Age structure and abundance in populations of muscoid flies from a poultry facility in Southeast Brazil

Muscina stabulans, M. domestica, Chrysomya putoria, C. megacephala and Stomoxys calcitrans were the most abundant muscoid flies captured in a poultry facility in southeastern Brazil. We examined the gonadotrophic profiles of the females caught at different sites and different times and found that Mu. stabulans and M. domestica, the predominant species, presented similar gonadotrophic profiles only when captured on the manure under the cages, but very different and sometimes opposite gonadotrophic profiles when sampled from wooden posts, vegetation or electric cords. We also determined sex ratios and relative abundance for these two species and found significant differences between them. More than 50% of the females of both species of Chrysomya captured on manure carried eggs or exhibited signs of recent oviposition. The vast majority of S. calcitrans presented ovaries with eggs or signs of recent oviposition. A small proportion of them had ovaries in the recent emerged condition. Our data on ovarian stages, sex ratio and relative abundance allowed us to associate different gonadotrophic profiles with each site and characterize each site as a resting, ovipositing or mating site.

Role of BRCA2 in control of the RAD51 recombination and DNA repair protein.

Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of RAD51, a protein essential for homologous recombination and DNA repair. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second, transport of RAD51 to the nucleus is defective in cells carrying a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular localization and DNA binding ability of RAD51. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.

Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells.

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(l2-g2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.

Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti-N-methyl-d-aspartate receptor encephalitis.

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti-NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al.,(1) and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.

PHA advises 'breast is best'!

The Public Health Agency is using National Breastfeeding Awareness Week (NBAW) to emphasise the message that breastfeeding is the healthiest option for both you and your baby and that by deciding to breastfeed, you will be giving your child the best possible start in life. NBAW runs from 19-25 June and highlights the fact that any period of breastfeeding, however short, will benefit your baby.Breast milk is different to formula milk as it contains antibodies that cannot be manufactured in formula. Antibodies help protect babies from infection and stimulate their immune system.Northern Ireland has the lowest breastfeeding rate in the UK, with an average of 63% of women breastfeeding their baby at birth. Janet Calvert, Regional Breastfeeding Coordinator at the PHA, said: "This is an issue that clearly needs addressed, as breastfeeding has many important health benefits for both mother and baby. These include a reduced risk of ear, chest, kidney and stomach infections and less risk of childhood diabetes and obesity."Breastfeeding can also significantly reduce the risk of hospital admission of children for gastroenteritis and chest infections. The health benefits for mothers who choose to breastfeed include a reduced risk of developing illnesses such as breast cancer, ovarian cancer and osteoporosis."There are other benefits as well as those to your health. Breastfeeding is free - you don't have to buy formula, bottles, teats, sterilising equipment etc. Breast milk is always available, with the right ingredients, at the right temperature, so it's easier to feed at night or on the go.The PHA recognises the importance of breastfeeding to health and the need to ensure that mothers get off to a good start with breastfeeding. It is vital that mothers get the right support and encouragement from their family and friends should they decide to breastfeed. Breastfeeding can be difficult at the start and mothers need reassurance while they learn."There are many local initiatives in the community to improve breastfeeding support. These include improving support in the health service and through Sure Start programmes, which work in areas of need to help ensure children get the best start in life," Janet added."Mother to mother peer support programmes are in place in many areas and are working with expectant and new mothers to help them breastfeed for longer. There are also 70 breastfeeding support groups, which provide ongoing support for breastfeeding mothers throughout Northern Ireland. "The PHA is also working to improve attitudes to breastfeeding in public through the Breastfeeding Welcome Here scheme, which began in 2005 and now has over 200 businesses and public facilities signed up to support and welcome breastfeeding families. All these initiatives, along with support from partners and family, are vital to help expectant and new mothers stay with breastfeeding."Health Minister Edwin Poots said: "There is clear evidence that breastfeeding offers health benefits for both babies and mothers. We know that breast milk gives baby the best start in life by providing all the nutrients and protection a baby needs for the first six months of life. That is why my Department is committed to promoting and supporting breastfeeding".For further information on breastfeeding visit www.breastfedbabies.org.uk

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor.

The HER-2/ErbB-2 oncoprotein is overexpressed in human breast and ovarian adenocarcinomas and is clearly associated with the malignant phenotype. Although no specific ligand for this receptor has been positively identified, ErbB-2 was shown to play a central role in a network of interactions with the related ErbB-1, ErbB-3 and ErbB-4 receptors. We have selected new peptides binding to ErbB-2 extracellular domain protein (ECD) by screening 2 newly developed constrained and unconstrained random hexapeptide phage libraries. Out of 37 phage clones, which bound specifically to ErbB-2 ECD, we found 6 constrained and 10 linear different hexapeptide sequences. Among the latter, 5 consensus motifs, all with a common methionine and a positively charged residue at positions 1 and 3, respectively, were identified. Furthermore, 3 representative hexapeptides were fused to a coiled-coil pentameric recombinant protein to form the so-called peptabodies recently developed in our laboratory. The 3 peptabodies bound specifically to the ErbB-2 ECD, as determined by enzyme-linked immunosorbent assay and BIAcore analysis and to tumor cells overexpressing ErbB-2, as shown by flow cytometry. Interestingly, one of the free selected linear peptides and all 3 peptabodies inhibited the proliferation of tumor cells overexpressing ErbB-2. In conclusion, a novel type of ErbB-2-specific ligand is described that might complement presently available monoclonal antibodies.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients.

Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. RESULTS: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

Increased neuroendocrine cells in resected metastases compared to primary colorectal adenocarcinomas.

Neuroendocrine differentiation has been described in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery, but its clinical relevance is controversial and no data are currently available in colorectal carcinoma metastases as compared to primary tumors. The presence of chromogranin A positive tumor cells was investigated by means of immunohistochemistry on surgical specimens from 54 primary colorectal carcinomas and their corresponding metastases, resected at diagnosis or during tumor progression. In 47 patients, tumor metastases were resected 1 month to 12 years after chemotherapy and/or radiotherapy, while in the remaining seven patients no additional therapy after primary surgery was performed. In primary tumors, neuroendocrine differentiation was found in 12/54 cases (22.2%) as compared to 25/54 metastatic lesions (46.3%; p?=?0.01). The presence of neuroendocrine phenotype was not correlated with any clinical pathological parameter nor with a different proliferation index. However, patients having neuroendocrine cells in the primary tumor had a significantly shorter survival from the time of metastatic spread than those having not (33.3 vs. 55.5 months; p?=?0.04). In summary, our data show that colorectal carcinoma metastases contain a higher percentage of neuroendocrine differentiated cells as compared to their corresponding primaries, a finding possibly related to the influence of chemotherapy in neuroendocrine differentiation during colorectal carcinoma progression.

Culex quinquefasciatus vitellogenesis: morphological and biochemical aspects

The vitellogenic process in Culex quinquefasciatus, which is triggered by a blood meal, involves the synthesis, distribution and storage of the nutrients necessary for embryo development. The fat body of an adult female Cx. quinquefasciatus revealed two cell types: large trophocytes and small, eosinophilic, "oenocyte-like" cells, which show no morphological changes throughout the gonotrophic cycle. Trophocytes, which only begin to synthesise vitellogenin (Vg) 12 h post-blood meal (PBM), undergo a series of morphological changes following engorgement. These changes include the expansion of the rough endoplasmic reticulum (RER) and Golgi complex, which are later destroyed by autophagosomes. At 84 h PBM, trophocytes return to their pre-engorgement morphology. The ovarian follicles of non-blood-fed Cx. quinquefasciatus contain a cluster of eight undifferentiated cells surrounded by follicular epithelium. After engorgement, the oocyte membrane facing the perioocytic space increases its absorptive surface by microvilli development; large amounts of Vg and lipids are stored between 24 and 48 h PBM. Along with yolk storage in the oocyte, follicular cells exhibit the development of RER cisternae and electron-dense granules begin to fill the perioocytic space, possibly giving rise to endochorion. Later in the gonotrophic cycle, electron-dense vesicles, which are possible exochorion precursors, fuse at the apical membrane of follicular cells. This fusion is followed by follicular cell degeneration.

Surgical menopause increases salt sensitivity of blood pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

The S. pombe cdc15 gene is a key element in the reorganization of F-actin at mitosis.

The S. pombe cdc15 gene is essential for cell division. cdc15ts mutants do not form a septum, but growth and nuclear division continue, leading to formation of multinucleate cells. The earliest step in septum formation and cytokinesis, rearrangement of actin to the center of the cell, is associated with appearance of hypophosphorylated cdc15p and formation of a cdc15p ring, which colocalizes with actin. Loss of cdc15p function impairs formation of the actin ring. The abundance of cdc15 mRNA varies through the cell division cycle, peaking in early mitosis before septation. Expression of cdc15 in G2-arrested cells induces actin rearrangement to the center of the cell. These data implicate cdc15p as a key element in mediating the cytoskeletal rearrangements required for cytokinesis.

Granular layer in the periplasmic space of gram-positive bacteria and fine structures of Enterococcus gallinarum and Streptococcus gordonii septa revealed by cryo-electron microscopy of vitreous sections.

High-resolution structural information on optimally preserved bacterial cells can be obtained with cryo-electron microscopy of vitreous sections. With the help of this technique, the existence of a periplasmic space between the plasma membrane and the thick peptidoglycan layer of the gram-positive bacteria Bacillus subtilis and Staphylococcus aureus was recently shown. This raises questions about the mode of polymerization of peptidoglycan. In the present study, we report the structure of the cell envelope of three gram-positive bacteria (B. subtilis, Streptococcus gordonii, and Enterococcus gallinarum). In the three cases, a previously undescribed granular layer adjacent to the plasma membrane is found in the periplasmic space. In order to better understand how nascent peptidoglycan is incorporated into the mature peptidoglycan, we investigated cellular regions known to represent the sites of cell wall production. Each of these sites possesses a specific structure. We propose a hypothetic model of peptidoglycan polymerization that accommodates these differences: peptidoglycan precursors could be exported from the cytoplasm to the periplasmic space, where they could diffuse until they would interact with the interface between the granular layer and the thick peptidoglycan layer. They could then polymerize with mature peptidoglycan. We report cytoplasmic structures at the E. gallinarum septum that could be interpreted as cytoskeletal elements driving cell division (FtsZ ring). Although immunoelectron microscopy and fluorescence microscopy studies have demonstrated the septal and cytoplasmic localization of FtsZ, direct visualization of in situ FtsZ filaments has not been obtained in any electron microscopy study of fixed and dehydrated bacteria.

Vertebral artery occlusion after chemotherapy

We present a patient who experienced a stroke due to vertebral artery occlusion after chemotherapy