Out of the silence: towards grassroots and trauma-informed support for people who have experienced sexual violence and abuse.

To experience sexual violence and abuse is to experience silence. This commentary explores some of the ways in which psychiatry reinforces the silencing of sexual violence survivors. We argue that current psychiatric responses to sexual violence typically constitute iatrogenic harm including through: a failure to provide services that meet survivors' needs, a failure to believe or validate disclosures; experiences of medicalisation and diagnoses which can delegitimise people's own knowledge and meaning; 'power over' relational approaches which can prevent compassionate responses and result in staff having to develop their own coping strategies; and poorly addressed and reported experiences of sexual violence within psychiatric settings. We argue that these multiple forms of silencing have arisen in part because of biomedical dominance, a lack of support and training in sexual violence for staff, inconsistent access to structured, reflective supervision, and the difficulties of facing the horror of sexual violence and abuse. We then describe community-based and grassroots responses, and consider the potential of trauma-informed approaches. Whilst this paper has a UK focus, some aspects will resonate globally, particularly given that Western psychiatry is increasingly being exported around the globe.

Ischemic gastritis: a rare but lethal consequence of celiac territory ischemic syndrome.

AIM: Ischemic gastritis is poorly known by physicians and is often fatal if not correctly diagnosed. Here, we report on the clinical, endoscopic and imaging features and treatment outcomes for five ischemic gastritis patients. METHODS: This was a retrospective, single-centre study of patients treated for ischemic gastritis between January 2009 and April 2012. All patients underwent transluminal angioplasty or open revascularization surgery. RESULTS: Five patients (4 men, 1 female) were included in the present study. The condition was diagnosed in two cases of peritonitis with gastric or duodenal perforation, two cases of acute epigastric pain and one case of gastric bleeding, profuse vomiting and hypovolemic shock. Three of the five patients had endoscopically proven gastric ulcerations or necrosis. A computed tomography scan contributed to the diagnosis in all cases. The symptoms resolved in all cases after gastric revascularization via an aortohepatic bypass (N.=1), a renohepatic bypass (N.=1), a retrograde iliosuperior mesenteric bypass (N.=2) with associated celiac artery angioplasty (N.=1) and celiac and superior mesenteric artery angioplasty (N.=1). During follow-up, three patients died of starvation due to short bowel syndrome (N.=1) or metastatic lung cancer (N.=2). CONCLUSION: Ischemic gastritis is a component of celiac territory ischemia syndrome and is closely associated with chronic or acute mesenteric ischemia. Computed tomography always informs the diagnosis. The rapid healing observed here after revascularization confirmed the ischemic nature of the condition and the inappropriateness of gastric resection in this context.

RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation.

Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from chimaeric fusion genes or point mutations such as BCR-ABL1 or JAK2 V617F. We report here the cloning and functional characterization of two novel fusion genes BCR-RET and FGFR1OP-RET in chronic myelomonocytic leukemia (CMML) cases generated by two balanced translocations t(10;22)(q11;q11) and t(6;10)(q27;q11), respectively. The two RET fusion genes leading to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. The RET fusion genes seem to constitutively mimic the same signaling pathway as RAS mutations frequently involved in CMML. One patient was treated with Sorafenib, a specific inhibitor of the RET TK function, and demonstrated cytological and clinical remissions.

Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases.

The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.

Is the maturation of monosynaptic stretch reflex in rats affected by neonatal malnutrition?

We compared the maturation of the monosynaptic stretch reflex in control rats and in rats submitted to neonatal malnutrition. Electrical stimulations of the sciatic nerve were applied in wakeful rats of different ages (21-90 days) to record, by surface electrodes, the maximal direct motor response (M(max)) or the maximal Hoffmann reflex (H(max)). Percussion on the Achilles tendon induced the T-reflex. Animals submitted to neonatal malnutrition showed significant reductions in H-reflex latency and in velocity index of nervous conduction. The H- or T-reflex amplitudes were lower for malnourished rats of 21 days but the difference was significant only for the T(max)/M(max) ratios. The reflexes evoked at older ages did not present differences between control and malnourished rats. In conclusion, rats submitted to neonatal malnutrition present long-term alteration in reflex latency and nervous conduction velocity. Neonatal malnutrition also alters the reflex excitability at weaning but, since the rat were submitted to a normal diet after weaning, a normal reflex excitability was rapidly recovered which indicates a remarkable plasticity of the reflex pathway.

Severe neurological crisis in a patient with hereditary tyrosinaemia type I after interruption of NTBC treatment.

Neurological crises do not occur in patients with tyrosinaemia type I treated with NTBC. We report an 8 month-old boy with severe neurological crisis after interruption of NTBC treatment including progressive ascending polyneuropathy and diaphragmatic paralysis, arterial hypertension, respiratory distress requiring mechanical ventilation who later also developed impaired liver function and tubulopathy. After re-introduction of NTBC the patient slowly regained normal neurological functions and recovered completely.

Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH).

A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.

