Connectivity of the Claustrum-Endopiriform Complex with the Presubiculum and Hippocampal Regions in the Common Marmoset (Callithrix jacchus).

We have investigated the hippocampal connectivity of the marmoset presubiculum (PreS) and reported that major connections of PreS in the rat were conserved in the marmoset. Moreover, our results indicated the presence of several additional projections that were almost absent in the rat brain, but abundant in the marmoset, such as direct projections from CA1 to PreS. However, little is known about the connectivity between the frontal brain regions and PreS or hippocampal formation. Therefore, we investigated the distribution of cells of the origins and terminals of the presubicular and hippocampal projections in the marmoset frontal brain regions using the retrograde and anterograde tracer cholera toxin B subunit. In cases of tracer injections into all layers of PreS, many neurons and terminals were labeled in the claustrum-endopiriform (Cl-En) complex almost entirely along the rostrocaudal axis. Even in cases where the injection site involved the superficial (not deep) layers of PreS, labeled neurons and terminals were distributed over a wide rostrocaudal range of the Cl-En complex, but their number and density were significantly lower than the whole-layer injection cases. In cases where the injection site was confined to the hippocampal formation, labeled cells and terminals were localized at a restricted portion of the Cl-En complex. Here, we demonstrate for what we believe to be the first time the strong, reciprocal connections of the Cl-En complex with PreS and projections from the Cl-En complex to the hippocampal regions (CA1 and the subiculum) in the marmoset. Our findings indicate that the Cl-En complex may exert a strong influence on the cortical and subcortical outputs from PreS and, in turn, the entire memory circuitry in the marmoset brain.

Genomic analysis of Vibrio cholerae O1 isolates from cholera cases, Europe, 2022.

BackgroundThe number of cholera cases reported to the World Health Organization (WHO) in 2022 was more than double that of 2021. Nine countries of the WHO European Region reported 51 cases of cholera in 2022 vs five reported cases in 2021.AimWe aimed to confirm that the Vibrio cholerae O1 isolates reported by WHO European Region countries in 2022 belonged to the seventh pandemic El Tor lineage (7PET). We also studied their virulence, antimicrobial resistance (AMR) determinants and phylogenetic relationships.MethodsWe used microbial genomics to study the 49 V. cholerae O1 isolates recovered from the 51 European cases. We also used > 1,450 publicly available 7PET genomes to provide a global phylogenetic context for these 49 isolates.ResultsAll 46 good-quality genomes obtained belonged to the 7PET lineage. All but two isolates belonged to genomic Wave 3 and were grouped within three sub-lineages, one of which, Pre-AFR15, predominated (34/44). This sub-lineage, corresponding to isolates from several countries in Southern Asia, the Middle East and Eastern or Southern Africa, was probably a major contributor to the global upsurge of cholera cases in 2022. No unusual AMR profiles were inferred from analysis of the AMR gene content of the 46 genomes.ConclusionReference laboratories in high-income countries should use whole genome sequencing to assign V. cholerae O1 isolates formally to the 7PET or non-epidemic lineages. Periodic collaborative genomic studies based on isolates from travellers can provide useful information on the circulating strains and their evolution, particularly as concerns AMR.

Ventilatory pressure parameters impact the association between acute gastrointestinal injury and all-cause mortality in mechanically ventilated patients.

