A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Localization of epitopes in the toxins of Tityus serrulatus scorpions and neutralizing potential of therapeutic antivenoms.

Overlapping pentadecapeptides covering the complete amino acid sequence of TsII, TsVII and TsIV toxins from the venom of scorpion Tityus serrulatus (Ts), were prepared by use of the Spot method of multiple peptide synthesis. Horse anti-Ts antisera for therapeutic use were tested for their binding to peptides. All nine antisera tested showed reactivity with several peptides from the three toxins. Three antigenic regions, one in the very N-terminal, the second in the central part and the other in the C-terminal part of the three toxins were frequently, but not constantly recognized, with an intensity that seemed to be related to the neutralizing potency of the tested antivenom. Thus the corresponding peptides (residues 1-15 and 48-62 of TsII; residues 1-15, 16-30 and 48-62 of TsIV and residues 1-15 and 47-61 of TsVII) were synthesized, coupled to KLH and used as antigens to coat the microtitration plates to determine any relationship between their ELISA reactivity with therapeutic horse antivenoms and the neutralizing potential of these antivenoms. The mixture of the N-terminal peptide of TsII, of the N-terminal TsVII peptide and of the C-terminal of TsIV was found to give a linear relationship with the neutralizing titer of horse serum of low neutralizing potency (< or =1 mg/ml). However, high neutralizing antivenoms did not show the expected response in peptide ELISA. This observation is discussed in the context of the occurrence of continuous and discontinuous epitopes on toxins.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

COVID-19 vaccination and recurrent anterior uveitis

A 35-year-old Asian Indian female previously diagnosed with bilateral anterior uveitis and on oral methotrexate developed bilateral anterior uveitis following first/second dose of coronavirus disease 2019 (COVID-19) vaccination. She had skipped her weekly dose of oral methotrexate following first dose of vaccination. Following the second dose, she reduced her oral methotrexate from 25 to 15 mg on her own, but did not stop like the previous occasion. She had extensive workup for her uveitis in the past with only positive severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies. She developed unilateral anterior uveitis after she had COVID-19 in July 2022, which resolved with topical steroids and continuation of immunosuppression. This report illustrates that COVID-19 or its vaccination may presumably play a role in triggering the immune system and can cause recurrent ocular inflammation even in the absence of an extraocular inflammation.     

An identification key for the five most common species of Metastrongylus

Species of the Metastrongylus genus, the lung nematodes of pigs that require an intermediate host (earthworm) to complete their cycle, pose a potential risk to both livestock and humans. This parasite which can result in lung pathology and mixed infections with other pathogens (e.g. viruses) can be fatal to pigs. Although this genus is distributed worldwide, there are no classification keys for identifying this common parasite species. In this work, we take advantage of parasitological surveys of wild boar (Sus scrofa) in northern and central Spain and southern Poland to develop a morphological identification key for the five most common Metastrongylus species (Metastrongylus apri, Metastrongylus pudendotectus, Metastrongylus salmi, Metastrongylus confusus and Metastrongylus asymetricus). In addition, we provide the first record of M. confusus in Spain, probably unidentified until now due to the lack of appropriate identification keys. We hope that this user-friendly identification key will enable parasitologists and veterinary practitioners to avoid further misclassifications of Metastrongylus species.     

Conservative management of unilateral condylar hyperplasia

Objective

The purpose of this study was to eliminate orthodontic treatment in mild to moderate cases of condylar hyperplasia in its early stages by condylectomy.

Patients and methods

A total of five patients (two females and three males) aged between 17 and 40 years were treated with unilateral condylectomy of the involved side without orthodontic treatment. All patients underwent standardized clinical and radiological examination at initial consultation, before surgery, immediately after surgery, and follow-up. Objective and subjective evaluation of temporomandibular joint (TMJ) included maximal incisal opening, lateral excursions, correction of facial asymmetry, occlusal harmony, TMJ pain, and jaw function. Results were recorded at 5-year follow-up.

Results

In all our cases, we achieved good mouth opening and near to normal occlusion. Good facial aesthetics was obtained after 3 months postoperative follow-up without secondary orthodontic treatment.

Conclusion

Thus, we conclude that treatment of mild to moderate cases of unilateral condylar hyperplasia during the inactive phase can be treated with condylectomy without orthodontic treatment, and it significantly improves long-term surgical outcomes.     

Toxoplasma gondii antibody profile in HIV-1-infected and uninfected pregnant women and the impact on congenital toxoplasmosis diagnosis in Rio de Janeiro, Brazil

ObjectiveCompare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women.MethodsThis study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women.ResultsThe average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL).ConclusionsCongenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.