The Role of Magnetic Resonance Imaging in the Pre-operative Evaluation of Women Diagnosed With Atypical Endometrial Hyperplasia.

BACKGROUND/AIM: To evaluate the role of MRI in patients with atypical endometrial hyperplasia (AEH) and incorporate MRI findings in predictive models estimating the risk of co-existent endometrial cancer (EC). PATIENTS AND METHODS: Data from 189 women diagnosed with AEH and had MRI scan prior to operation, over nine years, were retrospectively collected. RESULTS: Histology showed EC in 51 (27%) cases. Presence of myometrial invasion on MRI was more commonly detected in patients with EC compared to those with benign pathology (37.3% versus 10.9%, p<0.001). The sensitivity and specificity of MRI in identifying cancer were 37% and 89%, respectively. Age, menopausal status and presence of invasion on MRI were the best predictors for the presence of malignancy. CONCLUSION: Myometrial invasion on MRI is associated with increased risk of EC in women with AEH. Its accuracy in detecting malignancy improves when combined with clinical parameters. This could be of value for conservative-management candidates.

Cholecystectomy as Part of Cytoreductive Surgery for Advanced Ovarian Cancer: Perioperative Outcomes.

BACKGROUND/AIM: To assess the perioperative outcomes of cholecystectomy in cytoreductive procedures for epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Prospectively collected perioperative data of patients that underwent cytoreduction for advanced EOC, between 2014 and 2018, were analysed. Patients were divided in two groups on the basis of whether cholecystectomy was performed. RESULTS: A total of 144 patients with stage IIIC/IV EOC were included. Cholecystectomy was performed in 22 (15.3%) patients. Those who underwent cholecystectomy more likely required diaphragmatic peritonectomy, splenectomy, lesser omentectomy, excision of disease from the porta hepatis and liver's capsule (p<0.001). There was no difference in the cytoreductive outcomes (complete or optimal) and the rate of grade 3-5 complications between the two groups (p=0.10 & p=0.06, respectively). No direct complications related to cholecystectomy were observed. CONCLUSION: A significant percentage of patients with advanced EOC require cholecystectomy. Gynecologic oncologists should embrace the opportunity to develop advanced surgical skills including cholecystectomy.

The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian, fallopian tube, and peritoneal cancer.

OBJECTIVE: The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete). METHODS: Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016. RESULTS: Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen ('ultra-radical'), the combined rate of complete and optimal cytoreduction would be only 33.3%. CONCLUSIONS: Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.

Investigating vaginal bleeding in postmenopausal women found to have an endometrial thickness of equal to or greater than 10 mm on ultrasonography.

PURPOSE: This aim of this study is to determine the risk of endometrial cancer in symptomatic postmenopausal women, when endometrial thickness on transvaginal ultrasonography is equal to or greater than 10 mm, and subsequent office-based endometrial sampling histology is negative. METHODS: This is a prospective cross-sectional study, performed in a gynaecological oncology centre in the United Kingdom between February 2008 and July 2012. All postmenopausal women presenting with vaginal bleeding were investigated using transvaginal ultrasonography. Women with endometrial thickness measurements equal to or greater than 10 mm and negative office-based endometrial biopsy underwent hysteroscopy and endometrial biopsies. RESULTS: Over a 52-month period, 4148 women were investigated for postmenopausal vaginal bleeding. 588 (14.2%) women were found to have endometrial thickness measurements of equal to or greater than 10 mm on transvaginal ultrasonography. 170 (28.9%) cases of endometrial cancer were diagnosed in this group: 149 (87.6%) of the cancer cases were diagnosed in the outpatient setting with a Pipelle® endometrial sampler, whilst 21 (12.4%) had a negative Pipelle® sample and were diagnosed with hysteroscopy. The group diagnosed with hysteroscopy had lower BMI (32.7 kg/m2 versus 39.7 kg/m2, p < 0.001) whilst the group diagnosed with Pipelle was more likely to have a history of hypertension and diabetes mellitus (p = 0.019 for both). The sensitivity of Pipelle was 87.65%. CONCLUSION: For women presenting with postmenopausal bleeding and where the endometrial thickness is equal to or greater than 10 mm and Pipelle sampling is negative, hysteroscopic evaluation with directed biopsy is strongly recommended.

