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mTOR signaling has long been implicated in the mechanisms of cardiomyocyte survival in response to volume or pressure overload. Several studies have focused on the significance of mTORC1 in cardiomyocyte survival, questioning the role of mTORC2. mTORC2Akt signaling is an emerging axis implicated in cardiomyocyte compensation and thus heart failure. Upon being subjected to chronic stress, cardiomyocytes activate mTORC2Akt signaling pathway to promote survival by activating the ubiquitin proteasome system, inducing the degradation of pro-apoptotic proteins, and altering the actin cytoskeleton. Given the importance of mTORC2 in cardiomyocyte survival, studies suggest that loss of mTORC2 signaling would result in loss of cardiomyocytes, fibrosis, and heart failure. This review serves to elaborate on how mTORC2-Akt signaling plays a role in cardiomyocyte growth and survival under stress and how the loss of the axis would result in fibrosis and heart failure
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Obesity incidence has reached pandemic levels, and is accompanied by high incidence and poor prognosis of various types of cancers including gastrointestinal ones. Underlying mechanisms include elevated levels of insulin, IGF-I, and altered adipokine concentration, mainly towards leptin and adiponectin levels. However, it is not yet thoroughly understood. It is now widely known that obesity is associated with chronic low-grade inflammation, characteristic of altered immune cell infiltration in adipose tissue, and changed inflammatory cytokines and chemokines: tumor necrosis factor alpha (TNF-a), IL-6, and the chemoattractant monocyte chemoattractant protein 1 (MCP-1) and others, all together eventually promoting caner pathogenesis. Moreover, accumulating reports have shown that excess adipose tissue in obese individuals resulted in elevated levels of systematic oxidative stress, another way of promoting cancer development and progression. In general, altered immunological milieu and oxidative stress in obesity are important determinants for tumorigenesis
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Osteoporosis is the most important bone metabolic disorder characterized by reduction of bone mass and micro-architectural deterioration associated to an increased risk for fragility fractures. It involves millions of worldwide-dispersed individuals of both sexes and, consequently, the elevated morbidity and mortality of fractured subjects and the increased socio-economic costs suggest it must be faced as a major health problem. Thus, there is a need for either a precocious identification of subjects with fragile bones or the institution of specific diagnostic-therapeutical strategies. Improvement in bone pathophysiology knowledge, together with progress in pharmaceutical development has led to an opportunity for early identification and therapy of subjects at high risk of fragility fractures. In this review, we briefly describe the recent acquisitions in bone pathophysiology as well as in the anti-fracture drug development with a brief excursus on those already well established
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Shock waves have been widely recognized in literature as a biological regulator; accordingly we carried out a review on the effect of shock waves on the mesenchymal cells in their various expressions: bone, muscle, ligament and tendon tissue. To date, the application of Shock Wave Therapy (SWT) in musculoskeletal disorders has been primarily used in the treatment of tendinopathies (proximal plantar fasciopathy, lateral elbow tendinopathy, calcific tendinopathy of the shoulder, and patellar tendinopathy, etc.) and bone defects (delayed and non-union of bone fractures, avascular necrosis of femoral head, etc.). Although the mechanism of their therapeutic effects is still unknown, the majority of published papers have shown the positive and beneficial effects of using SWT as a treatment for musculoskeletal disorders, with a success rate ranging from 65% to 91%, while the complications are low or negligible. The purpose of this paper is to present the published data on the clinical application of SWT in the treatment of myofascial and nerve disorders. With the help of the relevant literature, in this paper we outline the indications and success rates of SWT, as well as the adequate SWT parameters (e.g., rate of impulses, energy flux density) defined according to the present state of knowledge
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Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders
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The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC₅₀ comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC
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The lymphedema is a high interstitial protein concentration edema, caused by impaired lymphatic transport capacity. It can be primary or secondary. The secondary form may be caused by a lesion of the lymphatic vessels and/or lymph nodes during diagnostic or therapeutic procedures such as surgical interventions. Often, in clinical practice, there is lymphedema after orthopedic surgery, even in minor orthopedic surgery. Lymphedema, typically presents symptoms of swelling, pain, inflammation, and itching, and it can generate, over the years, acute disability in the affected limbs. The standard therapy is mainly represented by medical treatment, such as manual lymphatic drainage and compression with bandages and stockings. In literature it is documented that lymphedema is responsive to alpha and the gamma benzopyrones. The aim of this study was to determine the effectiveness of delayed extended-release formulation of a compound containing apha-benzo-pyrone (Coumarin), benzo-gamma-pyrone (Troxuretina) and oligomeric proanthocyanidins from Vitis vinifera (OPC), in addition to compression therapy, in the reduction of lymphatic edema after prosthetic hip and knee surgery. In the group treated, after 30 days, a reduction was observed of the edema of 4.8% in the ankle area (p less than 0.008) and 2.7% in the calf area (p less than 0.013). The control group showed no significant reduction. The treated group showed a marked reduction of all the secondary symptoms considered in the study, although variations were not significant. The results show that the compound used was effective in reducing edema after major orthopedic surgery, and consequently in alleviating some related symptoms, such as pain, itching, and burning. As an edema has extensive inflammatory components in patients with reduced mobility, the final data seems interesting, however, further investigations and a better follow-up are required
