Polysubstance-Induced Hepatotoxicity and the Role of Supportive Management.

With the continued rise of polysubstance use throughout the country, it has been shown to affect a multitude of organ systems. Drug-induced liver injury (DILI) has been widely documented in its association with salicylates or acetaminophen and the utility of using N-acetylcysteine (NAC) for its hepatoprotective effects. However, DILI caused by illicit drug use and guideline-directed management has had little research. We present the case of a 29-year-old female who presented with altered mental status. She was found to have a concomitant liver injury and was treated supportively without the use of NAC, with gradual improvement.

The miRNA822 loaded by ARGONAUTE9 modulates the monosporic female gametogenesis in Arabidopsis thaliana.

KEY MESSAGE: The miR822 together with of AGO9 protein, modulates monosporic development in Arabidopsis thaliana through the regulation of target genes encoding Cysteine/Histidine-Rich C1 domain proteins, revealing a new role of miRNAs in the control of megaspore formation in flowering plants. In the ovule of flowering plants, the establishment of the haploid generation occurs when a somatic cell differentiates into a megaspore mother cell (MMC) and initiates meiosis. As most flowering plants, Arabidopsis thaliana (Arabidopsis) undergoes a monosporic type of gametogenesis as three meiotically derived cells degenerate, and a single one-the functional megaspore (FM), divides mitotically to form the female gametophyte. The genetic basis and molecular mechanisms that control monosporic gametophyte development remain largely unknown. Here, we show that Arabidopsis plants carrying loss-of-function mutations in the miR822, give rise to extranumerary surviving megaspores that acquire a FM identity and divides without giving rise to differentiated female gametophytes. The overexpression of three miR822 putative target genes encoding cysteine/histidine-rich C1 (DC1) domain proteins, At5g02350, At5g02330 and At2g13900 results in defects equivalent to those found in mutant mir822 plants. The three miR822 targets genes are overexpressed in ago9 mutant ovules, suggesting that miR822 acts through an AGO9-dependent pathway to negatively regulate DC1 domain proteins and restricts the survival of meiotically derived cells to a single megaspore. Our results identify a mechanism mediated by the AGO9-miR822 complex that modulates monosporic female gametogenesis in Arabidopsis thaliana.

Metastatic Melanoma Invading the Minor Duodenal Papilla in a Patient With Pancreas Divisum Causing Acute Recurrent Pancreatitis: A Case Report.

Metastasis to the gastrointestinal (GI) tract should always be a consideration when melanoma, particularly metastatic disease, is diagnosed. While metastasis to the small intestine is common, given its rich blood supply, metastasis to the pancreatic ducts is extremely rare. In patients with pancreatic divisum, disease spread to the minor papilla can greatly increase the chance of developing pancreatitis due to the potential for increased pancreatic intraductal pressure. We present one unique case of metastatic melanoma to the minor duodenal papilla causing pancreatitis.

Recurrent reactive infectious mucocutaneous eruption (RIME) secondary to Chlamydophila pneumoniae infection in an adult.

The terminology surrounding the clinical syndrome characterized by acute mucositis with minimal skin involvement has been a subject of debate over time. In recent years, terms such as mycoplasma-induced rash and mucositis and reactive infectious mucocutaneous eruption (RIME) have been introduced to encompass milder mucocutaneous diseases associated with respiratory infections, with implications for management and prognosis. We report the first case of recurrent RIME associated with Chlamydophila pneumoniae infection in an adult patient. RIME is likely underreported due to misclassification and a lack of testing for potential pathogens. Early recognition of recurrent RIME is of particular interest from the patient's perspective to reduce the frequency and duration of hospital admissions.

Beryllium compounds for the carbon-halogen bond activation of phenyl halides: the role of non-innocent ligands.

Beryllium is a metallomimetic main-group element, i.e., it behaves similarly to transition metals (TMs) in some bond activation processes. To investigate the ability of Be compounds to activate C-X bonds (X = F-I), we have computationally investigated, using DFT methods, the reaction of (CAAC)2Be (CAAC = 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) and a series of five-membered heterocyclic beryllium bidentate ligands with phenyl halides. We have analysed all plausible reaction mechanisms and our results show that, after the initial C-X oxidative addition, migration of the phenyl group occurs towards the less electronegative heteroatom. Our theoretical study highlights the important role of bidentate non-innocent ligands in providing the required electrons for the initial Ph-X oxidative addition. In contrast, the monodentate ligand, CAAC, does not favour this oxidative addition.

Effect of valproic acid upon skeletal muscle subjected to prolonged tourniquet application.

