A high-volume study on the impact of diabetes mellitus on clinical outcomes after surgical and percutaneous cardiac interventions.

BACKGROUND: Type I and type II diabetes mellitus (DM) patients have a higher prevalence of cardiovascular diseases, as well as a higher mortality risk of cardiovascular diseases and interventions. This study provides an update on the impact of DM on clinical outcomes, including mortality, complications and reinterventions, using data on percutaneous and surgical cardiac interventions in the Netherlands. METHODS: This is a retrospective, nearby nationwide study using real-world observational data registered by the Netherlands Heart Registration (NHR) between 2015 and 2020. Patients treated for combined or isolated coronary artery disease (CAD) and aortic valve disease (AVD) were studied. Bivariate analyses and multivariate logistic regression models were used to evaluate the association between DM and clinical outcomes both unadjusted and adjusted for baseline characteristics. RESULTS: 241,360 patients underwent the following interventions; percutaneous coronary intervention(N = 177,556), coronary artery bypass grafting(N = 39,069), transcatheter aortic valve implantation(N = 11,819), aortic valve replacement(N = 8,028) and combined CABG and AVR(N = 4,888). The incidence of DM type I and II was 21.1%, 26.7%, 17.8%, 27.6% and 27% respectively. For all procedures, there are statistically significant differences between patients living with and without diabetes, adjusted for baseline characteristics, at the expense of patients with diabetes for 30-days mortality after PCI (OR = 1.68; p <.001); 120-days mortality after CABG (OR = 1.35; p <.001), AVR (OR = 1.5; p <.03) and CABG + AVR (OR = 1.42; p =.02); and 1-year mortality after CABG (OR = 1.43; p <.001), TAVI (OR = 1.21; p =.01) and PCI (OR = 1.68; p <.001). CONCLUSION: Patients with DM remain to have unfavourable outcomes compared to nondiabetic patients which calls for a critical reappraisal of existing care pathways aimed at diabetic patients within the cardiovascular field.

Perceptions of Alcohol and Alcohol Use among Community Members and Young Adults in Ukraine.

Background: Unhealthy alcohol use is a public health issue, prioritized by the World Health Organization (WHO) for prevention and reduction. Ukraine falls in the highest WHO category of "years of life lost" due to alcohol use. Objective: To investigate perceptions of alcohol consumption in a sample of youth and adults in western Ukraine. Methods: In-depth semi-structured interviews were conducted with 38 adult stakeholders (aged 21-63 years), and 81 adolescents and young adults (aged 12-21 years) completed paper-and-pencil open-ended questions. A combined deductive-inductive thematic analysis of these qualitative data resulted in an initial coding scheme for both parts of the data. These initial codes were organized into patterns, which were further condensed to four themes. Results: The four themes that were developed are: (1) The general historical, socio-economic-political situation and its relation to alcohol use, (2) Alcohol in the home and daily environment, (3) Alcohol use, related feelings, peers, family, and burden to health, and (4) Perceptions of the consequences of alcohol (mis)use. Conclusions: Respondents indicated awareness that daily consumption, also in youth, as well as binge drinking and childhood sipping constitute a risk to health. These risks were described in the context of easy availability, low pricing, and peer pressure. The respondents mentioned awareness that alcohol dependence (AD) of parents affected families with the risk of disadvantageous child development. Interventions may include targeting current norms, stigmatizing beliefs and supporting subjects in developing coping skills.

Phylogenomics resolves major relationships and reveals significant diversification rate shifts in the evolution of silk moths and relatives.

