Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.

Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.

Getting more bang for their buck: BCL2 inhibitors boost dendritic-cell function to enhance anti-cancer immune surveillance.

The anti-apoptotic BCL-2 protein family regulates cancer cell survival, thus it represents an important therapeutic target. Indeed, a drug class, called BH3-mimetics, have been developed to directly target BCL2 proteins and promote cancer cell death. Conventional wisdom suggests that the primary anti-cancer effect of BCL-2 inhibition is through induction of cancer cell death. However, a recent study by Zhao and colleagues describes that BCL-2 inhibition also enhances the function of classical dendritic cells, unleashing their role in immunosurveillance, promoting T cell immunity and tumour regression. Thus, inhibiting anti-apoptotic BCL-2 function may have a multi-pronged anti-tumour action.

Depth of field and visual performance after implantation of a new hydrophobic trifocal intraocular lens.

PURPOSE: To assess the depth of field (DOF) by means of defocus curve analysis applying different visual acuity criteria in patients following cataract surgery and bilateral implantation of a new trifocal diffractive intraocular lens (IOL). METHODS: Fifty eyes of 25 consecutive patients who underwent implantation of the Asqelio™ trifocal IOL (AST Products Inc., USA) were enrolled in this observational prospective study. Monocular subjective DOF was obtained from defocus curves with absolute and relative criteria of tolerance for different visual acuities values. Patient's visual satisfaction, postoperative refraction and visual acuity at far, intermediate (67 cm) and near (40 cm) distances were also measured at 1 and 3-months post-surgery. Analysis of variance was used to assess differences in refractive error after the surgical procedure, and paired t-tests were used to assess differences in VA. Patient satisfaction results were reported as percentages. RESULTS: Spherical equivalent was 0.05 ± 0.23 D and residual cylinder 0.01 ± 0.23 D 3-months after the surgery. Absolute DOF obtained was 3.29 ± 0.91 D considering 0.1 LogMAR as cut-off value, and 4.82 ± 0.69 D when 0.3 logMAR as cutoff value. Relative DOF considering a drop of 0.1 logMAR from maximum visual acuity was 2.57 ± 0.82 D, and 1.27 ± 0.70 D when a drop of 0.04 logMAR was considered. Visual acuities obtained 3-months after the surgery were 0.03 ± 0.13, - 0.05 ± 0.06, 0.03 ± 0.08 and 0.04 ± 0.08 logMAR for uncorrected and best-corrected for distance, and best distance-corrected for intermediate and near distances, respectively. Average response to visual satisfaction queries was 8.24/10 at distance, 8.04/10 at intermediate, and 7.88/10 at near. CONCLUSIONS: Patients implanted with this trifocal IOL showed a significant improvement in visual acuity at different distances providing wide absolute and relative DOF values. The outcomes demonstrate that this lens is predictable yielding good patient satisfaction rates.

Providing Supportive and Palliative Care Using Telemedicine for Patients with Advanced Cancer During the COVID-19 Pandemic in Mexico.

COVID-19 has overwhelmed the capacity of health care systems, limiting access to supportive and palliative care for patients with advanced cancer. Telemedicine has emerged as a tool to provide care continuity to patients while limiting the risk of contagion. However, implementing telemedicine in resource-limited settings is challenging. We report the results of a multidisciplinary patient-navigator-led telemedicine supportive care program in Mexico City. One-hundred sixty-three telemedicine interventions were provided to 45 patients (median age 68, 57% female). A quarter of the patients had less than or equal to elementary school education, and 15% lived in a rural area. The most common interventions were psychological care (33%), pain and symptom control (25%), and nutritional counseling (13%). Half of the interventions were provided by video conferencing. The most common patient-reported barrier was limited experience using communication technology. Our results demonstrate the feasibility of providing supportive and palliative care interventions using telemedicine in resource-limited settings.

Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-Limited Settings: A Randomized Controlled Trial.

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.

Compartmentalized Response of IL-6/STAT3 Signaling in the Colonic Mucosa Mediates Colitis Development.

A single layer of polarized epithelial cells lining the colonic mucosa create a semipermeable barrier indispensable for gut homeostasis. The role of intestinal epithelial cell (IEC) polarization in the maintenance of the epithelial homeostasis and in the development of inflammatory bowel diseases is not fully understood. In this review, now we report that IEC polarization plays an essential role in the regulation of IL-6/STAT3 signaling in the colonic mucosa. Our results demonstrate that autocrine STAT3 activation in IECs is mediated by the apical secretion of IL-6 in response to the basolateral stimulation with IFN-γ. This process relies on the presence of functional, IFN-γ-producing CD4+ T cells. In the absence of basolateral IFN-γ, the compartmentalization of the IL-6/STAT3 signaling is disrupted, and STAT3 is activated mainly in macrophages. Thus, in this study, we show that during inflammation, IFN-γ regulates IL-6/STAT3 signaling in IEC in the colonic mucosa.

