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Background: To study the possible dosimetric benefits of a Hybrid planning technique that consists of combining intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) for whole brain radiation therapy hippocampal-sparing (WBRTHS). Materials and Methods: Three types of plans were made for 15 patients, namely Hybrid, pure IMRT, and pure VMAT and retrospectively compared. Each plan was made using contoured structures on computed tomographic (CT) images fused with magnetic resonance imaging (MRI). The homogeneity (HI) and conformity (CI) indices of the planning target volumes (PTVs) were calculated to establish the dosimetric quality in all plans. The dose received to organs at risk (OARs), number of monitor units (MUs) and treatment time were evaluated for each type of planning technique. Results: Hybrid plans showed superior homogeneity (p = 0.04) and conformity (p = 0.01) indices compared to IMRT and VMAT plans. In terms of hippocampus sparing, the Hybrid technique showed almost equal D100% and maximum dose (Dmax) values compared to the other techniques, but without statistical significance (p> 0.05); however, there was a significant difference for the left hippocampus, where the IMRT technique obtained the best result (p <0.001). Hybrid plan values for dose delivered to the remaining OARs, MUs and treatment times were intermediate between those of IMRT and VMAT. Conclusion: Compared to the IMRT and VMAT plans, the hybrid plan showed improved dosimetric plan quality along with intermediate dose values to the OARs. [ABSTRACT FROM AUTHOR]

In this study, we synthesized a series of seven benzimidazole derivatives incorporating the structural acidic framework of angiotensin II (Ang II) type 1 receptor (AT 1 R) antagonists (ARA-II) employing a three-step reaction sequence. The chemical structures were confirmed by 1 H NMR, 13 C NMR and mass spectral data. Through biosimulation, compounds 1-7 were identified as computational safe hits, thus, best candidates underwent ex vivo testing against two distinct mechanisms implicated in hypertension: antagonism of the Ang II type 1 receptor and the blockade of calcium channel. Molecular docking studies helped to understand at the molecular level the dual vasorelaxant effects with the recognition sites of the AT 1 R and the L-type calcium channel. In an in vivo spontaneously hypertensive rat model (SHR), intraperitoneally administration of compound 1 at 20 mg/kg resulted in a 25 % reduction in systolic blood pressure, demonstrating both ex vivo vasorelaxant action and in vivo antihypertensive multitarget efficacy. ©2024 Elsevier., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bocconia arborea S. Watson (Papaveraceae) is an abundant medicinal plant in the North of Morelos State, Mexico, which is used for the treatment of several diseases. The aim of current investigation was to isolate the compounds responsible of the relaxant effect shown by the active extracts. Thus, phytochemical bio-guided fractionation allowed the isolation of angoline (1), dihydrosanguinarine (2), bocconarborine A (3), oxisanguinarine (4), and oxychelerithrine (5) from dichloromethanic and methanolic extracts from the bark of Bocconia arborea (Papaveraceae). The relaxant study on aortic and tracheal rat rings of all benzophenanthridines indicates that 1 was the most active compound of the entire series investigated. Angoline (1) induces its relaxant effect by a concentration-dependent manner through the calcium channel blockade in both tissues., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Mexican children with obesity are at a higher risk of developing type 2 diabetes mellitus (T2DM). The aim of the study was to compare oral glucose tolerance test (OGTT) characteristics: time of peak glucose, glucose level ≥155 mg/dL at 1 h, presence of metabolic syndrome (MetS), sensitivity, secretion, and oral disposition index (oDI) in children with and without obesity, according to oral glucose tolerance curve shape: monophasic or biphasic., Methods: Cross-sectional study including 143 children. Groups were divided into (a) obese: biphasic (B-Ob) (n=55) and monophasic (M-Ob) (n=50), (b) without obesity: biphasic (B-NonOb) (n=20) and monophasic (M-NonOb) (n=18)., Results: Late glucose peak was more frequent in the M-Ob group (p<0.001). Glucose levels ≥155 mg/dL and MetS were more frequent in the M-Ob group but did not show significance. The groups with obesity (biphasic and monophasic) had higher indices of insulin resistance and insulin secretion compared to the nonobese groups (biphasic and monophasic) (p<0.001). AUC glucose was higher in the M-Ob group (p<0.05), and AUC insulin was higher in the M-NonOb group. oDI (Matsuda) was significantly lower in the M-Ob group compared to the other groups (p<0.001), and oDI-HOMA IR was higher in M-NonOb group (p=0.03)., Conclusions: All OGTT parameters could help to identify Mexican children at increased risk of developing T2DM, not only fasting plasma glucose and 2 h glucose. M-Ob in non-T2DM Mexican children reflects an early defect in glucose metabolism. Higher level of IR indexes in M-NonOb vs. B-NonOb could indicate an increased risk for T2DM of genetic origin., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes., Methods: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups., Results: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001)., Conclusions: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Median arcuate ligament syndrome (MALS), also known as Dunbar syndrome, is a rare but significant cause of chronic abdominal pain resulting from the extrinsic compression of the celiac trunk. This condition typically manifests with symptoms such as postprandial pain, nausea, vomiting, and weight loss, often leading to a diagnostic challenge due to its mimicry of other abdominal disorders. Diagnosis is based on exclusion and requires a high index of suspicion combined with precise imaging findings. This case report presents a 44-year-old female patient presenting with chronic abdominal pain, diaphoresis, and nausea, underscoring the complexity and diagnostic challenge of MALS, highlighting the significance of early intervention to mitigate morbidity and novelty treatment utilizing robotic-assisted surgical techniques. This report aims to contribute to the understanding of clinical presentations, diagnostic challenges, and treatment modalities of Dunbar syndrome, especially the option of minimally invasive robotic-assisted surgery for the treatment of this condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Barron-Cervantes et al.)

Seasonally tropical dry forests (SDTFs) in the American tropics are a highly diverse yet poorly understood and endangered ecosystem scattered from Northern Mexico to Southern Argentina. One floristic element of the STDFs is the genus Magoniella (Polygonaceae), which includes two liana species, M. laurifolia and M. obidensis , which have winged fruits and are distributed from Costa Rica to Southern Brazil. In a field expedition to the SDTFs of the Colombian Caribbean in 2015, morphologically distinctive individuals of Magoniella were found. In this study, we investigated the species boundaries within Magoniella and determined the phylogenetic position of these morphologically distinctive individuals in the tribe Triplaridae. We compiled morphological trait data across 19 specimens of both species and produced newly sequenced nuclear-plastid DNA data for M. obidensis . Morphometric analyses revealed significant differences in fruit length and perianth size among individuals from the Colombian Caribbean compared to M. obidensis and bract length when compared to M. laurifolia . Maximum likelihood analysis of non-conflicting nuclear and plastid datasets placed the Colombian Caribbean individuals as sister to M. obidensis with maximum statistical support. Additionally, pairwise sequence comparisons of the nuclear ribosomal ITS and the lfy2i loci consistently showed 15-point mutations (10 transitions, five transversions) and six 2 bp-long substitutions that differ between M. obidensis and the Colombian Caribbean individuals. Our morphological and molecular evidence thus suggests that the Colombian Caribbean individuals of Magoniella represent a divergent population from M. laurifolia and M. obidensis , which we describe and illustrate as a new species, M. chersina . Additionally, we provide nomenclatural updates for M. laurifolia and M. obidensis . This study highlights the power of combining morphological and molecular evidence in documenting and naming plant diversity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aguilar-Cano, Pérez-Escobar, Pizano, Tovar and Antonelli.)

