Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.

Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1ß, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear. While the role of microbial and cell death products has been previously described, we identified alloreactive memory CD4 T cells as the primary triggers of innate inflammation. Memory CD4 T cells engaged MHC II-mismatched dendritic cells (DCs), leading to the production of innate inflammatory cytokines. This innate inflammation was independent of several pattern recognition receptors and was primarily driven by TNF superfamily ligands expressed by alloreactive memory CD4 T cells. Blocking of CD40L and TNFα resulted in dampened inflammation, and mice genetically deficient in these molecules exhibited prolonged survival of cardiac allografts. Furthermore, myeloid cell and CD8 T cell infiltration into cardiac transplants was compromised in both CD40L- and TNFα-deficient recipients. Strikingly, we found that priming of naive alloreactive CD8 T cells was dependent on licensing of DCs by memory CD4 T cells. This study unravels the key mechanisms by which alloreactive memory CD4 T cells contribute to destructive pathology and transplant rejection.

Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

The possible impacts of nano and microplastics on human health: lessons from experimental models across multiple organs.

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemic rats.

BACKGROUND: Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. MATERIALS AND METHODS: Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. RESULTS: PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). CONCLUSION: PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Impacts of industrial actions, protests, strikes and lockouts by health and care workers during COVID-19 and other pandemic contexts: a systematic review.

BACKGROUND: Public health emergencies of international concern (PHEICs) as the COVID-19 pandemic and others that have occurred since the early 2000s put enormous pressure on health and care systems. This is being a context for protests by health and care workers (HCWs) because of additional workload, working conditions and effects on mental and physical health. In this paper, we intended to analyze the demands of HCWs associated with industrial actions, protests, strikes and lockouts (IAPSLs) which occurred during COVID-19 pandemic and other PHEICs; to identify the impact of these grievances; and describe the relevant interventions to address these IAPSLs. METHODS: We included studies published between January 2000 and March 2022 in PubMed, Embase, Scopus, BVS/LILACS, WHO's COVID-19 Research Database, ILO, OECD, HSRM, and Google Scholar for grey literature. Eligibility criteria were HCWs as participants, IAPSLs as phenomenon of interest occurring in the context of COVID-19 and other PHEICs. GRADE CERQual was used to assess risk of bias and confidence of evidence. RESULTS: 1656 records were retrieved, and 91 were selected for full-text screening. We included 18 publications. A system-wide approach, rather than a limited approach to institutions on strike, makes it possible to understand the full impact of the strike on health and care services. PHEICs tend to aggravate already adverse working conditions of HCWs, acting as drivers for HCWs strikes, leading to staff shortages, and financial issues, both in the North and in the Global South, particularly evident in Asia and Africa. In addition, issues related to deficiencies in leadership and governance in heath sector and lack of medical products and technologies (e.g., lack of personal protective equipment) were the main drivers of strikes, each contributing 25% of the total drivers identified. CONCLUSIONS: It is necessary to focus on the preparedness of health and care systems to respond adequately to PHEICs, and this includes being prepared for HCWs' IAPSLs, talked much in the context of COVID-19 pandemic. Evidence to assist policymakers in defining strategies to respond adequately to the health and care needs of the population during IAPSLs is crucial. The main impact of strikes is on the disruption of health care services' provision. Gender inequality being a major issue among HCWs, a proper understanding of the full impact of the strike on health and care services will only be possible if gender lens is combined with a systemic approach, rather than gender-undifferentiated approaches limited to the institutions on strike.

Impacts for health and care workers of Covid-19 and other public health emergencies of international concern: living systematic review, meta-analysis and policy recommendations.

