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Purpose: Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers. Methods: Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses. Results: In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05). Conclusions: Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker.
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INTRODUCTION: The purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy treatment-related side effects. By comprehending patient perceptions, it is important to implement change in order to improve patients' quality of life. METHODS: A literature review was conducted on advanced practice (AP) roles in Canada and world-wide; the roles searched were: APRT, nurse practitioner and pharmacist. The search focused on evidence demonstrating improvements made to patient care due to the implementation of these roles. Based on this review and input from a team of experts a qualitative semi-structured interview survey was designed, and pilot tested. The survey consisted of five open-ended questions, which were designed to determine patient satisfaction of an APRT prescribing medication over the course of their radiation therapy treatments. Patients undergoing head and neck radiation therapy treatments at a large, academic cancer centre were invited to participate. Six patients who had a head and neck APRT involved in their treatment were interviewed. A comprehensive thematic analysis was then conducted using the transcripts created from these interviews, which was followed by two independent blinded analyses to ensure validity of the results. DISCUSSION: The thematic analysis produced four salient themes which were: side effect management, care provided by the APRT in comparison to other healthcare workers, patients' access to care, and overall patient satisfaction. Common medications for head and neck radiation therapy treatment related side effects were discussed and these were: Magic Mouthwash, Xylocaine, Nystatin, Benadryl, Advil, Tylenol, Dexamethasone, Tantum, Biotene, Mucaine, Flamazine, Hydrocortisone, Ondansetron, Senokot, and narcotics. CONCLUSION: This study was valuable to understand patient experiences and provide evidence to change processes in order to improve quality of patient centered care. The study revealed that although patients were happy with the process of prescribing medication, they all agreed that having an advanced practice radiation therapist prescribe would improve care. Patient responses further demonstrated the need for future research in regards to side effect management as a whole by APRTs as well as how role clarification can impact patient perceptions of APRTs.
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The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem-loop structures interrupted by mismatch motifs are present in the functionally important 5'- and 3'-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive Uâ¢U base pairs is located in stem-loop 1 of the 3'-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three Uâ¢U base pairs feature two direct hydrogen bonds and are as stable as Watson-Crick A:U base pairs. Plasmodium falciparum 25S rRNA contains a triple Uâ¢U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two Uâ¢U mismatches was identical in both motifs the preferred orientation of the central Uâ¢U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.
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Regiones no Traducidas 3' , Disparidad de Par Base , Motivos de Nucleótidos , ARN Viral , SARS-CoV-2 , Humanos , Emparejamiento Base , COVID-19/virología , Genoma Viral , Enlace de Hidrógeno , Simulación de Dinámica Molecular , Conformación de Ácido Nucleico , Plasmodium falciparum/genética , ARN Viral/química , ARN Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/químicaRESUMEN
BACKGROUND: Depression is a hidden burden, yet it is a leading cause of disability worldwide. Despite the adverse effects of depression, fewer than one-third of patients receive care. Internet-based cognitive behavioral therapy (i-CBT) is an effective treatment for depression, and combining i-CBT with supervised care could make the therapy scalable and effective. A stepped care model is a framework for beginning treatment with an effective and low-intensity intervention while adapting care based on the patient's needs. OBJECTIVE: This study investigated the efficacy of a stepped care i-CBT model for depression based on changes in self-reported depressive symptoms. METHODS: In this single-blinded, randomized controlled trial, participants