs 29%): disfunción miocárdica (23.5 vs 11.3%) y derrame pericárdico (17.6 vs 2.9%). La concentración media de linfocitos fue: 2.07 + 2.03 vs4.28 + 3.01/mm3), plaquetas (197.89 + 187.51 vs 420.37 + 200.08/mm3); albúmina sérica (2.29 + 0.65 vs 3.33 + 0.06 g/dL) y PCR (21.4 + 11.23 vs 14.26 + 12.37 mg/dL). Los tratamientos en enfermedad de Kawasaki vssíndrome inflamatorio multisistémico: IVIG (96.8 vs 94.7%), corticosteroides sistémicos (4.82 vs 94.7%), resis-tencia a IVIG (19.4 vs 15.8). La mortalidad fue de 0 vs 5.3%. CONCLUSIONES: Se encontraron similitudes en cuanto a síntomas en ambos grupos (fiebre, exantema y conjun-tivitis); no obstante, hubo diferencias significativas respecto de las manifestaciones clínicas, con afección multiorgánico y peor respuesta inflamatoria en pacientes con síndrome inflamatorio multisistémico, incluso mayor requerimiento de reposición de líquidos, administración de agentes inotrópicos, dosis más altas de corticosteroides, y elevada tasa de mortalidad. Estos resultados se han observado en otros estudios, donde se compararon ambos trastornos.

First Ecuadorian statement consensus for the evaluation and treatment of osteoporosis.

Osteoporosis management has become more relevant as the life expectancy increases. In Ecuador, approximately 19% of adults over 65 years of age have been diagnosed with osteoporosis. There is no national consensus for the management and prevention of the disease being this proposal the first Ecuadorian consensus. INTRODUCTION: In Ecuador, it is estimated that around 19% of adults over 65 years of age have osteoporosis. Due to the increase in life expectancy in the world population, the evaluation and management of osteoporosis has become more relevant. Currently, there is no national consensus for the management and prevention of the disease. The Ecuadorian Society of Rheumatology presented the project for the elaboration of the first Ecuadorian consensus for the management and prevention of osteoporosis. METHODS: A panel of experts in multiple areas and extensive experience was invited to participate. The consensus was carried out using the Delphi method. Six working dimensions were created: definition and epidemiology of osteoporosis, fracture risk prediction tools, non-pharmacological treatment, pharmacological treatment, calcium and vitamin D, and glucocorticoid-induced osteoporosis. RESULTS: The first round was held in December 2021, followed by the second round in February 2022 and the third round in March 2022. The data was shared with the specialists at the end of each round. After three rounds of work, a consensus was reached for the management and prevention of osteoporosis. CONCLUSION: This is the first Ecuadorian consensus for the management and treatment of postmenopausal osteoporosis.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Infections in patients with adverse reactions to the use of unknown modeling substances for soft tissue enhancement in Cali, Colombia.

The infiltration of foreign materials not approved for medical purposes or of modeling substances used in soft tissue to modify the anatomical appearance for aesthetic purposes represents a serious health problem. These procedures lead to the development of delayed complications, including infections. The objective of this study was to characterize infections in patients with adverse reactions to the use of modeling substances in Cali, Colombia. A cross-sectional and descriptive study was used to determine the frequency of bacterial and fungal infections associated with complications from and adverse reactions to the use of modeling substances in 113 patients. We identified microorganisms in 22 patients and a frequency of 68.1% monomicrobial infections and 31.8% polymicrobial infections. The microorganisms identified in our study included Bacillus cereus, Mycobacterium fortuitum, and Pseudomonas stutzeri, among other microorganisms. The presence of adverse effects derived from the use of illegal modeling substances has been demonstrated; among these effects, infections occur with high frequency and place the health of the patient at risk and increase problems in health care.

A Novel Case of Acquired Isolated Left Ventricular Non-compaction in a Primigravida: Revisiting the Diagnostic Criteria of Left Ventricular Non-compaction.

Left ventricular non-compaction (LVNC) is rare cardiomyopathy characterized by the presence of a two-layered myocardium with prominent trabeculations. It has high rates of mortality and morbidity. Clinical presentation could vary from asymptomatic patients to developing ventricular arrhythmias, thromboembolism, heart failure, and even sudden cardiac death. We present a 23-year-old primigravida with a childhood history of dilated cardiomyopathy secondary to post-viral myocarditis presenting at 32 weeks gestation with dyspnea on exertion. Initial 2-D echocardiogram revealed a mildly dilated left ventricle with apical trabeculation and a 2-layer distinction between compacted and noncompacted myocardium indicating non-compaction of the left ventricle. This case presents a peculiar confluence of cardiac genetics, normal physiology, and infection. We describe a rare form of acquired LVNC that transformed from another type of cardiomyopathy to LVNC during pregnancy drawing attention to the causality pathways of LVNC.

High-sensitivity cardiac troponin I is a biomarker for increased arterial stiffness in systemic lupus erythematous women with normal kidney function.

