Gastric perforation and generalized peritonitis due to heterotopic pancreas, an unusual case report.

INTRODUCTION: Heterotopic pancreas is the presence of normal pancreatic tissue that is in an anatomical site different from the pancreas. CASE REPORT: Adolescent who was admitted to the emergency room due to intense, generalized abdominal pain, which did not go away with anything, was exacerbated with movements, 24 h later vomiting that occurred as soon as he ate food was added, and severe and progressive abdominal distention, reason for admission to the service of emergencies. He had no significant family or personal medical history. On physical examination, he was found to be sick with a painful appearance, pale, sweaty, feverish, with tachycardia, he complained of intense pain, distended abdomen, with loss of hepatic dullness, with involuntary muscular resistance, with positive rebound sign, absent peristalsis. Laboratory studies were taken that reported anemia, leukocytosis and neutrophilia, blood chemistry, electrolytes, and coagulation times within normal limits; abdominal x-rays showed subdiaphragmatic free air. DISCUSSION: The prevalence of pancreatic heterotopia in the literature varies from 0.6 % in autopsy series to 14 %, however, the increasingly frequent use of upper gastrointestinal endoscopy and endoscopic ultrasound allows early diagnosis, since whether directed or incidentally, which avoids serious complications such as gastric perforation, because it is unusual for it to occur as in this clinical case. Specifically in the stomach, involvement of the submucosa layer has been described in 73 %, muscular layer in 17 % and subserosa in 10 % of cases respectively. In cases where the disease is in an asymptomatic stage, it can be treated conservatively; it seems to be more common in men, as in our case, than in women. CONCLUSION: In patients with chronic epigastric pain, it is essential to rule out conditions such as heterotopic pancreas, to avoid serious complications such as perforation.

DRESS syndrome and tuberculosis: Implementation of a desensitization and re-desensitization protocol to recover antituberculosis drugs in a case series at a specialized TB Unit in Lima, Peru.

RATIONALE: Antituberculosis drugs (ATDs) could cause severe and rare reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Recovering ATDs might guarantee a higher cure rate for tuberculosis patients. Our aim was to evaluate the results of desensitization and re-desensitization to recover ATDs in a case series of patients with DRESS syndrome. PATIENT CONCERNS AND DIAGNOSES: A retrospective case series study was conducted on patients with DRESS syndrome due to therapy with ATDs from 2021 to 2023. Desensitization and re-desensitization protocols, designed with an algorithm proposed by the Tuberculosis Specialized Unit of the Dos de Mayo National Hospital in Lima, Peru, were implemented. INTERVENTIONS AND OUTCOMES: A total of 18 patients underwent desensitization or re-desensitization protocols, achieving an overall success rate of 72.2%. The average time for the development of DRESS syndrome due to ATDs was 19 days. Rifampicin (84.2%), isoniazid (68.4%), and pyrazinamide (26.3%) were identified as the main drugs responsible for this adverse reaction. All patients presented with fever and skin rash, with an average eosinophil percentage of 16.7% (interquartile range: 4.5-28.8). Organ involvement (liver, kidney, and heart) was observed in 8 patients, but only 2 patients experienced severe complications due to DRESS syndrome. A significant association was found between the number of ATDs used and eosinophil levels (P =.03). LESSONS: The study introduced a desensitization and re-desensitization algorithm for the treatment of DRESS syndrome, notable for its safety, adaptability, and high success rate. This advancement provided healthcare professionals with safer and more effective therapeutic approaches for managing this complex condition.

Role of the RNA binding protein IGF2BP1 in cancer multidrug resistance.

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), is expressed in a broad range of fetal tissues, placenta and more than sixteen cancer types but only in a limited number of normal adult tissues. IGF2BP1is required for the transport from nucleus to cytoplasm of certain mRNAs that play essential roles in embryogenesis, carcinogenesis, and multidrug resistance (MDR), by affecting their stability, translation, or localization. The purpose of this review is to gather and present information on MDR mechanisms in cancer and the significance of IGF2BP1 in this context. Within this review, we will provide an overview of IGF2BP1, including its tissue distribution, expression, molecular targets in the context of tumorigenesis and its inhibitors. Our main focus will be on elucidating the interplay between IGF2BP1 and MDR, particularly with regard to chemoresistance mediated by ABC transporters.

