Gastric neuroendocrine tumor presenting with carcinoid syndrome.

Carcinoid tumors are rare neoplasms, most frequently found in the gastrointestinal tract, responsible for the production of neuroendocrine mediators. Carcinoid syndrome is even rarer and consists of a set of symptoms characteristic of the release of these mediators into the systemic circulation. We present an interesting case of a patient with carcinoid syndrome as a late manifestation of a gastric neuroendocrine tumor with, highlighting the importance of knowing how to identify the carcinoid syndrome.

Capsule endoscopy: beyond the small bowel.

Capsule endoscopy (CE) is considered the first-line for the investigation of OGIB after conventional non-diagnostic endoscopic examinations. A detection rate of lesions outside the small bowel segment has been reported to range from 3.5% to >30%. Our primary objective was to analyze the role of CE in identifying lesions outside the small bowel segment that were not identified on conventional endoscopy in patients suspected of OGIB. In our study, CE appears to be effective and safe in diagnosing OGIB, also proving to be a tool in identifying lesions outside the small intestine segment.

Molecular characterization and virulence profile of Klebsiella pneumoniae and Klebsiella oxytoca isolated from ill cats and dogs in Portugal.

Klebsiella spp. are important pathogens of humans and companion animals such as cats and dogs, capable of causing severe life-threatening diseases. The aim of this study was to characterize the molecular and phenotypic properties of Klebsiella pneumoniae and Klebsiella oxytoca isolated from ill companion animals by whole genome sequencing, followed by in vitro assessment of biofilm formation and in vivo pathogenicity using the Galleria mellonella model. Two LPS O-types were identified for all the K. pneumoniae isolates tested (O3B and O1/O2v2) and only one for K. oxytoca isolates (OL104), and the most common STs found were ST11 and ST266. Furthermore, a high diversity of K-locus types was found for K. pneumoniae (KL102; KL105; KL31, and KL13). Within K. pneumoniae, one specific O/K/ST-types combination (i.e., KL105-ST11-O1/O2v2) showed results that were of concern, as it exhibited a high inflammatory response at 12 h post-infection in G. mellonella with 80% of the larvae dead at 72 h post-infection. This virulence potential, on the other hand, did not appear to be directly related to the biofilm-forming capacity. Also, virulence and resistance scores obtained for this set of strains did surpass score 1. The present study demonstrated that Klebsiella spp. isolated from companion animals belonging to STs that can cause human infections and present virulence on an invertebrate model. Thus, this study underscores the role of dogs and cats as reservoirs of resistant Klebsiella spp. that could potentially be transmitted to humans.

Anorectal melanoma: a rare entity.

Anorectal melanoma is a rare malignant tumor with the potential of simulating a benign anorectal disease, making its diagnosis difficult. We describe a case of anorectal melanoma, in which the interpretation of symptoms as hemorrhoidal disease delayed diagnosis and appropriate intervention.

Proteomic profiling of membrane vesicles from Mycobacterium avium subsp. paratuberculosis: Navigating towards an insilico design of a multi-epitope vaccine targeting membrane vesicle proteins.

Bacteria typically produce membrane vesicles (MVs) at varying levels depending on the surrounding environments. Gram-negative bacterial outer membrane vesicles (OMVs) have been extensively studied for over 30 years, but MVs from Gram-positive bacteria only recently have been a focus of research. In the present study, we isolated MVs from Mycobacterium avium subsp. paratuberculosis (MAP) and analyzed their protein composition using LC-MS/MS. A total of 316 overlapping proteins from two independent preparations were identified in our study, and topology prediction showed these cargo proteins have different subcellular localization patterns. When MVs were administered to bovine-derived macrophages, significant up-regulation of pro-inflammatory cytokines was observed via qRT-PCR. Proteome functional annotation revealed that many of these proteins are involved in the cellular protein metabolic process, tRNA aminoacylation, and ATP synthesis. Secretory proteins with high antigenicity and adhesion capability were mapped for B-cell and T-cell epitopes. Antigenic, Immunogenic and IFN-γ inducing B-cell, MHC-I, and MHC-II epitopes were stitched together through linkers to form multi-epitope vaccine (MEV) construct against MAP. Strong binding energy was observed during the docking of the 3D structure of the MEV with the bovine TLR2, suggesting that the putative MEV may be a promising vaccine candidate against MAP. However, in vitro and in vivo analysis is required to prove the immunogenic concept of the MEV which we will follow in our future studies. SIGNIFICANCE: Johne's disease is a chronic infection caused by Mycobacterium avium subsp. paratuberculosis that has a potential link to Crohn's disease in humans. The disease is characterized by persistent diarrhea and enteritis, resulting in significant economic losses due to reduced milk yield and premature culling of infected animals. The dairy industry in the United States alone experiences losses of approximately USD 250 million due to Johne's disease. The current vaccine against Johne's disease is limited by several factors, including variable efficacy, limited duration of protection, interference with diagnostic tests, inability to prevent infection, and logistical and cost-related challenges. Nevertheless, a multiepitope vaccine design approach targeting M. avium subsp. paratuberculosis has the potential to overcome these challenges and offer improved protection against Johne's disease.