Breast Aesthetic Preferences: Analysis of 1294 Surveys.

BACKGROUND: Aesthetic breast perceptions could be variable among cultures. Fullness, superior/inferior pole proportion and orientation and size of the nipple areolar complex are key elements in patient post-operative satisfaction and should be considered when planning breast aesthetic surgery. METHODS: A descriptive study was designed, using an online survey, sent via social media. Standardized software modified images of breasts with different pole proportions, areolar nipple complex orientation and size were used. RESULTS: From 1294 surveys collected, 1291 were analysed (969 women and 322 men). Significant differences in preferences of upper/lower pole breast proportions were found among groups of different age, gender, level of education and previous history of breast surgery. CONCLUSIONS: In the studied population, we found several variations in aesthetic breast preferences related to their demographic characteristics and for this reason we believe that this research may serve as a "macro" guide for both patient and surgeon in primary and secondary breast surgery. To our knowledge, this is the largest survey study concerning breast aesthetic preferences done in Colombia and second largest in the world. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Expression and purification of domain III proteins from Dengue and Zika viruses.

The envelope (E) protein from Dengue and Zika viruses comprises three functional and structural domains (DI, DII, and DIII). Domain III induces most of the neutralizing antibodies and, as such, is considered as having the highest antigenic potential for the evaluation of population-level surveillance and for detecting past infections in both Dengue and Zika patients. The present study aimed to clone and express recombinant proteins of domain III from Dengue virus serotype 2 and from Zika virus in a prokaryotic system, as well as evaluate their immunogenicity and cross-reactivity. Both antigens were successfully purified and their antigenicity was assessed in mice. The antibodies elicited by domain III of Zika and Dengue virus antigens recognized specifically the native proteins in infected cells. Furthermore, the antigens showed a more specific immunogenic response than that of domain III proteins from Dengue virus. The generated recombinant proteins can be potentially used in subunit vaccines or for surveillance studies.

Nanomechanical mass measurements through feature-based time series clustering.

Recent years have seen explosive growth in miniaturized sensors that can continuously monitor a wide variety of processes, with applications in healthcare, manufacturing, and environmental sensing. The time series generated by these sensors often involves abrupt jumps in the detected signal. One such application uses nanoelectromechanical systems (NEMS) for mass spectrometry, where analyte adsorption produces a quick but finite-time jump in the resonance frequencies of the sensor eigenmodes. This finite-time response can lead to ambiguity in the detection of adsorption events, particularly in high event-rate mass adsorption. Here, we develop a computational algorithm that robustly eliminates this often-encountered ambiguity. A moving-window statistical test together with a feature-based clustering algorithm is proposed to automate the identification of single-event jumps. We validate the method using numerical simulations and demonstrate its application in practice using time-series data that are experimentally generated by molecules adsorbing onto NEMS sensors at a high event rate. This computational algorithm enables new applications, including high-throughput, single-molecule proteomics.

Somatostatin: a possible mediator of the long-term effects of experimental vertical gastrectomy on glucose metabolism in rats?

BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries. SG treats type 2 diabetes mellitus better than several drugs. The mechanisms that underlie this phenomenon are not clear. This study proposed that somatostatin (SST) isoforms SST-14 and SST-28 are key in the carbohydrate after SG. METHODS: Surgeries were performed on 3 groups of Wistar rats: the fasting, surgery control, and SG groups. Plasma levels of glucose, insulin, SST-14, and SST-28 were measured at 2 survival periods after surgery. Islet SST receptor (SSTR) and cell populations were studied. We performed a pasireotide (SST-28 analogue) infusion assay in another group of rats to confirm the influence of SST-28 plasma levels on the delta-cell population. RESULTS: This study found an elevation in the insulin response after SG in animals but a decrease in the insulin response over the long term with a loss of beta-cell mass. An increase in duodenal SST-28-producing cells in the duodenum and a loss of pancreatic SST-14-producing cells were observed after SG in animals but not in controls. The expression of SSTR type 5 in delta-cell populations from each group and the ability of the pasireotide infusion assay to decrease the delta-cell population indicated the effect of SST-28 plasma levels on delta-cell maintenance. CONCLUSION: After SG initiates a compensatory response in the duodenum, beta-cell mass is depleted after loss of the brake that regulates SST-14 at the paracrine level in a nonobese, normoglycemic rat model. This was an experimental model, with no clinical translation to the human clinic, with a preliminary importance regarding new pathophysiologic perspectives or pathways.

