Suppression of MYC by PI3K/AKT/mTOR pathway inhibition in combination with all-trans retinoic acid treatment for therapeutic gain in acute myeloid leukaemia.

Aberrant activity of the phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR [PAM]) pathway, as well as suppressed retinoic acid signalling, contribute to enhanced proliferation and the differentiation blockade of immature myeloid cells in acute myeloid leukaemia (AML). Inhibition of the PAM pathway was shown to affect especially mixed-lineage leukaemia-rearranged AML. Here, we sought to test a combined strategy using small molecule inhibitors against members of the PAM signalling pathway in conjunction with all-trans retinoic acid (ATRA) to target a larger group of different AML subtypes. We find that ATRA treatment in combination with inhibition of PI3K (ZSTK474), mTOR (WYE132) or PI3K/mTOR (BEZ235, dactolisib) drastically reduces protein levels of the proto-oncogene MYC. In combination with BEZ235, ATRA treatment led to almost complete eradication of cellular MYC, G1 arrest, loss of clonal capacity and terminal granulocytic differentiation. We demonstrate that PAM inhibitor/ATRA treatment targets MYC via independent mechanisms. While inhibition of the PAM pathway causes MYC phosphorylation at threonine 58 via glycogen synthase kinase 3 beta and subsequent degradation, ATRA reduces its expression. Here, we present an approach using a combination of known drugs to synergistically reduce aberrant MYC levels, thereby effectively blocking proliferation and enabling differentiation in various AML subtypes.

Loss of function TRPV6 variants are associated with chronic pancreatitis in nonalcoholic early-onset Polish and German patients.

PURPOSE: Loss of function variants of the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been recently associated with chronic pancreatitis (CP) in Japanese, German and French patients. Here, we investigated the association of TRPV6 variants with CP in independent European cohorts of early-onset CP patients from Poland and Germany. PATIENTS AND METHODS: We enrolled 152 pediatric CP patients (median age 8.6 yrs) with no history of alcohol/smoking abuse and 472 controls from Poland as well as 157 nonalcoholic young CP patients (median age 20 yrs) and 750 controls from Germany. Coding regions of TRPV6 were screened by Sanger and next generation sequencing. Selected, potentially pathogenic TRPV6 variants were expressed in HEK293T cells and TRPV6 activity was analyzed using ratiometric Ca2+ measurements. RESULTS: Overall, we identified 10 novel (3 nonsense and 7 missenses) TRPV6 variants in CP patients. TRPV6 p.V239SfsX53 nonsense variant and the variants showing significant decrease in intracellular Ca2+ concentration in HEK293T cells (p.R174X, p.L576R, p.R342Q), were significantly overrepresented in Polish patients as compared to controls (6/152, 3.9% vs. 0/358, 0%; P = 0,0007). Nonsense TRPV6 variants predicted as loss of function (p.V239SfsX53 and p.R624X) were also significantly overrepresented in German patients (3/157; 2.0% vs 0/750; 0%, P = 0.005). CONCLUSIONS: We showed that TRPV6 loss of function variants are associated with elevated CP risk in early-onset Polish and German patients confirming that TRPV6 is a novel CP susceptibility gene.

Outcomes Following Arthroscopic Single and Double Bundle Anterior Cruciate Ligament (ACL) Reconstruction Supported by the Comprehensive Early Rehabilitation Program (CERP).

