Initial handgrip strength as a predictive factor for amputation risk in diabetic foot patients.

BACKGROUND: We aimed to analyze the prognostic significance of handgrip strength as predictor of lower extremity amputation at 1 year follow up in patients with type 2 diabetes. METHODS: We evaluated 526 patients with type 2 diabetes between August 2020, and, June 2022. We collected from the electronic medical records demographic variables, laboratory data and history of amputation. The handgrip strength was assessed using a handheld Smedley digital dynamometer following the NHANES Muscle Strenght/Grip Test Procedure. Low handgrip strength was defined for women as less than 16 kg and for men less than 27 kg. Outcome variable was major or minor lower extremity amputation. RESULTS: A total of 205 patients with complete data entered the study. Patients mean age was 59 years old, 37% were women and the mean diabetes disease duration was 14 years. Seventy-seven (37%) patients suffered from lower extremity mputations (26 major and 51 minor amputations). After controlling for age, gender, presence of peripheral artery disease, body mass index and white cell counts as confounder variables, patients with low handgrip had an increased risk for amputations (Odds Ratio 2.17; 95% confidence Interval: 1.09-4.32; <0.001). CONCLUSION: Low handgrip stregth is an independent prognostic marker for lower limb amputation at one year in patients with diabetes.

Effect of final irrigation protocols with chitosan nanoparticle and genipin on dentine against collagenase degradation: An ex-vivo study.

AIM: Endodontic irrigants may affect the mechanical and chemical properties of dentine. This study evaluated the effects of various final irrigation protocols including the use of chitosan nanoparticle (CSnp) and cross-linking with genipin on the (1) mechanical and (2) chemical properties of dentine against enzymatic degradation. METHODOLOGY: CSnp was synthesized and characterized considering physiochemical parameters and stability. The root canals of 90 single-rooted teeth were prepared and irrigated with NaOCl. Dentine discs were obtained and divided into groups according to the following irrigation protocols: Group NaOCl+EDTA, Group NaOCl+CSnp, Group NaOCl+EDTA+CSnp, Group NaOCl+CSnp+Genipin, Group NaOCl+EDTA+CSnp+Genipin and Group distilled water. (1) Mechanical changes were determined by microhardness analysis using Vickers-tester. (2) Chemical changes were determined by evaluating molecular and elemental compositions of dentine using Fourier transform infrared spectroscopy (FTIR) analysis and scanning electron microscope (SEM)/energy dispersive X-ray spectroscopy (EDS) analysis, respectively. All analyses were repeated after the discs were kept in collagenase for 24 h. Data were analysed with repeated measures analysis of variance and Bonferroni correction for microhardness analysis, and Kruskal-Wallis and Wilcoxon tests for FTIR and SEM/EDS analyses (p = .05). RESULTS: (1) Collagenase application did not have a negative effect on microhardness only in Group NaOCl+EDTA+CSnp+Genipin when compared with the post-irrigation values (p > .05). Post-collagenase microhardness of Group NaOCl+EDTA+CSnp and Group NaOCl+CSnp+Genipin was similar to the initial microhardness (p > .05). (2) After collagenase, Amide III/ PO 4 3 - ratio presented no change in Group NaOCl+EDTA+CSnp, Group NaOCl+CSnp+Genipin and Group NaOCl+EDTA+CSnp+Genipin (p > .05), while decreased in other groups (p < .05). Collagenase did not affect CO 3 2 - / PO 4 3 - ratio in the groups (p > .05). There were no changes in the groups in terms of elemental level before and after collagenase application (p > .05). CONCLUSIONS: CSnp and genipin positively affected the microhardness and molecular composition of dentine. This effect was more pronounced when CSnp was used after EDTA.

Chirality-induced avalanche magnetization of magnetite by an RNA precursor.

Homochirality is a hallmark of life on Earth. To achieve and maintain homochirality within a prebiotic network, the presence of an environmental factor acting as a chiral agent and providing a persistent chiral bias to prebiotic chemistry is highly advantageous. Magnetized surfaces are prebiotically plausible chiral agents due to the chiral-induced spin selectivity (CISS) effect, and they were utilized to attain homochiral ribose-aminooxazoline (RAO), an RNA precursor. However, natural magnetic minerals are typically weakly magnetized, necessitating mechanisms to enhance their magnetization for their use as effective chiral agents. Here, we report the magnetization of magnetic surfaces by crystallizing enantiopure RAO, whereby chiral molecules induce a uniform surface magnetization due to the CISS effect, which spreads across the magnetic surface akin to an avalanche. Chirality-induced avalanche magnetization enables a feedback between chiral molecules and magnetic surfaces, which can amplify a weak magnetization and allow for highly efficient spin-selective processes on magnetic minerals.

