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Studies T cell clonotypes in the airways of non-atopic asthma. Isolation of cells in BALF and peripheral blood lymphocytes; Cellular components of BALF and HLA typing of non-atopic asthmatics; Clonal expansion of T cells infiltrating in the airways of patients.

We describe a patient suffering from familial Mediterranean fever (FMF) who presented to our clinic with secondary infertility of 2 years due to amyloid A amyloidosis. His spermiogram disclosed azoospermia. A testicular biopsy revealed hyalinized tubules devoid of full spermatogenesis and containing abundant amyloid, confirmed by Congo red stain. We suggest that testicular amyloidosis be taken into consideration when dealing with azoospermic FMF patients. In view of the progressive nature of amyloid accumulation in the testis we propose to follow routinely the spermiogram of FMF patients with renal amyloidosis. Furthermore, consideration of sperm cryopreservation is suggested in these cases. In FMF patients with azoospermia consideration of testicular biopsy is recommended as early as possible in order to increase the chance of sperm retrieval. [ABSTRACT FROM AUTHOR]

Background: Histological evaluation of ovarian tissue harvested as part of the attempt to preserve fertility might clarify the mechanism by which ovarian failure is caused. The purpose of this study was to compare the histologic appearance of ovarian tissue harvested for ovarian tissue cryopreservation (OTC) in chemotherapy naïve and chemotherapy exposed patients regarding the presence of follicles in different stages of development and to explore ovarian tissue histology in patients exposed to low- and high-cytotoxicity risk chemotherapy., Methods: A cohort of post-pubertal cancer survivors who underwent OTC between 1997 and 2018 was evaluated. An expert pathologist reviewed the pathology slides taken during OTC. The assessment included counting number of primordial, primary, secondary, and antral follicles. A comparison was made between chemotherapy naïve and chemotherapy exposed women and further between women who previously received low- versus high-risk gonadotoxic regimens., Results: Seventy post-pubertal patients were included in the study. Seventeen (24.3%) received chemotherapy prior to OTC, and 53 (75.7%) were chemotherapy naïve at the time of OTC. A significant difference was found only in the number of secondary follicles, which was increased in chemotherapy naïve patients (2.81±4.26 vs. 0.88±1.18, respectively; P=0.005). Similar results were observed in a subgroup analysis of hematologic malignancies separately. Comparison of patients with previous exposure to chemotherapy revealed similar follicular appearance, except for the number of secondary follicles, which was higher in patients receiving low-risk compared to high-risk chemotherapy (1.40±1.28 vs. 0.14±0.35, respectively; P=0.006)., Conclusions: The ovarian follicular pool at OTC appears comparable between chemotherapy naïve individuals and those post-exposure, as well as among patients receiving low versus high-risk gonadotoxic regimens, with the exception of secondary follicles, which are presented in increased numbers in chemotherapy naïve and those exposed to low-risk gonadotoxic chemotherapy.

Group A Streptococcus (GAS; Streptococcus pyogenes ) is a facultative gram-positive coccus, uncommonly colonizing parturient genitalia, where its presence can potentially lead to a life-threatening invasive infection after delivery. GAS infection typically occurs within the first 4 days post-partum and is characterized by high fever, chills, flashing, abdominal pain, and uterine tenderness. Nonetheless, patients with GAS puerperal sepsis may have an unusual presentation, when fever is absent, and the symptoms and signs can be mild, non-specific, and not indicative of the severity of infection. This unusual presentation may lead to a delayed diagnosis and increase the risk for severe puerperal sepsis. Therefore, in these cases, a high index of suspicion and prompt early antibiotic and surgical treatment is crucial to saving the parturient's life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kabiri, Prus, Alter, Gordon, Porat and Ezra.)