BACKGROUND: Silkmoths and their relatives constitute the ecologically and taxonomically diverse superfamily Bombycoidea, which includes some of the most charismatic species of Lepidoptera. Despite displaying spectacular forms and diverse ecological traits, relatively little attention has been given to understanding their evolution and drivers of their diversity. To begin to address this problem, we created a new Bombycoidea-specific Anchored Hybrid Enrichment (AHE) probe set and sampled up to 571 loci for 117 taxa across all major lineages of the Bombycoidea, with a newly developed DNA extraction protocol that allows Lepidoptera specimens to be readily sequenced from pinned natural history collections. RESULTS: The well-supported tree was overall consistent with prior morphological and molecular studies, although some taxa were misplaced. The bombycid Arotros Schaus was formally transferred to Apatelodidae. We identified important evolutionary patterns (e.g., morphology, biogeography, and differences in speciation and extinction), and our analysis of diversification rates highlights the stark increases that exist within the Sphingidae (hawkmoths) and Saturniidae (wild silkmoths). CONCLUSIONS: Our study establishes a backbone for future evolutionary, comparative, and taxonomic studies of Bombycoidea. We postulate that the rate shifts identified are due to the well-documented bat-moth "arms race". Our research highlights the flexibility of AHE to generate genomic data from a wide range of museum specimens, both age and preservation method, and will allow researchers to tap into the wealth of biological data residing in natural history collections around the globe.

The prognostic value of residual disease after neoadjuvant chemotherapy in advanced ovarian cancer; A systematic review.

INTRODUCTION: The ability to minimize residual disease during primary cytoreductive surgery is the strongest predictor for improved overall survival in advanced ovarian cancer. But while the probability to achieve a macroscopic complete resection increases if surgery is preceded by neoadjuvant chemotherapy (NACT), survival rates after NACT are similar to those observed after primary surgery. This may suggest that the prognostic effect of residual disease is altered after NACT. More specifically, randomized data suggest that there is no difference between optimal (0.1-1 cm) and suboptimal (>1 cm) cytoreductive surgery after NACT. Therefore, the aim of the current review is to establish the prognostic effect of the amount of residual disease after interval cytoreductive surgery (ICS) on overall survival. METHODS: Potential articles for inclusion in the current review were systematically searched through Medline, Embase and Cochrane in September 2017. Median overall survival (mOS) was summarized by the outcome of ICS per study. In addition, mOS was summarized for all studies together stratified by the outcome of ICS, based on the principle of a weighted average. RESULTS: In total, 3677 unique manuscripts were individually screened on title and abstract, which resulted in 11 individual studies that comprised a total of 2178 patients. MOS was 41 months for patients with no residual disease (range 33-54 months), 27 months for patients with 0.1-1 cm of residual disease (range 19-38 months) and 21 months with >1 cm of residual disease (range 14-27 months). Six studies showed significant differences between optimal and suboptimal ICS, while five studies showed no differences. CONCLUSION: The summary of the currently available literature showed that after NACT, patients with optimal cytoreductive surgery experience lengthened survival compared to patients with suboptimal cytoreductive surgery. Patients with no macroscopic residual disease have, however, the most favorable survival outcomes, similar to what is seen after primary cytoreductive surgery.

Interval between debulking surgery and adjuvant chemotherapy is associated with overall survival in patients with advanced ovarian cancer.

OBJECTIVE: Treatment for advanced epithelial ovarian cancer (EOC) consists of debulking surgery and (neo)adjuvant platinum-based chemotherapy. The aim of this study was to evaluate whether the time from surgery to adjuvant chemotherapy (TTC) was associated with clinical outcome. METHODS: We identified all Dutch patients who received optimal or complete debulking surgery for primary EOC (FIGO IIb-IV) between 2008 and 2015 from the Netherlands Cancer Registry. TTC was divided into three groups based on the interquartile range (IQR). Early (<25%) and prolonged (>75%) TTC were compared to intermediate TTC (25-75%). Logistic regression was used to identify factors associated with a prolonged TTC and multivariable Cox regression to evaluate the independent effect of treatment interval on overall survival (OS). Patients receiving primary debulking surgery (PDS) and patients receiving interval debulking surgery (IDS) were analyzed separately. RESULTS: 4097 patients were included, 1612 underwent PDS and 2485 IDS. Median TTC was 29 days (IQR 24-37). Age ≥ 65, complete debulking surgery, postoperative complications, and hospitalization ≥10 days were independently associated with a longer TTC for both PDS and IDS. TTC in the longest quartile was associated with poor OS after both PDS (Hazard Rate (HR) 1.43, 95% CI 1.09-1.88) and NACT-IDS (HR 1.22 (1.02-1.47)) when compared to the intermediate TTC, but only in patients with no macroscopic residual disease after surgery. CONCLUSIONS: Our study provides evidence that delayed initiation of adjuvant chemotherapy is an independent prognostic factor for worse overall survival after complete (interval)debulking surgery. We advise to start adjuvant chemotherapy within five to six weeks after debulking surgery.