BACKGROUND: Health and care workers (HCW) faced the double burden of the SARS-CoV-2 pandemic: as members of a society affected by a public health emergency and as HWC who experienced fear of becoming infected and of infecting others, stigma, violence, increased workloads, changes in scope of practice, among others. To understand the short and long-term impacts in terms of the COVID-19 pandemic and other public health emergencies of international concern (PHEICs) on HCW and relevant interventions to address them, we designed and conducted a living systematic review (LSR). METHODS: We reviewed literature retrieved from MEDLINE-PubMed, Embase, SCOPUS, LILACS, the World Health Organization COVID-19 database, the ClinicalTrials.org and the ILO database, published from January 2000 until December 2021. We included quantitative observational studies, experimental studies, quasi-experimental, mixed methods or qualitative studies; addressing mental, physical health and well-being and quality of life. The review targeted HCW; and interventions and exposures, implemented during the COVID-19 pandemic or other PHEICs. To assess the risk of bias of included studies, we used the Johanna Briggs Institute (JBI) Critical Appraisal Tools. Data were qualitatively synthetized using meta-aggregation and meta-analysis was performed to estimate pooled prevalence of some of the outcomes. RESULTS: The 1013 studies included in the review were mainly quantitative research, cross-sectional, with medium risk of bias/quality, addressing at least one of the following: mental health issue, violence, physical health and well-being, and quality of life. Additionally, interventions to address short- and long-term impact of PHEICs on HCW included in the review, although scarce, were mainly behavioral and individual oriented, aimed at improving mental health through the development of individual interventions. A lack of interventions addressing organizational or systemic bottlenecks was noted. DISCUSSION: PHEICs impacted the mental and physical health of HCW with the greatest toll on mental health. The impact PHEICs are intricate and complex. The review revealed the consequences for health and care service delivery, with increased unplanned absenteeism, service disruption and occupation turnover that subvert the capacity to answer to the PHEICs, specifically challenging the resilience of health systems.

Photoprotective potential of Passiflora cincinnata Mast. (Passifloraceae) hydro-alcoholic extracts.

Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10%, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPFspectrophotometric values. When combined to commercial filters, Pc-1 (5%) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations.

Prioritization criteria in policies and management of human resources for health: a proposal for a validated methodology.

Objective: To create and validate criteria for prioritizing problems related to policies and management of the health workforce. Methods: This methodological study was divided into three stages. First, the criteria were elaborated by means of a systematized literature review. Second, the criteria were evaluated online by a committee of judges comprised of eight specialists. In the third stage, an evaluation was carried out by the target audience in a hybrid workshop. The participants evaluated the material using the Suitability Assessment of Materials instrument, adapted for the research. Results: Three prioritization criteria (relevance, window of opportunity and acceptability) and a scoring scale were developed based on the literature review. In the evaluation by the committee of judges, the approval percentage of the criteria and prioritization method was 84%. Modifications were made based on suggestions in relation to the material presented to the specialists. In the pre-test stage, the approval percentage varied by item, with six of them reaching a maximum approval of 100% (corresponding to approximately 46% of the items), four reaching 92% and three achieving 83% each, indicating positive results. Conclusions: The developed criteria were considered valid for use in the context of policies and management in the area of human resources for health.

Influence of conditioned medium from squamous cell carcinoma of the tongue on lymphoblasts and peripheral blood mononuclear cells.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity and is associated with high morbidity and mortality. Attention has been given to the role of inflammatory cells in carcinogenesis because of the ability of cancer cells to subvert the immune response. However, little is known about how molecules from neoplastic cells interact with lymphoblasts and circulating immune cells. This study aimed to understand the mechanisms by which SCC cells modulate the immune response by analyzing the influence of conditioned medium derived from SCC cell lines on immune cells. METHODS: Lymphoblastic cells (CEM) and peripheral blood mononuclear cells (PBMC) were cultured in a conditioned medium derived from squamous cell carcinoma cells (SCC9 or SCC4) and analyzed for cell viability, CD4/CD8/FOXP3 profile by flow cytometry, and chemokine levels. RESULTS: Conditioned medium derived from SCC4 and SCC9 presented higher concentrations of IL-6 and IL-8 than IL-1ß, IL-10, and IFN-γ. CEM and PBMCs when cultured with conditioned medium derived from SCC4 and SCC9 reduced IL-1ß, IL-8, and IFN-γ concentrations. Conditioned medium from SCC4 increased CD4+ population in both CEM and PBMCs, while in conditioned medium from SCC9 it occurred only in PBMCs. PBMCs when cultured with both conditioned mediums increased CD8+ /FOXP3+ cells. CEM cells when cultured with conditioned medium derived from SCC4 and SCC9 reduced. CONCLUSION: Collectively, our results suggest that the products derived from squamous cell carcinoma on inflammatory cells can promote an immunosuppressed environment by reducing cell viability, changing cytokine expression, and altering the cell immunoprofile.

