Encefalopatía de Hashimoto: reporte de un caso clínico

Hashimoto encephalopathy is an infrequent neurological entity, rarely suspected by the clinician. It is of a probable autoimmune nature, it generally presents with subacute symptoms; in thrusts and remissions, high titers of antithyroid antibodies and good response to corticosteroid treatment. We present the clinical case of a 78-year-old man with multiple pathological antecedents who consulted in Hospital Maciel, Montevideo, Uruguay for symptoms of 3 weeks of evolution characterized by psychomotor excitement, language and behavioral alterations. Other causes of encephalopathy were excluded. Clinical tests revealed euthyroidism with elevated antithyroid antibodies and the improvement of symptoms after starting corticotherapy was evidenced.La encefalopatía de Hashimoto es una entidad neurológica infrecuente, poco sospechada por el médico clínico. De probable naturaleza autoinmune, cursa generalmente con síntomas de instalación subaguda en empujes y remisiones, títulos elevados de anticuerpos antitiroideos y buena respuesta al tratamiento corticoideo. Se presenta el caso clínico de un hombre de 78 años, con múltiples antecedentes patológicos, que consultó por sintomatología de 3 semanas de evolución caracterizada por excitación psicomotriz, alteración del lenguaje y alteraciones conductuales. Se excluyeron otras causas de encefalopatía, encontrándose en eutiroidismo con anticuerpos antitiroideos elevados. Se evidenció la mejoría de los síntomas tras iniciar corticoterapia

Neumonía intersticial linfoidea de difícil diagnóstico como primera manifestación de inmunodeficiencia común variable

Lymphoid interstitial pneumonia is an uncommon idiopathic interstitial lung disease. It is generally difficult to diagnose, although the radiological and histopathological findings are determinant. Usually appears in association with variable common immunodeficiency, human immunodeficiency virus and autoimmune diseases like Sjögren syndrome or lupus. The aim of this paper is to report a rare lymphoid interstitial pneumonia case, due to its unusual radiological presentation, confirmed by pulmonary biopsy and associated with variable common immunodeficiency.La neumonía intersticial linfoidea es una enfermedad intersticial pulmonar idiopática infrecuente. Es una entidad de diagnóstico difícil, donde los hallazgos radiológicos e histológicos son claves. Es frecuente su asociación con patologías autoinmunitarias como el síndrome de Sjögren o el lupus, inmunodeficiencia común variable y virus de inmunodeficiencia humana. El objetivo del presente trabajo es comunicar un caso de neumonía intersticial linfoidea excepcional por su presentación radiológica inusual, confirmada por biopsia pulmonar y asociada a inmunodeficiencia común variable

A Sequence-to-Sequence Transformer Model for Disconnection Aware Retrosynthesis

Retrosynthesis is an approach commonly undertaken when considering the manufacture of novel molecules. During this process, a target molecule is broken down and analyzed by considering the bonds to be changed as well as the functional group interconversion. In modern computer-assisted synthesis planning tools, the predictions of these changes are typically carried out automatically. However there may be some benefit to the decision being guided by those executing the process: typically, chemists have a clear idea where the retrosynthetic change should happen, but not how such a transformation is to be realized. Using a data-driven model, the retrosynthesis task can be further explored by giving chemists the option to explore specific disconnections. In this work, we design an approach to provide this option by adapting a transformer-based model for single-step retrosynthesis. The model takes as input a product SMILES string, in which the atoms where the transformation should occur are tagged accordingly. This model predicts precursors corresponding to a disconnection occurring in the correct location in 88.9% of the test set reactions. The assessment with a forward prediction model shows that 76% of the predictions are chemically correct, with 14.1% perfectly matching the ground truth