Independent evolution of sexual dimorphism and female-limited mimicry in swallowtail butterflies (Papilio dardanus and Papilio phorcas).

Several species of swallowtail butterflies (genus Papilio) are Batesian mimics that express multiple mimetic female forms, while the males are monomorphic and nonmimetic. The evolution of such sex-limited mimicry may involve sexual dimorphism arising first and mimicry subsequently. Such a stepwise scenario through a nonmimetic, sexually dimorphic stage has been proposed for two closely related sexually dimorphic species: Papilio phorcas, a nonmimetic species with two female forms, and Papilio dardanus, a female-limited polymorphic mimetic species. Their close relationship indicates that female-limited polymorphism could be a shared derived character of the two species. Here, we present a phylogenomic analysis of the dardanus group using 3964 nuclear loci and whole mitochondrial genomes, showing that they are not sister species and thus that the sexually dimorphic state has arisen independently in the two species. Nonhomology of the female polymorphism in both species is supported by population genetic analysis of engrailed, the presumed mimicry switch locus in P. dardanus. McDonald-Kreitman tests performed on SNPs in engrailed showed the signature of balancing selection in a polymorphic population of P. dardanus, but not in monomorphic populations, nor in the nonmimetic P. phorcas. Hence, the wing polymorphism does not balance polymorphisms in engrailed in P. phorcas. Equally, unlike in P. dardanus, none of the SNPs in P. phorcas engrailed were associated with either female morph. We conclude that sexual dimorphism due to female polymorphism evolved independently in both species from monomorphic, nonmimetic states. While sexual selection may drive male-female dimorphism in nonmimetic species, in mimetic Papilios, natural selection for protection from predators in females is an alternative route to sexual dimorphism.

Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre.

RATIONALE: The European Position Paper on Sinusitis (EPOS) guidelines provide composite criteria to evaluate chronic rhinosinusitis (CRS) control, taking into consideration the severity of patients' symptoms, aspect of nasal mucosa and medical intake as parameters of CRS control. OBJECTIVES: To study the degree of CRS control using novel EPOS control criteria at 3-5 years after a functional endoscopic sinus surgery (FESS) and correlate these data to symptoms scores. METHODS: Adult CRS patients (n = 560) who had undergone bilateral FESS for chronic inflammatory sinonasal disease 3-5 years prior to the study were included. Patients received a postal questionnaire asking for control items according to EPOS control criteria, visual analogue scale (VAS) scores for total and individual sinonasal symptoms, sinonasal outcome test (SNOT)-22 and Short Form (SF)-36 questionnaires. MEASUREMENTS AND MAIN RESULTS: About 19.5% of CRS patients were well controlled, with 36.8% of patients being partly controlled and 43.7% uncontrolled. The levels of control corresponded to mean total VAS, SNOT-22 and SF-36 scores. Subgroup analysis revealed that female gender, aspirin intolerance and revision FESS were associated with higher prevalence of uncontrolled CRS, whereas allergy, asthma and smoking status did not alter the percentage of patients in each category of control. In 81 patients attending the outpatient clinic, nasal endoscopy changed classification in only four patients (4.9%). CONCLUSIONS: Based on the novel EPOS control criteria, at least 40% of CRS patients are uncontrolled at 3-5 years after FESS. Therefore, better treatment strategies leading to higher disease control are warranted in CRS care.

