Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.

Cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43 is a pathological hallmark of the motor neuron (MN) disease amyotrophic lateral sclerosis (ALS). Furthermore, while mutations in TARDBP (encoding TDP-43) have been associated with ALS, the pathogenic consequences of these mutations remain poorly understood. Using CRISPR-Cas9, we engineered two homozygous knock-in induced pluripotent stem cell lines carrying mutations in TARDBP encoding TDP-43A382T and TDP-43G348C, two common yet understudied ALS TDP-43 variants. Motor neurons (MNs) differentiated from knock-in iPSCs had normal viability and displayed no significant changes in TDP-43 subcellular localization, phosphorylation, solubility, or aggregation compared with isogenic control MNs. However, our results highlight synaptic impairments in both TDP-43A382T and TDP-43G348C MN cultures, as reflected in synapse abnormalities and alterations in spontaneous neuronal activity. Collectively, our findings suggest that MN dysfunction may precede the occurrence of TDP-43 pathology and neurodegeneration in ALS and further implicate synaptic and excitability defects in the pathobiology of this disease.

BatFly: A database of Neotropical bat-fly interactions.

Global changes have increased the risk of emerging infectious diseases, which can be prevented or mitigated by studying host-parasite interactions, among other measures. Bats and their ectoparasitic flies of the families Streblidae and Nycteribiidae are an excellent study model but, so far, our knowledge has been restricted to fragmented records at a local scale. To help boost research, we assembled a data set of bat-fly interactions from 174 studies published between 1904 and 2022 plus three original data sets. Altogether, these studies were carried out at 650 sites in the Neotropics, mainly distributed in Mexico, Brazil, Argentina, southern USA, and Colombia, among other countries. In total, our data set contains 3984 interaction records between 237 bat species and 255 fly species. The bat species with the largest number of recorded interactions were Carollia perspicillata (357), Artibeus jamaicensis (263), and Artibeus lituratus (228). The fly species with the largest number of recorded interactions were Trichobius joblingi (256), Megistopoda aranea (235), and Megistopoda proxima (215). The interaction data were extracted, filtered, taxonomically harmonized, and made available in a tidy format together with linked data on bat population, fly population, study reference, sampling methods and geographic information from the study sites. This interconnected structure enables the expansion of information for each interaction record, encompassing where and how each interaction occurred, as well as the number of bats and flies involved. We expect BatFly to open new avenues for research focused on different levels of ecological organization and spatial scales. It will help consolidate knowledge about ecological specialization, resource distribution, pathogen transmission, and the drivers of parasite prevalence over a broad spatial range. It may also help to answer key questions such as: Are there differences in fly prevalence or mean infestation across Neotropical ecoregions? What ecological drivers explain those differences? How do specialization patterns vary among fly species in the Neotropics? Furthermore, we expect BatFly to inspire research aimed at understanding how climate and land-use changes may impact host-parasite interactions and disease outbreaks. This kind of research may help us reach Sustainable Development Goal 3, Good Health and Wellbeing, outlined by the United Nations. The data are released under a Creative Commons Attribution 4.0 International License.

Impact of Standard Versus Low Pneumoperitoneum Pressure on Peritoneal Environment in Laparoscopic Cholecystectomy. Randomized Clinical Trial.

BACKGROUND: High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes. MATERIALS AND METHODS: One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure. RESULTS: Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups. CONCLUSIONS: Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise.

USP19 deubiquitinase inactivation regulates α-synuclein ubiquitination and inhibits accumulation of Lewy body-like aggregates in mice.

The USP19 deubiquitinase is found in a locus associated with Parkinson's Disease (PD), interacts with chaperonins, and promotes secretion of α-synuclein (α-syn) through the misfolding-associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of α-syn aggregates in PD, we inactivated USP19 (KO) in mice expressing the A53T mutation of α-syn and in whom α-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. This improvement was associated with less activation of microglia and improved performance in a tail-suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF nor propagation of aggregates in the cultured neurons. We conclude that USP19 instead modulates intracellular dynamics of aggregates. At an early time following PFF injection when the number of pSyn-positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from WT and KO brains with antibodies to pSyn showed higher levels of ubiquitinated oligomeric species in the KO samples. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of α-syn complexes.