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The effects of low-level laser therapy (LLLT) has been the focus of recent studies as being assumed responsible for promoting photostimulatory and photobiomodulatory effects in vivo and in vitro, increasing cell metabolism, improving cell regeneration and invoking an anti-inflammatory response. A positive effect of LLLT on the bone proliferation of some cell types has been observed, but little is known about its effect on dental pulp stem cells (DPSCs). Here, we accurately describe the technical procedure to isolate mesenchymal DPSCs, and assay their osteogenic capacity when irradiated with an LLLT source. These preliminary results show that LLLT irradiation influences the in vitro proliferation of DPSCs and increases the expression of essential proteins for bone formation, although it is necessary to carry out further experiments on other cell types and to uniform the methodological designs
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The antiproliferative and immunomodulatory effects of melatonin (MLT) have been demonstrated in a variety of neoplasms including colorectal cancer (CRC). In humans and other mammals, MLT acts on target tissues through membrane and retinoid nuclear receptors. The aim of this study was to evaluate transcription activity of melatonin receptors and genes associated with regulation of their activity in colorectal adenocarcinoma tissues in relation to clinical stage of cancer. A total of 24 pairs of surgically removed tumoral and healthy (marginal) tissue samples from colorectal cancer patients at clinical stages I-II and III-IV were collected. As an additional control, twenty normal samples were tak¬en from people whose large intestine tissues were reported as non-tumoral after colonoscopy. Expression of mRNA genes was studied by microarray HG-U133A analysis. The analysis of gene expression profile was performed using commercially available oligonucleotide microarrays of HG-U133A. High increase of MT1 mRNA expression levels in all cancerous samples vs non-cancerous tissues was observed. The MT2 mRNA expression levels increased slightly in marginal and malignant samples. Among the genes participating in the cascade of signal transfer in cells activated by MLT via melatonin receptors, we found encoding genes (GNA11, OXTR, TPH1) only for differentiating stage III - IV of CRC. Monitoring the expression levels of genes that are related to melatonin receptors may offer a strategy to anticipate tumour development and estimate the molecular changes that occur during carcinogenesis. The mechanism behind this association needs further elucidation
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Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 belong to the family of proteins known to be expressed in skin. Ablation of LRIG1 in mice results in epidermal hyperplasia and its aberrant expression levels have been reported in pathological conditions such as psoriasis, thus evident of an indispensible role of LRIG1 in maintaining epidermal homeostasis. In order to gain insight into the homeostatic expression of LRIG1 and in various stages of cutaneous wound healing, LRIG1 expression was immunohistochemically analyzed in full thickness skin wounds in mice. The full thickness skin wounds were established on the dorsal back of Balb/c mice (n=6). LRIG1 expression at various post wounding days (1, 2, 3, 6 and 14) was determined through Immunohistochemical analysis (IHC) of the murine skin sections. The injury caused a sharp decline in LRIG1 expression in the basal epidermal cells and appendages surrounding the wound which correlates with the re-epithelialization phase of healing. LRIG1 expression remained down regulated during most of the wound healing stages. LRIG1+ cells were found to re-populate the neo-epidermis on day 14, suggesting an important homeostatic role of LRIG1 in skin
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Using a microelectrode technique we studied the effects of vascular endothelial growth factor-B on the activity of rat atrial myocardium under normal conditions and after gradual stretching of the tissue. It was shown that vascular endothelial growth factor-B increased duration of the action potential only at the level of 90% re-polarization. Effects on the frequency and force of contraction were absent. The repetition frequency of the action potentials did not change. Close observation of the vascular endothelial growth factor-B-induced mechanisms and stretch-induced alteration in action potential durations to 90% of repolarization, confirmed the existence of a link between the examining growth factor-B and stretch induced mechanisms