Cardiovascular disease (CVD) is a main cause of death in patients with systemic lupus erythematous (SLE). Algorithms for cardiovascular risk stratification in general population underestimate the risk for CVD in SLE. Our study aimed to determine whether serum high-sensitivity cardiac troponin I (hs-cTnI) might help to identify SLE patients with subclinical atherosclerosis. Arterial stiffness was assessed measuring the carotid-femoral pulse wave velocity (PWV) in 68 SLE women with a normal or almost normal kidney function and in 71 controls of similar characteristics. None of the participants had a history of an overt CVD. Serum hs-cTnI level was measured using the chemiluminescence method. Factors associated with an increased PWV (iPWV) were identified and multivariate analysis was performed. When detectable, patients tended to have had higher hs-cTnI levels than controls [2.9 (2.3-4.0) vs 2.4 (2.2-4.1); p = 0.098] and were more likely to have detectable hs-cTnI [50% vs 28%, odds ratio (OR) 7.0; 95% confidence interval (CI) 0.008-0.013]. Also, patients with iPWV were more likely to have detectable hs-cTnI than those with normal PWV (OR 6.4; 95% CI 0.019-0.026). In the multivariate analysis, the age at SLE diagnosis (OR 1.24; 95% CI 1.04-1.48), systolic blood pressure (OR 1.28; 95% CI 1.10-1.48) and detectable hs-cTnI level (OR 2.04; 95% CI 1.18-3.50) were independently associated with an iPWV. The negative predictive value of having an iPWV with undetectable hs-cTnI levels was 88%. Hs-cTnI may be a useful biomarker for the identification of SLE patients with iPWV as a surrogated marker of subclinical atherosclerosis. Specifically targeted prospective studies are needed to confirm this hypothesis.

Traditional medicine in Incahuasi: An ethnobotanical study.

Introduction: Understanding the use of medicinal plants as herbal medicines is considered essential for the survival and continuity of humanity. Since ancient times, the origin and development of natural and traditional medicine have been intrinsically linked to humanity struggle for survival. Nowadays, ethnobotanical studies are employed as a tool for the preservation and conservation not only of taxonomic biodiversity but also of cultural biodiversity. Methodology: A descriptive research with a quantitative, non-experimental cross-sectional design was carried out. The study was conducted in six Quechua-speaking communities in the district of Incahuasi (3,000 meters above sea level), selected for convenience considering factors such as altitude, accessibility, and proximity to the city. A questionnaire was administered to 32 residents from the communities, who shared their knowledge about medicinal plants, providing relevant information about them. The gender of the participants was considered because men and women use traditional medicine and the knowledge of them is transmitted from parents to children. Results: During the study, a total of 46 medicinal species were recorded, belonging to 42 genera and 22 botanical families. The most representative medicinal families used by the informants of the communities were Asteraceae (30.4%) and Lamiaceae (15.2%). It is also worth mentioning the genera Salvia and Baccharis, with three and two species respectively, which are commonly used to treat various ailments and diseases. Conclusions: Ethnobotanical information was collected on the medicinal plants used by the community members of the selected communities in Incahuasi, and the corresponding data were recorded. A total of 46 plants were collected, with the majority belonging to the Asteraceae and Lamiaceae families.

Sclerostin as a biomarker of cardiovascular risk in women with systemic lupus erythematosus.

Cardiovascular disease is one of the main causes of death in patients with systemic lupus erythematosus (SLE). On the other hand, sclerostin is a reliable and early biomarker of vascular calcification. This study aimed to estimate the association between sclerostin and two markers of cardiovascular risk, carotid atherosclerotic plaque (CP) and carotid-femoral pulse wave velocity (PWV), in women with SLE. The presence of CP (determined by carotid artery ultrasound) and PWV were measured in 68 women with SLE and preserved renal function. None of the participants had a history of cardiovascular disease. Serum levels of sclerostin were determined using the ELISA method. Other factors associated with increased cardiovascular risk were also measured. The association between sclerostin, CP and PWV was assessed using Receiver Operating Characteristic (ROC) curves and multivariate regression models. The area under the ROC curve was 0.785 (95% confidence interval [CI] 0.662-0.871) for CP and 0.834 (95% CI 0.729-0.916) for dichotomized PWV. After adjusting for other cardiovascular risk factors, it was found that a 10-units increase in sclerostin values was associated with a 44% increase in the odds of CP (95% CI 1-105), but no adjusted association was observed between sclerostin and PWV. Predictive models included age (for both outcomes), hypertension, Framingham risk score and C-reactive protein (for PWV), but not sclerostin. Sclerostin is associated with the presence of CP in women with SLE. Further research should confirm its possible role as a biomarker of cardiovascular risk in these patients.