Investigation and management of abnormal peri-menopausal bleeding.

Abnormal peri-menopausal bleeding is a common clinical problem. Decisions to investigate if the menstrual disorders are related to an underlying pathology or represent physiologic changes are often complex especially as no clear guidance is available. The aim of this review is to present a summary of the current available evidence regarding the investigation tools used to evaluate women with abnormal uterine bleeding during menopausal transition and in the post-menopausal period. In this article, we focus mainly on the investigation and exclusion of endometrial carcinoma, as this represents the most common malignancy diagnosed.

Isoprenyl-thiourea and urea derivatives as new farnesyl diphosphate analogues: synthesis and in vitro antimicrobial and cytotoxic activities.

A series of new isoprenyl-thiourea and urea derivatives were synthesized by the reaction of alkyl or aryl isothiocyanate or isocyanate and primary amines. The structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and elemental analysis. The new compounds were screened for in vitro antimicrobial activity against seven strains representing different types of gram-positive and gram-negative bacteria. More than a third of the synthesized compounds showed variable inhibition activities against the tested strains. Best antimicrobial activities were found for those thiourea analogues with 3-methyl-2-butenyl, isobutyl or isopentyl groups and aromatic rings possessing electron withdrawing substituents. The new compounds were also subjected to a preliminary screening for antitumoral activity. The presence of a highly lipophilic group and an electron withdrawing group in the aromatic rings enhanced anticancer activity of the synthesized compounds, showing in most cases more activity than that of the controls.

A novel approach to postoperative bladder care in women after radical hysterectomy.

PURPOSE: Currently, controversy exists with regard to the duration of bladder drainage and choice of catheter used in women who undergo radical hysterectomy. In this manuscript, we propose a novel approach to improving postoperative bladder care in women who undergo radical hysterectomy. METHODS: This is a retrospective study of women who underwent Type 3 Piver radical hysterectomy in a gynaecological oncology centre in the United Kingdom from January 2009 to September 2011. We report the outcomes of removal of urinary catheter 48-72 h following radical hysterectomy. RESULTS: Over a 32-month period, 30 women underwent radical hysterectomy. 19 (63.3 %) women underwent surgery for treatment of cervical cancer, 5 (16.7 %) women for management of endometrial cancer, 6 (20 %) women for other conditions. One patient underwent partial cystectomy at the time of radical hysterectomy and was not included in the analysis. Of the 29 patients, only five (17.2 %) were found to have urinary residuals greater than 100 ml following the removal of the indwelling catheter on the second postoperative day and required recatheterisation. 82.8 % of the patients had the catheter removed within 48-72 h postoperatively. None of these patients required re-admission with urinary retention. CONCLUSION: Removal of urinary catheter on the second postoperative day following radical hysterectomy is feasible and not associated with increased morbidity. This approach may be particularly useful to complement the introduction of laparoscopic and robotic surgical approaches for surgical management of cervical cancer.

Management of postmenopausal women with vaginal bleeding when the endometrium can not be visualized.

OBJECTIVE: To determine the risk of endometrial cancer when endometrial thickness is not visualized using ultrasonography. DESIGN: Cross-sectional study. SETTING: Gynecological oncology center in the United Kingdom. POPULATION: All postmenopausal women referred with vaginal bleeding. METHODS: All women were investigated using gray-scale transvaginal ultrasonography. Women were arbitrarily stratified into four groups according to the endometrial thickness measurement. Women with endometrial thickness that was not adequately visualized on ultrasonography were included in a separate group. MAIN OUTCOME MEASURES: Endometrial cancer diagnosis. RESULTS: Over a 50-month period, 4454 women were investigated for postmenopausal vaginal bleeding. A total of 259 (6%) of women were diagnosed with endometrial carcinoma. Endometrial thickness measured 5-9.9 mm in 1201 (27%), 10-14.9 mm in 468 (11%), 15-19.9 mm in 209 (5%), and equal to or greater than 20mm in 197 (4%) of women. In 174 (4%) of women, the endometrial thickness was not visualized on transvaginal ultrasonography. For women where the endometrial thickness was not adequately visualized, the final histology included benign endometrium (124), endometrial cancer (26), endometrial polyps (11), endometritis (7), and other pathology (7). The odds of endometrial cancer in women where the endometrial thickness was not visualized were found to be significantly higher than the odds of cancer for women with an endometrial thickness of 5-9.9 mm (OR = 5.23, 95%CI 3.10-8.85, p-value <0.0001). CONCLUSIONS: For women presenting with postmenopausal bleeding and where the endometrial thickness cannot be adequately visualized on ultrasonography, hysteroscopic evaluation is recommended.

