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This study reports a simple template-based reverse transcription-polymerase amplification assay (ST-RT-RPA) for detection of citrus tristeza virus (CTV) from crude plant extract lysed in NaOH:EDTA (1:1) without the need of tedious RNA isolation. The developed assay showed versatility in its usage as amplification can be performed at wide temperature range (14°C to 42°C) and incubation time (4 to 32 min), although the best conditions were 38°C for 30 min. The developed ST-RT-RPA assay could detect the CTV up to 10-8 dilution of crude plant extract of NaOH:EDTA and up to 0.01 fg µl-1 of RNA of CTV-infected plant tissues and 0.001 ag µl-1 of plasmid DNA containing viral insert, thus exhibiting sufficient sensitivity. ST-RT-RPA assay showed high specificity without any cross-reaction with other citrus pathogens (Indian citrus ringspot virus, citrus yellow mosaic virus, citrus yellow vein clearing virus, and Candidatus Liberibacter asiaticus) and was more sensitive in detection of CTV infection in field samples as compared to standard reverse transcription-polymerase chain reaction (RT-PCR) with later showing false negative in 7.92% of samples tested after 1 week of sampling. The developed ST-RT-RPA assay used minimally processed crude plant extract as template, tolerant to sample degradation in transit and storage, while it can be easily performed at wide temperatures and could be adopted in resource-poor setup., (© The Author(s) 2022. Published by Oxford University Press on behalf of Applied Microbiology International.)

The objectives of this study were to evaluate the effectiveness and accuracy of monitoring feeding behavior patterns using cumulative summation (CUSUM) procedures to predict the onset of bovine respiratory disease (BRD) in beef cattle. Growing bulls (N = 231) on a 70-d growth and efficiency trial were used in this study. Between days 28 and 38 of the study, 30 bulls were treated for BRD based on observed clinical signs and elevated rectal temperature (>39.5 °C); remaining bulls (n = 201) were considered healthy. Clinically-ill and healthy bulls were used to evaluate sensitivity and specificity of CUSUM models, with accuracy calculated as the average of sensitivity and specificity. All data were standardized prior to generating CUSUM charts in a daily accumulative manner. Eight univariate CUSUM models were evaluated including DMI, bunk visit (BV) frequency, BV duration, head down (HD) duration, eating rate, maximal nonfeeding interval (NFI Max), SD of nonfeeding interval (NFI SD), and time to bunk (TTB). Accuracies for detection of BRD were 80.1, 69.4, 72.4, 79.1, 63.7, 64.6, 73.2, and 48.7%, respectively, and average day of detection prior to observed symptoms of BRD were 1.0, 3.2, 3.2, 4.8, 10.2, 2.7, 1.5, and 0.6 d, respectively. Principal component analysis (PCA) of all 8 univariate traits (full model) was used to construct multivariate factors that were similarly monitored with CUSUM. Two reduced multivariate models were also constructed that included the 3 best performing feeding behavior traits (BV duration, HD duration, NFI SD) with (RBD) and without DMI (RB). Accuracy of the full multivariate model was similar to the best of the univariate models (75.0%). However, both of the reduced multivariate models (RB and RBD) were more accurate (84.0%) than the full multivariate model. All 3 of the multivariate models signaled (P < 0.05) 2.0 to 2.1 d prior to clinical observation. These results demonstrate that the use of PCA-derived multivariate factors in CUSUM charts was more accurate compared with univariate CUSUM charts, for pre-clinical detection of BRD. Furthermore, adding DMI to the RB model did not further improve accuracy or signal day of BRD detection. The use of PCA-based multivariate models to monitor feeding behavior traits should be more robust than relying on univariate trait models for preclinical detection of BRD. Results from this study demonstrate the value of using CUSUM procedures to monitor feeding behavior patterns to more accurately detect BRD prior to clinical symptoms in feedlot cattle., (© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimer's disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aβ aggregation. While a variety of possible aggregation inhibitors have been explored, only nanoparticles (NPs) exhibit promise at low substoichiometric ratios. With tunable size, shape, and surface properties, NPs present an ideal platform for rationally designed Aβ aggregation inhibitors. In this study, we characterized the inhibitory capabilities of gold nanospheres exhibiting different surface coatings and diameters., Results: Both NP diameter and surface chemistry were found to modulate the extent of aggregation, while NP electric charge influenced aggregate morphology. Notably, 8 nm and 18 nm poly(acrylic acid)-coated NPs abrogated Aβ aggregation at a substoichiometric ratio of 1:2,000,000. Theoretical calculations suggest that this low stoichiometry could arise from altered solution conditions near the NP surface. Specifically, local solution pH and charge density are congruent with conditions that influence aggregation., Conclusions: These findings demonstrate the potential of surface-coated gold nanospheres to serve as tunable therapeutic agents for the inhibition of Aβ aggregation. Insights gained into the physiochemical properties of effective NP inhibitors will inform future rational design of effective NP-based therapeutics for AD.