BACKGROUND The aim of this study was to compare the level of functional condition in patients who had rehabilitation with the comprehensive early rehabilitation program (CERP) following either single bundle (SB) or double bundle (DB) anterior cruciate ligament reconstruction (ACLR) using semitendinosus-gracilis tendon graft (ST-G) method. We hypothesized that 12 weeks after reconstruction followed by a rehabilitation program, there would be a difference in clinical results and functional activity between patients. MATERIAL AND METHODS This study included 94 patients who had rehabilitation with CERP after knee surgery for a knee injury from a recreational sport. There were 49 patients in Group 1 (mean age, 36.5 years) who had CERP after SB ACLR, and 45 patients in Group 2 (mean age, 35.6 years) who had CERP after DB ACLR. Functional condition was tested using the Lysholm Knee Scoring Scale, and knee stability was measured using KT-2000. The first examination was performed before CERP and the second examination was performed 12 weeks later. RESULTS The level of functional condition in both groups was similar before rehabilitation with CERP, with no significant difference (P<0.958) and was considered relatively low. In the second examination, 12 weeks after starting CERP, the patients improved in both groups. The improvement was larger in the SB ACLR Group 1 than in the DB ACLR Group 2. The difference was significant (P<0.005). However, the patients in Group 2 achieved better knee stability scores in the KT-2000 examination than the patients in Group 1. The difference was significant (P=0.035). CONCLUSIONS We found that the patients from both groups after 12 weeks of CERP achieved an improvement in stability and functional activity within normal limits. However, SB ACLR was more effective than DB ACLR in terms of the level of functionality achieved with CERP but was less effective in terms of knee stability.

The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis.

Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

Application of principal component analysis for the optimisation of lead(II) biosorption.

Current study was focused on optimising lead(II) biosorption carried out by living cells of Arthrospira platensis using Principal Component Analysis. Various experimental conditions were considered: initial metal concentration (50 and 100 mg/l), solution pH (4.0, 4.5, 5.0, 5.5) and contact time (10, 20, 30, 40, 50 and 60 min) at constant rotary speed 200 rpm. It was found that when the biomass was separated from experimental solutions by the filtration, almost 50% of initial metal dose was removed by the filter paper. Moreover, pH was the most important parameter influencing examined processes. The Principal Component Analysis indicated that the most optimum conditions for lead(II) biosorption were metal initial concentration 100 mg/l, pH 4.5 and time 60 min. According to the analysis of the first component it might be stated that the lead(II) uptake increases in time. In overall, it was found to be useful for analysing data obtained in biosorption experiments and eliminating insignificant experimental conditions. Experimental data fitted Langmuir and Dubinin-Radushkevich models indicating that physical and chemical absorption take place at the same time. Further studies are necessary to verify how sorption-desorption cycles affect A. platensis cells.

Comparison of endometrial biopsy and postoperative hysterectomy specimen findings in patients with atypical endometrial hyperplasia and endometrial cancer.

OBJECTIVES: The aim of the study was to assess the concordance between the preoperative endometrial sampling and microscopic examination of the hysterectomy specimens in patients surgically treated for atypical endometrial hyperplasia and endometrial carcinoma. MATERIAL AND METHODS: We analysed a group of 204 patients, of whom 160 (78.43%) underwent surgical treatment for cancer of the corpus uteri and 44 (21.57%) for atypical endometrial hyperplasia. The preoperative diagnosis was based on the histological examination of endocervical and endometrial samples obtained by fractional curettage and it was compared to the histological findings at hysterectomy. The comparison was made for the basic diagnosis, the histological type of the cancer and the grade of tumour differentiation. RESULTS: When the histological types of cancer diagnosed in endometrial curettage and hysterectomy specimens were com-pared, the concordance was observed in 134/160 patients (83.75%). The highest concordance was found for endometrioid carcinoma (127/148 patients, 85.81%). The grade of tumour differentiation was accurate in 69.31% of patients. The highest concordance was for moderately differentiated carcinomas. Of 44 patients who underwent surgical treatment for atypical endometrial hyperplasia, the preoperative diagnosis was confirmed by the postoperative histopathological examination in 21 patients (47.73%). In 15 patients (34.09%) endometrial cancer was diagnosed at hysterectomy. CONCLUSIONS: In endometrial cancer our findings demonstrate a high level of concordance between the histological diagnosis on endometrial curettage and at hysterectomy. Own observations have confirmed that over 30% of patients undergoing surgical treatment for atypical endometrial hyperplasia have concurrent endometrial cancer which is determined by surgery.