Dipolar quantum solids emerging in a Hubbard quantum simulator.

In quantum mechanical many-body systems, long-range and anisotropic interactions promote rich spatial structure and can lead to quantum frustration, giving rise to a wealth of complex, strongly correlated quantum phases1. Long-range interactions play an important role in nature; however, quantum simulations of lattice systems have largely not been able to realize such interactions. A wide range of efforts are underway to explore long-range interacting lattice systems using polar molecules2-5, Rydberg atoms2,6-8, optical cavities9-11 or magnetic atoms12-15. Here we realize novel quantum phases in a strongly correlated lattice system with long-range dipolar interactions using ultracold magnetic erbium atoms. As we tune the dipolar interaction to be the dominant energy scale in our system, we observe quantum phase transitions from a superfluid into dipolar quantum solids, which we directly detect using quantum gas microscopy with accordion lattices. Controlling the interaction anisotropy by orienting the dipoles enables us to realize a variety of stripe-ordered states. Furthermore, by transitioning non-adiabatically through the strongly correlated regime, we observe the emergence of a range of metastable stripe-ordered states. This work demonstrates that novel strongly correlated quantum phases can be realized using long-range dipolar interactions in optical lattices, opening the door to quantum simulations of a wide range of lattice models with long-range and anisotropic interactions.

C-PEPTIDE AS AN INFLAMMATORY MARKER IN OBESE WOMEN.

Background: Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, "neutrophil-to-lymphocyte ratio" (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Material and methods: Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. Results: The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Conclusion: Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.

The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?

Biological systems are homochiral, raising the question of how a racemic mixture of prebiotically synthesized biomolecules could attain a homochiral state at the network level. Based on our recent results, we aim to address a related question of how chiral information might have flowed in a prebiotic network. Utilizing the crystallization properties of the central ribonucleic acid (RNA) precursor known as ribose-aminooxazoline (RAO), we showed that its homochiral crystals can be obtained from its fully racemic solution on a magnetic mineral surface due to the chiral-induced spin selectivity (CISS) effect [Ozturk et al., arXiv:2303.01394 (2023)]. Moreover, we uncovered a mechanism facilitated by the CISS effect through which chiral molecules, such as RAO, can uniformly magnetize such surfaces in a variety of planetary environments in a persistent manner [Ozturk et al., arXiv:2304.09095 (2023)]. All this is very tantalizing because recent experiments with tRNA analogs demonstrate high stereoselectivity in the attachment of L-amino acids to D-ribonucleotides, enabling the transfer of homochirality from RNA to peptides [Wu et al., J. Am. Chem. Soc. 143, 11836 (2021)]. Therefore, the biological homochirality problem may be reduced to ensuring that a single common RNA precursor (e.g., RAO) can be made homochiral. The emergence of homochirality at RAO then allows for the chiral information to propagate through RNA, then to peptides, and ultimately through enantioselective catalysis to metabolites. This directionality of the chiral information flow parallels that of the central dogma of molecular biology-the unidirectional transfer of genetic information from nucleic acids to proteins [F. H. Crick, in Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules, edited by F. K. Sanders (Cambridge University Press, Cambridge, 1958), pp. 138-163; and F. Crick, Nature 227, 561 (1970)].

The role of optic nerve sheath diameter measurement in the diagnosis of brain death.

OBJECTIVE: The aim of this study is to evaluate the correlation between optic nerve sheath diameter (ONSD) measured using computed tomography (CT), and ONSD measured using bedside ultrasonography (USG) in the diagnosis of brain death. PATIENTS AND METHODS: A total of 21 brain-dead patients were included in the study. The ONSD values of these patients were measured using both USG and CT before and after brain death, and the relationship between these measurements was evaluated. RESULTS: There was a high level of correlation between the right-left eye ONSD measurements conducted before brain death using USG and CT, respectively (p=0.000, p=0.001). There was a high level of correlation between the right-left eye ONSD measurements conducted after brain death using USG and CT, respectively (p=0.000, p=0.00). Pre-brain death ONSD mean values of both left and right eyes, measured using USG and CT, were found to be statistically significantly lower than the mean values of post-brain death measurements. CONCLUSIONS: In conclusion, a statistically significant difference was found between the optic nerve sheath diameter values measured before and after brain death using USG and CT. At the same time, it was determined that the values of the optic nerve sheath diameter measured using both CT and USG were correlated.