Supportive care needs among older Mexican adults with metastatic cancer.

INTRODUCTION: Supportive care needs may vary according to age. The purpose of this research is to describe and compare supportive care needs between older adults with metastatic cancer (age ≥ 65 years) and their younger counterparts. MATERIALS AND METHODS: We conducted a retrospective secondary analysis of a cohort of patients with newly diagnosed metastatic solid tumors. Supportive care needs were assessed at baseline and at a three-month follow-up. Patients were divided into two groups (aged ≥65/<65 years). Differences in clinical characteristics and supportive care needs were compared utilizing descriptive statistics. Multivariate logistic regression models were employed to identify patient characteristics associated with specific supportive care needs. RESULTS: Between 2018 and 2022, 375 patients were enrolled. Median age was 66 years (interquartile range 19-94). At baseline, older adults had a higher number of supportive care needs (4.8 vs. 4.2, p = 0.01) and were at higher risk of malnutrition (75 vs. 65%, p = 0.05). Increasing age (odds ratio [OR] 1.02 (95% confidence interval [CI] 1.0-1.04, p = 0.03) and an estimated life expectancy <6 months (OR 3.0, 95%CI 1.5-6.1; p < 0.01) were associated with higher odds of malnutrition, while a higher educational level was associated with decreased odds (OR 0.68, 95%CI 0.5-0.8; p < 0.01). At three-month follow-up, older adults still had a higher number of supportive care needs (3.8 vs.2.6, p < 0.01) and were more likely to have fatigue (62 vs. 47%, p = 0.02). An estimated life expectancy of <6 months was associated with increased odds of fatigue (OR 3.0, 95%CI 1.5-6.3; p < 0.01). DISCUSSION: Older adults reported significantly more supportive care needs, particularly risk of malnutrition and fatigue. This information can help in the creation of supportive care services tailored to the needs of older individuals.

Training in tools to develop quantitative microbial risk assessment of ready-to-eat food with a comparison between the Romanian and Spanish food supply chains.

The prevention and control of bacterial contamination on ready-to-eat (RTE) fresh produce is an essential task to ensure food safety. Therefore, the development of novel and effective decontamination technologies to ensure microbiological safety of fruits and vegetables has gained considerable attention and new sanitisation methods are needed. The antimicrobial activity of essential oils (EOs) is well documented, but their application in fresh produce remains a challenge due to their hydrophobic nature. Thus, nanoemulsions efficiently contribute to support the use of EOs in foods by enhancing their dispersibility, their contact area and facilitating the introduction into bacterial cells. The combination of these factors ultimately increases their antimicrobial activity. Quantitative microbial risk assessment (QMRA) is gaining more attention as an effective tool to assess and prevent potential risks associated with food-borne pathogens. In this context, the current project aims to study the effectiveness of different washing methods based on nanoemulsified EOs, comparing them against traditional methods, using a QMRA model for Escherichia coli O157:H7 on cherry tomatoes. Different simulations within a stochastic risk assessment model were implemented using the biorisk package for R, aiming to describe microbial behaviour and biological risk along the Romanian and Spanish food supply chains of RTE fresh produce. Nanoemulsions were prepared using oregano and rosemary EOs, each from Romania and Spain. The four nanoemulsions were evaluated as decontamination treatments to control the growth of E. coli O157:H7 on artificially contaminated cherry tomatoes. The decontamination treatments showed encouraging results, comparable to commonly used chlorine solutions. Therefore, oregano and rosemary nanoemulsions are promising and could be a feasible alternative for chlorine solutions in the reduction of microbiological contaminants.

Main applications of point-of-care ultrasound in palliative care.

Combined with a physical examination, clinical ultrasound offers a valuable complement that can help guide clinical decision-making. In various medical and surgical specialties, it is increasingly used for diagnostic and therapeutic purposes. Due to recent technological advances, smaller and more affordable ultrasound machines are now being developed for use in home hospice care. The purpose of this paper is to describe how clinical ultrasound may be applied in Palliative Care, where it can be a valuable tool to assist the clinician in making better clinical decisions and to assist in accurately guiding palliative procedures. Furthermore, it can be used to identify unnecessary hospitalizations and prevent them from occurring. Training programs with specific objectives are necessary to implement clinical ultrasound in Palliative Care, as well as defining learning curves and promoting alliances with scientific societies that recognize the teaching, care and research trajectory for accreditation of competencies.

Prescribing Trends in Psychotropic Medications Among Outpatients of a Latin American Healthcare Setting: A Five-Year Retrospective Study.

