Childhood Trauma and Premenstrual Symptoms: The Role of Emotion Regulation.

BACKGROUND: Women with Premenstrual Dysphoric Disorder (PMDD) are more likely to have a history of childhood trauma, and may experience more severe premenstrual symptomatology. However, the pathway in which childhood trauma affects the prevalence and severity of premenstrual symptoms remains largely unclear. OBJECTIVE: To determine whether childhood trauma is associated with increased premenstrual symptoms, and if so, whether emotional dysregulation mediates or moderates this relationship. PARTICIPANTS AND SETTINGS: A total of 112 women were recruited for the study among students at the Hebrew University of Jerusalem. METHODS: Participants completed the Premenstrual Symptoms Screening Tool (PSST), the Childhood Trauma Questionnaire (CTQ) and the Difficulties in Emotion Regulation Scale (DERS). To test the mediation hypothesis, direct and indirect effects of childhood trauma on premenstrual symptoms were calculated. To test moderation, we performed multiple regression, including the interaction term between childhood trauma and emotion dysregulation RESULTS: Twenty-two women (18.6%) met criteria for premenstrual syndrome (PMS) and sixteen (13.6 %) for PMDD. The number and severity of premenstrual symptoms increased with more childhood trauma (r = .282), and this relationship was completely mediated by emotion regulation difficulties. Specifically, exposure to Sexual abuse (r = .243) and Emotional neglect (r = .198) were significantly associated with premenstrual symptoms. Abuse predicted greater emotion dysregulation (r = .33), whereas, neglect did not. CONCLUSIONS: This study contributes to the current knowledge on the long-term effects of childhood trauma. Promoting use of adaptive emotion regulation strategies for women with a history of childhood trauma, could improve their capability to confront and adapt to premenstrual changes.

Three artificial intelligence data challenges based on CT and MRI.

PURPOSE: The second edition of the artificial intelligence (AI) data challenge was organized by the French Society of Radiology with the aim to: (i), work on relevant public health issues; (ii), build large, multicentre, high quality databases; and (iii), include three-dimensional (3D) information and prognostic questions. MATERIALS AND METHODS: Relevant clinical questions were proposed by French subspecialty colleges of radiology. Their feasibility was assessed by experts in the field of AI. A dedicated platform was set up for inclusion centers to safely upload their anonymized examinations in compliance with general data protection regulation. The quality of the database was checked by experts weekly with annotations performed by radiologists. Multidisciplinary teams competed between September 11th and October 13th 2019. RESULTS: Three questions were selected using different imaging and evaluation modalities, including: pulmonary nodule detection and classification from 3D computed tomography (CT), prediction of expanded disability status scale in multiple sclerosis using 3D magnetic resonance imaging (MRI) and segmentation of muscular surface for sarcopenia estimation from two-dimensional CT. A total of 4347 examinations were gathered of which only 6% were excluded. Three independent databases from 24 individual centers were created. A total of 143 participants were split into 20 multidisciplinary teams. CONCLUSION: Three data challenges with over 1200 general data protection regulation compliant CT or MRI examinations each were organized. Future challenges should be made with more complex situations combining histopathological or genetic information to resemble real life situations faced by radiologists in routine practice.

Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI.

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.

Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: results from a single institution.

The optimal management of recurrent glioblastoma (GBM) has yet to be determined. We aim to assess the benefits of re-operation and salvage therapies (chemotherapy and/or re-irradiation) for recurrent GBM and to identify prognostic factors associated with better survival. All patients who underwent surgery for GBM between January 2005 and December 2012 followed by adjuvant radiotherapy, and who developed GBM recurrence on imaging were included in this retrospective study. Univariate and multivariate analysis was performed using Cox models in order to identify factors associated with overall survival (OS). One hundred and eighty patients treated to a dose of 60 Gy were diagnosed with recurrent GBM. At a median follow-up time of 6.2 months, the median survival (MS) from time of recurrence was 6.6 months. Sixty-nine patients underwent repeat surgery for recurrence based on imaging. To establish the benefits of repeat surgery and salvage therapies, 68 patients who underwent repeat surgery were matched to patients who did not based on extent of initial resection and presence of subventricular zone involvement at recurrence. MS for patients who underwent re-operation was 9.6 months, compared to 5.3 months for patients who did not have repeat surgery (p < 0.0001). Multivariate analysis in the matched pairs confirmed that repeat surgery with the addition of other salvage treatment can significantly affect patient outcome (HR 0.53). Re-operation with additional salvage therapies for recurrent GBM provides survival prolongation at the time of progression.

