Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development.

In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.

Subclinical hypothyroidism in combination with vitamin D deficiency increases the risk of impaired left ventricular diastolic function.

OBJECTIVE: Subclinical hypothyroidism and vitamin D deficiency are common. The diastolic function of patients with both subclinical hypothyroidism and vitamin D deficiency remains unknown. This study aimed to investigate diastolic dysfunction in patients with both subclinical hypothyroidism and vitamin D deficiency. SUBJECTS AND METHODS: This study included 254 patients. All patients underwent standard Doppler echocardiography. Patients who had risk factors for diastolic dysfunction or had used L-thyroxine and vitamin D within the previous 3 months were excluded. Vitamin D deficiency was defined as a 25-OH-vitamin D level lower than 20 ng/ml, and vitamin D sufficiency was defined as a 25-OH-vitamin D level ≥ 30 ng/ml. Subclinical hypothyroidism was defined as a TSH level of 4.5-10 mU/l when the free T4 concentration was normal. RESULTS: The patients were divided into 4 groups. Group 1 (n=71) included patients with subclinical hypothyroidism and vitamin D deficiency; Group 2 (n=66) included patients with subclinical hypothyroidism and vitamin D sufficiency; Group 3 (n=65) included euthyroid patients with vitamin D deficiency; and Group 4 (n=52) included euthyroid patients with vitamin D sufficiency. LAVI (31.3 ± 3.2, 28.7 ± 3.0, 28.4 ± 3.4, and 27.9 ± 3.9; p<0.001) and E/E' values (11.2 ± 2.7, 8.9 ± 2.7, 9.1 ± 2.9, 8.8 ± 2.5; p<0.001) were significantly higher in Group 1 than in Groups 2, 3 and 4. E' values were significantly lower in Group 1 than in Groups 2, 3 and 4. CONCLUSION: The coexistence of subclinical hypothyroidism with vitamin D deficiency can lead to further deterioration in the LV diastolic function via the regulation of intracellular calcium and induction of inflammatory activity. Therefore, close follow-up of the diastolic functions of these patients could be beneficial.

Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis.

BACKGROUND/AIMS: Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients. METHODS: A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined. RESULTS: The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101-289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus. CONCLUSION: The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients.

Relationship of galectin-3 to left ventricular geometry and hypertrophy in chronic hemodialysis patients.

AIM AND BACKGROUND: Galectin-3 (Gal-3) is used to determine the prognosis of heart failure. Some studies revealed that Gal-3 promoted cardiac hypertrophy but there is no study in which the relationship between Gal-3 and left ventricular hypertrophy (LVH) geometry in patients without diastolic and systolic function impairment has been explored. The aim of the study was to analyze associations between plasma Gal-3 levels, LVH, and LV geometry in maintenance hemodialysis (HD) patients without systolic and diastolic dysfunction. PATIENTS AND METHODS: The study group included 105 patients (53 women and 52 men)--with an average age of 58.2 ± 12.6 years, treated with HD for an average of 45 ± 32 months--and 60 healthy controls. The Gal-3 and other biochemical parameters were measured and color Doppler echocardiography was performed. For this study LVH was considered present when the LV mass index (LVMI) exceeded 95 g/m(2) in women and 115 g/m(2) in men. Left ventricular geometry was classified into the four groups on the basis of left ventricular mass and relative wall thickness (RWT). RESULTS: Concentric hypertrophy (CH, 40.9 %, n = 43) was the commonest geometric pattern in our study. The Gal-3 levels in CH patients were not different from the patients with eccentric hypertrophy (EH). Plasma levels of Gal-3 correlated with LVMI (r = 0.617, p < 0.001), parathyroid hormone (PTH, r = 0.408, p < 0.001), uric acid (r = 0.281, p = 0.004), C-reactive protein (CRP, r = 0.412, p < 0.001), and RWT (r = 0.281, p = 0.004) but were inversely correlated with albumin (r = - 0.466, P < 0.001) in the whole group. Plasma levels of Gal-3 were associated with LVMI (r = 0.812, P < 0.001), RWT (r = 0.318, p = 0.001), and CRP(r = 0.381, p < 0.001) in maintenance hemodialysis patients. CONCLUSION: The Gal-3 level is related to left ventricular hypertrophy and it is independent of left ventricle geometry. The relationship between LVH and Gal-3 might be direct or it may also be inflammation-related.