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Traumatic shock is a serious threat to life and health. The aim of this study is to investigate the effect of different resuscitation fluid compositions on the emergency resuscitation for patients with traumatic shock. Sixty patients were enrolled and divided into two groups, Group A and Group B. The patients in Group A were treated with resuscitation fluid, with 2:1 ratio of crystal (0.9% sodium chloride injection) and colloid (hydroxyethyl starch 40 injection). The patients in Group B were treated with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40). Both vital signs and fluid dosage were monitored and recorded. At the beginning of resuscitation (T₀) and 30 min (T₁), 60 min (T₂) and 120 min (T₃) after resuscitation, indicator parameters including hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), arterial blood lacic acid (LA) and C-reactive protein (CRP) were monitored and recorded. Tissue oxygenation and hemodynamic profile were also analyzed. At T₁, T₂and T₃after fluid resuscitation, the heart rates of the patients in Group B were lower than those in Group A, whereas the average arterial pressure in Group B was significantly higher than that in Group A. Notably, significant decreases of HB and HCT were detected at T₁, T₂and T₃compared with T0 in Group A. In contrast, no significant difference was shown in detected HCT at T₂and T₃compared with T₀ in Group B, while the detected HB value was smaller. a statistically significant decrease of LA was detected at T₁, T₂and T₃in Group A and Group B compared with that at T₀. At T₂and T₃in Group A and Group B, a statistically significant increase of PT was detected compared with the beginning of resuscitation. At T₂and T₃after resuscitation, CRP in both Group A and Group B was significantly increased compared with that upon admission to hospital, and was lower in Group B than in Group A
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Spontaneous labor is the preferred delivery way ensuring health of fetus. However, recently, more and more puerperae tend to choose cesarean. However, cesarean delivery is likely to induce various short-term and long-term potential complications, severely threatening maternal and child health. To discuss the clinical effects of new-pattern obstetrical nursing in reducing cesarean delivery rate, 680 primiparas who delivered between December 2011 and December 2013 were selected from Beijing Obstetrics and Gynecology Hospital, Capital Medical University, China as research subjects. They were randomly divided into an observation group (n=340) and a control group (n=340). Primiparas in the observation group were taken care of by new-pattern nursing measures during pregnancy and the puerperal period, while primiparas in the control group received traditional nursing measures. Cesarean delivery rate was compared between two groups. Cesarean delivery rate was statistically significant between the observation group and the control group (21.8% vs 32.9%) (P less than 0.05). Also, it was found that, the incidence rate of perioperative complications of the observation group was much lower than the control group, and the difference was statistically significant (P less than 0.05). The findings suggest that new-pattern obstetrical nursing is effective in reducing the cesarean delivery rate, therefore is worth promoting and applying in clinical practice
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Glioma is a serious life-threatening disease, the pathogenesis of which remains to be investigated. The objective of the present investigation was to explore the expression and clinical significance of tumor suppressor gene (P53), O6-methylguanine-DNA methyltransferase (MGMT) and epidermal growth factor receptor (EGFR) in glioma. Immunohistochemical staining was applied to study the clinical characteristics of 40 samples from glioma patients, detect the expression of and analyse the relationship between P53, MGMT and EGFR and glioma. The results demonstrated that the positive expression rate of P53 was 47.5% in 40 cases of glioma samples, of which the expression of P53 in the high grade glioma was higher than that of the low grade samples (P < 0.05); the positive expression rate of MGMT was 37.5%, but there was no significant significance of MGMT expression between the high grade glioma and the low grade glioma (P >0.05); the positive expression rate of EGFR was 55%, of which the expression of EGFR of the high grade glioma was higher than that of the low grade glioma (P<0.05). There was no significant difference in the expressions of P53, MGMT and EGFR in the glioma patients of different ages, gender and with different tumor sizes. The expressions of P53 and MGMT were negatively correlated (P<0.05). The expressions of P53 and EGFR were positively correlated (P<0.05). In conclusion, P53, EGFR and MGMT could play a role in the occurrence, development and deterioration of glioma
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Raw milk contains diverse nutritional components that provide a suitable medium for spoilage and the growth of potentially pathogenic microorganisms. Unpasteurized milk consumption by a large number of people can threaten health and increase public concerns. In this study, sixty-two raw cow's milk samples were collected from the dairy farms of Ilam, Western Iran. All samples were collected in sterilized containers and were transferred via ice boxes to the laboratory. Isolates were then identified by standard methods. Totally, 88.7% (n=55) of samples were contaminated. Our study also showed that Escherichia coli had a high prevalence among isolates (43: 69.4%), while Klebsiella pneumoniae and Klebsiella planticola showed the lowest prevalence (1: 1.6%). Staphylococcus aureus was also detected in 17.7% (n=11) of samples. The raw milk microbial contamination is complex. Some of the microorganisms threaten public health via different traits, therefore it is recommended that raw milk consumption should be avoided