Mitogenomics of 'Old World Acraea' butterflies reveals a highly divergent 'Bematistes'.

Afrotropical Acraeini butterflies provide a fascinating potential model system to contrast with the Neotropical Heliconiini, yet their phylogeny remains largely unexplored by molecular methods and their generic level nomenclature is still contentious. To test the potential of mitogenomes in a simultaneous analysis of the radiation, we sequenced the full mitochondrial genomes of 19 African species. Analyses show the potential of mitogenomic phylogeny reconstruction in this group. Inferred relationships are largely congruent with a previous multilocus study. We confirm a monophyletic Telchinia to include the Asiatic Pareba with a complicated paraphylum, traditional (sub)genus Acraea, toward the base. The results suggest that several proposed subgenera and some species groups within Telchinia are not monophyletic, while two other (sub)genera could possibly be combined. Telchinia was recovered without strong support as sister to the potentially interesting system of distasteful model butterflies known as Bematistes, a name that is suppressed in some treatments. Surprisingly, we find that this taxon has remarkably divergent mitogenomes and unexpected synapomorphic tRNA rearrangements. These gene order changes, combined with evidence for deviating dN/dS ratios and evidence for episodal diversifying selection, suggest that the ancestral Bematistes mitogenome has had a turbulent past. Our study adds genetic support for treating this clade as a distinct genus, while the alternative option, adopted by some authors, of Acraea being equivalent to Acraeini merely promotes redundancy. We pave the way for more detailed mitogenomic and multi-locus molecular analyses which can determine how many genera are needed (possibly at least six) to divide Acraeini into monophyletic groups that also facilitate communication about their biology.

Real-life study showing better control of allergic rhinitis by immunotherapy than regular pharmacotherapy.

BACKGROUND: Treatment for allergic rhinitis (AR) aims at reducing the burden of allergic inflammation, either by suppression of the nasal inflammation with pharmacotherapy or by inducing tolerance via immunotherapy (IT). At present, we lack information on the comparison between the degree of symptom control in AR patients treated with IT and those on pharmacotherapy. AIMS: An observational study was conducted evaluating the degree of symptom control, the total and individual nasal symptom severity and current medication use at 3 years after starting either pharmacotherapy or subcutaneous immunotherapy (SCIT) for AR. METHODS: A total number of 800 patients diagnosed with AR between October 2007 and February 2010 at the Ear, Nose and Throat Unit and Allergology Clinical Department of the University Hospitals of KU Leuven, Belgium, were included. Among these patients, 120 had been started on IT at the time of their initial visit, and 680 were prescribed guideline-based pharmacotherapy. In 2013, patients were sent a questionnaire asking for the current severity of nasal symptoms using a visual analogue scale (VAS) score, duration of nasal symptoms and presence or absence of abnormal sleep, impairment of daily activities, sport, leisure, impaired functioning at work/school, troublesome symptoms, and current medication use. A VAS score for total nasal symptoms (TNS) was used to distinguish between controlled and uncontrolled AR. RESULTS: An overall response rate of 54%. At 3 years after the initiation of the treatment, the IT group showed lower VAS scores for TNS than the pharmacotherapy group, with lower percentages of patients having a VAS score of equal or higher than 5. The IT group consisted of more patients with mild AR than the pharmacotherapy group despite the higher percentage of polysensitization at the onset of treatment in the IT group. 18% of the IT patients met the criteria of persistent AR whereas this was 51% amongst non-IT patients. Interestingly, 70% of IT patients did not use any medical treatment for AR anymore, whereas 61% of pharmacotherapy patients were still on medical treatment. CONCLUSIONS: This observational study demonstrates that IT is associated with higher control of AR, reduced symptom severity and reduced medication use at 3 years after the onset of treatment. Therefore, this real-life study reinforces the clinical value of immunotherapy in allergic rhinitis.