Fabry-Perot Cavity Optimization for Absolute Strain Sensing Using Finite Element Analysis.

The finite element method (FEM) was used to investigate the optical-mechanical behavior of a Fabry-Perot Interferometer (FPI) composed of a capillary segment spliced between two sections of standard optical fiber. The developed FEM model was validated by comparing it with theory and with previously published experimental data. The model was then used to show that the absolute strain on the host substrate is usually smaller than the strain measurement obtained with the sensor. Finally, the FEM model was used to propose a cavity geometry that can be produced with repeatability and that yields the correct absolute strain experienced by the host substrate, without requiring previous strain calibration.

Esophagitis dissecans superficialis: a rare endoscopic finding.

Esophagitis dissecans superficialis is an extremely rare benign illness. Although an association with medications, skin conditions, heavy smoking, and physical trauma has been reported, most cases remain unexplained. We present a previously healthy 42-year-old woman found to have EDS secondary to trauma. The patient started on PPI therapy with rapid and complete resolution of the endoscopic abnormality. This case shows the importance of identification of EDS, a rare and often underdiagnosed entity.

Demographic and Clinical Characteristics of Mpox Patients Attending an STD Clinic in Lisbon.

Mpox is a viral disease caused by the monkeypox virus, which marked the year of 2022 with a global outbreak. While previously considered to be a zoonosis of almost exclusive animal-to-human transmission, the current outbreak has been attributed to human-to-human transmission, particularly sexual transmission. As a new sexually transmissible disease, we studied the epidemiological and clinical features, as well as the concomitant occurrence of other sexually transmissible diseases, treatment approach, and outcome of our 291 patients, in the current outbreak. We found a total of 169 concomitant sexually transmissible infections of bacterial and viral origins, corresponding to 107 patients. Neisseria gonorrhoeae was the most common agent, particularly in the anal location. With this work, we emphasize the need for a thorough epidemiological and medical history, as well as a concomitant complete laboratorial screening for other STIs in patients with confirmed or suspected mpox.

Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid.

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.

Iodine-Induced Hypothyroidism After Chemoembolization With Ethiodized Oil: A Case of Failure to Escape From Wolff-Chaikoff Effect (WCE).

Wolff-Chaikoff effect (WCE) is an acute physiologic response of the thyroid gland to high levels of iodine. The WCE is usually temporary, and the thyroid gland adjusts to high iodine levels within days or weeks. It is a protective mechanism and a failure to escape from it can result in thyroid dysfunction. Hypothyroidism is rare but more likely in patients who have had thyroid disease, are under stress, or are exposed to high iodine concentrations for a long time. The use of iodinated contrast media in radiologic studies or invasive medical procedures is a common source of excessive iodine exposure and can lead to thyroid disfunction. Despite the frequent use of contrast media in health care, the thyroid dysfunction associated with their use is poorly recognized. We report a patient who developed iodine-induced hypothyroidism after chemoembolization of recurrent chylothorax with ethiodized oil (Lipiodol®, Villepinte, France). This case report raises awareness of the importance of the physiologic WCE as well as the relevance of monitoring thyroid function when using iodinated contrast media in patients with specific risk factors.

First Report of IMI-2-Producing Enterobacter bugandensis and CTX-M-55-Producing Escherichia coli isolated from Healthy Volunteers in Tunisia.