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Although squamous cell carcinoma (SCC) is the most common type of lip cancer worldwide, its giant form is extremely rare, due to its easy detection and early diagnosis. The survival rate is good if early eradication is performed, as 5-year survival accounts for approximately 80-90%. We present a rare variant of giant form of SCC on the lower lip in a 70-year-old patient, which had been neglected for many years, due to social disadvantages and absence of any resources for adequate medical help, until the tumor caused total inability of administration of food and drink. The recent diagnostic and therapeutic options are considered. Despite well-known etiologic factors regarding squamous cell carcinoma and the newest prognostic factors on tumor differentiation, such as β-catenin abnormal expression, the negative influence of the demographic characteristics of the patient were also in focus. Certain outcast ways of living should be considered as potential risk factors for the development of giant forms of SCC. In addition, an improvement of the quality of life of these patients results as being critical for the prevention of various of risk factors, as well as improving the survival rate in general
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The aim of this study is to investigate the expression of mTOR in breast cancer and observe the effect of CCI-779 on proliferation and apoptosis of MDA-MB-231 cells. Immunohistochemical staining was used to detect the expression of mTOR protein in breast cancer tissues and MDA-MB-231 cells. MTT assay was used to assess the effect of CCI-779 on proliferation of MDA-MB-231 cells. Annex-inV-FITC/ PI assay was utilized to evaluate the effect of CCI-779 on apoptosis of MDA-MB-231 cells. Among the 71 cases of breast cancer tissues, 54.9% were mTOR-positive that exhibited significantly higher expression than the 32 cases of normal tissues (21.9%); mTOR protein was also found to be expressed in MDA-MB-231 cells. The mTOR inhibitor CCI-779 significantly inhibited the proliferation of MDA-MB-231 cells that was dose- and time-dependent. However, CCI-779 was unable to induce apoptosis of MDA-MB-231 cells as demonstrated with AnnexinV-FITC/PI assay. mTOR plays a key role in the initiation and development of breast cancer, and its inhibitor CCI-779 exerts a strong suppressive activity against MDA-MB-231 cells, suggesting its therapeutic potential to treat breast cancer
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This study was carried out to test expression of transient receptor potential vanilloid1 (TRPV1) in urothelium of female patients with overactive bladder (OAB) and explore clinical significance of TRPV1 in diagnosing female OAB. TRPV1 expression in urothelium of female OAB patients (n=21) and healthy females (n=9) was detected using Strept Avidin-Biotin Complex (SABC), an immunohistochemical method and image analysis system. Relative content of TRPV1 was expressed by average optical density (AOD) and was analyzed through data of urodynamics. Compared to TRPV1 expression in urothelium of healthy females (AOD 0.3658 ± 0.1009), TRPV1 expression in OAB patients was much higher (AOD 0.4834 ± 0.1252) and the difference was significant P less than 0.05. Observation and comparison in clinic of urodynamic parameters of female patients and healthy females revealed that the former had lower indexes with remarkable differences (P less than 0.05) such as Qmax, first desire volume (FDV), strong desire volume (SDV), maximum cyst capacity (MCC) and bladder compliance (BC). Thus high expression of TRPV1 in urothelium of female OAB patients is closely correlated to OAB occurrence, showing great importance of improved bladder sensitivity in female OAB occurrence mechanism
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Osteosarcoma represents an aggressive type of bone malignancy that poses a significant health threat. The objective of the current study was to analyze the effect and mechanism of dihydroartemisinin (DHA) on the proliferation, metastasis and apoptosis of human osteosarcoma cells. A gradient concentration of DHA (15, 25 and 35 μmol.L-1) was used to stimulate the cells, along with control and Dimethyl sulfoxide (DMSO). The phenotypic outcomes were characterized using MTT assay, clone formation assay, Hoechst 33258 staining assay, luciferase reporter plasmid assay, Western blot and wound healing assay. In addition, IBM SPSS Statistics 18.0 software was applied for statistical analysis and all experimental data were expressed as mean ± s.d. Analysis of variance (ANOVA) was applied to compare the differences among multiple groups. Our results demonstrated that DHA inhibited the proliferation and metastasis of osteosarcoma cells and promoted the apoptosis in the cytomorphosis
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Recently, abnormal tumor suppressor gene (TSG) methylation has become a hotspot in the research on colorectal cancer (CRC). This study aimed to explore the influence of CHD5 methylation of CRC TSG on its clinical and pathological characteristics. A total of 40 operation samples as well as corresponding tissue specimens were collected from CRC patients treated in the First Affiliated Hospital of Zhengzhou University from January to December in 2014. CHD5 gene methylation in tissue specimens was detected with methylation specific polymerase chain reaction (MSP); moreover, messenger ribose nucleic acid (mRNA) expression of CHD5 in each tissue was tested using reverse transcription-polymerase chain reaction (RT-PCR), and Western blot was applied to detect the expression of CHD5 protein in those tissues and to analyze the correlation between mRNA and protein of cancer tissue CHD5 as well as the relationship between CHD5 methylation and protein expression. Results revealed that the expression rate of CHD5 methylation in 40 normal mucosal tissues, para-carcinoma tissues, adenoma tissues and CRC tissues was 12.5% (5/40), 22.5% (9/40), 47.5% (19/40) and 72.5% (33/40), respectively. The mRNA expression of CHD5 in the above tissues was 0.225±0.276, 0.169±0.231, 0.147±0.159 and 0.013±0.011 and the protein expression of CHD5 was 0.438±0.205, 0.398±0.180, 0.156±0.1 and 0.024±0.311, respectively. Methylation rate of CHD5 was 87% (20/23) in 23 cases of CHD5 protein loss expression and 52.9% (9/17) in 17 cases of CHD5 protein expression. Results of chi-squared test indicated that there was a significant difference in methylation rate (P less than 0.05), that is, the methylation rate of negatively expressed CHD5 protein was obviously higher than positively expressed protein. Thus, it can be concluded that the CHD5 methylation rate rises gradually in the evolution of CRC, which is related to the occurrence and development of CRC. Furthermore, CHD5 mRNA is positively correlated with protein expression and CHD5 gene methylation is associated with protein loss expression. Therefore, TSG CHD5 methylation of rectal cancer has a great effect in influencing its clinical and pathological features