Acute gastrointestinal injury (AGI) is common in mechanically ventilated (MV) patients, but the potential association between ventilatory pressure parameters and AGI grade and their impact on mortality remains unclear. This study aimed to explore the association between ventilatory pressure parameters and AGI grade, and their interaction on all-cause mortality in MV patients. This study was a secondary analysis of a multicenter, prospective, observational study that enrolled adult patients with an expected duration of mechanical ventilation ≥ 48 h from 14 general intensive care units in Zhejiang Province between March and August 2014. The AGI grade was assessed daily on the basis of gastrointestinal symptoms, intra-abdominal pressures, and feeding intolerance in the first week of admission to the ICU. This study included 331 patients (69.2% men; mean age, 64.6 ± 18.9 years). Multivariate regression analysis showed that plateau pressure (Pplat) (OR 1.044, 95% CI 1.009-1.081, P = 0.013), serum creatinine (OR 1.003, 95% CI 1.001-1.006, P = 0.042) and APACHE II score (OR 1.035, 95% CI 1.021-1.072, P = 0.045) were independently associated with global AGI grade III/IV within 7 days of ICU admission. Moreover, global AGI grade (HR 2.228, 95% CI 1.561-3.182, P < 0.001), serum creatinine (HR 1.002, 95% CI 1.001-1.003, P = 0.012) and APACHE II score (HR 1.039, 95% CI 1.015-1.063, P = 0.001) were independently associated with 60-day mortality. In addition, there were significant (Pint ≤ 0.028) interactions of Pplat and DP with AGI grade in relation to 60-days mortality, whereas no interaction (Pint = 0.061) between PEEP and AGI grade on 60-days mortality was observed. In the presence of Pplat ≥ 19 cmH2O, the patients with AGI grade III/IV had 60-day mortality rate of 72.2%, significantly higher than those with AGI grade I/II (48.7%, P = 0.018), whereas there were no significant differences (27.9% vs. 33.7%, P = 0.39) in 60-days mortality between AGI grade I/II and III/IV among the patients with Pplat < 19 cmH2O. In comparison with Pplat, DP had a similar interaction (Pint = 0.028) with AGI grade on 60-day mortality. Ventilatory pressure parameters (Pplat and DP) are independent risk factors of AGI grade III/IV. Pplat and DP interact with AGI grade on 60-days mortality, highlighting the importance of optimizing ventilatory pressure parameters to improve gastrointestinal function and survival outcomes of MV patients.Trial registration: ChiCTR-OCS-13003824.

Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice.

Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of α-Syn in different tissues and detected phospho-α-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The SncaG51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.

Computational investigation in inhibitory effects of amantadine on classical swine fever virus p7 ion channel activity.

Classical swine fever virus (CSFV) p7 viroporin plays crucial roles in cellular ion balance and permeabilization. The antiviral drug amantadine effectively inhibits viral replication by blocking the activity of CSFV p7 viroporin. However, little information is available for the binding mode of amantadine with CSFV p7 viroporin, due to the lack of a known polymer structure for CSFV p7. In this study, we employed AlphaFold2 to predict CSFV p7 structures. Subsequently, we conducted a docking study to investigate the binding sites of amantadine to CSFV p7. Computational analysis showed that CSFV p7 forms a pore channel in a hexameric structure. Furthermore, molecular dynamics (MD) simulations and mutant analyses further suggest that CSFV p7 likely exists as a hexamer. Docking studies and MD simulations showed that amantadine interacts with the hydrophibic regions of tetramer and pentamer, as well as with the hydrophobic pore channel of the hexamer. Considering the potential hexameric assembly of CSFV p7, along with docking results, MD simulations, and the characteristics of the gated ion channels, we propose a model of CSFV p7 ion channel based on its hexameric configuration. In this model, residues E21, Y25, and R34 are suggested to selectively recruit and dehydrate ions, while residues L28 and L31 likely act as hydrophobic constrictors, thereby restricting the free movement of water. The binding of amantadine to residues I20, E21, V24 and Y25 effectively blocks ion transport. However, this proposed molecular model requires experimental validation. Our findings give a structural insight into the models of CSFV p7 as an ion channel and provide a molecular explanation for the inhibition effects of amantadine on CSFV p7-mediated ion channel conductance.

Can Faecal Zonulin and Calprotectin Levels Be Used in the Diagnosis and Follow-Up in Infants with Milk Protein-Induced Allergic Proctocolitis?