Background and objectives: The risk of low energy availability is related to various health problems in sports. This cross-sectional study aimed to identify a possible association between various dance factors, anthropometrics/body build, and energy availability with injury occurrence in contemporary dancers. Materials and Methods: The participants were 50 female competitive dancers (19.8 ± 4.1 years of age). The independent variables included age, dance factors (amount of training and competitions per week-exposure time, experience in dance), anthropometrics/body composition (body height, mass, BMI, body fat percentage (BF%), and fat-free mass (FFM)), and energy availability score (EAS; evaluated by accelerometer-based measurement of energy expenditure and Dance Energy Availability Questionnaires). The dependent variables were the occurrence of (i) soft-tissue injuries and (ii) bone injuries. The measurements were obtained by experienced technicians during the pre-competition period for each specific dance discipline. Univariate and multivariate logistic regressions were calculated to identify the associations between independent variables and injury prevalence. Results: The results showed that EAS (OR = 0.81, 95% CI:0.65-0.91), age (OR = 1.65, 95% CI: 1.1-2.46), higher BF% (OR = 1.23, 95% CI: 1.04-1.46) and BMI (OR = 1.61, 95% CI: 1.05-2.47) were correlated with soft-tissue injuries. Dancers who suffered from bone injuries reported higher exposure time (OR = 1.21, 95% CI: 1.05-1.37) and had lower values of FFM (OR = 0.73, 95% CI: 0.56-0.98). Multivariate regression analyses evidenced a higher likelihood of soft-tissue injuries in older dancers (OR = 1.75, 95% CI: 1.21-2.95) and the ones who had lower EAS (OR = 0.84, 95% CI: 0.71-0.95) while the exposure time was associated with a higher likelihood of bone injuries (OR = 1.21, 95% CI: 1.05-1.39). Conclusions: In order to decrease the injury prevalence among dancers, special attention should be paid to maintaining adequate nutrition that will provide optimal available energy for the demands of training and performing. Additionally, the control of training volume should be considered in order to reduce traumatic bone injuries.

Competing Interests: Competing interests:: None.

The positive effects of dance on health indices in youth are widely recognized, but participation in dance is accompanied with a certain risk of injury. This prospective study aimed to investigate injury occurrence and to evaluate the possible influences of specific predictors on the occurrence of musculoskeletal problems and injuries in adolescent dancers. Participants were 126 dancers (21 males; 11-18 years), who were competitors in the urban dance, rock and roll, and standard/Latin dance genres. Predictors included sociodemographic factors, anthropometric/body build indices, sport (dance) factors, and dynamic balance. The outcome variable was injury status, and this was evaluated by the Oslo Sports Trauma Research Centre Overuse Injury Questionnaire (OSTRC). Predictors were evaluated at baseline, and outcomes were continuously monitored during the study period of 3 months. During the study course, 53% of dancers reported the occurrence of a musculoskeletal problem/injury, and dancers suffered from an average of 0.72 injuries over the study period (95% CI: 0.28-1.41), giving a yearly injury rate of 280%. Gender and dance styles were not significantly related to the occurrence of injury. Higher risk for injury was evidenced in older and more experienced dancers. Dynamic balance, as measured by the Star Excursion Balance Test (SEBT), was a significant protective factor of injury occurrence, irrespective of age/experience in dance. Knowing the simplicity and applicability of the SEBT, continuous monitoring of dynamic balance in adolescent dancers is encouraged. In order to prevent the occurrence of musculoskeletal problems/injuries in youth dancers, we suggest the incorporation of specific interventions aimed at improving dynamic balance.

Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated. The hypothesis was that NAC and inulin attenuated cognitive decline in castrated-obese rats by improving gut dysbiosis, and decreasing oxidative stress, glial activation and apoptosis. Male Wistar rats (n = 36) were fed with either a normal diet (ND: n = 6) or a high-fat diet (HFD: n = 30) for twenty-eight weeks. The resultant obese rats had a bilateral orchiectomy (ORX) and were randomly divided into five subgroups (n = 6/ subgroup). Each subgroup was treated with one of five therapies: a vehicle; testosterone replacement (2 mg/kg/day); NAC (100 mg/kg); inulin (10%, w/w), or a combination of the NAC and inulin for four weeks. The results demonstrated that castrated-obese rats developed gut dysbiosis, metabolic disturbance, brain pathologies, and cognitive decline. All of the pathological conditions in the brain were ameliorated to an equal extent by testosterone replacement, NAC, and inulin supplementation. Interestingly, a combination of NAC and inulin had the greatest beneficial effect on cognitive function by synergistically reducing hippocampal inflammation and ameliorating glial dysmorphology. These findings suggest that a combination of NAC and inulin may confer the greatest benefits in improving cognitive function in castrated-obese male rats.

Objectives: High-fat diet (HFD) consumption caused metabolic disturbance, gut dysbiosis, brain pathology, microglia hyperactivity, and cognitive decline. However, the exact timeline of these abnormalities following HFD consumption is still elusive. Therefore, the aim of this study was to test the hypothesis that gut dysbiosis, peripheral inflammation, and peripheral insulin resistance occur before the brain inflammatory response, hippocampal synaptic dysplasticity, oxidative stress, apoptosis, and cognitive impairment in HFD-fed rats., Methods: Male Wistar rats received either a normal diet or an HFD for 2, 8, 12, 20, or 40 wk. At the end of each time point, cognitive functions and metabolic parameters were determined. Gut microbiota, brain immune cell activity, amyloid-β level, microglia morphology, hippocampal reactive oxygen species and apoptosis, hippocampal synaptic plasticity, and dendritic spine density were measured., Results: We found that HFD-fed rats developed gut dysbiosis at week 2 and peripheral insulin resistance at week 8. Rats fed an HFD for 12 wk displayed hippocampal synaptic dysplasticity, decreased dendritic spine density, an elevation of ionized calcium-binding adapter molecule 1 + cells, increased hippocampal reactive oxygen species levels and hippocampal apoptosis with cognitive decline. The decreased percentage of resident microglia and increased percentage of infiltrated macrophage were observed at weeks 20 and 40. Surprisingly, brain amyloid-β levels were increased after 40 wk of an HFD diet., Conclusions: These findings demonstrated that gut dysbiosis develops in the earliest phase of consumption of an HFD, followed by brain pathology, which leads to cognitive decline in obese insulin-resistant rats. Therefore, an improvement in gut dysbiosis should provide beneficial effects in the prevention of neuropathology and cognitive decline in the obese., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hip hop is a popular form of competitive and recreational sport worldwide, but studies rarely investigate injury prevalence and factors associated with injury occurrence in this sport. This study aimed to prospectively examine injury occurrence in hip hop dancers in a three-month period and to evaluate potential predictors of injury occurrence in hip hop dancers. The participants were 129 competitive hip hop dancers (114 females, 17.95 ± 4.15 years of age). Study predictors were obtained at study baseline and included sociodemographic factors, sport-related factors, previous injury status, anthropometric and body build indices (body height, mass, body mass index, and body composition variables), and dynamic balance performance (obtained by the Star Excursion Balance Test-SEBT). The outcome was injury occurrence, which was prospectively observed once a week by the Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC). During the course of the study, 101 injuries occurred, equating to an annual injury incidence of 312%. On average, each dancer suffered 0.78 injuries (95% Confidence Interval (95% CI): 0.61-0.97) across a study period of three months (0.76 (95% CI: 0.60-0.95) and 0.93 (95% CI: 0.75-1.13), in females and males, respectively; Mann Whitney Z-value: 0.68, p = 0.52). Seventeen percent of dancers suffered multiple injuries, and 49% of all injuries were time-loss injuries. The knee was the most frequently injured body location (42% of all reported injuries), followed by the back region (32%) and the ankle (15%). Previous injury was a strong predictor of injury occurrence (Odds Ratio: 3.76, 95% CI: 1.87-4.59). Lower injury risk was evidenced among those participants who achieved better scores on several SEBT variables, irrespective of gender and previous injury status; with no significant influence of anthropometric and body build variables on injury occurrence. This study highlighted a high injury rate in hip hop dancers. Dancers and coaches should be informed about the certain protective effects of dynamic balance on the prevention of musculoskeletal injury in hip hop in order to assure safe and effective practices. The usage of SEBT as a convenient and cheap testing procedure is encouraged in other dance disciplines.