[Initial training in psychotherapy for psychiatrists in France: results of a national survey]. / La formation aux psychothérapies des internes de psychiatrie en France : résultats d'une enquête nationale.

INTRODUCTION: According to a recent change in the French legislation (2010) regarding the regulation of the use of the title of "psychotherapist", psychiatrists are now allowed to use this title at the end of their training, without any additional training. However, various publications from 2000 have shown that there is no specific training in psychotherapy at a professional level during the training of psychiatrists. GOALS: To study the current situation of the Academic training of French psychiatrists in psychotherapy during their residency, their interest for these therapies, their level of satisfaction regarding their training, and the importance of additional private training programs. METHODOLOGY: A survey was carried out among residents in psychiatry from October 2010 until January 2011. An anonymous questionnaire covering five domains (academic teaching, psychoanalysis, extra-academic training, interest in a more developed model of training, supervision) was sent by the French Federative Association of Psychiatrists Trainees (AFFEP) to all French psychiatrist trainees, through their local trainee associations (n=26). RESULTS: The questionnaire was answered by 869 of the 1334 psychiatry residents (65%). The vast majority of the trainees reported being interested in psychotherapy, but 75% thought that their training in psychotherapy (psychoanalysis, cognitive-behavioral therapy [CBT] and systemic therapy) is insufficient. In 20 of the 26 universities, more than half of the trainees reported that their training was insufficient in the three fields; in four universities, more than half of the trainees were satisfied with at least one field. Yet, satisfaction rates were very different among universities: for example, 27% were satisfied with their psychoanalytic training in Paris and 87% in Strasbourg; 7% were satisfied with their CBT training in Strasbourg, but 65% in Nice. The vast majority (97%) believes that supervision about therapeutic relationship is necessary during residency rotations in the hospital. More than three quarters (78%) would like to have supervision at least twice a month. Yet, only 51% of respondents have such supervision. Once again, large disparities were observed between different Academies: for example 74% had supervision in Montpellier, but only 29% in Marseille. The vast majority (95%) of trainees would like a two-phase model of training (general theoretical teaching plus in-depth training in one or more methods), which is different to the current training model. CONCLUSION: Our results show a clear discrepancy between the importance of training in psychotherapy for psychiatrists, the interest of psychiatry students for these therapies, and the very high rate of dissatisfaction for the training received, as well as the rate of students supervised during their training period at the hospital. These results differ from what is observed in other countries, where satisfaction rates are much higher among students, and various psychotherapy training methods are proposed in a much more homogeneous manner. More research is required to understand the reasons for these difficulties with the psychotherapy training of psychiatrists in France, and to propose new models of training to improve this situation.

Cost-effectiveness of insulin glargine versus NPH insulin for the treatment of Type 2 diabetes mellitus, modeling the interaction between hypoglycemia and glycemic control in Switzerland.