were allocated to either the i-CBT-only group (28/56, 50%) or the i-CBT with stepped care group (28/56, 50%). Both groups received a 13-week i-CBT program tailored for depression. The i-CBT program was provided through a secure, online mental health clinic called the Online Psychotherapy Tool. Participants read through the sessions and completed the assignments related to each session. Participants in the stepped care group received additional interventions from their care provider based on standard questionnaire scores (ie, Patient Health Questionnaire-9 [PHQ-9], Quick Inventory of Depressive Symptomatology [QIDS], and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) and their assignment responses. From lowest to highest intensity, the additional interventions included SMS text messages, phone calls, video calls, or a video call with a psychiatrist. RESULTS: For this study, 56 participants were recruited to complete an i-CBT program (n=28, 50%; mean age 37.9; SD 13.08 y; 7/28, 27% were men) or an i-CBT with stepped care program (n=28, 50%; mean age 40.6; SD 14.28 y; 11/28, 42% were men). The results of this study indicate that the i-CBT program was effective in significantly reducing depressive symptoms, as measured by the PHQ-9 (F4,80=9.95; P<.001) and QIDS (F2,28=5.73; P=.008); however, there were no significant differences in the reduction of depressive symptoms between the 2 groups (PHQ-9: F4,80=0.43; P=.78; QIDS: F2,28=3.05; P=.06). The stepped care group was not significantly better in reducing depressive symptoms than the i-CBT group (PHQ-9, P=.79; QIDS, P=.06). Although there were no significant differences observed between the number of participants who completed the program between the groups (χ21=2.6; P=.10), participants in the stepped care group, on average, participated in more sessions than those who prematurely terminated participation in the i-CBT group (t55=-2; P=.03; 95% CI -4.83 to -0.002). CONCLUSIONS: Implementing a stepped care approach in i-CBT is an effective treatment for depression, and the stepped care model can assist patients to complete more sessions in their treatment. TRIAL REGISTRATION: Clinicaltrials.gov NCT04747873; https://clinicaltrials.gov/study/NCT04747873.
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Terapia Cognitivo-Conductual , Depresión , Masculino , Humanos , Adulto , Femenino , Depresión/terapia , Calidad de Vida , Terapia Cognitivo-Conductual/métodos , Psicoterapia/métodos , InternetRESUMEN
OBJECTIVES: Glaucoma care demand in UK hospitals has exploded in recent years. This has resulted in a push to community (shared, virtual, etc) care models to reduce the burden on hospital systems and on patients. The study aimed to ascertain patient's experiences around various aspects of their care delivered in community clinics. DESIGN: Observational study. SETTING: Glaucoma Community Clinic, Cambridge, UK. PARTICIPANTS: Ninety-six consecutive patients (M:F 47:49, mean age 70±12 years), recruited from July to September 2022. OUTCOME MEASURES: Patients completed a modified glaucoma patient-reported outcome and experience measure (POEM) regarding their clinic experience and perspective on their diagnosis, treatment and fear of blindness. Patient's thoughts of feeling safe under the community clinical team were gathered. Patient demographics including age, gender, postcodes and education history were used to find their corresponding Lower-Layer Super Output Areas and socioeconomic status. RESULTS: Patients had positive perceptions of their clinic experience. Ninety-six per cent of patients reported that their experience of attending the community clinic was comfortable, and 93% (n=92) felt the experience was the same as expected from the hospital. Feeling safe under the clinician team produced a mean Visual Analogue Scale (VAS) score of 90 (SD 15) and feeling care was organised produced a mean VAS score of 87 (SD 17). Age, gender, disease characteristics and socioeconomic status had no influence on perceived experience. Patients aged <60 years had significantly lower understanding of their diagnosis compared with older groups (p=0.027, η2=0.076), as did suspect glaucoma patients when compared with primary open glaucoma patients (p=0.045, η2=0.085). CONCLUSIONS: A large majority of patients expressed a positive experience, felt safe under the care of their clinical team and their care was well organised. Relatively younger patients (<60 years) and those with no confirmed diagnosis would likely benefit from more consultation time and educational materials to improve their understanding of glaucoma.