Implementation of policy and management interventions to improve health and care workforce capacity to address the COVID-19 pandemic response: a systematic review.

BACKGROUND: The COVID-19 pandemic highlighted pre-existing weaknesses in health and care systems and services and shortages of health and care workers (HCWs). As a result, policymakers needed to adopt measures to improve the health and care workforce (HCWF) capacity. This review aims to identify countries' range of policies and management interventions implemented to improve HCWs' capacity to address the COVID-19 pandemic response, synthesize their evidence on effectiveness, and identify gaps in the evidence. METHODS: The literature was searched in PubMed, Embase, Scopus, LILACS-BVS, WHO's COVID-19 Research Database and the ILO, OECD and HSRM websites for literature and documents published between January 2020 and March 2022. Eligibility criteria were HCWs as participants and policy and management interventions aiming to improve HCWF capacity to address the COVID-19 pandemic response. Risk of bias was assessed with Joanna Briggs Institute (JBI) Critical Appraisal Tools (CAT) and certainty of the evidence in presented outcomes with GRADE. RESULTS: The searches retrieved 3378 documents. A total of 69 were included, but only 8 presented outcomes of interventions implemented. Most of the selected documents described at least one intervention implemented by countries at the organizational environment level to increase the flexibility and capacity of the HCWF to respond to the pandemic, followed by interventions to attract and retain HCWs in safe and decent working environments. There was a lack of studies addressing social protection, human resources for health information systems, and regarding the role of community health workers and other community-based providers. Regarding the risk of bias, most of documents were rated as medium or high quality (JBI's CAT), while the evidence presented for the outcomes of interventions was classified as mostly low-certainty evidence (GRADE). CONCLUSIONS: Countries have implemented various interventions, some innovative, in response to the pandemic, and others had their processes started earlier and accelerated by the pandemic. The evidence regarding the impact and efficacy of the strategies used by countries during the pandemic still requires further research.

Hypolipidemic potential and safety profile of the ethanolic extract and flour of the peel of Passiflora Cincinnata Mast. (Passifloraceae) in mice.

Passiflora cincinnata Mast. is described as a native Caatinga species, used by nutritional and medicinal purposes, although there are still few studies and pharmacological data related to this species. This paper aims to evaluate the safety profile and hypolipidemic potential of the fruit peel of this species in mice. It was analyzed the chemical composition of ethanolic extract (EtOH-Pc) by HPLC-DAD-MS/MS, and the organic and inorganic composition of flour (MF-Pc). Also were evaluated the acute toxicity, the lipid-lowering potential of these samples, through of a pretreatment (oral: 100 and 200 mg/kg), and a single treatment with the same doses, after hyperlipidemic induction with triton WR-1339, using as animal model Swiss Mus musculus mice, besides histopathological analysis. The presence of flavonoids in the extract was confirmed, mainly C-glycosides, and antioxidant minerals and pectin, in flour. No clinical signs of toxicity or death were reported in the study. In the hyperlipidemia study model used, the analyzed substances, at all doses, notably decreased the lipid levels of TC, TG, LDL-c and VLDL-c and increase the HDL-c levels in the induced hyperlipidemic mice (p < 0.05). The results of the histopathological analysis showed that in the group only induced was identified the discrete presence of hepatic steatosis, in 2 animals at the analysis of 24 h, not being visualized in the groups treated with the substances evaluated. The results obtained in the present study suggest a hypolipidemic potential of the extract and flour, obtained from the fruit peel of Passiflora cincinnata Mast.

