Hyperechogenic fetal bowel: Current evidence-based prenatal diagnosis and management.

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.

Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy.

BACKGROUND: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation. METHODS: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women. RESULTS: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 × 10-5), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06). CONCLUSIONS: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes.

Fertility preservation in female cancer sufferers: (only) a moral obligation?

PURPOSE: Advances in cancer diagnostics and therapeutics have thankfully led to high numbers of young cancer survivors, although some interventions may sometimes threaten fertility. The authors aimed to assess how evidence-based oncofertility counselling can be adequately fulfilled for the sake of female cancer patients, in light of its complexities and multidisciplinary nature, which require thorough counselling and consent pathways. MATERIALS AND METHODS: A search has been conducted in the databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Google Scholar via search strings such as fertility preservation, reproductive counselling, oncofertility, cancer survivors, in order to identify relevant meaningful sources spanning the 2010-2021 period. RESULTS: Counselling needs to be implemented in compliance with international guidelines, so as to avoid medicolegal repercussions. Albeit fertility preservation is supported by most health care institutions, actual conditions at health care facilities often reflect several lingering difficulties in the oncofertility process. Oncofertility counselling should foster access to fertility preservation procedures. To best serve that purpose, it should be implemented in a manner consistent with ethical and legal standards, so that patients can make an informed decision based on comprehensive and relevant data. CONCLUSIONS: Counselling needs to be rooted in a close cooperation of oncologists, reproductive endocrinologists, mental health counsellors and clinical researchers. The provision of oncofertility services is grounded in the moral obligation to uphold individual autonomy, which is essential in a free society, unless the exercise thereof could pose a risk to the children conceived or to others.

Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification.

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.

Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer.

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse.

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer.

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues.

The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense.

Y RNA: An Overview of Their Role as Potential Biomarkers and Molecular Targets in Human Cancers.

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients.

The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory.

Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change.

Medicolegal Issues in Power Morcellation: Cautionary Rules for Gynecologists to Avoid Unfavorable Outcomes.

Power morcellation in laparoscopic surgery enables specialists to carry out minimally invasive procedures such as hysterectomies and myomectomies by cutting specimens into smaller pieces using a rotating blade and removing pieces through a laparoscope. Unexpected uterine sarcoma treated by surgery involving tumor disruption could be associated with poor prognosis. The current study aims to shed light on power morcellation from a medicolegal perspective: the procedure has resulted in adverse outcomes and litigation, and compensation for plaintiffs, as published in various journals cited in PubMed and MEDLINE, Cochrane Library, EMBASE, and GyneWeb. Considering the claims after the US Food and Drug Administration warnings on morcellation, the current study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia, superior court of New Jersey, and US district court of Minnesota) between 1995 and 2019. Legal records show that courts determine professional responsibility regarding complications, making it essential to document adherence to safety protocols and specific guidelines, when available. Sound medical practices and clearly stated institute best practices result in better patient outcomes and are important when unfavorable clinical outcomes occur; adverse legal decisions can be avoided if there are grounds to prove professional conformity with specific guidelines and the unpredictability of an event.

A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.

Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.

Non-Coding RNAs and Endometrial Cancer.

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.

A novel approach in the treatment of neonatal gastroschisis: a review of the literature and a single-center experience.

Gastroschisis is a congenital abdominal wall defect and its management remains an issue. We performed a review of the literature to summarize its evaluation, management and outcome and we describe a new type of surgical reduction performed in our center without anesthesia (GA), immediately after birth, in the delivery room. Between January 2002 and March 2013, we enrolled all live born infants with gastroschisis referred to the third-level Division of Obstetrics and Gynecology "San Camillo" of Rome. Two groups of infants were identified: group 1 in which gastroschis reduction was performed by the traditional technique and group 2 in which reduction was immediately performed after birth in the delivery room without GA. Twelve infants were enrolled in group 1, and seven infants in group 2. Statistical significance was observed between the groups regarding the hospital stay, for the duration of parenteral nutrition and full oral feeds (p = .004). Survival was similar between two groups. The reduction without GA performed immediately after birth in a delivery room encourages the relationship between the mother and her child and appears to be a safe and feasible technique in a selected group of patients with simple gastroschisis defect; for this reason, it could represent a valid alternative to traditional approach.