The coexistence of renal cell carcinoma and diffuse large B-cell lymphoma with hypercalcemic crisis as the initial presentation.

INTRODUCTOIN: Severe hypercalcemia can be life threatening. The causes of hypercalcemia can be divided into seven categories: hyperparathyroidism, vitamin D-related causes, malignancy, medications, other endocrine disorders, genetic disorders, and miscellaneous causes. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g. kidney stones). Hypercalcemia was clasified as serum levels of calcium: 1) mild hypercalcemia (calcium 14 mg/dl). We should keep in mind that severe hypercalcemia was originated from two or more causes. This is the first report in the literature; renal cell carcinoma (RCC) and diffuse large B-cell lymphoma (DLBCL) presented severe paraneoplastic hypercalcemia. CASE PRESENTATION: We report a case of a 63-year-old Turkish man with RCC and DLBCL who showed severe hypercalcemia (calcium=15.01 mg/dl) accompanied by elevation of serum parathyroid hormone-related protein (PTH-rP) as the initial presentation. While hypercalcemia is one of the complications of various types of cancerous diseases, it has not been reported still as the first presentation of the coexistence of RCC and DLBCL. After radical nephrectomy, the patient underwent six courses of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and achieved a complete remission that lasts 2 years. CONLUSION: This case report describes a patient with two different malignancies (RCC and DLBCL) with the unusual presentation of hypercalcemia. We review the differential diagnosis and treatment of malignant hypercalcemia. We suggest that coexistence of DLBCL with RCC, although rare, should be considered as a possible causative in hypercalcemia of unknown underlying disease.

Neutrophil-lymphocyte ratio may be superior to C-reactive protein for predicting the occurrence of postmenopausal osteoporosis.

OBJECTIVE: Recent studies revealed that inflammation plays a critical role in bone remodeling and the pathogenesis of postmenopausal osteoporosis, a major health concern. Neutrophil-lymphocyte ratio (NLR) is a cost-effective marker of inflammation that has been linked with several diseases. This study aimed to compare NLR and C-reactive protein (CRP) levels in osteopenic, osteoporotic, and control subjects and to assess the correlation between NLR levels, CRP, and bone mineral density (BMD) in postmenopausal women. METHODS: In this cross-sectional study, the relationship between NLR, CRP, and BMD in 438 women was investigated using uni- and multivariate analyses. BMD (g/cm²) was measured by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine and femur. Complete blood count (CBC), CRP, glucose/lipid metabolism, and established risk factors were determined. RESULTS: In the osteoporotic group, NLR and CRP levels were found to be elevated as compared to the osteopenic and control groups (NLR: 4.68 ± 0.72, 3.17 ± 0.43, 2.01 ± 0.54; CRP: 12.3 ± 4.1, 4.1 ± 2.7, 3.2 ± 2.1, respectively). A negative correlation was present between NLR and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. There was no correlation between CRP levels and BMD after adjusting other risk factors. NLR was significantly associated with L2-L4 BMD (ß = -0.653, p<0.001) and femoral neck BMD (ß = -0.178, p<0.001), but CRP level had no association with BMD in a multivariate model. CONCLUSIONS: Our data indicate that NLR may be a better predictor than CRP for occurrence of osteoporosis in postmenopausal women.

Benefits of the neutrophil-to-lymphocyte ratio for the prediction of gestational diabetes mellitus in pregnant women.