OBJECTIVE: The objective of this study was to evaluate the short-term and long-term clinical and economic outcomes associated with insulin glargine or NPH insulin in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic drugs in Switzerland, modeling the interaction between hypoglycemia and glycemic control (HbA1c). METHODS: A validated discrete event simulation model for T2DM was used to predict incidence of short-term complications (symptomatic, nocturnal and severe hypoglycemic events) and long-term complications (microvascular and macrovascular events), life expectancy, quality-adjusted life years (QALYs) and direct medical costs in patients treated with insulin glargine or NPH insulin. The model was populated with published Swiss patient characteristics with T2DM. Baseline risks of hypoglycemic events, utility decrements of diabetes-related long-term complications and the hypoglycemia fear score were derived from the literature. Relative risk reductions of hypoglycemia adjusted for HbA1c using insulin glargine compared with NPH insulin were based on a published negative binomial meta-regression analysis. Costs of severe hypoglycemia, micro- and macrovascular events were analyzed from literature whenever possible otherwise guideline-projected resource-use estimations were valued with Swiss official prices or tariffs in 2006 CHF. Simulations were run with 1,000 patients per cohort over a time horizon of 40 years. Incremental cost effectiveness ratios (ICERs) were presented as cost per QALY and per life year gained (LYG). Future costs and clinical benefits were discounted at 3.5%. Wide-range one-way sensitivity analyses were performed. RESULTS: Insulin glargine was associated with an improvement in quality of life (0.098 QALYs per patient) and additional life expectancy (0.05 life years gained per patient) compared to NPH insulin. Incremental costs of CHF 2,578 resulted in an ICER of CHF 26,271 per QALY and CHF 51,100 per LYG. The cost per QALY was most sensitive to changes in costs, utility decrements and relative risk reductions of hypoglycemia. CONCLUSIONS: This study evaluated, for the first time, the cost effectiveness of insulin glargine versus NPH insulin for the treatment of T2DM considering the interaction between glycemic control and hypoglycemia in Switzerland. The base case and sensitivity analyses demonstrated that insulin glargine proved to be cost-effective with respect to accepted willingness to pay thresholds and therefore represents good value for money.

Cost-effectiveness and cost-utility of insulin glargine compared with NPH insulin based on a 10-year simulation of long-term complications with the Diabetes Mellitus Model in patients with type 2 diabetes in Switzerland.

OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of insulin glargine compared with NPH insulin in patients with type 2 diabetes and in whom OAD (oral anti-diabetics) had failed in Switzerland. METHODS: Long-term diabetes outcomes were simulated with the Diabetes Mellitus Model (DMM) over a period of 10 years. The incidences of long-term complications (micro- and macrovascular events) were simulated for 10,000 patients over 10 years for six different scenarios. The scenarios were based on HbA1c reductions observed in clinical trials. For insulin glargine, HbA1c reductions of 0.96% (pessimistic case) and 1.24% (optimistic case) were simulated for three different HbA1c baseline values (10, 9 and 8%). For NPH insulin the HbA1c reduction was assumed to be 0.84%. A cost model and a utility model were developed in order to use the cumulated incidences of the simulations for the calculation of cost and QALYs (quality-adjusted life years). The unit costs of micro- and macrovascular events were assessed on the basis of published literature and guideline-projected resource-use estimations for Switzerland. Disutility values of diabetes-related long-term complications were derived from the literature. Total direct medical costs or QALYs were assessed by a combination of cumulated incidences of each event up to 10 years with the corresponding unit cost per event (in addition to the acquisition cost) or with disutility values per event, respectively. Events, total cost, and QALYs were discounted at 3%. In scenarios where no savings could be shown for insulin glargine, incremental cost-effectiveness ratios were calculated as the incremental cost per event prevented and the cost per QALY gained. RESULTS: Cost comparison demonstrated that insulin glargine is the dominant strategy for the optimistic case scenario starting at a baseline HbA1c value of 10% as savings in the management of complications exceeded the difference in acquisition costs after 8 years of treatment. Optimistic case scenarios for baseline HbA1c values of 9 and 8% achieved costs per QALY gained amounting to CHF 2,853 and CHF 5,711 and costs per event prevented amounting to CHF 2,054 and CHF 4,899, respectively. Pessimistic case scenarios for baseline HbA1c values of 10, 9 and 8% resulted in costs per QALY gained amounting to CHF 40,441, CHF 45,701 and CHF 49,468 and costs per event prevented amounting to CHF 27,742, CHF 32,451 and CHF 41,620, respectively. CONCLUSIONS: This study investigated the long-term health-economic implications of treating type 2 diabetes patients, in whom OAD had failed, with insulin glargine versus NPH insulin in Switzerland. The 10-year simulations demonstrated that the deltaHbA1c reductions of 0.4 and 0.12% achieved with insulin glargine led to a reduction of long-term complications, mortality and associated costs as well as to an improved quality of life. Insulin glargine proved to be cost-effective and represents good to excellent value for money compared to NPH insulin.