The issue of delivery room infections in the Italian law. A brief comparative study with English and French jurisprudence.

Delivery room infections are frequent, and many of them could be avoided through higher standards of care. The authors examine this issue by comparing it to English and French reality. Unlike England, in Italy and France the relationship established between health facility, physician and patient is outlined in a contract. In England, the judges' decisions converge toward a better and higher protection of the patient-the actor-and facilitate the probative task. In case of infections, including those occurring in the delivery room, three issues are evaluated: the hospital's negligent conduct, damages if any and causal nexus. Therefore, the hospital must demonstrate to have taken the appropriate asepsis measures according to current scientific knowledge concerning not only treatment, but also diagnosis, previous activities, surgery and post-surgery. In order to avoid a negative sentence, both physicians and hospital have to demonstrate their correct behavior and that the infection was caused by an unforeseeable event. The authors examine the most significant rulings by the Courts and the Supreme Court. They show that hospitals can avoid being accused of negligence and recklessness only if they can demonstrate to have implemented all the preventive measures provided for in the guidelines or protocols.

Role of Non-Coding RNAs in the Etiology of Bladder Cancer.

According to data of the International Agency for Research on Cancer and the World Health Organization (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organization Mortality), bladder is among the top ten body locations of cancer globally, with the highest incidence rates reported in Southern and Western Europe, North America, Northern Africa and Western Asia. Males (M) are more vulnerable to this disease than females (F), despite ample frequency variations in different countries, with a M:F ratio of 4.1:1 for incidence and 3.6:1 for mortality, worldwide. For a long time, bladder cancer was genetically classified through mutations of two genes, fibroblast growth factor receptor 3 (FGFR3, for low-grade, non-invasive papillary tumors) and tumor protein P53 (TP53, for high-grade, muscle-invasive tumors). However, more recently scientists have shown that this disease is far more complex, since genes directly involved are more than 150; so far, it has been described that altered gene expression (up- or down-regulation) may be present for up to 500 coding sequences in low-grade and up to 2300 in high-grade tumors. Non-coding RNAs are essential to explain, at least partially, this ample dysregulation. In this review, we summarize the present knowledge about long and short non-coding RNAs that have been linked to bladder cancer etiology.

Fetal intra-abdominal cysts: accuracy and predictive value of prenatal ultrasound.

OBJECTIVE: The finding of a fetal intra-abdominal cyst is relatively common and it can be due to a wide variety of clinical conditions. The aims of this study were to determine the accuracy of the prenatal ultrasound (US) in identifying the etiology of fetal intra-abdominal cysts and to describe the neonatal outcomes. METHODS: All cases of fetal intra-abdominal cystic lesion referred to our center between 2004 and 2012 were reviewed. Cysts of urinary system origin were excluded. Prenatal and postnatal data were collected. Our cohort was divided into subgroups according to the prenatal suspected origin of the lesion (ovarian, mesenteric, gastro-intestinal and other locations). For each subgroup, sensitivity, specificity, positive predictive value, false-positive rate and accuracy of fetal US were calculated. RESULTS: In total 47 fetuses (10/37 M/F) were identified. The mean gestational age at the time of diagnosis was 33 ± 4.9 weeks. Our cohort comprised of 25 ovarian cysts (10 simplex and 15 complex), 3 GI duplication, 6 mesenteric lesions, 4 meconium pseudocyst and 9 lesions of other origin. Surgery was performed in 38 cases (81%) at birth. The prenatally established diagnosis was exactly concordant with post-natal findings in 34 cases (72.3%). Sensitivity, specificity, positive predictive value and false-positive rate of US were 88.1%, 95.5%, 71% and 5.4%, respectively. Long-term outcome was good in almost 90% of the cases. CONCLUSIONS: The etiology of fetal intra-abdominal cysts can be prenatally diagnosed in about 70% cases. Despite the high risk of surgery at birth, the long-term outcome was good in most of the cases.