Background: Previous evaluations have supported the link between sun protection policies and improved sun protection behaviours. However these evaluations have relied on self-reported data., Methods: A cross-sectional design as part of an ongoing 18-month cluster-controlled trial in primary schools (n = 20) was used. Researchers conducted direct observations to record students' hat use and teachers' use of sun protective measures during recess and lunch. Researchers also recorded the volume of sunscreen consumed in each school., Results: Only 60% of primary school children wear a sun-safe hat during their breaks when observed using objective measures. Weak correlations were observed between the wearing of a sun-safe hat and a school's socio-economic status (r = 0.26). All other independent variables measured had only very weak correlations (r < 0.19) with sun-safe hat wearing behaviour of students. Sunscreen consumption by school students during the school day is negligible., Conclusions: A large percentage of NSW primary schools in this study wear sun-safe hats during the school day but this is well below what has been reported in previous national surveys. Given the finite resources of schools and the correlation, though small, with SES status for these behaviours, it behoves researchers to investigate low-cost solutions to these problems. Further qualitative data will also be needed to inform the enablers and barriers for sun-safe behaviour interventions to be adopted in NSW primary schools.

Methods to improve accuracy of preclinical detection of bovine respiratory disease (BRD) are needed to reduce the economic impact of this disease, improve animal welfare, and promote more judicious use of antimicrobials in beef cattle. The objectives of this study were to retrospectively characterize time-series deviations in DMI and feeding behavior patterns preceding the display of observed clinical symptoms associated with BRD and to identify those feeding behavior traits that would be most predictive of BRD. The study was conducted with 231 seed stock bulls (391 ± 55 kg initial BW) representing 5 breeds that were housed in a facility equipped with GrowSafe feed bunks at a commercial bull-test facility. All bulls were vaccinated against standard viral and bacterial pathogens before and on arrival at the facility. Daily DMI and feeding behavior traits (frequency and duration of bunk visit events, head-down duration, variance of nonfeeding intervals, and time to approach feed bunk following feed-truck delivery) were measured for 70 d with a GrowSafe system. During a 10-d period from Day 28 to 37 of the trial, 30 bulls were administered antimicrobial therapy for clinical symptoms of BRD (rectal temperatures > 39.5°C). All remaining bulls ( = 201) were administered metaphylactic therapy on Day 38 of the trial in response to an acute decrease in feed intake. A retrospective analysis was conducted using a 2-slope broken-line regression model to identify inflection points in DMI and feeding behavior traits relative to onset of illness. The bulls were separated into 2 cohort groups based on observed clinical illness ( = 30) or those metaphylactically treated ( = 201), with the 2-slope broken-line regression model applied separately to each cohort. The model-detected inflection points for DMI were 6.8 and 3.8 d before observed clinical illness and metaphylactic treatment, respectively, and the reductions in DMI from detected inflection points to the day of observed clinical illness and day of metaphylactic treatment were 39.3 and 49.8%, respectively. Furthermore, the model-detected inflection points for individual feeding behavior traits ranged from 1.3 to 14.2 d before observed clinical illness and from 3.8 to 12.6 d before metaphylactic treatment. Results from this study demonstrate the potential value of electronic behavior-monitoring systems to improve the sensitivity and specificity of preclinical detection of BRD in feedlot cattle.

