Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2-related pathogenesis.     

Evaluation and comparison of the marginal adaptation of two different substructure materials

PURPOSE

In this study, we aimed to evaluate the amount of marginal gap with two different substructure materials using identical margin preparations.

MATERIALS AND METHODS

Twenty stainless steel models with a chamfer were prepared with a CNC device. Marginal gap measurements of the galvano copings on these stainless steel models and Co-Cr copings obtained by a laser-sintering method were made with a stereomicroscope device before and after the cementation process and surface properties were evaluated by scanning electron microscopy (SEM). A dependent t-test was used to compare the mean of the two groups for normally distributed data, and two-way variance analysis was used for more than two data sets. Pearson''s correlation analysis was also performed to assess relationships between variables.

RESULTS

According to the results obtained, the marginal gap in the galvano copings before cementation was measured as, on average, 24.47 ± 5.82 µm before and 35.11 ± 6.52 µm after cementation; in the laser-sintered Co-Cr structure, it was, on average, 60.45 ± 8.87 µm before and 69.33 ± 9.03 µm after cementation. A highly significant difference (P<.001) was found in marginal gap measurements of galvano copings and a significant difference (P<.05) was found in marginal gap measurements of the laser-sintered Co-Cr copings. According to the SEM examination, surface properties of laser sintered Co-Cr copings showed rougher structure than galvano copings. The galvano copings showed a very smooth surface.

CONCLUSION

Marginal gaps values of both groups before and after cementation were within the clinically acceptable level. The smallest marginal gaps occurred with the use of galvano copings.     

A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells

Here, we describe the characteristics of a Pt‐blue complex [Pt₄(2‐atp)₈(H₂O)(OH)] (2‐atp: 2‐aminothiophenol) as a prodrug for its DNA‐binding properties and its use in cancer therapy. The nature of the interaction between the Pt‐blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single‐ and double‐stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST‐1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro‐apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt‐blue complex under study grants premise for further studies.     

HE4 Expression in Plasma Correlates with Surgical Outcome and Overall Survival in Patients with First Ovarian Cancer Relapse

Background

Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods

Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher’s exact test, Kendall’s tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan–Meier method.

Results

At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601–0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68–75.25; and p = 0.044, HR 3.33, 95 % CI 1.03–10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22–42.19 and p = 0.036, OR 10.18, 95 % CI 1.16–88.69, respectively).

Conclusions

HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.     

Nitric oxide levels of aqueous humor after photorefractive keratectomy

PURPOSE: To measure the nitric oxide (NO) levels of aqueous humor in rabbits after photorefractive keratectomy (PRK) and to evaluate the alterations of NO levels according to the PRK surgery steps, ablation depth, and time. METHODS: Fifty eyes of 25 New Zealand white rabbits were included in the study. One eye was later randomly excluded from the study in order to equalize the number of eyes in groups. Eyes were divided into seven groups, each comprising seven eyes: unwounded control (Group 1), epithelial scrape (Group 2; aqueous humor samples taken at the 4th hour), superficial PRK (Group 3; samples taken at the 4th hour), deep PRK (Group 4; samples taken at the 4th hour), epithelial scrape (Group 5; samples taken at the 24th hour), superficial PRK (Group 6; samples taken at the 24th hour), and deep PRK (Group 7; samples taken at the 24th hour). The corneal epithelium was mechanically removed in surgical groups. The authors performed superficial corneal ablation (59 microm) in Groups 3 and 6 and deep corneal ablation (99 microm) in Groups 4 and 7. Aqueous humor samples were taken at the 4th hour (Groups 2-4) or 24th hour (Groups 5-7) after corneal surgeries. NO measurements were performed indirectly by using the Griess reaction with a spectrophotometer. RESULTS: Aqueous humor NO levels 4 hours after corneal surgery were statistically significantly lower than the control group (p<0.05). However, there was no difference among the surgical groups at the 4th hour (p>0.05). At the 24th hour, the deep PRK group had significantly lower NO levels than both the control group and Groups 5 and 6 (p<0.05). NO levels were normalized at the 24th hour in epithelial scrape and superficial PRK groups (p>0.05) but remained stable at lower levels in deep PRK groups (p<0.05). CONCLUSIONS: Corneal surgery caused low NO levels in aqueous humor 4 hours after surgery. However, 24 hours after surgery, NO levels normalized following epithelial scrape and superficial PRK and were stable at lower levels in the deep PRK group. Complications of deep PRK application are possibly induced by low NO existence in the aqueous humor.     

Depression and anxiety in hypothyroidism

The aim of the study was to determine the prevalence and severity of depression and anxiety in patients with hypothyroidism and to compare this with euthyroid patients. Thirty patients with hypothyroidism and 30 euthyroid controls attending the Endocrinology outpatient department of Celal Bayar University, Medical Faculty were included in the study. The hormonal screening was done by immunoassay and haemagglutination methods. Then, for psychiatric assessment, Hospital Anxiety and Depression Scale (HAD), Hamilton Depression Rating Scale (HAM-D), and Hamilton Anxiety Rating Scale (HAM-A) were used. There was no difference between the two groups in terms of demographic features. Total scores obtained from the scales used in the study did not differ significantly (p > 0.05). The frequency of items of both HAM-D and HAM-A did not show any differences in the two groups. By Wilks' Lambda discriminant analysis, depressive mood (HAM-D#1) was found to be the discriminating feature between the hypothyroid group and the euthyroid group. Therefore, depression and anxiety were not outstanding features in hypothyrodism. However, depression was more significant in the hypothyroid than euthyroid group.     

Deletion of exons 2–4 in the <Emphasis Type="Italic">BSND</Emphasis> gene causes severe antenatal Bartter syndrome

BSND gene mutations usually cause severe forms of antenatal Bartter syndrome and sensorineural deafness (SND). Chronic renal failure and transient hypercalciuria are reported as controversial symptoms of this syndrome. All twelve reported BSND mutations cause SND, whereas only two of the mutations give rise to normal glomerular filtration rate (GFR) and two other mutations cause hypercalciuria. The case we report here, where the patient presented with severe clinical symptoms and deletion on exons 2-4 of the BSND gene, has not been reported previously. Decreased GFR, along with hypercalciuria and difficulties in managing fluid and electrolyte requirements, are the reasons why this patient was brought to attention.     

A case of aquaporin 2 R85X mutation in a boy with congenital nephrogenic diabetes insipidus

Autosomal recessive nephrogenic diabetes insipidus (ARNDI) is a rare disease usually seen in patients with consanguineous parents. We report on a case of ARNDI in a patient with non-consanguineous parents who presented with recurrent febrile attacks. The differential diagnosis of ARNDI was made by desmopressin infusion test. A homozygous mutation, R85X, was detected in the aquaporin 2 gene (AQP2) of our patient, which has been described only once previously. This case is presented to stress that even male patients with non-consanguineous parents could have ARNDI with a AQP2 gene defect, and the desmopressin infusion test is useful for differential diagnosis.