Polyamines metabolism and breast cancer: state of the art and perspectives.

Breast cancer (BC) is a common disease that generally occurs in women over the age of 50, and the risk is especially high for women over 60 years of age. One of the major BC therapeutic problems is that tumors initially responsive to chemotherapeutic approaches can progress to more aggressive forms poorly responsive to therapies. Polyamines (PAs) are small polycationic alkylamines, naturally occurring and essential for normal cell growth and development in eukaryotes. The intracellular concentration of PA is maintained within strongly controlled contents, while a dysregulation occurs in BC cells. Polyamines facilitate the interactions of transcription factors, such as estrogen receptors with their specific response element, and are involved in the proliferation of ER-negative and highly invasive BC tumor cells. Since PA metabolism has a critical role in cell death and proliferation, it represents a potential target for intervention in BC. The goal of this study was to perform a literature search reviewing the association between PA metabolism and BC, and the current evidence supporting the BC treatment targeting PA metabolism. We here describe in vitro and in vivo models, as well as the clinical trials that have been utilized to unveil the relationship between PA metabolism and BC. Polyamine pathway is still an important target for the development of BC chemotherapy via enzyme inhibitors. Furthermore, a recent promising strategy in breast anticancer therapy is to exploit the self-regulatory nature of PA metabolism using PA analogs to affect PA homeostasis. Nowadays, antineoplastic compounds targeting the PA pathway with novel mechanisms are of great interest and high social impact for BC chemotherapy.

Antiretroviral therapeutic drug monitoring in HIV-infected pregnant women: maternal immunovirological outcome at delivery and during the 18 month follow-up period.

No data are available on the long-term immunovirological outcome of HIV-positive pregnant women experiencing sub-therapeutic antiretroviral drug (ARV) concentrations during pregnancy. The objective of our study was to assess the long-term virological outcome in pregnant women treated with HAART. A prospective, multi-center study enrolled 60 HIV-infected pregnant women stratified into 3 groups according to the response to HAART. Group A, women successfully treated with HAART; Group B, women with confirmed virological failure during HAART; Group C, women successfully treated with HAART during pregnancy for prevention of vertical transmission only. Smoking, alcohol use, low adherence to therapy, and increased viral load at delivery were significantly associated to virological failure at univariate analysis. At multivariate regression analysis, only adherence to therapy was reported as an independent variable related to the virological response (p < 0.001). Virological failure during follow-up was reported in 2 (25.0%) of the 8 women with sub therapeutic Ctrough and in 4 of the 33 (12.1%) women with therapeutic Ctrough (p=0.33). In group C, the viro-immunological set points during follow-up did not differ from those observed before HAART initiation. No significantly increased rate of virological failure after delivery was reported in women with sub-therapeutic ARV concentrations during pregnancy and long-term follow-up. The long-term virological outcome was independently associated to reduced adherence to therapy. Evaluation of the clinical impact of the low plasma ARV concentrations during pregnancy on the long-term virological outcome deserves further larger studies.

Pregnancy in HIV-positive patients: effects on vaginal flora.

A high proportion of HIV-infected pregnant women present pathogenic organisms in their lower genital tract. This has been associated with the development of postpartum morbility, HIV transmission to the partner and offspring, and other gynaecological conditions, such as cervical dysplasia or cancer. Vaginal flora alterations can range from 47% in Western countries to 89% in Africa in pregnant HIV-positive patients, much higher than about 20% of the general population. Pathogen organism retrieval is high. As peripartum complications due to vaginal infections seem higher in HIV-positive patients, accurate investigation and treatment of such infections are strongly mandatory.