Effects of different doses of ionizing radiation on alveolar bone repair in post-extraction tooth socket: an experimental study in rats.

OBJECTIVE: This study aimed to evaluate the dose-response effects of ionizing radiation (IR) on alveolar bone repair and bone strength after tooth extraction. MATERIALS AND METHODS: A total of 32 male Wistar rats were used in the study, 28 animals were included in the final analysis, and n = 7 for each experimental group. Mandibular first molars were extracted. After 7 days, the animals were randomly divided into four groups according to single-dose irradiation: NIr, control group; Ir15, irradiated at 15 Gy; Ir20, irradiated at 20 Gy; and Ir30, irradiated at 30 Gy. The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric, and biomechanical analyses 14 days after extraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (α = 0.05). RESULTS: Micro-CT analysis revealed that IR led to lower values of bone volume (BV, in mm3) (0.68 ± 0.08, P < 0.001) and bone volume fraction, ratio of the segmented bone volume to the total volume of the region of interest (BV/TV, in %) (44.1 ± 8.3, P < 0.001) for the Ir30 group compared to the control group. A significantly lower amount of newly formed bone was observed in the Ir30 (P = 0.005) than in the Ir15 group. The histomorphometric results of quantification of bone matrix neoformation and the micro-CT were in agreement, demonstrating greater damage to the Ir30 group. IR30 cells showed a lower percentage of densely packed collagen than control cells. No significant differences were found in the biomechanical parameters. CONCLUSION: IR affects alveolar bone repair. A dose of 30 Gy reduced the bone healing process owing to a smaller amount of newly formed bone and a lower percentage of densely packed collagen. Therefore, a dose of 30 Gy can be used to successfully establish an animal model of an irradiated mandible that mimics the irradiated clinical conditions. CLINICAL RELEVANCE: Radiotherapy can lead to severe side effects and tooth extraction is a major risk factor. A proper understanding of the pathological mechanisms of radiation in alveolar bone repair requires the establishment of a suitable animal model of clinical conditions.

Evaluation of Genistein as a Mitochondrial Modulator and Its Effects on Sperm Quality.

Phytoestrogens, such as isoflavones, are bioactive compounds found in plants with defense and protection functions. In the human body, they simulate the behavior of the hormone estradiol and can modulate the function of the male hypothalamic-pituitary-gonadal axis. This study aims to describe the effects of genistein on sperm quality of Wistar rats (male/adult) after a short oral administration protocol (50 mg/day, for 5 days), focusing on mitochondrial function. No signs of toxicity were observed in the animals during the period. The testicular mass of rats from the genistein-treated group was lower than that from the control group. Isoflavone increased the number of viable Leydig and Sertoli cells, spermatogonia, and primary spermatocytes in the treated group. The rounded spermatid count was similar to the control group, and a decrease in elongated spermatids was observed in the treated group. Genistein treatment increased plasma testosterone levels in the treated group. To the best of our knowledge, this is the first report of an in vivo short protocol demonstrating that genistein administration stimulates the overall oxygen consumption in rat seminal samples. Therefore, genistein induced a pro-spermatogenesis effect, enhanced plasma testosterone levels, and increased oxygen consumption, improving sperm mitochondrial efficiency. Similar protocols can be explored in animal and human infertility issues.

Inflammatory myofibroblastic tumor presenting as a subepithelial lesion of the colon.

