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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.03.031 Byline: Sally F. Burn (a), Marit J. Boot (a), Carlo de Angelis (a), Roisin Doohan (b), Carlos G. Arques (b), Miguel Torres (b), Robert E. Hill (a) Keywords: Spleen; Nkx2-5; Bapx1; Mouse embryo; Morphogenesis; Gut culture Abstract: The mammalian spleen has important functions in immunity and haematopoiesis but little is known about the events that occur during its early embryonic development. Here we analyse the origin of the cells that gives rise to the splenic mesenchyme and the process by which the precursors assume their position along the left lateral side of the stomach. We report a highly conserved regulatory element that regulates the Nkx2-5 gene throughout early spleen development. A transgenic mouse line carrying this element driving a reporter gene was used to show that morphogenesis of the spleen initiates bilaterally and posterior to the stomach, before the splenic precursors grow preferentially leftward. In addition the transgenic line was used in an organ culture system to track spleen precursor cells during development. Spleen cells were shown to move from the posterior mesenchyme and track along the left side of the stomach. Removal of tissue from the anterior stomach resulted in splenic cells randomly scattering suggesting a guidance role for the anterior stomach. Using a mouse line carrying a conditional Cre recombinase to mark early precursor cell populations, the spleen was found to derive from posterior mesenchyme distinct from the closely adjacent stomach mesenchyme. Author Affiliation: (a) Medical and Developmental Genetics Section, MRC Human Genetics Unit, Edinburgh, EH4 2XU, UK (b) Departamento de Biologia del Desarrollo Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, E-28029 Madrid, Spain Article History: Received 11 February 2008; Revised 17 March 2008; Accepted 18 March 2008

Study Objective: To compare the effectiveness and safety of different techniques of hysteroscopic polypectomy.Design: Multicenter, prospective observational trial (Canadian Task Force classification II-2).Setting: Nineteen Italian gynecologic departments (university-affiliated or public hospitals).Patients: Consecutive patients suffering from endometrial polyps (EPs).Interventions: Hysteroscopic polypectomy, as performed through different techniques.Measurements and Main Results: Included in the study were 1404 patients (with 1825 EPs). The setting was an ambulatory care unit in 40.38% of the cases (567 women), of whom 97.7% (554) did not require analgesia/anesthesia. In the remaining 59.62% of women (837 women), the procedures were performed in an operating room under mild sedation, local or general anesthesia. Minor complications occurred in 32 patients (2.27%), without significant differences between the techniques used (p = ns). Uterine perforation occurred in 14 cases, all performed in the operating room with some kind of anesthesia, only 1 with a vaginoscopic technique and the remaining during blind dilatation (odds ratio [OR], 19.98; 95% confidence interval [CI], 1.19-335.79; p = .04). An incomplete removal of EPs was documented in 39 patients. Logistic regression analysis showed that a higher risk of residual EPs was associated with the use of a fiber-based 3.5-mm hysteroscope (OR, 6.78; 95% CI, 2.97-15.52; p <.001), the outpatient setting (OR, 2.17; 95% CI, 1.14-4.14; p = .019), and EPs located at the tubal corner (OR, 1.98; 95% CI, 1.03-2.79; p = .039). No association between incomplete EP removal and EP size or number was recorded (p = ns), as well as with the other variables evaluated.Conclusion: Outpatient polypectomy was associated with a minimal but significantly higher risk of residual EPs in comparison with inpatient polypectomy. Conversely, inpatient polypectomy was associated with a considerably higher risk of uterine perforation and penetration in comparison with office hysteroscopy. Because of lower intraoperative risks and higher cost-effectiveness, office hysteroscopy may be considered, whenever possible, as the gold standard technique for removing EPs. [ABSTRACT FROM AUTHOR]

Summary Expression of sonic hedgehog ( Shh ) in the limb bud is regulated by an enhancer called the zone of polarizing activity regulatory sequence (ZRS), which, in evolution, belongs to an ancient group of highly conserved cis regulators found in all classes of vertebrates. Here, we examined the endogenous ZRS in mice, using genome editing to establish the relationship between enhancer composition and embryonic phenotype. We show that enhancer activity is a consolidation of distinct activity domains. Spatial restriction of Shh expression is mediated by a discrete repressor module, whereas levels of gene expression are controlled by large overlapping domains containing varying numbers of HOXD binding sites. The number of HOXD binding sites regulates expression levels incrementally. Substantial portions of conserved sequence are dispensable, indicating the presence of sequence redundancy. We propose a collective model for enhancer activity in which function is an integration of discrete expression activities and redundant components that drive robust expression. [ABSTRACT FROM AUTHOR]

