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Journal of Medical Case Reports May 2024Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized...
BACKGROUND
Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized by partial or complete fusion of lower extremities, renal agenesis, absent urinary tract, ambiguous external genitalia, imperforate anus, and single umbilical artery. Sirenomelia is often associated with several visceral congenital malformations, rendering it invariably incompatible with extrauterine life.
CASE PRESENTATION
We present the case of 22-year-old Black African woman who delivered a term newborn by caesarean section at a gestation age of 37 weeks due to obstructed labor with fetal distress. The newborn was a fresh stillbirth weighing 2100 g and had fusion of the lower extremities, a single upper limb, ambiguous genitalia, imperforate anus, and a cleft lip. The mother had made only two prenatal visits, at which she was found to be normotensive and normoglycemic. She was not screened for routine fetomaternal infections and missed supplementation for folic acid during the critical first trimester. She did not undergo any obstetric ultrasonography. The parents of the newborn were not close relatives and there was no family history of consanguinity. Further genetic testing was not performed due to lack of laboratory capacity, and post mortem examination was not permitted due to cultural taboo and restrictions relating to handling of deceased newborns.
CONCLUSION
Sirenomelia is a rare congenital malformation with very poor prognosis. Specific interventions during pre-conception and early prenatal care are critical in the prevention of specific congenital anomalies. Early obstetric ultrasonography is invaluable for diagnosis of sirenomelia as well as counseling for possible termination of pregnancy.
Topics: Humans; Female; Infant, Newborn; Ectromelia; Cleft Lip; Pregnancy; Abnormalities, Multiple; Young Adult; Stillbirth; Tanzania
PubMed: 38706003
DOI: 10.1186/s13256-024-04549-5 -
Nature Communications Apr 2024The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity...
The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.
Topics: Humans; Female; Animals; Mice; Smallpox; Antibodies, Monoclonal; Poxviridae Infections; Vaccinia; Vaccinia virus; Orthopoxvirus; Antibodies, Viral
PubMed: 38627363
DOI: 10.1038/s41467-024-47328-y -
Frontiers in Genetics 2023spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies...
spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies with microcephaly, with a wide phenotypic continuum that ranges from Roberts syndrome (MIM #268300) at the severe end to SC phocomelia (MIM #269000) at the milder end. encodes a 601-amino acid protein belonging to the Eco1/Ctf7 family of acetyltransferases that is involved in the establishment of sister chromatid cohesion, which is essential for accurate chromosome segregation and genomic stability and thus belongs to a group of disorders called "cohesinopathies". We describe a 15-year-old Malaysian female who presented with the characteristic triad of spectrum disorder, with an equivocal chromosomal breakage study and normal karyotyping findings. She was initially suspected to have mosaic Fanconi anemia but whole exome sequencing (WES) showed a likely pathogenic homozygous splice variant c.955 + 2_955+5del in the gene. During the 15-year diagnostic odyssey, she developed type 2 diabetes mellitus, primary ovarian insufficiency, increased optic cup-to-disc ratio with tortuous vessels bilaterally, and an evolving but distinct facial and skin hypopigmentation phenotype. Of note, there was an absence of learning disabilities. Our findings provide further evidence for spectrum disorder in an Asian child and contribute to defining the clinical and radiographic spectrum.
PubMed: 38288163
DOI: 10.3389/fgene.2023.1286489 -
Journal of Anatomy Jun 2024The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular...
The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies.
Topics: Humans; Male; Ectromelia; Female; Magnetic Resonance Imaging; Abnormalities, Multiple; Pregnancy; Fetus
PubMed: 38267217
DOI: 10.1111/joa.14015 -
International Journal of Molecular... Dec 2023Ectromelia virus (ECTV) is a causative agent of mousepox. It provides a suitable model for studying the immunobiology of orthopoxviruses, including their interaction...
Ectromelia virus (ECTV) is a causative agent of mousepox. It provides a suitable model for studying the immunobiology of orthopoxviruses, including their interaction with the host cell cytoskeleton. As professional antigen-presenting cells, dendritic cells (DCs) control the pericellular environment, capture antigens, and present them to T lymphocytes after migration to secondary lymphoid organs. Migration of immature DCs is possible due to the presence of specialized adhesion structures, such as podosomes or focal adhesions (FAs). Since assembly and disassembly of adhesive structures are highly associated with DCs' immunoregulatory and migratory functions, we evaluated how ECTV infection targets podosomes and FAs' organization and formation in natural-host bone marrow-derived DCs (BMDC). We found that ECTV induces a rapid dissolution of podosomes at the early stages of infection, accompanied by the development of larger and wider FAs than in uninfected control cells. At later stages of infection, FAs were predominantly observed in long cellular extensions, formed extensively by infected cells. Dissolution of podosomes in ECTV-infected BMDCs was not associated with maturation and increased 2D cell migration in a wound healing assay; however, accelerated transwell migration of ECTV-infected cells towards supernatants derived from LPS-conditioned BMDCs was observed. We suggest that ECTV-induced changes in the spatial organization of adhesive structures in DCs may alter the adhesiveness/migration of DCs during some conditions, e.g., inflammation.