Increased SOCS1 and SOCS3 expression in papillary thyroid carcinoma and its association with prognosis.

OBJECTIVE: The majority of patients with papillary thyroid carcinoma (PTC) have good outcomes, although the identification of new predictors of a poor prognosis would be beneficial. Chronic thyroiditis is a precancerous condition in which proinflammatory cytokines enhance biologically aggressive features. This study investigated the expression of suppressor of cytokine signaling proteins (SOCS) 1 and 3, which are negative feedback inhibitors, in PTC and benign thyroid nodules (BTN), and analyzed the relations among biomarker expression, pathological prognosis, and clinical features. PATIENTS AND METHODS: The pathological materials and clinical data of 100 patients with PTC and 40 with BTN were retrospectively analyzed. Immunohistochemical SOCS1 and SOCS3 staining were performed. Besides comparing SOCS1 and SOCS3 expression between PTC and BTN, we analyzed the expression according to pathological factors and clinical variables. RESULTS: The expression levels of the proteins were significantly higher in PTC than in BTN (p=0.001). SOCS1 expression was higher in older patients with PTC than in younger patients (p=0.001). Unlike SOCS1, SOCS3 was related to the risk group; these groups were distinguished based on the American Thyroid Association (ATA) risk stratification system (p=0.001). SOCS3 was also significantly related to lymph node involvement (p=0.007), capsule invasion (p=0.005), and extrathyroid extension (p=0.009). CONCLUSIONS: The increased SOCS1 and SOCS3 expression in PTC confirms their roles in thyroid carcinogenesis. Antibodies to both SOCS1 and SOCS3 might aid the diagnosis of PTC through immunohistological staining. SOCS3 provides information on lymph node status and aids risk stratification.

Investigation of the efficacy of systemic N-Acetyl Cysteine therapy preventing nasal mucositis following radiotherapy.

BACKGROUND: Radiotherapy (RT) is one of the main methods used in the treatment of head and neck cancers but may cause mucosal side effects in the tumor area and surrounding structures. These include nasal mucosal disorders and chronic rhinosinusitis due to disruption of the mucociliary system. This situation seriously affects the quality of life of the patients and there is no accepted effective method for its treatment yet. In our study, we aimed to examine the side effects of RT on the nasal mucosa and mucociliary system and to investigate histopathologically and immunohistochemically the effectiveness of N-acetyl cysteine (NAC) in preventing these side effects of RT. METHODOLOGY: The study was carried out with 30 female Sprague Dawley rats devided in three groups. No intervention was made in the control group. On the second day of the experiment, 30 Gy radiotherapy was applied to the head area in the RT group. NAC was administered intraperitoneally at a dose of 1 g/kg/day for 14 days from the first day of the study to the RT+ NAC group. On the second day, 30 Gy of radiotherapy was applied to the head area 1 hour after the NAC application. On the 14th day, 1 hour after NAC was applied to the RT+NAC group, all animals were sacrificed. The nasal mucosa samples were stained with hematoxylin-eosin, and the intensity and extent of staining sentan in the nasopharyngeal tissue samples were evaluated by immunohistochemical staining using anti-SNTN antibody. RESULTS: The loss of cilia in the nasal tissue was lower in the RT+NAC group than in the RT group. The intensity and extent of staining in the nasopharyngeal tissue of Sentan was higher in the RT+NAC group than in the RT group. Mucosal neutrophil and mononuclear inflammatory cell infiltration in the nasal tissue, vascular dilatation, hyperemia and hemorrhage, erosion and shedding of the mucosal epithelium, mucosal ulceration were found to be similar in the RT+NAC group and the control group. It was milder in the RT+NAC group than in the RT group, but not statistically significant. CONCLUSIONS: Radiotherapy caused pathological changes in the nasal mucosa, caused loss of cilia and a decrease in the level of Sentan, the cilia apical protein. The results of our study showed that NAC treatment can reduce the side effects of RT on the nasal mucosa. It also showed that NAC was effective in preventing the loss of cilia, which is the building block of the mucociliary system, and improving the expression of Sentan.

Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface.