Two new mouse alleles of Ocm and Slc26a5.

The genes Ocm (encoding oncomodulin) and Slc26a5 (encoding prestin) are expressed strongly in outer hair cells and both are involved in deafness in mice. However, it is not clear if they influence the expression of each other. In this study, we characterise the auditory phenotype resulting from two new mouse alleles, Ocmtm1e and Slc26a5tm1Cre. Each mutation leads to absence of detectable mRNA transcribed from the mutant allele, but there was no evidence that oncomodulin regulates expression of prestin or vice versa. The two mutants show distinctive patterns of auditory dysfunction. Ocmtm1e homozygotes have normal auditory brainstem response thresholds at 4 weeks old followed by progressive hearing loss starting at high frequencies, while heterozygotes show largely normal thresholds until 6 months of age, when signs of worse thresholds are detected. In contrast, Slc26a5tm1Cre homozygotes have stable but raised thresholds across all frequencies tested, 3 to 42 kHz, at least from 4 to 8 weeks old, while heterozygotes have raised thresholds at high frequencies. Distortion product otoacoustic emissions and cochlear microphonics show deficits similar to auditory brainstem responses in both mutants, suggesting that the origin of hearing impairment is in the outer hair cells. Endocochlear potentials are normal in the two mutants. Scanning electron microscopy revealed normal development of hair cells in Ocmtm1e homozygotes but scattered outer hair cell loss even at 4 weeks old when thresholds appeared normal, indicating that there is not a direct relationship between numbers of outer hair cells present and auditory thresholds.

Association Between Alpha Angle and Acetabular Index in Screening for Developmental Dysplasia of the Hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a critical orthopedic condition ranging from minor hip joint instability to complete dislocations, demanding early intervention to avoid severe complications, especially in children. In Mexico, stringent regulations under the Norma Oficial Mexicana (NOM) mandate hip screening for pediatric patients. The primary objective of this study is to investigate the relationship between alpha angles and the acetabular index in patients at six months of age, aiming to determine whether an increase in the alpha angle correlates with a better acetabular index. METHODS: We included 120 patients who were screened for hip issues with Graf's methodology in June 2023 and September 2023 at the General Hospital of Mexico "Dr. Eduardo Liceaga" in Mexico City before three months of age and attended their follow-up appointment at six months of age, where acetabular index measurement was performed using the Carestream platform on institutional X-rays. RESULTS: In our statistical analysis, we obtained a statistically significant relationship between an increase in the left hip alpha angle and a decrease in the left hip acetabular index (p=0.015) although it was not significant for an acetabular index of less than 25° (p=0.055). A significant relationship was observed between the right hip acetabular index and the right hip alpha angle (p=0.017) but not significant for an acetabular index less than 25° (p=0.10). CONCLUSION: Universal hip screening is crucial for the early detection of DDH. Our study emphasizes using alpha-angle measurements (>70°) as reliable indicators of normal hip health.

Ohpikihâwasowin (grounding and guiding on the path to be a healthy parent): virtual adaptation of an Elders mentoring program to support maternal and child wellbeing during the COVID-19 pandemic.

BACKGROUND: The Elders Mentoring Program (EMP) is part of a strengths-based community-based participatory research partnership with the Cree communities of Maskwacîs, Alberta, Canada. The EMP objective is to promote maternal and child health through traditional Cree teachings and support from community Elders to pregnant women and their partners. During the COVID-19 pandemic, the Elders decided to shift the program to an online format in early 2021. The Elders continued to offer mentorship to program participants virtually by Zoom and telephone, and online workshops. The objective of this study was to qualitatively explore the experiences of women that took part in the virtual EMP. METHODS: We utilized qualitative description as our method, informed by our overarching community-led research partnership. Semi-structured phone interviews were conducted by Maskwacîs research assistants (RAs) with 11 women who participated in the virtual program. Interviews were conducted between December 2021 and June 2022. The participants were asked about their perceptions of the program and its benefits. The interviews were recorded, transcribed, and coded by four RAs using thematic analysis. RESULTS: Although cultural teachings are traditionally offered in person, the shift to the virtual platform was greatly appreciated by all the women. Technology can be a useful tool for cultural teachings and language to be shared among community members when they cannot be physically together. Four main themes emerged from the data, representing the participants' experiences, and learning through their interactions with the Elders from the EMP. The themes are: Ohpikihâwasowin (grounding and guiding on the path to be a healthy parent); Indigenous ways of healing; On the path of cultural learning; and Identity for self and baby. CONCLUSION: The virtual adaptation of the EMP allowed a space for Elders to offer support to women living in and out of the community to provide guidance with their pregnancies and into motherhood. The workshops and one-on-one calls allowed for cultural revitalization which is critical for Indigenous well-being. All the participants found that the teachings and interactions positively impacted their pregnancy and parenthood. Overall, the virtual program demonstrated a venue for intergenerational healing and resilience.