KIR2DS5 in the presence of HLA-C C2 protects against endometriosis.

Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity. Several hypotheses have attempted to explain the etiology and pathogenesis of endometriosis. Recently, it has been suggested that a defect of the natural killer (NK) activity in the recognition and lysis of endometrial cells is one of the crucial points in the development of this disease. Natural killer cells can express killer immunoglobulin-like receptors (KIR), which recognize class I human leukocyte antigens on target cells. We asked whether polymorphisms in KIR, HLA-C, and HLA-B genes are risk factors for endometriosis. We tested 153 women with endometriosis diagnosed on the basis of laparoscopic and histological examination, and 213 control healthy women, who gave birth to at least one child. The frequency of KIR genes in patients was similar to that in controls except for KIR2DS5, which exerted a protective effect only in HLA-C C2-positive individuals. Moreover, KIR2DS5-positive women with endometriosis had 13 times lower chance that the disease would occupy the peritoneum than KIR2DS5- and KIR2DS4del-negative ones (OR = 0.077, P = 0.0061). Similarly, KIR2DS4del-positive endometriotic persons had 11 times lower chance for peritoneal disease (OR = 0.094, P < 0.001). Negative linkage disequilibrium between KIR2DS5 and KIR2DS4del indicates that these genes are mutually exclusive. Our data suggest that KIR2DS5 may be associated with protection from endometriosis, whereas KIR2DS4del seems to be associated with higher disease stages, possibly by exclusion of protective KIR2DS5.

Endometrial polyps in female allograft recipients with abnormal bleedings.

INTRODUCTION: Endometrial polyps are a common focal endometrial pathology, with abnormal uterine bleeding (AUB) as a predominant symptom. Although the great majority of cases are benign, premalignancy or malignancy may develop within the polyp. The need for chronic immunosuppressive therapy in solid organ transplanted patients is associated with a significantly increased risk of malignant lesions. AIM OF THE STUDY: Aim of the study was to evaluate the risk of endometrial polyps in solid organ transplanted women with abnormal uterine bleeding. MATERIAL AND METHODS: The retrospective analysis of 125 cases of AUB in allograft recipients and 200 consecutive cases of AUB in patients from the general population was performed. Pathological findings from dilatation and curettage were analyzed and compared between the groups. RESULTS: Endometrial polyps were the only pathological findings in 12% and 21.5% of cases from the study and the control groups, respectively. In each of the groups, one case of endometrial cancer coexisted with an endometrial polyp. If cases of endometrial polyps coexisting with endometrial hyperplasia were taken into account, the rate of endometrial polyps was similar to that observed in the general population (20% vs. 21.5%, respectively). CONCLUSIONS: Chronic immunosuppression, associated with an increased risk of malignancy, does not increase the risk of endometrial polyps among female graft recipients.

Comparison of the Efficacy of Human Umbilical Cord-Derived and Bone Marrow Aspirate Concentrate Mesenchymal Stem Cells for Cartilage Repair Defects of the Knee via Arthroscopic Implementation on Scaffolds in a Retrospective Study.

Injuries to the articular cartilage of the human knee joint, commonly resulting from trauma, inflammation, or age- and activity-related wear and tear, have significant implications, primarily leading to osteoarthritis (OA). Conservative treatments for such injuries often yield suboptimal clinical outcomes. Surgical interventions using current methods may not consistently provide satisfactory results, largely due to the formation of low-quality scar tissue lacking the biomechanical properties of hyaline cartilage. In this retrospective study, we compared the results of two promising methods for regenerating cartilage defects in the knee joints using scaffolds soaked with stem cells of different origins: bone marrow aspirate concentrate mesenchymal stem cells (BMAC-MSCs) and human umbilical cord-derived mesenchymal stem cells (hUCB-MSCs). We evaluated 39 patients (39 knees, hUCB-MSCs: 20 knees, BMAC: 19 knees) at the 12-month follow-up using VAS, KOOS, Lysholm scales and radiologically with M-MOCART 2.0 score. The analysis demonstrated substantial overall improvement in both groups, notably reflected in enhanced quality of life for the patients. Interestingly, the final scores in the hUCB-MSCs group were comparable to those in the BMAC-MSCs group, with no statistically significant differences observed, despite variations in preoperative age and lesion size. Notably, the hUCB-MSCs group consisted of significantly older individuals with larger lesion sizes. Both procedures were found to be safe, and improvement was observed in both groups, which holds promise for future clinical investigations.