Late presentation of metastatic smooth muscle neoplasm of the uterus with low malignant potential.

A 48-year-old woman underwent total abdominal hysterectomy with conservation of the ovaries and tubes. Histology showed a well-circumscribed smooth muscle tumor with foci of degeneration (including infarct-type necrosis) but no coagulative tumor cell necrosis and only mild focal cytological atypia. She presented, 24 years later with shortness of breath and abdominal distension and underwent bilateral salpingo-oophorectomy, appendectomy, omental biopsy and para-aortic lymph node sampling. Histology showed bilateral ovarian smooth muscle tumors with no coagulative tumor cell necrosis or significant cellular atypia. The cells were mitotically active. The tumors in both ovaries were most likely secondary to the previous uterine smooth muscle neoplasm. To our knowledge, this case is the first in the literature to describe a benign cellular leiomyoma that subsequently behaved as a smooth muscle tumor of uncertain malignant potential, which recurred 24 years after the initial diagnosis.

Postmenopausal vaginal bleeding in women using hormone replacement therapy.

OBJECTIVE: To estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding using estrogen-progestogen hormone replacement therapy (HRT) regimens and to assess if the duration of HRT use has an effect on the risk of diagnosing endometrial cancer. STUDY DESIGN: Cross-sectional study of consecutive women presenting with postmenopausal vaginal bleeding at a gynaecological oncology centre in the UK. Main outcome measures Endometrial cancer diagnosis. RESULTS: Over a 62-month period, 4847 women were investigated for postmenopausal vaginal bleeding. The majority of women (4097, 84.5%) did not use any HRT preparation at the time of initial referral and 750 (15.5%) women were using combined HRT preparations. A total of 298 (6.1%) women were diagnosed with endometrial carcinoma. Women using HRT preparations were significantly less likely to be diagnosed with endometrial cancer compared with women not using HRT (adjusted odds ratio = 0.229, 95% CI 0.116-0.452; P < 0.0001). The longer duration of HRT use did increase the risk of diagnosing endometrial cancer in women presenting with postmenopausal vaginal bleeding, but this was not statistically significant. CONCLUSIONS: Postmenopausal women presenting with vaginal bleeding and using combined HRT preparations have significantly lower risk of being diagnosed with endometrial cancer when compared with women not using HRT.

Outcome of investigations for postmenopausal vaginal bleeding in women under the age of 50 years.

OBJECTIVE: The objective of this study is to determine the incidence of endometrial cancer in young postmenopausal women presenting with vaginal bleeding. METHODS: Cross-sectional study of postmenopausal women presenting with vaginal bleeding in a gynaecological oncology centre in the United Kingdom. All women underwent transvaginal ultrasound scanning (TVS) as the initial investigation tool to evaluate the endometrium. Endometrial biopsy was performed only in cases where endometrial thickness measured equal to or greater than 5mm. The patients were divided into two groups based on their age: less than 50 years (Group A) and 50 years or older (Group B). RESULTS: Over a 57-month period, 4454 women were investigated for postmenopausal vaginal bleeding. Of these, 259 (5.8%) women were diagnosed with endometrial carcinoma. 260 (5.8%) women were younger than 50 years. Endometrial biopsy was not performed in 130 women in Group A that had an endometrial thickness measurement of less than 5mm on ultrasonography. With a median follow-up period of 3 (1-5) years, we found no cases of endometrial cancer in women under the age of 50 that did not undergo endometrial biopsy at the time of initial evaluation. Overall, no cases of endometrial cancer were diagnosed in postmenopausal women under the age of 50 years. CONCLUSIONS: We found no cases of endometrial cancer amongst 260 women presenting with postmenopausal vaginal bleeding under the age of 50 years. These women could be investigated on a less urgent basis depending on the available resources.