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Emociones , Glaucoma , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Miedo , Medición de Resultados Informados por el Paciente , Reino UnidoRESUMEN
INTRODUCTION: Patients with kidney failure experience symptoms that are often under-recognised and undermanaged. These symptoms negatively impact health-related quality of life and are associated with adverse clinical outcomes. Regular symptom assessment, using electronic patient reported outcomes measure (ePROMs) linked to systematic symptom management, could improve such outcomes. Clinical implementation of ePROMs have been successful in routine oncology care, but not used for patients on dialysis. In this study, we describe a pilot study of ePROM-based systematic symptom monitoring and management intervention in patients treated with in-centre haemodialysis. METHODS AND ANALYSIS: This is a parallel-arm, controlled pilot of adult patients receiving in-centre maintenance haemodialysis. Participants in the intervention arm will complete ePROMs once a month for 6 months. ePROMs will be scored real time and the results will be shared with participants and with the clinical team. Moderate-severe symptoms will be flagged using established cut-off scores. Referral options for those symptoms will be shared with the clinical team, and additional symptom management resources will also be provided for both participants and clinicians. Participants in the control arm will be recruited at a different dialysis unit, to prevent contamination. They will receive usual care, except that they will complete ePROMs without the presentation of results to participants of the clinical team. The primary objectives of the pilot are to assess (1) the feasibility of a larger, randomised clinical effectiveness trial and (2) the acceptability of the intervention. Interviews conducted with participants and staff will be assessed using a content analysis approach. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the University Health Network (REB#21-5199) and the William Osler Health System (#23-0005). All study procedures will be conducted in accordance with the standards of University Health Network research ethics board and with the 1964 Helsinki declaration and its later amendments. Results of this study will be shared with participants, patients on dialysis and other stakeholders using lay language summaries, oral presentations to patients and nephrology professionals. We will also be publishing the results in a peer-reviewed journal and at scientific meetings. PROTOCOL VERSION: 4 (16 November 2022). TRIAL REGISTRATION NUMBER: NCT05515991.
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Calidad de Vida , Diálisis Renal , Adulto , Humanos , Estudios de Factibilidad , Proyectos Piloto , Autoinforme , Evaluación de Síntomas , Ensayos Clínicos Controlados como AsuntoRESUMEN
Mid-facial defects involving the eye can result in severe emotional and psychological trauma for the affected individual, apart from the loss of vision. Prosthetic rehabilitation with an orbital prosthesis can camouflage such defects when surgical treatments are limited. The fabrication of an orbital prosthesis requires precise positioning of the iris for an optimal esthetic outcome. Different techniques for accurate iris positioning in orbital or ocular prostheses have been described, but they have been subjective or require elaborate equipment. This clinical report describes a novel and digital solution for iris positioning with the help of augmented reality filters using a smartphone and Instagram app.
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Cell-free protein synthesis assays have become a valuable tool to understand transcriptional and translational processes. Here, we established a fluorescence-based coupled in vitro transcription-translation assay as a read-out system to simultaneously quantify mRNA and protein levels. We utilized the well-established quantification of the expression of shifted green fluorescent protein (sGFP) as a read-out of protein levels. In addition, we determined mRNA quantities using a fluorogenic Mango-(IV) RNA aptamer that becomes fluorescent upon binding to the fluorophore thiazole orange (TO). We utilized a Mango-(IV) RNA aptamer system comprising four subsequent Mango-(IV) RNA aptamer elements with improved sensitivity by building Mango arrays. The design of this reporter assay resulted in a sensitive read-out with a high signal-to-noise ratio, allowing us to monitor transcription and translation time courses in cell-free assays with continuous monitoring of fluorescence changes as well as snapshots of the reaction. Furthermore, we applied this dual read-out assay to investigate the function of thiamine-sensing riboswitches thiM and thiC from Escherichia coli and the adenine-sensing riboswitch ASW from Vibrio vulnificus and pbuE from Bacillus subtilis, which represent transcriptional and translational on- and off-riboswitches, respectively. This approach enabled a microplate-based application, a valuable addition to the toolbox for high-throughput screening of riboswitch function.