Draf III frontal sinusotomy: influence of patient characteristics on outcome.

Draf III frontal sinusotomy: influence of patient characteristics on outcome. OBJECTIVE: To identify positive and negative predictive outcome factors for the Draf III procedure based on the experience of a single center. METHODS: Seventy-two patients who underwent a Draf III procedure between 2005 and 2011 at the ENT department of University Hospitals Leuven were included. Patient demographics, history of frontal sinus surgery, clinical features, and computed tomographic evaluations were reviewed and analyzed for associations with symptom control and endoscopic outcome. RESULTS: The mean age was 48 years (16-82 years), and the male-to-female-ratio was 2:1. Major indications were chronic rhinosinusitis (with or without nasal polyps) and mucoceles. Supplementary frontal (recess) cells were found in the majority of patients. Osteoneogenesis was present in one out of four patients. At the end of follow-up (mean 35 months), the neo-ostium patency rate was 89%. Stenosis or closure of the neo-ostium was seen in 11% of patients, and 15% of patients required revision surgery. Subjective improvement was reported by 88%. CONCLUSION: The results of Draf III frontal sinusotomy were positive in the long term. Previous frontal sinus surgery, the presence of allergy or aspirin-exacerbated respiratory disease (AERD), asthma, smoking, and variants in frontal recess anatomy did not affect outcome. Osteoneogenesis and chronic mucosal inflammation could be controlled by creating a large drainage pathway.

Using second harmonic generation to predict patient outcome in solid tumors.

BACKGROUND: Over-treatment of estrogen receptor positive (ER+), lymph node-negative (LNN) breast cancer patients with chemotherapy is a pressing clinical problem that can be addressed by improving techniques to predict tumor metastatic potential. Here we demonstrate that analysis of second harmonic generation (SHG) emission direction in primary tumor biopsies can provide prognostic information about the metastatic outcome of ER+, LNN breast cancer, as well as stage 1 colorectal adenocarcinoma. METHODS: SHG is an optical signal produced by fibrillar collagen. The ratio of the forward-to-backward emitted SHG signals (F/B) is sensitive to changes in structure of individual collagen fibers. F/B from excised primary tumor tissue was measured in a retrospective study of LNN breast cancer patients who had received no adjuvant systemic therapy and related to metastasis-free survival (MFS) and overall survival (OS) rates. In addition, F/B was studied for its association with the length of progression-free survival (PFS) in a subgroup of ER+ patients who received tamoxifen as first-line treatment for recurrent disease, and for its relation with OS in stage I colorectal and stage 1 lung adenocarcinoma patients. RESULTS: In 125 ER+, but not in 96 ER-negative (ER-), LNN breast cancer patients an increased F/B was significantly associated with a favorable MFS and OS (log rank trend for MFS: p = 0.004 and for OS: p = 0.03). On the other hand, an increased F/B was associated with shorter PFS in 60 ER+ recurrent breast cancer patients treated with tamoxifen (log rank trend p = 0.02). In stage I colorectal adenocarcinoma, an increased F/B was significantly related to poor OS (log rank trend p = 0.03), however this relationship was not statistically significant in stage I lung adenocarcinoma. CONCLUSION: Within ER+, LNN breast cancer specimens the F/B can stratify patients based upon their potential for tumor aggressiveness. This offers a "matrix-focused" method to predict metastatic outcome that is complementary to genomic "cell-focused" methods. In combination, this and other methods may contribute to improved metastatic prediction, and hence may help to reduce patient over-treatment.

Interplay of robustness and plasticity of life-history traits drives ecotypic differentiation in thermally distinct habitats.