Our previous studies reported that testosterone-deprived rats developed cognitive decline as a result of increased brain oxidative stress, microglia hyperactivity, and hippocampal dysplasticity. In addition, gut dysbiosis occurred in these rats. Previous studies demonstrated that n-acetyl cysteine (NAC) and a prebiotic (inulin) improved cognition in several pathological conditions. However, its effects on cognition in the testosterone-deprived condition have never been investigated. This study hypothesized that the administration of NAC, inulin, and a combined therapy improved cognition in castrated rats. Here we report that metabolic disturbance was not observed in the ORX rats, but gut dysbiosis was found in these rats. ORX rats developed blood-brain-barrier (BBB) breakdown, and increased brain oxidative stress as indicated by increased hippocampal production of reactive oxygen species (ROS) and an increase in brain malondialdehyde level. ORX rats also demonstrated glia hyperactivation, resulting in hippocampal apoptosis, hippocampal dysplasticity, and cognitive decline. All treatments equally ameliorated cognitive decline by improving gut dysbiosis, alleviating BBB dysfunction, decreasing hippocampal ROS production, decreasing hippocampal apoptosis, and reducing microglia and astrocyte activity. These findings suggest that NAC, inulin, and the combined therapy ameliorated the deleterious effects on the brain in castrated male rats similar to those treated with testosterone.

Background: Serum amyloid A (SAA) is an acute phase protein expressed primarily in the liver in response to various injuries and inflammatory stimuli and is recognized as a modulator of inflammation. Ovarian reproductive functions including folliculogenesis and ovulation use inflammatory processes; thus, studying SAA in this context is of interest., Objectives: We investigated the expression and localization of SAA in ovarian developing follicles and its levels in follicular fluids., Methods and Participants: Nonradioactive in situ hybridization and immunohistochemical staining were applied on ovarian paraffin tissue sections. ELISA and RT-PCR were applied on follicular aspirates and blood samples from women undergoing controlled ovarian stimulation for in vitro fertilization., Results: Expression of SAA mRNA and protein was found in follicular cells at all stages of follicular development, from primordial and primary follicles through antral follicles and corpora lutea. Expression was observed in granulosa, theca and luteal cells, and oocytes. Expression of SAA was also found in granulosa cells recovered from follicular aspirates. The SAA protein was detected in follicular fluids. Its levels were somewhat lower than in peripheral blood with strong correlation between the two compartments and with significant correlation with patient's body mass index. High follicular fluid SAA levels were associated with reduced pregnancy rate., Conclusions: SAA is locally produced in ovarian developing follicles and is a constituent of follicular fluids, suggesting its role within the follicular environment. Elevated follicular SAA levels are associated with decreased pregnancy rate and may signify lower reproductive performance.

Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues.

Epiregulin (Ep) was found to be produced in non-cancer ovarian cells in response to gonadotropin stimulation as well in ovarian cancer cells in an autonomous manner. However, there were no systematic follow-up studies of Ep expression in the development of different stages of ovarian cancer. Using specific antibodies to Ep and the indirect immunocytochemistry methods, we found that in normal ovary the staining for Ep was mainly confined to the epithelial cells, while the stromal cells were only occasionally and moderately stained. In contrast in benign serous and mucinous tumors most of the tumor cells showed a clear staining in the cytoplasm. In borderline serous and mucinous tumors the staining was much more intensive, and appear occasionally in aggregated form. In serous, mucinous and endometrioid carcinomas labeling remain high, with more frequent aggregated form. It is suggested that follow-up of the expression of Ep can serve as a reliable early indication of the development of ovarian cancer. Moreover, the cytoplasmic aggregation of Ep may suggest a specific mechanism of the release of this growth factor to the extracellular space in order to exert its autocrine and paracrine effect on the family of the EGF receptors.

