All-photonic kinase inhibitors: light-controlled release-and-report inhibition.

Light-responsive molecular tools targeting kinases affords one the opportunity to study the underlying cellular function of selected kinases. In efforts to externally control lymphocyte-specific protein tyrosine kinase (LCK) activity, the development of release-and-report LCK inhibitors is described, in which (i) the release of the active kinase inhibitor can be controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the active kinase inhibitor. This introduces an unprecedented all-photonic method for users to both control and monitor real-time inhibitory activity. A functional cellular assay demonstrated light-mediated LCK inhibition in natural killer cells. The use of coumarin-derived caging groups resulted in rapid cellular uptake and non-specific intracellular localisation, while a BODIPY-derived caging group predominately localised in the cellular membrane. This concept of release-and-report inhibitors has the potential to be extended to other biorelevant targets where both spatiotemporal control in a cellular setting and a reporting mechanism would be beneficial.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback.

We investigated the role of ligand clustering and density in the activation of natural killer (NK) cells. To that end, we designed reductionist arrays of nanopatterned ligands arranged with different cluster geometries and densities and probed their effects on NK cell activation. We used these arrays as an artificial microenvironment for the stimulation of NK cells and studied the effect of the array geometry on the NK cell immune response. We found that ligand density significantly regulated NK cell activation while ligand clustering had an impact only at a specific density threshold. We also rationalized these findings by introducing a theoretical membrane fluctuation model that considers biomechanical feedback between ligand-receptor bonds and the cell membrane. These findings provide important insight into NK cell mechanobiology, which is fundamentally important and essential for designing immunotherapeutic strategies targeting cancer.

Generation of human alveolar epithelial type I cells from pluripotent stem cells.

Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.

Photoswitchable optoelectronic properties of 2D MoSe2/diarylethene hybrid structures.

The ability to modulate optical and electrical properties of two-dimensional (2D) semiconductors has sparked considerable interest in transition metal dichalcogenides (TMDs). Herein, we introduce a facile strategy for modulating optoelectronic properties of monolayer MoSe2 with external light. Photochromic diarylethene (DAE) molecules formed a 2-nm-thick uniform layer on MoSe2, switching between its closed- and open-form isomers under UV and visible irradiation, respectively. We have discovered that the closed DAE conformation under UV has its lowest unoccupied molecular orbital energy level lower than the conduction band minimum of MoSe2, which facilitates photoinduced charge separation at the hybrid interface and quenches photoluminescence (PL) from monolayer flakes. In contrast, open isomers under visible light prevent photoexcited electron transfer from MoSe2 to DAE, thus retaining PL emission properties. Alternating UV and visible light repeatedly show a dynamic modulation of optoelectronic signatures of MoSe2. Conductive atomic force microscopy and Kelvin probe force microscopy also reveal an increase in conductivity and work function of MoSe2/DAE with photoswitched closed-form DAE. These results may open new opportunities for designing new phototransistors and other 2D optoelectronic devices.

LncRNA MALAT1 in Keratinocyte function: A review of recent advances.

Keratinocytes, the principal epidermal cells, play a vital role in maintaining the structural integrity and functionality of the skin. Beyond their protective role, keratinocytes are key contributors to the process of wound healing, as they migrate to injury sites, proliferate, and generate new layers of epidermis, facilitating tissue repair and remodeling. Moreover, keratinocytes actively participate in the skin's immune responses, expressing pattern recognition receptors (PRRs) to detect microbial components and interact with immune cells to influence adaptive immunity. Keratinocytes express a diverse repertoire of signaling pathways, transcription factors, and epigenetic regulators to regulate their growth, differentiation, and response to environmental cues. Among these regulatory elements, long non-coding RNAs (lncRNAs) have emerged as essential players in keratinocyte biology. LncRNAs, including MALAT1, play diverse roles in gene regulation and cellular processes, influencing keratinocyte proliferation, differentiation, migration, and response to environmental stimuli. Dysregulation of specific lncRNAs such as MALAT1 can disrupt keratinocyte homeostasis, leading to impaired differentiation, compromised barrier integrity, and contributing to the pathogenesis of various skin disorders. Understanding the intricate interplay between lncRNAs and keratinocytes offers promising insights into the molecular underpinnings of skin health and disease, with potential implications for targeted therapies and advancements in dermatological research. Hence, our objective is to provide a comprehensive summary of the available knowledge concerning keratinocytes and their intricate relationship with MALAT1.

Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

Background: Rejection continues to be the main cause of renal graft loss. Currently, the gold standard for diagnosis is an allograft biopsy; however, because it is time-consuming, costly, and invasive, the pursuit of novel biomarkers has gained interest. Variation in the expressions of miRNAs is currently considered a probable biomarker for the diagnosis of acute rejection. This study aimed to determine whether miR-150-5p in serum is related to microvascular damage in patients with acute antibody-mediated rejection (ABMR). Methods: A total of 27 patients who underwent renal transplantation (RT) with and without ABMR were included in the study. We performed the quantification of hsa-miR-150-5p, hsa-miR-155, hsa-miR-21, hsa-miR-126, and hsa-miR-1 in plasma by RT-qPCR. The expressions between the groups and their correlations with the histological characteristics of the patients with ABMR were also investigated. Results: miR-150-5p significantly increased in the plasma of patients with rejection (p < 0.05), and the changes in miR-150-5p were directly correlated with microvascular inflammation in the allograft biopsies. Clinical utility was determined by ROC analysis with an area under the curve of 0.873. Conclusions: Our results show that the patients with RT with ABMR exhibited increased expression of miR-150-5p compared to patients without rejection, which could have clinical consequences, as well as probable utility in the diagnosis of ABMR, and bioinformatics may help in unraveling the molecular mechanisms underlying ABMR conditions.

A Novel Approach for Colloidal Lithography: From Dry Particle Assembly to High-Throughput Nanofabrication.

We introduce a novel approach for colloidal lithography based on the dry particle assembly into a dense monolayer on an elastomer, followed by mechanical transfer to a substrate of any material and curvature. This method can be implemented either manually or automatically and it produces large area patterns with the quality obtained by the state-of-the-art colloidal lithography at a very high throughput. We first demonstrated the fabrication of nanopatterns with a periodicity ranging between 200 nm and 2 µm. We then demonstrated two nanotechnological applications of this approach. The first one is antireflective structures, fabricated on silicon and sapphire, with different geometries including arrays of bumps and holes and adjusted for different spectral ranges. The second one is smart 3D nanostructures for mechanostimulation of T cells that are used for their effective proliferation, with potential application in cancer immunotherapy. This new approach unleashes the potential of bottom-up nanofabrication and paves the way for nanoscale devices and systems in numerous applications.

Modulating the properties and structure of lignins produced by alkaline delignification of sugarcane bagasse pretreated with two different mineral acids at pilot-scale.

Sugarcane bagasse was pretreated with dilute phosphoric acid or sulfuric acid to facilitate cellulose hydrolysis and lignin extraction. With phosphoric acid, only 8 % of the initial cellulose was lost after delignification, whereas pretreatment with sulfuric acid resulted in the solubilization of 38 % of the initial cellulose. After enzymatic hydrolysis, the process using phosphoric acid produced approximately 35 % more glucose than that using sulfuric acid. In general, the lignins showed 95-97 % purity (total lignin, w/w), an average molar mass of 9500-10,200 g mol-1, a glass transition temperature of 140-160 °C, and a calorific value of 25 MJ kg-1. Phosphoric acid lignin (PAL) was slightly more polar than sulfuric acid lignin (SAL). PAL had 13 % more oxidized units and 20 % more OH groups than SAL. Regardless of the acid used, the lignins shared similar properties, but differed slightly in the characteristics of their functional groups and chemical bonds. These findings show that pretreatment catalyzed with either of the two acids resulted in lignin with sufficiently good characteristics for use in industrial processes.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Wound Bed Preparation 2024: Delphi Consensus on Foot Ulcer Management in Resource-Limited Settings.

GENERAL PURPOSE: To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Summarize issues related to wound assessment.2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes.3. Synthesize strategies for wound management, including treatment in resource-limited settings.4. Specify the target time for edge advancement in chronic, healable wounds.

Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.

A Change of Paradigm in the Management of Acute Psychiatric Episodes? A Retrospective Cohort Study on Trajectories of Use of Clinical Resources After the Implementation of Intensive Home-Treatment.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Effect of turbinate surgery on mucociliary clearance. A systematic review and metanalysis / Efecto de la cirugía turbinal en el aclaramiento mucociliar. Revisión sistemática y metaanálisis

Despite the fact that turbinate surgery provides satisfactory results regarding nasal obstruction, most of these procedures are destructive, to some extent, for the respiratory epithelium. There are valid hypotheses suggesting either that turbinate surgery may improve mucociliary clearance (MCC) by improving rhinitis, as well hypotheses suggesting that these surgeries may impair it by damaging the nasal ciliated epithelia. This systematic review is designed with the objective of exploring the effect of turbinate surgery on MCC. Pubmed (Medline), the Cochrane Library, EMBASE, SciELO were analyzed. Four authors members of the YO-IFOS rhinology study group independently analyzed the articles. Extracted variables encompassed: sample size, age, indication for surgery, surgical technique, method used to measure mucociliary clearance, mucociliary transport time before and after surgery, and main outcome. 15 studies with a total population of 1936 participants (1618 patients excluding healthy controls) met the inclusion criteria. 9 studies could be combined in a metanalysis, wich revealed a non-statistically significant decrease of 3.86 min in MCTT after turbinate surgery (p = 0.06). The subgroup analysis of the 5 cohorts who underwent microdebrider turbinoplasty reached statistical significance under a random effect model, revealing a 7.02 min decrease in MCTT (p < 0.001). The laser turbinoplasty subgroup, composed of 4 cohorts, also reached significance, although the difference was lower than that for microdebrider turbinoplasty, 1.01 min (p < 0.001). This systematic review and meta-analysis suggests that turbinate surgery does not compromise mucociliary clearance. The available evidence also suggests that turbinate surgery with mucosa sparing techniques improves MCC, while with aggressive techniques it increases or remains the same. ... . (AU)