Background: Valproic acid (VPA), a histone deacetylase inhibitor, has shown improved outcomes when used as a pharmaceutical intervention in animal studies of hemorrhage, septic shock, and combined injuries. This study was designed to investigate the ability of VPA to mitigate ischemia-reperfusion injury produced by prolonged tourniquet application to an extremity. Methods: The ischemia-reperfusion model in anesthetized rats was established using hemorrhage and a 3-hour tourniquet application. VPA was administered intravenously prior to tourniquet wear and removal. Ischemia-reperfusion injury was evaluated by investigating pathway signaling, immune modulation of cytokine release, remote organ injury, and skeletal muscle function during convalescence. Results: We found that VPA sustained Protein kinase B (Akt) phosphorylation and Insulin-like growth factor signaling and modulated the systemic release of interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-6 after 2 hours of limb reperfusion. Additionally, VPA attenuated a loss in glomerular filtration rate at 3 days after injury. Histological and functional evaluation of extremity skeletal muscle at 3, 7, and 21 days after injury, however, demonstrated no significant differences in myocytic degeneration, necrotic formation, and maximal isometric tetanic torque. Conclusions: Our results demonstrate that VPA sustains early prosurvival cell signaling, reduces the inflammatory response, and improves renal function in a hemorrhage with prolonged ischemia and reperfusion model. However, these do not translate into meaningful preservation in limb function when applied as a pharmaceutical augmentation to tourniquet wear. Level of evidence: IV.

HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis.

INTRODUCTION: More than 180 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more than 4 million coronavirus disease-2019 (COVID-19) patients have died in 1.5 years of the pandemic. A novel therapeutic vaccine (NASVAC) has shown to be safe and to have immunomodulating and antiviral properties against chronic hepatitis B (CHB). MATERIALS AND METHODS: A phase I/II, open-label controlled and randomized clinical trial of NASVAC as a postexposure prophylaxis treatment was designed with the primary aim of assessing the local and systemic immunomodulatory effect of NASVAC in a cohort of suspected and SARS-CoV-2 risk-contact patients. A total of 46 patients, of both sexes, 60 years or older, presenting with symptoms of COVID-19 were enrolled in the study. Patients received NASVAC (100 µg per Ag per dose) via intranasal at days 1, 7, and 14 and sublingual, daily for 14 days. RESULTS AND DISCUSSION: The present study detected an increased expression of toll-like receptors (TLR)-related genes in nasopharyngeal tonsils, a relevant property considering these are surrogate markers of SARS protection in the mice model of lethal infection. The HLA-class II increased their expression in peripheral blood mononuclear cell's (PBMC's) monocytes and lymphocytes, which is an attractive property taking into account the functional impairment of innate immune cells from the periphery of COVID-19-infected subjects. NASVAC was safe and well tolerated by the patients with acute respiratory infections and evidenced a preliminary reduction in the number of days with symptoms that needs to be confirmed in larger studies. CONCLUSIONS: Our data justify the use of NASVAC as preemptive therapy or pre-/postexposure prophylaxis of SARS-CoV-2 and acute respiratory infections in general. The use of NASVAC or their active principles has potential as immunomodulatory prophylactic therapies in other antiviral settings like dengue as well as in malignancies like hepatocellular carcinoma where these markers have shown relation to disease progression. HOW TO CITE THIS ARTICLE: Fleites YA, Aguiar J, Cinza Z, et al. HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis. Euroasian J Hepato-Gastroenterol 2021;11(2):59-70.

COELOMIC STEATITIS IN TENTACLED SNAKES (ERPETON TENTACULATUM).

A retrospective study revealed seven cases of coelomic steatitis in adult tentacled snakes (Erpeton tentaculatum), including two males and five females, between May 2014 and August 2020. Common clinical signs included death after unusual floating, generalized weakness, inappetence, reduced body condition, coelomic distension, and reproductive pathology in females. Hematology of one specimen revealed marked monocytosis and lymphocytosis with mild heterophilia (chronic and active inflammation). Gross examination identified variable degrees of intracoelomic fat necrosis in all snakes. Consistent histopathologic features included necrotic adipocytes, lipid saponification, lipofuscin/ceroid deposition, granulomatous inflammation, and multinucleated giant cells (Langhans type). Three females exhibited intralesional yolk fluid associated with periovarian steatitis. Hepatic lipidosis was the second most frequent pathologic finding. Thawed frozen lesser sand eels (Ammodytes tobianus) were fed during this period, stored in vacuum-sealed or opened packets at -18°C (frozen). After the death of the last specimen, vitamin E concentrations and peroxide values of the diet were analyzed. For the sealed and opened frozen batches, respectively, vitamin E concentrations were 0.71 and 0.49 mg/100 g (compared with 4 to 8 mg/100 g in average, fresh, raw mixed eel species samples) and peroxide values were 62.5 and 48.6 meq/kg (exceeding the acceptable peroxide values of 8 meq/kg for fish oils). This case study represents the first report of coelomic steatitis in tentacled snakes of unconfirmed etiology but with a putative association with feeding a long-term frozen-stored sand eel diet containing low vitamin E concentrations and fish oils with high peroxide values at time of analysis.

