Behavioural, developmental and psychological characteristics in children with germline PTEN mutations: a carer report study.

BACKGROUND: PTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in this study. METHODS: The parents of 20 children with PTEN mutations completed an online survey exploring adaptive behaviour, ASC-associated behaviours, anxiety, mood, hypermobility, behaviours that challenge, sensory experiences, quality of life and parental wellbeing. Published normative data and data from groups of individuals with other genetic neurodevelopmental conditions were used to contextualise findings. RESULTS: Overall levels of adaptive behaviour were below the 'typical' range, and no marked relative differences were noted between domains. Higher levels of ASC-related difficulties, including sensory experiences, were found in comparison with 'typically developing' children, with a possible peak in restrictive/repetitive behaviour; ASC and sensory processing atypicality also strongly correlated with reported joint hypermobility. A relative preservation of social motivation was noted. Anxiety levels were found to be elevated overall (and to relate to sensory processing and joint hypermobility), with the exception of social anxiety, which was comparable with normative data. Self-injurious behaviour was common. CONCLUSIONS: Results suggest a wide range of possible difficulties in children with PTEN mutations, including elevated anxiety. Despite elevated ASC phenomenology, social motivation may remain relatively strong. Firm conclusions are restricted by a small sample size and potential recruitment bias, and future research is required to further explore the relationships between such characteristics.

Diagnosis of Apis dorsata venom allergy: use of recombinant allergens of Apis mellifera and a passive basophil activation test.

BACKGROUND: Allergy to Apis dorsata (Giant Asian Honeybee) venom is the commonest insect allergy in Sri Lanka and South East Asia. However, laboratory diagnosis is difficult as the pure venom and diagnostic reagents are not commercially available. OBJECTIVE: This study assessed the use of four recombinant allergens of A. mellifera venom and the passive basophil activation test in the diagnosis of A. dorsata venom anaphylaxis. METHODS: Serum IgE levels to four recombinant allergens of A. mellifera, rApi m 1, 2, 5 and 10 were assessed and compared with serum IgE to the crude venom of A. mellifera or V. vulgaris by Phadia ImmunoCAP, in patients who developed anaphylaxis to A. dorsata stings. Basophil activation in response to venom of A. dorsata or V. affinis was assessed using a passive basophil activation test. Association of the severity of the reaction with basophil activation was compared. RESULTS: rApi m 1 and 10 combinedly had significant correlation (r = 0.722; p < 0.001) with the crude venom of A. mellifera (Western honeybee) and a higher positivity rate of 90% (27/30). Whereas, IgE reactivity to rApi m 2 or 5 had significant correlation (p = 0.02 and p = 0.005 respectively) with V. vulgaris crude venom. All 30 (100%) were positive to A. dorsata venom in passive BAT; 70% (21/30) had over 80% activation, 96.7% (29/30) had over 60% activation and 100% had over 50% activation. Percentage activation of basophils in patients who had mild or moderate reactions (n = 20) was significantly low (p = 0.02) from that of patients who had severe reactions (n = 10). CONCLUSIONS: rApi m 1 and 10 when combined was sensitive for the diagnosis of A. dorsata allergy. This combination had the lowest cross-reactivity rate with Vespula vulgaris. The passive BAT is highly sensitive in A. dorsata allergy. The basophil reactivity was significantly higher in severe anaphylaxis compared to mild/moderate anaphylaxis. This finding should be further explored in further studies.

Performance of a targeted cell-free DNA prenatal test for 22q11.2 deletion in a large clinical cohort.

OBJECTIVE: 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell-free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples. METHODS: In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in-situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0-Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype. RESULTS: The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2-80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5-100%)). CONCLUSIONS: The results of this large-scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0-0.5%) false-positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false-positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Lactobacillus paracasei DTA81, a cholesterol-lowering strain having immunomodulatory activity, reveals gut microbiota regulation capability in BALB/c mice receiving high-fat diet.

