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The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby's microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11(26,797,508_27,052,080)×1∼2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.

Escherichia coli is an important microorganism for cattle breeding. The aim of this study was to investigate the presence of phylogenetic groups, virulence factors, genotyping with multi-locus variable tandem repeat analysis (MLVA), and susceptibility to commonly used antimicrobial agents in E. coli strains isolated from aborted bovine fetal samples. In this study, phylogrouping and various virulence genes were analyzed by PCR in E. coli strains isolated from 637 bovine fetal tissue samples. Consequently, E. coli was isolated and identified in 24 samples in culture. Of the 24 isolates identified as positive, 12.5% were defined as group A, 83.3% as B1, and 4.2% as group B2. Of the E. coli isolates, virulence factor fimH was identified in eight (33.3%), traT in 15 (62.5%), ompT in five (20.8%), CNF1 in one (4.16%), and CNF2 in six (25%). Seven genotypic groups were determined as a result of the analysis with the MLVA 10 method. According to the antimicrobial susceptibility test results, high resistance was determined against amoxicillin/clavulanic acid and oxytetracycline. In conclusion, strains of E. coli containing CNF1, CNF2, fimH, traT , and ompT virulence factors can be associated with bovine abortions. It is noteworthy that the dominant phylogenetic group B1 has been observed in cases of cattle abortions. [ABSTRACT FROM AUTHOR]

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

Fibrochondrogenesis 1, an autosomal recessive syndrome, is a rare disease that causes short‐limbed skeletal dysplasia. Mutations in the gene encoding the α1 chain of type XI collagen (COL11A1) are seen to be the main cause of this disease. We present an 18‐week Iranian male aborted fetus with Fibrochondrogenesis 1 from consanguineous parents. Whole‐exome sequencing revealed a novel missense variant from G to A in exon 45 of 68 in the COL11A1 gene (NM_080629.2: c.3440G > A, [p.G1147E, g.103404625]). The mutation was confirmed by Sanger sequencing and further, MutationTaster predicted this variant to be disease‐causing. Bioinformatic analysis suggests that this variant is highly conserved in both nucleotide and protein levels, suggesting that it has an important function in the proper role of COL11A1 protein. In silico analysis suggests that this mutation alters the COL11A1 protein structure through a Glycine to Glutamic acid substitution. A missense variant from G to A in exon 45 of 68 in the COL11A1 gene (NM_080629.2: c.3440G > A, [p.G1147E, g.103404625]) is a novel pathogenic mutation that is associated with Fibrochondrogenesis 1. [ABSTRACT FROM AUTHOR]

BackgroundWorkplace violence is a widely-reported phenomenon among healthcare providers and negatively affects quality of care and treatment. This study aims to understand the potential factors related to HCV through the experiences of women who have undergone a pregnancy termination due to fetal anomaly.MethodsQualitative interview was used to collect data in this case study. Forty-one pregnant women who decided to terminate their pregnancy due to fetal anomaly were recruited from four Chinese hospital facilities, including three general hospitals and one specialty hospital in Changsha, Hunan, China. In-depth interviews were conducted from May to September 2017. Content analysis was used to analyze the data.ResultsSeveral potential factors related to violence in healthcare facilities were identified, including preventive factors, which possibly relieve healthcare violence; and negative experiences, which potentially related to healthcare violence. Preventive factors include healthcare providers gaining patient trust with detailed observation, expressing patient-centered care through discreet behavior, and showing patience and professionalism. Factors related to violence include busy work schedules, hurried visits, mechanized process, patients' scant medical knowledge and mental distress.ConclusionsThis study highlights potential factors related to healthcare violence. The results will be submitted to the Chinese government's policy making department in order to improve the healthcare system. We also suggest several important strategies to prevent HCV in a healthcare setting, both in China and globally.

Background and Aim: Toxoplasma gondii is a protozoan parasite that is responsible for the major cause of congenital diseases, abortion, and stillbirth in humans and farm animals. Primary infection in pregnant goats due to T. gondii leads to abortion and significant economic losses in the livestock industry. Moreover, very few studies have been performed for the identification of T. gondii from aborted fetuses of goats. The study was conducted for the molecular identification of Toxoplasma gondii from aborted fetuses of goats in Chattogram, Bangladesh. Materials and Methods: Twenty aborted fetuses of goats were collected from 52 farms in the study area. A nested polymerase chain reaction (PCR) assay targeting the B1 gene was performed, and a positive sample yield of 197 bp amplified DNA products consistent with T. gondii. Results: The overall prevalence of toxoplasmosis in the aborted fetus of goats was 35.0%. Heart muscle, liver, brain, and placenta showed positive PCR results. The risk factors related to the does age, presence of cats in farms, and aborted fetus age were found to be statistically significant (p

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

Abstract Bacterial placentitis in horses commonly results in abortion, premature birth or compromised neonatal foal health. Although mycobacterial infections are generally uncommon in horses, 10 equine abortion cases caused by Mycobacterium avium subsp. hominissuis (MAH) infections occurred between 2018 and 2019 in Japan. They occurred on seven Thoroughbred horse farms in the Hidaka district of Hokkaido, but direct contact among the mares on different farms was not recorded. Most cases were characterized by extensive pathological lesions of the placenta, which are not typical in cases of common pathogenic bacteria such as Streptococcus zooepidemicus and Escherichia coli. All abortions featured white–yellow exudates on the surface of the placenta. Mycobacterial granuloma formations were histologically found in the placenta and fetal organs, and acid‐fast bacteria were isolated from the placenta, fetal samples (heart, lung, liver, kidney, spleen and stomach contents) or uterine lavage fluid. The greatest number of bacteria was isolated from necrotic lesions on the placenta, which could be an important site for bacterial isolation in mycobacterial equine abortions. The isolates were identified as MAH based on internal genome sequences. In variable number tandem repeat analysis, all patterns of the strains were identical. Single nucleotide polymorphism analysis of the core genome grouped all strains in the II‐a/SC3 subcluster. Both results reveal that these strains share the same genetic background, suggesting that the horses had been infected by the same unknown contagious source.

This review details methods for utilizing D & C suction abortus specimens as a source of human fetal organs to study the morphogenetic and molecular mechanisms of human fetal organ development. By this means it is possible to design experiments elucidating the molecular mechanisms of human fetal organ development and to compare and contrast human developmental mechanisms with that of laboratory animals. Finally human fetal organs can be grown in vivo as grafts to athymic mice, thus allowing ethical analysis of potential adverse effects of environmental toxicants.

