Use of music during vaginal birth and caesarean section: an interprofessional survey.

PURPOSE: Evidence abounds about the beneficial effects of music on patients and healthcare professionals for many medical indications. This study aimed to evaluate the dissemination and use of music in the obstetrical setting. METHODS: Invitations to an online survey were sent to physicians and midwives of all obstetrics departments in Germany. The survey gathered descriptive data as well as information about the personal relation to music and the use of it during vaginal birth (VB) and caesarean section (CS) and whether data about positive or negative effects of music were known to the participant. RESULTS: In total, there were 293 respondents. The 47% that had the means to play music during CS stated that music was played in 15% of the cases. Most respondents have the means to play music during VB (97%). Music is played in 38% of VB. Regardless of the mode of delivery, music was estimated to be positive for team communication and patient communication. It was also deemed calming and mood lifting on the respondents. Regarding the patient, music during CS and VB was rated as being positive on all scales. Listening to music was recommended more often during VB (66%) than CS (38%). CONCLUSIONS: Although healthcare professionals are mostly aware of the beneficial effects of music in obstetrics, our study shows that music plays a more important role during VB than during CS in Germanys obstetrical wards. There is a lack of equipment to play music in operation theatres where CS take place.

Perioperative management of positioning in gynecological cancersurgery: a national NOGGO-AGO intergroup survey.

INTRODUCTION: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany. METHODS: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management. RESULTS: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively. DISCUSSION: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications.

The Influence of Personality and Anxiety Traits on Birth Experience and Epidural Use in Vaginal Deliveries - A Cohort Study.

A positive birth experience for the mother is an important goal in obstetric health care and is influenced by several factors. For this study, 186 women filled in questionnaires between 24 and 72 hours after giving birth vaginally. We evaluated the Big-Five personality traits (extraversion, neuroticism, openness, conscientiousness and agreeableness), trait anxiety, different dimensions of childbirth experience and pain management. Correlation analysis revealed that trait anxiety and neuroticism were negatively associated with several dimensions of the birth experience. Furthermore, conscientiousness and extraversion were positively correlated with the dimension Participation. Regression analysis for the individual dimensions and overall score respectively, confirmed the independent impact of anxiety trait on Perceived Safety, Participation and Professional Support and the overall score as well as of neuroticism on Perceived Safety and conscientiousness on Participation. The significant regression models showed small R2-scores (.084-.154). The birth experience did not differ whether the women received an epidural or not. Women who did not receive an epidural displayed higher scores on the personality trait conscientiousness. The study highlights small but important associations between personality traits and birth experience in vaginal births which should sensitize the medical staff when supporting women during labor.

Structural Insight into IAPP-Derived Amyloid Inhibitors and Their Mechanism of Action.

Designed peptides derived from the islet amyloid polypeptide (IAPP) cross-amyloid interaction surface with Aß (termed interaction surface mimics or ISMs) have been shown to be highly potent inhibitors of Aß amyloid self-assembly. However, the molecular mechanism of their function is not well understood. Using solution-state and solid-state NMR spectroscopy in combination with ensemble-averaged dynamics simulations and other biophysical methods including TEM, fluorescence spectroscopy and microscopy, and DLS, we characterize ISM structural preferences and interactions. We find that the ISM peptide R3-GI is highly dynamic, can adopt a ß-like structure, and oligomerizes into colloid-like assemblies in a process that is reminiscent of liquid-liquid phase separation (LLPS). Our results suggest that such assemblies yield multivalent surfaces for interactions with Aß40. Sequestration of substrates into these colloid-like structures provides a mechanistic basis for ISM function and the design of novel potent anti-amyloid molecules.

Comparing birth experience and birth outcome of vaginal births between induced and spontaneous onset of labour: a prospective study.

PURPOSE: In developed countries, around 25% of all births involve labour induction. Studies have indicated that labour induction negatively influences the birth experience as well as the birth process. However, the impact of labour induction when only considering vaginal deliveries has not been studied yet, which was the purpose of the present study. METHODS: 186 women who gave birth vaginally took part in this prospective study. 95 women gave birth after spontaneous onset of labour (SL-group) and 91 women received a labour induction (LI-group). Eight to 72 h after birth, the women filled in the revised version of the standardised Childbirth Experience Questionnaire, which examines the birth experience in four dimensions (Own Capacity, Perceived Safety, Participation and Professional Support). Medical details regarding birth and fetal outcomes were taken from the medical records. RESULTS: Birth outcomes (the number of epidural anaesthesia, the duration of birth, birth risks and childbirth injuries) as well as fetal outcomes (APGAR after 1 and 5 min and arterial cord pH) did not differ between the groups. Regarding the subjective birth experience, the LI-group indicated significantly lower values for Perceived Safety and Participation compared to the SL-group, while there were no differences for the dimensions Own Capacity and Professional Support. DISCUSSION: Successful labour induction resulting in a vaginal birth did not negatively influence birth and fetal outcomes and only partly affected the women's birth experience. The negative impact of labour induction on the dimensions Perceived Safety and Participation should sensitize midwives in order to provide optimal support.