AIMS: In-vitro/In-vivo evaluation of cholesterol-lowering probiotic strain Lactobacillus paracasei DTA81 and the possible connection with the gut microbiota modulation. METHODS AND RESULTS: In the present study, strain DTA81 has been evaluated for the possible influence on blood lipid and glucose concentrations, modulation of the immune system, gastrointestinal survivability and modulation of gut microbiota in BALB/c mice receiving a high-fat diet. After 6 weeks of treatment, a significant reduction of total cholesterol and fasting blood sugar (FBS) among animals treated with L. paracasei DTA81 has been recorded. Comparison of colon tissue levels of different cytokines revealed a significant reduction of the inflammatory cytokine interleukin-6. The comparison of gut microbiota using the 16S rRNA approach indicated that the treatment with L. paracasei DTA81 significantly increased the taxa Bacteroidetes and Coprococcus. Moreover, the genome of DTA81 was sequenced for the in-silico assessment, and the analysis indicated the presence of cholesterol assimilation-related genes as well as the absence of negative traits such as transmissible antibiotic resistance genes, plasmids and prophage regions. CONCLUSION: The outcome of this study revealed the in-vitro and in-vivo properties of L. paracasei DTA81 and the possible mechanism between consumption of this strain, the abundance of Bacteriodetes/Coprococcus taxa, immunomodulatory activity and the subsequent reduction of cholesterol/FBS in BALB/c mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus paracasei DTA81 as a non-pharmacological potential probiotic supplement can influence metabolic homeostasis in individuals, particularly those adopting high-fat diets, and it can contribute to reduce coronary heart disease.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). CONCLUSIONS: Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The effect of school intervention programs on the body mass index of adolescents: a systematic review with meta-analysis.

Effective obesity interventions in adolescent populations have been identified as an immediate priority action to stem the increasing prevalence of adult obesity. The purpose of this meta-analysis was to make a quantitative analysis of the impact of school-based interventions on body mass index during adolescence. Studies were retrieved from PubMed, Scopus, Science Direct and Web of Science databases. Results were pooled using a random-effects model with 95% confidence interval considered statistically significant. Of the 18 798 possible relevant articles identified, 12 articles were included in this meta-analysis. The global result showed a low magnitude effect, though it was statistically significant (N = 14 428), global e.s. = -0.055, P = 0.004 (95% CI = -0.092, -0.017). Heterogeneity was low among the studies (I2 = 9.017%). The funnel plot showed no evidence of publication bias. The rank-correlation test of Begg (P = 0.45641) and Egger's regression (P = 0.19459) confirmed the absence of bias. This meta-analysis reported a significant effect favoring the interventions; however, future research are needed since the reported the evidence was of low magnitude, with the studies following a substantial range of approaches and mostly had a modest methodological quality.

Virulence factors and antimicrobial resistance of Staphylococcus aureus isolated from the production process of Minas artisanal cheese from the region of Campo das Vertentes, Brazil.

Staphylococcus aureus is one of the main pathogens found in cheeses produced with raw milk, including Minas artisanal cheese from Brazil. However, information about S. aureus isolated from artisanal cheeses and its sources of production in small-scale dairies is very limited. We aimed to characterize the virulence factors of S. aureus isolated from raw milk, endogenous starter culture, Minas artisanal cheese, and cheese handlers from the region of Campo das Vertentes, Minas Gerais, Brazil. We identified the staphylococcal isolates by MALDI-TOF mass spectrometry. We evaluated biofilm production on Congo red agar and polystyrene plates. We used PCR to detect icaA, icaB, icaC, sea, seb, sec, sed, see, tsst-1, agr, and mecA. We evaluated the expression of staphylococcal toxin genes in PCR-positive staphylococcal isolates using quantitative reverse-transcription PCR, and we evaluated the production of these toxins and their hemolytic activity in vitro. We also evaluated the antimicrobial resistance profile of the staphylococcal isolates. For statistical analysis, we used cluster analysis, χ2 tests, and correspondence tests. We analyzed 76 staphylococcal isolates. According to PCR, 18.42, 18.42, 2.63, and 77.63% were positive for sea, tsst-1, sec, and agr, respectively. We found low expression of staphylococcal toxin genes according to quantitative reverse-transcription PCR, and only 2 staphylococcal isolates produced toxic shock syndrome toxins. A total of 43 staphylococcal isolates (56.58%) had hemolytic activity; 53 were biofilm-forming on Congo red agar (69.73%), and 62 on polystyrene plates (81.58%). None of the staphylococcal isolates expressed the mecA gene, and none presented a multi-drug resistance pattern. The highest resistance was observed for penicillin G (67.11%) in 51 isolates and for tetracycline (27.63%) in 21 isolates. The staphylococcal isolates we evaluated had toxigenic potential, with a higher prevalence of sea and tsst-1. Biofilm production was the main virulence factor of the studied bacteria. Six clusters were formed whose distribution frequencies differed for hemolytic activity, biofilm formation (qualitative and quantitative analyses), and resistance to penicillin, tetracycline, and erythromycin. These findings emphasize the need for effective measures to prevent staphylococcal food poisoning by limiting S. aureus growth and enterotoxin formation throughout the food production chain and the final product.