Differentiating pagetoid Bowen disease from Paget disease on the nipple-areola complex: Two unique, challenging cases.

Pagetoid Bowen disease is a subtype of Bowen disease that accounts for 5% of Bowen disease. It is extremely rare for Bowen disease to appear on the nipple-areola complex, with only seven cases described in the previous literature. Of those seven cases, only one was of the pagetoid subtype. We report two cases of pagetoid Bowen disease on this location, one of them being the first case of pagetoid Bowen disease affecting the nipple reported to date. On this location, it is crucial to perform a meticulous differential diagnosis to rule out Paget disease, because of its contrasting therapeutic and prognostic implications. In order to do this, clinical and histopathological aspects must be considered. From a clinical point of view, previous literature has stated that nipple involvement can be a clue that points to Paget disease. However, one of our cases shows that this is not always true. Regarding histopathological analysis, a complete excision of the tumor might be necessary to observe clear features of Bowen disease, such as full-thickness atypia of the epidermis and intercellular bridges. An immunohistochemical panel comprising carcinoembryonic antigen, gross cystic disease fluid protein, epithelial membrane antigen, p63, CK34betaE12, periodic acid-Schiff, estrogen receptor, and progesterone receptor can be decisive in complicated cases.

A RETROSPECTIVE REVIEW OF POST-METAMORPHIC MOUNTAIN CHICKEN FROG (LEPTODACTYLUS FALLAX) NECROPSY FINDINGS FROM EUROPEAN ZOOLOGICAL COLLECTIONS, 1998 TO 2018.

The mountain chicken frog (Leptodactylus fallax) is the largest endemic amphibian species in the Western Hemisphere. Since 1998, this critically endangered species has been maintained as a European Endangered Species Programme, but low breeding success and a high mortality rate threaten the sustainability of the captive frog population. In the current study, we analyzed gross and histopathologic postmortem information from 212 mountain chicken frogs that died in European zoological collections from 1998 to 2018. Thin body condition was the most commonly reported finding across all submissions, observed in 125 frogs. The gastrointestinal and urinary systems were reported to have the highest prevalence of pathologic findings on gross and histopathologic examination. Inflammatory disease was the most frequent diagnosis after histopathologic examination of relevant tissues, with intestinal inflammatory disease (n = 76) followed by tubulointerstitial nephritis (n = 26) being the most commonly reported. Neoplasia was reported in 42 of 212 (19.8%) frogs, all of which were adults. A defined cause of death, or reason for euthanasia, was proposed for 164 of 212 (77.4%) frogs, with inflammatory diseases processes (74 of 212; 34.9%) most commonly implicated. Intestinal adenocarcinoma, seemingly restricted to the colon, caused the deaths of 31 adult frogs. Further investigations to determine factors contributing to the high incidence of inflammatory disease processes and neoplasia are advocated to improve the health and sustainability of the captive mountain chicken frog population.

Arabidopsis cysteine-rich receptor-like protein kinase CRK33 affects stomatal density and drought tolerance.

Cysteine-rich receptor-like protein kinases (CRKs) are transmembrane proteins containing two domains of unknown function 26 (DUF26) RLKs in their ectodomain. Despite that CRKs control important aspects of plant development, only few proteins have functionally been characterized. In this work, we analyzed the function of CRK33 by characterizing two insertional lines. The stomatal density and stomatal index were decreased in crk33-2 and crk33-3 plants in comparison to wild-type plants, correlating with a decreased transpiration in transgenic plants and a higher drought tolerance. Furthermore, photosynthesis and stomatal conductance changed. Finally, all four stomata cell fate genes were upregulated, especially the expression of TMM and SPCH in the mutant background, suggesting a role for CRK33 in stomatal spacing.

Effect of the Flipped Classroom and Gamification Methods in the Development of a Didactic Unit on Healthy Habits and Diet in Primary Education.