Background: Previous evaluations of the SunSmart Program have supported the link between a written sun protection policy and improved sun protection behaviours in New South Wales (NSW) primary schools. However these evaluations have relied on self-reported data and research suggests that direct observations are required to better represent schools' usual sun protective practices., Methods/design: Data will be collected in the summer months of 2014, 2015, and 2016 as part of an 18-month cluster-controlled trial in NSW primary schools (n = 20). Researchers will conduct three direct observations to record students' hat use and teachers' use of sun protective measures during recess and lunch periods in each school. Researchers will also record the volume of sunscreen that the Year 6 classes in each school utilise over the term. At the conclusion of baseline data collection, five schools will be randomised into an intervention group that will work with researchers to develop a policy-driven intervention to improve sun safety behaviour in NSW primary schools., Discussion: An initial review of relevant Australian and New Zealand literature suggests that provision of policy support is likely to improve school sun protection practices; however there is no suggested model for this support. This will be the first objective analysis of sun safe behaviours leading to a policy-driven intervention conducted in Australian primary schools since the 1990s, and will inform the future direction of sun safety in our schools., Trial Registration: Australian and New Zealand Clinical Trials Register ACTRN12614000926639 Registered 28(th) August 2014.

Differential anti-prion activity of polylysine enantiomers was studied. Based on our recent discovery that poly-L-lysine (PLK) is a potent anti-prion agent, we investigated suppression of prions in cultured cells using poly-D-lysine (PDK). The results showed that PDK was more efficacious than PLK to inhibit prions. Protein misfolding cyclic amplification assay demonstrated improved efficacy of PDK in inhibiting plasminogen-mediated prion propagation, corresponding to the enantio-preference of PDK observed in cultured cells. Furthermore, our study demonstrated that polylysines formed a complex with plasminogen. These results propose to hypothesize a plausible mechanism that elicits prion inhibition by polylysine enantiomers.

Gold nanorods show great promise as light-controlled molecular release systems. Dye molecules were loaded within a variable number of polyelectrolyte multilayers wrapped around gold nanorods. The dye photoinduced release rate depended on the quantity and type of polyelectrolyte trapping layers and could be tuned by a factor of 100. Only two molecular capping layers were sufficient to turn off release. Comparison of the phototriggered molecular release rate to a pure thermal experiment provides an estimate of the effective temperature of the nanorod solution upon irradiation.

Malocclusion with severe crowding is difficult to treat without extraction. However, in some cases extraction treatment can be compromised by a patient's profile and desire for shorter treatment duration. This article represents a Class II nonextraction treatment approach for a labially displaced canine in a patient with a dished-in profile and short mandibular first premolar roots.

Endometriosis-associated infertility has a multifactorial etiology. We tested the hypothesis that the endometrial response to the early embryonic signal, human chorionic gonadotropin (hCG), alters over time in a nonhuman primate model of endometriosis. Animals with experimental or spontaneous endometriosis were treated with hCG (30 IU/d), from d 6 after ovulation for 5 d, via an oviductal cannula. Microarray analysis of endometrial transcripts from baboons treated with hCG at 3 and 6 months of disease (n=6) identified 22 and 165 genes, respectively, whose levels differed more than 2-fold compared with disease-free (DF) animals treated with hCG (P<0.01). Quantitative RT-PCR confirmed abnormal responses of known hCG-regulated genes. APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG were up-regulated by hCG in animals with endometriosis. In contrast, the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry demonstrated dysregulation of C3 and superoxide dismutase 2 proteins. We demonstrate that this abnormal response to hCG persists for up to 15 months after disease induction and that the nature of the abnormal response changes as the disease progresses. Immunohistochemistry showed that this aberrant gene expression was not a consequence of altered LH/choriogonadotropin receptor distribution in the endometrium of animals with endometriosis. We have shown that endometriosis induces complex changes in the response of eutopic endometrium to hCG, which may prevent the acquisition of the full endometrial molecular repertoire necessary for decidualization and tolerance of the fetal allograft. This may in part explain endometriosis-associated implantation failure.