Spatiotemporal distribution of a non-haematophagous bat community and rabies virus circulation: a proposal for urban rabies surveillance in Brazil.

In Brazil, rabies surveillance is based on monitoring domestic and wild animals, although the most prevalent lineage of the rabies virus (RABV) currently diagnosed in Brazil is associated with bats, particularly non-haematophagous bats. Disease control is based on the mass vaccination of dogs and cats. We used data collected by the passive surveillance system of the city of Campinas from 2011 to 2015, to describe the temporal and geographic distributions of the bat specimens and RABV and discuss the current rabies surveillance with the advent of the declaration of canine and feline rabies-free areas in Brazil. We described the species, locations and health statuses of the collected bat specimens. Moreover, all samples were submitted for RABV diagnosis. Then, we performed a time series decomposition for each bat family. Additionally, we determined the spatiotemporal relative risk for RABV infection using the ratio of the kernel-smoothed estimates of spatiotemporal densities of RABV-positive and RABV-negative bats. From the 2537 bat specimens, the most numerous family was Molossidae (72%), followed by Vespertilionidae (14%) and Phyllostomidae (13%). The bat families behaved differently in terms of seasonal and spatial patterns. The distribution of bats varied geographically in the urban environment, with Molossidae and Phyllostomidae being observed downtown and Vespertilionidae being observed in peripheral zones. Concurrently, a significant relative risk of RABV infection was observed downtown for Vespertilionidae and in peripheral zones for Molossidae. No RABV-positive sample clusters were observed. As a result of the official declaration of RABV-free areas in southern Brazil, mass dog and cat vaccinations are expected to halt in the near future. This stoppage would make most dog and cat populations susceptible to other RABV lineages, such as those maintained by non-haematophagous bats. In this scenario, all information available on bats and RABV distribution in urban areas is essential. Currently, few studies have been conducted. Some local health authorities, such as that in Campinas, are spontaneously basing their surveillance efforts on bat rabies, which is the alternative in reality scenario of increased susceptibility to bat-associated RABV that is developing in Brazil.

Atypical Motor Neuron Disease variants: Still a diagnostic challenge in Neurology.

Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

Phytophthora parasitica Effector PpRxLR2 Suppresses Nicotiana benthamiana Immunity.

Phytophthora species secrete several classes of effector proteins during interaction with their hosts. These proteins can have multiple functions including modulation of host physiology and immunity. The RxLR effectors have the ability to enter plant cells using the plant machinery. Some of these effectors have been characterized as immunity suppressors; however, very little is known about their functions in the interaction between Phytophthora parasitica and its hosts. Using a bioinformatics pipeline, we have identified 172 candidate RxLR effectors (CREs) in the isolate IAC 01_95 of P. parasitica. Of these 172 CREs, 93 were found to be also present in eight other genomes of P. parasitica, isolated from different hosts and continents. After transcriptomics and gene expression analysis, we have found five CREs to be up-regulated in in-vitro and in-planta samples. Subsequently, we selected three CREs for functional characterization in the model plant Nicotiana benthamiana. We show that PpRxLR2 is able to completely suppress INF-1-induced cell death, whereas PpRxLR3 and PpRxLR5 moderately suppressed N. benthamiana immunity in a less-extensive manner. Moreover, we confirmed the effector-triggered susceptibility activity of these proteins after transient transformation and infection of N. benthamiana plants. All three CREs enhanced virulence of P. parasitica during the interaction with N. benthamiana. These effectors, in particular PpRxLR2, can be targeted for the development of biotechnology-based control strategies of P. parasitica diseases.

Systematic review of measurement tools to assess surgeons' intraoperative cognitive workload.