Currently, there are several methodological models that have broken into different disciplines of knowledge with the aim of making the teaching/learning process more dynamic, active and participatory for students. This is the case of Flipped Classroom, which is based on a mixed approach between e-learning and face-to-face teaching, as well as gamification, which bases its didactic principles on the recreational components of the games. Within this context, the aim of this research is to observe what effect the application of Flipped Classroom and gamification has in the development of motivation, autonomy and self-regulation towards learning through a didactic unit on healthy habits and diet in 202 students of 6th grade of Primary School from four different schools (public and state-subsidized) in the city of Granada (Spain). For this purpose, a methodological design was used with pre-test and post-test to check the effects of the experience on the students. The findings obtained showed that the application of these methods promoted an increase in students' motivation, as well as in their autonomy and self-regulation when facing the contents of the subject. For this reason, it is advocated that there is a need to continue promoting a quality and innovative educational practice according to the figure of the student today.

Evaluación del estado metabólico, el peso vivo y la condición corporal durante la gestación en vacas de carne en la Altillanura colombiana / Evaluation of the metabolic status, live weight and body condition during pregnancy in beef in the Colombian Altillanura cows / Avaliação do estado metabólico, peso vivo e condição corporal durante a gestação em vacas de corte no Altillanura colombiana

Resumen El objetivo de este estudio, fue conocer los valores promedios de diferentes metabolitos, la variación del peso vivo (PV) y la condición corporal (CC) en vacas Cebú (C) y Simmental x Cebú (SC) bajo pastoreo extensivo en una finca de la Altillanura colombiana. Se utilizaron 19 vacas multíparas y durante cada trimestre de la gestación, se evaluaron los niveles de Glucosa (Glu), Colesterol (Col), Proteína totales (Ptt), Albúmina (Alb), Globulinas (Glo), Hemoglobina (Hb), Hematocrito (Hto), Nitrógeno en sangre (BUN), Cobre (Cu), Zinc (Zn), Calcio (Ca), Magnesio (Mg), Fósforo (P), y Aspartato aminotransferasa (AST). Los niveles de Glu, Hb, Hto, BUN, Ca, presentaron variaciones significativas durante los trimestre evaluados (P<0,05), con deficiencias de Cu y Zn. El PV y la CC presentaron una relación lineal en función del avance de la gestación. Se reconoce la importancia de los perfiles metabólicos (PM) como una herramienta para identificar los posibles imbalances nutricionales y la manera de corregir las deficiencias, con el propósito de hacer mas eficiente el sistema productivo.

Abstract The objective of this study was to know the average values ​​of different metabolites, the variation of live weight (LW) and body condition (CC) in Cebu (C) and Simmental x Cebu (SC) cows under extensive grazing in a farm of the Colombian Altillanura. We used 19 multiparous cows and during each trimester of pregnancy, we evaluated the levels of Glucose (Glu), Cholesterol (Col), Total Protein (Ptt), Albumin (Alb), Globulins (Glo), Hemoglobin (Hb), Hematocrit (Hto), Nitrogen in blood (BUN), Copper (Cu), Zinc (Zn), Calcium (Ca), Magnesium (Mg), Phosphorus (P), and Aspartate aminotransferase (AST). The levels of Glu, Hb, Hto, BUN, Ca presented significant variations during the quarter evaluated (P <0.05), with deficiencies of Cu and Zn. The PV and CC presented a linear relationship based on the progress of pregnancy. The importance of metabolic profiles (PM) is recognized as a tool to identify possible nutritional imbalances and how to correct deficiencies, in order to make the productive system more efficient.

Resumo O objetivo deste estudo foi conhecer os valores médios dos diferentes metabólitos, a variação do peso vivo (PV) e a condição corporal (CC) em vacas Cebu (C) e Simmental x Cebu (SC) sob pastejo intenso numa fazenda da Altillanura colombiana. Foram utilizadas 19 vacas multíparas e, durante cada trimestre da gestação, foram avaliados os níveis de glicose (Glu), colesterol (Col), proteína total (Ptt), albumina (Alb), globulinas (Glo), hemoglobina (Hb) e hematócrito (Hto), nitrogênio sanguíneo (BUN), cobre (Cu), zinco (Zn), cálcio (Ca), magnésio (Mg), fósforo (P) e aspartato aminotransferase (AST). Os níveis de Glu, Hb, Hto, BUN, Ca apresentaram variações significativas durante os trimestres avaliados (P <0,05), com deficiências de Cu e Zn. O PV e o CC apresentaram uma relação linear com o progresso da gravidez. A importância dos perfis metabólicos (MP) é reconhecida como uma ferramenta para identificar possíveis desequilíbrios nutricionais e como corrigir deficiências, a fim de tornar o sistema de produção mais eficiente.