OBJECTIVE: The aim of our study was to investigate whether a 1-month-long milk-free diet results in a reduction in faecal calprotectin (FC) and faecal-zonulin-related proteins (FZRP) in children with milk-protein-induced allergic proctocolitis (MPIAP). MATERIALS AND METHODS: This is a single-centre, prospective, observational cohort study involving 86 infants with MPIAP, aged 1-3 months, and 30 healthy controls of the same age. The FC and FZRP were marked using the ELISA method (IDK® Calprotectin or Zonulin ELISA Kit, Immunodiagnostik AG, Bensheim, Germany). The diagnosis of MPIAP was confirmed with an open milk challenge test. RESULTS: FFC and FZRP proved useful in evaluating MPIAP treatment with a milk-free diet, and the resolution of allergic symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks on the diet. The FC and FZRP concentrations were still higher than in the control group. A high variability of FC concentrations was found in all the study groups. An important limitation is the phenomenon of FZRP not being produced in all individuals, affecting one in five infants. CONCLUSIONS: FC and FZRP can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk-free diet, indicating a slower resolution of allergic inflammation than of allergic symptoms. The diagnosis of MPIAP on the basis of FC concentrations is subject to considerable error, due to the high individual variability of this indicator. FZRP is a better parameter, but this needs further research, as these are the first determinations in infants with MPIAP.

Nutritional Management of Pediatric Gastrointestinal Motility Disorders.

Normal and optimal functioning of the gastrointestinal tract is paramount to ensure optimal nutrition through digestion, absorption and motility function. Disruptions in these functions can lead to adverse physiological symptoms, reduced quality of life and increased nutritional risk. When disruption or dysfunction of neuromuscular function occurs, motility disorders can be classified depending on whether coordination or strength/velocity of peristalsis are predominantly impacted. However, due to their nonspecific presenting symptoms and overlap with sensory disruption, they are frequently misdiagnosed as disorders of the gut-brain interaction. Motility disorders are a prevalent issue in the pediatric population, with management varying from medical therapy to psychological therapy, dietary manipulation, surgical intervention or a multimodal approach. This narrative review aims to discuss the dietary management of common pediatric motility disorders including gastroesophageal reflux, esophageal atresia, achalasia, gastroparesis, constipation, and the less common but most severe motility disorder, pediatric intestinal pseudo-obstruction.

[The development, implementation principles and application of the endoscopic super minimally invasive surgery].

Endoscopic therapy has gone through three stages of development: intraluminal treatment, endoscopic tunneling technology, and endoscopic super minimally invasive surgery (ESMIS). Compared to the drawbacks of traditional surgical methods"organ resection and anatomical reconstruction", super minimally invasive surgery (SMIS) emphasizes the surgical concept of"curing diseases while preserving organs and functions". SMIS conducts treatment through four channels: natural cavity channel, tunnel channel, puncture channel, and multi cavity channel. It offers dozens of surgical methods for diagnosing and treating gastrointestinal diseases. At present, relatively sound implementation principles for ESMIS treatment have been established to ensure the safety and effectiveness of surgery, and to continuously expand other diagnostic and therapeutic fields.

Prevalence and determinants of obesity and its association with upper gastrointestinal diseases in people aged 40-69 years in Yangzhong, southeast China.

Several international epidemiological studies have established a link between obesity and upper gastrointestinal cancer (UGC), but Chinese evidence is limited. This study aimed to determine the prevalence of obesity, especially central obesity, while investigating its association with upper gastrointestinal diseases in the high-risk population of Yangzhong, a typical high-risk area for UGC in southeastern China. We conducted a cross-sectional study from November 2017 to June 2021 involving 6736 residents aged 40-69. Multivariate logistic regression was used to assess independent factors influencing overweight/obesity and central obesity. We also analyzed the relationship between obesity and upper gastrointestinal diseases using multinomial logistic regression. The prevalence of overweight, obesity, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)-central obesity were 40.6%, 12.0%, 49.9%, 79.4%, and 63.7%, respectively. Gender, age, smoking, tea consumption, sufficient vegetable, pickled food, spicy food, eating speed, physical activity, family history of cancer, and family history of common chronic disease were associated with overweight /obesity and central obesity. Besides, education and missing teeth were only associated with central obesity. General and central obesity were positively associated with UGC, while general obesity was negatively associated with UGC precancerous diseases. There were no significant associations between obesity and UGC precancerous lesions. Subgroup analyses showed that general and central obesity was positively associated with gastric cancer but not significantly associated with esophageal cancer. Obesity is negatively and positively associated with gastric and esophageal precancerous diseases, respectively. In conclusion, general and central obesity were at high levels in the target population in this study. Most included factors influenced overweight/obesity and central obesity simultaneously. Policymakers should urgently develop individualized measures to reduce local obesity levels according to obesity characteristics. Besides, obesity increases the risk of UGC but decreases the risk of UGC precancerous diseases, especially in the stomach. The effect of obesity on the precancerous diseases of the gastric and esophagus appears to be the opposite. No significant association between obesity and upper gastrointestinal precancerous lesions was found in the study. This finding still needs to be validated in cohort studies.

