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Background. Mast cells are immune cells that mediate hypersensitivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue disorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. Objective. Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. Methods. Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spectrometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. Results. Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. Conclusion. Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema. [ABSTRACT FROM AUTHOR]

Background. Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease. AIM. This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction. Results. Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones. Conclusions. The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals. [ABSTRACT FROM AUTHOR]

Background: Human breast carcinoma is a complex disease, affecting 1 in 8 women worldwide. The seriousness of the disease increases when the definite cause of the disease remains obscure, thus making prognosis challenging. Researchers are emphasizing on adapting more advanced and targeted therapeutic approaches to address the multifaceted impacts of the disease. Hence, modern multi-omics systems have gained popularity among clinicians, as they offer insights into the genomic, pharmacogenomic, metabolomic, and micro-biomic factors, thus allowing researchers to develop targeted and personalized approaches for breast cancer prevention and early detection, and eventually improving patient outcomes. Aim. The primary focus of this study is to elucidate, through the integration of multi-omics research findings, the inherent molecular origins of diverse subtypes of breast cancer and to evaluate the effectiveness of these findings in reducing breast cancer-related mortalities. Methods. Thorough investigation was conducted by reviewing reputable and authoritative medical journals, e-books, and online databases dedicated to cancer research. The Mendelian inheritance in man database (OMIM) was used to scrutinize specific genes and their respective loci associated with the development of different types of breast cancer. Results. Our present research revealed the holistic picture of sundry molecular, genomic, pharmacogenomic, metabolomic, and micro-biomic features of breast cancer. Such findings, like genetic alterations in highly penetrant genes, plus metabolomic and micro-biomic signatures of breast cancer, unveil valuable insights and show great potential for multi-omics research in breast oncology. Conclusion. Further research in omics sciences pertaining to breast cancer are at the forefront of shaping precise treatment and bolstering patient survival. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly aggressive and malignant type of brain cancer with a poor prognosis, despite current treatment options of surgery, radiation therapy, and chemotherapy. These treatments have limitations due to the aggressive nature of the cancer and the difficulty in completely removing the tumor without damaging healthy brain tissue. Personalized medicine, using genomic profiling to tailor treatment to the patient's specific tumor, and immunotherapy have shown promise in clinical trials. The blood-brain barrier also poses a challenge in delivering treatments to the brain, and researchers are exploring various approaches to bypass it. More effective, personalized treatment approaches are needed to improve outcomes for glioblastoma patients. This tumor is studied using genomics, transcriptomics, and proteomics techniques, to better understand its underlying molecular mechanisms. Recent studies have used these techniques to identify potential therapeutic targets, molecular subtypes, and heterogeneity of tumor cells. Advancements in omics sciences have improved our understanding of glioblastoma biology, and precision medicine approaches have implications for more accurate diagnoses, improved treatment outcomes, and personalized preventive care. Precision medicine can match patients with drugs that target specific genetic mutations, improve clinical trials, and identify individuals at higher risk for certain diseases. Precision medicine, which involves customizing medical treatment based on an individual's genetic makeup, lifestyle, and environmental factors, has shown promise in improving treatment outcomes for glioblastoma patients. Identifying biomarkers is essential for patient stratification and treatment selection in precision medicine approaches for glioblastoma, and several biomarkers have shown promise in predicting patient response to treatment. Targeted therapies are a key component of precision medicine approaches in glioblastoma, but there is still a need to improve their effectiveness. Technical challenges, such as sample quality and availability, and challenges in analyzing and interpreting large amounts of data remain significant obstacles in omics sciences and precision medicine for glioblastoma. The clinical implementation of precision medicine in glioblastoma treatment faces challenges related to patient selection, drug development, and clinical trial design, as well as ethical and legal considerations related to patient privacy, informed consent, and access to expensive treatments. [ABSTRACT FROM AUTHOR]

In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumorrelevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible. [ABSTRACT FROM AUTHOR]

Lung cancer is a complex disease, with a wide range of genetic alterations and clinical presentations. Understanding the natural and clinical history of the disease is crucial for developing effective diagnostic and treatment strategies. Omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools for understanding the molecular mechanisms underlying lung cancer and for identifying novel biomarkers and therapeutic targets. These approaches enable researchers to examine the entire genome, transcriptome, proteome, or metabolome of a cell or tissue, providing a comprehensive view of the biological processes involved in lung cancer development and progression. Targeted therapies that address specific genetic mutations and pathways hold promise for improving the diagnosis and treatment of this disease. [ABSTRACT FROM AUTHOR]