Effects of music intervention during caesarean delivery on anxiety and stress of the mother a controlled, randomised study.

BACKGROUND: Stress and anxiety during pregnancy and childbirth have negative consequences for both mother and child. There are indications that music has a positive effect in this situation. The present study investigates the influence of music during the caesarean on anxiety and stress of the expectant mother. METHODS: The SAMBA study is a single-centre, controlled, randomized study including 304 patients. Women in the intervention group heard music via loudspeakers from one of four self-selected genres. The control group had standard treatment without music. The caesarean was performed in regional Anesthesia. At admission, at skin incision, during skin suture and two hours after completion of surgery, different subjective (State-Trait Anxiety Inventory, visual analogue scale for anxiety) and objective parameters (salivary cortisol/amylase, heart rate, blood pressure) were collected. Mixed-factorial Analysis of variances as well as independent sample t-tests were applied for data analysis. RESULTS: At skin suture, significantly lower anxiety levels were reported in the intervention group regarding State anxiety (31.56 vs. 34.41; p = .004) and visual analogue scale for anxiety (1.27 vs. 1.76; p = .018). Two hours after surgery, the measured visual analogue scale for anxiety score in the intervention group was still significantly lower (0.69 vs. 1.04; p = .018). The objective parameters showed significant differences between the groups in salivary cortisol increase from admission to skin suture (12.29 vs. 16.61 nmol/L; p = .043), as well as systolic blood pressure (130.11 vs. 136.19 mmHg; p = .002) and heart rate (88.40 vs. 92.57/min; p = .049) at skin incision. CONCLUSIONS: Music during caesarean is an easy implementable and effective way of reducing stress and anxiety of the expectant mother. TRIAL REGISTRATION: German registry for clinical trials ( DRKS00007840 ). Registered 16/06/2015. Retrospectively registered.

Survey of compartment syndrome of the lower extremity after gynecological operations.

PURPOSE: This study was aimed to investigate incidence, circumstances and consequences of acute compartment syndrome (CS) of the lower extremity after gynecological operations in lithotomy position by collecting data from departments of Obstetrics and Gynecology in Germany. DESIGN: Retrospective observational study. SETTING: Departments of Obstetrics and Gynecology in the area of North Rhine (Germany) METHODS: A 24-item questionnaire was sent to 168 gynecological departments. In addition, cases anonymously reported to the Expert Committee for Medical Malpractice Claims of the Medical Association of North Rhine between 2002 and 2012 were analyzed. MAIN OUTCOME MEASURE: Incidence of acute CS after gynecological operations. RESULTS: A total of 59 questionnaires (35 %) were returned for analysis, reporting 21 cases of CS. Based on the collected data, we calculated an incidence of postoperative CS ranging between 0.067 % and 0.28 %. All reported cases of postoperative CS occurred after surgeries in lithotomy position, 57.1 % of cases occurred after laparoscopic procedures and 76.2 % after procedures longer than 4 h. Overall, 61.0 % of departments do not routinely inform about the risk of this complication when they get patients' informed consent. Reported prevention strategies were inconsistent and ranged from none to multiple measures. CONCLUSION: CS is a complication clearly associated with long lasting gynecological operations in Lithotomy position. Despite a relatively high incidence, so far no guidelines on perioperative management and medicolegal aspects exist and preventive measures are heterogeneous among institutions. The need for guidelines and recommendations by an expert committee has been identified.

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

Diagnostic delay in moderately/poorly differentiated breast cancer types.

BACKGROUND: Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types. METHODS: Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician's assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay. RESULTS: We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR-/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay. CONCLUSION: Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy.

Factors Indicating Surgical Excision in Classical Type of Lobular Neoplasia of the Breast.

