Comparative Analysis of Thermal Adaptations of Extremophilic Prolyl Oligopeptidases.

Prolyl oligopeptidases (POPs) from psychrophilic, mesophilic, and thermophilic organisms found in a range of natural environments are studied using a combination of protein structure prediction, atomistic molecular dynamics, and trajectory analysis to determine how the S9 protease family adapts to extreme thermal conditions. We compare our results with hypotheses from the literature regarding structural adaptations that allow proteins to maintain structure and function at extreme temperatures, and find that in the case of POPs, only a subset of proposed adaptations are employed for maintaining stability. The catalytic and propeller domains are highly structured, limiting the range of mutations that can be made to enhance hydrophobicity or form disulfide bonds without disrupting the formation of necessary secondary structure. Rather, we observe a pattern in which overall prevalence of bound interactions (salt bridges and hydrogen bonds) is conserved by using increasing numbers of increasingly short-lived interactions as temperature increases. This suggests a role for an entropic rather than energetic strategy for thermal adaptation in this protein family.

The Functional Significance of High Cysteine Content in Eye Lens γ-Crystallins.

Cataract disease is strongly associated with progressively accumulating oxidative damage to the extremely long-lived crystallin proteins of the lens. Cysteine oxidation affects crystallin folding, interactions, and light-scattering aggregation especially strongly due to the formation of disulfide bridges. Minimizing crystallin aggregation is crucial for lifelong lens transparency, so one might expect the ubiquitous lens crystallin superfamilies (α and ßγ) to contain little cysteine. Yet, the Cys content of γ-crystallins is well above the average for human proteins. We review literature relevant to this longstanding puzzle and take advantage of expanding genomic databases and improved machine learning tools for protein structure prediction to investigate it further. We observe remarkably low Cys conservation in the ßγ-crystallin superfamily; however, in γ-crystallin, the spatial positioning of Cys residues is clearly fine-tuned by evolution. We propose that the requirements of long-term lens transparency and high lens optical power impose competing evolutionary pressures on lens ßγ-crystallins, leading to distinct adaptations: high Cys content in γ-crystallins but low in ßB-crystallins. Aquatic species need more powerful lenses than terrestrial ones, which explains the high methionine content of many fish γ- (and even ß-) crystallins. Finally, we discuss synergies between sulfur-containing and aromatic residues in crystallins and suggest future experimental directions.

Genome sequence of the lytic bacteriophage Alucard, a cluster EE actinophage.

Bacteriophage Alucard is a lytic phage isolated from the soil collected in southern Maine on Microbacterium foliorum NRRL B-24224. Alucard has siphovirus morphology with a 17,363-bp genome encoding 25 putative genes. Based on gene content similarity to actinobacteriophages, Alucard is assigned to cluster EE.

Transversus abdominis plane blocks in laparoscopic inguinal hernia repair: a review.

INTRODUCTION: Throughout its history, there have been significant advances in pain control of inguinal hernia repairs. One of the most recent developments is locoregional pain blocks. There is a multitude of literature available on laparoscopic inguinal hernia repair and transversus abdominis plane (TAP) blocks. OBJECTIVES: This paper seeks to provide a thorough and systematic literature review on the role of TAP blocks in laparoscopic inguinal hernia repairs. METHODS: PubMed and Google Scholar were searched for relevant literature using predetermined medical subject heading (MeSH) terms: "(TAP block)" AND "(Laparoscopic inguinal hernia repair)". RESULTS: A total of 166 publications were identified, from which 18 publications were included in the final review after eligibility criteria were applied. CONCLUSION: The majority of studies conclude that TAP blocks performed in the setting of laparoscopic inguinal hernia repair improve post-operative pain and mobility, decrease opiate analgesic usage, and are superior in pain control compared to other modalities of regional anesthesia. Thus, to improve post-operative outcomes and patient satisfaction, TAP blocks should be heavily considered for routine use in surgical practice for laparoscopic inguinal hernia repair.

Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.

Comparative Modeling and Analysis of Extremophilic D-Ala-D-Ala Carboxypeptidases.

