Enfermedad del legionario en Argentina: evolución de la estrategia diagnóstica en el laboratorio / Legionnaires' disease in Argentina: Evolution of the laboratory diagnostic strategy

Resumen La enfermedad del legionario (EL) es una neumonía aguda grave, que ocurre espo-rádicamente o como epidemias, y que, generalmente, requiere hospitalización. El objetivo deeste trabajo fue describir la experiencia en el abordaje diagnóstico de laboratorio de la ELen Argentina durante el período 2016-2021. Se analizaron 168 especímenes clínicos correspondientes a 93 casos de neumonía con sospecha de EL. Las pruebas de laboratorio incluyeron ladeterminación del antígeno soluble de Legionella pneumophila serogrupo 1 en orina, la detec-ción de ADN de Legionella spp. en secreciones respiratorias bajas, por métodos moleculares convencionales y comerciales de tipo sindrómico, y el cultivo en medio selectivo. Se confirmó EL en 12 pacientes. El antígeno urinario confirmó el diagnóstico de 8 de ellos. Se recuperó L. pneumophila mediante el cultivo del material respiratorio de 6 pacientes que correspondieron a casos de neumonía asociada a cuidados de la salud y que fueron previamente diagnosticados por el método molecular comercial. La mitad de ellos no presentó antigenuria detectable. En un único paciente no hubo antigenuria detectable ni recuperación de Legionella en cultivo, y la confirmación de EL se basó en la detección de ADN de Legionella spp. por PCR en secreción respiratoria y el vínculo epidemiológico con otro caso de EL confirmado por cultivo. La detección del antígeno urinario es la prueba diagnóstica de primera línea. Sin embargo, la incorporación de métodos moleculares complementarios ha demostrado evitar falsos negativos y contribuir a un mejor conocimiento de la verdadera incidencia de la enfermedad.

Abstract Legionnaires' disease (LD) is severe acute pneumonia that occurs in sporadic or epidemic form, and generally requires hospitalizaron. The objective of this work was to describe the experience in the LD laboratory diagnostic approach in Argentina during the period 2016-2021. The laboratory analyzed 168 clinical specimens from 93 cases of suspected LD pneu-monia. Laboratory tests included the detection of the soluble antigen of Legionella pneumophila serogroup 1 in urine sample, detection of DNA of Legionella spp. in lower respiratory secre-tions by conventional and commercial molecular methods and isolation in selective medium. LD was confirmed in 12 patients. The urinary antigen allowed the diagnosis for 8 patients. L. pneumophila was isolated from the respiratory material of 6 patients suffering from health care-associated pneumonia, who had been previously diagnosed using the commercial molecular method. Fifty percent of these cases did not show detectable urinary antigen. A single patient did not shows neither detectable antigenuria nor isolation of Legionella from the respiratory sample and was diagnosed as a confirmed case of LD by the detection of DNA of Legionella spp. by PCR directly from the respiratory secretion and the epidemiological link with another case of confirmed LD by culture. Urinary antigen detection is the first-line diagnostic test. However, the incorporation of complementary molecular methods has proved to avoid false negatives and contributed to a better understanding of the true incidence of the disease.

Laboratory detection of bacterial pathogens and clinical and laboratory response of syndromic management in patients with cervical discharge: A retrospective study

Background: Cervical discharge as part of cervicitis and pelvic inflammatory disease is a cause of significant morbidity in sexually active women worldwide. Non-gonococcal and non- chlamydial bacterial pathogens are becoming more prevalent. Aims: This study aims to determine bacterial pathogens causing cervical discharge using culture and/or polymerase chain reaction and assess the clinical and laboratory response to the conventional syndromic kit regimen established by the World Health Organisation. Methods: A retrospective review of records of women with cervical discharge over one year period. Culture and/or polymerase chain reaction results of endocervical swabs of various bacterial pathogens at baseline and after four weeks of treatment with syndromic kit regimen were recorded. Results: A total of 70 case records were reviewed for clinical details, out of which results of bacterial culture and polymerase chain reaction were available for 67 cases. Infectious aetiology was found in 30 (44.7%) patients with Ureaplasma species being the most common organism isolated on culture (18, 26.8%) and polymerase chain reaction (25, 37.3%), respectively. Polymerase chain reaction for Chlamydia trachomatis and Mycoplasma hominis was positive in ten (14.9%) and four (6%) cases, respectively. None of the patients showed positive culture for Neisseria gonorrhoeae. Coinfection was seen in eight (11.9%) patients with the majority showing Chlamydia trachomatis and Ureaplasma spp. coinfection (five patients). Forty one cases (58.5%) received tab. cefixime 400 mg and tab. azithromycin one gram stat (kit 1), while 29 cases (43.3%) received tab. cefixime 400 mg stat, tab. metronidazole 400 mg and cap. doxycycline 100 mg, both twice daily for 14 days (kit 6). Minimal to no clinical improvement with treatment was seen in 14 out of 32 cases (44%) at the end of four weeks with the conventional kit regimen. Post-treatment culture and/or polymerase chain reaction were positive in nine out of 28 cases (32.1%) with Ureaplasma spp. being the most common. Limitations: Retrospective study design, small sample size and fewer cases with follow-up data were the main limitations. Conclusion: Ureaplasma spp. was the most common infectious cause of cervical discharge in our patients. Treatment given as part of syndromic management led to a clinical and microbiological response in around half and two-third cases, respectively.

A Study on Sexually Transmitted Infections Using Syndromic Approach among Patients Attending Suraksha Clinic at a Tertiary Care Hospital of West Bengal

Introduction : A proper understanding of different aspects of Sexually Transmitted Infections (STIs) in different regions of a country like India is very essential for STI control. Objectives : To assess pattern of STIs using Syndromic approach among patients attending at Suraksha Clinic and to find out treatment seeking behaviour among them. Material and Method : A cross-sectional study was conducted at a Tertiary Care Hospital of West Bengal. This retrospective study was done selecting all patients who attended the Clinic for first time from 1st May, 2020 to 30th April, 2021. Relevant records were reviewed. Descriptive statistics and chi-square test were used. Observations : In present study Suraksha Clinic attendees were mainly comprised of female (95.8%); while 65.8% and 64.2% of patients were suffering from Lower abdominal pain and Cervicovaginal discharge respectively. Nearly one-third of them (37.9%) were suffering from more than one disease. About one-fourth of patients (28.2%) accessed the STI/RTI/Suraksha Clinic directly. The treatment seeking behaviour was significantly associated with gender and education of patients. Conclusions : This Tertiary Care Hospital based study highlighted higher prevalence of certain STIs among attendees to Suraksha Clinic as well as lower proportion of male and directly walk-in patient

Vulnerability of the young university population to HIV/AIDS and other sexually transmitted infections

Introduction: Brazilian universities receive annually thousands of young people who experience situations of vulnerability to the human immunodeficiency virus, sexually transmitted infections, and viral hepatitis. Objective: The aim of the present study was to analyze the secondary data obtained from the attendance record of the rapid testing campaign for these health problems at a federal university in the state of Minas Gerais, Brazil, in 2019. Methods: A cross-sectional study was conducted with secondary data of students (n=1,113) obtained from the standard attendance form by the Ministry of Health during the campaigns Fique Sabendo (Be Aware) in the period between November 25 and 29, 2019. Analyses were performed with the support of the Statistical Package for Social Sciences program, with the calculation of absolute and relative frequencies. Pearson's chi-square test (5%) was used for comparison. Results: The results revealed a young, heterosexual, white profile. More than half reported having consumed alcohol and drugs in their lives. Other findings were the non-use of condoms with steady partners (18.1%) and occasional partners (21.3%), oral sex (86.8%), and unprotected sex in the last intercourse (45.6%). Most declared never being tested for human immunodeficiency virus (74.5%), syphilis (67.4%), hepatitis B (76.1%), or hepatitis C (77.0%). Conclusion: The university population is vulnerable to human immunodeficiency virus and other sexually transmitted infections due to the number of sexual partners and discontinued use of condoms with occasional partners. Such vulnerability is increased by the use of alcohol and other drugs

Análisis molecular de un paciente boliviano con trombocitopenia sindrómica relacionada al gen myh9 / Análisis molecular de un paciente boliviano con trombocitopenia sindrómica relacionada al gen myh9

La trombocitopenia como motivo de consulta, requiere la búsqueda intencionada de orientar manifestaciones extrahematológicas. La megacariogénesis pasa por distintas etapas dependientes de la interacción de varios genes, entre ellos el MYH9, cuya expresión permite una adecuada formación y migración de las proplaquetas al ser liberadas al torrente sanguíneo, al mismo tiempo, existen estructuras con fisiología similar a nivel de citoesqueleto (podocitos, cilios cocleares, etc.) que podrían vincular a datos de pérdida de audición, enfermedad renal, cataratas y elevación de enzimas hepáticas conllevando a una enfermedad relacionada al gen MYH9. Se presenta el caso de un adolescente, de sexo masculino, con trombocitopenia recurrente, con el antecedente de padre con coagulopatía inespecífica, pérdida de audición, falla renal crónica, quien falleció a los 34 años por hemorragia intraparenquimatosa y edema cerebral severo, en quien se identifica una variante patogénica en heterocigosis en el gen MYH9, poniendo en relevancia la expresividad variable y efectos pleiotrópicos de este gen.

Thrombocytopenia as a reason for consultation requires an intense search to guide extrahematological manifestations. Megakaryogenesis goes through different stages depending on the interaction of several genes, including MYH9, whose expression allows proper formation and migration of proplatelets when released into the bloodstream, at the same time, there are structures with similar physiology at the cytoskeleton level (podocytes, cochlear cilia, etc.) that could be linked to data on hearing loss, kidney disease, cataracts and elevated liver enzymes leading to a disease related to the MYH9 gene. We present the case of an adolescent, male, with recurrent thrombocytopenia, with a history of a father with nonspecific coagulopathy, hearing loss, chronic kidney failure, who died at the age of 34 due to intraparenchymal hemorrhage and severe cerebral edema, in whom identifies a heterozygous pathogenic variant in the MYH9 gene, highlighting the variable expressivity and pleiotropic effects of this gene.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars.

Preliminary study of familial nonsyndromic tooth agenesis caused by ectodysplasin A mutation / 口腔疾病防治

Objective@# To explore the pathogenic genes in a Chinese family affected by nonsyndromic tooth agenesis so as to study the pathogenesis of oligodontia.@*Methods @# Hospital ethical approval and informed consent of the patients and family members were obtained. Clinical data of the proband and close family members were collected, peripheral venous blood was collected, and DNA was extracted. Gene sequencing was performed through whole-exome sequencing, and then the screened pathogenic genes were verified by Sanger sequencing. The three-dimensional structure of the mutant proteins was analyzed and compared with the wild-type using bioinformatics tools.@*Results@#The two patients with congenital majority tooth loss in this family were cousins, and there were no other patients with congenital majority tooth loss in the family. Besides congenital multiple tooth loss, the two patients had no obvious hair abnormalities, finger/toe abnormalities, sweating abnormalities or other abnormal manifestations of ectodermal tissue. We found a mutant gene that in this family by carrying out gene sequencing of the patients and their close family members. A novel EDA (ectodysplasin A) missense mutation c.983C>T (p. Pro328Leu) was identified, which changed the encoded amino acid from proline (Pro) to leucine (Leu). Analysis of the mutation site showed that the site was highly conserved, and three-dimensional structure modeling also found that it changed the structure of EDA. @* Conclusion@#A novel EDA missense variant (c.983C>T, p.Pro328Leu) was first identified in a Chinese family with nonsyndromic tooth agenesis, extending the mutation spectrum of the EDA gene.

Enhancing the Effectiveness of Surveillance Systems in Pacific Island Countries as Early Warning Systems for Detecting and Responding to COVID-19 Outbreaks: Key Strategies and Recommendations

@#The coronavirus disease 2019 (COVID-19) pandemic has uncovered the need for health systems to be strengthened in order to be able to respond quickly to any potential future outbreaks. In response, the Pacific Syndromic Surveillance System (PSSS) is currently being used by many countries within the Pacific Islands for tracking and addressing infectious disease outbreaks, including COVID-19. To maximise its usefulness as an early warning system, investments must be made in strengthening data quality, data sharing, health facility capacity, technology, and ongoing evaluation of surveillance systems. Doing so will ensure that the PSSS and other surveillance systems can remain effective tools for monitoring and respond to infectious disease outbreaks in the Pacific Islands

Application and development of orthognathic surgery in treatment of syndromic craniosynostosis / 中国修复重建外科杂志

OBJECTIVE@#To summarize the application and recent development of orthognathic surgery in treating syndromic craniosynostosis.@*METHODS@#The related literature at home and abroad in recent years was extensively reviewed, and the indications, routine procedures, and protocols of orthognathic surgery in the treatment of syndromic craniosynostosis were summarized and analyzed.@*RESULTS@#Craniosynostosis is a common congenital craniofacial malformation. Syndromic craniosynostosis usually involves premature fusion of multiple cranial sutures and is associated with other deformities. Orthognathic surgery is the necessary and effective means to improve the midfacial hypoplasia and malocclusion. Le Fort I osteotomy combined with sagittal split ramus osteotomy are the common surgical options. Orthognathic surgery should combine with craniofacial surgery and neurosurgery, and a comprehensive long-term evaluation should be conducted to determine the best treatment plan.@*CONCLUSION@#Orthognathic surgery plays an important role in the comprehensive diagnosis and treatment of syndromic craniosynostosis. The development of digital technology will further promote the application and development of orthognathic surgery in the treatment of syndromic craniosynostosis.

Prevalence and Patterns of Supernumerary Teeth in a Peruvian Non-Syndromic Population: A Radiographic Study

ABSTRACT: This study aims to evaluate the prevalence and patterns of supernumerary teeth in a Peruvian non- syndromic population. This retrospective study used 2500 panoramic radiographs from the archives of a radiology center from Tacna-Peru. Radiographs were taken in 2019 and corresponded to subjects with ages between 8 to 22 years. The patterns of the supernumerary teeth were recorded in a checklist. Descriptive statistics was used for the distribution of supernumerary teeth. The Chi-square test was used to compare the distribution between the patterns. A confidence level of 5 % was used. The prevalence of supernumerary teeth was 5.32 % (n=133), with a male: female ratio of 1.56:1. The most affected arch was the maxilla (79.7 %), single presentation was the most common (87.22 %), and no differences were observed by gender (p > 0.05). Mesiodens was the most frequent (53.38 %), followed by parapremolar (34.59 %) in both genders (p > 0.05). According to the morphology, conical presentation was presented in 46.62 % of the cases, and impacted status were seen in 69.92 %. There were significance differences when the distribution of morphology was compared by the affected arch (p < 0.05). Conical form was most common in the maxilla (53.77 %), meanwhile in the mandible was the euromorphic type (40.74 %). A prevalence of supernumerary teeth of 5.32 % was estimated. The most frequent affected arch was the maxilla. Mesiodens, conical type and impacted were the most frequent patterns.

RESUMEN: Los dientes supernumerarios son anomalías del desarrollo dentario y se pueden clasificar según diferentes patrones. Este estudio tiene como objetivo evaluar la prevalencia y patrones de dientes supernumerarios en una población peruana no sindrómica. Este estudio retrospectivo utilizó 2500 radiografías panorámicas de los archivos de un centro de radiología de Tacna-Perú. Las radiografías se tomaron en 2019 y correspondieron a sujetos con edades entre 8 y 22 años. Los patrones de los dientes supernumerarios se registraron en una lista de verificación. Se utilizó estadística descriptiva para describir la distribución de dientes supernumerarios. Se utilizó la prueba de Chi-cuadrado para comparar la distribución entre los patrones. Se utilizó un nivel de confianza del 5 %. La prevalencia de dientes supernumerarios fue de 5,32 % (n = 133), con una relación hombre: mujer de 1,56:1. El arco más afectado fue el maxilar (79,7 %), la presentación única fue la más común (87,22 %) y no se observaron diferencias por sexo (p > 0,05). Mesiodens fue el más frecuente (53,38 %), seguido del parapremolar (34,59 %) en ambos sexos (p > 0,05). Según la morfología, la presentación cónica se presentó en el 46,62 % de los casos y el estado impactado en el 69,92 %. Hubo diferencias significativas cuando se comparó la distribución de la morfología por arco afectado (p < 0,05). La forma cónica fue más común en el maxilar (53,77 %), mientras que en la mandíbula fue el tipo euromórfico (40,74 %). Se estimó una prevalencia de dientes supernumerarios de 5,32 %. El arco afectado con mayor frecuencia fue el maxilar. Los mesiodens, tipo cónico e impactado fueron los patrones más frecuentes.

Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations / 北京大学学报(医学版)

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Exploring the association between de novo mutations and non-syndromic cleft lip with or without palate based on whole exome sequencing of case-parent trios / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design.@*METHODS@#Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database.@*RESULTS@#A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes.@*CONCLUSION@#Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

A Systematic Review of the Role of Mitochondria in Cleft Pathology: A Forgotten General?

ABSTRACT@#Orofacial clefts (OFC) are one of the most common birth defects that affects the lip, palate, or lip and palate of an infant. The deterioration of clefts is multifactorial involving multiple genes, various interactions from environmental factor and most forgotten, mitochondrial abnormality. The aim of this review is to highlight the importance of mitochondrial activity related to non-syndromic OFC deformity. Despite its important role in cells, the study on mitochondrial activity in cleft pathology was scarce and almost forgotten compared to other genetic investigations. This systematic review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The literature search was done via the following databases: Google Scholar, Pubmed and Scopus with a total of nine studies of mitochondrial abnormalities were included. We hypothesise that mitochondria play an important role in early craniofacial development. A decreased in its function or activity may result in cleft lip formation. Hence, we would like to shed light on the remarkable role of mitochondria activity in the pathogenesis of non-syndromic OFC.

Whole-Exome Sequencing Reveals Pediatric Rare Syndromic Hearing Loss / 罕见病研究

  Objective  To discuss the significance of genetic diagnosis of children with syndromic hearing loss by using whole-exome sequencing.  Methods  The clinical data of 34 children with sensorineural hearing loss were collected and the whole exons of genome of the children and their parents were sequenced and analyzed.  Results  Genetic causative gene and mutations have been identified in 19 children, including 4 genes (HARS2, USH2A, GATA3, MITF) related to rare syndromic hearing loss. Fifteen children were diagnosed with non-syndromic hearing loss related gene, including 8 cases with GJB2 mutation, 5 cases with SLC26A4 mutation and 2 cases with MYO15A mutation. Mutations of c.435_437del(p.K147del) and c.1403G > C (p.G468A) in gene HARS2, c.11389+1del in gene USH2A, c.1327delA(p.M443Wfs*33) in gene GATA3, c.627C > A(p.C209X) in gene MITF and c.8033_8057delinsG(p.N2678_D2686delinsS) in gene MYO15A were first reported.  Conclusions  Whole-exome sequencing helps the accurate diagnosis of causes of hearing loss, especially for the rare syndromic hearing loss with atypical clinical manifestations. Information from genetic testing may highlight further recommended exams of structure and functions of related organs.

Atraso de escolaridade e dificuldade de socialização de pacientes com fissura labiopalatina não sindrômica / Scholar delay and socialization dificulty of patients with non syndromic cleft lip and palate

Dentre as principais consequências da fissura labial e/ou palatina não sindrômica (FL/ PNS) estão dificuldades com fonação e autoestima, a primeira uma questão funcional e a segunda um problema social derivado não raro de contextos de bullying que, dentre outros, podem levar o indivíduo à evasão escolar. O objetivo deste estudo foi avaliar o atraso de escolaridade e a dificuldade de socialização de pacientes com FL/PNS quando comparados a uma população não afetada da mesma faixa etária de 7 a 20 anos, atendidos na Universidade José do Rosário Vellano ­UNIFENAS, campus de Alfenas. Os sujeitos foram agrupados em duas categorias de indivíduos, o grupo caso composto por indivíduos com FL/PNS em tratamento no Centro Pró-Sorriso da UNIFENAS; e o grupo controle composto por indivíduos sem FL/PNS em tratamento nas clínicas de Odontopediatria e Integrada da UNIFENAS. Os resultados demonstraram que a proporção de pacientes com FL/PNS atrasados na escola foi de quase 5 vezes maior que o número de pacientes sem fissuras (p<0,01). Constatou-se que a presença da FL/PNS pode ser o ponto de partida para outros contribuintes, com interferências psicológicas e/ou sociais, interferindo negativamente no processo de socialização (bullying) do paciente (p=0,0018). Portanto devem ser tratadas com abordagem multidisciplinar, incluindo diversos profissionais, dentre eles pedagogos, psicólogos e odontólogos(AU)

Among the main consequences of Non Syndromic Cleft Lip and Palate (NSCLP) are the difficulties with phonation and self estime, the first being a functional issue na the later being social that is derived from, not rarely, bullying contexts, that among other things, may lead na individual to school evasion. The objective of this study was to avaluate the levels of scholarity of patients with NSCLP when compared to a non affected population of the same age in individuals from 7 to 20 years old, attended the Pediatric and Integrated Pediatric Clinic of UNIFENAS, Alfenas campus. The subjects were grouped into two categories of individuals, the case group was composed of individuals with FL/PNS with treatment at the ProSmile center at UNIFENAS. The control group was composed of individuals without FL/PNS in treatment at the clinics of pediatric and integrated denistry at UNIFENAS. The results demonstrated the number of patients with FL/PNS that presented scholar delay were almost 5 times the number of patients that didn't present FL/PNS (p<0,01). The presence of NFL/PNS may be the starting point for other contributors with psychological and/or social interferences, interfering negatively with the socialization process (bullying) of the patient (p=0,0018). They should be treated with a multidisciplinary manner, including multiple professionals, among them pedagogues, psychologist and dentist(AU)

Research progress on MAFB gene polymorphism and nonsyndromic cleft lip and palate / 口腔疾病防治

@#Nonsyndromic cleft lip with/without cleft palate is a common congenital birth defect of the maxillofacial region. The pathogenic mechanism is related to the interaction of genes and environmental factors. At present, there are many studies on genes, and genome-wide association analysis has found that the new susceptibility gene v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is associated with the development of nonsyndromic cleft lip with/without cleft palate. This paper reviews the research progress on the correlation between single nucletide polymorphism(SNPs) in MAFB and nonsyndromic cleft lip with/without cleft palate. The results of this review reveal how the MAFB gene is expressed and differentiated in various cell types and plays an important role in maintaining the development of various organs, such as the brain, pancreas, and parathyroid glands. The MAFB gene is significantly associated with the occurrence of nonsyndromic cleft lip with/without cleft palate in the Asian population. rs13041247, rs11696257, rs17820943 and other teratopoietic single nucleotide loci are the most commonly studied teratopoietic single nucleotide loci, and the research conclusions on the correlation between SNPs in MAFB genes are obviously different in different populations. The interaction between the MAFB gene and other susceptibility genes leads to the occurrence of nonsyndromic cleft lip with/without cleft palate; nevertheless, more in-depth research is needed on specific mechanisms and approaches based on the relationship between these two factors.

Two cases of female-restricted X-linked syndromic mental retardation-99 caused by USP9X gene variations / 中华实用儿科临床杂志

Objective:To summarize and analyze the clinical and genotype features of female-restricted X-linked syndromic mental retardation-99(MRXS99F, OMIM: 300968)caused by USP9 X gene mutation, and to improve the clinicians′ understanding of the disease. Methods:Clinical data and genotypes of 2 children with MRXS99F treated in the Children′s Hospital of Nanjing Medical University in March 2020 (case 1) and June 2020 (case 2) were analyzed, and the relevant databases at home and abroad were reviewed to summarize the clinical characteristics and gene variation characteristics of the disease.Results:The 2 cases were 6 months old (case 1) and 5 years old (case 2), both showed psychomotor retardation.Case 1 presented a short stature, pigment abnormality, characteristic facial features, hypotonia, recurrent respiratory tract infections, laryngeal cartilage hypoplasia, atrial septal defect, feeding difficulty, hearing loss and brain hypoplasia.Case 2 had abnormal electroencephalogram.As confirmed by whole-exome sequencing, two children carried c. 6972+ 1G>A, c.6437C>T of USP9 X, respectively.Neither of the 2 variations was previously reported.Twenty-two cases of MRXS99F caused by USP9 X gene mutation were reported in 4 literatures globally, and 24 cases were combined with this study.The clinical manifestations of 20/22 children had special faces.All of them accompanied mental retardation combined with motor and language retardation, and carried neonatal variation. Conclusions:This is the first case report of MRXS99F induced by USP9 X gene variation in China.MRXS99F caused by functional deletion and variation of USP9 X gene is mainly characterized by psychomotor retardation, language disorder, special face and multiple congenital malformations.For children with unexplained growth retardation, special face and multiple congenital malformations, genetic testing like high-throughput sequencing should be carried out as early as possible to determine the etiology.

Transverse Facial Cleft, Tessier number 7: Case Report of a Rare Congenital Anomaly

@#Transverse facial cleft (TFC), Tessier number 7, is a rare congenital anomaly commonly associated with other anomalies of the first and second branchial arch with varying severity. Risk factors such as alcohol abuse, folic acid deficiency, and ingestion of herbal concoctions in pregnancy have been implicated in this deformity. We report a case of a bilateral transverse facial cleft in a newborn and review the existing literature on the condition to increase awareness and knowledge.

Diagnosing Herpetic Genital Ulcers in a Resource-Limited Setting- What Works?

Aims: Globally, viral agents, especially herpes simplex virus (HSV), have overtaken the bacterial causes of genital ulcers. Very few laboratories in India, perform culture techniques and polymerase chain reaction (PCR) for diagnosis of genital ulcers. This study aimed to establish the utility of existing tests, which are cheaper and need less technical expertise, when compared to newer tests such as PCR.Study Design: This cross sectional study was carried out to determine the aetiology of genital ulcers, with emphasis on diagnosis of herpetic ulcers, using newer and more accurate methods of diagnosis and evaluating their performance by comparing against viral culture as gold standard test.Place and Duration of the Study: The study was carried out over a period of one year in the Apex Regional Sexually Transmitted Diseases (STD) Centre at Safdarjung Hospital, New Delhi and the Department of Microbiology, AIIMS, New Delhi.Methodology: Fifty three patients with genital ulcers were included in the study. Specimens from ulcers were taken for various tests, including Giemsa stain, ELISA for HSV-1 & 2, PCR and Viral culture for HSV.Results: HSV was identified in 31 of 53 cases (58.5%), including 03 cases of HSV-1, and 28 cases of HSV-2. Sensitivity and specificity of PCR was 90.0% and 84.85%, respectively. Viral culture positivity was 37.7%.Conclusion: Genital herpes is associated with an increased risk of Human Immunodeficiency Virus (HIV) acquisition, and clinical manifestations are diverse; hence a presumptive diagnosis should be confirmed by reliable laboratory tests. Nucleic acid amplification tests (NAAT) are the most sensitive methods for direct detection of HSV. The extensive validation of these tests allows for their application in routine laboratory settings with consistency and greater diagnostic accuracy. When standardised and used, PCR is a highly reproducible, rapid and labour efficient method for HSV detection.

Evaluating the effect of WNT pathway genes considering interactions on the risk of non-syndromic oral clefts among Chinese populations / 北京大学学报(医学版)

OBJECTIVE@#In this study, we used genome-wide association study (GWAS) data to explore whether WNT pathway genes were associated with non-syndromic oral clefts (NSOC) considering gene-gene interaction and gene-environment interaction.@*METHODS@#We conducted the analysis using 806 non-syndromic cleft lip with or without cleft palate (NSCL/P) case-parent trios and 202 non-syndromic cleft palate (NSCP) case-parent trios among Chinese populations selected from an international consortium established for a GWAS of non-syndromic oral clefts. Genotype data and maternal environmental exposures were collected through DNA samples and questionnaires. Conditional Logistic regression models were adopted to explore gene-gene interaction and gene-environment in teraction using trio package in R software. The threshold of significance level was set as 3.47×10-4 using Bonferroni correction.@*RESULTS@#A total of 144 single nucleotide polymorphisms (SNPs) in seven genes passed the quality control process in NSCL/P trios and NSCP trios, respectively. Totally six pairs of SNPs interactions showed statistically significant SNP-SNP interaction (P < 3.47×10-4) after Bonferroni correction, which were rs7618735 (WNT5A) and rs10848543 (WNT5B), rs631948 (WNT11) and rs556874 (WNT5A), and rs631948 (WNT11) and rs472631 (WNT5A) among NSCL/P trios; rs589149 (WNT11) and rs4765834 (WNT5B), rs1402704 (WNT11) and rs358792 (WNT5A), and rs1402704 (WNT11) and rs358793 (WNT5A) among NSCP trios, respectively. In addition, no significant result was found for gene-environment interaction analysis in both of the NSCL/P trios and NSCP trios.@*CONCLUSION@#Though this study failed to detect significant association based on gene-environment interactions of seven WNT pathway genes and the risk of NSOC, WNT pathway genes may influence the risk of NSOC through potential gene-gene interaction.