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This study explores the value of 64-layer spinal computed tomography (CT) in diagnosing hepatocellular carcinoma (HCC) through performing dynamic contrast-enhanced scans. The study includes analysis of enhancement presentation of HCC in dynamic contrast-enhanced scan performed by multislice spinal CT (MSCT), comparison of detection rate and positive predictive value of neoplastic foci in subdivided arterial phases and portal venous phases, optimization of optimal scanning scheme for diagnosing HCC and discussion of the value of quantitative indexes such as T-D curve, maximum enhancement rate and clearance rate in diagnosing and identifying HCC. A total of 61 lesions were detected in 40 patients with HCC who were selected from the First People's Hospital, Jining, Shandong, China. Density difference was observed with statistical significance between the solid part of tumor and normal liver in different periods after CT scan and enhanced scan (H = 45.208, P less than 0.01), and difference in the late arterial phase was the most obvious; enhanced peak value mostly appeared in the late arterial phase. In terms of lesion detection rate, the difference of HCC detection rate was statistically significant in early, middle and late arterial phase and early and late portal vein phases (χ² = 32.910, P = 0.001) and the rate was the highest in the late arterial phase (78.689%). Lesions were divided into 3 cm or less group (small HCC) and over 3 cm group based on the maximum parameter. Detection rate of the late arterial phase was the highest, 85% (3 cm or less) and 75.61% (over 3 cm), respectively. When lesions with high density in arterial phase and/or low density in portal venous phase were considered as positive, and moreover, those confirmed clinically or pathologically were as true positive, we found positive predictive value of the over 3 cm group reached 100% in all phases, but that of 3 cm or less group was the highest (100%) in early and late portal venous phases. Among four scanning schemes involving early, middle and late arterial phases, detection rate of the early and late arterial phases and three arterial phases were consistent, reaching the highest value (3 cm or less group: 90%; the 3 cm over group: 78.049%). This study confirmed that the late arterial phase was the best time to detect abundant blood supplied HCC. The scanning scheme involving double arterial phases (early and late), late portal venous phase and stable phase which can help improve detection rate and correct diagnosis rate of HCC, was thought to be the most effective. Using dynamic enhanced CT examination in the diagnosis of HCC is meaningful both in qualitative and quantitative diagnosis. T-D curve, in particular, can intuitively and objectively reflect enhanced characteristics of HCC, and can be used to make a preliminary diagnosis of some atypical liver cancers
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This study was designed to explore tissue hardness and distinguish benign and malignant endometrial cancer with the use of transvaginal ultrasonography combined with elastography. Color Doppler ultrasonic diasonograph was used to carry out transvaginal ultrasonography and elastography. Once the nidus was observed, features of the 2D image were analyzed. Then features of elasticity of the uterine cavity in different states were analyzed by elastography, and strain rate ratio was measured. Finally, elasticity scoring (0~5 points) was made. Receiver operating characteristic (ROC) curve was drawn based on elasticity score and strain rate ratio. The area under the elasticity score curve and strain rate ratio curve was 0.761 and 0.852, respectively, and there was no statistically significant difference between them (c2= 4.663, P>0.05). Then 2.98 was confirmed as the diagnostic cut-off value of benign and malignant lesions, based on strain rate ratio. Ultrasonic elastography as an effective assistance for transvaginal ultrasonography provides more valuable information for confirmation of lesions and offers more accurate evidence for diagnosis of disease in the uterine cavity
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The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS
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Involvement of 25-hydroxyvitamin D in the etiopathogenesis of tonsillar disease in children is still debated; this study assesses possible differences in serum 25-hydroxyvitamin D levels between 309 Caucasian children (58.1% males; mean age 55.7 ± 31.0 months) living in Milan with a history of recurrent tonsillitis (RT) and healthy controls. Mean serum 25(OH)D levels were significantly reduced in the children with a history of RT (22.0 ± 8.7 ng/mL vs 24.6 ± 7.8 ng/mL; p=0.03), and the proportion of children with insufficient or deficient serum 25(OH)D levels was higher in the RT group (81.5% and 6.5% respectively) than in the control group (75.1% and 3.5%) (not significant). The multivariable model created to test the independent association between serum 25(OH)D levels and a history of RT after adjusting for age and season showed that the association was not significant. Our study failed to find any significant reduction in serum 25(OH)D levels after adjustment for age and season in a case series of children with RT in comparison with healthy controls, which suggests that vitamin D does not play a relevant role in the etiology of pediatric tonsillar infections
