Do we trust scientific evidence? A multicentre retrospective analysis of first IVF/ICSI cycles before and after the OPTIMIST trial.

STUDY QUESTION: Has the practice of individualizing the recombinant-FSH starting dose been superseded after the largest randomized controlled trial (RCT) in assisted reproduction technology (ART), the OPTIMIST trial? SUMMARY ANSWER: The OPTIMIST trial has influenced our ART daily practice to a limited degree, but adherence is still generally poor. WHAT IS KNOWN ALREADY: Although the 'one size fits all' approach has been discouraged for decades by most authors, the OPTIMIST study group demonstrated in a large prospective RCT that, in general, dosage individualization does not improve the prospects for live birth, although it may decrease ovarian hyperstimulation syndrome (OHSS) risk in expected high responders. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles from 1st January 2017 to 31st December 2018, before and after the OPTIMIST publication on November 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two thousand six hundred and seventy-seven patients, between 18 and 42 years old, undergoing their first IVF-ICSI cycle in seven Italian fertility centres, were included. Patients were allocated to three groups according to their ovarian reserve markers: predicted poor ovarian responders (POR), predicted normo-responders (NR) and expected hyper-responders (HRs). MAIN RESULTS AND THE ROLE OF CHANCE: Between 2017 and 2018, there was an overall increase in prescription of the standard 150 IU dose proposed by the OPTIMIST trial and a reduction in the use of a starting dose >300 IU. After subgroup analysis, the decrease in doses >300 IU remained significant in the POR and NR sub-groups. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study. Physicians need time to adapt to new scientific evidence and a comparison between 2017 and 2019 may have found a greater impact of the Optimist trial, although other changes over the longer time span might have increased confounding. We cannot be sure that the observed changes can be attributed to knowledge of the OPTIMIST trial. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians may be slow to adopt recommendations based on RCTs; more attention should be given to how these are disseminated and promoted. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. E.P. reports grants and personal fees from MSD, grants from Ferring, from IBSA, grants and personal fees from Merck, grants from TEVA, grants from Gedeon Richter, outside the submitted work. E.S. reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, outside the submitted work. All other authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Healthy Eating for Life English as a second language curriculum: applying the RE-AIM framework to evaluate a nutrition education intervention targeting cancer risk reduction.

Medically underserved US immigrants are at an increased risk for death from preventable or curable cancers due to economic, cultural, and/or linguistic barriers to medical care. The purpose of this study was to describe the evaluation of the pilot study of the Healthy Eating for Life (HE4L) English as a second language curriculum. The Reach, Effectiveness Adoption, Implementation, Maintenance (RE-AIM) model was used to design a mixed-methods approach to the evaluation of the HE4L curriculum. Successful implementation was dependent upon enthusiastic teacher and manager support of the curriculum, teachers' ability to flexibly apply the curriculum to meet student needs, and researcher provision of curriculum workbooks. HE4L can be implemented successfully in various adult education settings to teach healthy eating behaviors and English language principles. Scale-up of HE4L may depend on the development of an online version of the curriculum to avoid the costs associated with printing and distributing curriculum materials.

Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

Interconnected microbiomes and resistomes in low-income human habitats.

Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities. We found that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but identified key resistance genes that cross habitat boundaries and determined their association with mobile genetic elements. We also assessed the effectiveness of widely used excreta management strategies in reducing faecal bacteria and resistance genes in these settings representative of low- and middle-income countries. Our results lay the foundation for quantitative risk assessment and surveillance of resistance gene dissemination across interconnected habitats in settings representing over two-thirds of the world's population.

Diagnostic role of (18)F-FDG-PET or PET/CT in salivary gland tumors: A systematic review.