Purpose: Classical type of lobular neoplasia (LN) encompassing both atypical lobular hyperplasia and classical lobular carcinoma in situ of the breast is a lesion with uncertain malignant potential and has been the topic of several studies with conflicting outcome results. The aim of our study was to clarify outcome-relevant factors and treatment options of classical LN. Methods: We performed a pathological re-evaluation of the preoperative biopsy specimens and a retrospective clinical and radiological data analysis of 160 patients with LN from the Breast Center Zurich. Open surgery was performed in 65 patients, vacuum-assisted biopsy (VAB) in 79 patients, and surveillance after breast core needle biopsy (CNB) in 16 patients. Results: The upgrade rate into ductal carcinoma in situ/invasive cancer was the highest in case of imaging/histology discordance (40%). If the number of foci in the biopsy specimen was ≥3, the upgrade rate in the consecutive surgical specimens was increased (p = 0.01). The association of classical LN with histological microcalcification correlated with shortened disease-free survival (p < 0.01), whereas other factors showed no impact on follow-up. Conclusions: Surveillance or subsequent VAB after CNB of LN is sufficient in most cases. Careful consideration of individual radiological and histological factors is required to identify patients with a high risk of upgrade into malignancy. In those cases, surgical excision is indicated.

Modifications of laparoscopic supracervical hysterectomy technique significantly reduce postoperative spotting.

STUDY OBJECTIVE: The aim of this study was to estimate the benefit of excision of the endocervix during laparoscopic supracervical hysterectomy (LSH) with regard to postoperative cyclical bleeding. DESIGN: Cohort study from 2 centers (Canadian Task Force classification II-2). SETTING: Two surgical teams at the University of Duesseldorf Medical Center and PAN Clinic, Cologne, Germany. PATIENTS: Women with menstrual bleeding disorders resistant to medical treatment, symptomatic leiomyomata, dysmenorrhea. INTERVENTION: Laparoscopic supracervical hysterectomy. The uterus was transsected from the cervix with 2 techniques with and without excision of cervical canal. MEASUREMENTS AND MAIN RESULTS: We evaluated 300 patients who underwent consecutive LSH procedures. In 150 patients the uterus was transsected from the cervix using a monopolar loop. In a second series of 150 patients a unipolar needle electrode was used for the uterine amputation and the excision of cervical canal. The mean duration of the transsection was 65 seconds (monopolar loop) versus 168 seconds (monopolar needle). The excision of the endocervix was performed without any complications in 148 procedures. Histologic examination of the removed tissue revealed endocervical tissue in 83.3% (n = 125), endometrium in 9.4% (n = 14), cervicoisthmic mucosa in 3.3% (n = 5), and myometrium only in 4% (n = 4). All 300 patients were contacted 12 months after surgery to inquire about bleeding status, and 282 (94%) responded. In patients who underwent excision of the endocervix, postoperative cyclical bleeding was significantly reduced compared with the control group (1.4% vs 10.7%). CONCLUSION: The results of this study indicate that the routine excision of the endocervix is a quick safe procedure which allows a significant reduction of postoperative cyclical bleeding in patients who undergo LSH.

The Prevention of Positioning Injuries During Gynecologic Surgery. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/077, October 2020).

Purpose Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.

Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management.

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

Clinical Imaging of the Heterogeneous Group of Triple-negative Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact. PATIENTS AND METHODS: Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies. RESULTS: Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders. CONCLUSION: The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC.

Hysteroscopy for asymptomatic postmenopausal women with sonographically thickened endometrium.

UNLABELLED: Endometrial carcinoma is the most common genital cancer in women. While patients usually present with vaginal bleeding, in 10-20% this characteristic symptom is absent. Endometrial thickness (double layer) is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyps). OBJECTIVE: We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (>6mm). STUDY DESIGN: A prospective observational study in a university hospital of 304 postmenopausal women referred between 1996 and 2006 because of a sonographically thickened endometrium in the absence of abnormal bleeding, who underwent continuous flow hysteroscopy (4.5mm Storz hysteroscope) and fractionated curettage of the uterine cervix and corpus (D & C) in addition to vaginal sonography (5MHz probe). RESULTS: The mean age of the women was 64.8 (range 57.7-71.9) years. Average endometrial thickness measured by ultrasound was 12mm+/-6.7mm. Hysteroscopy suggested the presence of endometrial polyps in 226 women (74.3%), simple endometrial hyperplasia in 34 (11.2%), atrophic endometrium in 18 (5.9%), complex endometrial hyperplasia in 2 (0.7%), atypical hyperplasia in 3 (1%) and leiomyoma in 9 (3.0%). In 12 women (3.9%), the hysteroscopic appearance suggested malignancy and histology revealed endometrial adenocarcinoma. All hysteroscopic results were confirmed by histological examination. CONCLUSION: Hysteroscopy represents an easy, safe and effective method for the investigation of asymptomatic women with a thickened endometrium found with transvaginal ultrasound. The commonest pathology was endometrial polyps.