We present the case of a 42-year-old male admitted to the emergency department for a 15-day history of diarrhea, with bloody stools in the past 7 days. The patient denied abdominal pain or distension as well as any constitutional symptoms. On physical examination he presented good general health condition, with abdomen slightly tender in the lower quadrants; digital rectal examination was remarkable for the presence of dark blood. Laboratory evaluation revealed new onset normocytic anemia (Hb 10.8 g/dL, MCV 89 fL) and RCP of 3.3 mg/dL. Colonoscopy was performed, which showed a large cecal subepithelial lesion, with surface ulcerations. Histology reported mixed inflammatory infiltrate but no malignancy. Further investigation was carried out with an abdominal and pelvic computerized tomography that, other than the cecal mass, showed multiple infracentimetric mesenteric lymph nodes. A right laparoscopic hemicolectomy was performed. Pathological analysis led to the unusual diagnosis of inflammatory myofibroblastic tumor (IMT) of the colon. There was no sign of recurrence after 6 months of follow-up.

Intestinal and perianal tuberculosis: an uncommon clinical presentation and challenging diagnosis.

We present the case of a 40-year-old immunocompetent man with complaints of perianal abscess, diarrhea, and weight loss for 3 months. He denied respiratory symptoms. Colonoscopy revealed ulcers and histopathology showed non-necrotizing granulomas and excluded acid-fast bacilli. Initially, the clinical and histological findings favored the diagnosis of Crohn's disease, however, further investigation by performing chest radiography in the context of a pre-immunomodulatory checklist, revealed pulmonary cavitations confirmed on computed tomography scan. Further mycobacteriological studies suggested the diagnosis of active pulmonary tuberculosis. Demonstration of the presence of Mycobacterium tuberculosis in the colon was possible by RT-PCR. Complete resolution of intestinal and perianal symptoms was achieved 2 weeks after treatment with anti-bacillary agents.

Henoch-Schönlein purpura masquerading as Crohn's disease flare.

We describe the case of a 69-year-old male with Crohn's disease (CD), treated with infliximab and undergoing intestinal resection. The surgery and postoperative period were unremarkable, with no CD-related symptoms. Two months after surgery and two weeks after the introduction of infliximab, he was admitted due to acute onset diffuse abdominal pain, hematochezia and arthralgia. On physical observation on admission, he showed signs of arthritis of the left knee. Laboratory tests revealed renal failure with nephrotic proteinuria, slightly low complement (C3) and IgA elevation. Remaining autoimmunity and viral panel were negative. Abdominal examination showed duodenum and thickening of the proximal wall of the jejunum. Biopsies excluded active CD. Colon and ileum mucosa were normal. The patient met EULAR criteria for Henoch-Schönlein purpura and was started on prednisolone with response. Although no clear trigger was pointed out, we switched anti-TNF to ustekinumab. We present this case given its endoscopic exuberance, and because of the high index of suspicion to make the diagnosis in adult patients with previous inflammatory bowel disease. The distinction between this vasculitis and CD is of utmost importance, given the therapeutic implications.

Gastroduodenal artery pseudoaneurysm presenting with hyperamylasemia.

We present the case of a 75-year-old male admitted due to severe epigastric pain. His medical history was remarkable for chronic alcohol abuse, diabetes mellitus type 2, arterial hypertension, dyslipidemia. At admission he was hemodynamically stable. The initial workup showed elevated amylase, and the abdominal ultrasound excluded gallstone disease, so the diagnosis of acute pancreatitis was assumed. Despite appropriate fluid therapy, the patient developed hemodynamic instability. No signs of GIB were detected. An urgent laboratory workup revealed a new onset anemia and liver tests, including hyperbilirrubinemia. He underwent an urgent abdominal computed tomography with contrast, which showed a bleeding gastroduodenal artery (pseudoaneurysm and a hematoma adjacent to the second part of the duodenum. The patient underwent coil embolization achieving hemostasis without complications. GAD (pseudo)aneurysm is rare, accounting for 1.5% of all visceral artery aneurysms. Our patient presented with elevated pancreatic and liver enzymes, a more unique and challenging presentation since another more common differential diagnosis should be considered. The aneurysm can cause extrinsic common bile duct and main pancreatic duct pressure, which could explain the raised liver tests. Gastroenterologists should be aware of this rare and life-threatening entity, especially among patients presenting with common findings such as elevated amylase, jaundice, or altered liver tests. Hemodynamic instability is the main clue unmasking this diagnosis.