An Optimized Workflow to Generate and Characterize iPSC-Derived Motor Neuron (MN) Spheroids.

A multitude of in vitro models based on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) have been developed to investigate the underlying causes of selective MN degeneration in motor neuron diseases (MNDs). For instance, spheroids are simple 3D models that have the potential to be generated in large numbers that can be used across different assays. In this study, we generated MN spheroids and developed a workflow to analyze them. To start, the morphological profiling of the spheroids was achieved by developing a pipeline to obtain measurements of their size and shape. Next, we confirmed the expression of different MN markers at the transcript and protein levels by qPCR and immunocytochemistry of tissue-cleared samples, respectively. Finally, we assessed the capacity of the MN spheroids to display functional activity in the form of action potentials and bursts using a microelectrode array approach. Although most of the cells displayed an MN identity, we also characterized the presence of other cell types, namely interneurons and oligodendrocytes, which share the same neural progenitor pool with MNs. In summary, we successfully developed an MN 3D model, and we optimized a workflow that can be applied to perform its morphological, gene expression, protein, and functional profiling over time.

A Pathogenic Variant Reclassified to the Pseudogene PMS2P1 in a Patient with Suspected Hereditary Cancer.

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM_000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

Mutational Landscape of Bladder Cancer in Mexican Patients: KMT2D Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute-Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in both familial and sporadic ALS. In ALS, disruption of neuromuscular junctions (NMJs) constitutes a critical event in disease pathogenesis, leading to denervation atrophy, motor impairments and disability. Morphological defects and impaired synaptic transmission at NMJs have been reported in several TDP-43 animal models and in vitro, linking TDP-43 dysregulation to the loss of NMJ integrity in ALS. Through the lens of the dying-back and dying-forward hypotheses of ALS, this review discusses the roles of TDP-43 related to synaptic function, with a focus on the potential molecular mechanisms occurring within MNs, skeletal muscles and glial cells that may contribute to NMJ disruption in ALS.

Efecto de la determinación sobre el compromiso en el trabajo de estudiantes de cirugía: un estudio transversal

Introducción: la determinación (grit) es un rasgo de personalidad deseable en los estudiantes de medicina, en pro de un rendimiento académico favorable. El compromiso con el trabajo es una competencia deseada en los procesos de enseñanza-aprendizaje en el pregrado. Se evalúa el efecto de la determinación en el compromiso con el trabajo de los estudiantes, durante su rotación por la asignatura de cirugía general. Métodos: los estudiantes calificaron su determinación en la Escala Corta de Determinación (GSS) y su compromiso con el trabajo mediante la escala de compromiso con el trabajo de Utrecht (UWES17-S). Mediante un análisis de regresión lineal de efectos mixtos, las relaciones de las anteriores variables fueron establecidas. Resultados: se incluyeron 327 estudiantes, de diez facultades de medicina. La puntuación de GSS fue 2,96 ± 0,58 (1-5) y de UWES-S17 fue 3,94 ± 0,85 (rango de 2,4-7,0). En el modelo fijo, el efecto de la determinación en el compromiso con el trabajo de los estudiantes no fue significativo (b = 0,04; IC del 95 %: -0,11; 0,19), así como tampoco en el análisis aleatorio que exploró la interacción por facultad de medicina (b = 0,02; IC del 95 %: 0,0044; 0,15). La determinación, no influyó en el compromiso con el trabajo de los estudiantes. Conclusiones: no se encontró un efecto significativo de la determinación en el compromiso con el trabajo de los estudiantes durante la rotación en cirugía general. Otros aspectos como el contexto y la interacción social deben ser explorados.