A pesar de que la cirugía turbinal tiene efectos positivos en la ventilación nasal, gran parte de estos procedimientos son agresivos con el epitelio respiratorio. Existen hipótesis que sugieren que la cirugía turbinal puede mejorar el aclaramiento mucociliar (AMC) al mejorar la rinitis, así como alterarlo al lesional el epitelio nasal. Esta revisión se diseña con el objetivo de explorar el efecto de la cirugía turbinal en el AMC. Se revisó Pubmed (Medline), the Cochrane Library, EMBASE, SciELO. 4 autores miembros de YO-IFOS grupo de estudio en rinología, analizaron de manera independiente los artículos. Las variables analizadas fueron tamaño muestral, edad, indicación quirúrgica, técnica quirúrgica, método de medición de AMC, AMC antes y después de la cirugía y resultado principal. Se incluyeron 15 estudios con 1936 participantes (1618 excluyendo controles sanos). 9 estudios fueron combinados en un metanálisis que demostró una diferencia no estadísticamente significativa de -3,86 minutos en AMC tras cirugía (p = 0,06). El análisis por subgrupos de las 5 cohortes sometidas a turbinoplastia con microdebridador si fueron estadísticamente significativas con una diferencia de -7,02 minutos (p < 0,001). El grupo sometido a laser (4 cohortes) también obtuvo diferencia estadística, aunque menor, -1,01 minutos (p < 0,001). Esta revision y metaanálisis sugiere que la cirugía turbinal no afecta al aclaramiento mucociliar. La evidencia disponible también sugiere que las técnicas menos agresivas con la mucosa mejoran el AMC, mientras que las agresivas podrían aumentarlo o no modificarlo. Este efecto beneficioso se observa desde el 1º al 3º mes postquirúrgico. Sin embargo, para poder obtener adecuadas conclusiones, debe existir un método estandarizado para medir el AMC, así como un método para describir adecuadamente la extensión quirúrgica. (AU)

Compressive stress triggers fibroblasts spreading over cancer cells to generate carcinoma in situ organization.

At the early stage of tumor progression, fibroblasts are located at the outer edges of the tumor, forming an encasing layer around it. In this work, we have developed a 3D in vitro model where fibroblasts' layout resembles the structure seen in carcinoma in situ. We use a microfluidic encapsulation technology to co-culture fibroblasts and cancer cells within hollow, permeable, and elastic alginate shells. We find that in the absence of spatial constraint, fibroblasts and cancer cells do not mix but segregate into distinct aggregates composed of individual cell types. However, upon confinement, fibroblasts enwrap cancer cell spheroid. Using a combination of biophysical methods and live imaging, we find that buildup of compressive stress is required to induce fibroblasts spreading over the aggregates of tumor cells. We propose that compressive stress generated by the tumor growth might be a mechanism that prompts fibroblasts to form a capsule around the tumor.

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.

Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations.

Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP fusion reporter lines for in vitro disease modeling. We observed an expected decreased capacity for surfactant secretion in ABCA3-mutant iPSC-derived AEC2s (iAEC2s), but we also found an unexpected epithelial-intrinsic aberrant phenotype in mutant iAEC2s, presenting as diminished progenitor potential, increased NFκB signaling, and the production of pro-inflammatory cytokines. The ABCA3:GFP fusion reporter permitted mutant-specific, quantifiable characterization of lamellar body size and ABCA3 protein trafficking, functional features that are perturbed depending on ABCA3 mutation type. Our disease model provides a platform for understanding ABCA3 mutation-mediated mechanisms of alveolar epithelial cell dysfunction that may trigger chILD pathogenesis.

Postural tremor and sexual chromosome aneuploidies: case report and review of literature.

PURPOSE: To examine the link between tremor and sex chromosome abnormalities, emphasizing the necessity of comprehensive physical examination. CASE DESCRIPTION: An 18-year-old man exhibited an isolated action tremor in both hands. Despite having no familial history of tremors and no identifiable secondary causes, his tall stature and learning difficulties suggested a genetic origin. His karyotype confirmed the diagnosis of Jacob's syndrome (XYY syndrome). Therapies with primidone and propranolol were ineffective for his tremor. CONCLUSIONS: Tremor can be caused by various conditions, and aneuploidies might often be overlooked as a cause. They should be considered in young patients with concrete phenotypes and negative familiar history of tremors. Karyotyping is a cost-effective diagnostic tool crucial for genetic counselling. Common treatments for tremors often yield unsatisfactory results in these cases.