BACKGROUND: Surgeons in the operating theatre deal constantly with high-demand tasks that require simultaneous processing of a large amount of information. In certain situations, high cognitive load occurs, which may impact negatively on a surgeon's performance. This systematic review aims to provide a comprehensive understanding of the different methods used to assess surgeons' cognitive load, and a critique of the reliability and validity of current assessment metrics. METHODS: A search strategy encompassing MEDLINE, Embase, Web of Science, PsycINFO, ACM Digital Library, IEEE Xplore, PROSPERO and the Cochrane database was developed to identify peer-reviewed articles published from inception to November 2016. Quality was assessed by using the Medical Education Research Study Quality Instrument (MERSQI). A summary table was created to describe study design, setting, specialty, participants, cognitive load measures and MERSQI score. RESULTS: Of 391 articles retrieved, 84 met the inclusion criteria, totalling 2053 unique participants. Most studies were carried out in a simulated setting (59 studies, 70 per cent). Sixty studies (71 per cent) used self-reporting methods, of which the NASA Task Load Index (NASA-TLX) was the most commonly applied tool (44 studies, 52 per cent). Heart rate variability analysis was the most used real-time method (11 studies, 13 per cent). CONCLUSION: Self-report instruments are valuable when the aim is to assess the overall cognitive load in different surgical procedures and assess learning curves within competence-based surgical education. When the aim is to assess cognitive load related to specific operative stages, real-time tools should be used, as they allow capture of cognitive load fluctuation. A combination of both subjective and objective methods might provide optimal measurement of surgeons' cognition.

The roles of mucus-forming mucins, peritrophins and peritrophins with mucin domains in the insect midgut.

Most insects have a gut lined with a peritrophic membrane (PM) consisting of chitin and proteins, mainly peritrophins that have chitin-binding domains. The PM is proposed to originate from mucus-forming mucins (Mf-mucins), which acquired a chitin-binding domain that interlocked with chitin, replacing mucus in function. We evaluated the expression of Mf-mucins and peritrophins by RNA-sequencing (RNA-seq) throughout the midgut of four distantly related insects. Mf-mucins were identified as proteins with high o-glycosylation and a series of uninterrupted Pro/Thr/Ser residues. The results demonstrate that the mucus layer is widespread in insects, and suggest that insect Mf-mucins are derived from those found in other animals by the loss of the cysteine knot and von Willebrand domains. The data also support a role of Mf-mucins in protecting the middle midgut of Musca domestica against acidic buffers. Mf-mucins may also produce a jelly-like material associated with the PM that immobilizes digestive enzymes in Spodoptera frugiperda. Peritrophins with a domain similar to Mf-mucins may be close to the ancestor of peritrophins. Expression data of peritrophins and chitin synthase genes throughout the midgut of M. domestica, S. frugiperda and Tenebrio molitor indicated that peritrophins were incorporated along the PM, according to their preferential sites of formation. Finally, the data support the view that mucus has functions distinct from the PM.

Diarrhoeagenic Escherichia coli and Escherichia albertii in Brazil: pathotypes and serotypes over a 6-year period of surveillance.

Diarrhoeagenic Escherichia coli (DEC) is a leading cause of infectious diarrhoea worldwide. In recent years, Escherichia albertii has also been implicated as a cause of human enteric diseases. This study describes the occurrence of E. coli pathotypes and serotypes associated with enteric illness and haemolytic uremic syndrome (HUS) isolated in Brazil from 2011 to 2016. Pathotypes isolated included enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and Shiga toxin-producing E. coli (STEC). PCR of stool enrichments for DEC pathotypes was employed, and E. albertii was also sought. O:H serotyping was performed on all DEC isolates. A total of 683 DEC and 10 E. albertii strains were isolated from 5047 clinical samples. The frequencies of DEC pathotypes were 52.6% (359/683) for EPEC, 32.5% for EAEC, 6.3% for ETEC, 4.4% for EIEC and 4.2% for STEC. DEC strains occurred in patients from 3 months to 96 years old, but EPEC, EAEC and STEC were most prevalent among children. Both typical and atypical isolates of EPEC and EAEC were recovered and presented great serotype heterogeneity. HUS cases were only associated with STEC serotype O157:H7. Two E. albertii isolates belonged to serogroup O113 and one had the stx2f gene. The higher prevalence of atypical EPEC in relation to EAEC in community-acquired diarrhoea in Brazil suggests a shift in the trend of DEC pathotypes circulation as previously EAEC predominated. This is the first report of E. albertii isolation from active surveillance. These results highlight the need of continuing DEC and E. albertii surveillance, as a mean to detect changes in the pattern of pathotypes and serotypes circulation and provide useful information for intervention and control strategies.

Comparison of management regimens following ultrasound diagnosis of nontubal ectopic pregnancies: a retrospective cohort study.