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Parathormone (PTH) has been suggested to affect the cardiovascular system. Teriparatide (TPT), the hormonally active 1-34 fragment of PTH, provides an anabolic treatment for osteoporosis. The aim of the present study was to evaluate the cardiometabolic effects of 18-month treatment with 20 μg/ die teriparatide subcutaneosly. Fourteen women with postmenopausal severe osteoporosis treated with once-daily sc 20 μg TPT (67.6 ± 2.5 years; BMI 27.7 ± 1.0 kg/m²) and 24 age- and BMI-matched severe osteoporotic women treated with iv yearly 5 mg zoledronate (ZLN) were evaluated at baseline and at 12-18 months of treatment for anthropometric measures, calcium, glucose and lipid metabolic parameters, and assessment of cardiac geometry by conventional echocardiography. TPT was effective in increasing mean lumbar spine bone mineral density with no clinically relevant changes in calcium metabolism parameters. TPT patients experienced an increase of BMI (27.7 ± 1.0 at baseline vs 29.0 ± 1.0 kg/m² at last evaluation, P=0.005) and mean whole body fat percentage (37.0 ± 2.1 vs 40.3 ± 1.9%, P=0.05), associated with increased serum leptin levels (17.3 ± 2.1 vs 22.9 ± 3.0 ng/ml; P=0.049). Glucose and lipid parameters were not affected by TPT as well as by ZLN treatment. Furthermore, TPT was associated with a decrease in systolic blood pressure; a decrease in the fractional shortening (41.2 ± 2.3 vs 36.9 ± 1.2; P=0.05) and an increase in the relative wall thickness (0.39 ± 0.01 vs 0.48 ± 0.01 mm; P=0.002), suggestive for concentric cardiac remodeling, was detected by echocardiographic monitoring. These changes could not be detected in bone active drug-free age- and metabolic-matched controls. In conclusion, long-term TPT therapy might affect cardiometabolic and cardiac geometry parameters in severe osteoporotic women, though changes are not clinically relevant
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Allergic rhinitis is considered a strong risk factor for the onset of asthma. However, few studies have addressed this issue from a functional point of view. In this work the close link between upper and lower airways is highlighted, suggesting that spirometry should be precociously performed on patients with allergic rhinitis
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Persistent shoulder pain is a highly prevalent problem, due to different pathologies, that is frequently associated with limited range of motion and decreased function. The correct diagnosis can lead to the best treatment for each pathology. In this study we tried to understand what could be the role of hyaluronic acid and its effective benefit in patients affected by mild-to-moderate glenohumeral osteoarthritis. From January 2013 to June 2014, we prospectively followed-up 61 consecutive patients with shoulder osteoarthritis degrees I, II, and III. We divided the patients into 2 homogeneous groups: 31 patients in the first group treated with 5 intra-articular injections of Hyalgan 20mg/2ml and a specific physiotherapy program, and 30 patients in the second group treated only with physical therapy. The mean follow-up examination was carried out 5.2 months after the beginning of the therapy for both groups. The statistical analysis revealed a significant difference (P less than 0.05) between the two groups in terms of pain reduction and improvement in the activities of daily living. The present study demonstrates the greater and long-lasting efficacy of a five-injection treatment with hyaluronic acid (Hyalgan 20mg/2ml) combined with a physical therapy program in comparison with physical therapy only in patients affected by glenohumeral osteoarthritis degree I, II or III
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Sex hormones play a role in pain perception, a key variable in evaluating the progression and treatment of osteoarthritis. The aim of this study was to determine the relationship between salivary concentrations of four steroid hormones and functional/clinical outcomes after hip and knee arthroplasty. Saliva samples were collected from 24 otherwise healthy patients with osteoarthritis before surgery, on admission to rehabilitation, and at hospital discharge. Salivary concentrations of testosterone, 17β-estradiol, dehydroepiandrosterone (DHEA), and cortisol were immunoassayed. Changes in hormone levels were compared with clinical outcomes, as assessed by functional independence measure (FIM®), Barthel Index (BI), and visual analog scale for pain (VAS) scores. Changes in testosterone levels were significantly inversely correlated with VAS (r= -0.53, p=0.043) and FIM® and BI scores in all patients (r= -0.30, p= 0.043, and r= -0.35, p=0.031, respectively). The testosterone to cortisol ratio was inversely correlated with BI scores in all patients (r= -0.30, p=0.040), and in the men (r= -0.55, p=0.005) and the women (r= -0.28, p=0.042) when analyzed separately. Changes in salivary testosterone concentrations closely correlated with clinical outcome measurements for total hip and knee arthroplasty. Clinical outcome after arthroplasty was generally better among the men