Homochirality is a signature of life on Earth, yet its origins remain an unsolved puzzle. Achieving homochirality is essential for a high-yielding prebiotic network capable of producing functional polymers like RNA and peptides on a persistent basis. Because of the chiral-induced spin selectivity effect, which established a strong coupling between electron spin and molecular chirality, magnetic surfaces can act as chiral agents and be templates for the enantioselective crystallization of chiral molecules. Here, we studied the spin-selective crystallization of racemic ribo-aminooxazoline (RAO), an RNA precursor, on magnetite (Fe3O4) surfaces, achieving an unprecedented enantiomeric excess (ee) of about 60%. Following the initial enrichment, we then obtained homochiral (100% ee) crystals of RAO after a subsequent crystallization. Our results demonstrate a prebiotically plausible way of achieving system-level homochirality from completely racemic starting materials, in a shallow-lake environment on early Earth where sedimentary magnetite deposits are expected to be common.

Prevalence and Associates of Frailty Status in Different Stages of Chronic Kidney Disease: A Cross-Sectional Study.

OBJECTIVES: Frailty is a state of homeostenosis associated with adverse outcomes. Chronic kidney disease (CKD) increases considerably by aging and shares the common risk factors with frailty. We aimed to examine the prevalence and independent associates of frailty status in CKD patients. DESIGN: In this single-centre, cross-sectional study, we used the five-item Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight (FRAIL) scale to evaluate frailty. A binary logistic regression analysis model including the parameters found to have relationship with frailty in univariate analyses was used to detect independent associates of frailty status. Odds ratio (OR) and 95% confidence interval (CI) were given. PARTICIPANTS: Study included 148 patients aged 18-80. Sixty (60) patients were end stage renal disease (ESRD) patients on maintenance hemodialysis (HD) (at least for 3 months) and 88 were stage 3-4 CKD patients. Thirty-seven (37) patients (42%) were eGFR G3a, 31 patients (35.3%) were eGFR G3b and 20 patients (22.7%) were eGFR G4 in stage 3-4 CKD patients. MEASUREMENTS: Demographics, etiology of CKD, comorbidities, regular drugs, dialysis-related and laboratory data were recorded. FRAIL scale was scored as follows; 0=robust, 1-2=prefrail, and ≥3= frail. The frailty status was compared between frail+prefrail group vs robust (non-frail) group. RESULTS: The prevalences of prefrailty and frailty were 68.3% and 3.3% in HD group and 53.4% and zero in stage 3-4 CKD group, respectively (p = 0.025). In the multivariate logistic regression analysis, being in HD group (OR=3.87, 95% CI= 1.06-14.19, p=0.04), older age (OR=1.09, 95% CI= 1.04-1.13) and female sex (OR=9.13, 95%CI= 2.82-29.46) were independent risk factors for frailty (p<0.001, for both). CONCLUSION: Prefrailty and frailty are quite common among HD and CKD stage 3-4 patients. Being an HD patient is an independent risk factor for non-robust (frail or prefrail) status. Our findings point out a remarkably high prevalence of frailty severity (prefrailty/frailty) phenotype among patients with advanced CKD stages.

On the origins of life's homochirality: Inducing enantiomeric excess with spin-polarized electrons.

Life as we know it is homochiral, but the origins of biological homochirality on early Earth remain elusive. Shallow closed-basin lakes are a plausible prebiotic environment on early Earth, and most are expected to have significant sedimentary magnetite deposits. We hypothesize that ultraviolet (200- to 300-nm) irradiation of magnetite deposits could generate hydrated spin-polarized electrons sufficient to induce enantioselective prebiotic chemistry. Such electrons are potent reducing agents that drive reduction reactions where the spin polarization direction can enantioselectively alter the reaction kinetics. Our estimate of this chiral bias is based on the strong effective spin-orbit coupling observed in the chiral-induced spin selectivity (CISS) effect, as applied to energy differences in reduction reactions for different isomers. In the original CISS experiments, spin-selective electron transmission through a monolayer of double-strand DNA molecules is observed at room temperature-indicating a strong coupling between molecular chirality and electron spin. We propose that the chiral symmetry breaking due to the CISS effect, when applied to reduction chemistry, can induce enantioselective synthesis on the prebiotic Earth and thus facilitate the homochiral assembly of life's building blocks.

The success of dorsal onlay buccal mucosal graft urethroplasty in challenging urethral stricture cases after multiple failed urethrotomies.