Context: Chromosomal abnormalities in embryos are the most common cause of early spontaneous abortions. Chromosome 1p36 deletion syndrome (OMIM 607872) is the most common subtelomeric, terminal microdeletion syndrome., Objective: The study intended to analyze miscarriage samples using chromosomal microarray analysis (CMA), to explore the mechanism of chromosomal aberrations, and to identify the recurrence risk and a prenatal diagnostic strategy for couples experiencing spontaneous abortions., Design: The research team performed a narrative review by searching PubMed databases. The search used the keywords 1p36 deletion, CMA, karyotype analysis, FISH and aborted fetus. The team also conducted case studies using genetic analyses., Setting: The study took place at Wuxi Maternity and Child Health Care Hospital in Wuxi, Jiangsu, PR China., Participants: Out of 673 abortion samples, six had 1p36 deletions (0.89%). Participants were the six families who had had those spontaneous abortions., Outcome Measures: The research team evaluated the fetal samples using: (1) CMA, (2) karyotype analysis, and (3) novel fluorescence in-situ hybridization (FISH)., Results: The CMA showed that: (1) fetus 1 had a 1.75 MB microdeletion at the 1p36.32p36.31 band, which testing didn't detect in fetus 1's parents, but the research team couldn't exclude the possibility that one of the parents was a carrier of a chromosomal insertional translocation; and (2) fetus 2 had a 5.10 MB microdeletion at the 1p36.13p36.12 segment, and fetus 3 had a 9.21 MB deletion at the 1p36.33p36.22 band, and the high-resolution karyotype analysis and FISH of the parents of both fetuses appeared normal, indicating that the chromosomal abnormalities were de novo; (3) fetus 4 had a 9.28 MB deletion at 1p36.33p36.22, although the high-resolution karyotype analysis of fetus 4's parent was normal; (4) fetuses 5 and 6 had a 7.64 MB microdeletion at 1p36.33p36.23 and a 4.45 MB deletion at 1p36.33p36.32, respectively, although the parents of both fetuses waived further testing., Conclusions: This study provides the first report of recurrent spontaneous and sporadic abortions with 1p36 deletion syndrome. The CMA combined with a reasonable family-pedigree investigation can detect cryptic chromosomal aberrations in miscarriages and can determine the mechanism of the chromosomal variations. It thus is invaluable in assessing recurrence risk and providing appropriate prenatal diagnostic strategies for affected families.

Bacterial placentitis in horses commonly results in abortion, premature birth or compromised neonatal foal health. Although mycobacterial infections are generally uncommon in horses, 10 equine abortion cases caused by Mycobacterium avium subsp. hominissuis (MAH) infections occurred between 2018 and 2019 in Japan. They occurred on seven Thoroughbred horse farms in the Hidaka district of Hokkaido, but direct contact among the mares on different farms was not recorded. Most cases were characterized by extensive pathological lesions of the placenta, which are not typical in cases of common pathogenic bacteria such as Streptococcus zooepidemicus and Escherichia coli. All abortions featured white–yellow exudates on the surface of the placenta. Mycobacterial granuloma formations were histologically found in the placenta and fetal organs, and acid‐fast bacteria were isolated from the placenta, fetal samples (heart, lung, liver, kidney, spleen and stomach contents) or uterine lavage fluid. The greatest number of bacteria was isolated from necrotic lesions on the placenta, which could be an important site for bacterial isolation in mycobacterial equine abortions. The isolates were identified as MAH based on internal genome sequences. In variable number tandem repeat analysis, all patterns of the strains were identical. Single nucleotide polymorphism analysis of the core genome grouped all strains in the II‐a/SC3 subcluster. Both results reveal that these strains share the same genetic background, suggesting that the horses had been infected by the same unknown contagious source. [ABSTRACT FROM AUTHOR]

Introduction: The safety and acceptability of medical abortion using mifepristone and misoprostol at home at ≤9+0 weeks' gestation is well established. However, the upper gestational limit at which the procedure remains safe and acceptable at home is not known. To inform a national guideline on abortion care we conducted a systematic review to determine what gestational limit for expulsion at home offers the best balance of benefits and harms for women who are having medical abortion. Material and methods: We searched Embase, MEDLINE, Cochrane Library, Cinahl Plus and Web‐of‐Science on 2 January 2020 for prospective and retrospective cohort studies with ≥50 women per gestational age group, published in English from 1995 onwards, that included women undergoing medical abortion and compared home expulsion of pregnancies of ≤9+0 weeks' gestational age with pregnancies of 9+1‐10+0 weeks or >10+1 weeks' gestational age, or compared the latter two gestational age groups. We assessed risk‐of‐bias using the Newcastle‐Ottowa scale. All outcomes were meta‐analyzed as risk ratios (RR) using the Mantel‐Haenszel method. The certainty of the evidence was assessed using GRADE. Results: Six studies (n = 3381) were included. The "need for emergency care/admission to hospital" (RR = 0.79, 95% confidence interval [CI] 0.45‐1.4), "hemorrhage requiring transfusion/≥500 mL blood loss" (RR = 0.62, 95% CI 0.11‐3.55), patient satisfaction (RR = 0.99, 95% CI 0.95‐1.03), pain (RR = 0.91, 95% CI 0.82‐1.02), and "complete abortion without the need for surgical intervention" (RR = 1.03, 95% CI 1‐1.05) did not differ statistically significantly between the ≤9+0 and >9+0 weeks' gestation groups. The rates of vomiting (RR = 0.8, 95% CI 0.69‐0.93) and diarrhea (RR = 0.85, 95% CI 0.73‐0.99) were statistically significantly lower in the ≤9+0 weeks group but these differences were not considered clinically important. We found no studies comparing pregnancies of 9+1‐10+0 weeks' gestation with pregnancies of >10+0 weeks' gestation. The certainty of this evidence was predominantly low and mainly compromised by low event rates and loss to follow up. Conclusions: Women who are having a medical abortion and will be taking mifepristone up to and including 10+0 weeks' gestation should be offered the option of expulsion at home after they have taken the misoprostol. Further research needs to determine whether the gestational limit for home expulsion can be extended beyond 10+0 weeks. [ABSTRACT FROM AUTHOR]

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases.

Background: It has been seen that there is progressive loss of Purkinje cells in various genetic conditions like ataxia telangiectasia and Niemann Pick disease type C. So, this study was carried out to analyse the histogenesis of human fetal cerebellar cortex. Methods: The study was conducted in the 30 aborted foetuses. The development of various layers of the cerebellar cortex is studied. All the layers of cerebellum were measured using image analyzer software-image pro premier 9.1. Data analysis was done by regular Statistical method. Results: The thickness of the 3 layers shows a gradual increase that indicates the developmental aspect of the 3 layers of the Embryo. The Purkinje cells appeared during the 4th month of embryonic period. Conclusion: The present study will facilitates in the identification of various pathological lesion of cerebellum which may develop in intrauterine life of fetus.