Primary gastric leiomyosarcoma presenting as a giant polyp.

We present the case of a 35-year-old woman with previous hereditary retinoblastoma treated with radiotherapy, admitted due to severe iron deficiency anemia. Upper endoscopy and endoscopic ultrasound revealed a 5-cm polypoid lesion in the fundus arising from muscularis mucosa. Histological findings favored a sarcoma with muscular differentiation. After exclusion of metastatic disease, the patient underwent surgery and diagnosis of primary gastric leiomyosarcoma was confirmed. We report a case of double rarity of gastric leiomyosarcoma, as she presented with severe anaemia from a polypoid lesion of the gastric fundus.

Isolated Jejunal Crohn's Disease: a challenging diagnosis.

A 27-year-old Nepalese male presented with recurrent abdominal pain accompanied by a lower stool consistency over the past 2 years. These episodes occurred several times a year, lasting 1 to 2 weeks, and resolved spontaneously, after adjustment of diet and/or medication for symptomatic control (e.g., antispasmodics, probiotics). Over the last year, the patient had undergone an extensive diagnostic investigation, which revealed no alterations in the laboratory workup, abdominal scan, esophagogastroduodenoscopy, and colonoscopy, including biopsies of the duodenum, and colon, so the symptoms have been attributed to irritable bowel syndrome. However, the symptoms had become more frequent, so the patient was referred to our gastroenterology department. We repeated and extended the work-up. Laboratory investigations showed an elevated erythrocyte sedimentation rate and faecal calprotectin. The remaining laboratory as well an extensive stool workup for infection were unremarkable. Esophagogastroduodenoscopy and ileocolonoscopy were normal. Small bowel capsule endoscopy revealed jejunal mucosa with lymphangiectasias, pseudopolypoids formations and superficial longitudinal ulcers, these findings were corroborated by the double-balloon enteroscopy, and biopsies showed marked architectural distortion, chronic inflammatory infiltrate, and an epithelioid granuloma. The clinical, endoscopic, biochemical, and histological findings were consistent with isolated jejunal Crohn's disease. The patient started adalimumab with complete remission after one year. We present this case given its exuberant endoscopic findings and due to the difficulty in making the diagnosis due to its rarity, location, and unspecific presentation.

Hyperphagia and hyperleptinemia induced by low-protein, high-carbohydrate diet is reversed at a later stage of development in rats.

This study investigated whether increased food intake after 15 days of low-protein, high-carbohydrate (LPHC) and its normalization in the later period of development change the content of key proteins related to leptin or adiponectin signaling in the hypothalamus. Male rats were divided into five groups: Control groups received a control diet (17% protein, 63% carbohydrate) for 15 (C15) or 45 (C45) days; LPHC groups received an LPHC diet (6% protein, 74% carbohydrate) for 15 (LPHC15) or 45 (LPHC45) days; and Reverse group (R): received LPHC diet for 15 days followed by control diet for another 30 days. The LPHC15 group showed increased adiposity index, leptin level, and adiponectin level, as well as decreased the leptin receptor (ObRb) and pro-opiomelanocortin (POMC) content in the hypothalamus compared with the C15 group. LPHC diet for 45 days or diet reversion (R group) rescued these alterations, except the adiponectin level in LPHC45 rats, which was higher. In summary, LPHC diet reduced hypothalamic leptin action by diminishing ObRb and POMC levels, leading to hyperphagia and adiposity body. Medium-term administration of LPHC diet or reverting to control diet restored the levels of these proteins, thereby improving body lipid mass rearrangement in adulthood.