Comparing the performance of two clinical models in estimating the risk of endometrial cancer in symptomatic postmenopausal women.

OBJECTIVE: The aim of this study was to internally evaluate the accuracy measures of the two newly developed predictive models, called DEFAB and DFAB, used to estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding. STUDY DESIGN: Prospective study including postmenopausal women presenting with vaginal bleeding. RESULTS: Over a 46-month-period, 3795 postmenopausal women presented with vaginal bleeding and were included in the study. A total of 221 (6%) women were diagnosed with endometrial carcinoma. The DEFAB predictive model incorporates known risk factors such as presence of Diabetes, Endometrial thickness measurement on transvaginal ultrasonography, Frequency of bleeding, Age, and Body mass index. The DFAB model is based on the above clinical characteristics excluding the ultrasonography result. For the recommended cut-off values, there was no evidence (p-value=0.221) of a difference in the diagnostic ability with respect to sensitivity, specificity, area under receiver operating curve, positive predictive value and negative predictive value. There was strong evidence (p-value<0.0001) to suggest that the diagnostic ability of DEFAB and DFAB agree as evidenced by the excellent Kappa statistic 0.950 (95% CI 0.940-0.960). We found strong evidence (p-value<0.0001) that the variables incorporated in both predictive models simultaneously correctly classify an individual to either having cancer or not having cancer with respect to logistic discriminant analysis. CONCLUSION: We recommend that these two predictive models can be used interchangeably.

How to improve training in bowel surgery for gynecological oncologists-experience from a single center in the United kingdom.

INTRODUCTION: There is now a growing realization of the lack of experience of gynecological oncology trainees in gastrointestinal surgery. Advanced fellowship programs in gastrointestinal surgery have been suggested as a potential solution to this problem. PATIENTS AND METHODS: We present data relating to gastrointestinal procedures performed by the gynecological oncology trainee during a fellowship program over a 3-year period in a single gynecological oncology center in the United Kingdom. RESULTS: Over a 36-month period, 369 cases of invasive ovarian cancer were diagnosed in our institute, of which 278 (75.3%) were stage III/IV disease. Bowel surgery was performed in 86 patients (30.9%) with stage III/IV ovarian cancer. A total of 121 gastrointestinal procedures were performed during the study period, as some patients had more than one procedure. We present the procedures the gynecological oncology fellow performed and assisted during this period. DISCUSSION: To improve competencies in performing bowel surgery among gynecological oncology trainees, we suggest sustained exposure in bowel surgery over the entire duration of the training program.

Estimating the risk of endometrial cancer in symptomatic postmenopausal women: a novel clinical prediction model based on patients' characteristics.

INTRODUCTION: The aim of this study was to develop a multivariable model to predict the risk of endometrial carcinoma in postmenopausal women with vaginal bleeding using individuals' clinical characteristics. PATIENTS AND METHODS: This prospective study of consecutive postmenopausal women presenting with vaginal bleeding was conducted at a gynecological oncology center in the United Kingdom for a 46-month period. All women underwent transvaginal ultrasound scanning as the initial investigation tool to evaluate the endometrium. Women found to have an endometrial thickness 5 mm or more had endometrial sampling performed. RESULTS: Of a total of 3548 women presenting with vaginal bleeding during the study period, 201 (6%) women had a diagnosis of endometrial carcinoma. An investigator-led best model selection approach used to select the best predictors of cancer in the multiple logistic regression model showed that patient's age (odds ratio [OR], 1.06), body mass index (OR, 1.07), recurrent episodes of bleeding (OR, 3.64), and a history of diabetes (OR, 1.48) increased the risk of endometrial malignancy when corrected for other characteristics. The mentioned clinical variables satisfied the criteria for inclusion in our predictive model called FAD 31 (F for the frequency of bleeding episodes, A for the age of the patient, D for diabetes, and the number 31 represents the BMI cut-off value). The total score for the model varies from 0 to 8. The area under the receiver operating characteristics curve for the developed model was 0.73 (95% confidence interval, 0.70-0.77). DISCUSSION: We have developed a simple model based on patients' clinical characteristics in estimating the risk of endometrial cancer for postmenopausal women presenting with vaginal bleeding. The model shows reasonable discriminatory ability for women with cancer and without, with an area under the receiver operating characteristics curve of 0.73. This will allow clinicians to individualize the diagnostic pathway for women with postmenopausal vaginal bleeding.

Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women.

OBJECTIVE: The aim of this study is to identify the causes of vaginal bleeding in different age groups of postmenopausal women. Also, we attempt to estimate the incidence of postmenopausal vaginal bleeding and endometrial cancer in a defined geographical area. STUDY DESIGN: The study was conducted at a gynaecological oncology centre in the United Kingdom, between February 2006 and May 2009. Patients were investigated according to established evidence-based departmental guidelines. RESULTS: During the study period 3047 women were referred with postmenopausal vaginal bleeding. In 1356 women (44.5%) the endometrial thickness measured less than 5 mm on transvaginal ultrasound scan. Benign histology was found in 1144 women (37.5%). Benign endometrial polyps were the cause of bleeding in 10.1% of the cases. The incidence of endometrial cancer in our study population was 5%. The rate of postmenopausal vaginal bleeding during the study period peaks at the age of 55-59 years (25.9/1000 postmenopausal women/year) and declines thereafter. The peak incidence of endometrial cancer during the study period (12.6/10,000 postmenopausal women/year) was seen between the ages of 60 and 64 years and similarly declines with increasing age. CONCLUSION: To our knowledge, this is the first population-based estimation of the incidence of genital tract bleeding and endometrial cancer among postmenopausal women in the United Kingdom. The results of this study showing the age-related differential diagnosis can be used to inform clinical practice when counselling postmenopausal women with vaginal bleeding.

Interplay between iron homeostasis and the osmotic stress response in the halophilic bacterium Chromohalobacter salexigens.

In this study, the connection between iron homeostasis and the osmostress response in the halophile Chromohalobacter salexigens was investigated. A decrease in the requirement for both iron and histidine and a lower level of siderophore synthesis were observed at high salinity, and these findings were correlated with a lower protein content in salt-stressed cells. A six-gene operon (cfuABC-fur-hisI-orf6 operon) located downstream of the ectABC ectoine synthesis genes was characterized. A fur strain (in which the ferric iron uptake regulator Fur was affected) had the Mn resistance phenotype typical of fur mutants, was deregulated for siderophore production, and displayed delayed growth under iron limitation conditions, indicating that fur encodes a functional iron regulator. hisI was essential for histidine synthesis, which in turn was necessary for siderophore production. Fur boxes were found in the promoters of the cfuABC-fur-hisI-orf6 and ectABC operons, suggesting that Fur directly interacts with DNA in these regions. Fur mediated the osmoregulated inhibition of cfuABC-fur-hisI-orf6 operon expression by iron and functioned as a positive regulator of the ectABC genes under high-salinity conditions, linking the salt stress response with iron homeostasis. Excess iron led to a higher cytoplasmic hydroxyectoine content, suggesting that hydroxyectoine protects against the oxidative stress caused by iron better than ectoine. This study provides the first evidence of involvement of the iron homeostasis regulator Fur as part of the complex circuit that controls the response to osmotic stress in halophilic bacteria.

Phenotypic and genotypic characterization of rhizobia associated with Acacia saligna (Labill.) Wendl. in nurseries from Algeria.