Favourable Outcome in Two Pregnancies in a Patient with 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency.

In patients with 3-hydroxy-3-methylglutaryl(HMG)-CoA lyase deficiency (OMIM 246450), five pregnancies have been described worldwide, which were either terminated or resulted in severe metabolic sequelae during pregnancy or delivery. Here, we report on a patient with HMG-CoA lyase deficiency, who underwent two uncomplicated pregnancies. The 19-year-old patient was admitted because of recurrent vomiting and nausea. Diagnostics revealed pregnancy at week 8 of gestation. Metabolic analyses revealed normal lactate and blood glucose levels and normal acid-base status. Urine organic acid analysis showed an elevated excretion of 3-CH3-glutaric acid, 2,3-CH3-glutaconic acid, and 3-CH3-3-OH-glutaric acid. Oral treatment with carnitine and glucose wes administered intravenously during the period of nausea and vomiting. After clinical recovery, a diet with 0.89 g/kg of protein/d and 38 kcal/kg body weight/d was given. Meals were taken every 3 h. Additionally, 70 g of starch was given at midnight to maintain normoglycemia at night time. Peripartum, a complete parenteral nutrition, was delivered through a central venous catheter. The patient delivered a healthy male infant by Caesarean section at week 38 of gestation (Apgar 9/10/10) and remained metabolically stable throughout the peripartum period. Postpartum nutrition was gradually changed from parenteral to oral diet. Two years later, the patient became pregnant again and presented with hyperemesis gravidarum. With metabolic monitoring and treatment as before no decompensation occurred. At week 38 of gestation, she delivered a healthy female infant by elective Caesarian section (Apgar 9/10/10). This case report describes the metabolic and obstetric management of two pregnancies in a patient with HMG-CoA lyase deficiency with favorable outcome without metabolic complications.

BRCA1 controls the cell division axis and governs ploidy and phenotype in human mammary cells.

BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features. BRCA1 depletion stabilizes HMMR abundance and disrupts cortical asymmetry of NUMA-dynein complexes in dividing cells such that polarity cues provided by cell-matrix adhesions were not able to orient division. We also show that immortalized mammary cells carrying a mutant BRCA1 allele (BRCA1 185delAG/+) reproduce many of these effects but in this model, oriented divisions were maintained through cues provided by CDH1+ cell-cell junctions. These findings reveal a previously unknown effect of BRCA1 suppression on mechanisms that regulate the cell division axis in proliferating, non-transformed human mammary epithelial cells and consequent downstream effects on the mitotic integrity and phenotype control of their progeny.

Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate.

Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique ß-strand structure distinct from the conventional amyloid ß-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.

The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs.

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary glands. This review will address the role of TGF-beta in regulating hormone-dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition, will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

Intensity-based signal separation algorithm for accurate quantification of clustered centrosomes in tissue sections.

Centrosomes are small organelles that organize the mitotic spindle during cell division and are also involved in cell shape and polarity. Within epithelial tumors, such as breast cancer, and some hematological tumors, centrosome abnormalities (CAs) are common, occur early in disease etiology, and correlate with chromosomal instability and disease stage. In situ quantification of CA by optical microscopy is hampered by overlap and clustering of these organelles, which appear as focal structures. CA has been frequently associated with Tp53 status in premalignant lesions and tumors. Here the authors described an approach to accurately quantify centrosome frequencies in tissue sections and tumors, independently of background or noise levels. Applying simple optical rules in nondeconvolved conventional 3D images of stained tissue sections, the authors showed that they could evaluate more accurately and rapidly centrosome frequencies than with traditional investigator-based visual analysis or threshold-based techniques. The resulting population-based frequency of centrosomes per nucleus could then be used to approximate the proportion of cells with CA in that same population. This was done by taking into account baseline centrosome amplification and proliferation rates measured in the tissue. Using this technique, the authors showed that 20-30% of cells have amplified centrosomes in Tp53 null mammary tumors.