Intraplacental Fetal Vessel Diameter May Help Predict for Placental Invasiveness in Pregnant Women at High Risk for Placenta Accreta Spectrum Disorders.

Background Prenatal identification of placenta accreta spectrum (PAS) disorder is essential for treatment planning. More objective means for predicting PAS and clinical outcome may be provided by MRI descriptors. Purpose To investigate the association of intraplacental fetal vessel (IFV) diameter at MRI with PAS and peripartum complications. Materials and Methods Between March 2016 and October 2019, 160 gravid women suspected of having PAS underwent placental MRI as part of a prospective trial. Secondary analysis was performed by two experienced genitourinary radiologists for presence and maximum diameter of IFVs. Relative risk ratios were computed to test the association of IFVs with presence and depth of PAS invasiveness. Receiver operating characteristic analysis was used to evaluate the ability of IFV diameter to help predict PAS, placenta percreta, and peripartum complications and for comparison of the area under the curve (AUC) versus that from other combined MRI predictors of PAS (eg, myometrial thinning, intraplacental T2-hypointense bands, uterine bulge, serosal hypervascularity, and signs of extrauterine placental spread). Intraoperative and histopathologic findings were the reference standard. Results A total of 155 women were evaluated (mean age, 35 years ± 5 [standard deviation]; mean gestational age, 32 weeks ± 3). PAS was diagnosed in 126 of 155 women (81%) (placental percreta in 68 of 126 [54%]). At delivery, 30 of 126 women (24%) experienced massive blood loss (>2000 mL). IFVs were detected at MRI in 109 of 126 women with PAS (86%) and in 67 of 68 women with placental percreta (98%). The relative risk ratio was 2.4 (95% CI: 1.6, 3.4; P < .001) for PAS and 10 (95% CI: 1.5, 70.4; P < .001) for placental percreta when IFVs were visible. IFVs of 2 mm or greater were associated with PAS (AUC, 0.81; 95% CI: 0.67, 0.95; P = .04). IVFs of 3 mm or greater were associated with placenta percreta (AUC, 0.81; 95% CI: 0.73, 0.89; P < .001) and with peripartum complications, including massive bleeding (AUC, 0.80; 95% CI: 0.71, 0.89; P < .001). Combining assessment of IFVs with other MRI descriptors improved the ability of MRI to predict PAS (AUC, 0.94 vs 0.89; P = .009). Conclusion Assessment of intraplacental fetal vessels with other MRI descriptors improved the ability of MRI to help predict PAS. Vessel diameter of 3 mm or greater was predictive of placenta percreta and peripartum complications. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Dighe in this issue.

Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin.

Carfilzomib (Cfz), an irreversible proteasome inhibitor licensed for relapsed/refractory myeloma, is associated with cardiotoxicity in humans. We sought to establish the optimal protocol of Cfz-induced cardiac dysfunction, to investigate the underlying molecular-signaling and, based on the findings, to evaluate the cardioprotective potency of metformin (Met). Mice were randomized into protocols 1 and 2 (control and Cfz for 1 and 2 consecutive days, respectively); protocols 3 and 4 (control and alternate doses of Cfz for 6 and 14 days, respectively); protocols 5A and 5B (control and Cfz, intermittent doses on days 0, 1 [5A] and 0, 1, 7, and 8 [5B] for 13 days); protocols 6A and 6B (pharmacological intervention; control, Cfz, Cfz+Met and Met for 2 and 6 days, respectively); and protocol 7 (bortezomib). Cfz was administered at 8 mg/kg (IP) and Met at 140 mg/kg (per os). Cfz resulted in significant reduction of proteasomal activity in heart and peripheral blood mononuclear cells in all protocols except protocols 5A and 5B. Echocardiography demonstrated that Cfz led to a significant fractional shortening (FS) depression in protocols 2 and 3, a borderline dysfunction in protocols 1 and 4, and had no detrimental effect on protocols 5A and 5B. Molecular analysis revealed that Cfz inhibited AMPKα/mTORC1 pathways derived from increased PP2A activity in protocol 2, whereas it additionally inhibited phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase pathway in protocol 3. Coadministration of Met prevented Cfz-induced FS reduction and restored AMPKα phosphorylation and autophagic signaling. Conclusively, Cfz decreased left ventricular function through increased PP2A activity and inhibition of AMPKα and its downstream autophagic targets, whereas Met represents a novel promising intervention against Cfz-induced cardiotoxicity.