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a clinically and genetically heterogeneous disorder primarily characterized by susceptibility to fracture. Although OI generally results from mutations in the type I collagen genes, COL1A1 and COL1A2, the relationship between genotype and phenotype is not yet well understood. To provide additional data for genotype-phenotype analyses and to determine the proportion of mutations in the type I collagen genes among subjects with lethal forms of OI, we sequenced the coding and exon-flanking regions of COL1A1 and COL1A2 in a cohort of 63 subjects with OI type II, the perinatal lethal form of the disease. We identified 61 distinct heterozygous mutations in type I collagen, including five non-synonymous rare variants of unknown significance, of which 43 had not been seen previously. In addition, we found 60 SNPs in COL1A1, of which 17 were not reported previously, and 82 in COL1A2, of which 18 are novel. In three samples without collagen mutations, we found inactivating mutations in CRTAP and LEPRE1, suggesting a frequency of these recessive mutations of approximately 5% in OI type II. A computational model that predicts the outcome of substitutions for glycine within the triple helical domain of collagen alpha1(I) chains predicted lethality with approximately 90% accuracy. The results contribute to the understanding of the etiology of OI by providing data to evaluate and refine current models relating genotype to phenotype and by providing an unbiased indication of the relative frequency of mutations in OI-associated genes.

BackgroundIn China, fetal brain tissue has been transplanted into the lesions of more than 400 patients with spinal cord injury (SCI). Anecdotal reports have been the only basis for assuming that the procedure is safe and effective.ObjectiveTo compare available reports to the experiences and objective findings of patients who received pre-operative and postoperative assessments before and up to 1 year after receiving cellular implants.MethodsIndependent observational study of 7 chronic SCI subjects undergoing surgery by Dr Hongyun Huang in Beijing. Assessments included lesion location by magnetic resonance imaging, protocol of the American Spinal Injury Association (ASIA), change in disability, and detailed history of the perioperative course.ResultsInclusion and exclusion criteria were not clearly defined, as subjects with myelopathies graded ASIA A through D and of diverse causes were eligible. Cell injection sites did not always correlate with the level of injury and included the frontal lobes of a subject with a high cervical lesion. Complications, including meningitis, occurred in 5 subjects. Transient postoperative hypotonicity may have accounted for some physical changes. No clinically useful sensorimotor, disability, or autonomic improvements were found.ConclusionsThe phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, are unknown. Perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings. The procedures observed did not attempt to meet international standards for either a safety or efficacy trial. In the absence of a valid clinical trials protocol, physicians should not recommend this procedure to patients.

The domestic animal, known as a main reservoir of Coxiella burnetii, is susceptible to the occurrence of coxiellosis, which can lead to abortions in domestic animals, causing significant economic damage and posing risks to human health. Therefore, the purpose of this study is to investigate C. burnetii as the causative agent of Q fever in abortion samples of small ruminants in southeastern Iran. This study was conducted between 2020 and 2021 in Zarand city, located in Kerman province (southeast Iran). In this study, 50 abomasum swab samples of aborted sheep and goat fetuses were collected and analyzed using molecular methods to identify C. burnetii. The results revealed that 26% (n: 13) of the collected abortion samples were infected with C. burnetii. Among the positive samples, two (50%) belonged to goat abortion samples while 11 (23.9%) belonged to sheep abortion samples. This study demonstrates that C. burnetii is one of the causes of abortion in small ruminants in southeastern Iran. It is recommended to pay more attention to C. burnetii in domestic animals due to its significant economic impact on livestock and its potential implication for human health in Iran., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

The study is aimed at observing melanocytes in fetal scalp epidermis, their dendrites and the ultrastructure of the melanin granules in those cells. To study the ultrastructure of melanocytes in human fetal interfollicular epidermis, we obtained a human fetal scalp specimen from an induced abortion of 140 to 150 days estimated gestational age. The scalp specimen was divided into two parts: one part was subjected to immunohistochemical staining with an anti-human HMB-45 antibody specific for melanosomes, while the other part underwent conventional preparation and staining for observation by transmission electron microscopy (TEM). Immunohistochemical analysis revealed that HMB-45 positive cells, namely melanocytes, were scattered at the base of the epidermal layer and in hair follicles especially within the outer root sheath. Analysis by TEM showed that melanocytes in the fetal scalp specimen had a clear cytoplasm and heterochromatic nuclei and contained various stages of melanosomes, most of them being immature (stages I-II). Furthermore, these cells contained abundant mitochondria, endoplasmic reticulum (ER), Golgi apparatus and ribosomes, as well as numerous cytoplasmic vacuoles. The dendrites from melanocytes that extended among keratinocytes contained many melanized melanosomes. However, the melanosomes were distributed in keratinocytes individually and sparsely. These observations revealed large numbers of immature melanosomes and a rich rough ER in epidermal melanocytes of the fetal scalp tissue compared to adult epidermis. Although the dendrites contained many mature melanosomes, few had been transferred to surrounding keratinocytes. [ABSTRACT FROM AUTHOR]

Newcastle disease virus (NDV) causes morbidities and mortalities in wild and domestic birds globally. For humans, exposure to infected birds can cause conjunctivitis and influenza-like symptoms. NDV infections in mammals are rarely reported. In this study, using next-generation sequencing, an NDV was identified and isolated from Vero cells inoculated with the nasal swab of an aborted dromedary fetus in Dubai, during the time when an NDV outbreak occurred in a pigeon farm located in close proximity to the dairy camel farm where the mother of the aborted dromedary fetus resided, and there were a lot of pigeons in the camel farm. Genome analysis revealed that the structurally and functionally important features of other NDVs were also present in this dromedary NDV genome. Phylogenetic analysis based on the nucleotide sequences of fusion protein (F), hemagglutinin-neuraminidase protein (HN) and complete polyprotein showed that the virus belonged to sub-genotype VIg of class II NDV and is most closely related to pigeon NDVs in Egypt in the same year. The present study is the first that demonstrated isolation of NDV in dromedaries. Further study is warranted to investigate the relationship between NDV infection and abortion.

Pestiviruses are distributed worldwide and are responsible for a variety of economically important diseases. They are not very host-specific, and thus sheep can be infected by well-known pestiviruses like bovine viral diarrhea virus (BVDV) and border disease virus (BDV), as well as by other recently discovered pestivirus species. The aim of this study is to describe the isolation and characterization of four pestivirus strains detected in aborted lamb fetuses from a single farm in the Brescia province (Northern Italy). A total of twelve aborted fetuses were collected and examined. After necropsy, organs were tested for the presence of infectious agents known as potential causes of abortion (Brucella spp., Listeria spp., Coxiella burnetii, Chlamydophila spp., Mycoplasma spp., Neospora caninum, and Toxoplasma gondii), and submitted to viral identification by isolation on Madin Darby bovine kidney (MDBK) cell culture and by PCR assay for Schmallenberg virus and pan-pestivirus RT-PCR real time assay. Three viral strains (Ovine/IT/1756/2017, Ovine/IT/338710-2/2017, and Ovine/IT/338710-3/2017) were isolated in the absence of cytopathic effects (CPEs) in cell cultures and identified with RT-PCR. Another pestivirus strain (Ovine/IT/16235-2/2018) was detected by PCR, but was not successfully isolated. Complete sequence genomic data of the three isolated viruses showed that they were highly similar, differed genetically from known pestivirus species, and were closely related to classical swine fever virus (CSFV). Beyond the identification of new ovine pestiviruses, this study indicates that a systematic diagnostic approach is important to identify the presence and map the distribution of both known and emerging pestiviruses.

Toxoplasmosis is a worldwide disease of various animals and human and results from infection with the Toxoplasma gondii parasite. Abortion and congenital defects are important consequences of the T. gondii infection. The aim of this study was to determine the Toxoplasma-induced abortions among women with miscarriage and the presence of T. gondii in their aborted fetuses in Urmia, the northwest of Iran. This cross-sectional study was conducted with 215 women with abortion and their aborted fetuses, from 2020 to 2021. Seroprevalence of anti-Toxoplasma IgG and IgM were determined using the sera of the aforesaid women. Nested PCR was carried out using RE-529 gene sequences, and sequencing was performed using the T. gondii GRA6 gene on the remnant of pregnancy after abortion. The tissue positive samples were then subjected to another PCR on GRA6 gene and sequenced for genotyping. Among 215 serum samples of women with abortion, 70 (32.6%) were positive for anti-Toxoplasma IgG, and three (1.4%) were positive for IgM. The RE-529 sequence of T. gondii was positive in three (1.4%) of the aborted fetuses. The analysis of GRA6 gene indicated that all three positive samples carried a GRA6 allele (GRA6I) of T. gondii type I genotype. Our findings suggest that T. gondii is one of the causative agents of spontaneous abortion in West Azerbijan Province, the northwest of Iran., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zeinali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fetal tissue research refers to research using several types of tissue, including but not limited to samples obtained from aborted fetuses, cell lines derived from aborted fetuses, and in rarer cases, living previable neonates who have survived an abortion attempt. The ethical questions surrounding each type of tissue procurement are not identical, but do share similarities., This guideline on fetal tissue research discusses the moral status of the human fetus, the state of ethics for medical research on vulnerable subjects, aspects of medical research using human fetal tissue, and the necessity of including fetuses as a protected class under vulnerable populations in research. The debates connected to embryo stem cell research and other research related to embryos are beyond the scope of this document., (Copyright © 2023 by the National Legal Center for the Medically Dependent and Disabled, Inc.)

Objective: To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus., Methods: A couple who had presented at the Affiliated Hospital of Putian College on March 3, 2021 was selected as the study subject. Following elective abortion, fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple, and were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing., Results: The fetus was found to harbor compound heterozygous variants of the B3GALNT2 gene, namely c.261-2A>G and c.536T>C (p.Leu179Pro), which were inherited from its father and mother, respectively.According to the guidelines of American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM2_Supporting; PM3+PM2_Supporting+PP3+PP4)., Conclusion: The compound heterozygous variants of the B3GALNT2 gene probably underlay the α-dystroglycanopathy in this fetus. Above results have provided a basis for genetic counseling of this pedigree.

Coxiella burnetii (C. burnetii) is a causative microorganism that causes the zoonotic Q fever disease, which is generally asymptomatic in animals, but causes reproductive issues such as abortion, stillbirth, and infertility. C. burnetii infection poses a threat to farm economies as it affects productivity in farm animals. The purpose of this research was to look into the incidence of Q fever in eight provinces in the Middle and East Black Sea region and to measure reactive oxygen and reactive nitrogen species as well as antioxidant levels in bovine aborted fetal livers infected with C. burnetii. The study material consisted 670 bovine aborted fetal liver samples delivered to Samsun Veterinary Control Institute from eight provinces between 2018 and 2021. C. burnetii was analyzed by PCR in these samples and 47 (7,01%) were positive while 623 negative. Nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) activities were analyzed by spectrophotometric method in both 47 positive samples and 40 negative samples as control group. In the C. burnetii positive and control groups, MDA levels were determined to be 2.46 ± 0.18 and 0.87 ± 0.07 nmol/ml, NO levels were determined to be 1.77 ± 0.12 and 1.09 ± 0.07 nmol/ml, and reduced GSH activity was determined to be 5.14 ± 0.33 and 6.62 ± 0.46 µg/dl, respectively. In C. burnetii positive fetal liver tissue, MDA and NO levels were higher than the control group, while reduced GSH levels were lower than the control group. As a result, C. burnetii caused changes in free radical level and antioxidant activity in bovine aborted fetus liver., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Porcine parvovirus 7 (PPV7) was first detected in Korean pig farms in 2017. The detection rate of PPV7 DNA was 24.0% (30/125) in aborted pig fetuses and 74.9% (262/350) in finishing pigs, suggesting that PPV7 has circulated among Korean domestic pig farms. Phylogenetic analysis based on capsid protein amino acid sequences demonstrated that the nine isolated Korean strains (PPV-KA1-3 and PPV-KF1-6) were closely related to the previously reported USA and Chinese PPV7 strains. In addition, the Korean strains exhibit genetic diversity with both insertion and deletion mutations. This study contributes to the understanding of the molecular epidemiology of PPV7 in Korea. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is an important zoonotic disease that can cause abortion in humans and animals. The aim of this study was isolation and subsequent genotyping of Toxolasma gondii isolates in ovine aborted fetuses. During 2012- 2013, 39 ovine aborted fetuses were collected from sheep flocks in Khorasan Razavi Province, Iran. The brain samples were screened for detection of the parasite DNA by nested PCR. The positive brain samples were bioassayed in Webster Swiss mice. The serum samples of mice were examined for T. gondii antibodies by IFAT at 6 weeks post inoculation, and T. gondii cysts were searched in brain tissue samples of seropositive mice. The positive samples were genotyped by using a PCR-RLFP method. Subsequently, GRA6 sequences of isolates were analyzed using a phylogenetic method. The results revealed that T. gondii DNA was detected in 54% (20/37, 95% CI 38.4-69.0%) brain samples of ovine aborted fetuses. In bioassay of mice, only 2 samples were virulent and the mice were killed at 30 days post inoculation, while the others were non-virulent to mice. The size of cysts ranged 7-22 ìm. Complete genotyping data for GRA6 locus were observed in 5 of the 20 samples. PCR-RLFP results and phylogenetic analysis revealed that all of the isolated samples were closely related to type I. For the first time, we could genotype and report T. gondii isolates from ovine aborted fetuses in Khorasan Razavi Province, Iran. The results indicate that the T. gondii isolates are genetically related to type I, although most of them were non-virulent for mice. [ABSTRACT FROM AUTHOR]

Sexual violence represents a widespread social problem associated with serious lifelong consequences. In many cases, an outcome of sexual violence is the victim's unwanted pregnancy, usually ended in an abortion. The objective of this paper is to report five rape cases, including rapes of a minor and young woman, two incest cases and a case of human trafficking for sexual exploitation, where every case resulted in the victim's pregnancy. In each case, pregnancy was terminated in the first trimester or at the beginning of the second trimester in the relevant medical center or clinic. Fresh fetal blood or aborted tissue samples were delivered to our laboratory in order to perform paternity testing for the purpose of proving the crime. DNA extraction using Qiagen Dneasy™ Tissue Kit was optimized according to the sample type. Amplification of autosomal STR (Short Tandem Repeat) markers was performed using the PowerPlex®16 System. In two cases, mixtures of maternal and fetal DNA in the aborted fetal material were found. Using the LRmix Studio v.2.1.5 Software for interpreting DNA mixtures based on a probabilistic model, the likelihoods of maternal contribution and presence of fetal allelic variants inherited from the alleged father/suspect were calculated. Based on these results, we confirmed the presence of assumed fetal fractions (determined before software analysis) in the mixtures. In all cases, positive paternity proved the crime (probabilities of paternity >99.9999%). This cases report once again pointed out the importance of DNA analysis in the process of clarifying and solving forensic cases and demonstrated that the LRmix Studio v.2.1.5 Software can deal with complex cases such as sexual assaults., 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 and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objetivo. Identificar los factores asociados al aumento en la probabilidad de ocurrencia del aborto bovino, permitiendo la implementación de programas de control efectivos. Materiales y métodos. Se trabajó con una prevalencia superior al 5% según datos obtenidos por Colácteos en el 2003 de la cuenca lechera. Los factores de riesgo asociados a la presentación de aborto se agruparon en agentes etiológicos de origen infeccioso y de origen no infeccioso. Para la identificación de los factores de riesgo se analizó la información para los años 2006-2007, obtenida de registro que reportan la presentación de abortos en fincas de la cuenca lechera. Los datos insuficientes se complementaron con la aplicación de una encuesta para cada finca que incluyó las variables consideradas como factores de riesgo. El diseño para identificar los factores correspondió a un estudio de casos y controles, donde se calculó el Odds Ratio para cada variable en estudio y se validó con el modelo de regresión logística multivariado. Resultados. Se encontró en las variables, ausencia de sistemas de drenaje con un OR 4.42(P 0.006) y la ausencia de pozo séptico con OR 5.59(P 0.033).Conclusiones. Los abortos se presentan con mayor frecuencia en vacas adultas entre el segundo y cuarto parto, durante el último tercio de la gestación y en los primeros 5 meses del año. Los factores de riesgo asociados a la presentación de aborto fueron la ausencia de sistemas de drenaje y de pozo séptico para el manejo de aguas residuales y aguas lluvias.

Objectives: This qualitative study explores how individuals recently experiencing abortions feel about donating fetal tissue for research. In addition, we sought to identify motivating or discouraging factors that influence decision making for these individuals., Study Design: We recruited individuals living in Hawaii who reported undergoing an abortion in the previous 6 months for one-on-one semi-structured interviews as part of a broader study investigating views on peri-abortion research practices and protections. We devoted approximately 15 minutes of each 1-hour interview to discussing the donation of aborted fetal tissue for research. We double coded transcribed interviews and identified themes related to fetal tissue donation., Results: We interviewed 25 respondents and identified 4 themes. (1) Individuals viewed fetal tissue donation as an opportunity to help others. (2) Respondents preferred for aborted fetal tissue to be used rather than discarded. (3) Respondents viewed the fetal tissue to be an extension of themselves, so informed consent is critical. (4) Information found online promotes mistrust of fetal tissue handling., Conclusions: Individuals who have had an abortion are open to fetal tissue donation for research purposes. Pre-abortion counseling could be improved by clarifying the process of fetal tissue handling and, when available, discussing options for fetal tissue donation., Implications: Informed pregnant individuals who have had an abortion appear to be supportive of fetal tissue research and their views can differ from the concerns of ethicists, politicians, and scientists. The perspective of the individuals donating fetal tissue should be included in future discussions of fetal tissue research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bovine gammaherpesvirus 6 (BoGHV6), formerly known as bovine lymphotropic virus, is a member of the Macavirus genus, subfamily Gammaherpesvirinae, family Herpesviridae, that was initially associated with proliferative diseases in cattle. While the Macavirus genus contains agents, including alcelaphine gammaherpesvirus 1 (AlGHV1), ovine gammaherpesvirus 2 (OvGHV2), and caprine gammaherpesvirus-2 (CpGHV2), known to cause malignant catarrhal fever (MCF), and are collectively referred to as MCF virus (MCFV) group of organisms, diseases and/or clinical syndromes have not been associated with BoGHV6 and porcine lymphotropic herpesvirus (PLHV). This report investigated the occurrence of BoGHV6 in tissues of aborted dairy fetuses known to be infected by Histophilus somni to identify possible disease patterns associated with infection by this Macavirus. A nested-PCR (nPCR) assay was used to amplify the BoGHV6 polymerase gene from multiple tissues of 13 fetuses and the cow of one of these which were derived from seven dairy herds located in three geographical regions of Brazil. Direct sequencing confirmed the results of the nPCR assays. Additionally, all fetal tissues were previously investigated for the presence of H. somni, Listeria monocytogenes, Neospora caninum, Brucella abortus, Leptospira spp., bovine alphaherpesvirus 1, and bovine viral diarrhea virus (BVDV) by PCR and/or RT-PCR assays. The nPCR assay amplified BoGHV6 DNA from fetuses of most dairy herds (85.7%; 6/7) investigated, resulting in the amplification of BoGHV6 from 76.9% (10/13) of all fetuses evaluated from two geographical and important cattle-producing regions of Brazil. Furthermore, only BoGHV6 was identified in the spleen (n = 3), myocardium, and kidney (n = 2) of five fetuses, and BoGHV6 was the only agent associated with myocarditis in one of these. Nevertheless, dual, triple, and quadruple infections (including BVDV, B. abortus, and N. caninum) were identified in fetuses that were concomitantly infected by H. somni. Phylogenetic analysis revealed that the strain herein identified has 100% nucleotide (nt) sequence identity with wild type strains of BoGHV6 circulating in ruminants from Brazil and 99.8% nt identity with the reference strain of BoGHV6 but was 72.2-73.3% and 67.4-68.2% different from members of the MCFV group and PLHV, respectively. These results demonstrated that 76.9% of the fetuses evaluated were infected by BoGHV6, most likely via vertical infection resulting in transplacental transmission. Considering that most fetuses were concomitantly infected by BoGHV6 and H. somni the real impact of this viral infection cannot be efficiently determined. However, since BoGHV6 was the only pathogen identified in the myocardium of one fetus with myocarditis by histopathology, the possible participation of this Macavirus in the etiopathogenesis of the myocardial disease observed in this fetus cannot be ignored or discarded. However, the mere amplification of BoGHV6 DNA from the myocardium is not enough to establish a definite association between cause and effect, since in situ evaluations and experimental studies would be needed to confirm this agent in the etiopathogenesis of fetal diseases and/or abortions in cattle. Consequently, additional studies are needed to determine the exact role, if any, of BoGHV6 in the development of fetal disease, and possibly fetal mortality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the incidence and types of chromosomal abnormalities in pregnancy loss and aborted fetuses with anomaly and compare the performance of subtelomeric MLPA and chromosomal microarray analysis (CMA) in these specimens., Methods: Samples were collected from spontaneous miscarriages, stillbirths and aborted fetuses with anomaly between January 2015 and April 2019. Chromosomal abnormalities were detected using subtelomeric MLPA and CMA., Results: Among the 172 miscarriage samples, CMA detected pathogenic chromosomal abnormalities in 88 cases. MLPA could identified all aneuploidies and most pathogenic CNVs, missing all polyploidies; Of the 30 stillbirths, one pathogenic CNV and two VOUS were identified by CMA, all of which were missed from MLPA; Of the 135 aborted fetuses with anomaly, CMA identified pathogenic chromosomal abnormalities in 32 fetuses (23.7%); 18.95% in fetuses with isolated, and 35% in fetuses with multiple anomalies. MLPA can identify all aneuploidies but missing most pathogenic CNVs., Conclusion: Our systematical comparison of subtelomeric MLPA and CMA for chromosomal analysis of tissue from pregnancy loss and aborted fetuses with anomaly is useful for assessing clinical utility of these techniques. MLPA screening, coupled with CMA analysis, is a cost-effective approach to detect chromosomal abnormalities in miscarriage and anomalous fetuses. However, MLPA might not be appropriate for chromosome analysis in stillbirth without structural anomaly; further research with more samples is needed.

Introduction. Pentalogy of Cantrell is a very rare congenital multiple malformation with the poor outcome. Syndrome included the following pentad: abdominal wall defect, a defect of the lower sternum, anterior diaphragm defect, ectopia cordis, as well as a variety of intracardiac anomalies. Case Report. In the fifteenth week of the twin pregnancy, ultrasound examination showed multiple anomalies in one, as well as the absence of the nose apex in the other twin. The autopsy of the fetuses was performed after the abortion had been approved by the Ethics Committee. The external examination of the fetus number one showed ectopic heart and omphalocele. The internal examination revealed the existence of sternum cleft, ectopic heart and part of the left lung outside the thoracic cavity, the presence of diaphragmatic hernia with protrusion of abdominal organs, heart with only one large vessel and the horseshoe kidney. The full expression of the Pentalogy of Cantrell was confirmed. The external and internal examination of the other twin showed just agenesis of the nose apex. Conclusion. Recognition and diagnosis of the syndrome is of the exceptional importance. Proper and timely diagnosis should contribute to good outcome of the pregnancy and delivery. [ABSTRACT FROM AUTHOR]

Holoprosencephaly is a central nervous system malformation, characterized by incomplete or total lack of division of prosencephalon hemispheres, which is commonly accompanied by craniofacial malformations. A 9-month-gestation aborted American Quarter Horse fetus was submitted for postmortem examination. The fetus lacked haircoat and had severe facial malformations including marked shortening/absence of the maxillary, incisive and nasal bones, bilateral anophthalmia, and pre-maxillary agenesis. The prosencephalon was small and nearly spherical, represented by a single lobe, with no visible separation between cerebral hemispheres. The olfactory bulbs, piriform lobes, and the optic chiasm were absent. At cross sectioning of the prosencephalon, the inner structures of the brain were completely absent, and replaced by a monoventricle lined by the remaining compressed cortex, and the thalami were fused. Since mutations in the sonic hedgehog (SHH) gene have been associated with human holoprosencephaly, the three coding SHH exons were sequenced using liver DNA of the aborted foal. The obtained SHH sequence was similar to the Equus caballus SHH mRNA sequence deposited in Genbank (XM_023640069.1); therefore, no polymorphism in the coding region of this gene justifying the phenotype was observed. This is the first report of alobar holoprosencephaly in horses., (Copyright © 2022. Published by Elsevier Inc.)

Bovine herpesvirus 1 (BHV-1) is frequently associated with abortion in naturally and experimentally infected cattle. Most of the virus isolation and immunofluorescent antibody protocols described in the literature for detecting BHV-1 in bovine foetuses are rather laborious, costly and time-consuming. The detection is described of BHV-1 in the tissues of a naturally aborted bovine foetus by a nested PCR assay with no further hybridization procedures. Optimal results were achieved by filtering the foetal tissues on a chromatography column before DNA extraction, by using two pairs of primers in a nested PCR and by evaluating the amplification products on silver-stained polyacrylamide gels. This nested PCR was faster and easier to perform than the virus isolation test. To our knowledge, this is the first time that BHV-1 has been detected in the tissues of a naturally infected bovine foetus by means of a nested PCR. The test seems to be a practical alternative for rapid detection of BHV-1 in bovine foetus. [ABSTRACT FROM AUTHOR]

Background: Desbuquois dysplasia type 2 (DBQD2) is an infrequent dysplasia with a wide range of symptoms, including facial deformities, growth retardation and short long bones. It is an autosomal recessive disorder caused by mutations in the XYLT1 gene that encodes xylosyltransferase-1., Case Presentation: We studied an aborted fetus from Iranian non-consanguineous parents who was therapeutically aborted at 19 weeks of gestation. Ultrasound examinations at 18 weeks of gestation revealed growth retardation in her long bones and some facial problems. Whole-exome sequencing was performed on the aborted fetus which revealed compound heterozygous XYLT1 mutations: c.742G>A; p.(Glu248Lys) and c.1537 C>A; p.(Leu513Met). Sanger sequencing and segregation analysis confirmed the compound heterozygosity of these variants in XYLT1., Conclusion: The c.1537 C>A; p.(Leu513Met) variant has not been reported in any databases so far and therefore is novel. This is the third compound heterozygote report in XYLT1 and further supports the high heterogeneity of this disease., (© 2022. The Author(s).)

Objective: The evaluation of quantitative fluorescence PCR (QF-PCR) and single nucleotide polymorphism array (SNP array) analysis for the identification of chromosomal abnormalities in products of conception (POC)., Materials and Methods: A total of 1,094 POC samples were processed at Gennet in the years 2018-2020. Chromosomal aneuploidies were tested by QF-PCR using a Omnibor set (STR markers 13, 18, 21, X a Y), SAB-I set (STR markers 2, 7, 15, 16, 22), SAB-II set (from November 2019, STR markers 4, 6, 14) followed by SNP array analysis (Illumina) on samples with a negative QF-PCR result. All POC samples were tested for maternal contamination., Results: After exclusion of maternal contamination (32% samples) the total number of 742 POC samples were tested by QF-PCR. Chromosomal aneuploidies were found in 273 POC samples (36.8%). Then, 469 QF-PCR negative POC samples were tested by SNP array analysis. Normal female/male profile was confirmed in 402 samples (85.7%) and chromosomal aneuploidies and chromosomal aberrations (deletion/duplication > 10 Mb) in 51 samples (10.9%). Microdeletion/microduplication was found in 16 POC samples (3.4%), two were classified as pathogenic variants and 14 as variants of unknown significance. In a group of women > 35 years of age, statistically significant increase of the chromosomal abnormalities was confirmed. No statistically significant difference between the in vitro fertilization group and the group of spontaneous conception was found., Conclusion: The application of the molecular work-up based on the stepwise use of QF-PCR and SNP array clarifies the cause of the abortion in 43% POC samples. The overall detection rate in the I. trimester was 50.4%.

Toxoplasma gondii (T. gondii) is an intracellular protozoan that infects the fetus through the placenta and leads to severe complications in the fetus. One of the complications of congenital toxoplasmosis is spontaneous abortion. The prevalence of toxoplasmosis infection was investigated among spontaneously aborted fetuses (SAFs), and the genotypes of parasite isolates were determined in the present study. Placentas from 330 samples of SAFs were collected in Jahrom (Fars province) from February to September 2018. DNA was extracted from each placental tissue. The T. gondii infection was detected using nested polymerase chain reaction (Nested-PCR) assay based on a 529 bp repeat element (RE) gene. Afterward, Toxoplasma was genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) based on the GRA6 gene. The frequency of T. gondii infection was found to be 14.5% (48 out of 330 samples). Genotyping of nine T. gondii isolates revealed that all belonged to genotype II. Statistically, the prevalence of T. gondii infection was significantly correlated with the education levels of the mothers and the age of the fetus (P < 0.05). The lowest prevalence of Toxoplasma infection belonged to mothers with university education and the highest frequency of infection was observed among the fetuses in the age group of 8-9 weeks. The findings of the present study suggest a significant role for toxoplasmosis in SAFs in Jahrom city., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission., (© 2021. The Author(s).)

Porcine circovirus type 3 (PCV3) is an emerging circovirus that is highly distributed among swine worldwide and associated with porcine dermatitis and nephropathy syndrome, reproductive failure, and multisystemic inflammation. Here, we investigated and characterized PCV3 from aborted fetuses in Vietnam. We found that the whole genomes of PCV3 collected in these Vietnamese pig farms share 98.4-99.45% sequence identity with reference PCV3 sequences. Several distinct mutation were identified in both the Rep protein and Cap protein of these strains. These strains were clustered into two distinct subtypes (3a1 and 3b). This study contributes to a better understanding of the molecular characteristics and genetic diversity of PCV3 in Vietnam., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The progress in morphological science results from the greater possibilities of intra-pubic diagnosis and treatment of congenital disabilities, including the motor system. However, the structure and macroscopic development of the calcaneal tendon have not been investigated in detail. Studies on the adult calcaneal tendon showed that the calcaneal tendon is composed of twisted subtendons. This study aimed to investigate the internal structure of the fetal calcaneal tendon in the second trimester., Materials and Methods: Thirty-six fetuses fixed in 10% formaldehyde were dissected using the layer-by-layer method and a surgical microscope., Results: The twisted structure of the calcaneal tendon was revealed in all specimens. The posterior layer of the calcaneal tendon is formed by the subtendon from the medial head of the gastrocnemius muscle. In contrast, the anterior layer is formed by the subtendon from the lateral head of the gastrocnemius muscle. The subtendon from the soleus muscle constitutes the anteromedial outline of the calcaneal tendon. The lateral outline of the calcaneal tendon is formed by the subtendon originating from the medial head of the gastrocnemius muscle. In contrast, the medial outline is formed by the subtendon from the soleus muscle. In most of the examined limbs, the plantaris tendon attached to the tuber calcanei was not directly connected to the calcaneal tendon., Conclusions: The twisted structure of the subtendons of the fetal calcaneal tendon is already visible in the second trimester and is similar to that seen in adults., (© 2020. The Author(s).)

Purpose: To establish normal reference values for the human Tympanic Ring (TR) during prenatal development, and to describe and interpret its growth dynamics., Methods: Fifty spontaneously aborted human fetuses aged 12-37 weeks with normal external characteristics were evaluated. The parameters measured in the TR were the cephalocaudal and dorsoventral axes, total area, thickness, height, and length and angle of the notch of Rivinus (NR). Data were subjected to statistical analysis., Results: The following values were obtained at the end of fetal development: cephalocaudal and dorsoventral axes, 10.03 and 8.3 mm, respectively; ratio between the two axes, 120%; total area, 65.63 mm 2 ; height and thickness, 0.88 mm and 1.10 mm, respectively; and length and angle of the NR, 4.66 mm and 26.2 degrees, respectively. There were variations in the length of the dorsoventral axis throughout fetal development that affected all other parameters, except for the cephalocaudal axis. There were no sex-based differences in TR size., Conclusion: The prenatal development of the TR is dynamic as evidenced by the size variations noted throughout fetal development. Notwithstanding, this structure is a reliable and sensitive marker of developmental abnormalities of the external and middle ear., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Human organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell-cell interactions, we describe InterCom, an R-Package we developed for identifying receptor-ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2-dimensions and those expanded in 3-dimensions to fetal tissue identifies that progenitors expanded in 3-dimensions are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.

Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease., Competing Interests: RK, FL, SN, CC, AB, SH No competing interests declared, AD serves on the advisory boards of Triplet Therapeutics. and holds partly a Patent B 06291873.5, "Anaplerotic therapy of HD and other polyglutamine diseases.", (© 2021, Kacher et al.)

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo . Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: The majority of early pregnancy losses are due to chromosomal abnormalities, which can be evaluated by testing the products of conception (POCs). Traditionally, a dilation and curettage (D&C) is recommended to patients to obtain suitable tissue for analysis. This case series sought to determine whether patients with first-trimester pregnancy losses can successfully obtain analysis of POCs if they pass tissue with expectant management or misoprostol, rather than D&C., Materials and Methods: This is a retrospective cohort study of patients who desired analysis of POCs following an early pregnancy loss. The POCs were collected either at home by patients, or by providers following a D&C, and sent to an outside laboratory for single nucleotide polymorphism (SNP) microarray analysis., Results: Of 50 identified patients, chromosomal analysis was successfully completed on: 22/34 (65%) of patients who passed pregnancy with misoprostol, 14/14 (100%) with D&C, and 1/2 (50%) with expectant management (x 2 , p = 0.03). Analysis was successful up to 9 days after tissue was collected, and 55 days after diagnosis of loss., Conclusion: In our study, D&C was the superior method to obtain POCs for chromosomal analysis following a miscarriage, but medical and expectant management still had clinically acceptable success rates as well. Although further study is indicated, this small case series suggests that patient counselling regarding miscarriage management and desired chromosomal analysis should continue to include misoprostol and expectant management as inferior but still appropriate alternatives to D&C., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Dry age-related macular degeneration (AMD) is marked by the accumulation of extracellular and intracellular lipid-rich deposits within and around the retinal pigment epithelium (RPE). Inducing autophagy, a conserved, intracellular degradative pathway, is a potential treatment strategy to prevent disease by clearing these deposits. However, mTOR inhibition, the major mechanism for inducing autophagy, disrupts core RPE functions. Here, we screened autophagy inducers that do not directly inhibit mTOR for their potential as an AMD therapeutic in primary human RPE culture. Only two out of more than thirty autophagy inducers tested reliably increased autophagy flux in RPE, emphasizing that autophagy induction mechanistically differs across distinct tissues. In contrast to mTOR inhibitors, these compounds preserved RPE health, and one inducer, the FDA-approved compound flubendazole (FLBZ), reduced the secretion of apolipoprotein that contributes to extracellular deposits termed drusen. Simultaneously, FLBZ increased production of the lipid-degradation product β-hydroxybutyrate, which is used by photoreceptor cells as an energy source. FLBZ also reduced the accumulation of intracellular deposits, termed lipofuscin, and alleviated lipofuscin-induced cellular senescence and tight-junction disruption. FLBZ triggered compaction of lipofuscin-like granules into a potentially less toxic form. Thus, induction of RPE autophagy without direct mTOR inhibition is a promising therapeutic approach for dry AMD.

Introduction: The tibialis anterior muscle originates from the medial part of the anterior compartment, from the upper two-thirds of the lateral surface of the tibia and the adjacent part of the interosseous membrane, and typically inserts to the medial cuneiform and first metatarsal bone. The goal of the study was to examine the insertion of the tibialis anterior tendon and create a classification in human fetuses., Materials and Methods: Fifty spontaneously-aborted human fetuses (26 male, 24 female, 100 lower limbs), aged 18-38 weeks of gestation at death were examined., Results: The classification comprised five types of tibialis anterior tendon insertion. The most common was Type V (60%), which was characterized by a single tendon inserting onto the medial cuneiform bone. The second most frequent was Type I (19%), which was characterized by a tendon which split into two equal-sized parts that insert to the medial cuneiform bone and the base of the first metatarsal. The third was Type II (12%), which was characterized by a tendon splitting into two different-sized parts that inserted onto the medial cuneiform bone (larger component) and the base of the first metatarsal (smaller component). The fourth type was Type III (5%), which was also characterized by a tendon splitting into two different-sized parts that inserted onto the medial cuneiform bone (smaller component) and the base of the first metatarsal (larger component). Finally, Type VI (4%), the least frequent type, was characterized by a tendon splitting into three different-sized parts, inserting onto the medial cuneiform bone (the smallest component) and the base of the first metatarsal (the middle and larger component)., Conclusion: The tibialis anterior muscle is characterized by high variability in the approach of its tendon to the foot, at least in fetuses. This is classified in the present study for the first time., (© 2020 Wiley Periodicals LLC.)

Abortion providers' approaches to patient-centred pregnancy tissue viewing (PCV) - when a patient requests to see their products of conception - is understudied in abortion care. This mixed-method study aimed to identify: (1) if, when, and how PCV is facilitated at US independent abortion clinics; (2) how staff are trained to offer viewing; and (3) provider experiences facilitating PCV. We surveyed administrators from 22 independent abortion clinics affiliated with the Abortion Care Network about their PCV practices and then completed in-depth semi-structured interviews with 25 providers to better understand their experiences facilitating PCV. Results indicate that most of the clinics that provide PCV do so by patient request. A variety of providers facilitate viewing, including counsellors, educators, physicians, nurses, and medical assistants. Timing, viewing location, and staff training vary by facility. Benefits of and barriers to PCV emerged through three themes: (1) patient-centred care; (2) misinformation about fetal tissue; and (3) personal navigations as providers. Providers and administrators report PCV aligns with their patient-centred clinic missions and offers patients opportunities for choice, closure, and access to information. Yet, anti-abortion misinformation about fetal tissue impacts the ways providers must navigate complex conversations about PCV professionally and personally. Clinic resources and concern about adverse patient reactions to identifiable fetal parts present barriers to offering viewing. Understanding providers' experiences and approaches to PCV is an important first step to developing quality practices that can be shared across clinics. The findings of this study support the need for more research and training on PCV in abortion care.