2-Nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine beta-glucuronidase.

4-Benzylamino-(and 4-chloromethyl)-2-nitro-beta-D-glucuronides (4, 10) and their 2-substituted-4-nitro regioisomers (7, 13) were prepared by glycosidation of the 3-nitro-4-hydroxy- and the 2-hydroxy-5-nitro-benzylic alcohol, respectively, with a glucuronyl donor. Carbonate activation followed by reaction with benzylamine or methanesulfonyl chloride afforded, after complete deprotection, the target molecules 4, 7, 10 and 13. These compounds have been synthesized to determine whether these molecules are (or not) glucuronidase inhibitors. After incubation with bovine liver beta-glucuronidase, none of the cleavage products (the titled quinone-methides) showed to be irreversible inhibitors of this enzyme.

Prodrugs of anthracycline antibiotics suited for tumor-specific activation.

The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D-galactopyranose and doxorubicin in three and six steps, respectively. Their low cytotoxicity, high stability in plasma and, in the case of 11, efficient hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions for their use in combination with monoclonal antibody-enzyme conjugates.

[A case of cervico-isthmic pregnancy with delayed development]. / A propos d'un cas de grossesse cervico-isthmique à développement tardif.

This is the case of a para three, gravida three, who had a caesarean section for her first pregnancy and a normal delivery for the second one. During her third pregnancy the patient is hospitalised for first trimester bleeding. Ultrasounds show two liquid compartments separated by placenta. The lower one in cervico-isthmic position contains the foetus. During the 24th week gestation the pregnancy is complicated by severe metrorrhagia that leads to abdominal exploration and total hysterectomy. The pathology conclusions confirmed the per-operative impression of cervico-isthmic pregnancy. The authors emphasise the rarity of the cervico-isthmic pregnancy (1 for 10,000 pregnancies) and wonder about atypical evolution of this case and about the possibilities of saving the uterus by an earlier intervention in view of ultrasonographic data.

Improvement of flow cytometry analysis and sorting of bull spermatozoa by optical monitoring of cell orientation as evaluated by DNA specific probing.

Flow cytometry is a potential method for the separation of X and Y bearing spermatozoa, on the basis of their relative DNA content evaluated by the fluorescence emission intensity due to specific fluorochrome DNA staining. However, spermatozoa DNA is highly condensed and nuclei exhibit flat non spherical shape, which can produce artefacts impeding accurate analysis. In order to avoid these limitations, decondensation of DNA performed by enzymatic treatment and a modification of the flow cytometer that orients the spermatozoa relative to the laser beam are generally used. In this work, we describe alternative methods and materials for selection of 1) decondensed and thus dead spermatozoa without orientation, sorted on the basis of only the 10% spermatozoa containing the least DNA (expected Y) and the 10% spermatozoa containing the more DNA (expected X), or 2) native spermatozoa homogeneously oriented using a simultaneous measurement of Axial light loss (extinction) and Forward angle light scatter. For testing enrichment of each selected fraction we have worked out a molecular hybridization procedure using X and Y specific DNA probes. We analyse and sort bull spermatozoa on these basis: the purity obtained for these fractions is 80% without orientation after enzymatic treatment, and 70% on live spermatozoa "optically" oriented.

Metabolism of glutamine in erythrocytes infected with the human malaria parasite: Plasmodium falciparum.

The metabolism of glutamine was studied in erythrocytes infected with Plasmodium falciparum, comparatively to normal cells, in presence or not of DON (6-diazo-5-oxo-L-norleucine) or acivicin, two glutamine antagonists which have been shown to inhibit the growth of P. falciparum in vitro. Extracellular glutamine was partially converted into glutamate using two routes corresponding to gamma-glutamyl transpeptidase (GGT) and glutaminase activities. In cells infected with mature trophozoites, the observed enhancement of the glutamine influx and of the glutamate formation was consistent with the enhancement of GGT and glutaminase activities.