Understanding the molecular adaptations of organisms to extreme environments requires a comparative analysis of protein structure, function, and dynamics across species found in different environmental conditions. Computational studies can be particularly useful in this pursuit, allowing exploratory studies of large numbers of proteins under different thermal and chemical conditions that would be infeasible to carry out experimentally. Here, we perform such a study of the MEROPS family S11, S12, and S13 proteases from psychophilic, mesophilic, and thermophilic bacteria. Using a combination of protein structure prediction, atomistic molecular dynamics, and trajectory analysis, we examine both conserved features and trends across thermal groups. Our findings suggest a number of hypotheses for experimental investigation.

Mutation Effects on Structure and Dynamics: Adaptive Evolution of the SARS-CoV-2 Main Protease.

The main protease of SARS-CoV-2 (Mpro) plays a critical role in viral replication; although it is relatively conserved, Mpro has nevertheless evolved over the course of the COVID-19 pandemic. Here, we examine phenotypic changes in clinically observed variants of Mpro, relative to the originally reported wild-type enzyme. Using atomistic molecular dynamics simulations, we examine effects of mutation on protein structure and dynamics. In addition to basic structural properties such as variation in surface area and torsion angles, we use protein structure networks and active site networks to evaluate functionally relevant characters related to global cohesion and active site constraint. Substitution analysis shows a continuing trend toward more hydrophobic residues that are dependent on the location of the residue in primary, secondary, tertiary, and quaternary structures. Phylogenetic analysis provides additional evidence for the impact of selective pressure on mutation of Mpro. Overall, these analyses suggest evolutionary adaptation of Mpro toward more hydrophobicity and a less-constrained active site in response to the selective pressures of a novel host environment.

CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database.

The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded ß-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.

Co-design, implementation, and evaluation of plain language genomic test reports.

Understanding and communicating genomic results can be challenging for families and health professionals without genetic specialty training. Unlike modifying existing laboratory reports, plain language genomic test reports provide an opportunity for patient/family-centered approaches. However, emerging examples generally lack co-design and/or evaluation in real-world settings. Through co-design involving patient groups, plain language experts, educators, and genetic health professionals, plain language genomic test report templates were produced for common test outcomes in rare diseases. Eight plain language genomic test report templates were developed. These reports were piloted and evaluated as part of a national pediatric ultra-rapid genomic testing program. Family and genetic health professional experiences with report layout, content, and use were explored using surveys. Of 154 families and 107 genetic health professionals issued with reports, 51 families and 57 clinicians responded (RR = 33% and 53%, respectively). Most families (82%) found their report helpful in understanding the result. Reports were shared by 63% of families, predominantly with family members (72%), or health professionals (68%). Clinicians (15%) adapted the reports for other settings. Through co-design, plain language genomic test reports implemented in a real-world setting can facilitate patient/family and caregiver understanding and communication of genomic test purpose, outcome, and potential clinical implications.

'Diagnostic shock': the impact of results from ultrarapid genomic sequencing of critically unwell children on aspects of family functioning.

Rapid genomic sequencing (rGS) is being increasingly used in neonatal and paediatric intensive care units. While there is emerging evidence of clinical utility and cost-effectiveness, concerns have been raised regarding the impact of delivering genomic results in an acute care setting. To help investigate these concerns, we analysed survey data collected from caregivers whose children had received rGS through a national rapid genomic diagnosis program. The impact of rGS on families was assessed through the PedsQL2.0 Family Impact Module and the State-Trait Anxiety Inventory (STAI-6). Sixty-one parents/carers completed the survey during the study period (response rate 48%; 61/128). Mean parent and family functioning was reduced in this sample, reflecting the stressful conditions facing families with critically unwell children. We found caregivers whose children had received a diagnostic result through rGS reported a reduced family relationships score compared to caregivers of children who did not receive a diagnosis. These findings have implications for genetic counselling practice in this setting.

Enabling genomic island prediction and comparison in multiple genomes to investigate bacterial evolution and outbreaks.