Background. Sarcomas are a relatively rare but diverse group of cancers that typically develop in the mesenchymal cells of bones and soft tissues. Occurring in more than 70 subtypes, sarcomas have broad histological presentations, posing significant challenges of prognosis and treatment. Modern multi-omics studies, which include genomics, proteomics, metabolomics, and micro-biomics, are vital to understand the underlying mechanisms of sarcoma development and progression, identify molecular biomarkers for early detection, develop personalized treatment plans, and discover drug resistance mechanisms in sarcomas to upsurge the survival rate. Aim. This study aims to highlight the genetic risk factors responsible for sarcoma-genesis, and to present a comprehensive review of multi-omics studies about sarcoma. Methods. Extensive literature research was undertaken using reliable and authentic medical journals, e-books, and online cancer research databases. Mendelian inheritance in man database (OMIM) was explored to study particular genes and their loci that are responsible to cause various sarcomas. Result. This in-depth research led to the finding out that omics studies provide a more comprehensive understanding of underlying molecular mechanisms of sarcomas. Through genomics, we can reveal genetic alterations that predispose to sarcoma, like mutation in TP53, NF1, and so on. Pharmacogenomics enable us to find molecular targets for specific drugs. Whereas, proteomic and metabolomic studies provide insights into the biological pathways involved in sarcoma development and progression. Conclusion. Future advancements in omics sciences for sarcoma are on the cutting-edge of defining precision treatment plans and improved resilience of sarcoma patients. [ABSTRACT FROM AUTHOR]

Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcriptomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research. [ABSTRACT FROM AUTHOR]

Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in KIF26A, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic KIF26A variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging KIF26A-related disorder., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Background: Intrauterine fetal death and perinatal death represent one of the most relevant medical scientific problems since, in many cases, even after extensive investigation, the causes remain unknown. The considerable increase in medical legal litigation in the obstetrical field that has witnessed in recent years, especially in cases of stillborn births, has simultaneously involved the figure of the forensic pathologist in scientific research aimed at clarifying the pathophysiological processes underlying stillbirth., Methods: our study aims to analyze cases of sudden intrauterine unexplained death syndrome (SIUD) to evaluate the role of oxidative stress in the complex pathogenetic process of stillbirth. In particular, the immunohistochemical expression of specific oxidative stress markers (NOX2, NT, iNOS, 8-HODG, IL-6) was evaluated in tissue samples of placentas of SIUDs belonging to the extensive case series (20 cases), collected from autopsy cases of the University of Ferrara and Politecnica delle Marche between 2017 and 2023., Results: The study demonstrated the involvement of oxidative stress in intrauterine fetal deaths in the placenta of the cases examined. In SIUD, the most expressed oxidative stress markers were NOX2 and 8-HODG., Conclusions: The study contributes to investigating the role of oxidative stress in modulating different pathways in unexplained intrauterine fetal death (SIUD) tissues.

Objective: To develop a differential diagnosis of a mass retrieved alongside skeletal remains in the crypt of the church of Santissima Annunziata of Valenza (Province of Alessandria, Northern Italy)., Material: A calcified mass measuring 40 × 39 mm and 17.62 × 16.3817.62 × 16.38 mm., Method: The analysis utilized macroscopic assessment and histologic examination (including histochemical and immunohistochemical analyses)., Results: Morphological traits include an irregular and spongy external surface. Holes of different sizes lead toward the inner part of the object. A section of the mass shows an "intertwined bundle" pattern, confirmed by microscopic examination., Conclusions: Differential diagnosis determined the mass to be consistent with calcified leiomyoma., Significance: Identifying uterine leiomyoma adds to the paucity of paleopathological literature on the condition and to calcified tumors more broadly. It also allows for an important discussion of women's gynecological health in the past and potentially among nulliparous women., Limitations: Neither histochemical staining nor immunohistochemical analysis demonstrated the certain muscular nature of the specimens due to the rehydration and decalcification processes, for which there are no gold standards., Suggestions for Further Research: Calcified masses are common in the clinical literature but remain rare in paleopathological literature. Careful excavation and improved recognition of apparently calcified masses are necessary to improve recognition, diagnosis, and interpretation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Early-onset neonatal sepsis (EONS), a serious infection in newborns within 3 days, is challenging to diagnose. The current methods often lack accuracy, leading to unnecessary antibiotics or delayed treatment. This study investigates the role of the frozen section examination of placental membranes and umbilical cord (FSMU) to improve EONS diagnosis in the daily lab practice. This retrospective study reviewed data from 59 neonates with EONS risk factors who underwent FSMU according to our institutional protocol. Concordance between the FSMU and the Final Pathological Report (FPR) was assessed. The FSMU demonstrated a high concordance (Kappa = 0.88) for funisitis diagnosis, with excellent accuracy (98.3%). A moderate concordance was observed for chorioamnionitis stage and grade. The FSMU shows promise as a rapid and accurate tool for diagnosing EONS, particularly for funisitis. This study suggests that the FSMU could be a valuable tool for EONS diagnosis, enabling a more judicious antibiotic use and potentially improving outcomes for newborns.