Objective: To evaluate perioperative surgical outcomes and resection size for laparoscopically assisted radical vaginal hysterectomy (LARVH) compared with radical abdominal hysterectomy (RAH)., Design: A prospective randomised phase II trial., Population: Early stage IB cervical cancer requiring radical surgical treatment., Setting: Northern Gynaecological Oncology Centre, Gateshead, UK., Methods: Fifteen women were randomised to LARVH and to RAH., Main Outcome Measures: Outcomes included requirement in days for bladder catheterisation after surgery, operating time, blood loss, hospital stay, opiate pain relief, complication rate, time to normal activities and resection size of major ligaments and vaginal cuff. Results Statistically significant differences were found between LARVH and RAH, respectively: median duration of bladder catheterisation, 4 days versus 21 days (P = 0.003); median operating time, 180 minutes versus 138 minutes (P = 0.05); median blood loss, 400 ml versus 1000 ml (P = 0.05), median hospital stay, 5 days versus 7 days (P = 0.04) and median opiate requirement in the first 36 hours postoperatively, 30 mg versus 53 mg (P = 0.004). The mean resected lengths for LARVH versus RAH, respectively, were: mean resected vaginal cuff, 1.26 cm versus 2.16 cm (P = 0.014); mean resected cardinal ligament length, 1.30 cm versus 2.79 cm (P = 0.013) and mean resected uterosacral ligament length, 1.47 cm versus 4.68 cm (P = 0.034)., Conclusions: This study confirms the short-term surgical benefits of LARVH. In addition, LARVH has been shown to be a less radical procedure than RAH, supporting the need for strict patient selection and to restrict the procedure to small tumours.

Estrogen non-responsive estrogen receptor alpha (ERalpha) knock-in (ENERKI) mice have a mutation (glycine 525 to leucine, G525L) in the ligand-binding domain of ERalpha. The mutant ERalpha protein has a significantly lower affinity and response to endogenous estrogens, while not altering growth factor activated ligand-independent pathways. ENERKI females demonstrated signs of early follicle development as determined by a significant increase in antral follicle formation by 20 days of age. Adult ENERKI females were infertile, had hemorrhagic ovarian follicular cysts, and failed to develop corpora lutea in response to a superovulation regimen. These results illustrate the importance of ERalpha ligand-induced signaling for ovarian development and for estrogen feedback on the hypothalamus and pituitary. Although ERalpha ligand-induced signaling by endogenous estrogens is lost in ENERKI females, the ERalpha selective agonist propyl pyrazole triol (PPT), a synthetic nonsteroidal compound, is still able to activate G525L ERalphain vivo to increase uterine weight. To test whether PPT could restore ligand-dependent receptor activation, ENERKI females were treated with PPT and evaluated for spontaneous ovulation, ovarian hemorrhagic cysts, and LH serum levels. Daily PPT treatments beginning on day 4 of life prevented formation of ovarian hemorrhagic cysts in adult ENERKI animals. In accordance with this result, preputial gland weight and LH levels were also lowered in these animals, indicating PPT treatments most likely led to restoration of ERalpha negative feedback of the hypothalamic-pituitary axis.