Summary Introduction: Determination (grit) is a desirable personality trait in medical students for favorable academic performance. Commitment to work is a desired competence in undergraduate teaching-learning processes. The effect of the determination in the commitment to the work of the students is evaluated during their rotation. Methods: Students rated their determination on the Short Grit Scale (GSS) and their commitment to work on the Utrecht Work. Engagement Scale (UWES17-S). Through a mixed effects linear regression analysis, the relationships of the previous variables were established. Results: 327 students from ten medical schools were included. The GSS score was 2.96 ± 0.58 (1-5) and the UWES-S17 score was 3.94 ± 0.85 (range 2.4-7.0). In the fixed model, the effect of the determination on the students' commitment to work was not significant (b = 0.04; 95% CI: -0.11; 0.19, neither in the random model that explored the interaction by medical school (b = 0.02; 95% CI: 0.0044; - 0.15). The determination did not influence the commitment to the work of the students. Conclusions: No significant effect of determination was found on student work commitment during rotation in the general surgery course. Other aspects such as context and social interaction, should be explored.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Comparison of satisfaction degree of patients treated at the Inflammatory Bowel Disease Unit (IBDU) of Hospital Universitario 12 de Octubre between previous face-to-face care and telephone care during the COVID-19 pandemic.

The aim of the IBDU is to provide comprehensive care for patients with IBD (1,2). During the COVID-19 pandemic, telephone medical consultations and telemedicine training sessions were implemented to ensure patient safety (3). The aim of this study was to determine whether there was a difference in the degree of satisfaction between face-to-face and telephone care, as well as in the annual patient sessions.

A streamlined CRISPR workflow to introduce mutations and generate isogenic iPSCs for modeling amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) represents a complex neurodegenerative disorder with significant genetic heterogeneity. To date, both the genetic etiology and the underlying molecular mechanisms driving this disease remain poorly understood, although in recent years several studies have highlighted a number of genetic mutations causative for ALS. With these mutations pointing to potential pathways that may be affected within individuals with ALS, having the ability to generate human neurons and other disease relevant cells containing these mutations becomes even more critical if new therapies are to emerge. Recent developments with the advent of induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing fields gave us the tools to introduce or correct a specific mutation at any site within the genome of an iPSC, and thus model the specific contribution of risk mutations. In this study we describe a rapid and efficient way to either introduce a mutation into a control line, or to correct an allele-specific mutation, generating an isogenic control line from patient-derived iPSCs with a given mutation. The mutations introduced were the G94A (also known as G93A) mutation into SOD1 or H517Q into FUS, and the mutation corrected was a patient iPSC line with I114T mutation in SOD1. A combination of small molecules and growth factors were used to guide a stepwise differentiation of the edited cells into motor neurons in order to demonstrate that disease-relevant cells could be generated for downstream applications. Through a combination of iPSCs and CRISPR editing, the cells generated here will provide fundamental insights into the molecular mechanisms underlying neuron degeneration in ALS.

Sustainable Biocatalytic Procedure for Obtaining New Branched Acid Esters.

Biocatalytic synthesis of 2-ethylhexyl 2-methylhexanoate is described in this work for the first time. This branched-chain ester is suitable for use at low temperatures in numerous applications. The immobilized lipase Novozym® 435 has demonstrated its ability to catalyze the ester synthesis from 2-ethylhexanol and 2-methylhexanoic acid in a solvent-free medium. The high reaction times that are required result in a loss of alcohol by evaporation, which must be compensated for with an excess of this substrate if high conversions are to be achieved. Therefore, two strategies are established: 70 °C with a 10% excess of alcohol, which requires a longer operating time and provides conversions of 97%, and 80 °C with a 20% excess of alcohol, which allows for the achievement of a 99% conversion in a shorter time. The optimal reaction conditions have been chosen based on reusability of the enzyme, process productivity, green metrics and preliminary economic study. When the synthesis is carried out under the best conditions (70 °C, 10% molar excess of alcohol and six uses of the immobilized enzyme) a productivity of 203.84 kg product × kg biocatalyst-1 is attained. The biocatalytic procedure matches many of the objectives of "green chemistry" and is suitable to be scaled up and used in industrial manufacturing.