We examined the possibility that the localization of phosphorylated ERK1 and ERK2 (pERK1/2) can serve as a marker for the development of benign and borderline tumors as well as carcinoma of the ovary by an immunohistochemical method on ovarian paraffin sections, obtained from women aged 41-83 years. In normal tissue, 28.3% of nuclei were labeled, mainly confined to the epithelial cells at the surface of the ovary. In benign serous tumors, the label rose to 55.0%, while the intensity of the staining was weak. In contrast, in borderline serous tumors and in ovarian serous carcinoma (stage II) 52.1% and 70.3% of nuclei, respectively, were labeled with a high intensity. In mucinous benign tumors, the number of labeled nuclei was as in the control, but in addition, 49.4% of the cells demonstrated high concentration of pERK1/2 in aggregated form that was evident in the cytoplasm of the cells. In the mucinous and endometrioid ovarian carcinomas (stage II) very intensive labeling was found in 60% and 77.3% of cells, respectively. It is, therefore, suggested that since nuclear pERK1/2 can be mitogenic, it can serve as a reliable marker for the progression of ovarian cancer. Interestingly, the intense labeling of pERK1/2 was mainly confined to the peripheral areas of ovarian endometrioid carcinoma (stage II). In addition, all tumor cells in this class of cancer were positively stained with mutated p53. It seems, therefore, that immunohistochemical staining of normal and ovarian tumor cells with anti-pERK1/2 is a reliable marker for early detection of the cancer, which may assist in the early diagnosis and prognosis of this lethal disease.

Pilonidal disease is common among adolescents and adults, mainly located in the sacral area. Pilonidal disease involving the clitoris is extremely rare and has not been described in premenarcheal girls. We present a case of a recurrent pilonidal periclitoral cyst in an 8-year-old girl which was surgically treated., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application.

Objective: To define the role of prostaglandins (PG) in the endometrium of patients with repeated failure of embryo implantation. Prostaglandins are produced after the sequential oxidation of arachidonic acid by cyclooxygenases (COX-1 and COX-2) and terminal PG synthases., Design: Case-control study., Setting: In vitro fertilization unit at a university hospital., Patient(s): Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility., Intervention(s): Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups., Main Outcome Measure(s): Cytosolic phospholipase A2 (cPLA2alpha) expression and activity were assessed by Western blot. Expression of cyclooxygenase-2, secretory phospholipase A2 group IIA, V, and IB (sPLA2-IIA, sPLA2-V, sPLA2-IB), glypican-1, PG E synthase, PG E receptors, and lysophosphatidic acid receptor 3 (LPA3) was measured by real-time polymerase chain reaction (PCR). Localization of COX-2, sPLA2-IIA, and LPA3 within the secretory endometrium was detected by immunohistochemistry., Result(s): Patients displaying recurrent implantation failure expressed reduced levels of cPLA2alpha and COX-2 compared with controls. In response to this deficiency, sPLA2-IIA was found to be overexpressed. Interestingly, LPA3, which is known to converge on the cPLA2-arachidonic acid-COX-PG signaling pathway, was also decreased in these patients., Conclusion(s): Prostaglandin synthesis appears to be disrupted in patients with repeated IVF failure compared with fertile controls. We therefore suggest that reduced PG synthesis in the human endometrium may lead to poor endometrial receptivity., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

To determine the predictive value of a previous testicular biopsy to the chance of sperm retrieval in the next testicular sperm extraction (TESE) procedure, we retrospectively analyzed the outcome of past sperm collection procedures and histopathology diagnoses of patients with nonobstructive azoospermia. Repeated TESE ensured a high recovery rate (96%) when the first recovery procedure had been successful and when hypospermatogenesis was diagnosed (77%); when no spermatozoa were found on the first attempt, a repeat TESE procedure was successful in one-third of the patients.

