Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

BACKGROUND: Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT) has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemotherapy as treatment modalities in the specific indication of operable patients with advanced ovarian carcinoma (no medical contraindication to debulking surgery). PATIENTS AND METHODS: A total of 59 patients with stage III or IV epithelial ovarian carcinomas were evaluated between 1998 and 2003. All patients were submitted to surgical exploration aiming to evaluate tumor resectability. Neoadjuvant chemotherapy was given (in 27 patients) where optimal cytoreduction was not feasible. Conversely primary debulking surgery was performed when we considered that optimal cytoreduction could be achieved by the standard surgery (32 patients). RESULTS: Optimal cytoreduction was higher in the NACT group (72.2%) than the conventional group (62.4%), though not statistically significant (P = 0.5). More important was the finding that parameters of surgical aggressiveness (blood loss rates, ICU stay and total hospital stay) were significantly lower in NACT group than the conventional group. The median overall survival time was 28 months in the conventional group and 25 months in NACT group with a P value of 0.5. The median disease free survival was 19 months in the conventional group and 21 months in NACT group (P = 0.4). In multivariate analysis, the pathologic type and degree of debulking were found to affect the disease free survival significantly. Overall survival was not affected by any of the study parameters. CONCLUSION: Primary chemotherapy followed by interval debulking surgery in select group of patients doesn't appear to worsen the prognosis, but it permits a less aggressive surgery to be performed

Qualitative Analysis Methods Review

Qualitative research plays an important role in business research. The popular research methods that researchers used are; Qualitative, Quantitative, and Mixed Methods. Researchers who conduct qualitative studies, often struggle to pick the best technique to analyse their data. This report aims to present six different methods that can be used to analyse qualitative data collected for business studies. A comparison between the techniques is found useful to present in order to help decision made by researchers who are embarking upon qualitative research studies. Qualitative Analysis Methods (QAM) can be used in some of the mixed-methods approaches as appropriate

Little qualitative RNA misexpression in sterile male F(1) hybrids of Drosophila pseudoobscura and D. persimilis

BACKGROUND: Although the genetics of hybrid sterility has been the subject of evolutionary studies for over sixty years, no one has shown the reason(s) why alleles that operate normally within species fail to function in another genetic background. Several lines of evidence suggest that failures in normal gene transcription contribute to hybrid dysfunctions, but genome-wide studies of gene expression in pure-species and hybrids have not been undertaken. Here, we study genome-wide patterns of expression in Drosophila pseudoobscura, D. persimilis, and their sterile F(1) hybrid males using differential display. RESULTS: Over five thousand amplifications were analyzed, and 3312 were present in amplifications from both of the pure species. Of these, 28 (0.5%) were not present in amplifications from adult F(1) hybrid males. Using product-specific primers, we were able to confirm one of nine of the transcripts putatively misexpressed in hybrids. This transcript was shown to be male-specific, but without detectable homology to D. melanogaster sequence. CONCLUSION: We tentatively conclude that hybrid sterility can evolve without widespread, qualitative misexpression of transcripts in species hybrids. We suggest that, if more misexpression exists in sterile hybrids, it is likely to be quantitative, tissue-specific, and/ or limited to earlier developmental stages. Although several caveats apply, this study was a first attempt to determine the mechanistic basis of hybrid sterility, and one potential candidate gene has been identified for further study

What can you do with 0.1× genome coverage? A case study based on a genome survey of the scuttle fly Megaselia scalaris (Phoridae)