[Decisiones de no ingreso en las Unidades de Cuidados Intensivos como medida de limitación de los tratamientos de soporte vital: variabilidad geográfica en España]. / Decisions of refusal intensive Care Units' admission as a measure of limitation of life support treatments: geographical variability in Spain.

From a post hoc analysis of the ADENI-UCI study (multicenter, observational, cohort, prospective study, with a follow-up period of 13 months, in 62 Intensive Medicine Services in Spain. geographical differences in the reason for denial of income in UCI as a LTSV measure are analyzed. A total of 2284 with an average age of 75.25 (12.45) years were included. 59.43% male. By means of multinominal regression adjusted by age, sex, APACHE and SOFA, was evident (by choosing the northern for reference) that age in the south was a less significantly exposed reason (OR: 0.48 (IC95%: 0.35-0.65). p.

Decisiones de no ingreso en las Unidades de Cuidados Intensivos como medida de limitación de los tratamientos de soporte vital: variabilidad geográfica en España / Decisions of refusal intensive Care Units’ admission as a measure of limitation of life support treatments: geographical variability in Spain

A través de un análisis post hoc del estudio ADENI-UCI (estudio multicéntrico, observacional, de co-hortes, prospectivo, con un período de seguimiento de 13 meses, en un total de 62 servicios de MedicinaIntensiva en España; se analizan las diferencias geográficas del motivo de negación de ingreso en UCI comomedida de LTSV. Se incluyeron 2284 pacientes con una edad media de 75,25 (12,45) años. El 59,43% varones.Mediante regresión multinominal ajustada por edad, sexo, APACHE II y SOFA, se evidenció (al elegir lazona norte como referencia) que la edad en la zona sur fue un motivo menos expuesto de forma significati-va (OR: 0.48 (IC95%: 0.35-0.65). p<0,001), que la enfermedad crónica severa era menos valorada en la zona mediterránea (OR: 0.70 (IC95%: 0.56-0.87). p=0,001), mientras que presentaba más peso en la zona centro(OR: 1.78 (IC95%: 1.43-2.23). p<0,001). La limitación funcional previa fue el motivo más esgrimido en regio-nes centro y sur (OR: 1.39, (IC95%: 1.12-1.72). p=0,002; OR: 1.50, (IC95%:1.15-1.94). p=0,002). Fue la futilidaden el tratamiento el motivo que mayores diferencias presentó entre las diversas regiones analizadas (dif:37,2%-68,8%). Por lo tanto, se puede concluir que existen diferencias geográficas en el territorio españolen las decisiones de rechazar el ingreso en una UCI como medida de LTSV, probablemente justificadas pordiferencias organizativas de los servicios de medicina intensiva participantes en el ADENI-UCI.(AU)

From a post hoc analysis of the ADENI-UCI study (multicenter, observational, cohort, prospective study,with a follow-up period of 13 months, in 62 Intensive Medicine Services in Spain. geographical differencesin the reason for denial of income in UCI as a LTSV measure are analyzed. A total of 2284 with an averageage of 75.25 (12.45) years were included. 59.43% male. By means of multinominal regression adjusted byage, sex, APACHE and SOFA, was evident (by choosing the northern for reference) that age in the southwas a less significantly exposed reason (OR: 0.48 (IC95%: 0.35-0.65). p<0.001), that severe chronic diseasewas less valued in the Mediterranean area (OR: 0.7% 0 (IC95%: 0.56-0.87). p-0.001), while it had moreweight in the central area (OR: 1.78 (95% CI: 1.43-2.23). The previous functional limitation was more raisedin central and southern regions (OR: 1.39, (IC95%: 1.12-1.72). p-0.002; OR:1.50, (IC95%:1.15-1.94). 0.002).It was futility in treatment that had the greatest differences between the various regions analysed (dif:37,2% - 68,8%). There are geographical differences in the Spanish territory in decisions to refuse entry intoan ICU as an LTSV measure, probably justified by organizational differences in intensive medicine servicesparticipating in the ADENI-UCI.(AU)

Enfermedad inflamatoria intestinal y trasplante de órganos sólido / No disponible