Abstract: Twenty years ago, pioneer Doctor of Nursing Practice (DNP) program students completed the first DNP projects. Today, DNP projects remain a requirement for graduation. This article illustrates how the DNP project can be integrated throughout the DNP curriculum to maximize effectiveness and promote the introduction, reinforcement, and evaluation of competencies in the new American Association of Colleges of Nursing Essentials., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The severity of fibrosis is central to the therapeutic course for patients with chronic liver disease; therefore, early detection of liver fibrosis is critical for timely therapeutic interventions. Liver biopsy is the gold standard for the diagnosis of liver fibrosis; however, it is contraindicated in several pathological conditions. Activated hepatic stellate cells (HSCs) are the main cells for fibrotic tissue synthesis, such as that of alpha-smooth muscle actin (α-SMA). This study aimed to determine whether serum α-SMA levels are a suitable noninvasive, sensitive, and reliable liver fibrosis marker. Fibrosis was induced in male Wistar rats via chronic CCl 4 administration. Fibrosis was determined in the liver tissues by quantifying the hydroxyproline content and visualized using Masson's trichrome staining. Rats chronically administered CCl 4 exhibited a progressive increment in the hepatic collagen content, as well as both hepatic and serum α-SMA levels in a time-dependent manner. Moreover, serum levels of α-SMA significantly correlated with hepatic α-SMA levels ( p  ≤ 0.001), as well as with the severity of liver fibrosis ( p  ≤ 0.001). These findings suggest that increased levels of serum α-SMA can be considered a potential reliable and noninvasive biomarker for early liver fibrosis.

Objectives: Preeclampsia (PE) is a complication of pregnancy that might increase progeny risk of cardiovascular and metabolic problems, mainly in males. Renin angiotensin aldosterone system is known to be involved. (Pro) renin/renin receptor ((P)RR) has been shown to participate in cardiovascular pathology. The aim of this work was to evaluate (P)RR expression and function upon cardiovascular and renal tissues from PE dams' offspring., Materials and Methods: We used offspring from normal pregnant and preeclamptic rats, evaluating body, heart, aorta and kidney weight, length, and blood pressure along 3 months after birth. Subsets of animals received handle region peptide (HRP) (0.2 mg/Kg, sc). Another group received vehicle. Animals were sacrificed at first, second, and third months of age, tissues were extracted and processed for immunoblot to detect (P)RR, PLZF, β-catenin, DVL-1, and PKCα. (P)RR and PLZF were also measured by RT-PCR., Results: We found that offspring developed hypertension. Male descendants remained hypertensive throughout the whole experiment. Female animals tended to recover at second month and returned to normal blood pressure at third month. HRP treatment diminished hypertension in both male and female animals. Morphological evaluations showed changes in heart, aorta, and kidney weight, and HRP reverted this effect. Finally, we found that (P)RR, PLZF, and canonical WNT transduction pathway molecules were stimulated by PE, and HRP treatment abolished this increase., Conclusion: These findings suggest that PE can induce hypertension in offspring, and (P)RR seems to play an important role through the canonical WNT pathway and that gender seems to influence this response., Competing Interests: The authors declare that there are no conflicts of interest.

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway is mainly responsible for the activation and release of a cascade of proinflammatory mediators that contribute to the development of hepatic diseases. During alcoholic liver disease development, the NLRP3 inflammasome pathway contributes to the maturation of caspase-1, interleukin (IL)-1β, and IL-18, which induce a robust inflammatory response, leading to fibrosis by inducing profibrogenic hepatic stellate cell (HSC) activation. Substantial evidence demonstrates that nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) via NLRP3 inflammasome activation, ultimately leading to fibrosis and hepatocellular carcinoma (HCC). Activation of the NLRP3 inflammasome in NASH can be attributed to several factors, such as reactive oxygen species (ROS), gut dysbiosis, leaky gut, which allow triggers such as cardiolipin, cholesterol crystals, endoplasmic reticulum stress, and uric acid to reach the liver. Because inflammation triggers HSC activation, the NLRP3 inflammasome pathway performs a central function in fibrogenesis regardless of the etiology. Chronic hepatic activation of the NLRP3 inflammasome can ultimately lead to HCC; however, inflammation also plays a role in decreasing tumor growth. Some data indicate that NLRP3 inflammasome activation plays an important role in autoimmune hepatitis, but the evidence is scarce. Most researchers have reported that NLRP3 inflammasome activation is essential in liver injury induced by a variety of drugs and hepatotropic virus