Pleiotropic Effects of Peroxisome Proliferator-Activated Receptor Alpha and Gamma Agonists on Myocardial Damage: Molecular Mechanisms and Clinical Evidence-A Narrative Review.

Cardiovascular diseases remain the leading cause of death in the world, and that is why finding an effective and multi-functional treatment alternative to combat these diseases has become more important. Fibrates and thiazolidinediones, peroxisome proliferator-activated receptors alpha and gamma are the pharmacological therapies used to treat dyslipidemia and type 2 diabetes, respectively. New mechanisms of action of these drugs have been found, demonstrating their pleiotropic effects, which contribute to preserving the heart by reducing or even preventing myocardial damage. Here, we review the mechanisms underlying the cardioprotective effects of PPAR agonists and regulating morphological and physiological heart alterations (metabolic flexibility, mitochondrial damage, apoptosis, structural remodeling, and inflammation). Moreover, clinical evidence regarding the cardioprotective effect of PPAR agonists is also addressed.

An approach to autologous stem cell mobilization: trying to define good mobilizers.

BACKGROUND AND OBJECTIVES: Stem cell mobilization is a well-known procedure to harvest hematopoietic stem cells for autologous stem cell transplantation in certain hematologic diseases. Numerous studies have been conducted to identify risk factors for poor mobilization but there are no studies that identify good mobilizers. In our hospital, we decided to explore good mobilizers, defining them as those with ≥40 CD34+ cells/µL on Day +4 in order to start early apheresis. MATERIAL AND METHODS: A descriptive retrospective study was performed at Hospital Universitari Son Espases. A total of 198 patients mobilized with doses of around 10 µg/kg of granulocyte colony-stimulating factor (G-CSF) every 12 h were analyzed for autologous collection between January 2015 and September 2022. Fifty patients who had ≥40 CD34+ cells/µL on Day +4 started early apheresis; the rest continued mobilization as planned. Success was defined as obtaining over 2.5 × 106 CD34+ cells/kg in a single apheresis. RESULTS: The necessary number of CD34+ cells/kg to perform an autologous stem cell transplantation was reached in a single apheresis session in 62 % of patients with ≥40 CD34+ cells/µL in peripheral blood. A cutoff of 102 CD34+ cells/µL on Day +4 was shown to have the best success rate (94 %). In an analysis of success, age, previously failed mobilization and having one or more adverse factors for bad mobilization were statistically significant. CONCLUSION: Patients considered as good mobilizers were matched with our factors of poor mobilization, revealing that most patients (79 %) had none or only one risk factor for poor mobilization. Apheresis on Day +4 in good mobilizers was shown to be an effective alternative to reduce mobilization duration and decrease the amount of granulocyte-colony stimulating factor administered.

Clinical outcomes and complications of a new high-density polyethylene-based spherical integrated porous orbital implant.