La población de pacientes con enfermedad inflamatoria intestinal (EII) y trasplante de órgano sólido (TOS) va en aumento. Existen dos escenarios clínicos: la recurrencia de la EII preexistente al TOS, que es más frecuente, y la aparición de EII de novo, cuya incidencia es mucho más elevada que la de la población general. El curso clínico de ambas es diferente y puede tener impacto negativo en el injerto. Los mecanismos fisiopatológicos se desconocen. No existen recomendaciones específicas de tratamiento. La combinación entre la terapia biológica de la EII y el régimen inmunosupresor, para evitar el rechazo, obliga a una vigilancia estrecha para detectar infecciones, eventos autoinmunes y neoplasias. El cáncer colorrectal (CCR) está aumentando en esta población. El grupo de mayor riesgo es el de trasplante hepático (TH) por colangitis esclerosante (CEP) con EII

No disponible

Preferences and satisfaction of IBD patients after switching from adalimumab 40 mg weekly to 80 mg every other week given as a single injection: the ADASCAL study.

BACKGROUND: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen. METHODS: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life-5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9). RESULTS: In total, 77 patients (64 Crohn's disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7). CONCLUSION: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW.

Inflammatory bowel disease and solid organ transplantation.

The population of patients with inflammatory bowel disease (IBD) and solid organ transplant (SOT) is increasing. Two clinical scenarios exist, recurrence of pre-existing IBD, which is more common, and de novo development of IBD, with a much higher incidence than in the general population. Their clinical course differs and may have a negative impact on the graft in both cases. The pathophysiological mechanisms remain unknown and no specific treatment recommendations are available. The combined effect of biologic therapy against IBD and immunosuppressive therapy against a potential rejection means that close monitoring is mandatory to identify infection, autoimmune events and malignancies. The colorectal cancer (CRC) rate is higher in this population. The group at greatest risk are patients with IBD undergoing liver transplantation (LT) for primary sclerosing cholangitis (PSC).

Modeling the neuromuscular junction in vitro: an approach to study neuromuscular junction disorders.

The neuromuscular junction (NMJ) is a specialized structure that works as an interface to translate the action potential of the presynaptic motor neuron (MN) in the contraction of the postsynaptic myofiber. The design of appropriate experimental models is essential to have efficient and reliable approaches to study NMJ development and function, but also to generate conditions that recapitulate distinct features of diseases. Initial studies relied on the use of tissue slices maintained under the same environment and in which single motor axons were difficult to trace. Later, MNs and muscle cells were obtained from primary cultures or differentiation of progenitors and cocultured as monolayers; however, the tissue architecture was lost. Current approaches include self-assembling 3D structures or the incorporation of biomaterials with cells to generate engineered tissues, although the incorporation of Schwann cells remains a challenge. Thus, numerous investigations have established different NMJ models, some of which are quite complex and challenging. Our review summarizes the in vitro models that have emerged in recent years to coculture MNs and skeletal muscle, trying to mimic the healthy and diseased NMJ. We expect our review may serve as a reference for choosing the appropriate experimental model for the required purposes of investigation.

Sustainable synthesis of branched-chain diesters.

Esters from branched alcohols and dicarboxylic linear acids are widely used as lube bases due to their good performance at low temperatures. This work proposes a new process to synthesize bis(2-ethylbutyl) adipate and bis(2-ethylbutyl) sebacate by using the lipase-based catalyst Novozym® 435 in a solvent-free system. Different reaction strategies have been tested in order to minimize 2-ethyl-1-butanol losses due to its evaporation and optimum operation conditions have been determined: 2.5 % of biocatalyst, 50 °C and a molar excess of alcohol of 15 % for the adipic diester and of 25 % for the sebacic one. It has also been proven that the immobilized enzyme can be reused in seven successive reaction cycles, achieving high yields without an appreciable reduction of activity. This biocatalytic pathway is a promising basis for the development of a more sustainable large scale process for obtaining biodegradable lubricants, as it is pointed out by productivity, economic and green metrics calculations.