Background: Urethroplasty is the gold standard treatment procedure for male patients with urethral stricture and is becoming increasingly popular among urologists worldwide. Procedure success rates have risen with increased experience. Aims: Here we aimed to examine the results of urethroplasty in challenging cases of urethral stricture and its effect on sexual function. Patients and Methods: Data were collected retrospectively from the patients who had undergone urethroplasty after multiple failed direct vision internal urethrotomy (DVIUs) from 2017 to 2020. All patients were monitored for a minimum of 12 months. Outcomes of urethroplasty were analyzed according to stricture location, length, and the number of prior DVIUs. Penile length and sensation, erectile, and ejaculatory function of the patients were evaluated pre- and postoperatively. Results: The patient cohort consisted of 36 males with a mean age of 63 ± 3.2 years. The most prevalent stricture etiology was iatrogenic (83%). Patients who underwent three or more DVIUs before urethroplasty and stricture length >4 cm were included in the analysis. Accordingly, the overall success rate was 83% (30/36). When the success rate and the IIEF5 scores were assessed separately, there was no significant relationship between the number of DVIUs (P > 0.05). Similarly, no significant relationship was also found with the stricture length (P > 0.05). Conclusion: Appropriate and correctly applied surgical technique does not impair sexual activity, even in patients with severe urethral stricture, regardless of the length or location of the stricture and the number of prior endoscopic procedures.

Association of TRPM5 Asn235Ser Polymorphism and Trace Elements/Minerals in Chronic Gastritis Patients: a Case-Control Study.

The link between chronic gastritis and chemosensory receptors is considered promising for disease prediction and treatment. The transient receptor potential melastatin member channel 5 (TRPM5) is an ion channel and may be a chemosensor in the gastrointestinal tract. Trace elements and minerals involved in many protein structures can change ion channel activity. Our study aimed to determine trace element and mineral levels according to TRPM5 Asn235Ser missense polymorphism distributions in patients with H. pylori (+) and (-) gastritis and to uncover their possible association with disease pathogenesis. In 109 volunteer patients diagnosed with gastritis [64 H. pylori (+), 45 H. pylori (-)], TRPM5 (Asn235Ser) polymorphism was detected by Kompetitive Allele-Specific PCR method (KASP), but no difference was found between the groups. There are differences between the serum trace element (Se, Zn, Cu, Mg, and Cu/Zn) levels of the two groups. High serum Se and Cu/Zn ratios were detected in H. pylori (+) patients. Cu/Zn ratio can be used as a marker of bacterial inflammation. The amount of Se was found to be statistically significant in the serums of H. pylori (+) patients carrying TT and CT genotype, while the amounts of Zn, Cu, and Mg were found as significant of H. pylori (-) patients. The relationship of Se with the H. pylori needs to be investigated further. In addition, H. pylori (+) patients have a significantly higher neutrophils/lymphocytes ratio (NLR) compared to those with H. pylori (-) NLR can be used as an indicator of inflammation.

Potential therapeutic road for targeting the SARS-CoV-2 at throat.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has become a serious public health problem for    183 out of 197 countries in the world. Understanding the routes and pathogenesis of the coronavirus is important and it is considered that the studies on host cell receptor Angiotensin Converting Enzyme 2 (ACE2) may be valuable for the treatment and prevention of the disease. AIM: To evaluate the possibility of inhibition of SARS-CoV-2 at throat. METHODS: A comprehensive literature search was conducted. CONCLUSION: In view of the fact that the mouth and nose have higher number of ACE2 expressed cells, they serve as a gateway for the virus to enter. Thus, blocking the gate could be a good choice to reduce or even prevent the transmission. Small interfering RNAs (siRNAs) are double-stranded RNA molecules and could be designed easily and directed against many strains of a virus. Due to their features, siRNAs can provide a potential strategy to interfere with the replication of viral diseases. We think that since oral and nasal epithelial cells are relatively easily accessible it may allow to develop siRNA molecules to inhibit SARS-CoV-2 already at the entry where it continues to replicate for a period (Fig. 1, Ref. 50).

miR-145 suppresses epithelial-mesenchymal transition by targeting stem cells in Ewing sarcoma cells.

