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Voprosy Virusologii Sep 2023The mouse-specific orthopoxvirus, ectromelia virus, is one of the best models that can be used to study key issues of pathogenesis, prevention, and treatment of...
INTRODUCTION
The mouse-specific orthopoxvirus, ectromelia virus, is one of the best models that can be used to study key issues of pathogenesis, prevention, and treatment of smallpox, and to develop measures to increase virulence, transmissibility, or the ability to overcome vaccine immunity. The aim of the work is to screen the antiviral activity of samples from chaga and humic acid from brown coal against ectromelia virus.
MATERIALS AND METHODS
We used ectromelia virus, strain K-1 (reg. No V-142), obtained from the State Collection of Pathogens of Viral Infections and Rickettsioses of the State Scientific Center of Virology and Biotechnology "Vector"; cell culture (No 70) from the Collection of cell cultures of the State Scientific Center of Virology and Biotechnology "Vector". Nine samples from chaga and humic acid from brown coal were used to evaluate the changes in the infectivity of the ectromelia virus on cell culture using 2 schemes of application of drugs and virus (preventive and therapeutic schemes), and to assess their cytotoxicity and antiviral activity.
RESULTS
50% cytotoxic concentration, 50% virus-inhibiting concentrations and selectivity index were determined for all samples. The studied samples were shown to be non-toxic to the monolayer of cell culture in a dilution of 300 and more micrograms/ml, while demonstrated high antiviral activity against strain K-1 of ectromelia virus in two application schemes - preventive and curative.
CONCLUSION
All samples tested for ectromelia virus can be considered promising for further development of drugs against diseases caused by orthopoxviruses.
Topics: Animals; Antiviral Agents; Cell Culture Techniques; Coal; Ectromelia virus; Ectromelia, Infectious; Humic Substances; Vero Cells; Chlorocebus aethiops; Inonotus
PubMed: 38156584
DOI: 10.36233/0507-4088-174 -
Microorganisms Jul 2023The phenomenon of pathogen co-infection detected in a half-fed tick taken from a human in the south of the Far East was studied. Research was carried out on , , and...
The phenomenon of pathogen co-infection detected in a half-fed tick taken from a human in the south of the Far East was studied. Research was carried out on , , and cell lines, outbred mice, and chicken embryos using ELISA, PCR, IMFA, plaque formation, and electron microscopy. The tick contained an antigen and a genetic marker of the tick-borne encephalitis virus (TBEV). The patient had post-vaccination antibodies in a titer of 1:200, as a result of which, obviously, an antibody-dependent elimination of TBEV occurred. The tick-borne co-isolate also contained an unknown pathogen ( virus), which, in our opinion, was a trigger for the activation of chronic infection in suckling white mice. In the laboratory co-isolate, ectromelia virus was present, as evidenced by paw edema during the intradermal infection of mice, characteristic rashes on the chorioallantoic envelope of chicken embryos, and typical plaques on Vero-E6. The virus was not pathogenic for white mice and chicken embryos, but it successfully multiplied in the , , and lines. Viral co-infection was confirmed by electron microscopy. Passaging on mice contributed to an increase in the virulence of the co-isolate, whose titer increased by 10,000 times by the fifth passage, which poses an epidemiological danger.
PubMed: 37512963
DOI: 10.3390/microorganisms11071791 -
Acta Naturae 2023Among the nonvirion proteins of the vaccinia virus (VACV), a 94-kDa long protein is most abundantly present; the protein is a truncated form of the 150-kDa A-type...
Among the nonvirion proteins of the vaccinia virus (VACV), a 94-kDa long protein is most abundantly present; the protein is a truncated form of the 150-kDa A-type inclusion (ATI) protein of the cowpox virus encoded by the gene. This VACV protein does not form intracellular ATIs, being as it is a major immunogen upon infection/immunization of humans or animals with the VACV. Antibodies specific to this protein are not virus-neutralizing. The present study focused on the effect of the production of this nonstructural major immunogenic VACV protein on the manifestation of pathogenicity and immunogenicity of the virus in the BALB/c mouse model of infection. In order to introduce a targeted deletion into the VACV LIVP genome, the recombinant integration/deletion plasmid pΔati was constructed and further used to generate the recombinant virus LIVPΔati. The pathogenicity of the VACV LIVP and LIVPΔati strains was studied in 3-week-old mice. The mice were intranasally infected with the viruses at a dose of 107 pfu; 50% of the animals infected with the parent LIVP strain died, while infection with the LIVPΔati strain led to the death of only 20% of the mice. Intradermal vaccination of mice aged 6- weeks with the LIVPΔati virus statistically significantly increased the production of VACV-specific IgG, compared to that after intradermal vaccination with VACV LIVP. Meanwhile, no differences were noted in the cell-mediated immune response to the vaccination of mice with VACV LIVP or LIVPΔati, which was assessed by ELISpot according to the number of splenocytes producing IFN-γ in response to stimulation with virus-specific peptides. Intranasal infection of mice with lethal doses of the cowpox virus or the ectromelia virus on day 60 post-immunization with the studied VACV variants demonstrated that the mutant LIVPΔati elicits a stronger protective response compared to the parent LIVP.
PubMed: 37908769
DOI: 10.32607/actanaturae.17872 -
Congenital Anomalies Nov 2023
Topics: Mice; Animals; Ectromelia; Survival Rate; Limb Deformities, Congenital; Mutation; Genetic Background
PubMed: 37726960
DOI: 10.1111/cga.12541 -
Journal of the College of Physicians... Mar 2024Null.
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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 -
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 -
The Iowa Orthopaedic Journal 2024Fibular hemimelia is the most common congenital long bone deficiency. It is often associated with femoral and tibial deficiencies which result in a clinically evident...
BACKGROUND
Fibular hemimelia is the most common congenital long bone deficiency. It is often associated with femoral and tibial deficiencies which result in a clinically evident leg length discrepancy. The primary soft tissue concern is ACL/PCL deficiency. If treatment includes bony lengthening, joint stability is imperative to avoid complications. In this study, we detail a novel technique for long bone lengthening and ACL reconstruction in a single, cohesive surgery. This consolidates the need for multiple procedures and offers improved limb length symmetry and knee stability for this patient population. Clinical outcomes of pediatric patients with hemimelia who underwent either femoral or tibial lengthening with PRECICE® nail and concomitant ACL reconstruction are presented.
METHODS
After IRB approval, we identified five patients with complex fibular hemimelia who underwent ACL reconstruction and concomitant lengthening with at least two years of follow-up. Two patients (40%) presented with congenital short femur, and three (60%) with congenital short tibia. In each case, ACL reconstruction and either femoral or tibial guided growth via PRECICE® nail were performed. Operative techniques involving both soft tissue and bony methodology are described in detail.
RESULTS
All patients had objective improvement in knee stability as assessed both intra and post operatively, as well as successful intermedullary lengthening without complications related to joint stability. Three patients had minor complications unrelated to joint stability that did not interfere with overall result.
CONCLUSION
Fibular hemimelia associated with hypoplasia of bony and soft tissue structures can be successfully addressed with concomitant ligamentous reconstruction at the time of implantation of lengthening devices. This addresses knee instability and reduces both number of operative procedures and potential complications related to joint instability while pursuing bony lengthening. .
Topics: Humans; Retrospective Studies; Ectromelia; Male; Female; Fibula; Child; Anterior Cruciate Ligament Reconstruction; Bone Lengthening; Treatment Outcome; Adolescent; Tibia; Femur
PubMed: 38919371
DOI: No ID Found -
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 Water and Health Feb 2024This study addresses the limited understanding of factors affecting the efficiency of water treatment plants in reducing trihalomethane (THM) formation through total...
This study addresses the limited understanding of factors affecting the efficiency of water treatment plants in reducing trihalomethane (THM) formation through total organic carbon (TOC) removal, highlighting significant challenges in improving treatment effectiveness. The aim of this study was to examine the influence of water quality on the efficiency of water treatment plants to remove TOC and reduce THM formation. Linear regression and correlation analyses were conducted to examine the relationship between water quality parameters and THM concentrations. The results showed that there was a negative relationship between turbidity, metals, and TOC concentration with TOC removal efficiency. Positive correlations were found between parameters and the formation of THMs in water. Of these parameters, water temperature was observed to have relatively less influence on THM formation. It was observed that seasonal variations in water quality affect the efficiency of TOC removal and THM content in treated water. THM levels in chlorinated water were found to be within the permissible range of the World Health Organization's drinking water quality guidelines. However, it is still important to maintain continuous monitoring and take measures to reduce THMs. The model demonstrated a strong correlation (R = 0.906) between predicted and measured THM values.
Topics: Ethiopia; Water Quality; Trihalomethanes; Carbon; Ectromelia; Tibia
PubMed: 38421628
DOI: 10.2166/wh.2024.276