MRI prognosticators for adverse maternal and neonatal clinical outcome in patients at high risk for placenta accreta spectrum (PAS) disorders.

BACKGROUND: Placenta accreta spectrum (PAS) disorders may be associated with significant mortality and morbidity for both mother and fetus. PURPOSE/HYPOTHESIS: To identify MRI risk factors for poor peripartum outcome in gravid patients at risk for PAS. STUDY TYPE: Prospective. POPULATION: One hundred gravid women (mean age: 34.9 years) at third trimester, with placenta previa. FIELD STRENGTH/SEQUENCE: T2 -SSTSE (single-shot turbo spin echo), T2 -TSE, T1 -TSEFS (TSE images with fat-suppression) at 1.5T. ASSESSMENT: Fifteen MRI features considered indicative of PAS were recorded by three radiologists and were tested for any association with the following adverse peripartum maternal and neonatal events: increased operation time, profound blood loss, hysterectomy, bladder repair, ICU admission, prematurity, low birthweight, and 5-minute APGAR score <7. STATISTICAL TESTS: Kappa (K) coefficients were computed as a measure of agreement between intraoperative information/histology and MRI results as well as for interobserver agreement; chi-square and Fisher's exact tests were used to explore the association of the MRI signs with clinical complications. A score was calculated by adding all recorded MRI signs and its predictive ability was tested using receiver operating characteristic (ROC) analysis, against all complications, separately; odds ratios (ORs) for optimal cutoffs were determined with logistic regression analysis. RESULTS: There was excellent agreement (K >0.75, P < 0.001) between MRI and intraoperative findings for invasive placenta, bladder and parametrial involvement. Intraplacental T2 dark bands, myometrial disruption, uterine bulge, and hypervascularity at the utero-placental interface or parametrium, showed significant association (P < 0.005) with poor clinical outcome for both mother and fetus. The MRI score showed significant predictive ability for each adverse maternal event (area under the curve [AUC]: 0.85-0.97, P < 0.001). The presence of ≥3 MRI signs was the cutoff point for a complicated delivery (OR: 19.08, 95% confidence interval [CI]: 6.05-60.13) and ≥6 MRI signs was the cutoff point for massive bleeding (OR: 90.93, 95% CI: 11.3-729.23), hysterectomy (OR: 72.5, 95% CI: 17.9-293.7), or extensive bladder repair (OR: 58.74, 95% CI: 7.35-469.32). The MRI score was not significant for predicting adverse neonatal events including preterm delivery (P = 0.558), low birthweight (P = 0.097), and 5-minute Apgar score (P = 0.078). DATA CONCLUSION: Preoperative identification of specific MRI features may predict peripartum course in high-risk patients for PAS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:602-618.

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate.

We have previously shown that perinatal hypoxic/ischemic injury (HII) may cause selective vulnerability of the mesencephalic dopaminergic neurons of human neonate. In the present study, we investigated the effect of perinatal HII on the noradrenergic neurons of the locus coeruleus (LC) of the same sample. We studied immunohistochemically the expression of tyrosine hydroxylase (TH, first limiting enzyme for catecholamine synthesis) in LC neurons of 15 autopsied infants (brains collected from the Greek Brain Bank) in relation to the neuropathological changes of acute or chronic HII of the neonatal brain. Our results showed that perinatal HII appears to affect the expression of TH and the size of LC neurons of the human neonate. In subjects with neuropathological lesions consistent with abrupt/severe HII, intense TH immunoreactivity was found in almost all neurons of the LC. In most of the neonates with neuropathological changes of prolonged or older injury, however, reduction in cell size and a decrease or absence of TH staining were observed in the LC. Intense TH immunoreactivity was found in the LC of 3 infants of the latter group, who interestingly had a longer survival time and had been treated with anticonvulsant drugs. Based on our observations and in view of experimental evidence indicating that the reduction of TH-immunoreactive neurons occurring in the LC after perinatal hypoxic insults persists into adulthood, we suggest that a dysregulation of monoaminergic neurotransmission in critical periods of brain development in humans is likely to predispose the survivors of perinatal HII, in combination with genetic susceptibility, to psychiatric and/or neurological disorders later in life.

Compound heterozygosity of a paternal submicroscopic deletion and a maternal missense mutation in POR gene: Antley-bixler syndrome phenotype in three sibling fetuses.