Abstract: Study Objective: To describe the hysteroscopic findings in patients complaining of menorrhagia to establish any significant association between menorrhagia and benign/malignant intrauterine disorders. Design: Prospective cohort study (Canadian Task Force classification II). Setting: University La Sapienza, Rome, Italy. Patients: One hundred eighteen premenopausal women undergoing office hysteroscopy for menorrhagia (group A) and 344 premenopausal patients undergoing office hysteroscopy for other indications (noncyclic abnormal uterine bleeding, infertility, ultrasonographic abnormalities, etc) (group B). Interventions: Office hysteroscopy. Measurement and Main Results: Data on the prevalence of hysteroscopic findings (cervical polyps, endometrial polyps, submucous myomas, low-grade hyperplasia and high-grade hyperplasia/endometrial carcinoma) were compared between group A and group B. The total prevalence, as well as the prevalence of type 0 and type I myomas (totally or >50% intracavitary, respectively), and the mean number per patients with submucous myomas was significantly higher in group A compared with group B (p = .0001, p = .024, and p = .017, respectively). Multivariable logistic regression analysis showed a statistically significant association between age (odds ratio 4.15, 95% confidence interval 1.55–11.1 in the 40- to 49-year age group), presence of submucous myomas (odds ratio 2.76, 95% confidence interval 1.52–5.00), and menorrhagia. Conclusions: Menorrhagia seems to be associated with aging, the presence and number of submucous myomas, and with the degree of their intracavitary development. [Copyright &y& Elsevier]

: ObjectiveTo evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) as a pain control method during office hysteroscopy.: DesignA prospective, randomized study.: SettingCentre for Minimally Invasive Surgery, Department of Gynecological Science and Perinatology, “La Sapienza” University, Rome, Italy.: Patient(s)One hundred forty-two patients undergoing office hysteroscopy.: Intervention(s)Application of a TENS device on the patient’s abdomen before and during office hysteroscopy.: Main outcome measure(s)The level of pain experienced by the patients was assessed using a 10 cm visual analog scale; the side effects and changes in the hemodynamic parameters were evaluated.: Result(s)The patients treated with TENS during hysteroscopy (group A, n = 71) were compared with a control group (group B, n = 71) on whom the TENS device was not used. The women in the TENS group experienced a significantly lower level of pain during hysteroscopy. No differences in side effects were observed between both group.: Conclusion(s)TENS is a simple, efficient, and safe method of relieve pain during office hysteroscopy. [Copyright &y& Elsevier]

Study Objectives: To describe and demonstrate a technique for laparoscopic removal of a perforating intrauterine device (IUD) during pregnancy, and to provide tips to facilitate safe laparoscopic surgery during pregnancy.Design: Video presentation of the technique for laparoscopic removal of a perforating IUD in a pregnant woman.Setting: Department of Neuroscience, Reproductive Sciences, and Dentistry, University of Naples Federico II, Naples, Italy.Intervention: A 30-year-old woman, gravida 3, para 2, with a copper T IUD (Nova T 380; Bayer, Leverkusen, Germany) perforating the left adnexa presented to the emergency room complaining of left lower quadrant pain. The patient had the IUD inserted by her gynecologist 3 months before the onset of the symptoms. Ultrasound revealed a 6-week intrauterine pregnancy with the presence of fetal cardiac activity along with the IUD perforating the left adnexa. The patient returned at 11 weeks of gestation complaining of worsening abdominal pain and excruciating left lower quadrant pain. She was scheduled for laparoscopic excision of the perforating IUD [1-3]. Considering her pregnancy, laparoscopy under regional anesthesia was performed in the minimal Trendelenburg position at 12 degrees, through open laparoscopic access [4]. Intra-abdominal pressure of 8 mmHg and ultrasound energy to cut and coagulate, avoiding monopolar/bipolar energy owing to the presence of a copper IUD, were used. The IUD and tube were extracted in an endobag through umbilical access, under a 5-mm, 0-degree telescope in left lateral access [5]. The procedure was carried out uneventfully, and the IUD was removed. Fetal viability was confirmed after the procedure. At the time of this report, the patient was in the 23rd week of gestation, and the pregnancy was progressing without any problems.Conclusion: Laparoscopic removal of perforated IUD during pregnancy under regional anesthesia is a feasible and safe option that should be considered when needed. [ABSTRACT FROM AUTHOR]