Analysis of Cholera Risk in India: Insights from 2017-18 Serosurvey Data Integrated with Epidemiologic data and Societal Determinants from 2015-2019.

BACKGROUND: Indian subcontinent being an important region in the fight to eliminate cholera needs better cholera surveillance. Current methods miss most infections, skewing disease burden estimates. Triangulating serosurvey data, clinical cases, and risk factors could reveal India's true cholera risk. METHODS: We synthesized data from a nationally representative serosurvey, outbreak reports and risk factors like water, sanitation and the Multidimensional Poverty Index, to create a composite vulnerability index for assessing state-wise cholera risk in India. We tested 7,882 stored sera samples collected during 2017-18 from individuals aged 9-45 years, for vibriocidal antibodies to Vibrio cholerae O1 using a cut-off titre ≥320 defining as elevated titre. We also extracted data from the 2015-19 Integrated Disease Surveillance Programme and published cholera reports. RESULTS: Overall, 11.7% (CI: 10.4-13.3%) of the sampled population had an elevated titre of cholera vibriocidal antibodies (≥320). The Southern region experienced the highest incidence (16.8%, CI: 12.1-22.8), followed by the West (13.2%, CI: 10.0-17.3) and North (10.7%, CI: 9.3-12.3). Proportion of samples with an elevated vibriocidal titre (≥320) was significantly higher among individuals aged 18-45 years (13.0% CI: 11.2-15.1) compared to children 9-17 years (8.6%, CI 7.3-10.0, p<0.05); we found no differences between sex or urbanicity. Between 2015-2019, the Integrated Disease Surveillance Program (IDSP) reported 29,400 cases of cholera across the country. Using the composite vulnerability index, we found Karnataka, Madhya Pradesh, and West Bengal were the most vulnerable states in India in terms of risk of cholera. CONCLUSION: The present study showed that cholera infection is present in all five regions across India. The states with high cholera vulnerability could be prioritized for targeted prevention interventions.

Genomic evolution and rearrangement of CTX-Φ prophage elements in Vibrio cholerae during the 2018-2024 cholera outbreaks in eastern Democratic Republic of the Congo.

ABSTRACTBetween 2018 and 2024, we conducted systematic whole-genome sequencing and phylogenomic analysis on 263 V. cholerae O1 isolates from cholera patients across four provinces in the Democratic Republic of Congo (North-Kivu, South-Kivu, Tanganyika, and Kasai Oriental). These isolates were classified into the AFR10d and AFR10e sublineages of AFR10 lineage, originating from the third wave of the seventh El Tor cholera pandemic (7PET). Compared to the strains analysed between 2014 and 2017, both sublineages had few genetic changes in the core genome but recent isolates (2022-2024) had significant CTX prophage rearrangement. AFR10e spread across all four provinces, while AFR10d appeared to be extinct by the end of 2020. Since 2022, most V. cholerae O1 isolates exhibited significant CTX prophage rearrangements, including a tandem repeat of an environmental satellite phage RS1 downstream the ctxB toxin gene of the CTX-Φ-3 prophage on the large chromosome, as well as two or more arrayed copies of an environmental pre-CTX-Φ prophage precursor on the small chromosome. We used Illumina data for mapping and coverage estimation to identify isolates with unique CTX-Φ genomic features. Gene localization was then determined on MinION-derived assemblies, revealing an organization similar to that of non-O1 V. cholerae isolates found in Asia (O139 VC1374, and environmental O4 VCE232), but never described in V. cholerae O1 El Tor from the third wave. In conclusion, while the core genome of AFR10d and AFR10e showed minimal changes, significant alterations in the CTX-Φ and pre-CTX-Φ prophage content and organization were identified in AFR10e from 2022 onwards.