BACKGROUND: Antley-Bixler syndrome (ABS) is an exceptionally rare craniosynostosis syndrome that can be accompanied by disordered steroidogenesis, and is mainly caused by mutations in the POR gene, inherited in an autosomal recessive manner. Here we report the prenatal and postmortem findings of three sibling fetuses with ABS as a result of compound heterozygosity of a paternal submicroscopic deletion and a maternal missense mutation in the POR gene. METHODS: Prenatal ultrasound and postmortem examination were performed in three sibling fetuses with termination of pregnancy at 22, 23, and 17 weeks of gestation, respectively. Molecular analysis of fetus 2 and 3 included (a) bidirectional sequencing of exon 8 of the POR gene after amplification of the specific locus by polymerase chain reaction, to detect single nucleotide variants (SNVs) and (b) high resolution comparative genomic hybridization (CGH) positive single nucleotide polymorphism array CGH (aCGH) analysis to detect copy number variants (CNVs), copy neutral areas of loss of heterozygosity and uniparental disomy. RESULTS: The diagnosis of ABS was suggested by the postmortem examination findings. The combination of the POR gene molecular analysis and aCGH revealed a compound heterozygous genotype of a maternal SNV (p.A287P) and a paternal CNV (NC_000007.13:g.(?_75608488)_(75615534_?)del). CONCLUSION: To the best of our knowledge, these sibling fetuses add to the few reported cases of ABS, caused by a combination of a SNV and a CNV in the POR gene. The detailed description of the pathologic and radiographic findings of second trimester fetuses affected with ABS adds novel knowledge concerning the early ABS phenotype, in lack of previous relevant reports. Birth Defects Research (Part A) 106:536-541, 2016. © 2016 Wiley Periodicals, Inc.

Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature.

BACKGROUND: Partial trisomy of the long arm of chromosome 1 (1q) is an exceptionally rare chromosomal abnormality and most of the prenatally diagnosed cases are associated with either complete (q11-qter) or large (q21-qter) duplications with pre- or perinatal demise of all reported cases. The most common sonographic findings associated with this karyotype abnormality include ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac abnormalities, craniofacial dysmorphism, and limb deformities. However, there is a wide spectrum of clinical manifestations due to the great variability in the extent of the duplication size and the possible contribution of additional genetic rearrangements in the final phenotype. CASE REPORT: We report on a female fetus with sole partial trisomy 1q presenting with multiple structural malformations in the second trimester scan. Standard karyotyping demonstrated a large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter→q31::q31→q12::q31→qter)] and further application of comparative genomic hybridization array confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSION: A fetus with nonmosaic partial trisomy 1q that was prenatally diagnosed upon multiple abnormal ultrasound findings is presented. A detailed review of the currently available literature on the prenatal diagnostic approach of partial trisomy 1q in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided. The use of novel molecular techniques such comparative genomic hybridization array could shed further light on the correlation between the genes identified in the chromosomal region of interest and the resultant phenotype.

Mandibulofacial dysostosis (Treacher-Collins syndrome) in the fetus: novel association with Pectus carinatum in a molecularly confirmed case and review of the fetal phenotype.

BACKGROUND: Treacher Collins syndrome is the most common mandibulofacial dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case of perinatal death or pregnancy termination. METHODS: We describe the ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected fetus, and review the clinical, prenatal, and postmortem findings in 15 previously reported fetal and perinatal cases. RESULTS: A nearly complete spectrum of the typical facial characteristics can be present by the early second trimester of gestation, including subtle defects such as lower eyelid colobomas. Mandibular hypoplasia and bilateral auricle defects were constant findings in the affected fetal population. Downslanting palpebral fissures were the second more common feature, followed by midface hypoplasia, polyhydramnios, and ocular defects. Association with Pierre Robin sequence was common (38%) in the reviewed series. Previously unreported pectus carinatum was noted in our case bearing a heterozygous TCOF1 mutation. Other unique reported findings include salivary gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all in molecularly unconfirmed cases. CONCLUSION: Treacher Collins syndrome can be prenatally detected by ultrasound and should be included in the wide range of genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses tend to have a more severe phenotype than living patients. The reported association of Treacher Collins syndrome type 1 with pectus carinatum expands the phenotype, provides information on genotype-phenotype correlation, and suggests possible pathogenetic interactions between neural crest cell disorders and the formation of the sternum that merit investigation.

Incorporating Medical Museum Specimens Into the Training of Environmental Health Students.