Study Object: To describe 3 cases of misplaced or retained Intrauterine Contraceptive (IUC) that were successfully resolved by hysteroscopy performed in an ambulatory setting using miniaturized electrosurgical and mechanical operative instruments.Design: Step-by-step description of the technique using slides, pictures, and video (educative video) (Canadian Task Force classification III).Setting: Misplaced or retained IUC may be related to several causes; incorrect insertion is the leading cause. In these cases, patients may complain of abnormal bleeding, pelvic pain, or pregnancy or they may remain asymptomatic. When a displaced IUC is suspected, transvaginal ultrasonography is the primary investigation followed by radiography in cases in which the IUC is not seen within the uterus. Additional imaging such as computed tomographic scanning or magnetic resonance imaging may be needed. Hysteroscopy represents the gold standard for diagnostic clarification and management of a dislocated or embedded IUC.Interventions: The hysteroscopic approach of the 3 cases was the following: removal of a partially perforating IUD in the cesarean scar pouch, repositioning of a dislocated IUS in the isthmocele, and removal of an embedded IUS in the cornual area. The procedures were performed in an ambulatory setting using a 5-mm continuous flow hysteroscope and vaginoscopic approach without any analgesia and/or anesthesia. The alternate use of mechanical and electrosurgical 5F instruments allowed us to separate the IUC from the myometrial uterine wall, respecting the healthy myometrium and without causing significant patient discomfort or complications.Conclusion: The possibility of using miniaturized electrosurgical and mechanical instruments with small-diameter hysteroscopes offers the possibility of an effective, safe, cost-efficient, and well-tolerated removal or repositioning of a misplaced or retained IUC. This minimally invasive approach can be performed in an office setting to avoid more invasive and traumatic approaches. [ABSTRACT FROM AUTHOR]

: ObjectiveTo report hemolytic crisis in a woman with glucose-6-phosphate dehydrogenase (G6PD) deficiency who underwent diagnostic hysteroscopy using endoscopic instruments sterilized in gluteraldehyde and phenol disinfectant.: DesignCase report.: SettingSurgical unit of a university hospital.: Patient(s)A 53 year-old woman with endometrial thickening on ultrasonography.: Intervention(s)Diagnostic hysteroscopy.: Main outcome measure(s)Laboratory tests.: Result(s)The patient experienced abdominal pain and acute hypotension 10 minutes after diagnostic hysteroscopy. We attributed this event to the exposure of her genital mucosa caused by the hysteroscopic chemical disinfectant.: Conclusion(s)Chemical sterilization of endoscopes can cause clinical manifestations in people with G6PD deficiency, a common enzyme abnormality. The phenol content in some chemical disinfectants for endoscopic instruments can also cause hemolytic crisis. [Copyright &y& Elsevier]

Abstract: Constipation is a highly prevalent and distressing symptom in patients with advanced, progressive illnesses. Although opioids are one of the most common causes of constipation in patients with advanced, progressive illness, it is important to note that there are many other potential etiologies and combinations of causes that should be taken into consideration when making treatment decisions. Management approaches involve a combination of good assessment techniques, preventive regimens, appropriate pharmacological treatment of established constipation, and frequent monitoring. In this vulnerable patient population, maintenance of comfort and respect for individual preferences and sensitivities should be overriding considerations when making clinical decisions. This consensus document was developed by a multidisciplinary group of leading Canadian palliative care specialists in an effort to define best practices in palliative constipation management that will be relevant and useful to health care professionals. Although a wide range of options exists to help treat constipation and prevent its development or recurrence, there is a limited body of evidence evaluating pharmacological interventions. These recommendations are, therefore, based on the best of the available evidence, combined with expert opinion derived from experience in clinical practice. This underscores the need for further clinical evaluation of the available agents to create a robust, evidence-based foundation for treatment decisions in the management of constipation in patients with advanced, progressive illness. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Association of two experimental compounds has synergistic anti-psoriatic activity. • The mixture exhibits anti-proliferative activity in keratinocyte cultures. • The mixture induces terminal differentiation in keratinocyte cultures. Abstract Psoriasis is one of the most common chronic autoinflammatory skin disease, associated with hyperproliferation and abnormal differentiation of keratinocytes, inflammation, and angiogenesis. The available treatments for psoriasis are not curative and may have numerous side effects, and topical administration is preferred over systemic therapy due to the reduced systemic burden of the drug. Thus, novel and more efficacious formulations of anti-inflammatory and/or differentiating compounds for topical application could be very useful for the disease management and for improving the quality of life of the patients. Here we evaluated the potential as anti-psoriatic of an equimolar mixture of two compounds, 2,4-Monofurfurylidene-tetra- O -methylsorbitol (Compound A) and 4,6-dimethyl-2-(3,4,5-trimethoxyphenylamino)pyrimidine (Compound B), that, used individually, are known to possess immunomodulating properties (Compound A) and keratolitic and anti-inflammatory activity (Compound B). Human immortalized keratinocyte cell line (HaCaT cells) and primary human keratinocyte cells from adult donor (HEKa) were used as in vitro experimental models. We show that the mix A + B exhibits antiproliferative activity and induces terminal differentiation more efficiently than compounds A and B used individually. We confirm that the compound B is the active ingredient of the mixture and the mainly responsible for anti-psoriatic activity, but the mix A + B is more effective and possesses lower cytotoxicity than the compound B alone. This could be ascribable to the association with compound A, that is known to possess, in addition to the immunomodulating ability, antioxidant and antiradical action. Our results indicate that mix A + B could be a suitable candidate for a new cosmeceutical formulation for topical treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT)3 receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations. [Copyright &y& Elsevier]