infection; however, few reports indicate that this pathway can play a beneficial role by inducing liver regeneration. Modulation of the NLRP3 inflammasome appears to be a suitable strategy to treat liver diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Non-alcoholic steatohepatitis (NASH) is a global public health concern that may progress into fibrosis, cirrhosis, and liver cancer, with limited curative treatment options. While the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is closely linked to NASH progression, nicotinic acid (NA), a vitamin used for the treatment of dyslipidemia, is an emerging pharmaceutical treatment for hepatic steatosis and fibrosis. Here, we investigated pharmacological effects of NA on experimental NASH and whether NLRP3 inflammasome/pyroptosis inhibition is an associated mechanism of action. Rats were fed a high-fat sucrose diet supplemented with cholesterol and a low dose of CCl 4 . NA significantly reduced inflammation by decreasing the protein levels of tumor necrosis factor-alpha and nuclear factor kappa B. Moreover, NA inhibited the formation of NLRP3- apoptosis-associated speck-like protein containing caspase recruitment domain-Caspase-1, decreasing interleukin-1beta, interleukin-18, and gasdermin D protein. In addition, NA reduced tumor growth factor-beta, alpha-smooth muscle actin, and hepatic levels of collagen-1, consequently decreasing extracellular matrix synthesis. Our results indicate that NA can inhibit NASH progression and encourage further basic and clinical studies on the use of NA for the treatment of human NASH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this work, we propose a theoretical finite element description of the ionic profiles of a general mixture of n species of spherical charged particles dissolved in an implicit solvent, with arbitrary size and charge asymmetries, neutralizing a spherical macroion. This approach aims to close the gap between the nano- and the micro-scales in macroion solutions, taking into account the ion correlations and ionic excluded volume effects consistently. When these last two features are neglected, the classical non-linear Poisson-Boltzmann theory for n ionic species-with different ionic closest approach distances to the colloidal surface-is recovered as a limit case. As a proof of concept, we study the electrical double layer of an electroneutral mixture of oppositely charged colloids and small microions, with an asymmetry 1:333 in size and 1:10 in valence, in salt-free and added salt environments. Our theoretical approach displays a good agreement regarding the ionic profiles, the integrated charge, and the mean electrostatic potential obtained from molecular dynamics simulations with explicit-sized microions. Although the non-linear Poisson-Boltzmann colloid-colloid and colloid-microion profiles differ notably from those obtained via molecular dynamics simulations with explicit small-sized ions, the associated mean electrostatic potential agrees well with the corresponding explicit microion simulations., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

While non-alcoholic fatty liver disease (NAFLD) without inflammation or fibrosis is considered a relatively 'benign' disease, non-alcoholic steatohepatitis (NASH), by contrast, is characterized by marked inflammation in addition to lipid accumulation, and may include fibrosis, progression to cirrhosis and hepatocellular carcinoma. Obesity and type II diabetes are frequently associated with NAFLD/NASH; however, a significant number of lean individuals may develop these diseases. Little attention has been paid to the causes and mechanisms contributing to NAFLD development in normal-weight individuals. One of the main causes of NAFLD in normal-weight individuals is the accumulation of visceral and muscular fat and its interaction with the liver. Myosteatosis (triglyceride accumulation in the muscle) induces a loss of muscle by reducing blood flow and insulin diffusion, contributing to NAFLD. Normal-weight patients with NAFLD exhibit higher serum markers of liver damage and C-reactive protein levels, as well as more pronounced insulin resistance, compared to healthy controls. Notably, increased levels of C-reactive protein and insulin resistance are strongly correlated with the risk of developing NAFLD/NASH. Gut dysbiosis has also been associated with NAFLD/NASH progression in normal-weight individuals. More investigation is required to elucidate the mechanisms leading to NAFLD in normal-weight individuals., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Recent declines of insect populations at high rates have resulted in the need to develop a quick method to determine their diversity and to process massive data for the identification of species of highly diverse groups. A short sequence of DNA from COI is widely used for insect identification by comparing it against sequences of known species. Repositories of sequences are available online with tools that facilitate matching of the sequences of interest to a known individual. However, the performance of these tools can differ. Here we aim