Ovarian cancers are primarily derived from a single layer of epithelial cells surrounding the ovary, the ovarian surface epithelium (OSE). Ovarian surface proliferation is associated with ovulation and has been suggested to play a role in ovarian surface transformation and cancer progression. Aspects of ovarian surface repair after ovulation include proliferation, migration, and surface regeneration. To study ovarian surface repair, an organ culture system was developed that supports the proliferation, encapsulation, and repair of an artificially wounded surface. Wounded mouse ovaries embedded into an alginate hydrogel matrix have normal OSE cells as demonstrated by expression of cytokeratin 8, vimentin, N-cadherin, and a lack of E-cadherin. Normal OSE cells began proliferating and migrating around wounded surfaces after 1 d of culture. Organ cultures were propagated in medium supplemented with BSA and fetal bovine serum to determine optimal growth conditions. BSA cultured organs had OSE that proliferated significantly more than controls until d 4, whereas fetal bovine serum cultured organs had significantly more surface area encapsulated by OSE. Overall, a three-dimensional ovarian organ culture supports the growth of normal OSE in response to artificial wounding and provides a novel system for investigating wound repair as it relates to the possible role of ovulation and ovarian cancer.

Endometriosis is a poorly understood gynaecologic disorder that is associated with infertility. In this study, we examined the expression of HOXA10 in the eutopic endometrium of baboons with induced endometriosis. A decrease in HOXA10 mRNA was observed after 3, 6, 12 and 16 months of disease, which reached statistical significance at 12 and 16 months. HOXA10 protein levels were decreased in both the epithelial and stromal cells of the endometrium. Furthermore, expression of beta3 integrin (ITGB3), which is upregulated by HOXA10, was decreased, whereas EMX2, a gene that is inhibited by HOXA10, was increased. Next, methylation patterns of the HOXA10 gene were analysed in the diseased and control animals. The F1 region on the promoter was found to be the most significantly methylated in the endometriosis animals and this may account for the decrease in HOXA10 expression. Finally, we demonstrate that stromal cells from the eutopic endometrium of baboons with endometriosis expressed significantly higher levels of insulin-like growth factor binding protein-1 (IGFBP1) mRNA than disease-free animals in response to estradiol, medroxyprogesterone acetate and dibutyryl cAMP (H + dbcAMP). The functional role of HOXA10 in IGFBP1 expression was further explored using human endometrial stromal cells (HSC). Overexpression of HOXA10 in HSC resulted in a decrease of IGFBP1 mRNA, whereas silencing HOXA10 caused an increase of IGFBP1 mRNA, even in the presence of H + dbcAMP. These data demonstrate that HOXA10 negatively influences IGFBP1 expression in decidualizing cells. Thus, the decrease in HOXA10 levels may in part be involved with the altered uterine environment associated with endometriosis.

This study examines the distribution of estrogen receptors (ESR), progesterone receptors (Pgr), and the chaperone immunophilin FKBP52 in the eutopic endometrium in a baboon model of endometriosis during the window of receptivity to determine if their aberrant distribution contributes to reduced fecundity. Endometriosis was induced by inoculation of menstrual endometrium into the peritoneal cavity. Eutopic endometrium was collected at 3, 6, 9, 12, and 15 months postinoculation. Western blot (WB) and immunohistochemical analyses were performed. Isolated endometrial stromal cells were cultured in the presence or absence of steroid hormones. In animals with endometriosis, ESR-1 (ER-alpha) decreased in endometrial stromal cells, while ESR-2 (ER-beta) was reduced in both glandular epithelial (GE) and stromal cells. Immunoreactive total Pgr was markedly diminished in the GE, which was confirmed by WB analysis. Furthermore, treatment of isolated stromal cells from baboons with endometriosis with hormones did not increase levels of PRA or PRB as in control baboons. FKBP52 was also reduced in the eutopic endometrium of baboons with endometriosis. Endometriosis results in an aberrant distribution of ESR-1, ESR-2, Pgr, and FKBP52 in the eutopic endometrium. The authors propose that a dysregulation in the paracrine signaling between the endometrial stromal and GE cells reduces the responsiveness of Pgr, creating an endometrial environment that is unsuitable for implantation.