Novel Triamcinolone Acetonide-Loaded Liposomal Topical Formulation Improves Contrast Sensitivity Outcome After Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To assess visual results, macular modifications, and the incidence of clinically significant macular edema (CSME) in patients using a topical triamcinolone acetonide-loaded liposomal formulation (TA-LF) after femtosecond laser-assisted cataract surgery (FLACS). Methods: Fifty-six eyes after FLACS were selected. Twenty-eight eyes in the combined therapy group (P + N) were treated with prednisolone 1% and nepafenac 0.1% for 21 days postoperatively, whereas 28 eyes in the TA-LF group received a liposomal formulation containing 2 mg/mL of TA (0.2%) for the same period of time. Follow-up visits at 1 day, 6 weeks, and 12 weeks after surgery consisted of visual acuity, contrast sensitivity (CS), central foveal thickness (CFT), total macular volume (TMV) measurements, and the detection of CSME. Results: CS improved in the TA-LF group (basal value: 1.087 ± 0.339 vs. 1.276 ± 0.147 at week 12, P = 0.0346), whereas in the P + N group, CS was not different from the baseline (basal value: 1.130 ± 0.331 vs. 1.274 ± 0.133 at week 12, P = 0.1276). There were similar increases in postoperative CFT and TMV in both groups. CFT and TMV significantly correlate with CS only in the TA-LF group. The r2 for CFT and CS was 0.1963 (P = 0.0206), whereas the r2 for TMV and CS was 0.3615 (P = 0.0007) at 12 weeks. No difference was observed in the incidence of CSME between the groups. Conclusion: TA-LF is associated with better CS outcomes compared to combined therapy after FLACS.

Neuroendocrine tumor associate with inflammatory bowel disease: two cases report.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) have a higher risk of developing gastrointestinal tumors, the adenocarcinoma is the most frequently associated, and neuroendocrine tumor (NET) the most rare. CLINICAL CASES: We present two patients, one with Crohn's disease and the other with ulcerative colitis, who present nonspecific symptoms, and after resection of an intestinal lesion, a gastrointestinal NET (GINET) is diagnosed. DISCUSSION AND CONCLUSION: The GINET have an insidious clinic and these can be confused with those of the IBD. There could be an association between both pathologies; an important role of the chronic intestinal inflammatory process is suggested. The best treatment for GINET is the resection.

INTRODUCCIÓN: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen mayor riesgo de desarrollar neoplasias gastrointestinales y el adenocarcinoma es el relacionado con más frecuencia y el tumor neuroendocrino (TNE) el más raro. CASO CLÍNICO: Se presentan los casos de dos pacientes, uno con enfermedad de Crohn y otro con colitis ulcerosa, que cursan con clínica inespecífica, y tras resección de la lesión intestinal se diagnostica un TNE gastrointestinal (TNEGI). DISCUSIÓN Y CONCLUSIONES: Los TNEGI tienen una clínica insidiosa y pueden confundirse con los de la EII. Es posible un nexo entre ambas entidades, lo que sugiere un papel importante del proceso inflamatorio crónico intestinal. El tratamiento de elección de los TNEGI es la resección.

Design of Silica-Oligourethane-Collagen Membranes for Inflammatory Response Modulation: Characterization and Polarization of a Macrophage Cell Line.

The polarization of macrophages M0 to M1 or M2 using molecules embedded in matrices and hydrogels is an active field of study. The design of biomaterials capable of promoting polarization has become a paramount need nowadays, since in the healing process macrophages M1 and M2 modulate the inflammatory response. In this work, several immunocytochemistry and ELISA tests strongly suggest the achievement of polarization using collagen-based membranes crosslinked with tri-functionalized oligourethanes and coated with silica. Measuring the amount of TGF-ß1 secreted to culture media by macrophages growth on these materials, and quantifying the macrophage morphology, it is proved that it is possible to stimulate the anti-inflammatory pathway toward M2, having measurements with p ≤ 0.05 of statistical significance between the control and the collagen-based membranes. Furthermore, some physicochemical characteristics of the hybrid materials are tested envisaging future applications: collagenase degradation resistance, water uptake, collagen fiber diameter, and deformation resistance are increased for all the crosslinked biomaterials. It is considered that the biological and physicochemical properties make the material suitable for the modulation of the inflammatory response in the chronic wounds and promising for in vivo studies.