to assess the accuracy in identification of insect taxonomic categories from two repositories, BOLD Systems and GenBank. This was done by comparing the sequence matches between the taxonomist identification and the suggested identification from the platforms. We used 1,160 COI sequences representing eight orders of insects from Colombia. After the comparison, we reanalyzed the results from a representative subset of the data from the subfamily Scarabaeinae (Coleoptera). Overall, BOLD systems outperformed GenBank, and the performance of both engines differed by orders and other taxonomic categories (species, genus and family). Higher rates of accurate identification were obtained at family and genus levels. The accuracy was higher in BOLD for the order Coleoptera at family level, for Coleoptera and Lepidoptera at genus and species level. Other orders performed similarly in both repositories. Moreover, the Scarabaeinae subset showed that species were correctly identified only when BOLD match percentage was above 93.4% and a total of 85% of the samples were correctly assigned to a taxonomic category. These results accentuate the great potential of the identification engines to place insects accurately into their respective taxonomic categories based on DNA barcodes and highlight the reliability of BOLD Systems for insect identification in the absence of a large reference database for a highly diverse country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Baena-Bejarano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The antioxidant effect of caffeine, associated with its ability to upregulate the nuclear factor-E2-related factor-2 (Nrf2)-signaling pathway, was explored as a possible mechanism for the attenuation of liver damage. Nonalcoholic steatohepatitis (NASH) was induced in rats by the administration of a high-fat, high-sucrose, high-cholesterol diet (HFSCD) for 15 weeks. Liver damage was induced in rats by intraperitoneal administration of thioacetamide (TAA) for six weeks. Caffeine was administered orally at a daily dose of 50 mg/kg body weight during the period of NASH induction to evaluate its ability to prevent disease development. Meanwhile, rats received TAA for three weeks, after which 50 mg/kg caffeine was administered daily for three weeks with TAA to evaluate its capacity to interfere with the progression of hepatic injury. HFSCD administration induced hepatic steatosis, decreased Nrf2 levels, increased oxidative stress, induced the activation of nuclear factor-κB (NF-κB), and elevated proinflammatory cytokine levels, leading to hepatic damage. TAA administration produced similar effects, excluding steatosis. Caffeine increased Nrf2 levels; attenuated oxidative stress markers, including malondialdehyde and 4-hydroxynonenal; restored normal, reduced glutathione levels; and reduced NF-κB activation, inflammatory cytokine levels, and damage. Our findings suggest that caffeine may be useful in the treatment of human liver diseases.

Caterpillars of the Neotropical genus Lonomia (Lepidoptera: Saturniidae) are responsible for some fatal envenomation of humans in South America inducing hemostatic disturbances in patients upon skin contact with the caterpillars' spines. Currently, only two species have been reported to cause hemorrhagic syndromes in humans: Lonomia achelous and Lonomia obliqua. However, species identifications have remained largely unchallenged despite improved knowledge of venom diversity and growing evidence that the taxonomy used over past decades misrepresents and underestimates species diversity. Here, we revisit the taxonomic diversity and distribution of Lonomia species using the most extensive dataset assembled to date, combining DNA barcodes, morphological comparisons, and geographical information. Considering new evidence for seven undescribed species as well as three newly proposed nomenclatural changes, our integrative approach leads to the recognition of 60 species, of which seven are known or strongly suspected to cause severe envenomation in humans. From a newly compiled synthesis of epidemiological data, we also examine the consequences of our results for understanding Lonomia envenomation risks and call for further investigations of other species' venom activities. This is required and necessary to improve alertness in areas at risk, and to define adequate treatment strategies for envenomed patients, including performing species identification and assessing the efficacy of anti-Lonomia serums against a broader diversity of species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 González et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction and Objectives: Administration of carbon tetrachloride (CCl 4 ), along with an hepatopathogenic diet, is widely employed as a chemical inducer to replicate human nonalcoholic steatohepatitis (NASH) in rodents; however, the role of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in this model remains unclear. We aimed to determine the relevance of NLRP3 inflammasome activation in the development of NASH induced by CCl 4 along with an hepatopathogenic diet