PURPOSE: To describe our experience over 6 years using a new high-density polyethylene-based spherical integrated porous orbital implants (Oculfit). METHODS: This is an observational retrospective case series study analyzing all cases requiring Oculfit implants between February 2015 and September 2021. Clinical information regarding the population included, the characteristics of the implant, and the outcomes and complications during the follow-up were noted. The success of the implant was defined according to anatomical and functional parameters. RESULTS: The study analyzed 90 cases of anophthalmic patients. The main causes for enucleation or evisceration were ocular decompensations (36.7%) and neoplasms (27.8% uveal melanoma and 7.8% retinoblastoma). Anatomical success was identified in 63 (70.0%) cases, functional success in 79 (87.8%) and complete success (anatomical + functional) in 61 (67.7%) cases. Factors associated with the functional success were age and exposure of the primary orbital implant. Complications appeared in 11 (12.2%) cases, which were completely resolved without sequelae in 4 (4.4%). Orbital explant was required in 5 (5.6%) cases. CONCLUSION: In our experience, Oculfit can be considered a useful alternative among the currently available options for orbital implants and has a good efficacy/safety profile.

Gingival margin stabilization using the final prosthetic restoration (BOPT). A case report.

One of the most contentious and extensively discussed topics in the field of dentistry when fabricating prosthetic restorations is the location and design of the finishing line in relation to the gingival tissues. Upon completion of the temporary crown and subsequent fabrication of the final restoration, two potential issues may arise: 1) the analog or digital impression may not accurately reflect the shape of the gingiva obtained with the temporary crown due to gingival collapse upon crown removal, even in the presence of retraction cords; and 2) the desired gingival shape may not have been achieved with the temporary crown. The objective of this article is to describe the stabilization of gingival tissues following twelve weeks of clinical observation. During this period, the provisional crown is recontoured twice in the apical-coronal direction with a four-week interval. This approach allows for the growth of sufficient gingival tissue in the horizontal direction at the point of the vestibular emergence profile, which will then stabilize once more following a slight recontouring of the final restoration, which will be performed in the clinic. The amount of gingival adaptation is not quantifiable in a numerical sense; rather, it is directly proportional to the amount of tissue that can be obtained with the new emergence profile of the temporary crown. The outcome is contingent upon the operator and there is no fixed quantity that can be achieved in every instance. In essence, there is no fixed numerical value that can be relied upon to lower the gingival parabola in the apical-coronal direction through the adaptation of tissues to the new shape of the temporary crown emergence profile. Key words:Vertical preparation, BOPT technique, tissue stabilization, final restoration.

Cytotoxic effects induced by combined exposure to the mycotoxins sterigmatocystin, ochratoxin A and patulin on human tumour and healthy 3D spheroids.

Humans are exposed to complex mixtures of mycotoxins through diet. Despite the serious threat they pose, mycotoxin risk assessment often overlooks co-exposure. With the aim of filling this gap, the present study investigates the combined cytotoxicity of sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) in human tumour Neuroblastoma and healthy Mesenchymal Stem Cells three-dimensional (3D) spheroids. The range of concentrations tested (1.56-50 µM for STE, 0.78-25 µM for OTA and 0.15-5 µM for PAT) was selected considering the IC50 values obtained in previous studies and the estimated dietary exposure of consumers. To ensure appropriate experimental conditions, assessments for single mycotoxins and their combinations were conducted simultaneously. The nature of the toxicological interactions among the mycotoxins was then defined using the isobologram analysis. Our results demonstrated increased cytotoxicity in mycotoxin mixtures compared to individual exposure, with abundance of synergistic interactions. These findings highlight that the co-occurrence of STE, OTA and PAT in food may increase their individual toxic effects and should not be underestimated. Moreover, the use of advanced culture models increased the reliability and physiological relevance of our results which can serve as a groundwork for formulating standardized regulatory approaches towards mycotoxin mixtures in food and feed.

Durable benefit and slowdown in tumor growth dynamics with erdafitinib in a FGFR3-TACC3 fusion-positive IDH-wild type glioblastoma.

FGFR3-TACC3 fusion-positive IDH-wild-type (IDH-WT) glioblastoma (GB) is a rare GB subtype occurring in approximately 3% of cases. It is clinical behavior and molecular profile is different from those of fusion-negative IDH-WT GBs. Evidence on the role of FGFR inhibitors in FGFR-altered gliomas is limited. We present the case of a patient with a FGFR3-TACC3 fusion-positive IDH-WT GB that at its second recurrence was treated with the FGFR inhibitor erdafitinib through a compassionate use program. Although no objective response was achieved, an overt deceleration in tumor growth was evidenced and the patient remained on treatment for 5.5 months.