OBJECTIVES: We aimed to examine the performance of stem cell markers and epithelial-mesenchymal transition (EMT) process in miR-145 transfected EWS cells (TC71, TC106). METHODS: EWS cells were utilized for functional analysis of mir-145. Proliferation, migration, invasion and soft agar colony assay were performed to observe the alterations in migration behavior of transfected cells. Caspase assay was used to investigate the underlying reasons of proliferative inhibition in cells in whichmiR-145 is overexpressed. QRT-PCR was used to determine the role of miR-145 in EMT transcription markers and mir-145 targeted genes, KLF4, SOX2 and OCT4 expression levels. RESULTS: The miR-145 expression has been shown to be down-regulated in EWS. The miR-145 overexpression caused inhibition of proliferation and reduced migration in EWS cells through induction of apoptosis. Mir-145 suppresses EMT capacity and SOX2, KLF4 and OCT4 expression levels. CONCLUSION: This is the first time in the literature we have shown deregulation of miR-145 inhibits EMT process by targeting stem cell properties leading to the inhibition of tumor growth and metastasis in TC71 and TC106 cells. Based on these results, we propose that miR-145, as an important regulator of SOX2, KLF4 and OCT4 carries crucial roles in EWS tumorigenesis and EMT (Tab. 1, Fig. 4, Ref. 26).

Swallowing-induced supraventricular arrhythmia: A different perspective to mechanism.

Atypical presentations of supraventricular arrhythmias constitute a diagnostic challenge which are not frequently reported in literature. Swallowing-induced supraventricular arrhythmia (SI-SVA), which was first described in 1926, is an intriguing presentation of supraventricular tachycardia and occurs during a wet or solid swallow. A 67-year-old man presented to our outpatient clinic complaining from recurrent episodes of sensation of palpitations and short duration pressure on his chest while swallowing since the last 2 weeks. Ambulatory rhythm Holter monitoring was suggestive of atrial fibrillation (AF) or atrial tachycardia attacks during swallowing. In addition, electrocardiography performed during solid food swallowing, showed short duration of AF consistent with the patient's symptoms. The patient was successfully treated with amiodarone. The main cause of SI-SVA is not known. Cross-talk of nerves during the impulse propagation might be the underlying cause of this phenomenon.

Renal Autotransplantation in a Patient with Bilateral Renal Artery Stenosis Secondary to Takayasu Arteritis.

Involvement of the renal artery is common in Takayasu arteritis. We, herein, present on a patient with Takayasu arteritis causing severe renal failure and a successful auto-transplantation. This case shows that early diagnosis and immediate appropriate interventions are life-saving in patients with Takayasu arteritis. Renal auto-transplantation performed in selected cases increases dialysis-free survival.

Relationship between Chromosomal Aberrations and Gene Expressions in the p53 Pathway in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a neoplasm characterized by excessive accumulation of B lymphocytes in the peripheral blood, bone marrow and lymph nodes. We assessed the expressions of 22 genes in the p53 pathway in 30 CLL patients and 15 healthy subjects by a RT2 Profiler PCR (polymerase chain reaction) Array technique and their relation to cytogenetic aberrations detected by fluorescent in situ hybridization (FISH). Our Student's t-test results indicated that ATM, ATR, BAX, CASP9, CDK4, CDKN2A, CHEK1, CHEK2, E2F3, MCL1, MDM2, MDM4, PCNA, RB1, P53 and BCL2 genes were statistically significant (p <0.001). For six genes (APAF1, CDKN1A, E2F1, GADD45A, PTEN and PTX3) were not statistically significant. The ATM, ATR, BAX, CASP9, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, MDM4, PCNA, RB1, P53, E2F1, GADD45A and BCL2 genes were found to be upregulated by the 2-ᐃᐃCt (relative fold change in gene expression) method. The highest up-regulation was detected in CDKN2A and BCL2 genes, 10.22- and 8.51-fold, respectively. On the other hand, the PTX3 gene with a fold regulation of 1.84 was found to the highest downregulation. Overall, the CDNK2A BCL2 and PTX3 genes are related to the mechanism of the disease in the p53 pathway and may be an important predictor of the prognosis of the disease. The BCL2 gene may be associated with increased risk of developing CLL. We suggest that the PTX3 gene may be considered as a marker associated with CLL disease. The CDKN2A gene expression seems to play a protective role in CLL.

CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue microarray study.

INTRODUCTION: CIP2A is an oncoprotein involved in the progression of several human malignancies. It has recently been described as a prognostic marker in many cancers. The present study aimed to investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the association with the clinicopathological parameters in PC cases to define its role in the development and progression of PC. MATERIALS AND METHODS: Immunohistochemical staining for CIP2A was performed on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression scores were compared with several clinicopathological parameters. RESULTS: CIP2A was expressed in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039). Nevertheless, there was no statistically significant association between the expression of CIP2A and perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there was no significant difference between the survival times of patients according to CIP2A expression (p=0.174). CONCLUSIONS: According to our results, the expression of CIP2A protein is increased in PC and its expression may be involved in the development, differentiation, and aggressiveness of PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A in the development of PC.