Outbreaks of virulent and/or drug-resistant bacteria have a significant impact on human health and major economic consequences. Genomic islands (GIs; defined as clusters of genes of probable horizontal origin) are of high interest because they disproportionately encode virulence factors, some antimicrobial-resistance (AMR) genes, and other adaptations of medical or environmental interest. While microbial genome sequencing has become rapid and inexpensive, current computational methods for GI analysis are not amenable for rapid, accurate, user-friendly and scalable comparative analysis of sets of related genomes. To help fill this gap, we have developed IslandCompare, an open-source computational pipeline for GI prediction and comparison across several to hundreds of bacterial genomes. A dynamic and interactive visualization strategy displays a bacterial core-genome phylogeny, with bacterial genomes linearly displayed at the phylogenetic tree leaves. Genomes are overlaid with GI predictions and AMR determinants from the Comprehensive Antibiotic Resistance Database (CARD), and regions of similarity between the genomes are also displayed. GI predictions are performed using Sigi-HMM and IslandPath-DIMOB, the two most precise GI prediction tools based on nucleotide composition biases, as well as a novel blast-based consistency step to improve cross-genome prediction consistency. GIs across genomes sharing sequence similarity are grouped into clusters, further aiding comparative analysis and visualization of acquisition and loss of mobile GIs in specific sub-clades. IslandCompare is an open-source software that is containerized for local use, plus available via a user-friendly, web-based interface to allow direct use by bioinformaticians, biologists and clinicians (at https://islandcompare.ca).

A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial.

BACKGROUND: The c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model. METHODS: HT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1-3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry. FINDINGS: c-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression. INTERPRETATION: EMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery.

Timing and Dose of Upper Limb Motor Intervention After Stroke: A Systematic Review.

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22-66) and study sample size remains small (median n=30, IQR 20-48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1-7 days), 176 early subacute (8-90 days), 34 late subacute (91-180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600-1430) min/session, 1 (IQR, 1-1) session/d, 5 (IQR, 5-5) d/wk for 4 (IQR, 3-5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.

The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer.

The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.

Changes Associated with the Peri-Ovulatory Period, Age and Pregnancy in ACTH, Cortisol, Glucose and Insulin Concentrations in Mares.

Although there are many hormonal changes associated with reproduction, the effects of ovulation and early pregnancy on adrenocorticotropic hormone (ACTH) and insulin concentrations are poorly described. We hypothesise that both ovulation and early pregnancy will alter ACTH and insulin concentrations in healthy mares. Eighteen mares showing no clinical signs suggestive of, or laboratory findings consistent with, pituitary pars intermedia dysfunction PPID and insulin dysregulation (ID) are enrolled. ACTH, cortisol, insulin and glucose concentrations are measured over their peri-ovulatory period, as determined via ultrasounds and progesterone concentrations. The mares are grouped by age and gestation status, and a two-way repeated-measures ANOVA is used to determine the effects of age and early pregnancy, along with the peri-ovulatory period, on analyte concentrations. No significant effect of age, ovulation or early pregnancy is detected on the mares' cortisol, insulin or glucose concentrations; however, there is a significant effect of early pregnancy and ovulation on ACTH concentrations (p = 0.04 and p = 0.04 respectively). ACTH concentrations change around ovulation and with early pregnancy. Therefore, knowledge of a mare's reproductive status might be beneficial when interpreting ACTH concentrations.

Learning from scaling up ultra-rapid genomic testing for critically ill children to a national level.

In scaling up an ultra-rapid genomics program, we used implementation science principles to design and investigate influences on implementation and identify strategies required for sustainable "real-world" services. Interviews with key professionals revealed the importance of networks and relationship building, leadership, culture, and the relative advantage afforded by ultra-rapid genomics in the care of critically ill children. Although clinical geneticists focused on intervention characteristics and the fit with patient-centered care, intensivists emphasized the importance of access to knowledge, in particular from clinical geneticists. The relative advantage of ultra-rapid genomics and trust in consistent and transparent delivery were significant in creating engagement at initial implementation, with appropriate resourcing highlighted as important for longer term sustainability of implementation. Our findings demonstrate where common approaches can be used and, significantly, where there is a need to tailor support by professional role and implementation phase, to maximize the potential of ultra-rapid genomic testing to improve patient care.