Xenobiotics, radiation, and other environmental health risk factors leave their mark on human organs. This can be demonstrated through the use of pathology museum specimens. Upon completing two semesters of postgraduate studies in environmental health, a tour of the Museum of Pathology is offered to postgraduate students at Athens Medical School who are being trained in environmental health. A structured questionnaire is employed to assess the specimens' impact on several aspects: improving students' observational skills, reinforcing the taught material, acquiring new relevant knowledge, and cultivate the social-cognitive ability of empathy. Additionally, students are asked to evaluate the necessity of preserving metadata associated mainly with the social context of the specimens. This research-educational initiative, a component of an ongoing larger project, underscores the significant educational and research value of museum specimens pertaining to environmental health. Furthermore, effectively utilizing such exhibits can enrich the museum experience for visitors and increase public awareness of environmental health issues.

Rare case of XX/XY mosaicism and trisomy 13 in early prenatal diagnosis.

Coexistence of XX/XY sex mosaicism and autosomal trisomy in prenatal diagnosis is particularly rare. Herein, we report the first, to our knowledge, case of a fetus with cyclopia, ambiguous genitalia and a 47,XX,+13,inv9[47]/47,XY,+13[13] karyotype detected at 13 weeks of gestation after chorionic villus sampling. Molecular analysis after prenatal diagnosis suggests that this is a case of sex mosaicism coexisting with trisomy 13, rather than chimera.

Familial Pelizaeus-Merzbacher disease caused by a 320.6-kb Xq22.2 duplication and the pathological findings of a male fetus.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) is a recessive, X-linked leukoencephalopathy attributed to impaired myelination during central nervous system development, caused by defects in the proteolipid protein 1 (PLP1) gene. PMD presents clinical variability, ranging from the severe connatal form to the classic form. CASES: We report the clinical and molecular findings of two affected males, three carrier females, and an aborted male fetus with familial PMD. The two male probands presented with severe PMD phenotype and intellectual disability. High-resolution oligonucleotide-based array comparative genomic hybridization (aCGH) identified an Xq22.2 duplication of 320.6 kb (102641391-102961998, hg18), including the PLP1 gene and surrounding chromosomal region. Postmortem examination of the aborted fetus at 25 weeks' gestation showed focal subcortical white matter degeneration, focal gliosis, and cerebellar atrophy. CONCLUSIONS: Genotype-phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the PLP1 gene has a more complex role in human brain development, exceeding its structural function in myelin formation.

Clinical symptoms associated with laboratory findings and placental histopathology in full-term, non-infected neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive mothers.

This study comprehensively examines clinical symptoms, laboratory findings, and placental pathology in 40 cases of singleton full-term SARS-CoV-2 negative neonates. Their mothers, previously healthy, with uncomplicated pregnancies, were infected peripartum and presented COVID-19 symptoms of various severity. Neonates had predominately diarrhea, the yet unreported absent sucking reflex, elevated COVID-19 inflammatory and ischemia/asphyxia markers as serum ferritin, interleukin-6 and cardiac troponin-T, while placentas demonstrated mild vascular and/or inflammatory lesions. We hypothesize that the above placental lesions may be associated with transient perinatal hypoxia resulting in absent sucking reflex, as well as with inflammatory cytokines transfer causing diarrhea.

Microglia Activation in the Midbrain of the Human Neonate: The Effect of Perinatal Hypoxic-Ischemic Injury.

Perinatal hypoxia-ischemia (PHI) is a major risk factor for the development of neuropsychiatric deficits later in life. We previously reported that after prolonged PHI, the dopaminergic neurons of the human neonate showed a dramatic reduction of tyrosine hydroxylase (TH) in the substantia nigra, without important signs of neuronal degeneration despite the significant reduction in their cell size. Since microglia activation could precede neuronal death, we now investigated 2 microglia activation markers, ionized calcium-binding adapter molecule 1 (Iba1), and the phagocytosis marker Cd68. The highest Iba1 immunoreactivity was found in neonates with neuropathological lesions of severe/abrupt PHI, while the lowest in subjects with moderate/prolonged or older PHI. Subjects with very severe/prolonged or chronic PHI showed an increased Iba1 expression and very activated microglial morphology. Heavy attachment of microglia on TH neurons and remarkable expression of Cd68 were also observed indicating phagocytosis in this group. Females appear to express more Iba1 than males, suggesting a gender difference in microglia maturation and immune reactivity after PHI insult. PHI-induced microglial "priming" during the sensitive for brain development perinatal/neonatal period, in combination with genetic or other epigenetic factors, could predispose the survivors to neuropsychiatric disorders later in life, possibly through a sexually dimorphic way.

Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature.

BACKGROUND: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. METHODS: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. RESULTS: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. CONCLUSION: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.

Comparison between 1.5-T and 3.0-T MRI for the diagnosis of placenta accreta spectrum disorders.

PURPOSE: Accurate antenatal diagnosis of placenta accreta spectrum (PAS) is important for optimal management. The purpose of this study was to compare the respective capabilities of 1.5-T and 3.0-T MRI in the diagnosis of PAS. MATERIALS AND METHODS: Between March 2016-March 2021, 190 pregnant women at high risk for PAS underwent dedicated prenatal MRI with either 1.5-T or 3.0-T units at a tertiary imaging center. Cesarian section and MRI were performed less than 6 weeks from each other. Prospectively collected data were evaluated by two experienced genitourinary radiologists for presence and extent of PAS. A comparative study was designed to investigate differences in predictive ability between 1.5-T and 3.0-T MRI groups. Sensitivity, specificity, accuracy, negative and positive prognostic values relative to intraoperative/histological findings, were computed for both groups and were compared with chi-square (χ 2) test. Interobserver agreement was estimated using Kappa test. RESULTS: One hundred-eighty-two gravid women were included in the study; of these, 91/182 (50%) women were evaluated with 1.5-T (mean age, 35 ± 5.1 [SD] years; mean gestational age: 32.5 weeks) and 91/182 (50%) with 3.0-T MRI (mean age, 34.9 ± 4.9 [SD] years; mean gestational age, 32.1 weeks). 1.5-T MRI yielded 95.7% sensitivity (95% CI: 87.8-99.1) and 81.8% specificity (95% CI: 59.8) and 3.0-T MRI 93.8% sensitivity (95% CI: 86.0-97.9) and 83.3% specificity (95% CI: 48.2-97.7) for PAS identification, with no differences between the two groups (P = 0.725 and P >0.999, respectively). MRI showed excellent predictive ability for detecting extrauterine placental spread with 100% sensitivity (95% CI: 89.4-100.0), 96.7% specificity (95% CI: 88.1-99.6) for 1.5-T and 97% sensitivity (95% CI: 84.2-99.9), 96.7% specificity (95% CI: 88.1-99.6) for 3.0-T without differences between the two groups (P > 0.999). Interobserver agreement was excellent for both groups. The most frequently detected MRI signs of PAS for both 1.5-T and 3.0-T groups were placental heterogeneity (n = 85, 93.5% vs. n = 90, 98.9%; P = 0.413), and intraplacental fetal vessels (n = 64, 70.3% vs. n = 65, 71.4%; P = 0.870). CONCLUSION: This study suggests that 3.0-T MRI and 1.5-T MRI are equivalent for the diagnosis of PAS.

FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases.

Fibroblast Growth Factor Receptor 3 (FGFR3) related skeletal dysplasias are caused by mutations in the FGFR3 gene that result in increased activation of the receptors causing alterations in the process of endochondral ossification in all long bones, and include achondroplasia, hypochondroplasia, thanatophoric dysplasia, and SADDAN. Reports of prenatal diagnosis of FGFR3 related skeletal dysplasias are not rare; however, the correlation between 2nd trimester ultrasonographic findings and underlying molecular defect in these cases is relatively poor. There is a need for specific ultrasound (U/S) predictors than can distinguish lethal from non-lethal cases and aid an earlier prenatal diagnosis. Here we present one familial and 16 sporadic cases with FGFR3 related skeletal dysplasia, and we evaluate biometric parameters and U/S findings consistent with the diagnosis of skeletal dysplasia. U/S scan performed even at the 18th week of gestation can indicate a decreased rate of development of the femora (femur length (FL) <5th centile), while the mean gestational age at diagnosis is still around the 26th week. The utility of other biometric parameters and ratios is discussed (foot length, BPD, HC, FL/foot, and FL/AC). Prenatal cytogenetic and molecular genetic analyses were performed. A final diagnosis was reached by molecular analysis. In two cases of discontinued pregnancy, fetal autopsy led to a phenotypic diagnosis and confirmed the prenatal prediction of lethality. We conclude that the combination of U/S and molecular genetic approach is helpful for establishing an accurate diagnosis of FGFR3-related skeletal dysplasias in utero and subsequently for appropriate genetic counselling and perinatal management.

Environmental Health Education: From Museum Specimens and Math Word Problems to Virtual and Augmented Reality.

Environmental degradation and its severe impact on human health has revealed the necessity for effective educational interventions. Given the importance of "Environment," "Health," and "Education," as key pillars for the achievement of sustainable development, the education for environmental health is evolving into a main component of current strategies against environmental health threats, such as climate change and urban air pollution. Environmental Health Education, which must be considered as a strategical response against environmental degradation, offers vast capacity for innovation alongside every educational stage. For instance, the application of new technologies, such as virtual and augmented reality applications, the adoption of innovative interdisciplinary educational approaches, and the incorporation of Arts are evolving into a new era's educational perspectives. All the new trends in formal, non-formal and informal Environmental Health Education should be captured and assessed, in favor of protecting both local and global natural environment, human and animal health, and promoting sustainability.

Pharyngeal sampling for PCR-testing in the investigation of SARS-COV-2 vertical transmission in pregnancy.

The novel COVID-19 global pandemic has raised, among many others, major concerns regarding the impact of infection during pregnancy. Current evidence suggests that vertical transmission from mother to baby, antenatally or intrapartum, does occur, but is uncommon. According to the published reports of infants born to COVID-19-affected mothers, as well as the anecdotal experience of current practices worldwide, it appears that investigations regarding the potential of SARS-COV-2 vertical transmission in pregnancy have so far been based, to a large extent, on PCR testing of neonatal pharyngeal swab samples. Given that the transplacental route of intrauterine transmission for SARS-COV-2 is less likely to immediately involve the upper respiratory tract of the newborn, contrary to what happens after birth, it would be advisable to include appropriate biological samples, such as cord blood, placenta, amniotic fluid and neonatal blood, along with the pharyngeal samples, in order to contribute significantly to such investigations. It is important to point out that negative PCR tests of neonatal pharyngeal samples do not exclude the possibility of intrauterine viral transmission, while positive pharyngeal swabs are more likely to reflect intrapartum or postpartum contaminants, rather than antenatal intrauterine transmission, in the absence of other criteria. Revision and enhancement of the so far prevailing practices appear important, in order to facilitate the development of good clinical practice for managing neonates and ensuring safety of families and healthcare providers.

Adenovirus genome in the placenta: association with histological chorioamnionitis and preterm birth.

Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi-square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy-one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4-5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty-seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus-positive placentas compared to preterm adenovirus-negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus-positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth.

Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury.

Our previous postmortem studies on neonates with neuropathological injury of perinatal hypoxia/ischemia (PHI) showed a dramatic reduction of tyrosine hydroxylase expression (dopamine synthesis enzyme) in substantia nigra (SN) neurons, with reduction of their cellular size. In order to investigate if the above observations represent an early stage of SN degeneration, we immunohistochemically studied the expression of cleaved caspase-3 (CCP3), apoptosis inducing factor (AIF), and DNA fragmentation by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin 3'-end-labeling (TUNEL) technique in the SN of 22 autopsied neonates (corrected age ranging from 34 to 46.5 gestational weeks), in relation to the severity/duration of PHI injury, as estimated by neuropathological criteria. No CCP3-immunoreactive neurons and a limited number of apoptotic TUNEL-positive neurons with pyknotic characteristics were found in the SN. Nuclear AIF staining was revealed only in few SN neurons, indicating the presence of early signs of AIF-mediated degeneration. By contrast, motor neurons of the oculomotor nucleus showed higher cytoplasmic AIF expression and nuclear translocation, possibly attributed to the combined effect of developmental processes and increased oxidative stress induced by antemortem and postmortem factors. Our study indicates the activation of AIF, but not CCP3, in the SN and oculomotor nucleus of the human neonate in the developmentally critical perinatal period.

Cranioectodermal dysplasia: a probable ciliopathy.

Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare autosomal recessive genetic disorder characterized by typical craniofacial, skeletal and ectodermal defects, and tubulointerstitial nephritis leading to early end-stage renal failure. We report on a new familial case of a 9-year-old patient and two fetuses of 23 and 19 weeks of gestation respectively. Hypohidrosis was an additional ectodermal finding is the patient with CED. Postmortem findings in the two fetuses included acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals and roughly unremarkable histopathology of the physeal growth plate. Posterior fossa anomalies were additional findings in this patient and included an enlarged cisterna magna and a posterior fossa cyst. The above findings, in association with renal cysts, persistent ductal plate and portal fibrosis, introduce CED, a nonlethal genetic skeletal disorder of yet unknown molecular origin, as a possible member of the expanding group of ciliopathies.