The aim of this study was to characterize the prevalence of fecal carriage of extended-spectrum beta-lactamases and carbapenemase-producing Gram-negative bacteria among healthy humans in Tunisia. Fifty-one rectal swabs of healthy volunteers were plated on MacConkey agar plates supplemented with cefotaxime or imipenem. The occurrences of resistance genes, integrons, and phylogroup typing were investigated using PCR and sequencing. The genetic relatedness of isolates was determined by pulsed-field-gel-electrophoresis (PFGE) and multilocus-sequence-typing (MLST). Whole-genome-sequencing (WGS) was performed for the carbapenem-resistant isolate. Sixteen ESBL-producing Escherichia coli isolates and one carbapenem-resistant Enterobacter bugandensis were detected out of the fifty-one fecal samples. The ESBL-producing E. coli strains contained genes encoding CTX-M-15 (n = 9), CTX-M-1 (n = 3), CTX-M-27 (n = 3), and CTX-M-55 (n = 1). Three CTX-M-1-producers were of lineages ST131, ST7366, and ST1158; two CTX-M-15-producers belonged to lineage ST925 and ST5100; one CTX-M-27-producer belonged to ST2887, and one CTX-M-15-producer belonged to ST744. Six isolates contained class 1 integrons with the following four gene cassette arrangements: dfrA5 (two isolates), dfrA12-orf-aadA2 (two isolates), dfrA17-aadA5 (one isolate), and aadA1 (one isolate). E. bugandensis belonged to ST1095, produced IMI-2 carbapenemase, and contained qnrE1 and fosA genes. A genome-sequence analysis of the E. bugandensis strain revealed new mutations in the blaACT and qnr genes. Our results reveal an alarming rate of ESBL-E. coli in healthy humans in Tunisia and the first description of IMI-2 in E. bugandensis.

Cross-Cultural Adaptation and Validation of the European Portuguese Dysphagia Handicap Index.

The Dysphagia Handicap Index (DHI) is a valid Health-related Quality of Life (HRQoL) 25-item questionnaire assessing the physical, functional, and emotional aspects of patients with oropharyngeal dysphagia (OD), of heterogeneous etiologies. The purpose of this study is to translate and validate the European Portuguese-DHI (EP-DHI). This is a prospective study that was carried out at Centro Hospitalar Universitário do Porto (CHUPorto). The generated EP-DHI was administered to 132 patients with OD and 112 healthy control subjects. 132 patients undergoing fiberoptic endoscopic examination of swallowing (FEES). 15 patients were contacted by phone, 2 or 3 weeks later after the first interview to repeat the questionnaire. The validity of concurrent criteria was evaluated by comparing the results of the EP-DHI score with the score attributed to the pathological findings found in FEES and, consequently, Functional Oral Intake Scale (FOIS). The internal consistency of EP-DHI was successful: Cronbach's alpha coefficient for total EP-DHI was 0.874. The test-retest reliability for the total and the three EP-DHI subscales obtained a Pearson's correlation coefficient ranged from 0.990 to 0.712. This study demonstrates that EP-DHI is a valid tool for self-assessment of the handicapping effect of dysphagia on physical, functional, and emotional aspects of patient's quality of life, among an European Portuguese sample.

Strengthening the genomic surveillance of Francisella tularensis by using culture-free whole-genome sequencing from biological samples.

Introduction: Francisella tularensis is a highly infectious bacterium that causes the zoonotic disease tularemia. The development of genotyping methods, especially those based on whole-genome sequencing (WGS), has recently increased the knowledge on the epidemiology of this disease. However, due to the difficulties associated with the growth and isolation of this fastidious pathogen in culture, the availability of strains and subsequently WGS data is still limited. Methods: To surpass these constraints, we aimed to implement a culture-free approach to capture and sequence F. tularensis genomes directly from complex samples. Biological samples obtained from 50 common voles and 13 Iberian hares collected in Spain were confirmed as positive for F. tularensis subsp. holarctica and subjected to a WGS target capture and enrichment protocol, using RNA oligonucleotide baits designed to cover F. tularensis genomic diversity. Results: We obtained full genome sequences of F. tularensis from 13 animals (20.6%), two of which had mixed infections with distinct genotypes, and achieved a higher success rate when compared with culture-dependent WGS (only successful for two animals). The new genomes belonged to different clades commonly identified in Europe (B.49, B.51 and B.262) and subclades. Despite being phylogenetically closely related to other genomes from Spain, the detected clusters were often found in other countries. A comprehensive phylogenetic analysis, integrating 599 F. tularensis subsp. holarctica genomes, showed that most (sub)clades are found in both humans and animals and that closely related strains are found in different, and often geographically distant, countries. Discussion: Overall, we show that the implemented culture-free WGS methodology yields timely, complete and high-quality genomic data of F. tularensis, being a highly valuable approach to promote and potentiate the genomic surveillance of F. tularensis and ultimately increase the knowledge on the genomics, ecology and epidemiology of this highly infectious pathogen.