Endometriosis, the presence of a functional endometrium outside of the uterine cavity, is associated with infertility. In our simulated model of pregnancy in baboons with experimental endometriosis, hCG infusion fails to induce expression of the immunoregulatory protein glycodelin. To test the hypothesis that the development of endometriosis is associated with an aberrant endometrial immunological environment, we examined the expression of a series of immunoregulatory genes in endometrium from baboons with and without endometriosis. Six months following intraperitoneal inoculation with menstrual endometrium, eutopic endometrium was surgically collected between Days 9 and 11 postovulation. Control endometrium was similarly collected from disease-free animals. Total RNA was extracted, and biotinylated cDNA probes were hybridized to the SuperArray GEArray Q series Th1/Th2/Th3 cDNA array, representing 96 genes. Gene expression levels were determined using ScanAlyze and GEArray Analyzer software. Seven genes were upregulated, including JUND, FOS, CCL11, NFKB1 and others, in the endometrium from baboons with endometriosis compared with the endometrium from disease-free animals; one gene, IL1R1, was downregulated. Quantitative RT-PCR confirmed upregulation of FOS and CCL11 in endometriotic eutopic endometrium. Immunohistochemical analysis revealed altered levels and distribution of FOS protein in the eutopic endometrium of baboons with induced endometriosis. These data suggest that in an induced model of endometriosis an aberrant eutopic immunological environment results in a decreased apoptotic potential and in rapid alterations in endometrial gene expression. We propose that the reduced fecundity associated with endometriosis has a multifold etiology in spontaneous and induced disease.

The expression of human CYR61 (cysteine-rich, angiogenic inducer, 61; CCN1) mRNA has been previously shown to be deregulated in the endometrium of women with endometriosis. We have chosen the baboon model (Papio anubis) of induced endometriosis to clarify whether CYR61 mRNA upregulation is predisposed to an inappropriately differentiated endometrium or is deregulated as a response to the presence of ectopic lesions. In the baboon, endometrial CYR61 mRNA expression underwent moderate cyclical variation, with a significant 7.3-fold increase detected at Day 2 postmenses when compared to endometrium from the proliferative and secretory phases. The CYR61 transcript was extensively upregulated in the eutopic endometrium from all baboons with induced endometriosis, as early as 1 mo postinoculation of menstrual tissue into the peritoneal cavity. CYR61 mRNA expression then decreased throughout progression of the disease, but remained higher compared to control tissues. Ectopic endometriotic lesions showed a further increase in CYR61 mRNA, with highest expression found in red lesions. Moreover, the expression levels of CYR61 transcripts correlated significantly with those of VEGF. Immunohistochemistry revealed the presence of CYR61 protein in glandular and luminal epithelial cells as well as in blood vessels of eutopic and ectopic endometrium. As in humans, increased levels of CYR61 mRNA correlated with the development of endometriosis in baboons. The increase of CYR61 mRNA in eutopic endometrium of baboons following peritoneal inoculation with menstrual endometrium provides evidence for a feedback mechanism from resulting lesions to induce a shift in gene expression patterns in the eutopic endometrium.