Genetic estimation of causalities between educational attainment with common digestive tract diseases and the mediating pathways.

BACKGROUND: The association between education, intelligence, and cognition with digestive tract diseases has been established. However, the specific contribution of each factor in the pathogenesis of these diseases are still uncertain. METHOD: This study employed multivariable Mendelian randomization (MR) to assess the independent effects of education, intelligence, and cognition on gastrointestinal conditions in the FinnGen and UK Biobank European-ancestry populations. A two-step MR approach was employed to assess the mediating effects of the association. RESULTS: Meta-analysis of MR estimates from FinnGen and UK Biobank showed that 1- SD (4.2 years) higher education was causally associated with lower risks of gastroesophageal reflux (OR: 0.58; 95% CI: 0.50, 0.66), peptic ulcer (OR: 0.57; 95% CI: 0.47, 0.69), irritable bowel syndrome (OR: 0.70; 95% CI: 0.56, 0.87), diverticular disease (OR: 0.69; 95% CI: 0.61, 0.78), cholelithiasis (OR: 0.68; 95% CI: 0.59, 0.79) and acute pancreatitis (OR: 0.54; 95% CI: 0.41, 0.72), independently of intelligence and cognition. These causal associations were mediating by body mass index (3.7-22.3%), waist-to-hip ratio (8.3-11.9%), body fat percentage (4.1-39.8%), fasting insulin (1.4-5.5%) and major depression (6.0-12.4%). CONCLUSION: Our findings demonstrate a causal and independent association between education and six common digestive tract diseases. Additionally, our study highlights five mediators as crucial targets for preventing digestive tract diseases associated with lower education levels.

Utilizing CT imaging for evaluating late gastrointestinal tract side effects of radiotherapy in uterine cervical cancer: a risk regression analysis.

BACKGROUND: Radiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation. METHODS: We retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital's databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs. RESULTS: This study included 153 patients, with a median age of 57 years (IQR 49-65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64-36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30-11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96-7.44, p < 0.001) associated with higher late GI toxicity grades. CONCLUSIONS: Our study shows CT findings correlate with grade 2-4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value.

[Effect of non-pharmacological preventive measures on the incidence of respiratory and gastrointestinal pathologies]. / Efecto de las medidas preventivas no farmacológicas en la incidencia de patología respiratoria y gastrointestinal.

OBJECTIVE: The use of non-pharmacological preventive measures during the COVID-19 pandemic has helped to reduce the incidence of multiple airborne or contact diseases. The objective of this paper was to evaluate the impact that all preventive measures have had on the transmission of different microorganisms, both by respiratory and contact transmission. METHODS: We compared the incidence of different infectious episodes coded with the CIAP-2 code (International Classification of Primary Care second edition of the WONCA International Classification Committee) collected from the computerized history of primary care, both with respiratory tract and digestive tract involvement, in the period from March 2018 to February 2020 (pre-pandemic period) and from March 2020 to February 2022 (pandemic period). The data corresponded to the entire region, with an estimated average population for the four years of 650,000 people. The statistical treatment of the data consisted of a descriptive analysis with the calculation of absolute values and percentages. Rates were calculated and compared using data provided by the National Institute of Statistics as a denominator. The P was obtained by statistical comparison by the exact method. A comparison of rates was made. RESULTS: The incidence in the number of CIAP-2 episodes studied, both corresponding to respiratory and gastrointestinal pathologies, comparing the period March 2018-February 2020 with the period March 2020-February 2022 decreased by 65.81%, from 534,439 cases to 182,707. CONCLUSIONS: The preventive measures applied during the pandemic produce a significant decrease in pathology involving the respiratory or the digestive tract.