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Tooth replantation, as a treatment concept, has been subject to controversies regarding the mechanism as well as the various parameters underlying this process. This work aimed to study time-related changes in the pulp of replanted mature human premolars through the changes in the levels of certain factors involved in the underlying mechanisms of pulpal tissue healing after replantation. Eleven experimental mature teeth were extracted, immediately replanted in the original socket and left without any other intervention for 1, 2, 3 and 12 weeks before re-extraction. Three premolars served as control. All specimens were subject to histological analysis and the levels of MMP-2, MMP-9, Annexin V, iNOS and BCL-2 (anti-apoptotic family) were analyzed employing immunohistochemistry. The results showed degradation of the extracellular matrix (ECM), inflammatory cell infiltrate, loss in pulpo-dentine interface and loss of odontoblasts in the dental pulp tissue. This was accompanied by increase over time of MMP-9, Annexin V, iNOS and a decrease of BCL-2 and MMP-2, suggesting that apoptosis increased throughout the experimental period
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Nitric oxide (NO) is involved in eosinophilic inflammation. The fraction of exhaled nitric oxide (FENO) is increased in chronic rhinosinutis with nasal polyps (CRSwNP), whereas nasal NO (nNO) is reduced in chronic rhinosinutis. Nasal cytology can detect eosinophilic inflammation in CRSwNP. We aimed to describe the baseline rhinocytological characteristics and NO (FENO and nNO) levels in patients with CRSwNP, and assess their possible correlations. This longitudinal study involved 37 consecutive adult outpatients with CRSwNP and 36 healthy controls. They underwent a complete clinical otolaryngological assessment, measurement of FENO and nNO levels, and nasal scraping in order to collect material for nasal cytology. Disease severity was evaluated by means of endoscopic and Lund-Mackay radiological scores. Median FENO level was higher (p less than 0.001) in CRSwNP (28.3 ppb, 95%CI 13.0-33.6 ppb) than in the controls (7.5 ppb, 95%CI 6.1-8.9 ppb). Median nNO levels were lower (255.7, 95%CI 199.7-311.6 vs 385.5, 95%CI 345.0-425.9 ppb; p less than 0.001), and were lower in the patients with severe endoscopic obstruction (p=0.05). Lund-Mackay scores positively correlated with median FENO levels (R=0.11; p=0.05), and inversely with median nNO levels (R=-0.31; p=0.04). Metachromatic nasal cytotypes were more prevalent among CRSwNP patients who had previously undergone surgery (p=0.05). The number of metachromatic elements in the patients with CRSwNP positively correlated with their median FENO levels (R=0.24; p=0.002). Our results confirm the dynamic interplay between the upper and lower airways in patients with CRSwNP. FENO/nNO and nasal cytology can be useful for detecting and monitoring nasal inflammation in CRSwNP
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Medication-related osteonecrosis of the jaw (MRONJ) is a well-recognized severe complication of bisphosphonate (BPs) treatment in patients with osteoporosis or metastatic cancer. Microbiological infection has been hypothesized as a contributing factor to bisphosphonate related osteonecrosis of the jaw (BRONJ). Despite infection being present in BRONJ patients, there is no clear data as to whether infection plays a role in the pathophysiology. Moreover, microbial cultures have not been helpful in directing therapy because specific pathogens have not been identified. The objective of this study was to determine the bacterial colonization of jawbone and identify the bacterial phylotypes associated with BRONJ. Twenty oncologic patients, aged 48-87 years (average age 70.65 ± 8.86 years) with BRONJ were enrolled in this study and underwent three different microbiological samplings. Overall, 60 samples were obtained from oral mucosa, necrotic bone fragments and fistula drainage. The same procedure was performed for the laboratory culture of all these specimens. No significant differences regarding either gram+ and gram species (Chi-squared= 0.1642; p = 0.6854) or aerobes and anaerobes bacteria (Chi-squared= 3.084; p = 0.0791) were found. Compared to other sampling techniques, the oral swab allowed to obtain valuable microbial data in order to recognize pathogens responsible for the infection and to outline a focused antimicrobial therapy
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Osteoarthritis is being increasingly characterised as an inflammatory incoming and recurrent disease, with the specific symptoms of inflammation at every stage of the disease. With regard to the pathogenesis over time, the degenerative and inflammatory components are combined and lead to osteocartilaginous degeneration. Such deterioration involves other joint tissues as well as the subchondral bone tissue, the suffering of which is the key event of the beginning and progression of OA; its involvement concerns the same pathogenetic mechanisms and the same chemical mediators of the chondropathy. The increase in joint inflammatory events leads to suspect the onset or the worsening of the osteometabolic disorder, which is documented by the MR as bone edema or as algodystrophic syndrome. The pain appears both while moving and resting and with signs of inflammation. The treatment of OA requires drugs, such as paracetamol, selective and nonselective NSAIDs and opiates, for pain control. Treatment should ensure the pharmacological control of the pain related to the osteometabolic juxta-articular alteration, through bisphosphonates, favouring those which can control bone loss, inflammation and pain
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Dental pulp stem cells (DPSCs) are stem cells found in the dental pulp. The ability of DPSCs to differentiate towards odontoblastic and osteoblastic phenotype was reported first in the literature, then in the following years, numerous studies on odontogenesis were carried out, starting from mesenchymal stem cells isolated from tissues of dental and oral origin. The aim of this research was to evaluate the behaviour of DPSCs grown on silicon nanoporous and mesoporous matrices and differentiated towards the osteogenic phenotype, but also to investigate the use of DPSCs in pilot studies focused on the biological compatibility of innovative dental biomaterials. Twenty-eight silicon samples were created with standardized procedures. These scaffolds were divided into samples made of silicon bulk, nanoporous silicon, mesoporous silicon, nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH), nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene, mesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH) andmesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene. DPSC proliferation on the tested silicon scaffolds was analyzed at 3 and 5 days. The assay showed that DPSCs proliferated better on mesoporous scaffolds functionalized with APTMS/toluene compared to a silicon one. These results show that the functionalization of silicon scaffold with APTMS/toluene supports the growth of DPSCs and could be used for future applications in tissue engineering