Phenotypic plasticity describes the ability of an individual to alter its phenotype in response to the environment and is potentially adaptive when dealing with environmental variation. However, robustness in the face of a changing environment may often be beneficial for traits that are tightly linked to fitness. We hypothesized that robustness of some traits may depend on specific patterns of plasticity within and among other traits. We used a reaction norm approach to study robustness and phenotypic plasticity of three life-history traits of the collembolan Orchesella cincta in environments with different thermal regimes. We measured adult mass, age at maturity and growth rate of males and females from heath and forest habitats at two temperatures (12 and 22 °C). We found evidence for ecotype-specific robustness of female adult mass to temperature, with a higher level of robustness in the heath ecotype. This robustness is facilitated by plastic adjustments of growth rate and age at maturity. Furthermore, female fecundity is strongly influenced by female adult mass, explaining the importance of realizing a high mass across temperatures for females. These findings indicate that different predicted outcomes of life-history theory can be combined within one species' ontogeny and that models describing life-history strategies should not assume that traits like growth rate are maximized under all conditions. On a methodological note, we report a systematic inflation of variation when standard deviations and correlation coefficients are calculated from family means as opposed to individual data within a family structure.

[Belgian register and reference centers for gestational trophoblastic diseases]. / REGISTRE BELGE ET CENTRES DE RÉFÉRENCE POUR LES MALADIES TROPHOBLASTIQUES GESTATIONNELLES.

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion.

Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.

Why barcode? High-throughput multiplex sequencing of mitochondrial genomes for molecular systematics.

Mitochondrial genome sequences are important markers for phylogenetics but taxon sampling remains sporadic because of the great effort and cost required to acquire full-length sequences. Here, we demonstrate a simple, cost-effective way to sequence the full complement of protein coding mitochondrial genes from pooled samples using the 454/Roche platform. Multiplexing was achieved without the need for expensive indexing tags ('barcodes'). The method was trialled with a set of long-range polymerase chain reaction (PCR) fragments from 30 species of Coleoptera (beetles) sequenced in a 1/16th sector of a sequencing plate. Long contigs were produced from the pooled sequences with sequencing depths ranging from ∼10 to 100× per contig. Species identity of individual contigs was established via three 'bait' sequences matching disparate parts of the mitochondrial genome obtained by conventional PCR and Sanger sequencing. This proved that assembly of contigs from the sequencing pool was correct. Our study produced sequences for 21 nearly complete and seven partial sets of protein coding mitochondrial genes. Combined with existing sequences for 25 taxa, an improved estimate of basal relationships in Coleoptera was obtained. The procedure could be employed routinely for mitochondrial genome sequencing at the species level, to provide improved species 'barcodes' that currently use the cox1 gene only.

Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours.

BACKGROUND: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem- and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms--OCT4A, OCT4B and OCT4B1--only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues. METHODS: This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts. RESULTS: Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4 protein is detected. Significant positive correlations between all isoforms of OCT3/4 were identified in both tumours with and without a known stem cell component, possibly indicating synergistic roles of these isoforms. CONCLUSION: This study confirms that OCT4A protein only appears in seminomatous GCTs, embryonal carcinoma and representative cell lines. Furthermore, it emphasises that in order to correctly assess the presence of functional OCT3/4, both isoform specific mRNA and protein detection are required.

Type III frontal sinusotomy: surgical technique, indications, outcomes, a multi-university retrospective study of 120 cases.

Draf in 1991. The procedure--which is also known as the modified endoscopic Lothrop procedure--aims to create the largest possible anteroposterior and lateral to lateral opening between both frontal sinuses and the nasal cavities. This requires the resection of the medial floor of both frontal sinuses, the intersinus septum and the superior nasal septum. The authors present a retrospective study including a cohort of 120 patients who underwent surgery in six Belgian university ENT departments. Mean follow-up was 24.6 months (range: 5-36 months). This paper describes the surgical procedure and reviews the indications, comorbidities, outcomes and complications of the type III frontal sinusotomy. Some correlations are also established with the data published in the worldwide literature. The authors conclude that the Draf III is a demanding procedure requiring considerable expertise in endoscopic sinus surgery. The procedure is effective with a success rate of 87.5%. Indeed, 12.5% of patients only experienced closure of the neoostium while 20% of all the patients had unchanged or worse symptomatology. The percentage of post-operative complications is 7.5%. All complications were managed successfully.