Deep-level defects induced by implantations of Si and Mg ions into undoped epitaxial GaN.

The properties and concentrations of deep-level defects induced by implantations of Si and Mg ions into unintentionally doped (UID) epitaxial GaN have been revealed by using the Laplace-transform photoinduced transient spectroscopy (LPITS) and molecular dynamics (MD) calculations. The material lattice damage, produced by the Si ions implanted at room temperature in the single process at the energies of 200 and 340 keV, is compared with that produced by the Mg ions implanted in the similar process at the energies of 150, 210, and 270 keV. The LPITS results indicate that the same deep traps with the activation energies of 396, 512, 531, 587, 635, and 736 meV are present in the tail regions of the semi-insulating Si- and Mg-implanted films. It is argued that the predominant implantation-induced point defects in the tail region of the Si-implanted films are nitrogen vacancies, whose concentration is 7.7 × 1017 cm-3. In the Mg-implanted films, the predominant implantation-induced point defects are gallium interstitials, whose concentration is 1.2 × 1 018 cm-3.

Formation of Grown-In Nitrogen Vacancies and Interstitials in Highly Mg-Doped Ammonothermal GaN.

The formation of intrinsic point defects in the N-sublattice of semi-insulating Mg-doped GaN crystals grown by the ammonothermal method (SI AT GaN:Mg) was investigated for the first time. The grown-in defects produced by the displacement of nitrogen atoms were experimentally observed as deep traps revealed by the Laplace transform photoinduced transient spectroscopy in the compensated p-type crystals with the Mg concentrations of 6 × 1018 and 2 × 1019 cm-3 and resistivities of ~1011 Ωcm and ~106 Ωcm, respectively. In both kinds of materials, three closely located traps with activation energies of 430, 450, and 460 meV were revealed. The traps, whose concentrations in the stronger-doped material were found to be significantly higher, are assigned to the (3+/+) and (2+/+) transition levels of nitrogen vacancies as well as to the (2+/+) level of nitrogen split interstitials, respectively. In the material with the lower Mg concentration, a middle-gap trap with the activation energy of 1870 meV was found to be predominant. The results are confirmed and quantitatively described by temperature-dependent Hall effect measurements. The mechanism of nitrogen atom displacement due to the local strain field arising in SI AT GaN:Mg is proposed and the effect of the Mg concentration on the charge compensation is discussed.

Sex Differentiation of Trabecular Bone Structure Based on Textural Analysis of Pelvic Radiographs.

Objectives: The purpose of this paper is to assess the determination of male and female sex from trabecular bone structures in the pelvic region. The study involved analyzing digital radiographs for 343 patients and identifying fourteen areas of interest based on their medical significance, with seven regions on each side of the body for symmetry. Methods: Textural parameters for each region were obtained using various methods, and a thorough investigation of data normalization was conducted. Feature selection approaches were then evaluated to determine a small set of the most representative features, which were input into several classification machine learning models. Results: The findings revealed a sex-dependent correlation in the bone structure observed in X-ray images, with the degree of dependency varying based on the anatomical location. Notably, the femoral neck and ischium regions exhibited distinctive characteristics between sexes. Conclusions: This insight is crucial for medical professionals seeking to estimate sex dependencies from such image data. For these four specific areas, the balanced accuracy exceeded 70%. The results demonstrated symmetry, confirming the genuine dependencies in the trabecular bone structures.

Cardiovascular risk and the use of oral contraceptives.