OBJECTIVE: To review management options for nontubal ectopic pregnancies. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital in Melbourne, Australia. POPULATION: A total of 100 nontubal pregnancies: 1 abdominal, 32 caesarean scar, 14 cervical, 41 cornual-interstitial, 12 ovarian. METHODS: Cases were classified according to ectopic site. Management categories were medical, surgical, combination or expectant. Use of minimally invasive approaches (ultrasound-guided intra-sac injections or selective surgical techniques) was identified. Primary management was considered to be successful if no further unplanned interventions were required. MAIN OUTCOME MEASURES: Success of primary management and frequency of unplanned interventions. RESULTS: A high rate of success (82%) was demonstrated for all management regimens, with minimal morbidity and no deaths occurring. A high success rate was shown when the primary management regimen was systemic methotrexate or ultrasound-guided intra-sac injection (88%). The success rate for primary surgical management was 57%. High success rates were reported for both primary management with ultrasound-guided injections or in combination with systemic methotrexate (94%) and for primary management with systemic methotrexate alone (81%). Seventy-five per cent of women managed with minimally invasive surgical approaches avoided the need for more extensive surgery, but required longer follow up and additional interventions. CONCLUSION: Minimally invasive approaches were found to be safe and effective treatment for women desiring to conserve fertility. Ultrasound-guided intra-sac injection and laparoscopic ectopic removal procedures aimed at preserving reproductive organs should be included as minimally invasive primary management tools in addition to the well-recognised option of systemic methotrexate. TWEETABLE ABSTRACT: Nontubal ectopics: minimally invasive procedures a safe alternative to surgery in selected cases.

17α-Ethinylestradiol and 17ß-estradiol removal from a secondary urban wastewater using an RBC treatment system.

The presence of micropollutants that include endocrine-disrupting compounds (EDC) in aquatic environments is currently one of the most relevant aspects of water quality due to their adverse effects on aquatic organisms and human health. From the several categories of EDC, 17ß-estradiol (E2) is a natural hormone, which is prevalent in vertebrates, associated with the female reproductive system and maintenance of the sexual characters. 17α-Ethinylestradiol (EE2) is a synthetic hormone produced from the natural hormone E2 and is an essential component of oral contraceptives. These compounds are susceptible to bioconcentration and have high potential to bioaccumulation. Wastewater treatment plants are the main point source of E2 and EE2 into aquatic environments, but conventional wastewater treatment systems are not specifically designed for steroid removal. To overcome this problem, biological tertiary treatment may be a solution for the removal of emergent pollutants such as E2 and EE2. The main purpose of the present study is to provide a solution based on the optimization of a rotating biological contactor system to remove estrogens, specifically E2 and EE2, and to quantify their removal efficiency on different matrices, namely real wastewater and different synthetic wastewaters. All assays presented viable removal efficiencies for compound E2 with values always above 50%; real wastewater yielded the highest removal efficiencies. EE2 removal had better removal efficiencies with synthetic wastewater as feed solution, with removals above 15%, whereas the removal efficiency with real wastewater was inexistent.

Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

A Single Bout of Arm-crank Exercise Promotes Positive Emotions and Post-Exercise Hypotension in Patients with Symptomatic Peripheral Artery Disease.

OBJECTIVE/BACKGROUND: The objective was to analyze the acute effects of a single bout of arm cranking exercise on affective and cardiovascular parameters in patients with symptomatic peripheral artery disease (PAD). METHODS: This was a prospective, controlled, crossover study. Eleven men with symptomatic PAD underwent two experimental sessions in a random order: control or arm crank exercise (15 × 2 minutes bouts of arm crank exercise interrupted by 2 minutes rest intervals). During exercise, ratings of perceived exertion (Borg scale) and affective responses (pleasure/displeasure) were obtained at the first, fifth, tenth, and fifteenth bouts. Before and after the experimental sessions, cardiovascular parameters (blood pressure and heart rate) were obtained. Data were analysed by a two-way repeated measure analysis of variance with significance achieved at p < .05. RESULTS: During the arm crank exercise, patients reported positive feelings of pleasure. During exercise, heart rate (HR) remained within 80-90% of peak HR. Additionally, patients performed arm crank exercise with moderate levels of perceived exertion (Borg rating of 11-13) and with pleasant affective scores (Feeling Scale of +1 to +5). Blood pressure (systolic, diastolic, and mean) increase was lower after arm crank exercise than for control (greatest net effect: -15 ± 11 mmHg [p < .001]; -9 ± 5 mmHg [p < .001]; -9 ± 6 mmHg [p < .001], respectively), while HR increased (greatest net effect: +9 ± 6 beats per minute; p < .001). CONCLUSION: A single bout of arm crank exercise promotes pleasurable feelings while reducing blood pressure in patients with symptomatic PAD.

