First Reported Case of Gabriele-de Vries Syndrome with Spinal Dysraphism.

Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in the Yin Yang 1 (YY1) gene. Individuals with this syndrome present with multiple congenital anomalies, as well as a delay in development and intellectual disability. Herein, we report the case of a newborn male patient with a novel de novo pathogenic variant in the Guanine Nucleotide-Binding Protein, Alpha Stimulating (GNAS) gene, which was identified by whole-exome sequencing. Our patient suffered from a large open spinal dysraphism which was treated surgically immediately after birth. During the follow-up, facial dysmorphism, bladder and bowel incontinence, and mildly delayed motor and speech development were observed. Congenital central nervous system disorders were also confirmed radiologically. In this case report, we present our diagnostic and treatment approaches to this patient. To our knowledge, this is the first reported case of Gabriele-de Vries syndrome presenting with spinal dysraphism. Extensive genetic evaluation is the cornerstone in treatment of patients with suspected Gabriele-de Vries syndrome. However, in cases with potentially life-threatening conditions, surgery should be strongly considered.

Esterase Sequence Composition Patterns for the Identification of Catalytic Triad Microenvironment Motifs.

Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials' development. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. For this purpose, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique and well-defined mechanisms. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. Moreover, fragmentation schemes of the primary sequence of selected enzymes alongside the study of their amino acid frequencies, composition, and physicochemical properties are proposed. The results showed highly conserved catalytic sites with distinct positional patterns and chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts.

Impact of Immediate and Delayed Breast Reconstruction on Quality of Life of Breast Cancer Patients.

A mastectomy affects the psychological, social, and sexual well-being of patients. Research has confirmed that breast reconstruction is important for improving the quality of life in patients with breast cancer. The aim of this study was to assess the quality of life of patients who underwent a mastectomy followed by immediate or delayed breast reconstruction. This prospective study was conducted from January 2018 to March 2020 at the Clinical Hospital Center Osijek, using the health questionnaire SF-36. The study included 79 patients. The results of the study showed that patients who underwent a mastectomy had the lowest scores in the domain of restriction due to physical difficulties, 18.8 (6.3−31.3), in physical functioning and limitation due to emotional difficulties, 16.7 (8.3−33.3), in mental health. In immediate breast reconstruction, patients rated better physical health (p < 0.001), while patients who underwent delayed breast reconstruction rated their mental health worse (p < 0.001) as measured by the SF-36 questionnaire. Conclusion: The results of this study show that patients without breast reconstruction rated their quality of life worse than patients who underwent immediate and delayed breast reconstruction after mastectomy. There is no difference in the quality of life between patients who underwent immediate and delayed breast reconstruction after mastectomy.

Independent factors FOR poor prognosis in young patients with stage I-III breast cancer.

Breast cancer is the most common malignancy in the population of women under 40 years of age. Young age is an independent factor for poor prognosis. In this research, we tried to establish other factors for poor prognosis in stage I-III breast cancer. The following parameters were observed: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2 neu status, histologic type of the tumor, local recurrence and metastases. Logistic regression was used to evaluate the effect of specific factors on the probability of lethal outcome and development of distant metastases. Our patients showed a predominance of T1 tumor (49.4%), had positive lymph nodes (62%) and most of them were pN1 (61.2%). Up to one-third of patients had triple negative status. Ki-67 proliferation index was high (25%). Multicentric tumor was detected in 23% of patients. There was no difference in overall survival between the two types of surgical procedures. Patients with pN0 status had better overall survival. Breast cancer in the population of young women has a more aggressive nature. Study results indicated positive lymph node status as an independent factor for poor prognosis of stage I-III breast cancer.

BREAST CANCER IN YOUNG WOMEN: PATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES.

- A young woman with breast cancer is considered to be a woman younger than 40. According to the literature, breast cancer in the population of young women usually is of a higher histologic grade, unfavorable hormonal status, and overall higher mortality rate when compared with breast cancer occurring in older population. We compared pathologic and immunohistochemical features of breast carcinoma in women under 40 years of age with the respective features in women over 60 years of age. The following parameters were observed in these two groups: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2/neu status, and histologic type of the tumor. Early onset breast carcinoma was found to have a higher frequency of tumor grade 3 (29% vs. 17%) and estrogen receptor negativity (45% vs. 23%). In the group of young women, breast carcinoma was mostly multicentric (23% vs. 5%), triple-negative (32% vs. 10%), and was found to have higher proliferation index Ki-67 (25% vs. 10%). Our results confirmed differences between the young and older groups of patients. In the group of young women, we found predominantly unfavorable prognostic parameters of the disease.