It is essential that any patient with resected vulval cancer and significant nodal disease receive optimal adjuvant treatment with radiation. Adequate radiotherapy for such patients with unilateral positive groin nodes has not been defined. Whether both groins and pelvic sidewalls should be irradiated or only the affected (node positive) side remains unclear. From our registry, we identified all patients with primary, previously untreated squamous cell carcinoma of the vulva undergoing bilateral inguinofemoral lymphadenectomy (superficial and deep nodes) and having unilaterally positive groin nodes treated with unilateral groin and pelvic radiotherapy (44 Gy in 22 fractions). Clinical and pathologic records were reviewed to identify the anatomical site and timing of recurrences in these patients and determine whether unilateral groin and pelvic irradiation was sufficient for disease control on the node-negative side. From 1983 to 2002, 20 patients with unilateral positive nodes treated with unilateral groin and pelvic irradiation were identified. Nineteen patients were classed as having FIGO stage III disease and one as FIGO stage IV due to involvement of the rectal mucosa. There were nine patients with disease recurrences in this group (45%). The disease-free interval ranged from 4 to 31 months (median time to recurrence, 9 months). All nine patients had local or regional failures, the most common site being the ipsilateral groin (six of nine patients). One patient was also found to have distant metastases. There were no recurrences noted in the contralateral (nonirradiated) groin or pelvic sidewall. Recurrence was generally fatal. Eight of the nine patients subsequently died of their disease. The ninth patient died of another cause. There was a high incidence of regional failure after unilateral groin and pelvic radiotherapy, but there were no recurrences on the nonirradiated, node-negative side. Although a small series, we speculate that there is no apparent disadvantage to administering unilateral adjuvant radiotherapy for unilaterally positive groin nodes and encourage further studies in order to more confidently determine whether the tendency observed in our center holds true.

Although the survival outcome for treated, early-stage, node-negative cervical cancer is excellent, the operation of radical hysterectomy conveys major morbidity, particularly with respect to bladder and bowel function. There may be some degree of spontaneous recovery, but a significant proportion of postoperative women will have to live with the disabling effects of surgery for decades, and few seek help for their distress. As such, quality of life issues have become highly relevant in the management of this disease, and attention has turned to reducing morbidity, especially to the pelvic viscera. This review presents an overview of the surgical mechanisms presumed to be responsible for pelvic floor denervation and describes subsequent bladder and bowel dysfunction, together with future possibilities for minimizing morbidity, including less radical, more individual surgery, and nerve-sparing techniques.

Both human chorionic gonadotropin (hCG) and IL-1beta induce changes in the endometrium that are associated with the establishment of pregnancy. We investigated the synergistic effect of these two embryonic signals on endometrial function using a baboon model of simulated pregnancy. Recombinant hCG (30 IU/d) was infused between d 6 and 10 post ovulation (PO) to mimic blastocyst transit. On the expected day of implantation (d 10 PO), IL-1beta (12 ng/d) or IL-1 receptor antagonist (IL-1Ra; 12 ng/d) was infused for an additional 5 d. Endometria were harvested on d 15 PO. Both hCG and hCG plus IL-1beta induced marked differences in the distribution of alpha-smooth muscle actin, proliferation marker Ki67, decidualization marker IGF-binding protein-1, and cyclooxygenase-1. The most marked effect of IL-1beta was the induction of IGF-binding protein-1 protein in stromal cells close to the apical surface, whereas cyclooxygenase-1 was down-regulated in the glandular epithelium. Protein arrays of uterine flushings showed significant suppression of death receptors, Fas and TNF receptor 1, in the hCG- with or without IL-1beta-treated groups, suggesting an inhibition of apoptosis. Additionally, cytotoxic T lymphocyte antigen-4, matrix metalloproteinase-3, and IL-4 were suppressed in treated animals compared with controls. However, no differences were observed in cytokine profile between hCG-treated and hCG- plus IL-1beta-treated baboons. This study confirms that in preparation for pregnancy, the primate endometrium undergoes both morphological and functional changes, which are modulated by hCG and IL-1beta, that lead to the inhibition of apoptosis and the development of an immunotolerant environment. These changes suggest that infusion of IL-1beta at the time of implantation into the nonpregnant baboon treated with hCG synergizes with hCG and mimics the early endometrial events associated with the presence of an embryo.