Background: Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease., Aim: This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction., Results: Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones., Conclusions: The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.

Abstract: Glioblastoma is a highly aggressive and malignant type of brain cancer with a poor prognosis, despite current treatment options of surgery, radiation therapy, and chemotherapy. These treatments have limitations due to the aggressive nature of the cancer and the difficulty in completely removing the tumor without damaging healthy brain tissue. Personalized medicine, using genomic profiling to tailor treatment to the patient's specific tumor, and immunotherapy have shown promise in clinical trials. The blood-brain barrier also poses a challenge in delivering treatments to the brain, and researchers are exploring various approaches to bypass it. More effective, personalized treatment approaches are needed to improve outcomes for glioblastoma patients. This tumor is studied using genomics, transcriptomics, and proteomics techniques, to better understand its underlying molecular mechanisms. Recent studies have used these techniques to identify potential therapeutic targets, molecular subtypes, and heterogeneity of tumor cells. Advancements in omics sciences have improved our understanding of glioblastoma biology, and precision medicine approaches have impli-cations for more accurate diagnoses, improved treatment outcomes, and personalized preventive care. Precision medicine can match patients with drugs that target specific genetic mutations, improve clinical trials, and identify individuals at higher risk for certain diseases. Precision medicine, which involves customizing medical treatment based on an individual's genetic makeup, lifestyle, and environmental factors, has shown promise in improving treatment outcomes for glioblastoma patients. Identifying biomarkers is essential for patient stratification and treatment selection in precision medicine approaches for glioblastoma, and several biomarkers have shown promise in predicting patient response to treatment. Targeted therapies are a key component of precision medicine approaches in glioblastoma, but there is still a need to improve their effectiveness. Technical challenges, such as sample quality and availability, and challenges in analyzing and interpreting large amounts of data remain significant obstacles in omics sciences and precision medicine for glioblastoma. The clinical implementation of precision medicine in glioblastoma treatment faces challenges related to patient selection, drug development, and clinical trial design, as well as ethical and legal considerations related to patient privacy, informed consent, and access to expensive treatments.

Abstract: Lung cancer is a complex disease, with a wide range of genetic alterations and clinical presentations. Understanding the natural and clinical history of the disease is crucial for developing effective diagnostic and treatment strategies. Omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools for understanding the molecular mechanisms underlying lung cancer and for identifying novel biomarkers and therapeutic targets. These approaches enable researchers to examine the entire genome, transcriptome, proteome, or metabolome of a cell or tissue, providing a comprehensive view of the biological processes involved in lung cancer development and progression. Targeted therapies that address specific genetic mutations and pathways hold promise for improving the diagnosis and treatment of this disease.

Background: Sarcomas are a relatively rare but diverse group of cancers that typically develop in the mesenchymal cells of bones and soft tissues. Occurring in more than 70 subtypes, sarcomas have broad histological presentations, posing significant challenges of prognosis and treatment. Modern multi-omics studies, which include genomics, proteomics, metabolomics, and micro-biomics, are vital to understand the underlying mechanisms of sarcoma development and progression, identify molecular biomarkers for early detection, develop personalized treatment plans, and discover drug resistance mechanisms in sarcomas to upsurge the survival rate., Aim: This study aims to highlight the genetic risk factors responsible for sarcoma-genesis, and to present a comprehensive review of multi-omics studies about sarcoma., Methods: Extensive literature research was undertaken using reliable and authentic medical journals, e-books, and online cancer research databases. Mendelian inheritance in man database (OMIM) was explored to study particular genes and their loci that are responsible to cause various sarcomas., Result: This in-depth research led to the finding out that omics studies provide a more comprehensive understanding of underlying molecular mechanisms of sarcomas. Through genomics, we can reveal genetic alterations that predispose to sarcoma, like mutation in TP53, NF1, and so on. Pharmacogenomics enable us to find molecular targets for specific drugs. Whereas, proteomic and metabolomic studies provide insights into the biological pathways involved in sarcoma development and progression., Conclusion: Future advancements in omics sciences for sarcoma are on the cutting-edge of defining precision treatment plans and improved resilience of sarcoma patients.