<p>Abstract</p> <p>Background</p> <p>The declining cost of DNA sequencing is making genome sequencing a feasible option for more organisms, including many of interest to ecologists and evolutionary biologists. While obtaining high-depth, completely assembled genome sequences for most non-model organisms remains challenging, low-coverage genome survey sequences (GSS) can provide a wealth of biologically useful information at low cost. Here, using a random pyrosequencing approach, we sequence the genome of the scuttle fly <it>Megaselia scalaris </it>and evaluate the utility of our low-coverage GSS approach.</p> <p>Results</p> <p>Random pyrosequencing of the <it>M. scalaris </it>genome provided a depth of coverage (0.05x0.1x) much lower than typical GSS studies. We demonstrate that, even with extremely low-coverage sequencing, bioinformatics approaches can yield extensive information about functional and repetitive elements. We also use our GSS data to develop genomic resources such as a nearly complete mitochondrial genome sequence and microsatellite markers for <it>M. scalaris</it>.</p> <p>Conclusion</p> <p>We conclude that low-coverage genome surveys are effective at generating useful information about organisms currently lacking genomic sequence data.</p

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

Clinico-epidemiologic features of oculocutaneous albinism in northeast section of Cairo – Egypt

Background: Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by the absence or reduced pigmentation of the skin, hair and eyes. To assess the clinico-epidemiologic features of different forms of OCA among Egyptian patients, we performed a retrospective study to determine the frequency, types, clinical presentation and associated genomic errors in albino patients and their relatives consulting the Genetics Clinic, Pediatric Hospital, Ain Shams University, Cairo, Egypt.Methods: We used the outpatients index files to identify diagnosed cases of albinism referred from the dermatologic and ophthalmologic departments with different genodermatoses over 43 year period.We used specifically designed data collection protocol forms to extract epidemiological and clinical data from the patients medical records. These were entered into a computer database and analyzed using standard statistical software.Results: The occurrence rate of albinism in our study was 20.4% of genodermatoses patients and 1 per 5843 patients attending the Pediatric hospital. Consanguineous marriage was reported among parents of 66.37% of patients and positive family history was reported in 46.01% of patients. Complete OCA was detected in 48.59% of patients, partial albinism in 41.59% of patients and syndromic albinism was detected in 7.96%. Associated genomic errors were detected in 36.28% of our albino patients and seventy one multiple mutant genomic errors were defined among relatives of thirty seven index families of oculocutaneous albinism patients.Conclusion: To the best of our knowledge, this preliminary study is the first report of its kind from Egypt. The high rate of parental consanguinity among the parents of our Egyptian albino patients may account for the frequency of this genodermatosis in Egypt

Knowledge Management in the Pharmaceutical Industry: Between Academic Research and Industry Regulations

The pharmaceutical sector is one of the pillars of the world’s economy. A significant proportion of its value lies in intellectual assets generated through continuous innovation and lengthy development cycles within a strictly regulated environment. The purpose of this paper is to address the gap between knowledge management (KM) as an expanding academic discipline in the pharmaceutical industry and at the same time a growing regulatory expectation. A systematic review of 137 refereed KM articles revealed six empirical research themes in the pharmaceutical industry. In a subsequent step, the discovered themes and subthemes were compared with the extant regulatory expectations as explained in 128 regulatory guidelines. Findings shed the light on the gap between academic KM research and the current thinking of regulatory bodies. Some regulated knowledge processes were underrepresented in academic literature. The paper offers also novel insights and recommendations for future developments in academic research, regulations and/or industry

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

A microsatellite linkage map of Drosophila mojavensis

BACKGROUND: Drosophila mojavensis has been a model system for genetic studies of ecological adaptation and speciation. However, despite its use for over half a century, no linkage map has been produced for this species or its close relatives. RESULTS: We have developed and mapped 90 microsatellites in D. mojavensis, and we present a detailed recombinational linkage map of 34 of these microsatellites. A slight excess of repetitive sequence was observed on the X-chromosome relative to the autosomes, and the linkage groups have a greater recombinational length than the homologous D. melanogaster chromosome arms. We also confirmed the conservation of Muller's elements in 23 sequences between D. melanogaster and D. mojavensis. CONCLUSIONS: The microsatellite primer sequences and localizations are presented here and made available to the public. This map will facilitate future quantitative trait locus mapping studies of phenotypes involved in adaptation or reproductive isolation using this species