The use of combined oral contraceptives (COCs) is associated with approximately 2-fold and over 4-fold increased relative risks of arterial and venous thromboembolic events, respectively. The highest risk of venous thromboembolism occurs in the first year of use (OR: 4.17) and is reduced to 2.76 over baseline risk after 4 years of therapy. The risk of myocardial infarction does not correlate to the length of therapy and disappears after treatment termination. Most of women, using COCs, have low absolute cardiovascular risks and benefits outweigh the risk associated with this method of birth control. However, in some cases, COCs may be contraindicated due to excessively increased cardiovascular risks. Current users of COCs, older than 35 years, appear to show an estimated 2.5-fold and 10-fold increased risk of venous thromboembolism in comparison to younger than 35 years COCs non-users and users, respectively. COCs users, who are current smokers, have 10-fold increased risk of myocardial infarction, whereas the risk of stroke increases nearly 3-fold. The presence of poorly controlled hypertension is associated with approximately 3-fold increased risks of myocardial infarction and ischemic stroke, while the risk of haemorrhagic stroke rises 15-fold. In women suffering from hypertension, discontinuation of COCs may improve blood pressure control. Women, who had their blood pressure measured before COCs use, have 2-2.5-fold decreased risk of myocardial infarction and ischaemic stroke. In women with multiple cardiovascular risk factors the use of progestogen-only contraceptives (POCs) should be considered. POC therapy is associated with substantially less risk of cardiovascular events than COCs.

Urogenital mycoplasmas and human papilloma virus in hemodialysed women.

Bacterial infections, especially endogenous, are the frequent complications among hemodialyzed and renal transplant patients. In this study we assumed the prevalence of urogenital mycoplasmas and HPV among hemodialysed women. We examined 32 hemodialysed women aged 20-48 (mean 35.6 ± 8.23) and 100 healthy controls of the same ages. Two swabs were collected for detection of mycoplasmas and HPV. Culture of Ureaplasma spp. and M. hominis was performed using Mycoplasma IST2 (bioMérieux, France), Identificaton of U. parvum and U. urealyticum was performed by Kong. Primers described by Jensen were used for M. genitalium. For detection of high-risk HPV types Amplicor HPV (Roche Molecular System, CA) was used. Prevalence of urogenital mycoplasmas in the hemodialysed women (53.1%) was significantly higher (P = 0.0059), compared with controls (25%). In both groups, U. parvum was the most frequently isolated. Cooccurrence of urogenital mycoplasmas was shown in 75% of the HPV-positive hemodialysed women and in 30.4% of HPV-positive controls (P = 0.0461). Cooccurrence of urogenital mycoplasmas with HPV was significantly higher in hemodialysed women. The need to take into account these microorganisms in routine diagnostic, especially for hemodialysed patients, was demonstrated. Further studies to demonstrate the role of this cooccurrence in etiopathogenesis of infection in hemodialysed patients are required.

[Huge uterine leiomyoma with degenerative changes mimicking ovarian carcinoma--a case report]. / Olbrzymi miesniak gladkokomórkowy macicy ze zmianami degeneracyjnymi imitujacy raka jajnika--opis przypadku.