Salivary gland tumors are rare neoplasms that have not been extensively studied with (18)F-FDG-PET- or PET/CT up to now. This review aims to evaluate the diagnostic performance of PET in this particular setting, analyzing the available literature. A comprehensive literature search in the PubMed/MEDLINE, Embase and Scopus databases was performed including articles up to November 2014, resulting in the selection of 22 articles. The studies selected suggest that: (1) PET is not useful in discriminating benign from malignant SGTs because of the overlap of uptake in both conditions; (2) PET not only is complementary to conventional imaging techniques for the staging and restaging but in some cases could also be superior to them; (3) PET may often have a highly positive impact on clinical decision making. Despite many limitations affecting the analysis, PET seems to be useful in SGTs. However, more extensive studies and cost-effectiveness analyses are desirable to determine its correct position in the diagnostic flow chart.

Complete Genome Sequences of Two Helicobacter pylori Strains from a Canadian Arctic Aboriginal Community.

We report here the complete genome sequences of two Amerind Helicobacter pylori strains from Aklavik, Northwest Territories, Canada. One strain contains extra iron-cofactored urease genes and ~140 rearrangements in its chromosome relative to other described strains (typically differing from one another by <10 rearrangements), suggesting that it represents a novel lineage of H. pylori.

Genome Sequences of Three hpAfrica2 Strains of Helicobacter pylori.

We present the genome sequences of three hpAfrica2 strains of Helicobacter pylori, which are postulated to have evolved in isolation for many millennia in people of San ethnicity. Although previously considered to be ancestral to Helicobacter acinonychis, the hpAfrica2 strains differ markedly from H. acinonychis in their gene arrangement. These data provide new insights into Helicobacter evolution.

Another patient with 12q13 microduplication.

Interstitial duplication of the long arm of chromosome 12 is a rare cytogenetic condition. While several reports describe distal 12q duplication, only one case report of homogeneous, non-mosaic interstitial 12q13 duplication has been documented to date. The authors of that observation proposed that the associated phenotype represented a phenocopy of Wolf-Hirschhorn syndrome [Dallapiccola et al., 2009]. Only a few other recorded patients with deletion 12q13 → 12q21 involved mosaicism. We describe a new patient with homogeneous 12q13 duplication in a 6-year-old girl who, in early infancy, presented with dysmorphic features suggesting Wolf-Hirschhorn syndrome. What is potentially significant about this patient is that her facial phenotype evolved with age, suggesting a different gestalt in older patients.

Needs and challenges of daily life for people with Down syndrome residing in the city of Rome, Italy.

BACKGROUND: Population-based surveys on the quality of life of people with Down syndrome (DS) are difficult to perform because of ethical and legal policies regarding privacy and confidential information, but they are essential for service planning. Little is known about the sample size and variability of quality of life of people with DS living in the city of Rome, which has a population of 2.7 million inhabitants. The aim of the present study is to explore the needs and challenges in health, social integration and daily life, of people with DS living in Rome. METHODOLOGY: A cross-sectional, census-based survey was conducted in 2006. All family doctors (3016 in total) of the National Health Service were involved by the Statistical Bureau of the Municipality of Rome. As per the census, every resident citizen is registered with a family doctor and every person with disabilities is coded. Associations for Down Syndrome encouraged their members to participate in the research. Questionnaires were completed by families of people with DS, in accordance with privacy laws. FINDINGS: An initial survey, conducted via a letter and a telephone contact with family doctors, identified 884 people with DS residing in the city of Rome. Data on the medical and social conditions of 518 people with DS, ranging in age from 0 to 64 years, were collected. Some 88% of these were living with their original family; 82.1% had one or more siblings, and 19.5% had lost one or both parents. A full 100% of children with DS were enrolled in the public school system. This ensures that they are fully occupied and entirely integrated in society. After secondary school there is a lack of opportunities. Thus, only 10% of adults were working with a regular contract. A mere 42.2% of people with DS aged 25-30 were involved in some form of regular activity (although not always on a daily basis). After the age of 30, the percentage of people demonstrating decline in function increased sharply, while disability-related support decreased. In other words, as people with DS age, daily life evolves increasingly around the home, with only occasional outdoor activities. CONCLUSION: The health, employment and social needs of the majority of people with DS in the city of Rome are not being met. The findings of this study underscore the urgent need for more comprehensive inclusion in society of adults with DS and for the provision of support services to create an enabling environment for inclusion. Because of the variability of performance among individuals with DS, there is a need to create more case-specific options in terms of work, living arrangements, social networking and medical services. Schooling and social inclusion in childhood alone do not guarantee a satisfactory quality of life in adulthood. It is argued herewith that policy of inclusion and support should extend over the entire lifetime of people with DS.

Genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiPoco6, ReqiPine5, and ReqiDocB7.

The isolation and results of genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiDocB7, ReqiPine5, and ReqiPoco6 (hereafter referred to as Pepy6, DocB7, Pine5, and Poco6, respectively) are reported. Two phages, Pepy6 and Poco6, more than 75% identical, exhibited genome organization and protein sequence likeness to Lactococcus lactis phage 1706 and clostridial prophage elements. An unusually high fraction, 27%, of Pepy6 and Poco6 proteins were predicted to possess at least one transmembrane domain, a value much higher than the average of 8.5% transmembrane domain-containing proteins determined from a data set of 36,324 phage protein entries. Genome organization and protein sequence comparisons place phage Pine5 as the first nonmycobacteriophage member of the large Rosebush cluster. DocB7, which had the broadest host range among the four isolates, was not closely related to any phage or prophage in the database, and only 23 of 105 predicted encoded proteins could be assigned a functional annotation. Because of the relationship of Rhodococcus to Mycobacterium, it was anticipated that these phages should exhibit some of the features characteristic of mycobacteriophages. Traits that were identified as shared by the Rhodococcus phages and mycobacteriophages include the prevalent long-tailed morphology and the presence of genes encoding LysB-like mycolate-hydrolyzing lysis proteins. Application of DocB7 lysates to soils amended with a host strain of R. equi reduced recoverable bacterial CFU, suggesting that phage may be useful in limiting R. equi load in the environment while foals are susceptible to infection.

[Work as a possible means of self-esteem]. / Il lavoro come spazio per una autostima possibile.

Work is recommended as a therapeutic tool in dealing with mental disorders because it makes individuals feel useful since they can use their skills to fulfill what is required. The authors designed customized rehabilitation projects, including work, spread over 25 different manufacturing processes. Every morning, 120 subjects under treatment at the Department of Mental Health were admitted to work, with the chance of being hired by the enterprise that the cooperative society represented. Twenty-one people were hired within the first year of inclusion with more satisfactory results than those reported in the literature. It should be noted that none of the subjects hired ever resorted again to hospitalisation in the psychiatric department.

Mandibuloacral dysplasia type A in childhood.

Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation, postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive acral osteolysis, and skin changes including mottled pigmentation, skin atrophy, and lipodystrophy. Owing to its slowly progressive course, the syndrome has been recognized in adults, and pediatric case reports are scarce. We present the clinical case of two children in whom the diagnosis of MADA was made at an unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose, and short and bulbous distal phalanges of fingers. A 4-year-old girl presented with round face and chubby cheeks, thin nose, bulbous fingertips, and type A lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles, short distal phalanges of fingers and toes with acro-osteolysis. Both children were found to be homozygous for the recurrent missense mutation, c.1580G>A, (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest in preschool age; diagnosis may be suggested by short and bulbous fingertips, facial features, and lipodystrophy, supported by the finding of acral osteolysis, and confirmed by mutation analysis.

Endocrine and neuropsychological assessment in a child with a novel mutation of thyroid hormone receptor: response to 12-month triiodothyroacetic acid (TRIAC) therapy.