PSORTdb 4.0: expanded and redesigned bacterial and archaeal protein subcellular localization database incorporating new secondary localizations.

Protein subcellular localization (SCL) is important for understanding protein function, genome annotation, and aids identification of potential cell surface diagnostic markers, drug targets, or vaccine components. PSORTdb comprises ePSORTdb, a manually curated database of experimentally verified protein SCLs, and cPSORTdb, a pre-computed database of PSORTb-predicted SCLs for NCBI's RefSeq deduced bacterial and archaeal proteomes. We now report PSORTdb 4.0 (http://db.psort.org/). It features a website refresh, in particular a more user-friendly database search. It also addresses the need to uniquely identify proteins from NCBI genomes now that GI numbers have been retired. It further expands both ePSORTdb and cPSORTdb, including additional data about novel secondary localizations, such as proteins found in bacterial outer membrane vesicles. Protein predictions in cPSORTdb have increased along with the number of available microbial genomes, from approximately 13 million when PSORTdb 3.0 was released, to over 66 million currently. Now, analyses of both complete and draft genomes are included. This expanded database will be of wide use to researchers developing SCL predictors or studying diverse microbes, including medically, agriculturally and industrially important species that have both classic or atypical cell envelope structures or vesicles.

Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10.

The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet need. Following uninformative exome and genome sequencing of a family quartet including two siblings with suspected mitochondrial disorder, RNA sequencing (RNAseq) was pursued in one sibling. Long-read amplicon sequencing was used to determine and quantify transcript structure. Immunoblotting studies and quantitative proteomics were performed to demonstrate functional impact. Differential expression analysis of RNAseq data identified significantly decreased expression of the mitochondrial OXPHOS Complex I subunit NDUFB10 associated with a cryptic exon in intron 1 of NDUFB10, that included an in-frame stop codon. The cryptic exon contained a rare intronic variant that was homozygous in both affected siblings. Immunoblot and quantitative proteomic analysis of fibroblasts revealed decreased abundance of Complex I subunits, providing evidence of isolated Complex I deficiency. Through multiomic analysis we present data implicating a deep intronic variant in NDUFB10 as the cause of mitochondrial disease in two individuals, providing further support of the gene-disease association. This study highlights the importance of transcriptomic and proteomic analyses as complementary diagnostic tools in patients undergoing genome-wide diagnostic evaluation.

Sequence Characterization and Molecular Modeling of Clinically Relevant Variants of the SARS-CoV-2 Main Protease.

The SARS-CoV-2 main protease (Mpro) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant neutral drift and selection pressure, with new Mpro mutations arising over time. Identification and structural characterization of Mpro variants is thus critical for robust inhibitor design. Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Residue substitution is widely distributed, with some tendency toward larger and more hydrophobic residues. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery.

Intoxicació per infusió de fonoll: causa d'irritabilitat en el lactant I el nounat / Intoxicación por infusión de hinojo: causa de irritabilidad en el lactante y el recién nacido / Intoxication by fennel infusion: cause of irritability in the infant and the newborn