Leiomyomas are the most common benign uterine tumors. Although 20-40% of all women in reproductive age may have uterine leiomyomas, they are not very common in pregnancy. Only 0.3-2.6% af all pregnant women are diagnosed with leiomyomas. The leiomyomas are symptomatic in 20-50% of all cases. Clinical symptoms are usually excessive or irregular menstrual bleeding, problems resulting from adjacent organs pressure, sterility miscarriage or problems during the labour. Leiomyomas are known to have estrogen receptors and can demonstrate an extensive growth in high estrogens concentration environment. During the pregnancy they can grow, stay the same size or as well decrease. Rapid leiomyoma's growth, caused by its transformation into sarcoma, takes place in about 0.1-0.8% of all cases. In this article we present a case of patient with leiomyoma, which rapid growth, which imitated ovarian tumor. A 40-year old patient was admitted to the 1st Department of Obstretrics and Gynecology Medical University of Warsaw, in May 2012 because of a large abdominal tumor. She had four vaginal deliveries and one cesarean section. The patients delivered three months before admission. Since the labour she had suffered from dysuria and noticed a quick waits enlargement. On admission the patient was in good general condition, without any stomachache. A giant tumor in her lower and middle abdomen was found. The tumor reached three fingers above the navel. In the ultrasound scan a large solid-cystic the tumor with moderate vascularization was described. It looked like the ovarian neoplasm. The CA-125 plasma concentration was 389,5 IU/ml. After giving a written informed consent the patient had an operation. During the operation a solid-cystic peducled uterine tumor was diagnosed. The diameter of the tumor was about 25 cm. The uterine and uterine appendages had no pathological macroscopic changes. Intraoperative histopathological examination was carried out and revealed mesenchymal tumor without evident polymorphism or mitosis. Because of lack of any signs of malignancy during the operation only the tumor with its peduncle was removed. The patient was discharged in good general condition after three day of postoperative hospitalization. The final histopathological examination revealed leiomyoma with cystic degeneration changes. A small focus of necrosis and extravasation was found. 4 weeks after the operation there were no abnormalities in the gynecological examination and the CA-125 concentration was 27 IU/ml. The presented case illustrates diagnostic difficulties, which may occur when atypical rapid tumor enlargement and its ultrasound image and laboratory tests results imitate ovarian tumor.

Asymmetric dimethylarginine reduces nitric oxide donor-mediated dilation of arterioles by activating the vascular renin-angiotensin system and reactive oxygen species.

INTRODUCTION: We tested the hypothesis that asymmetric dimethylarginine (ADMA) interferes with other mechanisms in addition to inhibition of nitric oxide synthase (NOS). Thus, in skeletal muscle arterioles, in the presence of ADMA, we investigated the dilator effect of an NO donor and increases in flow and aimed to elucidate the underlying mechanisms, including the role of oxidative stress, which is known to reduce the bioavailability of NO. METHODS AND RESULTS: In isolated rat gracilis skeletal muscle arterioles (∼160 µm at 80 mm Hg), ADMA (similarly to pyrogallol) reduced dilations to sodium nitroprusside (SNP), which was significantly prevented by the presence of superoxide dismutase (SOD) and catalase (CAT): SNP 10(-8)M; control: 43.2 ± 3%, ADMA: 4.9 ± 1%, ADMA + SOD/CAT: 30.2 ± 9% (p < 0.05). Also, ADMA reduced basal diameter and flow-induced dilations, which were not restored by L-arginine, but prevented by SOD/CAT and by inhibition of NAD(P)H oxidase (but not xanthine oxidase) and by an angiotensin-converting enzyme inhibitor or an angiotensin type 1 receptor blocker (ARB). ADMA increased the production of reactive oxygen species detected by lucigenin-enhanced chemiluminescence, which was significantly inhibited by SNP or ARB. CONCLUSION: We suggest that by activating the vascular renin-angiotensin-NAD(P)H oxidase pathway, ADMA elicits oxidative stress, which interferes with the bioavailability of NO and consequently reduces NO-mediated dilations.

Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study.

BACKGROUND: Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN) and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV). METHODS: The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. RESULTS: The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p = 0.37). There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had ≥ 2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. CONCLUSIONS: Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have developed in the cervical canal.

Potential mechanisms of low-sodium diet-induced cardiac disease: superoxide-NO in the heart.