AIMS: There is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity, Type 2 Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM) and cardiovascular complications. Measuring the neutrophil-to-lymphocyte ratio (NLR) provides a simple inexpensive method for the assessment of inflammatory status. We investigated the predictive value of pre-procedural (before the oral glucose tolerance test (OGTT)) NLR on the development of GDM in pregnancy. METHODS: 42 women with GDM and 68 women without GDM were included in the study. Complete Blood Count and biochemical tests were followed by a diagnostic 4-point 100-g-OGTT within 2 weeks. GDM was diagnosed by the Carpenter and Coustan criteria. The NLR was calculated from the data. RESULTS: The mean NLR level was significantly higher in GDM women (3.00±0.83 vs. 2.26±0.43 p<0.001, respectively). In ROC analysis, NLR>2.93 had 76.2% sensitivity and 94.1% specificity in predicting GDM. Logistic regression analysis showed that elevated NLR (OR: 5.512, 95% CI: 1.352-22.475, p=0.017) was an independent variable for predicting GDM in pregnancy. CONCLUSIONS: An elevated NLR level is a powerful and independent predictor of GDM. The results of this study suggested that inflammation plays a central role in the pathogenesis of GDM.

Is vitamin D supplementation a new hope for the therapy of the septic shock?

Vitamin D is mainly known for its traditional role in the bone mineralization and calcium homeostasis. Recent studies have shown that vitamin D receptors (VDR) are present in almost all the tissues and cells in the human body. In addition, several studies have revealed that vitamin D is important in immunomodulation, regulation of inflammation and cytokines, cell proliferation, cell differentiation, apoptosis, angiogenesis, muscle strength, and muscle contraction. Patients with sepsis have high mortality rate and high deficiency in vitamin D. In addition, septic patients have decreased vitamin D binding-protein (DBP) levels which further exacerbate the vitamin D deficiency. The role of vitamin D treatment in sepsis syndrome has been evaluated in animal model of sepsis where 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] administration was associated with improved blood coagulation parameters in sepsis associated with a disseminated intravascular coagulation. Vitamin D treatment in vitro has also been demonstrated to modulate levels of the systemic inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as inhibit the lipopolysaccharide (LPS)-induced activation and vasodilation of vascular endothelium. Vitamin D may enhance the induction of the antimicrobial peptides, cathelicidin and b-defensin, which have been described on mucosal and epithelial surfaces acting as the body's first line of defense against viral and bacterial pathogens. Vitamin D supplementation may divert attention from relatively simple, natural, and low-costmethods of preventing severe sepsis and septic shock. Further prospective, randomized and controlled clinical trials of adjunctive vitamin D therapy in patients who are vitamin D deficient are needed in the management of human sepsis syndrome.

An unusual complication following eyelid ptosis surgery: superior rectus paralysis.

Blepharoptosis (ptosis) is one of the most common eyelid disorders encountered in ophthalmology. Several procedures have been developed to correct ptosis. The most common complications of ptosis surgery are well defined in the literature. Herein, we report a rare complication of superior rectus muscle paralysis following levator resection surgery for a blepharoptosis. Surgeons may well be aware of its occurrence.

[Cryosurgical ablation of bone tissue with a newly developed miniature cryoprobe--adaptation of the method for use in bones in vitro and in vivo]. / Die kryochirurgische Ablation von Knochengewebe mittels einer neuartigen Miniaturkryosonde--Adaptation der Methodik für die Anwendung am Knochen in vitro und in vivo.

AIM: Up to now, modern miniature cryoprobes have been used successfully for local destruction of soft tissue tumors without damaging adjacent healthy tissue. In this study, the methodology of cryoablation was applied to bone and the freezing effect as well as the cooling capacity of the probe was examined in vivo and in vitro. METHODS: Freezing was performed by cooling one or two probes, with a diameter of 3.2 mm to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined under thermic control by an in vitro measurement on human bone, followed by an in vivo measurement on femoral and tibia bones of a sheep. RESULTS: The in vitro freezings achieved a sufficient tissue cooling using one or two cryoprobes. The simultaneous use of 2 probes resulted in a synergistic effect between the probes. According to the body heat, the registered temperature curves, during the in vivo freezings, showed a more flat trend. Nevertheless, temperatures below -50 degrees C were achieved at a distance of 1 cm from the probe due to the synergistic effect. Local or systematical intraoperative complications have not been observed. CONCLUSION: An adequate tissue cooling of bone matrix can be achieved within in vivo freezings through the use of one or more miniature cryoprobes so that the use of this probe could possibly become an alternative or supplement to the surgical resection of pathologic bone processes.