The interglenoid tubercle of the atlas is ancestral to lissamphibians.

Lissamphibians, represented today by frogs, salamanders, and caecilians, diverged deep in the tetrapod tree of life. Extensive morphological adaptations to disparate lifestyles have made linking extant lissamphibians to one another and to their extinct relatives difficult and controversial. However, the discovery of a feature on the atlas of the frog Xenopus laevis, may add to the small set of osteological traits that unite lissamphibians. In this study, we combine our observations of atlas development in X. laevis with a deep examination of atlantal interglenoid tubercle (TI) occurrence in fossil taxa. The TI is shown herein to occur transiently on the ossifying atlas of roughly one-third of X. laevis tadpoles but is absent in adults of this species. In ancestral character state estimations (ACSE), within the evolutionary context of lissamphibians as dissorophoid temnospondyls, this feature is found to be ancestrally shared among lissamphibians, its presence is uncertain in stem batrachians, and then the TI is lost in extant caecilians and frogs. However, our data suggests apparent TI loss around the origin of frogs may be explained by its ontogenetically transient nature. The only nonamphibian tetrapods with a TI are "microsaurs," and this similarity is interpreted as one of many convergences that resulted from convergent evolutionary processes that occurred in the evolution of "microsaurs" and lissamphibians. The TI is thus interpreted to be ancestral to lissamphibians as it is found to be present in some form throughout each extant lissamphibian clade's history.

Liver transplantation for pediatric genetic and metabolic disorders.

Pediatric genetic and metabolic liver diseases comprise a broad spectrum of conditions and represent the second most common indication for liver transplantation following biliary atresia. The decision to transplant can be challenging and requires consideration of several factors including hepatic involvement, extra-hepatic manifestations, and anticipated post-transplant outcomes. This review examines pediatric genetic and metabolic liver diseases, their pathophysiology, clinical presentation, and the role of liver transplantation.

Primary hyperoxaluria: Long-term outcomes of isolated kidney versus simultaneous liver/kidney transplant.

OBJECTIVES: To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH). METHODS: The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models. RESULTS: We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness. CONCLUSIONS: Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Clinical Implications for Children Developing Direct Hyperbilirubinemia on Extracorporeal Membrane Oxygenation.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO)-associated direct hyperbilirubinemia (DHB) is likely multifactorial. The objective of this study is to assess the frequency and risk factors for developing direct hyperbilirubinemia while on ECMO, and its implication on the mortality of children. METHODS: We performed a retrospective study between January 2010 and January 2020. Using Mayo Clinic electronic health record, we identified children (<18 years) who required veno-arterial (VA) ECMO support. Demographics, ECMO indication, laboratory findings, and outcomes were abstracted. Illness acuity scores, including vasoactive-ionotropic score (VIS), were used to assess disease severity at time of admission. Study cohort was divided into two groups: children who developed direct hyperbilirubinemia (DHB) on ECMO and children who did not (control). DHB was defined as direct bilirubin (DB) of >1.0 mg/dL. Disease acuity and mortality rates were compared between the two groups. Logistic regression was used to analyze the risk of mortality independent of potential confounding variables. RESULTS: We identified 106 children who required ECMO support during the study period. Of those, 36 (34%) children developed DHB on ECMO. Illness acuity scores were significantly higher in the DHB group on ECMO day 2 (P = 0.046) and day 7 (P = 0.01). Mortality rate was higher in the DHB group 72%, versus 29% in the control group (P < 0.001). CONCLUSION: DHB was associated with a higher mortality rate than the control group.

The inhibitory mechanisms of losartan and vitamin D on amiodarone-induced lung inflammation in rats: Role of mitogen-activated protein kinases/activator protein-1.

Amiodarone (AMD), an antiarrhythmic drug, is used cautiously due to its lung toxicity that is characterized by alveolar inflammation followed by fatal fibrosis. AMD induces lung inflammation via increasing the alveolar macrophages and disturbing the balance of T-helper-1 (Th1) and Th2 cells cytokines. In this study, the role of the mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway in AMD-induced lung inflammation was evaluated. Also, the anti-inflammatory and antifibrotic effects of losartan and/or vitamin D were investigated following 7, 14, and 28 days of AMD administration. AMD resulted in lung injury, inflammatory infiltration, and increased pulmonary levels of inflammatory cytokines starting from Week 1 of exposure. A significant increase in serum levels of interleukin-4 along with a significant reduction of interferon-gamma, in addition to strong expression of CD68, were reported after 14 and 28 days of AMD administration reflecting Th1/Th2 cytokines imbalance and the accumulation of alveolar macrophages, respectively. The phosphorylation of MAPKs (ERK1/2, JNK, p38) and AP-1 was significantly enhanced starting from Week 1 of exposure. Marked expression of transforming growth factor beta-1 and massive deposition of collagen were detected after 28 days reflecting late fibrosis. All these abnormalities were significantly mitigated by vitamin D and its combination with losartan. Losartan alone has less prominent anti-inflammatory effects particularly after 28 days; however, it efficiently prevented late fibrosis. This study concludes that MAPKs/AP-1 pathway is involved in AMD-induced lung inflammation and that vitamin D and/or losartan could be used as a prophylactic agent to prevent AMD-induced lung toxicity.

It takes a village: primary care of the pediatric liver transplant recipient.

PURPOSE OF REVIEW: Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. RECENT FINDINGS: Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. SUMMARY: Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.

Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV infected patients.

Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma (HCC). Although the early diagnosis of HCC is vital for successful curative treatment, the majority of lesions are diagnosed in an irredeemable phase. This work deals with a comparative ultrastructural study of experimentally gradually induced HCC, surgically resected HCC, and potential premalignant lesions from HCV-infected patients, with the prospect to detect cellular criteria denoting premalignant transformation. Among the main detected pathological changes which are postulated to precede frank HCC: failure of normal hepatocyte regeneration with star shape clonal fragmentation, frequent elucidation of hepatic progenitor cells and Hering canals, hepatocytes of different electron density loaded with small sized rounded monotonous mitochondria, increase junctional complexes bordering bile canaliculi and in between hepatocyte membranes, abundant cellular proteinaceous material with hypertrophied or vesiculated rough endoplasmic reticulum (RER), sequestrated nucleus with proteinaceous granular material or hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro-vesicular fat deposition. In conclusion, the present work has visualized new hepatocytic division or regenerative process that mimic splitting or clonal fragmentation that occurs in primitive creature. Also, new observations that may be of value or assist in predicting HCC and identifying the appropriate patient for surveillance have been reported. Moreover, it has pointed to the possible malignant potentiality of liver stem/progenitor cells. For reliability, the results can be subjected to cohort longitudinal study.

Comparison of Microbial Communities Associated with Halophyte (Salsola stocksii) and Non-Halophyte (Triticum aestivum) Using Culture-Independent Approaches.

Halophyte microbiome contributes significantly to plant performance and can provide information regarding complex ecological processes involved in osmoregulation of these plants. The objective of this study is to investigate the microbiomes associated with belowground (rhizosphere), internal (endosphere) and aboveground (phyllosphere) tissues of halophyte (Salsola stocksii) through metagenomics approach. Plant samples were collected from Khewra Salt Mines. The metagenomic DNA from soil, root and shoot samples was isolated with the help of FastDNA spin kit. Through PCR, the 16S rRNA gene from four different Salsola plants and wheat plants was amplified and cloned in InsTAclone PCR cloning kit. Metagenomic analyses from rhizosphere, endosphere and phyllosphere of Salsola showed that approximately 29% bacteria were uncultured and unclassified. Proteobacteria and Actinobacteria were the most abundant phyla in Salsola and wheat. However, Firmicutes, Acidobacteria, Bacteriodetes, Planctomycetes, Cyanobacteria, Thermotogae, Verrucomicrobia, Choroflexi and Euryarchaeota were predominant groups from halophyte whereas Actinobacteria, Proteobacteria, Firmicutes, Cyanobacteria, Acidobacteria, Bacteriodetes, Planctomycetes and Verrucomicrobia were predominant phyla of wheat samples. Diversity and differences of microbial flora of Salsola and wheat suggested that functional interactions between plants and microorganisms contribute to salt stress tolerance.

Repurposing Phytochemicals against Breast Cancer (MCF-7) using Classical Structure-Based Drug Design.

BACKGROUND: The significant public health effect of breast cancer is demonstrated by its high global prevalence and the potential for severe health consequences. The suppression of the proliferative effects facilitated by the estrogen receptor alpha (ERα) in the MCF-7 cell line is significant for breast cancer therapy. OBJECTIVE: The current work involves in-silico techniques for identifying potential inhibitors of ERα. METHODS: The method combines QSAR models based on machine learning with molecular docking to identify potential binders for the ERα. Further, molecular dynamics simulation studied the stability of the complexes, and ADMET analysis validated the compound's properties. RESULT: Two compounds (162412 and 443440) showed significant binding affinities with ERα, with binding energies comparable to the established binder RL4. The ADMET qualities showed advantageous characteristics resembling pharmaceutical drugs. The stable binding of these ligands in the active region of ERα during dynamic conditions was confirmed by molecular dynamics simulations. RMSD plots and conformational stability supported the ligands' persistent occupancy in the protein's binding site. After simulation, two hydrogen bonds were found within the protein-ligand complexes of 162412 and 443440, with binding free energy values of -27.32 kcal/mol and -25.00 kcal/mol. CONCLUSION: The study suggests that compounds 162412 and 443440 could be useful for developing innovative anti-ERα medicines. However, more research is needed to prove the compounds' breast cancer treatment efficacy. This will help develop new treatments for ERα-associated breast cancer.

Does local vaginal estrogen after tension-free transobturator vaginal tape reduce overactive bladder symptoms in postmenopausal women? A prospective randomized, controlled study.

Objective: We aimed to evaluate the efficacy of topical estrogen after transvaginal tension-free vaginal tape-obturator (TVT-O) in the treatment of de novo overactive bladder symptoms that appear after surgery. Methods: This is a prospective randomized controlled study performed in the Urology and Gynecology Departments, Kasr Al Ainy Hospital, Cairo University, Cairo, Egypt. Two hundred and ten postmenopausal females presenting during the period between January 2017 and November 2020 with stress urinary incontinence were included in the study. Patients were divided into two groups, 105 patients in Group A (treatment group) and 105 patients in Group B (control group). Patients in Group A underwent transvaginal TVT-O followed by local vaginal estrogen treatment for 6 months, while patients in Group B underwent transvaginal TVT-O only. The study included any postmenopausal female with urodynamic stress urinary incontinence. All patients had to fulfill a 3-day bladder diary, overactive bladder symptoms score, urine analysis, urodynamic study, and post-voiding residual urine measurement by abdominal ultrasound preoperatively and at 3-month and 6-month follow-ups. Results: At 6-month follow-up, daytime frequency was reduced to 8% in Group A (increased to 21% in Group B) with a statistically significant difference between both groups (p=0.009). At 6-month follow-up, nocturia was 8% in Group A (11% in Group B) with no statistically significant difference between both groups (p=0.469). There was a statistically significant difference between both groups as regards to urinary urgency at 6-month follow-up (p=0.024). There was a statistically significant difference in postoperative wound healing events as regards to cure, hyperemia, gapping, and wound infection 1 week after intervention between both groups (p=0.008). No local or systemic side-effects were reported from local estrogen use. Conclusion: Local vaginal estrogen treatment given to postmenopausal patients after midurethral sling procedures can reduce the symptoms of daytime frequency and urinary urgency. Long-term follow-up is needed.

Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights.

Cancer remains a formidable global health challenge, with current treatment modalities such as chemotherapy, radiotherapy, surgery, and targeted therapy often hindered by low efficacy and adverse side effects. The indole scaffold, a prominent heterocyclic structure, has emerged as a promising candidate in the fight against cancer. This review consolidates recent advancements in developing natural and synthetic indolyl analogs, highlighting their antiproliferative activities against various cancer types over the past five years. These analogs are categorized based on their efficacy against common cancer types, supported by biochemical assays demonstrating their antiproliferative properties. In this review, emphasis is placed on elucidating the mechanisms of action of these compounds. Given the limitations of conventional cancer therapies, developing targeted therapeutics with enhanced selectivity and reduced side effects remains a critical focus in oncological research.

Cardiometabolic Risk Markers in Children With Obesity and Variants in MC4R Pathway-related Genes.

Context: Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective: We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods: A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results: Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion: Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels.

Granulomatous Mastitis With Breast Abscess Caused by Salmonella.

Granulomatous mastitis (GM) is a rare disease that occurs in young premenopausal women, is mostly idiopathic, and is less likely to be caused by infection and trauma. It is also strongly associated with pregnancy, lactation, and hyperprolactinemia. GM superimposed by infection with abscess formation caused by Salmonella is extremely rare. Upon reviewing the literature, our case is considered to be the first reported case globally. Most breast abscesses are caused by Staphylococcus aureus.

Clarifying solvent effect during photocatalytic glycerol conversion on TiO2/GQD as selective photocatalyst.

Nowadays, dealing with the growing chemical and energy demands is important without compromising the environment. So, this work studies photocatalytic glycerol conversion (as biomass derivativ feedstock) into value-added products using an eco-friendly synthesized catalyst. Graphene quantum dots (GQDs) were prepared from available/cheap precursors like glucose via the hydrothermal method and used as a support for TiO2. TiO2/GQDs were characterized via different analytical techniques, revealing very small particle sizes of ~ 3-6 nm with a large surface area of ~ 253 m2/g and a band gap of ~ 2.6 eV. The prepared photocatalyst shows good efficiency during photocatalytic glycerol conversion to dihydroxyacetone (DHA). Different reaction conditions were tested: reaction time, catalyst amount, presence of oxidant (H2O2), and biphasic media (aqueous/organic phases). Comparing a monophasic (H2O) photoreactor with a biphasic reactor containing 90% organic phase (ethyl acetate) and 10% aqueous phase (H2O and/or H2O2) indicates that the presence of H2O2 increases glycerol conversion and liquid selectivity to reach 57% and 91%, respectively after 120 min. However, it still suffers a low DHA/GA ratio (2.7). On the other hand, using a biphasic reactor in the presence of an H2O2 oxidant increases the DHA/GA ratio to ~ 6.6, which was not reached in previous research. The formation of H2O/H2O2 as micro-reactors dispersed in the ethyl acetate phase increased the average light intensity effect of the glycerol/photocatalyst system in the micro-reactors. Unlike previous work, this work presents a facile way to prepare eco-friendly/cheap (noble metal free) photocatalysts for glycerol conversion to ultrapure DHA using a biphasic photoreactor.

Overview of Progressive Familial Intrahepatic Cholestasis.

Bile acid transport is a complex physiologic process, of which disruption at any step can lead to progressive intrahepatic cholestasis (PFIC). The first described PFIC disorders were originally named as such before identification of a genetic cause. However, advances in clinical molecular genetics have led to the identification of additional disorders that can cause these monogenic inherited cholestasis syndromes, and they are now increasingly referred to by the affected protein causing disease. The list of PFIC disorders is expected to grow as more causative genes are discovered. Here forth, we present a comprehensive overview of known PFIC disorders.

Evaluation of MMR live attenuated vaccine oncolytic potential using Ehrlich ascites carcinoma in a murine model.

MMR vaccine is a common vaccine that contains oncolytic viruses (Measles, Mumps, and Rubella) and could be used as a potential anti-cancer treatment. In this study, we assessed the anti-tumor activity of the MMR vaccine against Ehrlich ascites carcinoma (EAC) solid tumor induced in mice. The in vitro assay showed that vaccine IC50 in EAC was approximately 200 CCID50. The vaccine was intratumorally administrated twice weekly in EAC-bearing mice. The antitumor response of the vaccine was measured by tumor growth, survival rate, histopathologic examination, flow cytometry analysis, and body biochemical parameters. The MMR vaccine demonstrated a substantial reduction of tumor growth and prolongation of life span as well. The proliferation marker was significantly lower in the vaccine-treated group. Moreover, the apoptosis key parameter Casp-3 was also higher in the vaccine-treated group. The vaccine somewhat restored the deterioration of the biochemical parameters (LDH, GOT, GPT, MDA, NO, and PON-1) in the tumor-bearing mice. Finally, this study indicated the potential antitumor effect of MMR vaccine via anti­proliferative, apoptotic activities, and modulating the antioxidant parameters. This study opens a new field of inquiry for future research on the vaccine's anti-cancer properties.