[Transient myeloproliferative disorder in a neonate without Down syndrome]. / Syndrome myélo-prolifératif transitoire chez un nouveau-né indemne de toute pathologie constitutionnelle.

We report a new case of transient myeloproliferative disorder (TMD) in a non Down syndrome neonate. The cytogenetic and molecular studies within from the blood blast cells identified a trisomy 21 and a partial deletion in exon 2 of the transcription factor GATA1. Spontaneous regression of the TMD was achieved at the age of 1 month as the clonal and molecular abnormalities. A survey by periodic cytological examinations of peripheral blood cells and GATA1 mutation analysis was instituted since three years and has not detected up to date acute leukaemia.

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

Adaptation of rat soleus muscle spindles after 21 days of hindlimb unloading.

Spindle discharges are affected by muscle unloading, and changes in passive stiffness of the muscle-tendon unit may contribute to the changes in spindle solicitation. To test this hypothesis, we determined the spindle sensitivity from electroneurograms of the soleus nerve, and, concomitantly, we measured the incremental passive muscle tension. Both measurements were done from ramp and hold stretches imposed to the soleus muscle after the Achilles tendon was severed. The ratio between the spindle sensitivity and the passive stiffness gave a "spindle efficacy index" (SEI). The experiments were conducted on control rats (C, n = 12) and on rats that had undergone hindlimb unloading (HU, n = 12) for 21 days. The muscle threshold lengths for electroneurogram to discharge (neurogram length, Ln) and for detecting passive tension (slack length, Ls) were determined, and, when these lengths differed, the stretches were imposed at these two initial lengths. The contralateral muscles were used to count muscle spindles and spindle fibers (ATPase staining) and to identify MyHC isoforms by immunostaining. Ln and Ls values were identical for the C muscles, while after HU, Ln was significantly shorter than Ls, which indicated that spindle afferents were more sensitive since they discharged before any passive tension was developed by the soleus muscle. At Ln, spindle sensitivity and passive stiffness did not differ for C and HU muscles. Consequently, when calculated at this relatively short initial muscle length, the SEI was maintained (or even slightly increased) after HU. This held under dynamic conditions (ramp phase of the stretch) and under static conditions (hold phase of the stretch). At Ls, the dynamic and static incremental stiffness values increased significantly after HU. Under dynamic conditions, the spindle sensitivity also increased after HU but to a less degree than incremental stiffness, which led to a significant decrease in SEI. Under static conditions, the spindle sensitivity presented a high increase, and, consequently, SEI was not modified. These functional changes were associated with structural adaptations: HU did not alter the total number of muscle spindles, but the number of spindles containing three nuclear chain fibers increased significantly. The main change in intrafusal MyHC content concerned the slow type I MyHC isoform. In conclusion, after a period of muscle unloading, the spindle discharges were maintained or even enhanced in several experimental conditions. This may be due to a better transmission of the external stretch to muscle spindles through stiffer elastic structures but also to own muscle spindle adaptations which reinforce the spindle sensitivity, notably under static conditions.

Plantar flexion torque as a function of time of day.

The possible peripheral and/or central origin in the mechanisms responsible for day-time fluctuation in maximal torque of the triceps surae muscle were investigated with a special emphasis on antagonist muscle coactivation. Eleven healthy male subjects (physical education students) took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different times of day: between 06:00 h and 08:00 h in the morning and between 17:00 h and 19:00 h in the evening. To investigate peripheral mechanisms, the posterior tibial nerve was stimulated at rest, using percutaneous electrical stimuli, to evoke single twitch, double twitch, and maximal tetanic contraction (100 Hz). Maximal voluntary contraction of the plantar flexors was also assessed by means of the relative electromyographic activity of respective agonist and antagonist muscles (soleus, gastrocnemius medialis, gastrocnemius lateralis, and tibialis anterior). A double twitch was delivered during maximal voluntary plantar flexion to record muscle activation (i.e., interpolated twitch technique). The coactivation level of the tibialis anterior muscle during plantar flexion was calculated. The results indicated a significant decrease in maximal voluntary muscle torque of triceps surae in the evening as compared with the morning (-7.0 %; p < 0.05). Concerning the central command, when extrapolated by the twitch interpolation technique, the decrease in mean activation level of -6.8 % was consistent with the fluctuation in torque (-7.0 %). Soleus muscle electromyographic activity (normalized to the M-wave) showed a significant decline (21.6 %; p < 0.001). Moreover, individual changes in MVC percentage were significantly related to those of normalized electromyographic activity of the soleus muscle (r = 0.688; p < 0.01). Thus, it indicated that the subject's capacity to activate the soleus muscle was affected by the time of day. The coactivation level in the tibialis anterior muscle during plantar flexion did not change significantly in the evening. Concerning peripheral mechanisms, we observed a decrease in maximal M-wave amplitude for soleus and gastrocnemii, associated with unchanged single twitch and tetanus torque. To conclude, impairment in soleus muscle central command seemed to be the mechanism in the origin of torque failure. Such information would be of importance in the investigation of day-time fluctuations in complex motor task performances implicating the triceps surae muscle.

NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.

Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system.

AIMS: Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. METHODS AND RESULTS: We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. CONCLUSIONS: Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.

Adaptive filtering for ECG rejection from surface EMG recordings.

Surface electromyograms (EMG) of back muscles are often corrupted by electrocardiogram (ECG) signals. This noise in the EMG signals does not allow to appreciate correctly the spectral content of the EMG signals and to follow its evolution during, for example, a fatigue process. Several methods have been proposed to reject the ECG noise from EMG recordings, but seldom taking into account the eventual changes in ECG characteristics during the experiment. In this paper we propose an adaptive filtering algorithm specifically developed for the rejection of the electrocardiogram corrupting surface electromyograms (SEMG). The first step of the study was to choose the ECG electrode position in order to record the ECG with a shape similar to that found in the noised SEMGs. Then, the efficiency of different algorithms were tested on 28 erector spinae SEMG recordings. The best algorithm belongs to the fast recursive least square family (FRLS). More precisely, the best results were obtained with the simplified formulation of a FRLS algorithm. As an application of the adaptive filtering, the paper compares the evolutions of spectral parameters of noised or denoised (after adaptive filtering) surface EMGs recorded on erector spinae muscles during a trunk extension. The fatigue test was analyzed on 16 EMG recordings. After adaptive filtering, mean initial values of energy and of mean power frequency (MPF) were significantly lower and higher respectively. The differences corresponded to the removal of the ECG components. Furthermore, classical fatigue criteria (increase in energy and decrease in MPF values over time during the fatigue test) were better observed on the denoised EMGs. The mean values of the slopes of the energy-time and MPF-time linear relationships differed significantly when established before and after adaptive filtering. These results account for the efficacy of the adaptive filtering method proposed here to denoise electrophysiological signals.

Neuromuscular efficiency of the triceps surae in induced and voluntary contractions: morning and evening evaluations.

Variations in force and electromyographic (EMG) activities of skeletal muscles with the time-of-day have been previously described, but not for a postural muscle, submitted to daily postural and locomotor tasks. In this article, mechanical performances, EMGs, and the ratio between these parameters, i.e., the neuromuscular efficiency (NME), were measured on the triceps surae (TS) of eight subjects, two times each day, at 6:00 and 18:00 h. NME was evaluated under different experimental conditions (electrically induced contractions, reflex contractions, maximal and submaximal voluntary isometric contractions, and during a natural movement, a drop jump) to determine whether mechanisms, peripheral or central in origin, were responsible for the eventual changes in NME with time-of-day. To calculate NME in induced conditions (NMEind), a supramaximal electrical stimulus was applied to the tibial nerve, and the maximal M wave of TS (TS Mmax) and the amplitude of the twitch tension (PtMmax) in response to this electrical stimulation were quantified. TS Mmax was significantly lower in the evening (mean gain value -10.7 +/- 5.5%, p < 0.05), whereas PtMmax was not significantly modified. NMEind (PtMmax/TS Mmax) was significantly higher in the evening (mean gain of 17.6 +/- 5.8%, p < 0.05), and this increase was necessarily peripheral in origin. Secondly, maximal tendon taps were applied to the Achilles tendon in order to quantify at the two times-of-day the reflexes in response to a mechanical stimulus. The maximal reflex, TS Tmax/Mmax (%), the peak amplitude of the twitch tension associated to this tendon jerk (PtTmax), and the corresponding NME (NMEreflex = PtTmax/TS Tmax/Mmax) were not affected by time-of-day, indicating that reflex excitability did not present daytime variations when tested under these conditions. Voluntary isometric contractions were required under maximal (MVC) and submaximal (25% MVC) conditions, and the corresponding torques and TS EMG were measured. MVC was higher in the evening (mean gain: 8.6 +/- 2.7%, p < 0.05) and TS EMGmax (normalized with regard to TS Mmax) also increased in the evening but not significantly; thus, NMEMvc was not modified. At 25% of MVC, TS EMG was significantly higher in the evening (mean gain of 23 +/- 13.9%, p <0.05) and a trend for a lower NME25%MVC in the evening was observed, a result probably representative of a higher muscle fatigue state in the evening. Finally, to test the muscle capacities during a natural task, a NME index was calculated during a drop jump (DJ). The NMEDJ was defined as the ratio between jump height and mean amplitude of TS EMG (% of TS Mmax) between the drop and the jump. Both jump height and NMEDJ were significantly higher in the evening (mean gains of 10.9 +/- 4.5% and 15.7 +/- 7.4%, respectively, p <0.05). In conclusion, daytime changes in the efficiency of postural muscles seem to depend on both peripheral and central mechanisms. According to the experimental conditions, NME of the postural muscle could increase, remain constant, or even decrease in the evening, and this result may reflect reverse effects of better contractile capacities and higher fatigue state.