Daily practice management of septate uterus: reproductive outcome after septoplasty.

Background: Septate uterus is the most common uterine malformation found in women presenting poor reproductive history. Hysteroscopic septoplasty (HS) restores the uterine anatomy in a safe procedure. Objectives: The goal of our study is to determine the reproductive outcomes after HS of symptomatic septate uterus. Materials and Methods: In a retrospective observational single centre study the reproductive outcomes and complications after HS were evaluated in 31 women with symptomatic septate uterus. The patients were separated into two groups according to the symptoms - infertility or recurrent pregnancy loss (RPL). Main outcome measures: were the pregnancy and live birth rate and secondarily the complication rate. Furthermore, the results were analysed depending on the need of assisted reproductive techniques (ART). Results: The treatment has resulted in an overall pregnancy rate of 71% for both groups. The spontaneous pregnancy rate is 45% and 8 pregnancies resulted from ART (26%). The overall first live birth rate is 51.6%. A decrease has been noticed in the miscarriage rate from 95.24% to 24% (p<0.001) in the overall population. Conclusions: In patients with a symptomatic septate uterus hysteroscopic septoplasty is a safe and effective procedure. The favourable results pointing out the benefits of surgery on the reproductive outcomes as well as the relatively simple and safe technique of HS make the intervention attractive.

The role of stressful events in the development of behavioural and emotional problems from early childhood to late adolescence.

BACKGROUND: There is growing evidence on the importance of experiences of stressful events in the development of psychopathology. This study aimed to investigate the role of stressful events in the continuity of internalizing and externalizing problems, as well as the cross-influence of these problems from early childhood to late adolescence. METHOD: Data came from a general population sample of 396 children followed from the ages of 3 to 18 years. Parent-ratings of internalizing and externalizing problems at ages 3, 5, 10 and 18 years were used. Parents also reported on the presence of stressful events between the ages of 3 and 5 years, and 5 and 10 years. Adolescent reports on stressful events over the ages of 10-18 years were used. Structural equation models were used to disentangle/analyse the role of stressful events in the development of internalizing and externalizing problems. RESULTS: From the age of 3 years onwards externalizing symptoms predicted experiences of stressful events. In turn, these experiences predicted later externalizing problems. Stressful events also explained part of the continuity of internalizing problems from the age of 10 years onwards, but not during childhood. From childhood onwards, cross-influences from externalizing problems to subsequent internalizing problems were found to run through stressful events. Only in adolescence cross-influences from internalizing problems to externalizing problems were found, again via stressful events. CONCLUSIONS: From childhood onwards to late adolescence, stressful events play a significant role in both the continuity and the co-occurrence of externalizing and internalizing problems. Theoretical and methodological implications of these findings are discussed.

Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine.

OBJECTIVE: In a previous paper, we reported about the efficacy of the addition of lamotrigine to lithium in patients with bipolar depression. In the second phase of this study paroxetine was added to ongoing treatment in non-responders. METHOD: Bipolar depressed patients (n = 124) treated with lithium were randomized to addition of lamotrigine or placebo. In non-responders after 8 weeks, paroxetine 20 mg was added for another 8 weeks to ongoing treatment. RESULTS: After 8 weeks the improvement in patients treated with lamotrigine vs. patients treated with placebo was significant. After addition of paroxetine this difference disappeared as a result of greater further improvement in the non-responders to placebo. CONCLUSION: Addition of lamotrigine to lithium was found effective in bipolar depressed patients. Further addition of paroxetine in non-responders to lithium plus lamotrigine did not appear to provide additional benefit, while it appeared to do so in non-responders to lithium plus placebo.