Abstract: Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.

Abstract: In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.

Background: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema., Objective: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema., Methods: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks., Results: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity., Conclusion: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

Background: Human breast carcinoma is a complex disease, affecting 1 in 8 women worldwide. The seriousness of the disease increases when the definite cause of the disease remains obscure, thus making prognosis challenging. Researchers are emphasizing on adapting more advanced and targeted therapeutic approaches to address the multifaceted impacts of the disease. Hence, modern multi-omics systems have gained popularity among clinicians, as they offer insights into the genomic, pharmacogenomic, metabolomic, and microbiomic factors, thus allowing researchers to develop targeted and personalized approaches for breast cancer prevention and early detection, and eventually improving patient outcomes., Aim: The primary focus of this study is to elucidate, through the integration of multi-omics research findings, the inherent molecular origins of diverse subtypes of breast cancer and to evaluate the effectiveness of these findings in reducing breast cancer-related mortalities., Methods: Thorough investigation was conducted by reviewing reputable and authoritative medical journals, e-books, and online databases dedicated to cancer research. The Mendelian inheritance in man database (OMIM) was used to scrutinize specific genes and their respective loci associated with the development of different types of breast cancer., Results: Our present research revealed the holistic picture of sundry molecular, genomic, pharmacogenomic, metabolomic, and microbiomic features of breast cancer. Such findings, like genetic alterations in highly penetrant genes, plus metabolomic and microbiomic signatures of breast cancer, unveil valuable insights and show great potential for multi-omics research in breast oncology., Conclusion: Further research in omics sciences pertaining to breast cancer are at the forefront of shaping precise treatment and bolstering patient survival.

Introduction: hematopoietic stem cells transplantation (HSCT) is a treatment option for malignant and non-malignant haematological diseases. Because of the improved survival rates and the more widespread use of reproductive technologies in the last two decades, the number of patients who conceive is increasing while the pathogenesis of some obstetrical complications observed is not yet fully clarified., Methods: we present complete data about two pregnancies in women who had previously undergone HSTC, with conditioning regimen including total body irradiation. One pregnancy is spontaneous and one after oocytes donation., Results: In both pregnancies we observed relevant intrauterine growth retardation, attributable to a deficit in implantation and placentation. Ultrasound and histological data point to a defective placenta development, possibly sustained by uterine vessel damage caused by irradiation. A deeper understanding of factors influencing placentation post total body irradiation and HSCT, including the possible role of donor's sex and graft versus host disease, is pivotal to improve pregnancy outcomes in this specific population., 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 © 2022 Elsevier Ltd. All rights reserved.)

Abstract: Sudden death due to massive hemorrhage after a mini-invasive ambulatory diagnostic procedure is extremely rare. Fine-needle aspiration (FNA) of thyroid nodules is very safe, displaying a low rate of complications, all of which mild and often self-limiting. In few cases do these complications necessitate surgical decompression, and rarely does FNA of a thyroid nodule lead to the death of the patient.We report a case of sudden death caused by respiratory insufficiency after compression of the vascular and nervous structures of the neck and obstruction of the upper airways by hemorrhages dissecting the thyroidal and perithyroidal tissues in a 78-year-old woman. These hemorrhages were the result of vascular lacerations caused during diagnostic FNA of a nodule suspected of malignancy. In such cases, it is important to conduct a complete autopsy and histological analysis to ascertain the origin of massive hemorrhage involving the structures of the neck and to attribute the cause of death to the aforementioned procedure. The forensic pathologist must bear in mind that even extremely small damage, such as that produced by a fine needle, may cause a fatal hemorrhage in subjects with a subverted anatomo-pathological picture (such as, for example, the massive fibrosis of an organ)., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The variety of placental morphological findings with SARS-CoV-2 maternal infections has raised the issue of poor agreement in histopathological evaluation. The aims of this study were: to describe the histopathological placental features of a large sample of SARS-CoV-2-positive women who gave birth in Italy during the COVID-19 pandemic, to analyse the factors underlying these lesions, and to analyse the impact of placental impairment on perinatal outcomes. From 25 February 2020 to 30 June 2021, experienced perinatal pathologists examined 975 placentas of SARS-CoV-2-positive mothers enrolled in a national prospective study, adopting the Amsterdam Consensus Statement protocol. The main results included the absence of specific pathological findings for SARS-CoV-2 infections, even though a high proportion of placentas showed signs of inflammation, possibly related to a cytokine storm induced by the virus, without significant perinatal consequences. Further research is needed to better define the clinical implications of placental morphology in SARS-CoV-2 infections, but the results of this large cohort suggest that placentas do not seem to be a preferential target for the new Coronavirus infection.