Introduction Mental health problems affect millions worldwide, and the prescription of psychotropic drugs is increasing globally. The World Health Organization (WHO) has emphasized the need for proper monitoring of psychotropic drug prescriptions. This study aims to characterize and find trends in the prescription of psychotropics in a Latin American General Hospital. Methods The study analyzed the dispensation of psychotropic prescriptions to outpatients at three pharmacies in the central headquarters of Hospital Clínica Bíblica in San José, Costa Rica, from 2017 to 2021. Psychotropic drugs were classified by the Anatomical Therapeutic Chemical (ATC) code, and the amount of each medication dispensed was standardized using the defined daily dose per 10,000 population per day metric. Patients' ages were categorized into four groups: under 18 years, 18 to 39 years, 40 to 64 years, and 65 years and above. The prescriptions were categorized according to medical specialty. Regression analyses were performed to determine the significance of trends observed in the data Results A total of 5793 psychotropic prescriptions were recorded. The average age of the patients was 58 years. The total consumption of psychotropics decreased by 33.94% from 2017 to 2021, with the most significant decline until 2020. However, there was an increase in consumption in 2021. Clonazepam was the most consumed medication, followed by bromazepam and alprazolam, which was the sole drug to exhibit an escalation in usage between 2017 and 2021. Regression analysis showed that only alprazolam and zopiclone had statistically significant trends. The highest number of prescriptions was dispensed to patients aged between 40 and 64 years, followed by those aged over 65 years. Anxiolytics were also the most commonly prescribed group of drugs. General medicine (20.22%), psychiatry (19.95%), and internal medicine (12.73%) were the primary specialties that prescribed psychotropic; 38.6% of prescriptions were associated with the 10th decile of patients, and 44.9% of prescriptions were issued by the 10th decile of physicians.  Conclusion The consumption of psychotropic drugs decreased from 2017 to 2020 but increased in 2021, with alprazolam being the only drug that showed an increase in consumption throughout the entire period. General practitioners and psychiatrists were found to be the specialties that most commonly prescribe these medications. The study found significant trends only for the consumption of alprazolam and zopiclone and for prescription patterns among psychiatrists and internal medicine physicians.

Acute lichenoid and varioliform pityriasis in a pediatric patient.

BACKGROUND: Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare dermatosis recognized as a benign condition of unknown etiopathogenesis. It is more common in pediatric patients and young adults and is characterized by multiple small or large erythematous plaques spread over the trunk and extremities. CASE REPORT: We describe the case of a 5-year-old male, previously healthy, with multiple erythematous lesions that disappeared leaving hypopigmented macules. The biopsy reported histological changes suggestive of mycosis fungoides. After a second revision of lamellae in this hospital, lymphocytic vasculitis (LV) with focal epidermal necrosis consistent with acute pityriasis lichenoides (PL) was identified. CONCLUSIONS: The existing knowledge about PLEVA lacks a consensus in specifying its classification, etiopathogenesis, diagnosis, and treatment, so this clinical condition represents a medical challenge. The diagnosis is made by clinical suspicion and confirmed by histology. The objective of this article was to report a case of PLEVA with an atypical presentation due to its histopathological findings, being the first report showing LV in children, as well as a review of the literature.

INTRODUCCIÓN: La pitiriasis liquenoide y varioliforme aguda (PLEVA) es una dermatosis poco frecuente, de etiopatogenia desconocida y evolución autolimitada. Es más común en pacientes pediátricos y adultos jóvenes, y está caracterizada por la presencia de múltiples placas eritematoescamosas pequeñas o grandes, diseminadas en el tronco y las extremidades. CASO CLÍNICO: Se describe el caso de un escolar de 5 años, de sexo masculino, previamente sano, que presentó múltiples cuadros de lesiones eritematosas que desaparecían dejando máculas hipopigmentadas. La biopsia reportó cambios histológicos sugestivos de micosis fungoide. Se realizó una segunda revisión de laminillas, identificando vasculitis linfocítica con necrosis epidérmica focal, consistente con pitiriasis liquenoide aguda. CONCLUSIONES: El conocimiento acerca de la PLEVA carece de un consenso que especifique su clasificación, etiopatogenia, diagnóstico y tratamiento, por lo que esta condición clínica representa un desafío médico. El diagnóstico se realiza por sospecha clínica y se confirma por histología. El objetivo de este artículo fue reportar un caso de PLEVA con presentación atípica por los hallazgos histopatológicos, siendo este el primer reporte de vasculitis linfocítica en niños, y además se realiza una revisión de la literatura.