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Due to its physical and biological characteristics and safety profile, hyaluronic acid is very widely used in numerous clinical conditions, ranging from its best-known use in cosmetic surgery (as a filler and for its ability to promote tissue regeneration and therefore minimise scarring) to lesser-known fields such as ophthalmic surgery, major abdominal surgery (where it is used to prevent the complication of adhesion bands) and intra-articular use. Studies were recently published in which this type of device was also used in paediatric patients for the management of inflammatory disorders of the oral cavity and teething symptoms. As this is a highly topical field for dentists, we felt it would be useful to review the efficacy and safety of the device in the paediatric population treated, and analyse any discrepancies with the results obtained in the adult population. The preparations of hyaluronic acid used in pediatric dentistry, thanks to their anti-inflammatory and angiogenic properties, proved to be very effective in therapy of oral diseases in children. Further clinical research is needed to confirm the effectiveness of these products to dispel doubts about any side effects
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Orthopaedic specialists should completely and sequentially manage osteoarthritis, from the onset to the prosthesis, with no attitude of resignation, complying with national and international Guidelines (GLs) and abiding by the criteria of appropriateness of drugs, rehabilitation and orthopaedic device prescription, in line with the ethics of the medical profession. The GLs are a paper that rationalises the quantity of existing information for a disease, without abusing the decision of the doctor; a large volume of scientific knowledge is concentrated in a format that is easily accessible to doctors when carrying out their work. The use of drugs has taken on a connotation of a rational and multifactorial choice, rather than an accidental and incremental choice - inspired only by safety, rather than efficacy criteria. The Notes compiled by the Italian Medicines Agency - a legal instrument to define the reimbursability of medicines and, therefore, an instrument for managing pharmaceutical expenditure are, in reality, a means to guarantee the appropriateness of the use of medicines, orienting the therapeutic choices according to established Guidelines. In the specific case of osteoarthritis, the knowledge of the GLs is the most appropriate and complete approach towards the disease, in the context of its pathogenetic complexity in its natural history. Moreover, pharmacological treatment of the subchondral osteometabolic damage becomes necessary when documented by magnetic resonance or a scintigraphy; the bone-related pain cannot be challenged through symptomatic analgesic treatment alone
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The biophysical stimulation of bone and cartilage, using Pulsed ElectroMagnetic Fields (PEMF), covers many different aspects of bone formation and/or cartilage repair, such as healing of delayed or non-union of fracture, bone necrosis, osteocartilagineous defects. To date there are no specific data on the effects of PEMFs in osteointegration of prosthetic implants but there are some papers that denote clinical advantages, in terms of early recovery, in patients treated with these procedures. Considering these clinical applications, PEMF stimulation around hip or knee joint implants could be useful to reduce the bone oedema, pain and to reduce excessive bone reabsorption around the femoral stems
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The aim of this work is to assess the level of the human alkaline phosphatase enzyme (ALP) during palatal expansion with Quad-Helix (QH) appliance. A total of twenty-two orthodontic patients characterized by contraction of the upper jaw, that needed application of a QH in order to treat their condition, were included in this study. Gingival crevicular fluid (GCF) was collected at four different times: before cementation (T0), after two weeks (T1), after four weeks (T2) and after one year (T3) from application of QH. In each patient maxillary first molars, right (UM-right) and left (UM-left), which were connected with bands to QH, were used for testing; first lower molars were used as Controls (LM-right, LM-left). Data show that ALP level in tension sites was proportional to the average increase of the inter-molar distance; on the contrary, the enzymatic level in compression sites was characterized by an inverse trend. The only exception to this phenomenon was recorded after one year (T3), when the increase of ALP level in both sites of tension and compression was ascribed to a mild inflammation due to bacterial plaque accumulation. The level of ALP in control sites was constant for the whole period of observation. The described ALP fluctuations in accordance with the inter-molar distance increment, shows that the main action of QH on bone remodelling was exerted during the fourth week (T2); for this reason, the monitoring of this enzyme could be used as a marker of effective function of the QH appliance