Objective: Patients with vulvar vestibulitis syndrome (VVS) and control subjects were tested for a polymorphism in the gene coding for the NALP3 component of inflammasomes, cytoplasmic structures regulating interleukin (IL)-1beta production., Study Design: DNA from 143 women with VVS and 182 control women were tested for a length polymorphism in intron 4 of the gene (CIAS1) that codes for NALP3. Vestibular tissue was examined for NALP3 expression. Whole blood cultures were tested for Candida albicans-induced IL-1beta production., Results: The allele 12 frequency was higher in control subjects than in the patients with VVS (P = .02). Among patients with VVS and a self-reported history of recurrent vulvovaginal candidiasis (RVVC), the allele 7 frequency was 43.9% as compared with 30.8% in patients with no history of RVVC and 26.9% in control women (P = .035 vs other patients and .001 vs control subjects). NALP3 was identified in vestibular tissue. C albicans-induced IL-1beta production was reduced in samples from women with the 7,7 genotype (P = .030)., Conclusion: Polymorphism in the CIAS1 gene may play a central role in the triggering of VVS in a subset of patients.

Despite extensive efforts toward elucidation of the molecular pathway controlling cytotrophoblast (CTB) invasion to the uterine decidua, it remains poorly defined. There are striking similarities between tumor cell invasion and cytotrophoblast implantation to the deciduas whereby the role of Protease Activated Receptors (PARs) and wnt signaling is well recognized. We examine here consequences of modulation of PAR1 and PAR2 expression and function on CTB invasion and beta-catenin stabilization. Toward this end, we utilized a model system of extravillous trophoblast (EVT) organ culture and various placenta cell lines (e.g., JAR and HTR-8/Svneo). Activation of PAR1 induces EVT invasion while hPar1-SiRNA and PAR1 antagonist SCH79797--effectively inhibited it. In parallel, the Wnt inhibitor Dickkopf-1 (Dkk1) similarly inhibited it. Nuclear localization of beta-catenin is seen only after PAR1 activation, and is markedly reduced following the application of hPar1-SiRNA construct and PAR1 antagonist in CTBs. In contrast, PAR2 elicited a low cytoplasmic beta-catenin level as also proliferation and invasion. In the non-activated CTBs in-comparison, beta-catenin appeared limited to the membrane pools. Concomitantly, a temporal regulated pattern of Wnt-4, 5a, 7b, 10a, 10b expression is seen along PAR1 appearance. Enforced expression of Wnt antagonists, Secreted Frizzled Related Proteins; SFRP2 & 5; into HTR-8/Svneo, resulted with a markedly reduced nuclear beta-catenin levels, similar to the effect obtained by hPar1-SiRNA treatment. Identification of PAR1 downstream target/s may nonetheless contribute to the formation of a future platform system for eliciting a firm placenta-uterus interactions and to the definition of late pregnancy outcomes.

Objective: To determine the predictive value and the quality of supernatant sperm (SS) achieved by a simple laboratory technical modification after testicular sperm extraction (TESE)., Design: A retrospective analysis., Setting: An IVF unit in a university medical center., Patient(s): Azoospermic patients undergoing TESE between January 2001 and December 2006., Intervention(s): Before the mechanical shredding, the testicular specimen in toto was placed in medium. The medium was spun and the pellet resuspended and transferred for SS detection. Then a wet preparation of the testicular tissue was shredded roughly and inspected for tissue sperm (TS) as described., Main Outcome Measure(s): Detection of SS versus TS, fertilization and pregnancy rates (PR) after intracytoplasmic sperm injection (ICSI) with SS versus TS., Result(s): The SS was detected in all specimens where TS was eventually found, independent of their testicular pathology. When the supernatant was spermatozoa-negative, no spermatozoa were detected in the tissue. For embryos derived from ICSI the fertilization rate of SS was significantly higher than TS (52% vs. 44%), whereas the PR was comparable., Conclusion(s): The SS serves as an excellent predictor of TESE outcome and as a superior source for fertilization. This modified technique enables faster decision of TESE outcome and an easier switch to donor sperm when available.