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Aptámeros de Nucleótidos , Riboswitch , Adenina/química , Aptámeros de Nucleótidos/genética , Aptámeros de Nucleótidos/metabolismo , Fluorescencia , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Conformación de Ácido Nucleico , Sistema Libre de CélulasRESUMEN
Background: Consultation-liaison psychiatry (C-LP) is an interface between physical and psychological health where the psychiatrists become a part of the medical team for a holistic approach in the treatment of the patient. Aims: Our study aimed to see the pattern and utility of C-LP services among inpatient referrals to the department of psychiatry. Settings and Design: This observational descriptive study recorded inpatient referrals to the department of psychiatry of a tertiary care hospital for 2 months. Subjects and Methods: The Mini-International Neuropsychiatric Interview (M. I. N. I.) was administered for identifying the comorbid psychiatric diagnoses. Results: Most of the received inpatient referrals were for male patients (73.7%) in the age group of 30-60 years (58%). Overall, the referral rate was significantly higher from the emergency department and intensive care units (ICU) (50%), followed by specialty (medicine and surgery) wards (20%) and super specialty (cardiology, gastroenterology, and oncology) wards (16%). Altered sensorium and restlessness were the most common reasons for referral (42%), followed by alcohol/drug withdrawal (21.6%), somatic complaints (7.3%), sadness of mood, disturbed sleep, and deliberate self-harm (6% each). Substance use disorders, including alcohol and opioid (32%), delirium (25%), and depression (19%), were among the most common psychiatric diagnoses seen in the referred patients. Conclusions: The pattern observed indicates that most inpatient referrals for psychological evaluation are received for altered sensorium from emergency and ICU than wards. The utility of C-LP helps to understand the reciprocal interdependence between the medical illness and the psychiatric comorbidity.
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Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via an RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and found that this FendrrBox is partially required for Fendrr function in vivo. We found that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs associated with lung fibrosis. A set of these genes contain a triplex site directly at their promoter and are expressed in lung fibroblasts. We biophysically confirmed the formation of an RNA:dsDNA triplex with target promoters in vitro. We found that Fendrr with the Wnt signalling pathway regulates these genes, implicating that Fendrr synergizes with Wnt signalling in lung fibrosis.
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Fibrosis Pulmonar , ARN Largo no Codificante , Animales , Ratones , Fibrosis , Pulmón/crecimiento & desarrollo , Pulmón/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , ARN Largo no Codificante/metabolismoRESUMEN
Background: The COVID-19 pandemic has shifted healthcare from physical in-person patient visits to teleconsultations in order to curtail the spread of this virus. Dermatology, being a visual science, lends itself amenably to teleconsultation. Objective: This study was performed to assess the basic dermatological diseases which are more easily diagnosable and managed through teleconsultation, distinguishing them from diseases for which a face-to-face consultation may be a better option and to delineate the factors affecting the image quality which is the cornerstone of a teledermatology consultation. Methods: A retrospective observational study was conducted over a three-month period during the pandemic. Store and forward, video conferencing, and hybrid consultations were included. Two dermatologists of different clinical experience independently assessed the clinical photographs of the patients and gave each photograph an objective score (Physician Quality Rating Scale) and a diagnosis. The diagnostic concordance between the two dermatologists as well as the correlation of this score with the certainty of diagnosis was calculated. Results: A total of 651 patients completed the study. Mean PQRS score of Dermatologist 1 was 6.22 while the mean score of Dermatologist 2 was 6.24. Patients in whom both the dermatologists were absolutely certain about their diagnosis had a higher PQRS score and interestingly had a higher education level than the rest. There was 97.7 percent diagnostic concordance between the two dermatologists. Infections, acne, follicular disorders, pigmentary disorders, tumors, and STDs had the largest proportion of cases wherein both the dermatologists were in total agreement with each other. Conclusion: Teledermatology might be best for the care of patients with characteristic clinical presentation or for follow-up of already diagnosed patients. It can be used in the post-COVID era to triage patients requiring emergency care and reduce patient wait times.
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Camouflage is defined as a combination of materials, colouration or illumination for concealing something. Skin camouflage therapy is the use of specially formulated products to conceal skin diseases and disfigurements, with the goal of giving a temporarily normal appearance. It gives immediate relief in various dermatological disorders, especially those affecting the visible areas, which are known to be associated with profound psychosocial impact. Despite considerable evidence for its emotional benefits, its utilisation among dermatologists in clinical practice remains low. This article is intended to familiarise dermatologists with the use of skin camouflage therapy including its availability, indications, contraindications, techniques, limitations and future trends.