This study clinically and histologically evaluated the performance of implants with different crestal morphologies: tissue-level implants and bone-level implants. Nine patients received at least two adjacent implants in an edentulous area: one bone-level implant (EO) and one tissue-level implant (TG) (total: 23 implants), placed beside each other using a single-stage delayed loading protocol. The implants were rehabilitated with screw-retained fixed partial dentures. Plaque Index (PI), bleeding on probing (BOP), probing depth (PD), and peri-implant bone level were recorded at various postsurgical follow-ups, including 2 and 6 months as well as 1 and 4 years. At 3 months postsurgery, soft tissue biopsy samples were taken from all implant sites and histologically analyzed. Longitudinal assessment of the results (TG vs EO implants) was performed using a linear mixed model with random intercept and by using Spearman correlation or chi-square after visual inspection of the probability distribution. Student t test was used to compare means, and chi-square test was used for dichotomic variables. P < .05 was considered statistically significant. All implants were functional at 4 years. Peri-implant bone resorption was limited, with means of 1.20 ± 0.71 mm and 1.24 ± 0.82 mm for TG and EO implants, respectively. No significant differences in clinical parameters were identified between EO and TG implants. Histologic analysis revealed normal peri-implant soft tissue healing with poor inflammatory infiltrate. Differences in the histologic appearance of soft tissues were more related to patients than implant type. Both implants appeared to be suitable for partial rehabilitation of edentulous arches without differences in the investigated clinical and histologic parameters. However, TG implants showed a greater risk of implant collar exposure.

Adipocytes express various enzymes, such as aldo-keto reductases (AKR1C), 11β-hydroxysteroid dehydrogenase (11β-HSD), aromatase, 5α-reductases, 3β-HSD, and 17β-HSDs involved in steroid hormone metabolism in adipose tissues. Increased activity of AKR1C enzymes and their expression in mature adipocytes might indicate the association of these enzymes with subcutaneous adipose tissue deposition. The inactivation of androgens by AKR1C enzymes increases adipogenesis and fat mass, particularly subcutaneous fat. AKR1C also causes reduction of estrone, a weak estrogen, to produce 17β-estradiol, a potent estrogen and, in addition, it plays a role in progesterone metabolism. Functional impairments of adipose tissue and imbalance of steroid biosynthesis could lead to metabolic disturbances. In this review, we will focus on the enzymes involved in steroid metabolism and fat tissue deposition.

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation., (© 2021. The Author(s).)

Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic-mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: We conducted a retrospective analysis of cases of sudden unexpected infant death (SUID) referred to the SIDS-ALTE Center of the Liguria Region (Italy) from 2010 to 2018. In all cases, the death scene was inspected, and a multidisciplinary post-mortem evaluation was conducted. Our aim was to analyze the epidemiological data and etiological distribution., Evidence Acquisition: We examined 15 cases initially classified as sudden infant death., Evidence Synthesis: In all cases, the death was initially unexplained. Seven cases involved males and eight involved females. Their mean age was 67.47 days; the youngest victim was 2 days old, while the oldest was 8.5 months (253 days). In 7 cases, the post-mortem analysis showed an infection of lung. In 4 cases, the prone position of the infant during sleep was identified as a risk factor. Only in one case the cause of death remains unexplained, and it was classified as sudden infant death syndrome II according to San Diego Classification., Conclusions: In the forensic approach to cases of SUID, it is always important to conduct a thorough multidisciplinary investigation. In order to avoid procedural errors that might compromise the post-mortem investigation, it is necessary to consider the medical and social history of both mother and child, in addition to the circumstances of the death. Moreover, a complete pediatric post-mortem examination and multidisciplinary discussion are required in order to identify potentially important causative or contributory factors.