Growth hormone positive effects on craniofacial complex in Turner syndrome.

OBJECTIVE: Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. DESIGN: In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. RESULTS: In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. CONCLUSIONS: Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features.

Ontogenetic changes of craniofacial complex in Turner syndrome patients treated with growth hormone.

OBJECTIVE: The present study assessed changes of craniofacial complex in Turner syndrome (TS) patients treated with growth hormone (GH) during development. The objective was to examine the growth rate and pattern of craniofacial structures and to establish effects of GH on craniofacial development. MATERIALS AND METHODS: The study population consisted of 15 TS patients treated with GH aged 5-18.5 years (13.3 ± 4.4) and corresponding control group of 45 females aged 6.8-18.7 (11.4 ± 2.6). According to the stage of cervical vertebral maturation, subjects were categorized into pre-growth (5 TS and 15 controls) and growth (10 TS and 30 controls) subgroups. The cephalometric analysis comprised angular and linear variables, measured on lateral cephalometric radiographs. RESULTS: The mandibular corpus/anterior cranial base ratio increased significantly only in controls during development. In growth period, ramus/corpus ratio was significantly larger in TS group. SNA and SNB angles were significantly smaller in TS growth subgroup compared to corresponding controls. Among other variables, no statistically significant differences were revealed. CONCLUSIONS: In TS patients treated with GH, growth capacities of cranial base and maxilla are adequate which can be attributed to GH treatment. Shape of mandible is altered due to decreased growth of corpus and overdeveloped ramus. Both maxillary and mandibular retrognathism are becoming more expressed during development. CLINICAL RELEVANCE: Favorable influence of GH on craniofacial complex growth rate and altered growth pattern revealed in this study should be considered while planning both orthodontic treatment and retention.

Cancer genes alterations and HPV infection in oral squamous cell carcinoma.

The aim of this study was to gain a better understanding of cancer genes contributing to oral squamous cell (OSCC) development and progression and correlate genetic changes to clinical parameters. Human papilloma virus (HPV) 16 detection is also included in the study. 60 samples of OSCC were analysed for c-erbB2 and c-myc amplification by dPCR, H-ras and p53 point mutations by PCR/SSCP. HPV was detected via amplification of its E1 and E6 genes. c-erbB2 was altered in 45%, c-myc in 35%, H-ras in 22% and p53 in 60% of samples. HPV was detected in 10% of cases. The frequency of p53 gene mutations showed a statistically significant association with tumour stage. Patients with c-erbB2 and H-ras alterations had lower survival than patients without these alterations. The number of detected genetic changes was remarkable but statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis.

Craniofacial complex specificities in five men with sex reversal syndrome.

In order to clarify the role of sex chromosome constitution in craniofacial growth control, we compared craniofacial morphology of men with sex reversal syndrome (46, XX) with the morphology of normal men, Klinefelter's syndrome and normal women, using cephalometric measurements. Due to physical resemblance between men with 46, XX karyotype and men with 47, XXY karyotype, cephalometric analysis comprised parametres which had already been found to be specific for Klinefelter's syndrome, i.e. cranial base length and flexion, maxillary and mandibular base length, jaw position in relation to cranial base and sagittal jaw relationship. Linear measurements showed reduction of about 10% in maxillary base length in 46, XX men in relation to normal men. Mandibular base in men with sex reversal syndrome was also shortened for about 10% in relation to both normal men and Klinefelter's syndrome. Cranial base flexion in men with Klinefelter's syndrome and in men with sex reversal syndrome showed similarity. The basal angle was found to be more acute, for about 4 degrees , in comparison to individuals with normal karyotype. Unlike in men with Klinefelter's syndrome, mandibular and maxillary prognathism were not registered in men with sex reversal syndrome.