Outpatient interviews to collect criminal history data were conducted with 55 women and 77 men who had the dual diagnosis of rapid-cycling bipolar disorder with co-morbid substance abuse disorders (DD-RCBD), to ascertain gender-related similarities and differences. Fifty-three percent of women and 79 percent of men reported that they had been charged with a crime, and nearly half of those charged had been incarcerated. Men with DD-RCBD were more likely to have committed a felony and had a trend of committing more misdemeanors. Although women with DD-RCBD were less likely to have a criminal history than their male counterparts, they were far more likely to have a criminal history than were women in the general population. Implications from this pilot study include the need for earlier identification of bipolar disorder and for the increased availability of psychiatric and substance abuse services within correctional facilities.

Objectives: The technical feasibility of laparoscopically assisted radical vaginal hysterectomy has been well described, but its advantages over the open technique remain largely unproven. We reviewed and compared our experiences with both approaches., Methods: All patients undergoing laparoscopically assisted radical vaginal hysterectomy (LARVH) between 1996 and 2003 were identified and matched for age, FIGO stage, histological subtype and nodal metastases using a control group of women who underwent radical abdominal hysterectomy (RAH) during the same time period., Results: Fifty-seven women were listed for LARVH, resulting in five conversions. Fifty cases were matched successfully using the criteria above. The majority of cases were FIGO stage 1B1. Statistically significant differences (P < 0.05) were present when the following were compared for LARVH vs. RAH: duration of surgery (median 180 vs. 120 min), blood loss (median 350 vs. 875 ml), hospital stay (median 5 days vs. 8 days) and duration of continuous bladder catheterisation (median 3 days vs. 7 days). There were no statistically significant differences with regard to nodal yield, completeness of surgical margins or perioperative complication rate. Four major complications (8%, three cystotomies and one enterotomy) occurred in the LARVH group and three in the RAH group (6%, one pulmonary embolism, one ureteric injury and one major haemorrhage). Three women in LARVH group had seen a specialist regarding postoperative bladder dysfunction, versus 12 in the RAH group (P = 0.04). No patients in the LARVH group reported constipation requiring regular laxatives, versus six in the RAH group (P = 0.03). Median follow-up was 52 months for LARVH and 49 months for RAH. There was no significant difference between recurrence rates or overall survival (94% for LARVH vs. 96% for RAH)., Conclusions: Despite the inherent limitations of LARVH and its associated learning curve, the procedure conveys many advantages over the open technique in terms of blood loss, transfusion requirement and hospital stay. In addition, the incidence of postoperative bladder and bowel dysfunction appears low-suggesting improved quality of life-without compromising survival.

Background: The majority of vulval cancers are of the squamous cell type. Current operative management strategies are based on modifications of radical vulvectomy and groin node dissection, enabling a more individualised and conservative approach to surgery. This has led to interesting dilemmas regarding the most appropriate management in certain individuals., Case: We describe a case of a contralateral recurrence following unilateral groin node dissection for vulval cancer, with an initial single microscopically positive node. The patient did not receive adjuvant treatment. Evidence regarding the safety of this approach is discussed., Conclusion: The subject remains controversial, and further such cases should be recorded in the literature in order to gather more information on this difficult problem.

During the past decade, botulinum toxin (Botox) has emerged as the accepted treatment for adductor spasmodic dysphonia (ASD). This therapy, which produces bilateral weakness of the thyroarytenoid muscle, undoubtedly produces physiologic effects that are beneficial to patients with ASD. However, it also has important limitations, including the need for repeated injections, the unpredictable relationship between dosage and response, and the possibility of short-term swallowing and voice problems. In this study, we will report our preliminary experience with a new surgical treatment for ASD. In this new procedure, the adductor branch of the recurrent laryngeal nerve is selectively denervated bilaterally, and its distal nerve stumps are reinnervated with branches of the ansa cervicalis nerve. Each of the patients was followed for at least 12 months; the median follow-up is 36 months. The outcome of the operation in 21 consecutive patients is reported. Nineteen of the 21 patients were judged to have an overall severity of dysphonia that was "absent to mild" following the procedure. Only 1 patient underwent further treatment with Botox postoperatively. The implications of this new procedure for ASD are discussed.