Background: Electrical impedance scanning (EIS) identifies tissue impedance changes associated with malignancy. Methods to distinguish benign from malignant thyroid nodules, particularly in patients with indeterminate cytology are lacking., Purpose: To determine the diagnostic accuracy of EIS in the preoperative evaluation of thyroid nodules., Patients and Methods: From September 2002 to December 2006, 216 patients underwent thyroid fine needle aspiration (FNA) and EIS prethyroidectomy in this prospective cohort study. EIS, either positive or negative for malignancy, was correlated with final histopathology. A focal bright spot over a thyroid nodule correlating with increased conductivity and/or capacitance >25% baseline sternocleidomastoid muscle impedance defined positive EIS. Study endpoints were EIS accuracy, sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV). This study has been registered in the National Institutes of Health's public trials registry at ClinicalTrials.gov. The registration number is NCT00571077., Results: EIS correctly diagnosed 96 of 110 patients with malignant and 75 of 106 patients with benign dominant thyroid nodules: Sn = 87%, Sp = 71%, PPV = 76%, NPV = 84%: overall EIS accuracy = 79%. Pretest cancer probability of 51% (110 of 216) increased to 76% (96 of 127) post-EIS, and preoperative use of EIS would result in a significant reduction (71%, 75 of 106) in number of operations performed for benign nodules. EIS performance was similar for 109 patients with indeterminate FNA: Sn = 83%, Sp = 67%, PPV = 61%, NPV = 87%, accuracy = 73%. Pretest probability of cancer increased from 39% (42 of 109) to 61% (35 of 57) post-EIS. The use of EIS would result in a significant reduction (67%, 45 of 67) in the number of purely diagnostic thyroidectomy for indeterminate FNA., Conclusion: EIS shows promise in differentiating thyroid nodules. Further EIS hardware and software optimization is warranted to improve upon the already favorable negative predictive value in indeterminate thyroid nodules.

Background: This study was conducted to determine survival according to the expression of molecular markers in colorectal cancer (CRC) patients of various ethnic origins., Methods: Resection of primary tumor was conducted on 171 patients with CRC. Corresponding archived paraffin-embedded blocks were retrieved and tissue microarray (TMA) constructed. Immunohistochemical staining of the TMA for p53, p27 and Ki-67 was quantified by two independent pathologists. Survival was analyzed using the Kaplan-Meier product limit method., Results: With a median follow-up of 65 months, 56 patients (32.7%) died of disease. AJCC stage correlated with disease-free (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). IHC staining was positive for Ki-67 in 77.4%, p53 in 55.8% and p27 in 54.2% of patients. Primary tumor marker expression did not correlate with DFS or OS. The 5-year DFS for Ashkenazi Jews was 75%, significantly higher than Sephardic Jews (SJ) 64% and Palestinian Arabs (PA) 38%, P = 0.001., Conclusions: Ethnicity among Ashkenazi and SJ and PA appears to have a significant impact on disease outcome in patients with CRC patients, while primary tumor expression of p53, p27 and Ki-67 was unrelated to disease outcome., ((Copyright) 2008 Wiley-Liss, Inc.)