Increased illness burden in women with comorbid bipolar and premenstrual dysphoric disorder: data from 1 099 women from STEP-BD study.

BACKGROUND: The impact of comorbid premenstrual dysphoric disorder (PMDD) in women with bipolar disorder (BD) is largely unknown. AIMS: We compared illness characteristics and female-specific mental health problems between women with BD with and without PMDD. MATERIALS & METHODS: A total of 1 099 women with BD who participated in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were studied. Psychiatric diagnoses and illness characteristics were assessed using the Mini International Neuropsychiatric Interview. Female-specific mental health was assessed using a self-report questionnaire developed for STEP-BD. PMDD diagnosis was based on DSM-5 criteria. RESULTS: Women with comorbid BD and PMDD had an earlier onset of bipolar illness (P < 0.001) and higher rates of rapid cycling (P = 0.039), and increased number of past-year hypo/manic (P = 0.003), and lifetime/past-year depressive episodes (P < 0.05). Comorbid PMDD was also associated with higher proportion of panic disorder, post-traumatic stress disorder, generalized anxiety disorder, bulimia nervosa, substance abuse, and adult attention deficit disorder (all P < 0.05). There was a closer gap between BD onset and age of menarche in women with comorbid PMDD (P = 0.003). Women with comorbid PMDD reported more severe mood symptoms during the perinatal period and while taking oral contraceptives (P < 0.001). DISCUSSION: The results from this study is consistent with research suggesting that sensitivity to endogenous hormones may impact the onset and the clinical course of BD. CONCLUSIONS: The comorbidity between PMDD and BD is associated with worse clinical outcomes and increased illness burden.

Self-initiated changes in physical activity levels improve cardiometabolic profiles: A longitudinal follow-up study.

BACKGROUND AND AIMS: While studies have described the importance of higher physical activity levels (PAL) in weight loss, the impact of self-initiated PAL on health status warrants further study. We aimed to prospectively examine the effects of self-initiated longitudinal PAL changes on body mass index (BMI) and cardiometabolic parameters in normal weight, overweight and obese adults. METHODS AND RESULTS: We included 4840 adults (mean age 41.6 ± 7.9 years, 79% male) undergoing routine health screening examinations. Self-reported PAL, height, weight, blood pressure and blood samples were collected at baseline and after a mean (95% confidence interval) follow up of 536 (531-541) days. Subjects were stratified according to BMI [39.8% normal weight (<25 kg/m2), 45.1% overweight (25.0-29.9 kg/m2), and 19.1% obese (≥30 kg/m2)]. In normal weight individuals, BMI increased from baseline to follow-up, irrespective of PAL changes. On the other hand, overweight and obese individuals that increased PAL experienced a decrease in BMI by -0.9% and -3.1%, respectively (p < 0.05). Overweight and obese individuals that increased PAL also experienced a decrease in -5.8% -4.6% in non-HDL concentrations from baseline to follow-up (p < 0.05). Finally, in overweight individuals, LDL cholesterol concentrations decreased from baseline to follow-up, irrespective of PAL changes whereas in obese individuals, a maintenance or increased PAL were associated with a decrease in -4.7% and -6.1% (p < 0.05), respectively. CONCLUSIONS: In a large cohort of screening patients, longitudinal self-initiated PAL is associated with improved BMI and cardiometabolic profile in overweight and obese individuals.

Comparison among three different serological methods for the detection of equine influenza virus infection.

The equine influenza virus (EIV) H3N8 subtype is responsible for all EIV outbreaks worldwide while the H7N7 subtype is less pathogenic and is considered extinct as it has not been confirmed in outbreaks since 1980. Although EIV is enzootic in Brazil, few reports describe the actual EIV antibody status in the country. The aims of this study were: - to evaluate the efficiency of different serum treatments described by the World Organisation for Animal Health (OIE) and the World Health Organization (WHO) to remove non-specific haemagglutination inhibitors for the haemagglutination inhibition (HI) assay for EIV - to evaluate the presence of EIV antibodies by HI, enzyme-linked immunosorbent assay and agar gel immunodiffusion in 83 non-vaccinated equines from São Paulo State - to evaluate a strategy to better analyse equine sera for EIV antibodies. Although there was no statistical difference among treatments, receptor-destroying enzyme treatment followed by chicken erythrocyte adsorption showed more consistent results, which corroborate the OIE and WHO recommendation to use this treatment preferentially. The HI results suggest equine H3N8 virus circulation among the animals tested from São Paulo State. The algorithm suggested here could be used to guide antibody detection against equine influenza virus in equines, improving the test specificity by aiming to avoid false positive results.