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Cosméticos , HumanosRESUMEN
DNA:DNA:RNA triplexes that are formed through Hoogsteen base-pairing of the RNA in the major groove of the DNA duplex have been observed in vitro, but the extent to which these interactions occur in cells and how they impact cellular functions remains elusive. Using a combination of bioinformatic techniques, RNA/DNA pulldown and biophysical studies, we set out to identify functionally important DNA:DNA:RNA triplex-forming long non-coding RNAs (lncRNA) in human endothelial cells. The lncRNA HIF1α-AS1 was retrieved as a top hit. Endogenous HIF1α-AS1 reduces the expression of numerous genes, including EPH Receptor A2 and Adrenomedullin through DNA:DNA:RNA triplex formation by acting as an adapter for the repressive human silencing hub complex (HUSH). Moreover, the oxygen-sensitive HIF1α-AS1 is down-regulated in pulmonary hypertension and loss-of-function approaches not only result in gene de-repression but also enhance angiogenic capacity. As exemplified here with HIF1α-AS1, DNA:DNA:RNA triplex formation is a functionally important mechanism of trans-acting gene expression control.
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ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Endoteliales/metabolismo , ADN/genética , ADN/metabolismo , Emparejamiento Base , Oligonucleótidos , Regulación Neoplásica de la Expresión GénicaRESUMEN
RNA.DNA:DNA triple helix (triplex) formation is a form of RNA-DNA interaction which regulates gene expression but is difficult to study experimentally in vivo. This makes accurate computational prediction of such interactions highly important in the field of RNA research. Current predictive methods use canonical Hoogsteen base pairing rules, which whilst biophysically valid, may not reflect the plastic nature of cell biology. Here, we present the first optimization approach to learn a probabilistic model describing RNA-DNA interactions directly from motifs derived from triplex sequencing data. We find that there are several stable interaction codes, including Hoogsteen base pairing and novel RNA-DNA base pairings, which agree with in vitro measurements. We implemented these findings in TriplexAligner, a program that uses the determined interaction codes to predict triplex binding. TriplexAligner predicts RNA-DNA interactions identified in all-to-all sequencing data more accurately than all previously published tools in human and mouse and also predicts previously studied triplex interactions with known regulatory functions. We further validated a novel triplex interaction using biophysical experiments. Our work is an important step towards better understanding of triplex formation and allows genome-wide analyses of RNA-DNA interactions.
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Estudio de Asociación del Genoma Completo , ARN , Humanos , Ratones , Animales , ARN/genética , ADN/genética , ADN/metabolismo , Replicación del ADN , Conformación de Ácido NucleicoRESUMEN
Nanoscale stepper motors such as kinesin and dynein play a key role in numerous natural processes such as mitotic spindle formation during cell division or intracellular organelle transport. Their high efficacy in terms of operational speed and processivity has inspired the investigation of biomimetic technologies based on the use of programmable molecules. In particular, several designs of molecular walkers have been explored using DNA nanotechnology. Here, we study the actuation of a DNA-origami walker on a DNA-origami track based on three principles: 1) octapedal instead of bipedal walking for greater redundancy; 2) three pairs of orthogonal sequences, each of which fuels one repeatable stepping phase for cyclically driven motion with controlled directionality based on strain-based step selection; 3) designed size of only 3.5 nm per step on an origami track. All three principles are innovative in the sense that earlier demonstrations of steppers relied on a maximum of four legs on at least four orthogonal sequences to drive cyclic stepping, and took steps much larger than 3.4 nm in size. Using gel electrophoresis and negative-stain electron microscopy, we demonstrate cyclic actuation of DNA-origami structures through states defined by three sets of specific sequences of anchor points. However, this mechanism was not able to provide the intended control over directionality of movement. DNA-origami-based stepper motors will offer a future platform for investigating how increasing numbers of legs can be exploited to achieve robust stepping with relatively small step sizes.