RATIONALE: Patients on a low salt (LS) diet have increased mortality. OBJECTIVE: To determine whether reduction in NO bioactivity may contribute to the LS-induced cardiac dysfunction and mortality. METHODS AND RESULTS: Adult male mongrel dogs were placed on LS (0.05% sodium chloride) for 2 weeks. Body weight (25.4 + or - 0.4 to 23.6 + or - 0.4 kg), left ventricular systolic pressure (137.0 + or - 3.4 to 124.0 + or - 6.7 mm Hg), and mean aortic pressure (111 + or - 3.1 to 98 + or - 4.3 mm Hg) decreased. Plasma angiotensin II concentration increased (4.4 + or - 0.7 to 14.8 + or - 3.7 pg/mL). Veratrine-induced (5 microg/kg) NO-mediated vasodilation was inhibited by 44% in LS; however, the simultaneous intravenous infusion of ascorbic acid or apocynin acutely and completely reversed this inhibition. In LS heart tissues, lucigenin chemiluminescence was increased 2.3-fold to angiotensin II (10(-8) mol/L), and bradykinin (10(-4) mol/L) induced reduction of myocardial oxygen consumption in vitro was decreased (40 + or - 1.3% to 16 + or - 6.3%) and completely restored by coincubation with tiron, tempol or apocynin. Switching of substrate uptake from free fatty acid to glucose by the heart was observed (free fatty acid: 8.97 + or - 1.39 to 4.53 + or - 1.12 micromol/min; glucose: 1.31 + or - 0.52 to 6.86 + or - 1.78 micromol/min). Western blotting indicated an increase in both p47(phox) (121%) and gp91(phox) (44%) as did RNA microarray analysis (433 genes changed) showed an increase in p47(phox) (1.6-fold) and gp91(phox) (2.0 fold) in the LS heart tissue. CONCLUSIONS: LS diet induces the activation of the renin-angiotensin system, which increases oxidative stress via the NADPH oxidase and attenuates NO bioavailability in the heart.

Expression of ghrelin and its receptors in ovarian endometrioma.

Endometriosis is a common gynaecological disorder manifesting by implantation and growth of endometrial tissue outside the uterine cavity. The evidence accumulates that endometriosis may be associated with abrogated regulation of energy balance. Ghrelin is one of the most important orexigenic factor which may also play a role in regulation of inflammatory and angiogenic reactions. The present study was aimed at investigating expression profile of ghrelin and its receptors (GHSR1α and GHSR1ß) in endometriotic lesions. The study included ovarian cysts and peritoneal fluid specimens obtained laparoscopically from 20 women with revised American Fertility Society stage III or IV endometriosis. Expression of specific mRNAs was assessed by reverse transcription-polymerase chain reaction. Expression of ghrelin and GHSR1α protein was studied by immunohistochemical staining with specific antibodies. Ghrelin and its receptors mRNA expression was found in all tested specimens. Specific mRNAs for these factors were also expressed in the peritoneal leukocytes. Immunohistochemical staining revealed expression of ghrelin and GHSR1α both in glandular endometrioid epithelium and in some stromal cells, particularly in some fibroblasts, blood vessels and infiltrating leukocytes. Co-localization of ghrelin and its receptors strongly suggests that this neuropeptide may affect development and growth of endometriotic lesions and may influence local inflammatory and angiogenic response.

Compressive Strength Evaluation of Ultra-High-Strength Concrete by Machine Learning.

In civil engineering, ultra-high-strength concrete (UHSC) is a useful and efficient building material. To save money and time in the construction sector, soft computing approaches have been used to estimate concrete properties. As a result, the current work used sophisticated soft computing techniques to estimate the compressive strength of UHSC. In this study, XGBoost, AdaBoost, and Bagging were the employed soft computing techniques. The variables taken into account included cement content, fly ash, silica fume and silicate content, sand and water content, superplasticizer content, steel fiber, steel fiber aspect ratio, and curing time. The algorithm performance was evaluated using statistical metrics, such as the mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2). The model's performance was then evaluated statistically. The XGBoost soft computing technique, with a higher R2 (0.90) and low errors, was more accurate than the other algorithms, which had a lower R2. The compressive strength of UHSC can be predicted using the XGBoost soft computing technique. The SHapley Additive exPlanations (SHAP) analysis showed that curing time had the highest positive influence on UHSC compressive strength. Thus, scholars will be able to quickly and effectively determine the compressive strength of UHSC using this study's findings.