Tous les foyers de grippe équine dans le monde sont dus au sous-type H3N8 du virus. Le sous-type H7N7, moins pathogène, est considéré comme éteint, sa présence n'ayant été confirmée dans aucun des foyers enregistrés depuis 1980. Au Brésil, la grippe équine est enzootique mais la prévalence d'anticorps dans le pays est peu documentée. La présente étude avait trois objectifs : ­ évaluer l'efficacité de plusieurs traitements de sérums décrits par l'Organisation mondiale de la santé animale (OIE) et l'Organisation mondiale de la santé (OMS) sur la suppression des inhibiteurs d'hémagglutination non spécifiques, afin de pouvoir utiliser l'épreuve d'inhibition de l'hémagglutination pour la détection de la grippe équine, ­ évaluer la présence d'anticorps dirigés contre la grippe équine chez 83 chevaux non vaccinés de l'état de São Paulo en utilisant l'inhibition de l'hémagglutination, l'épreuve immuno-enzymatique (ELISA) et l'épreuve d'immunodiffusion en gélose (IDG) ; ­ évaluer une stratégie visant à améliorer les techniques sérologiques de détection des anticorps dirigés contre la grippe équine. S'il n'y a pas eu de différence statistique significative entre les traitements, celui faisant appel à l'enzyme de destruction du récepteur suivi d'une adsorption sur érythrocytes de poule a permis d'obtenir les résultats les plus cohérents, ce qui corrobore les recommandations de l'OIE et de l'OMS en faveur de ce traitement. Les résultats obtenus au moyen de l'inhibition de l'hémagglutination indiquent que le virus H3N8 est présent parmi les animaux testés de l'état de São Paulo. L'algorithme présenté par les auteurs pourrait servir de modèle pour détecter la présence d'anticorps dirigés contre le virus de la grippe équine chez les chevaux : en effet, il permet d'éviter les résultats faussement positifs, ce qui améliore la spécificité du test utilisé.

El subtipo H3N8 del virus de la gripe equina (VGE) es el agente etiológico de todos los brotes que se producen en el mundo, mientras que el subtipo H7N7, menos patogénico, se da por extinto, en la medida en que desde 1980 no se ha confirmado su intervención en brote alguno. Aunque en el Brasil el VGE es enzoótico, existen pocos trabajos que den cuenta de la situación real del país en cuanto a la presencia de anticuerpos contra el virus. Los autores describen un estudio que perseguía los siguientes objetivos: ­ evaluar la eficacia de distintos tratamientos séricos descritos por la Organización Mundial de Sanidad Animal (OIE) y la Organización Mundial de la Salud (OMS) para eliminar los inhibidores inespecíficos de la hemaglutinación con objeto de aplicar la técnica de inhibición de la hemaglutinación a la detección del VGE; ­ evaluar la presencia de anticuerpos contra el VGE por inhibición de la hemaglutinación, ensayo inmunoenzimático (ELISA) e inmunodifusión en gel de agar en 83 ejemplares equinos no vacunados del estado de São Paulo; ­ evaluar una estrategia encaminada a analizar más eficazmente sueros equinos para detectar en ellos anticuerpos anti-VGE. Aunque no se observaron diferencias estadísticamente significativas entre los tratamientos, el uso de enzimas destructores de receptores seguido de la técnica de adsorción de eritrocitos de pollo arrojó resultados más coherentes, cosa que avala la recomendación de la OIE y la OMS de privilegiar este tratamiento. Los resultados obtenidos por inhibición de la hemaglutinación parecen indicar que el virus H3N8 equino circula entre los animales analizados del estado de São Paulo. El algoritmo aquí propuesto podría servir de guía para detectar en equinos la presencia de anticuerpos contra el VGE. Puesto que apunta a evitar falsos positivos, su aplicación mejoraría la especificidad de la prueba.