Unbiasing Retrosynthesis Language Models with Disconnection Prompts

Data-driven approaches to retrosynthesis have thus far been limited in user interaction, in the diversity of their predictions, and the recommendation of unintuitive disconnection strategies. Herein, we extend the notions of prompt- based inference in natural language processing to the task of chemical language modeling. We show that by using a prompt describing the disconnection site in a molecule, we can steer the model to propose a wider set of precursors, overcoming training data biases in retrosynthetic recommendations and achiev- ing a 39 % performance improvement over the baseline. For the first time, the use of a disconnection prompt empowers chemists by giving them back greater control over the disconnection predictions, resulting in more diverse and creative recommendations. In addition, in place of a human-in-the-loop strategy, we propose a schema for automatic identification of disconnection sites, followed by prediction of reactant sets, achieving a 100 % improvement in class diversity as compared to the baseline. The approach is effective in mitigating prediction biases deriving from training data. In turn, this provides a larger variety of usable building blocks, which improves the end-user digital experience. We demonstrate its application to different chemistry domains, from traditional to enzymatic reactions, in which substrate specificity is key

Functional assessment of the stomatognathic system. Part 1: The role of static elements of analysis

To review the elements of static analysis in the functional assessment of the stomatognathic system, as promoted for more than a century by gnathologists, and summarize the available scientific evidence, including anthropologic observations. A thorough search was conducted using PubMed, the Cochrane Library database, and Google Scholar. From peer-reviewed articles and other scientific literature, up-to-date information addressing three topics was identified: (a) the anthropologic perspective with particular consideration for the role of progressive dental wear over time, (b) descriptions of gnathologic principles and evidence on their scientific validity, and (c) the methodologic inaccuracies introduced by seeking to correlate variables directly rather than allowing for causal inference. For decades gnathology attempted to describe a structure-function correlation within the stomatognathic system by means of a model whose principles were static and mechanistic references. No scientific validation was ever achieved, placing clinical and research consensus out of reach. A historical perspective helps to place the fundamentals of gnathology into context: They were conceived to solve technical difficulties but were then assumed to be physiologic stereotypes. This misconception led to a decades-long promotion of mechanistic theories to describe oral function, but the evidence available today supports a more flexible and adaptable approach. Gnathologic arguments have been relegated to become exclusively of technical relevance in oral rehabilitation.</p

Association Between Sleep Microstructure and Incident Hypertension in a Population‐Based Sample: The HypnoLaus Study

Background Poor sleep quality is associated with increased incident hypertension. However, few studies have investigated the impact of objective sleep structure parameters on hypertension. This study investigated the association between sleep macrostructural and microstructural parameters and incident hypertension in a middle‐ to older‐aged sample. Methods and Results Participants from the HypnoLaus population‐based cohort without hypertension at baseline were included. Participants had at‐home polysomnography at baseline, allowing assessment of sleep macrostructure (nonrapid eye movement sleep stages 1, 2, and 3; rapid eye movement sleep stages; and total sleep time) and microstructure including power spectral density of electroencephalogram in nonrapid eye movement sleep and spindles characteristics (density, duration, frequency, amplitude) in nonrapid eye movement sleep stage 2. Associations between sleep macrostructure and microstructure parameters at baseline and incident clinical hypertension over a mean follow‐up of 5.2 years were assessed with multiple‐adjusted logistic regression. A total of 1172 participants (42% men; age 55±10 years) were included. Of these, 198 (17%) developed hypertension. After adjustment for confounders, no sleep macrostructure features were associated with incident hypertension. However, low absolute delta and sigma power were significantly associated with incident hypertension where participants in the lowest quartile of delta and sigma had a 1.69‐fold (95% CI, 1.00–2.89) and 1.72‐fold (95% CI, 1.05–2.82) increased risk of incident hypertension, respectively, versus those in the highest quartile. Lower spindle density (odds ratio, 0.87; 95% CI, 0.76–0.99) and amplitude (odds ratio, 0.98; 95% CI, 0.95–1.00) were also associated with higher incident hypertension. Conclusions Sleep microstructure is associated with incident hypertension. Slow‐wave activity and sleep spindles, 2 hallmarks of objective sleep continuity and quality, were inversely and consistently associated with incident hypertension. This supports the protective role of sleep continuity in the development of hypertension

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (&gt;30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or &lt;15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P &lt; 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk