Search

Abstract: Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM)., Objectives: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM., Methods: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed., Results: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively., Conclusions: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Little is known about the long-term course of polymorphic light eruption (PLE). Objective: To predict disease course, a questionnaire was sent to patients whose PLE had been diagnosed between March 1990 and December 2018 and documented in the Austrian Cooperative Registry for Photodermatoses. Methods: In January 2019, 205 PLE patients were contacted by mail and asked to complete a questionnaire on their disease course, including whether the skin's sun sensitivity had normalized (i.e., PLE symptoms had disappeared), improved, stayed the same, or worsened over time. Patients who reported normalization of sun sensitivity were asked to report when it had occurred. Results: Ninety-seven patients (79 females, 18 males) returned a completed questionnaire. The mean (range) duration of follow-up from PLE onset was 29.6 (17-54) years for females and 29.4 (16-47) years for males. The disease disappeared in 32 (41%) females after 17.4 (2-41) years and in 4 (24%) males after 11.8 (5-26) years. Twenty-nine (37%) females and 6 (35%) males reported improvement of symptoms over time; 15 females (19%) and 7 males (41%) reported no change; and 3 females (4%) and no males reported worsening of symptoms. Kaplan-Meier analysis revealed that after 20 years 74% (95%CI, 64-82%) of patients still suffered from PLE. PLE lesion persistence (>1 week) tended to predict a prolonged course of PLE. Conclusions: PLE usually takes a long-term course over many years though in most patients its symptoms improve or disappear over time. How improvement relates to the pathophysiology of the disease remains to be determined., 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 © 2021 Gruber-Wackernagel, Schug, Graier, Legat, Rinner, Hofer, Quehenberger and Wolf.)

Competing Interests: None declared.

In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS ( p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly ( p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations ( SRSF2 / ASXL1 / RUNX1 profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background., Competing Interests: Competing Interests: Hanneke C. Kluin-Nelemans: institutional financial support from Novartis; honoraria from Novartis for participating in e-learning program. Andreas Reiter: Novartis Pharma - research support, advisory board, honoraria, travel reimbursement, Blueprint Medicines - advisory board, honoraria, travel reimbursement, Deciphera - advisory board, travel reimbursement. Bjorn van Anrooij: financial support from Novartis for research and advisory boards. Jason Gotlib: Funding to support conduct of clinical trial: Blueprint Medicines, Deciphera; advisory board/honoraria: Blueprint Medicines, Deciphera, Allakos. Karin Hartmann: advisory board/honoraria: Allergopharma, ALK-Abelló, Blueprint, Deciphera, Menarini, Novartis and Takeda; research grant: Euroimmun. Hanneke Oude Elberink: honoraria from ALK-Abelló, Chiesi, MEDA Pharma, Novartis, and Blueprint. Magdalena Lange: honoraria from Novartis for lectures. Chiara Elena: advisory board Novartis, Pfizer. David Fuchs, Julien Rossignol: advisory board Novartis. Khalid Shoumariyeh: travel support from Abbvie and consultancy fees from Novartis. Nikolas von Bubnoff: institutional financial support from Novartis. Massimo Triggiani: advisory board BluePrint Medicines, Deciphera, Novartis. Akif SelimYavuz: honoraria from Novartis. Jens Panse: funding to support conduct of clinical trial: Blueprint Medicines, Deciphera; advisory board/honoraria: Blueprint Medicines, Novartis. Vito Sabato: advisory board/honoraria: Blueprint Medicines, Novartis. Madlen Jentzsch: honoraria from Novartis. Olivier Hermine: Research funding support from AB science and Novartis. Advisory board of AB science. Wolfgang R. Sperr: honoraria from Novartis, Pfizer, AbbVie, Daiichi Sankyo, Amgen, Thermo Fisher, Deciphera, Incyte, Celgene and Jazz. Michel Arock: advisory board/honoraria Blueprint Medicines, Deciphera. All other authors: none., (© The author(s).)

Environmental exposures have a significant influence on the chronic health conditions plaguing children and adults. Although the Developmental Origins of Health and Disease (DOHaD) paradigm historically has focused on nutrition, an expanding body of research specifically communicates the effects of chemical exposures on early-life development and the propagation of non-communicable disease across the lifespan. This paper provides an overview of 20 years of research efforts aimed at identifying critical windows of susceptibility to environmental exposures and the signaling changes and epigenetic influences associated with disease progression. DOHaD grants funded by the National Institute of Environmental Health Sciences (NIEHS) in 1991, 2001 and 2011 are identified by grant-analysis software, and each portfolio is analyzed for exposures, disease endpoints, windows of exposure, study design and impact on the field based on publication data. Results show that the 1991 and 2001 portfolios comprised metals, PCBs and air pollutants; however, by 2011, the portfolio has evolved to include or expand the variety of endocrine disruptors, pesticides/persistent organic pollutants and metals. An assortment of brain-health endpoints is most targeted across the portfolios, whereas reproduction and cancer increase steadily over the same time period, and new endpoints like obesity are introduced by 2011. With mounting evidence connecting early-life exposures to later-life disease, we conclude that it is critical to expand the original DOHaD concept to include environmental chemical exposures, and to continue a research agenda that emphasizes defining sensitive windows of exposure and the mechanisms that cause disease. [ABSTRACT FROM PUBLISHER]

Identifying chemicals, beyond those already implicated, to test for potential endocrine disruption is a challenge and high throughput approaches have emerged as a potential tool for this type of screening. This review focused the Environmental Protection Agency's (EPA) ToxCast(TM) high throughput in vitro screening (HTS) program. Utility for identifying compounds was assessed and reviewed by using it to run the recently expanded chemical library (from 309 compounds to 1858) through the ToxPi(TM) prioritization scheme for endocrine disruption. The analysis included metabolic and neuroendocrine targets. This investigative approach simultaneously assessed the utility of ToxCast, and helped identify novel chemicals which may have endocrine activity. Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast.

Emerging contaminants (ECs) of significant concern are widely distributed throughout the environment due to various industrial practices and human activities. Given the alarming ecological threats and potential risks that ECs pose to human health and aquatic life, even at trace concentrations, it is imperative to develop innovative technologies to effectively address these challenges. The biophotoelectrochemistry (BPEC) system, which integrates microbial cells with photosensitizers for solar-to-chemical conversion, holds great potential as an efficient strategy for the removal of ECs. In this review, we provide new insights into the BPEC system for the ECs treatment by systematically summarizing the classification, sources, and environmental occurrence of ECs. Additionally, we explore the research progress and degradation mechanisms in ECs removal with BPEC. Finally, the current challenges and future perspectives for the applications of the BPEC system in the ECs treatment are analyzed. This review aims to promote the development of BPEC technology for ECs treatment, offering a promising prospect for environmental remediation, circular economy, and clean-energy production. [ABSTRACT FROM AUTHOR]

The article examines how outdated testing and static risk management in the U.S. delay the protection of human health, despite advancements in scientific knowledge. Topics discussed include the need for updated, sensitive testing methods, the importance of class-based regulation, and the challenge of evaluating chronic disease impacts from chemical exposures.

Objective: To document the successful surgical reconstruction of a composite nasomaxillary and superior labial defect using a fascia lata graft, titanium mesh and angularis oris axial pattern flap in a dog. Case summary: An estimated 2-year-old female intact mixed-breed dog was presented with a composite (hard and soft tissue) nasomaxillary defect, suspected to be caused by a chemical burn. Physical examination revealed nasal discharge, exposed bilateral maxilla and nasal bone, nasomaxillary fistula with air movement, and intrinsic discoloration of the left maxillary canine tooth. The soft tissue lesion extended from the nasal planum rostrally to the medial canthus of the left eye distally and from the right maxillary bone to include a full thickness loss of the left maxillary labium laterally. Computed tomographic images of the head showed chronic osteomyelitis of the maxilla, zygomatic and nasal bones with nasomaxillary fistula and numerous exposed roots of the left maxillary premolars. Staged surgical procedures to address the dentition and nasomaxillary defect were planned. The first procedure consisted of the extraction of periodontally compromised left maxillary premolars, and standard root canal therapy of bilateral maxillary canine teeth. The second procedure consisted of debridement of the non-vital soft and hard tissues and surgical reconstruction of the nasomaxillary defect after virtual surgical planning. Head computed tomography performed 5 months post-operatively revealed a decrease in the size of the osseous defect as well as the resolution of rhinitis. Clinical relevance: This case demonstrates the feasibility of using a combination of soft tissue graft, titanium mesh, and axial pattern flap in managing nasomaxillary defects. Such defects can lead to chronic rhinitis, infection, discomfort, and long-term morbidity. This case report provides a novel but practical approach for managing defects in the nasomaxillary region in dogs. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with homeostatic processes. They are a major concern for public health, and they can cause adverse long-term effects such as cancer, intellectual impairment, obesity, diabetes, and male infertility. The endocrine system is a complex machinery, with the estrogen (E), androgen (A), and thyroid hormone (T) modes of action being of major importance. In this context, the availability of in silico models for the rapid detection of hazardous chemicals is an effective contribution to toxicological assessments. We developed Qualitative Gene expression Activity Relationship (QGexAR) models to predict the propensities of chemically induced disruption of EAT modalities. We gathered gene expression profiles from the LINCS database tested on two cell lines, i.e., MCF7 (breast cancer) and A549 (adenocarcinomic human alveolar basal epithelial). We optimized our prediction protocol by testing different feature selection methods and classification algorithms, including CATBoost, XGBoost, Random Forest, SVM, Logistic regression, AutoKeras, TPOT, and deep learning models. For each EAT endpoint, the final prediction was made according to a consensus prediction as a function of the best model obtained for each cell line. With the available data, we were able to develop a predictive model for estrogen receptor and androgen receptor binding and thyroid hormone receptor antagonistic effects with a consensus balanced accuracy on a validation set ranging from 0.725 to 0.840. The importance of each predictive feature was further assessed to identify known genes and suggest new genes potentially involved in the mechanisms of action of EAT perturbation. [ABSTRACT FROM AUTHOR]

Background: The Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA) was a collaborative research effort to better link academic research with governmental guideline studies. This review explores the secondary goal of CLARITY-BPA: to identify endpoints or technologies from CLARITY-BPA and prior/concurrent literature from these laboratories that may enhance the capacity of rodent toxicity studies to detect endocrine disrupting chemicals (EDCs)., Methods: A systematic literature search was conducted with search terms for BPA and the CLARITY-BPA participants. Relevant studies employed a laboratory rodent model and reported results on 1 of the 10 organs/organ systems evaluated in CLARITY-BPA (brain and behavior, cardiac, immune, mammary gland, ovary, penile function, prostate gland and urethra, testis and epididymis, thyroid hormone and metabolism, and uterus). Study design and findings were summarized, and a risk-of-bias assessment was conducted., Results: Several endpoints and methods were identified as potentially helpful to detect effects of EDCs. For example, molecular and quantitative morphological approaches were sensitive in detecting alterations in early postnatal development of the brain, ovary, and mammary glands. Hormone challenge studies mimicking human aging reported increased susceptibility of the prostate to disease following developmental BPA exposure. Statistical analyses for nonmonotonic dose responses, and computational approaches assessing multiple treatment-related outcomes concurrently in linked hormone-sensitive organ systems, reported effects at low BPA doses., Conclusions: This review provided an opportunity to evaluate the unique insights provided by nontraditional assessments in CLARITY-BPA to identify technologies and endpoints to enhance detection of EDCs in future studies., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Copyright of Journal of Pharmaceutical Practice & Service is the property of Journal of Pharmaceutical Practice Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Pharmaceutical Practice & Service is the property of Journal of Pharmaceutical Practice Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

HELLP syndrome is a hemolysis syndrome with microangiopathic blood smears, increased liver enzymes, and low platelets in pregnant and postpartum patients. HELLP syndrome may be a complication or progression of severe preeclampsia. The death rate due to HELLP syndrome is relatively high. The use of corticosteroids is expected to increase platelet counts, reduce LDH values, and reduce liver function parameters to speed up the duration of healing and reduce mortality. Corticosteroids inhibit endothelial activation, reduce vascular endothelial injury, increase hepatic blood flow, prevent thrombotic microvascular hemolysis, and reduce platelet consumption. Objective: To evaluate the effectiveness of corticosteroids in patients with HELLP syndrome. Method: This research was conducted using a literature review method by searching articles from Google Scholar, PubMed, and Science Direct. Results: Administration of corticosteroids can increase platelet counts, reduce AST/ALT values, and reduce the need for blood product transfusions. Conclusion: Corticosteroids effectively increase platelet counts in patients with HELLP syndrome. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) may mimic the endogenous neuroendocrine and endocrine messengers and interfere with developmental, reproductive, immune, metabolic and other physiological functions. Modulation of basal metabolic rate, energy metabolism, food intake and engorgement by endocrine disruptors may lead to loss of metabolic equilibrium. EDC-induced loss of metabolic homeostasis and obesity gave rise to the concept of metabolic-disrupting chemicals (MDC) and environmental obesogens. Elevated oxidative stress, alterations in the circadian clock, and energy-sensing homeostasis are some of the major pathophysiological conditions implicated in promoting metabolic disruption. Reportedly, fish are the most vulnerable candidate due to their direct exposure to metabolic disruptors in aquatic habitats. Though limited, studies conducted using piscine models have helped to identify MDCs in the aquatic environment. Notably, the molecular mechanisms through which MDCs can negatively influence the metabolism of hormones, epigenetic alteration, gut dysbiosis, and changes in endocrine and metabolic receptor expression and functions have recently gained considerable attention. In this review, we provide an update on the impact of MDCs on the initiators, cellular mediators, and hormone receptors related to the maintenance of metabolic homeostasis, with particular emphasis on fish models. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shanghai Ocean University is the property of Editorial Department of Journal of Shanghai Ocean University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article explores the role of glucose-6-phosphate dehydrogenase (G6PD) in various diseases, including neurodegenerative disorders, tumor development, viral infections, and gene expression changes in cancer. It discusses how both hyperactivation and inactivation of G6PD can lead to metabolic imbalances and the occurrence of diseases. The article also highlights the impact of endocrine-disrupting chemicals (EDCs) on the expression and activity of G6PD, which can lead to metabolic and cardiovascular disorders, particularly in individuals with G6PD deficiency. It provides insights into the regulation of G6PD enzyme activity and expression, as well as potential therapeutic strategies for related diseases. [Extracted from the article]

Introduction: The treatment of complex fractures with miniplates is often difficult and unsatisfactory. Such fractures include extremely atrophic mandibles, discontinuity defects, and marked comminuted fractures., Aim: With this paper we want to call to mind once more that titanium mesh is useful for the treatment of such fractures and its use can reduce the number of complications., Patients: Between January 1996 and December 1998 we treated with titanium mesh 17 patients with fractures of extremely atrophic mandibles, mandibular discontinuity defects or comminuted fractures., Results: Union occurred without complication in 70% of fractures treated with titanium mesh. In 20% there were minor complications such as postoperative haematoma. In only one case did infection occur, a more severe complication., Conclusion: Because of its geometry and the excellent physical and biomechanical properties, titanium mesh helps to achieve better stabilization of complex mandibular fractures than conventional miniplates do. Complications such as infection and non union can largely be avoided and bony continuity of the mandible can be restored.

Miniplate osteosynthesis is a standard method for the surgical treatment of mandible fractures today. Apart from easy handling, in the majority of cases it also ensures adequate fracture stability. The treatment of fractures of very atrophic mandibles as well as mandibular defects and comminuted fractures with miniplates and rigid plates is often difficult or only possible to an inadequate extent. Titanium mesh has proved successful for the treatment of such fractures. Compared with conventional miniplates this mesh is outstanding for its considerably higher stability due to its given geometry. The titanium mesh can be adapted and screwed individually in any situation, in contrast to miniplates and rigid plates. As a result, complications such as fracture gap infections and pseudoarthrosis can be avoided to a great extent.

Copyright of Oral & Maxillofacial Surgery is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Complications in connection with implantological measures will occur with greater frequency in the future, purely from the point of view of quantity, owing to the increasing number of implantations. One of the most serious, yet extremely rare consequences of implantation is fracture of the mandible. It occurs predominantly in older patients with extremely atrophic mandibles, especially if the dental implants are anchored bicortically, or after explantation of dental implants. The risk of a fracture is increased in addition by weakening of the mandible as a result of osteomyelitis, especially in patients with weak immune systems. In order to avoid fractures of the mandible, therefore, endosseous implants should not be placed into extremely atrophic mandibles, unless the opposing corticalis is protected or only after alveolar augmentation. Furthermore, close scrutiny is advisable during clinical and radiological post-check-ups, so that any periimplantitis or bone infections, which additionally increase the risk of mandibular fracture, can be detected in good time.

A recently available portable clinical analyzer (PCA), which examines sodium, potassium, chloride, glucose, urea nitrogen, and hematocrit levels on 60 microL of blood and calculates hemoglobin and osmolality levels within 2 minutes, was evaluated. Blood from 574 patients was drawn by emergency department staff, who immediately tested the samples with the PCA and transported them for plasma analysis on a reference analyzer in the clinical laboratory. Correlations between the PCA and the reference analyzer were as follows: R2 = 0.987 for urea nitrogen; R2 = 0.97, glucose; R2 = 0.937, K;R2 = 0.79, hematocrit; R2 = 0.751, sodium; and R2 = 0.689 for chloride. With its rapid turnaround, small sample requirement, and ease of operation, the PCA is most useful in an emergency department setting, where immediate access to clinically relevant laboratory testing is required in support of urgent clinical decision-making.

Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With over 95% of bisphenol-A (BPA) used in the production of polycarbonate (PC) and epoxy resins, termed here as BPA-based plastic materials, components, and products (MCPs), an investigation of human exposure to BPA over the whole lifecycle of BPA-based plastic MCPs is necessary. This mini-review unpacks the implications arising from the long-term human exposure to BPA and its potential accumulation across the lifecycle of BPA-based plastics (production, use, and management). This investigation is timely and necessary in promoting a sustainable circular economy model. Restrictions of BPA in the form of bans and safety standards are often specific to products, while safety limits rely on traditional toxicological and biomonitoring methods that may underestimate human health implications and therefore the "safety" of BPA exposure. Controversies in regards to the: (a) dose-response curves; (b) the complexity of sources, release mechanisms, and pathways of exposure; and/or (c) the quality and reliability of toxicological studies, appear to currently stifle progress toward the regulation of BPA-based plastic MCPs. Due to the abundance of BPA in our MCPs production, consumption, and management systems, there is partial and inadequate evidence on the contribution of BPA-based plastic MCPs to human exposure to BPA. Yet, the production, use, and end-of-life management of plastic MCPs constitute the most critical BPA source and potential exposure pathways that require further investigation. Active collaboration among risk assessors, government, policy-makers, and researchers is needed to explore the impacts of BPA in the long term and introduce restrictions to BPA-based MCPs. Integr Environ Assess Manag 2023;19:45-62. © 2022 SETAC., (© 2022 SETAC.)

Obesity is a worldwide epidemic disease that induces important structural and functional changes to the heart and predisposes a patient to devastating cardiac complications. Sirtuin1 (SIRT1) has been found to have roles in regulating cardiac function, but whether it can help in cardioprotection is not clear. The aim of the present study was to determine whether melatonin, by modulating SIRT1 and in turn mitochondria signaling, may alleviate obesity-induced cardiac injuries. We investigated 10 lean control mice and 10 leptin-deficient obese mice (ob/ob) orally supplemented with melatonin for 8 weeks, as well as equal numbers of age-matched lean and ob/ob mice that did not receive melatonin. Hearts were evaluated using multiple parameters, including biometric values, morphology, SIRT1 activity and expression of markers of mitochondria biogenesis, oxidative stress, and inflammation. We observed that ob/ob mice experienced significant heart hypertrophy, infiltration by inflammatory cells, reduced SIRT1 activity, altered mitochondrial signaling and oxidative balance, and overexpression of inflammatory markers. Notably, melatonin supplementation in ob/ob mice reverted these obesogenic heart alterations. Melatonin prevented heart remodeling caused by obesity through SIRT1 activation, which, together with mitochondrial pathways, reduced oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

TP53 has been shown to be involved in lactation in cattle. However, the role of TP53 in buffalo lactation remains unknown. To this end, we isolated and identified the complete coding sequence (CDS) of the TP53 gene from the buffalo mammary gland and further analyzed its molecular characteristics, function, tissue differential expression, and single-nucleotide polymorphism (SNP). A transcript of this gene was cloned with a CDS length of 1161 bp, encoding a protein consisting of 386 amino acid residues. Bioinformatics analysis showed that buffalo TP53 CDS and the physicochemical characteristics, conserved domains, structure, and function of its encoded protein are highly similar to those of other species in Bovidae. The buffalo TP53 protein contains an N-terminal activation domain, a DNA-binding domain, and a tetrameric domain, and it plays a functional role in the nucleus. TP53 was found to express in all 11 detected buffalo tissues, and its expression in the heart, kidney, brain, muscle, and rumen during lactation was significantly higher than that during non-lactation (p<0.05), while in the liver, lung, and mammary gland, its expression was the opposite (p<0.05). Interference experiments in buffalo mammary epithelial cells (BuMECs) showed that TP53 inhibits the expression of genes related to milk protein and milk fat synthesis through the PI3K–AKT–mTOR pathway. A synonymous nucleotide substitution (c.204C > T) was found in the TP53 CDS of river buffalo, which is the CC homozygote in swamp buffalo. The results indicate that the TP53 gene is involved in buffalo lactation by negatively regulating the synthesis of milk protein and milk fat. [ABSTRACT FROM AUTHOR]

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis. [ABSTRACT FROM AUTHOR]

Background: Titanium mesh provides three-dimensional stability, it is easier and quick in placement, highly malleable and adaptable hence, proved to be worth in restoring the function and form in cases of comminuted maxillofacial fractures. Materials and Methods: A total of 12 patients were included in this retrospective study at Department of Oral and maxillofacial surgery, Sri Rajiv Gandhi College of Dental Science and Hospital, from December 2015 to June 2020. Out of 12 patients, 7 reported with frontal bone fracture and 5 reported with mandibular fracture. Patients were followed up for upto 18 months to evaluate efficacy of titanium mesh on postoperative long-term healing, aesthetic outcomes and return to normal function were evaluated. Results: The results have shown that titanium mesh has low complication rates and the ability to maintain occlusion and chewing postoperatively. Union occurred without complication in 90% of fractures, and patients treated for frontal bone fracture had excellent cosmetic results. Conclusion: The semi rigid nature of the titanium mesh fixation allows micro movement at the healing bone ends, reduces stress shielding effect which may improve functional bone healing. Bony continuity of the mandible can be restored providing three-dimensional morphology and stability. The versatile placement of screws is the principal advantage. [ABSTRACT FROM AUTHOR]

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case–control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33–0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia. [ABSTRACT FROM AUTHOR]

Oral leukoplakia (OLK) is one of the most common oral potentially malignant disorders (OPMDs). Preventing malignant transformation is the main purpose of OLK treatment. The treatment approaches of OLK include surgery, chemotherapy, and other therapies, such as photodynamic therapy and CO2 laser. The application of genomic variation-based chemotherapy in OLK deserves further exploration. As chemopreventive drugs, drug resistance and disease recurrence have limited their use in OLK. In this review, we concentrate on the retinoid treatment for OLK, summarizing the current status of retinoids in the treatment of OLK, the mechanism of retinoid action, and the mechanisms of resistance to retinoid therapy, and we highlight the strategies to improve retinoid efficacy in the treatment of OLK, such as the combination of retinoids and epigenetic regulators or metabolism-blocking agents, new synthetic retinoids, and new drug delivery systems of retinoids, providing new methods for the successful clinical application of retinoids in the treatment of OLK. [ABSTRACT FROM AUTHOR]

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects. [ABSTRACT FROM AUTHOR]

Despite the incredible progress of experimental techniques, protein structure determination still remains a challenging task. Due to the rapid improvements of computer technology, simulations are often used to complement or interpret experimental data, particularly for sparse or low-resolution data. Many such in silico methods allow us to obtain highly accurate models of a protein structure either de novo or via refinement of a physical model with experimental restraints. One crucial question is how to select a representative member or ensemble out of the vast number of computationally generated structures. Here, we introduce such a method. As a representative task, we add co-evolutionary contact pairs as distance restraints to a physical force field and want to select a good characterization of the resulting native-like ensemble. To generate large ensembles, we run replica-exchange molecular dynamics (REMD) on five mid-sized test proteins and over a wide temperature range. High temperatures allow overcoming energetic barriers while low temperatures perform local searches of native-like conformations. The integrated bias is based on co-evolutionary contact pairs derived from a deep residual neural network to guide the simulation toward native-like conformations. We shortly compare and discuss the achieved model precision of contact-guided REMD for mid-sized proteins. Finally, we discuss four robust ensemble-selection algorithms in great detail, which are capable to extract the representative structure models with a high certainty. To assess the performance of the selection algorithms, we exemplarily mimic a "blind scenario," i.e., where the target structure is unknown, and select a representative structural ensemble of native-like folds. [ABSTRACT FROM AUTHOR]