OBJECTIVE: To determine the endocrine, neuropsychological and genetic features of a child with resistance to thyroid hormone (RTH), and his response to long-term triiodothyroacetic acid (TRIAC) therapy. METHODS: Growth, thyroid function, and neuropsychology were assessed at baseline and during 12-month TRIAC therapy. Genetic analysis was performed by PCR and denaturing high performance liquid chromatography. RESULTS: The main clinical finding was the attention deficit-hyperactivity disorder (ADHD). A novel mutation in exon 10 (phenylalanine to isoleucine in codon 455) was found. Long-term TRIAC therapy was effective in the management of the endocrine and neuropsychological manifestations of the syndrome. CONCLUSIONS: ADHD was the only phenotypic manifestation of this novel mutation of thyroid hormone (TH) receptor. TRIAC is an effective and safe drug in the long-term treatment of children with RTH.

High frequency of Candida parapsilosis on the hands of healthy hosts.

The presence of yeasts on the hands of 86 healthy hosts (62 hospital workers and 24 healthy members of the community with no hospital exposure) was investigated. A high rate of colonization was found (59.3%). Candida parapsilosis was the most frequently isolated species (51%), independent of the origin of the samples. The potential virulence and resistance to antifungals of the 26 C. parapsilosis isolates were determined. All were proteinase producers and formed biofilms. The haemolytic activity was variable, with a predominance of total haemolysis of sheep erythrocytes. All isolates were susceptible to amphotericin B but two showed reduced susceptibility to fluconazole. Healthy people may be colonized by a species of yeast with a high capacity for adhesion to plastic surfaces, providing an infection risk to susceptible individuals.

Emergence of tetracycline resistance in Helicobacter pylori: multiple mutational changes in 16S ribosomal DNA and other genetic loci.

Tetracycline is useful in combination therapies against the gastric pathogen Helicobacter pylori. We found 6 tetracycline-resistant (Tet(r)) strains among 159 clinical isolates (from El Salvador, Lithuania, and India) and obtained the following four results: (i) 5 of 6 Tet(r) isolates contained one or two nucleotide substitutions in one part of the primary tetracycline binding site in 16S rRNA (AGA(965-967) [Escherichia coli coordinates] changed to gGA, AGc, guA, or gGc [lowercase letters are used to represent the base changes]), whereas the sixth (isolate Ind75) retained AGA(965-967); (ii) PCR products containing mutant 16S ribosomal DNA (rDNA) alleles transformed recipient strains to Tet(r) phenotypes, but transformants containing alleles with single substitutions (gGA and AGc) were less resistant than their Tet(r) parents; (iii) each of 10 Tet(r) mutants of reference strain 26695 (in which mutations were induced with metronidazole, a mutagenic anti-H. pylori agent) contained the normal AGA(965-967) sequence; and (iv) transformant derivatives of Ind75 and of one of the Tet(r) 26695 mutants that had acquired mutant rDNA alleles were resistant to tetracycline at levels higher than those to which either parent strain was resistant. Thus, tetracycline resistance in H. pylori results from an accumulation of changes that may affect tetracycline-ribosome affinity and/or other functions (perhaps porins or efflux pumps). We suggest that the rarity of tetracycline resistance among clinical isolates reflects this need for multiple mutations and perhaps also the deleterious effects of such mutations on fitness. Formally equivalent mutations with small but additive effects are postulated to contribute importantly to traits such as host specificity and virulence and to H. pylori's great genetic diversity.

[Malaria in the state of Paraná, Brazil]. / Malária no Estado do Paraná, Brasil.

To collect data regarding registered cases of malaria in the state of Paraná, attendance reports of suspected cases of malaria performed by Fundação Nacional de Saúde, Paraná regional center, were analyzed from January, 1994 through December, 1999. Of 31,975 blood samples examined, 7.4% were positive: 86.4% for Plasmodium vivax, 12.7% for P. falciparum, 0.04% for P. malariae and 0.9% for P. vivax and P. falciparum. As to the epidemiological classification, 84.5% represented heterochthonous cases and 15.5% represented autochthonous cases. The municipalities showing higher rates of autochthonous cases were Foz do Iguaçu, Santa Terezinha do Itaipu and Santa Helena, a region influenced by the Itaipu reservoir, where prevention and control actions must be concentrated.