INTRODUCCIÓ: La irritabilitat en el lactant és un motiu de consulta habitual que inclou les intoxicacions en el diagnòstic diferencial. L'ús de remeis casolans, com ara infusions, és freqüent en la població pediàtrica, en concret per tractar còlics, diarrees o vòmits. Aquest ús és més alt entre la població immigrant, amb la qual sovint existeix una barrera idiomàtica. Això pot dificultar la prevenció, la identificació I la resolució de possibles intoxicacions. En aquest treball es presenta el cas d'un nadó afectat per la ingesta d'infusió de fonoll, I s'insisteix en els efectes tòxics potencials. CAS CLÍNIC: Es presenta el cas d'un lactant de 16 dies de vida que consulta a infermeria per dificultats en l'alletament. S'observa una presa a la consulta, s'objectiva molta irritabilitat durant l'intent d'aferrament I es constata un escàs guany ponderal. Fent èmfasi en l'anamnesi, s'identifica l'administració durant dues setmanes de tres biberons al dia de 60 ml d'infusió de fonoll amb sucre com a remei per al còlic del lactant. COMENTARIS: Hi ha poca evidència de la tolerància al fonoll en lactants. Alguns dels seus compostos s'han aïllat en llet materna en cas que la mare n'hagi ingerit. La intoxicació depèn de la dosi I pot provocar cianosi sense resposta a oxigenoteràpia per metahemoglobinèmia. En quantitats més reduïdes, el component neurotòxic anetol provoca letargia, escàs guany ponderal, irritabilitat o vòmits; les proves complementàries no mostren alteracions, I la recuperació és completa al suprimirne la ingesta. És important detectar aquestes pràctiques potencialment perjudicials fent èmfasi en l'anamnesi

INTRODUCCIÓN: La irritabilidad en el lactante es un motivo de consulta habitual que incluye las intoxicaciones en su diagnóstico diferencial. El uso de remedios caseros a base de hierbas o infusiones es frecuente en la población pediátrica, en concreto para el tratamiento de cólicos, diarreas o vómitos. Dicho uso es mayor en la población inmigrante, con la cual suele existir también barrera idiomática. Esto puede dificultar la prevención, identificación y resolución de posibles intoxicaciones. Este trabajo presenta el caso de un recién nacido afectado por infusión de hinojo, haciendo hincapié en sus potenciales efectos tóxicos. CASO CLÍNICO: Se presenta el caso de un lactante de 16 días de vida que consulta a enfermería por dificultades en la lactancia. Se observa una toma en la consulta, se objetiva irritabilidad marcada y se constata una escasa ganancia ponderal. Poniendo énfasis en la anamnesis, se identifica la administración durante dos semanas de tres biberones al día de 60 ml de infusión de hinojo con azúcar como remedio para los cólicos del lactante. COMENTARIOS: Existe poca evidencia de la tolerancia al hinojo en lactantes. Algunos de sus compuestos han sido aislados en la leche materna en caso de ingesta por su parte. La intoxicación es dosis-dependiente y puede provocar cianosis sin respuesta a oxigenoterapia por metahemoglobinemia. En cantidades más reducidas, el compuesto neurotóxico anetol puede provocar letargia, fallo de medro, irritabilidad y vómitos. Las pruebas complementarias no muestran alteraciones y la recuperación es completa al suprimir la ingesta de la sustancia. Es importante detectar estas prácticas potencialmente perjudiciales para la población pediátrica haciendo hincapié en la anamnesis de forma activa

INTRODUCTION: Irritability in the newborn is a usual reason for consultation. It may include intoxications in its differential diagnosis. Herbal medicines and infusions are commonly used in paediatric patients, especially for infantile colic, diarrhoea and vomiting. These practices are common among the immigrant population, in which idiomatic barrier is frequent. Thus, prevention, identification and resolution of eventual intoxications can be difficult. In this paper a case report of a newborn being affected by fennel infusion is presented. The focus is put on fennel's potential toxic effects. CASE REPORT: A case of a 16-day-old infant who consults the nurse due to breastfeeding difficulties is presented. A breast milk intake with marked irritability is observed during the consultation and a low weight gain is detected. On further questioning, the administration of 3 bottles per day of 60 ml of infusion of fennel with sugar over the previous two weeks was documented, as a remedy for the infant's colics. COMMENTS: There is little evidence about fennel tolerance in new-borns. Some of its compounds have been found in breast milk in case of ingestion by the mother. Intoxication is dose-dependent and can cause cyanosis unresponsive to oxygen due to metahaemoglinaemia. In smaller quantities, the neurotoxic compound anethole can cause lethargy, failure to thrive, irritability and vomiting. Additional diagnostic tests show no alterations. Recovery after interruption of the substance's intake is ad integrum. It is important to focus on the anamnesis in order to identify dietary habits and home remedies, which could be potentially harmful in the paediatric population