D-Dimer trend in a long-term rheumatoid arthritis patient with tofacitinib treatment and recent COVID-19 infection

The SARS-CoV-2 virus was first identified in December 2019, the infection was named COVID-19. The initial symptoms and evolution of the disease have been described over the past year. The virus has been shown to increase the risk of thromboembolic events due to the hypercoagulable state triggered by systemic endothelial inflammation. We present the case of a patient with a history of rheumatoid arthritis under prolonged treatment with tofacitinib, who presented COVID-19 and subsequently developed a hypercoagulable state of approximately 6 months' duration. The possible association between viral infection and the use of tofacitinib is debated.

El virus SARS-CoV-2 se identificó por primera vez en diciembre de 2019; la infección se denominó COVID-19. Los síntomas iniciales y la evolución de la enfermedad se han descrito durante el último anno. Se ha demostrado que el virus aumenta el riesgo de eventos trom-boembólicos debido al estado de hipercoagulabilidad desencadenado por la inflamación endotelial sistêmica. Se presenta el caso de un paciente con antecedente de artritis reuma-toide en tratamiento prolongado con tofacitinib, que presentó COVID-19 y posteriormente desarrolló un estado de hipercoagulabilidad de aproximadamente seis meses de duración. Se debate la posible asociación entre la infección viral y el uso de tofacitinib.

Nailfold capillaroscopy in diabetes mellitus: a case of neo-angiogenesis after achieving normoglycemia.

Diabetes mellitus (DM) is a disease process characterized by a chronic hyperglycemic milieu that leads to micro and macrovascular complications, including diabetic retinopathy, diabetic nephropathy and diabetic neuropathy. During the last decade, researchers have used nail-fold capillaroscopy to study the microvascular alterations in rheumatologic diseases; however, the technology is gaining momentum in other disease processes that alter microvascular architecture. We observed a drastic improvement in the nail-fold capillary architecture in a patient with uncontrolled DM. After achieving excellent glycemic control 6 months after diagnosis, increased capillary density and evident rearrangement of the capillaries replaced the avascular areas and giant capillaries found at the time of diagnosis.

Ultra-low-energy programmable non-volatile silicon photonics based on phase-change materials with graphene heaters.

Silicon photonics is evolving from laboratory research to real-world applications with the potential to transform many technologies, including optical neural networks and quantum information processing. A key element for these applications is a reconfigurable switch operating at ultra-low programming energy-a challenging proposition for traditional thermo-optic or free carrier switches. Recent advances in non-volatile programmable silicon photonics based on phase-change materials (PCMs) provide an attractive solution to energy-efficient photonic switches with zero static power, but the programming energy density remains high (hundreds of attojoules per cubic nanometre). Here we demonstrate a non-volatile electrically reconfigurable silicon photonic platform leveraging a monolayer graphene heater with high energy efficiency and endurance. In particular, we show a broadband switch based on the technologically mature PCM Ge2Sb2Te5 and a phase shifter employing the emerging low-loss PCM Sb2Se3. The graphene-assisted photonic switches exhibited an endurance of over 1,000 cycles and a programming energy density of 8.7 ± 1.4 aJ nm-3, that is, within an order of magnitude of the PCM thermodynamic switching energy limit (~1.2 aJ nm-3) and at least a 20-fold reduction in switching energy compared with the state of the art. Our work shows that graphene is a reliable and energy-efficient heater compatible with dielectric platforms, including Si3N4, for technologically relevant non-volatile programmable silicon photonics.

Diffuse large B cell lymphoma and a novel gammaherpesvirus in northern elephant seals Mirounga angustirostris.

Two emaciated male northern elephant seal (NES) Mirounga angustirostris pups were admitted to The Marine Mammal Center (Sausalito, California, USA) and treated for malnutrition. Complete blood counts showed a progressive moderate to marked leukocytosis characterized by a predominance of large monomorphic mononuclear cells of probable lymphoid origin, frequently with flower-shaped nuclei. Both seals were euthanized due to suspected lymphoid neoplasia. At necropsy, most lymph nodes in both pups were markedly enlarged, some with distinct white nodules, the spleens were diffusely enlarged, and the intestinal mucosae were thickened. Histopathologic features consistent with disseminated large cell lymphoma were identified to varying degrees of severity in lymph nodes, bone marrow, liver, tonsils, spleen, liver, intestines, kidneys, lower urinary tract, and several other organs. Immunohistochemical staining of neoplastic cells was most consistent with B lymphocyte origin, with most cells staining positively for Pax 5 and CD20 with admixed small CD3-positive T lymphocytes and CD204-positive macrophages. PCR and sequencing identified a novel gammaherpesvirus, herein called miroungine gammaherpesvirus 3, from affected tissues. This virus is in a clade outside of named genera that utilize hosts in the suborder Caniformia. The present study is the first description of diffuse large B cell lymphoma with leukemic manifestation and concomitant detection of a novel gammaherpesvirus in free-living NESs. Further research regarding the prevalence of this new gammaherpesvirus and its associated pathogenesis in this species is indicated.