Twenty seven rhizobial strains associated with Acacia saligna grown in northern and southern Algeria were characterized, including generation time, host-range, the 16S rRNA gene and 16S-23S rRNA intergenic spacer restriction patterns, 16S rRNA gene sequence analysis and tolerance to salinity and drought. Cross inoculation tests indicated that 11 slow-growing isolates from northern nurseries were able to nodulate introduced Australian acacias exclusively, whereas 16 fast-growing isolates, mainly from southern nurseries, were capable of also nodulating native acacias. Restriction patterns and sequence analysis of the 16S rRNA gene showed that strains of the first group belonged to Bradyrhizobium while strains of the second group were related to Sinorhizobium meliloti and Rhizobium gallicum. Interestingly, five strains of the first group formed a distinct cluster phylogenetically close to Bradyrhizobium betae, a non-nodulating species causing tumour-like deformations in sugar beet roots. Bradyrhizobium strains were in general more sensitive to NaCl and PEG than the S. meliloti and R. gallicum representatives. Among the latter, strains S. meliloti BEC1 and R. gallicum DJA2 were able to tolerate up to 1M NaCl and 20% PEG. This, together with their wide host-range among Acacia species, make them good candidates for developing inoculants for A. saligna and other acacia trees growing in arid areas.

Synchronous diagnosis of multiple tumours in a postmenopausal woman.

We report an unusual case of a postmenopausal woman that was diagnosed with multiple tumours derived from different embryogenic tissues. She presented with postmenopausal vaginal bleeding. Clinical examination revealed a large pelvic mass, tender on palpation. Serum CA-125 level was elevated at 8,985 kU/l (normal range 0-35). A CT scan showed a malignant-appearing right ovarian mass with a peritoneal nodule, small amount of free fluid in the pelvis and evidence of a colonic intussusception. The patient underwent total abdominal hysterectomy, bilateral salpingo-ophorectomy, partial omentectomy and right hemicolectomy with side-to-side anastomosis. Histopathology showed a Grade 3 endometrial adenocarcinoma. Both ovaries were completely replaced by partially necrotic poorly differentiated endometrioid adenocarcinoma. Small deposits of metastatic adenocarcinoma were seen within the omentum. Sections from the retroperitoneal mass showed a low-grade liposarcoma. A large polypoid tumour within the right colon was a tubulo-villous adenoma.

Complex regulation of the synthesis of the compatible solute ectoine in the halophilic bacterium Chromohalobacter salexigens DSM 3043T.

The synthesis of the compatible solute ectoine, mediated by the ectABC gene products, is the main mechanism used by the halophilic bacterium Chromohalobacter salexigens to cope with osmotic stress. Evidence was found that this process is regulated at the transcriptional level. S1 protection analyses performed with RNA extracted from cells grown in minimal medium at low (0.75 M NaCl) or high (2.5 M NaCl) osmolarity suggested the existence of four promoters upstream of ectA. Two of these (PectA1 and PectA2) might be recognized by the main vegetative sigma factor sigma(70), and one (PectA3) might be dependent on the general stress sigma factor sigma(S). The S1 protection assays suggest that PectA1 and PectA3 may be osmoregulated promoters. In addition, an internal promoter showing sequences homologous to promoters dependent on the heat-shock sigma factor sigma(32) was found upstream of ectB. Transcription from PectA in C. salexigens followed a pattern typical of sigma(S)-dependent promoters, and was reduced by 50 % in an E. coli rpoS background. These data strongly suggest the involvement of the general stress sigma factor sigma(S) in ectABC transcription in C. salexigens. Expression of PectA-lacZ and PectB-lacZ trancriptional fusions was very high at low salinity, suggesting that ectABC may be a partially constitutive system. Both transcriptional fusions were induced during continuous growth at high temperature and their expression was reduced in cells grown in the presence of osmoprotectants (ectoine or glycine betaine) or the DNA gyrase inhibitor nalidixic acid. Moreover, PectA-lacZ expression was negatively modulated in cells grown with an excess of iron (FeCl(3)). Measurement of ectoine levels in the presence of glycine betaine at different NaCl concentrations suggests that an additional post-transcriptional control may occur as well.