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Nanoestructuras , Nanotecnología , Nanotecnología/métodos , ADN/química , Dineínas/química , Cinesinas/química , Nanoestructuras/química , Conformación de Ácido NucleicoRESUMEN
OBJECTIVES: To explore patients' experiences of getting a diagnosis of eye disease, the psychological impact of this and how this could be improved. DESIGN: An exploratory qualitative interview study using a narrative approach and inductive methods. SETTING: This study was conducted with patients who had attended ophthalmic appointments in primary and secondary care and in opticians located in the South of England. PARTICIPANTS: 18 people diagnosed with eye disease in England. RESULTS: Four themes were identified: the convoluted process of being diagnosed, the impact of clinicians' words, the search for information and reflections on what could be improved. The prolonged wait for a definitive diagnosis was a source of frustration and anxiety for many patients. Professionals' words and tone when delivering a diagnosis sometimes affected a patient's view of their diagnosis and their later ability to come to terms with it. Patients were desperate for information, but many felt they were not provided with sufficient information at the time of diagnosis and did not know whether to trust information found online. Participants felt the provision of a hospital liaison service and/or counselling could mitigate the impact on patients and families. CONCLUSIONS: Interactions with clinicians can have a lasting impact on how a diagnosis is experienced and how well the patient is able to come to terms with their visual impairment. Receiving little or no information left patients feeling lost and unsupported. This led them to search for information from less reliable sources. Clinicians should consider how they communicate a diagnosis to patients, how and when they offer information about diagnosis and prognosis and where possible signpost patients to additional support systems and counselling services as early as possible.
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Oftalmopatías , Atención Secundaria de Salud , Inglaterra , Oftalmopatías/diagnóstico , Humanos , Investigación CualitativaRESUMEN
Refractory coeliac disease (RCD) occurs when patients with confirmed CD have continuous or recurrent malabsorption and enteropathy after at least 12 months on a gluten-free diet. Differentiating between type I and type II RCD is key as the latter is associated with T-cell aberrancy and considered prelymphoma, with high mortality rates. Current treatment regimens for type II RCD include corticosteroids, biologics and chemotherapy, but there are no proven therapies for this serious condition. Our patient is a middle-aged woman who developed postpartum type II RCD. When she failed multiple drug classes, we did a trial of tofacitinib. Our clinical experience with use of a janus kinase inhibitor was successful, with no associated adverse events. This is the first report in the literature of RCD remission in response to tofacitinib. The use of this novel agent shows promise in reversing this potentially fatal condition.
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Enfermedad Celíaca , Enfermedad Celíaca/diagnóstico , Diagnóstico Diferencial , Dieta Sin Gluten , Femenino , Humanos , Persona de Mediana Edad , Piperidinas , Pirimidinas , Linfocitos T/patologíaRESUMEN
The ongoing pandemic of the respiratory disease COVID-19 is caused by the SARS-CoV-2 (SCoV2) virus. SCoV2 is a member of the Betacoronavirus genus. The 30 kb positive sense, single stranded RNA genome of SCoV2 features 5'- and 3'-genomic ends that are highly conserved among Betacoronaviruses. These genomic ends contain structured cis-acting RNA elements, which are involved in the regulation of viral replication and translation. Structural information about these potential antiviral drug targets supports the development of novel classes of therapeutics against COVID-19. The highly conserved branched stem-loop 5 (SL5) found within the 5'-untranslated region (5'-UTR) consists of a basal stem and three stem-loops, namely SL5a, SL5b and SL5c. Both, SL5a and SL5b feature a 5'-UUUCGU-3' hexaloop that is also found among Alphacoronaviruses. Here, we report the extensive 1H, 13C and 15N resonance assignment of the 37 nucleotides (nts) long sequence spanning SL5b and SL5c (SL5b + c), as basis for further in-depth structural studies by solution NMR spectroscopy.