Background: Fine-needle aspiration (FNA) is widely used as a diagnostic tool to assess thyroid nodules. This study correlates FNA cytology results with surgical pathologic findings., Methods: All thyroidectomies performed between 1994 and 2004 were reviewed, identifying 242 patients. Data were obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic findings., Results: Among 89 patients with a carcinoma on FNA, 89% of cases were verified on final histopathology. Of 78 patients with "follicular lesion" on FNA, only 36% of cases were verified to be malignant at surgery. Only 13% of the 75 cases diagnosed as benign, mostly colloid nodules, on FNA were found to have a carcinoma on histopathology., Conclusion: A cytologic diagnosis of papillary carcinoma has a highly predictive of thyroid cancer. When dealing with follicular lesions the predictive value of FNA drops considerably. However, we found a 13% false positive result to occur in FNA declared benign lesions.

Background: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial., Purpose: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer., Patients and Methods: Between August 2002 and April 2006 we randomly assigned 161 patients with stage I-III colon cancer to standard histopathologic evaluation or SLN mapping (ex vivo, subserosal, peritumoral, 1% isosulfan blue dye) and ultrastaging with pan-cytokeratin IHC in conjunction with standard histopathology. SLN-positive disease was defined as individual tumor cells or cell aggregates identified by hematoxylin and eosin (H&E) and/or IHC. Primary end point was the rate of nodal upstaging., Results: Significant nodal upstaging was identified with SLN ultrastaging (Control vs. SLN: 38.7% vs. 57.3%, P = 0.019). When SLNs with cell aggregates < or =0.2 mm in size were excluded, no statistically significant difference in node-positive rate was apparent between the control and SLN arms (38.7% vs. 39.0%, P = 0.97). However, a 10.7% (6/56) nodal upstaging was identified by evaluation of H&E stained step sections of SLNs among study arm patients who would have otherwise been staged node-negative (N0) by conventional pathologic assessment alone., Conclusion: SLN mapping, step sectioning, and immunohistochemistry (IHC) identifies small volume nodal disease and improves staging in patients with resectable colon cancer. A prospective trial is ongoing to determine the clinical significance of colon cancer micrometastasis in sentinel lymph nodes.

Objective: Protease Activated Receptors (PARs) form a family of G-protein-coupled proteins uniquely activated by proteolytic cleavage. While the role of either soluble or matrix-immobilized protease in tumor invasion is well established, the part of cell surface PARs is beginning to emerge. We sought to investigate the expression pattern of Protease Activated Receptor 1 (hPar1) in endometrial carcinoma, the most common type of gynecological malignancy., Methods: Tissue biopsy specimens taken from seventy-four formalin-fixed, paraffin-embedded endometrial tissue blocks were obtained from archival material. Analysis of PAR1 expression was evaluated by riboprobe in situ hybridization for detection of RNA and immunohistochemistry techniques for localization of protein. Histological scoring was performed., Results: The levels of hPar1 mRNA and protein were high and abundant in high-grade endometrial carcinoma, regardless of the histological subtype. In contrast, no hPar1 was detected in endometrial epithelia with conserved glandular structure represented by normal, hyperplastic or low-grade carcinomas., Conclusions: PAR1 over-expression is selectively confined to the highly aggressive, high-grade endometrial carcinoma and absent in tissue obtained from benign endometrium or low-grade endometrial cancer. This finding highlights the significance of hPar1 gene involvement in invasive endometrial carcinoma and appoints it an attractive candidate for anti-cancer therapy.

Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy and are found in direct contact with fetal trophoblasts. Several mechanisms have been proposed to explain the inability of NK cells to kill the semiallogeneic fetal cells. However, the actual functions of decidual NK (dNK) cells during pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein-10 chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic factors and induce vascular growth in the decidua. Notably, such functions are regulated by specific interactions between dNK-activating and dNK-inhibitory receptors and their ligands, uniquely expressed at the fetal-maternal interface. The overall results support a 'peaceful' model for reproductive immunology, in which elements of innate immunity have been incorporated in a constructive manner to support reproductive tissue development.