Topics: Animals; Mice; Ectromelia virus; Ectromelia, Infectious; Adhesives; Adhesiveness; Dendritic Cells
PubMed: 38203729
DOI: 10.3390/ijms25010558 -
Cells Dec 2023Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability...
Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability to prime and polarize naïve T cells into different effector T helper (Th) subsets. The two major subpopulations of cDCs, cDC1 (CD8α in mice and CD141 in human) and cDC2 (CD11b in mice and CD1c in human), can preferentially polarize T cells toward a Th1 and Th2 phenotype, respectively. During infection with ectromelia virus (ECTV), an orthopoxvirus from the family, the timing and activation of an appropriate Th immune response contributes to the resistance (Th1) or susceptibility (Th2) of inbred mouse strains to the lethal form of mousepox. Due to the high plasticity and diverse properties of cDC subpopulations in regulating the quality of a specific immune response, in the present study we compared the ability of splenic cDC1 and cDC2 originating from different ECTV-infected mouse strains to mature, activate, and polarize the Th immune response during mousepox. Our results demonstrated that during early stages of mousepox, both cDC subsets from resistant C57BL/6 and susceptible BALB/c mice were activated upon in vivo ECTV infection. These cells exhibited elevated levels of surface MHC class I and II, and co-stimulatory molecules and showed enhanced potential to produce cytokines. However, both cDC subsets from BALB/c mice displayed a higher maturation status than that of their counterparts from C57BL/6 mice. Despite their higher activation status, cDC1 and cDC2 from susceptible mice produced low amounts of Th1-polarizing cytokines, including IL-12 and IFN-γ, and the ability of these cells to stimulate the proliferation and Th1 polarization of allogeneic CD4 T cells was severely compromised. In contrast, both cDC subsets from resistant mice produced significant amounts of Th1-polarizing cytokines and demonstrated greater capability in differentiating allogeneic T cells into Th1 cells compared to cDCs from BALB/c mice. Collectively, our results indicate that in the early stages of mousepox, splenic cDC subpopulations from the resistant mouse strain can better elicit a Th1 cell-mediated response than the susceptible strain can, probably contributing to the induction of the protective immune responses necessary for the control of virus dissemination and for survival from ECTV challenge.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Ectromelia, Infectious; Poxviridae Infections; Cytokines; Dendritic Cells
PubMed: 38201217
DOI: 10.3390/cells13010013 -
Comparative Medicine Oct 2023Four strains of experimentally naïve mice (NOD. Cg- Il2rg /SzJ [NSG], NOD. Cg- /SzJ [NRG], B6.129S(Cg)-/J [STAT1 ], and B6.129S7- /J[IFNγR ] housed in a barrier...
Four strains of experimentally naïve mice (NOD. Cg- Il2rg /SzJ [NSG], NOD. Cg- /SzJ [NRG], B6.129S(Cg)-/J [STAT1 ], and B6.129S7- /J[IFNγR ] housed in a barrier facility developed unusual and seemingly unrelated clinical signs. Young NSG/NRG mice ( = 49, mean age = 4 ± 0.4 mo) exhibited nonspecific clinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRG mice, the STAT1 and IFNγ R mice ( = 5) developed large subcutaneous abscesses on the head and neck. These mice were euthanized, and samples were collected for culture. NSG/NRG mice had moderate-markedly enlarged livers (20 of 49, 40%) and spleens (17 of 49, 35%). The livers contained multiple, variably-sized, tan regions throughout all lobes. Histology revealed necrotizing hepatitis (13 of 17, 77%), splenic and hepatic extramedullary hematopoiesis (17 of 17, 100%), glomerular histiocytosis (6 of 17, 35%), and metritis (6 of 11, 55%) with perivascular inflammation, suggesting hematogenous spread Differentials for these lesions included mouse hepatitis virus, ectromelia virus, spp., and was cultured from liver lesions and subcutaneous abscesses and confirmed with 16S ribosomal RNA sequencing. After completing systematic testing of the environment, failure of the water autoclave cycle was suspected as the cause of the outbreak. To address the situation, individually ventilated racks were sanitized and new breeders were purchased; these actions dramatically reduced infections. The current literature contains few reports of infections in immunocompromised mice, and its typical presentation is torticollis and rolling. infection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice. Careful monitoring of sterilization techniques is essential to prevent such infections in a barrier facility.
Topics: Animals; Mice; Abscess; Burkholderia gladioli; Burkholderia Infections; Hepatitis; Mice, Inbred NOD; Mice, SCID
PubMed: 38087404
DOI: 10.30802/AALAS-CM-23-000016 -
BMC Veterinary Research Dec 2023Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase...
BACKGROUND
Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method.
RESULTS
In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of the crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed. The lowest detection limit of the ECTV RT- RPA assay was 100 copies of DNA mol-ecules per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 135 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement.
CONCLUSIONS
In conclusion, this RPA assay offers a novel alternative for the simple, sensitive, and specific identification of ECTV, especially in low-resource settings.
Topics: Animals; Mice; Recombinases; Ectromelia virus; Sensitivity and Specificity; Nucleic Acid Amplification Techniques; Real-Time Polymerase Chain Reaction
PubMed: 38053140
DOI: 10.1186/s12917-023-03703-3 -
International Journal of Molecular... Oct 2023The recent spread of the monkeypox virus among humans has heightened concerns regarding orthopoxvirus infections. Consequently, conducting a comprehensive study on the...
The recent spread of the monkeypox virus among humans has heightened concerns regarding orthopoxvirus infections. Consequently, conducting a comprehensive study on the immunobiology of the monkeypox virus is imperative for the development of effective therapeutics. Ectromelia virus (ECTV) closely resembles the genetic and disease characteristics of monkeypox virus, making it a valuable research tool for studying orthopoxvirus-host interactions. Guanylate-binding proteins (GBPs), highly expressed interferon-stimulated genes (ISGs), have antagonistic effects against various intracellular pathogenic microorganisms. Our previous research has shown that GBP2 has a mild but statistically significant inhibitory effect on ECTV infection. The presence of a significant number of molecules in the poxvirus genome that encode the host immune response raises questions about whether it also includes proteins that counteract the antiviral activity of GBP2. Using IP/MS and co-IP technology, we discovered that the poly(A) polymerase catalytic subunit (PAPL) protein of ECTV is a viral regulatory molecule that interacts with GBP2. Further studies have shown that PAPL antagonizes the antiviral activity of GBP2 by reducing its protein levels. Knocking out the gene of ECTV with the CRISPR/Cas9 system significantly diminishes the replication ability of the virus, indicating the indispensable role of PAPL in the replication process of ECTV. In conclusion, our study presents preliminary evidence supporting the significance of PAPL as a virulence factor that can interact with GBP2.
Topics: Animals; Mice; Humans; Ectromelia virus; Viral Proteins; Polynucleotide Adenylyltransferase; Catalytic Domain; Ectromelia, Infectious; Antiviral Agents
PubMed: 37958732
DOI: 10.3390/ijms242115750 -
Simultaneous femoral and tibial lengthening for severe limb length discrepancy in fibular hemimelia.Journal of Orthopaedic Surgery and... Nov 2023Fibular Hemimelia (FH) is the most common longitudinal limb deficiency. Significant limb length discrepancy (LLD) will necessitate long treatment times and multiple... (Review)
Review
BACKGROUND
Fibular Hemimelia (FH) is the most common longitudinal limb deficiency. Significant limb length discrepancy (LLD) will necessitate long treatment times and multiple settings to compensate for LLD when associated with femoral shortening. This study evaluates the outcome of simultaneous femoral and tibial lengthening using the Ilizarov frame.
METHODS
This retrospective study included the cases of 12 children with severe limb length discrepancy caused by combined FH and ipsilateral femoral shortening from May 2015 to August 2022. The total LLD ranged from 7 to 14.5 cm. All patients underwent single-session femoral and tibial lengthening using the Ilizarov ring external fixator technique. Additional procedures were performed in the same setting, including Achilles tendon lengthening, fibular anlage excision, peroneal tendons lengthening, and iliotibial band release. Follow-up ranged from 2 to 4 years.
RESULTS
The planned limb lengthening was achieved in ten cases (83%). No cases of joint subluxation or dislocation were encountered. No neurovascular injury has occurred during the treatment course. In all cases, the bone healing index was better on the femoral side than on the tibia. Poor regeneration and deformity of the tibia occurred in two cases (16.6%).
CONCLUSION
Simultaneous femoral and tibial lengthening using the Ilizarov fixator is a relatively safe procedure with the result of correction of total LLD in one session in a shorter time and less morbidity.
Topics: Child; Humans; Tibia; Ectromelia; Retrospective Studies; Fibula; Bone Lengthening; Ilizarov Technique; Leg Length Inequality; Leg; Treatment Outcome
PubMed: 37936235
DOI: 10.1186/s13018-023-04229-y