Characterization of a panel of somatic cell hybrids for subregional mapping along 11p and within band 11p13. Subdivision of the WAGR complex region.

The short arm of chromosome 11 carries genes involved in malformation syndromes, including the aniridia/genitourinary abnormalities/mental retardation (WAGR) syndrome and the Beckwith-Wiedemann syndrome, both of which are associated with an increased risk of childhood malignancy. Evidence comes from constitutional chromosomal aberrations and from losses of heterozygosity, limited to tumor cells, involving regions 11p13 and 11p15. In order to map the genes involved more precisely, we have fused a mouse cell line with cell lines from patients with constitutional deletions or translocations. Characterization of somatic cell hybrids with 11p-specific DNA markers has allowed us to subdivide the short arm into 11 subregions, 7 of which belong to band 11p13. We have thus defined the smallest region of overlap for the Wilms' tumor locus bracketed by the closest proximal and distal breakpoints in two of these hybrids. The region associated with the Beckwith-Wiedemann syndrome spans the region flanked by two 11p15.5 markers, HRAS1 and HBB. These hybrids also represent useful tools for mapping new markers to this region of the human genome.

Reaction of o-phthalaldehyde with amino acids and glutathione. Application to high-performance liquid chromatography determination.

Experimental conditions were found for the preparation of stable fluorescent adducts of o-phthalaldehyde with glutathione and its metabolites: glutamine, glutamic and aspartic acids, gamma-glutamylglutamine and gamma-glutamylglutamylglutamine. The structure of the glutathione isoindole derivative obtained was confirmed by NMR studies. The procedure was applied to reversed-phase high-performance liquid chromatographic separation of the previous compounds. The method was extended to glutathione and "total glutathione" determinations.

Molecular definition of de novo and genetically transmitted WAGR-associated rearrangements of 11p13.

We describe a family in whom the phenotypically normal father carries a balanced insertional translocation, ins(14;11)(q23;p12p14). This individual fathered three mentally retarded children, two with a del(11)(p13) and one with a dup(11)(p13). Two other cases of a de novo del(11)(p13) are also described. All four del(11)(p13) cases presented with WAGR, a complex syndrome associated with a predisposition to Wilms' tumor (WT), aniridia (A), genitourinary abnormalities (G), and mental retardation (R). Using an approach combining karyotype analysis, determination of the gene copy number, and RFLP studies employing five 11p13 DNA markers, we were able to define the chromosomal rearrangement involved in each case. Analysis of these WAGR deletions provides further subdivision of band p13 on chromosome 11.

The gene for catalase is assigned between the antigen loci MIC4 and MIC11.

Genetic analysis of the cells of a WAGR patient (W, predisposition to Wilms tumor; A, aniridia; G, genitourinary abnormalities; R, mental retardation), bearing a partial deletion of band 11p13, was performed with biochemical and antigenic 11p markers by using gene dosage, somatic hybridization, molecular hybridization, and indirect immunofluorescence techniques. These studies allowed the regional assignment of the gene for catalase, which is linked to the Wilms tumor locus, between MIC4 and MIC11, two loci encoding for membrane antigens previously mapped to band 11p13.

Molecular analysis of a reciprocal translocation t(5;11) (q11;p13) in a WAGR patient.

Most patients with the complex association aniridia - predisposition to Wilms' tumor (WAGR syndrome) present with a de novo constitutional deletion of band 11p13. We report a patient with WAGR syndrome and a reciprocal translocation between chromosomes 5 and 11 t(5;11) (q11;p13). High resolution banding cytogenetic analysis and molecular characterization using 11p13 DNA markers showed a tiny deletion encompassing the gene for CAT but sparing the gene for FSHB. This suggests that syndromes associated with apparently balanced translocations may be due to undetectable loss of material at the breakpoint(s) rather than to breakage in the gene itself.