OBJETIVO: El uso de medidas preventivas no farmacológicas durante la pandemia de la COVID-19 ayudó a reducir la incidencia de múltiples enfermedades de transmisión aérea o por contacto. El objetivo de este trabajo fue evaluar el impacto que habían tenido todas las medidas preventivas en la transmisión de diferentes microorganismos, tanto por transmisión respiratoria como por contacto. METODOS: Comparamos la incidencia de diferentes episodios infecciosos codificados con el código CIAP-2 (Clasificación Internacional de Atención Primaria, segunda edición, del Comité de Clasificación Internacional WONCA-World Organization of Family Doctors) recogidos de la historia informatizada de Atención Primaria, tanto con afectación del tracto respiratorio como del tracto digestivo, en el período de marzo de 2018 a febrero de 2020 (período prepandemia) y de marzo de 2020 a febrero de 2022 (período de pandemia). Los datos correspondieron a toda la región, con una población media estimada para los cuatro años de 650.000 personas. El tratamiento estadístico de los datos consistió en un análisis descriptivo con el cálculo de valores absolutos y porcentajes. Se calcularon y compararon tasas tomando como denominador los datos proporcionados por el Instituto Nacional de Estadística. La P fue obtenida mediante comparación estadística por el método exacto. Se realizó una comparación de tasas. RESULTADOS: La incidencia en el número de episodios CIAP-2 estudiados, tanto correspondientes a patología respiratoria como gastrointestinal, comparando el periodo de marzo de 2018-febrero de 2020 con el periodo marzo de 2020-febrero de 2022, disminuyó en un 65,81%, pasando de 534.439 casos a 182.707. CONCLUSIONES: Las medidas preventivas aplicadas durante la pandemia producen una disminución significativa de la patología del tracto respiratorio o digestivo.

The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Vibrio cholerae serogroup O5 was responsible for the outbreak of gastroenteritis in Czechoslovakia in 1965.

Several authors have attributed the explosive outbreak of gastroenteritis that occurred in Czechoslovakia in 1965 to a toxigenic strain of Vibrio cholerae serogroup O37 based on unverified metadata associated with three particular strains from the American Type Culture Collection. Here, by sequencing the original strain preserved at the Czech National Collection of Type Cultures since 1966, we show that the strain responsible for this outbreak was actually a V. cholerae O5 that lacks the genes encoding the cholera toxin, the toxin-coregulated pilus protein and Vibrio pathogenicity islands present in V. cholerae O37 strains.

The activity of the quorum sensing regulator HapR is modulated by the bacterial extracellular vesicle (BEV)-associated protein ObfA of Vibrio cholerae.

Vibrio cholerae, a facultative human pathogen and causative agent of the severe diarrheal disease cholera, transits between the human intestinal tract and aquatic reservoirs. Like other bacterial species, V. cholerae continuously releases bacterial extracellular vesicles (BEVs) from its surface, which have been recently characterised for their role during in vivo colonisation. However, between epidemic outbreaks, V. cholerae persists in the biofilm mode for extended periods in aquatic reservoirs, which enhances environmental fitness and host transition. In this study, we investigated the effect of V. cholerae BEVs on biofilm formation, a critical feature for ex vivo survival. In contrast to BEVs from planktonic cultures, our results show that physiological concentrations of BEVs from dynamic biofilm cultures facilitate V. cholerae biofilm formation, which could be linked to a proteinaceous factor. Comparative proteomic analyses of planktonic- and biofilm-derived BEVs identified a previously uncharacterised outer membrane protein as an abundant component of dynamic biofilm-derived BEVs, which was found to be responsible for the BEV-dependent enhancement of biofilm production. Consequently, this protein was named outer membrane-associated biofilm facilitating protein A (ObfA). Comprehensive molecular studies unravelled ObfA as a negative modulator of HapR activity. HapR is a key transcriptional regulator of the V. cholerae quorum sensing (QS) cascade acting as a potent repressor of biofilm formation and virulence. Consistently, obfA mutants not only exhibited reduced biofilm production but also reduced colonisation fitness. Surprisingly, our results demonstrate that ObfA does not affect HapR through the canonical QS system but via the Csr-cascade altering the expression of the small regulatory RNAs CsrC and CsrD. In summary, this study elucidates a novel intraspecies BEV-based communication in V. cholerae that influences biofilm formation and colonisation fitness via a new regulatory pathway involving HapR, Csr-cascade and the BEV-associated protein ObfA.