Primary Hepatic Neuroendocrine Carcinoma with Metastasis to the Mesentery: A Case Report.

Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 90 cases having been reported in the English-language literature. Among all neuroendocrine neoplasms, primary hepatic neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are extremely rare, accounting for 0.3% of NETs and 0.28-0.46% of malignant liver tumors. Additionally, primary hepatic NECs occur infrequently. The clinical diagnosis of primary hepatic NEC remains challenging because of its rarity and the lack of information about its characteristic appearance on images. Consequently, pathological examination through the performance of a preoperative liver tumor biopsy is essential for diagnosis. Due to the lack of availability of substantial high-quality data, there is no standard therapy for primary hepatic NEC. We present the first case of PHNEC metastasized to the mesentery reported in the English-language literature.

The role of glucagon after bariatric/metabolic surgery: much more than an "anti-insulin" hormone.

The biological activity of glucagon has recently been proposed to both stimulate hepatic glucose production and also include a paradoxical insulinotropic effect, which could suggest a new role of glucagon in the pathophysiology type 2 diabetes mellitus (T2DM). An insulinotropic role of glucagon has been observed after bariatric/metabolic surgery that is mediated through the GLP-1 receptor on pancreatic beta cells. This effect appears to be modulated by other members of the proglucagon family, playing a key role in the beneficial effects and complications of bariatric/metabolic surgery. Glucagon serves a dual role after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). In addition to maintaining blood glucose levels, glucagon exhibits an insulinotropic effect, suggesting that glucagon has a more complex function than simply an "anti-insulin hormone".

Somatostatin: From a supporting actor to the protagonist to explain the long-term effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Bariatric/metabolic surgery has become the most effective treatment against type 2 Diabetes mellitus (T2DM). The role of many gastrointestinal hormones in T2DM has been proposed, but the pathophysiological models described vary greatly depending on the anatomical rearrangements after surgery. We focus on somatostatin as a common factor in two of the most commonly performed surgical procedures in a healthy rodent model. We performed sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and also an experimental surgery without gastric involvement (intestinal resection of 50 % jejunum-ileum portion -IR50 %). METHODS: We used five groups of Wistar rats: fasting control, sham-operated, SG-operated, RYGB-operated and IR50-operated. We analysed several parameters 4 and 23 weeks after surgery: plasma SST-14/28 fractions, plasma glucose, insulin release and SST-producing cell expression in the duodenum and pancreatic islets. RESULTS: Numerous SST-producing cells in the duodenum but a low number in the pancreas and a long-term loss of glucose tolerance were observed in SG and RYGB animals. Additionally, a high plasma SST-28 fraction was found in animals after SG but not after RYGB. Finally, IR50 animals showed no differences versus controls. CONCLUSIONS: In our SG model the amplitude of insulin response after metabolic surgeries, is mediated by SST-28 plasma levels derived from the proportional compensatory effect of gastric SST-producing tissue ablation. In addition, a strong compensatory response to the surgical loss of gastric SST-producing cells, leads to long-term loss of insulin production after SG but not in the others.

Dual effect of RYGB on the entero-insular axis: How GLP-1 is enhanced by surgical duodenal exclusion.

BACKGROUND: The role of the ileum and Glucagon Like Peptide-1 (GLP-1) secretion in the pathophysiological processes underlying the effects of Roux-en-Y gastric bypass (RYGB) on type 2 Diabetes mellitus (T2DM) improvement has been previously determined. However, the roles of duodenal exclusion and Glucose Insulinotropic Peptide (GIP) secretion change is not clear. To clarify this aspect, we compared the pathophysiological mechanisms triggered by RYGB, which implies the early arrival of food to the ileum with duodenal exclusion, and through pre-duodenal ileal transposition (PdIT), with early arrival of food to the ileum but without duodenal exclusion, in a nondiabetic rodent model. METHODS: We compared plasma and insulin, glucose (OGTT), GIP and GLP-1 plasma levels, ileal and duodenal GIP and GLP-1 tissue expression and beta-cell mass for n = 12 Sham-operated, n = 6 RYGB-operated, and n = 6 PdIT-operated Wistar rats. RESULTS: No surgery induced changes in blood glucose levels after the OGTT. However, RYGB induced a significant and strong insulin response that increased less in PdIT animals. Increased beta-cell mass was found in RYGB and PdIT animals as well as similar GLP-1 secretion and GLP-1 intestinal expression. However, differential GIP secretion and GIP duodenal expression were found between RYGB and PdIT. CONCLUSION: The RYGB effect on glucose metabolism is mostly due to early ileal stimulation; however, duodenal exclusion potentiates the ileal response within RYGB effects through enhanced GIP secretion.