in male Wistar rats., Materials and Methods: Animals were fed either a high fat, sucrose, and cholesterol diet (HFSCD) or a HFSCD plus intraperitoneal injections of low doses of CCl 4 (400 mg/kg) once a week for 15 weeks. Liver steatosis, inflammation, fibrosis, and NLRP3 inflammasome activation were evaluated using biochemical, histological, ultrastructural, and immunofluorescence analyses, western blotting, and immunohistochemistry., Results: Our experimental model reproduced several aspects of the human NASH pathophysiology. NLRP3 inflammasome activation was induced by the combined effect of HFSCD plus CCl 4 and significantly increased levels of both proinflammatory and profibrogenic cytokines and collagen deposition in the liver; thus, NASH severity was higher in the HFSCD+CCl 4 group than that in the HFSCD group, to which CCl 4 was not administered. Hepatic stellate cells, the most profibrogenic cells, were activated by HFSCD plus CCl 4 , as indicated by elevated levels of α-smooth muscle actin. Thus, activation of the NLRP3 inflammasome, triggered by low doses of CCl 4 , exacerbates the severity of NASH., Conclusions: Our results indicate that NLRP3 inflammasome activation plays a key role and may be an important therapeutic target for NASH treatment., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Abstract: This article describes how an unfolding case study can be used to promote the development of clinical reasoning through students' self-reported perceptions, although at the same time facilitating collaboration among providers from various specialties. An unfolding case (evolving case) provides sequential information about a patient's illness trajectory as they experience the illness and related symptomology. An unfolding case study was implemented during a college skills laboratory immersion experience for 33 nurse practitioner (NP) students who were in their final year of the NP program. Students were invited per email to complete a confidential REDCap survey after the case presentation and discussion. Twenty-three students completed the survey. More than half of the students (52%) stated the review of the unfolding case offered "significant learning value" and 78% rated the unfolding case as being "very to extremely" helpful in creating opportunities for critical thinking and engagement in clinical reasoning. Implementing unfolding case studies in NP student program curricula promotes critical thinking, clinical reasoning, and allows opportunities to engage in interprofessional collaboration., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2022 American Association of Nurse Practitioners.)

The liver performs various biochemical and molecular functions. Its location as a portal to blood arriving from the intestines makes it susceptible to several insults, leading to diverse pathologies, including alcoholic liver disease, viral infections, nonalcoholic steatohepatitis, and hepatocellular carcinoma, which are causes of death worldwide. Illuminating the molecular mechanism underlying hepatic injury will provide targets to develop new therapeutic strategies to fight liver maladies. In this regard, reactive oxygen species (ROS) are well-recognized mediators of liver damage. ROS induce nuclear factor-κB and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 inflammasome, which are the main proinflammatory signaling pathways that upregulate several proinflammatory and profibrogenic mediators. Additionally, oxygen-derived free radicals induce hepatic stellate cell activation to produce exacerbated quantities of extracellular matrix proteins, leading to fibrosis, cirrhosis and eventually hepatocellular carcinoma. Exogenous and endogenous antioxidants counteract the harmful effects of ROS, preventing liver necroinflammation and fibrogenesis. Therefore, several researchers have demonstrated that the administration of antioxidants, mainly derived from plants, affords beneficial effects on the liver. Notably, nuclear factor-E2-related factor-2 (Nrf2) is a major factor against oxidative stress in the liver. Increasing evidence has demonstrated that Nrf2 plays an important role in liver necroinflammation and fibrogenesis via the induction of antioxidant response element genes. The use of Nrf2 inducers seems to be an interesting approach to prevent/attenuate hepatic disorders, particularly under conditions where ROS play a causative role., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Bocconia arborea S. Watson (Papaveraceae) is known as "palo llora sangre" and is used in Mexican traditional medicine for the treatment of infections, it is also used as anxiolytic, analgesic, and antidiabetic, among others., Aim of the Study: to evaluate the antinociceptive and gastroprotective activities of extracts from B. arborea and dihydrosanguinarine (DHS) in murine models., Materials and Methods: Organic extracts [hexane (HEX), dichloromethane (DCM) and methanol (MeOH)] were obtained by maceration. DHS was isolated and purified from HEX and DCM by precipitation and chromatographic column, respectively. Organic extracts and DHS were evaluated to determine their antinociceptive effect using formalin test in murine model. Also, the ambulatory effect of the HEX and DHS was determined in Open field test. The possible mechanism of action of DHS was explored in the presence of naltrexone (NTX, 1 mg/kg, i.p.), and picrotoxin (PTX, 1 mg/kg, i.p.). Gastric damage as possible adverse effect or gastroprotection were also investigated. Whereas DHS acute toxicological study was done, and 100 mg/kg of DHS was examined by electroencephalographic (EEG) analysis to discard neurotoxic effects., Results: The B. arborea extracts significantly showed effects in both neurogenic and inflammatory phases of the formalin test, where the HEX extract reached the major antinociceptive effect. A significant and dose-response (10, 30, and 100 mg/kg) antinociceptive activity was observed with the HEX (ED 50  = 69 mg/kg) and DHS (ED 50  = 85 mg/kg) resembling the effect of the reference analgesic drug tramadol (30 mg/kg). The significant effect of DHS was inhibited in the presence of NTX and PTX. Neither the extracts or DHS produced sedative effects or gastric damage per se at antinociceptive doses. The EEG analysis demonstrated central depressant activity but not sedative or neurotoxic effects at the highest antinociceptive dosage tested, and LD 50 is higher than 2000 mg/kg., Conclusions: HEX, DCM, and MeOH extracts showed significant antinociceptive activity, and DHS was identified as one of bioactive compounds without producing sedative, neurotoxic or gastric damage effects, as possible adverse effects reported for analgesic drugs. A role of opioid and GABA A neurotransmission appears to be involved as mechanisms of action of DHS, suggesting its potential for pain therapy and reinforcing the traditional use of B. arborea., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl 4 . Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl 4 and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl 4 -treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.

Background: Bacterial infections are responsible of high economic losses in aquaculture. Mexican golden trout (Oncorhynchus chrysogaster) is a threatened native trout species that has been introduced in aquaculture both for species conservation and breeding for production and for which no studies of bacterial infections have been reported., Case Presentation: Fish from juvenile stages of Mexican golden trout showed an infectious outbreak in a farm in co-culture with rainbow trout (Oncorhynchus mykiss), showing external puntiform red lesions around the mouth and caudal pedunculus resembling furuncles by Aeromonas spp. and causing an accumulated mortality of 91%. Isolation and molecular identification of bacteria from lesions and internal organs showed the presence of Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator isolated from a single individual. All bacterial isolates were resistant to amoxicillin-clavulanic acid and cefazoline. P. shigelloides was resistant to third generation β-lactamics., Conclusions: This is the first report of coinfection by Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator in an individual of Mexican golden trout in co-culture with rainbow trout. Resistance to β-lactams suggests the acquisition of genetic determinants from water contamination by human- or livestock-associated activities., (© 2022. The Author(s).)

Introduction and Objectives: Caffeine consumption is associated with beneficial effects on hepatic disorders. The objectives of this study were to evaluate the antifibrotic effects of caffeine on experimental nonalcoholic steatohepatitis (NASH) induced with a high-fat, high-sucrose, high-cholesterol diet (HFSCD), as well as to evaluate the ability of caffeine to prevent the progression of experimental liver fibrosis induced by the administration of thioacetamide (TAA) in rats and explore the mechanisms of action., Methods: NASH and fibrosis were induced in rats by the administration of an HFSCD for 15 weeks, and liver fibrosis was induced by intraperitoneal administration of 200 mg/kg TAA 3 times per week, for 6 weeks. Caffeine was administered at a dose of 50 mg/kg body weight. The effects of diet, TAA, and caffeine on fibrosis were evaluated by biochemical and histological examinations. The profibrotic pathways were analyzed by western blotting and immunohistochemistry., Results: Rats exhibited liver fibrosis after HFSCD feeding and the administration of TAA. Caffeine could reduce the hepatic level of collagen and the fibrotic area in the liver. Caffeine prevented the progression of liver fibrosis by decreasing transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (α-SMA) expression and by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and Smad3 phosphorylation., Conclusions: Caffeine attenuates NASH and the progression of liver fibrosis due to its antifibrotic effects and modulating the MAPK and TGF-β pathways. Therefore, caffeine could be a suitable candidate for treating liver diseases associated with fibrosis., Competing Interests: Conflicts of interest None, (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)