Efficacy of Eggshell Membrane in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Osteoarthritis (OA) is a prevalent, degenerative joint disease, with knee OA being particularly common and impactful. This systematic review and meta-analysis aimed to assess the efficacy of eggshell membrane (ESM) supplementation in improving joint functionality and reducing pain in individuals with knee OA. A comprehensive search was conducted across PubMed, Scopus, Web of Science, and Cochrane Database up to July 2024, following PRISMA guidelines. Seven randomized controlled trials (RCTs) met the inclusion criteria, with five included in the meta-analysis. The studies compared ESM to a placebo, evaluating outcomes based on assessment tools such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Results indicated that ESM significantly reduced pain and improved functionality, with notable improvements in total WOMAC score (effect size -0.34; 95% CI: -0.56 to -0.13; p < 0.001) and pain subscale (SMD -0.23; 95% CI: -0.42 to -0.04; p < 0.02). The findings support ESM as a promising adjunctive treatment for knee OA, offering a safe, natural supplement to enhance quality of life. Further high-quality RCTs are needed to confirm these results and explore the long-term effects and mechanisms of ESM.

NKG2C/KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma.

BACKGROUND: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment. METHODS: We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response. RESULTS: We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association. CONCLUSIONS: This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials.

Time perspective and attachment predict perceived stress in Lebanese undergraduates: The mediating role of trait emotional intelligence.

BACKGROUND: Lebanese university students experience high levels of stress, which are linked to poor academic and health outcomes. Therefore, understanding the psychological predictors of this stress is crucial. The present study examines the roles of emotional, cognitive, and interpersonal factors in predicting perceived stress, namely trait emotional intelligence (trait EI), time perspective, and attachment. METHODS: The sample included 283 Lebanese undergraduate university students aged 18 to 33 years (M = 19.89, SD = 1.87). The main variables were assessed using the Trait Emotional Intelligence Questionnaire - Short Form, The Zimbardo Time Perspective Inventory, The Revised Adult Attachment Scale - Close Relationships Version, and the Perceived Stress Scale. RESULTS: Path analysis showed that trait EI mediated the relationship between time perspective and attachment (predictors) and perceived stress (outcome). In particular, the Past Positive and Future time perspectives positively predicted trait EI, while insecure attachment negatively predicted it. In turn, higher trait EI predicted lower perceived stress. CONCLUSION: The findings help inform theory and application, suggesting that managing stress and mitigating its impact on well-being can be achieved through interventions targeting time perspective, attachment, and trait EI.

Sunflower Oil and Cholesterol Nanoemulsion: A Novel Carrier for Micafungin to Combat Multi-Resistant Candida auris.

Candida auris is an emerging, multidrug-resistant yeast that causes systemic infections, mainly in hospitalized or immunosuppressed patients. This pathogen has a high mortality and morbidity rate. This study aims to evaluate the antifungal potential of micafungin (MICA) encapsulated in a nanoemulsion (NEM) against four clades of C. auris and other non-C. auris species. The antifungal potential of MICA and NEM was evaluated by determining mature biofilm inhibition (0.78-50 µg/mL). The antifungal activities of MICA and NEM (5.92 mg/Kg) were evaluated using an in vivo model of Galleria mellonella. The results showed that NEM intensified the antibiofilm action of MICA, especially in 48 h mature biofilms. In vivo results displayed a higher effectiveness of NEM against all clades of C. auris tested, inhibiting the fungal load in the hemolymph and tissues of G. mellonella with a difference of 3 log10. In addition, C. auris infection caused granulomas surrounded by hemocytes, mainly at the lower and upper ends. Conversely, C. albicans developed pseudohyphae, biofilms, filaments, and chlamydospores. In conclusion, encapsulation of MICA in a nanoemulsion enhances its antifungal activity against mature biofilms of C. auris. This strategy may be considered a therapeutic approach for the control of infections and the dissemination of this new global health threat.

Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases.

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype-phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C>T in KARS1, c.475C>T, c.728A>C and c.1012G>A in HARS2, and c.795A>G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence.