No / Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

A perda auditiva é uma característica importante da Síndrome de Stickler. Na literatura, poucos trabalhos têm caracterizado essa perda, e não há estudos do efeito de outros fatores de risco sobre a audição no Stickler. Realizou-se este trabalho com a finalidade de verificar o fenótipo clínico e audiológico de um grupo de 26 crianças, com idade média de cinco anos e sete meses, afetadas pela SS, no Hospital de Reabilitação de Anomalias Craniofaciais. Após análise dos dados dos exames clínico e audiológico, concluiu-se que 80,76% (IC 95%, 60, 65 – 93, 44) das crianças apresentaram perda auditiva, sendo 34,61% (IC 95%, 17, 21 – 55, 66), de perda sensorioneural associada à SS, tipicamente para altas freqüências; 11,53% (IC 95%, 2, 44 – 30, 15) de perda mista, e 34,61% (IC 95%, 17, 21 – 55, 66) de perda auditiva condutiva, que é comum nas crianças com SS, devido à presença da fissura de palato e outras anomalias craniofaciais, levando a uma disfunção da orelha média com o comprometimento da sensibilidade auditiva. O grau de perda auditiva variou de leve a grave. A análise estatística pelo teste de Fisher (p<0,05) não revelou qualquer efeito significativo da exposição das crianças a outros fatores de risco de perda auditiva sobre a perda sensorioneural, mostrando ser este tipo de perda auditiva característica da SS. Na impossibilidade da realização do exame genético molecular, o fenótipo clínico, associado à avaliação audiológica, pode sugerir o diagnóstico do tipo da SS. / Hearing loss is an important characteristic of the Stickler’s Syndrome. In literature, few studies have defined the characterization of this loss, and there are no studies about the effect of other risk factors of hearing in Sticker. This present work has been made with the purpose of verifying the clinical and audiological phenotype of a group of 26 children with average age of 5 years and 7 months, affected by SS, at the Hospital de Reabilitação de Anomalias Craniofaciais. After analyzing the data of the clinical and audiological exams, we concluded that 80.76% (IC 95%, 60,65 – 93,44) of the children have presented hearing loss, being 34.61% (IC 95%, 17,21 – 55,66) of sensorial neural loss, associated with SS, typically for high frequencies; 11.53% (IC 95%, 2,44 – 30,15) of mixed loss; and 34.61% (IC 95%, 17,21 – 55,66) of conductive hearing loss, which is common in children with SS, due to the presence of cleft palate and other craniofacial anomalies, leading to a disfunction of the mid ear, with harming of hearing sensibility. The degree of hearing loss has varied from mild to severe. The statistical analysis through Fisher’s test (p<0.05) didn’t reveal any significant effect of the exposition of children to other risk factors of hearing loss to the sensorial neural loss of SS. Due to the impossibility of the realization of the molecular genetic exam, the clinical phenotype, associated with the audiological evaluation, may suggest the diagnosis of the kind of SS.

A perda auditiva é uma característica importante da Síndrome de Stickler. Na literatura, poucos trabalhos têm caracterizado essa perda, e não há estudos do efeito de outros fatores de risco sobre a audição no Stickler. Realizou-se este trabalho com a finalidade de verificar o fenótipo clínico e audiológico de um grupo de 26 crianças, com idade média de cinco anos e sete meses, afetadas pela SS, no Hospital de Reabilitação de Anomalias Craniofaciais. Após análise dos dados dos exames clínico e audiológico, concluiu-se que 80,76% (IC 95%, 60, 65 – 93, 44) das crianças apresentaram perda auditiva, sendo 34,61% (IC 95%, 17, 21 – 55, 66), de perda sensorioneural associada à SS, tipicamente para altas freqüências; 11,53% (IC 95%, 2, 44 – 30, 15) de perda mista, e 34,61% (IC 95%, 17, 21 – 55, 66) de perda auditiva condutiva, que é comum nas crianças com SS, devido à presença da fissura de palato e outras anomalias craniofaciais, levando a uma disfunção da orelha média com o comprometimento da sensibilidade auditiva. O grau de perda auditiva variou de leve a grave. A análise estatística pelo teste de Fisher (p<0,05) não revelou qualquer efeito significativo da exposição das crianças a outros fatores de risco de perda auditiva sobre a perda sensorioneural, mostrando ser este tipo de perda auditiva característica da SS. Na impossibilidade da realização do exame genético molecular, o fenótipo clínico, associado à avaliação audiológica, pode sugerir o diagnóstico do tipo da SS. / Hearing loss is an important characteristic of the Stickler’s Syndrome. In literature, few studies have defined the characterization of this loss, and there are no studies about the effect of other risk factors of hearing in Sticker. This present work has been made with the purpose of verifying the clinical and audiological phenotype of a group of 26 children with average age of 5 years and 7 months, affected by SS, at the Hospital de Reabilitação de Anomalias Craniofaciais. After analyzing the data of the clinical and audiological exams, we concluded that 80.76% (IC 95%, 60,65 – 93,44) of the children have presented hearing loss, being 34.61% (IC 95%, 17,21 – 55,66) of sensorial neural loss, associated with SS, typically for high frequencies; 11.53% (IC 95%, 2,44 – 30,15) of mixed loss; and 34.61% (IC 95%, 17,21 – 55,66) of conductive hearing loss, which is common in children with SS, due to the presence of cleft palate and other craniofacial anomalies, leading to a disfunction of the mid ear, with harming of hearing sensibility. The degree of hearing loss has varied from mild to severe. The statistical analysis through Fisher’s test (p<0.05) didn’t reveal any significant effect of the exposition of children to other risk factors of hearing loss to the sensorial neural loss of SS. Due to the impossibility of the realization of the molecular genetic exam, the clinical phenotype, associated with the audiological evaluation, may suggest the diagnosis of the kind of SS.

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early- and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS.

Background: We aimed to increase the knowledge regarding the familial arrhythmogenic disorder Long QT Syndrome (LQTS) and its recessive variant Jervell and Lange-Nielsen Syndrome (JLNS) in Sweden, including prevalences and clinical phenotypes. A specific focus was directed towards two KCNQ1 mutations –p.Y111C and p.R518X- commonly identified in Swedish LQTS index cases. Methods: Cases and families with LQTS (p.Y111C or p.R518X) and JLNS were recruited via regional clinical practices, national referrals to the Clinical Genetics laboratory, Umeå University Hospital, and a national inventory. Molecular genetics methods were used for case ascertainment. Clinical data was obtained via medical records, a questionnaire, and/or an interview. Electrocardiograms were manually assessed. In p.R518X heterozygotes intra-familial phenotypic variability (QTc and cardiac events) was assessed by analysis of sequence variants (modifier genes). The origins of the mutations p.Y111C and p.R518X were investigated using genealogical and haplotype analysis (microsatellite markers). In families sharing a common haplotype mutation age and associated prevalence was analyzed using ESTIAGE and DMLE computer software. Results: We identified p.Y111C (170 mutation-carriers) and p.R518X (101 mutation-carriers) as two major causes of LQTS/JLNS in Sweden. LQTS phenotype was revealed to be relatively benign in p.Y111C and p.R518X (annual incidence of life-threatening cardiac events, before therapy 0.05% and 0.04%, respectively). Gender-specific effects of genetic modifiers on phenotypic expression were seen. A founder origin, approximately 600-700 years ago in two northern river valleys was established for p.Y111C and p.R518X, and a high prevalence of LQTS founder descendants suggested. A minimum JLNS prevalence of 1:200 000 in preadolescent Swedish children was revealed. JLNS phenotype was mainly severe, with a cumulative incidence of life-threatening cardiac events of 53% (annual incidence rate before therapy 5%) and four sudden deaths. Possible founder effects regarding four KCNQ1 mutations; p.Y111C (8%), p.R518X (50%), c.572_576del (17%) and p.Q530X (8%) together explained 83% of the JLNS mutation-spectrum in Sweden, consisting of 8 KCNQ1 mutations. Conclusion: The high prevalence of p.Y111C- and p.R518X-related LQTS as well as JLNS revealed in Sweden could be explained by the combination of mild clinical phenotypes in heterozygotes and strong founder effects present during the population development of northern Sweden. Increased knowledge regarding the occurrence of LQTS and JLNS as well as mutation- and/or genotype-specific data constitute prerequisites for possible improvement of patient management.