The Dutch Protocol for Juvenile Transsexuals: Origins and Evidence.

It has been a quarter of a century since Dutch clinicians proposed puberty suppression as an intervention for "juvenile transsexuals," which became the international standard for treating gender dysphoria. This paper reviews the history of this intervention and scrutinizes the evidence adduced to support it. The intervention was justified by claims that it was reversible and that it was a tool for diagnosis, but these claims are increasingly implausible. The main evidence for the Dutch protocol came from a longitudinal study of 70 adolescents who had been subjected to puberty suppression followed by cross-sex hormones and surgery. Their outcomes shortly after surgery appeared positive, except for the one patient who died, but these findings rested on a small number of observations and incommensurable measures of gender dysphoria. A replication study conducted in Britain found no improvement. While some effects of puberty suppression have been carefully studied, such as on bone density, others have been ignored, like on sexual functioning.

Glycolysis and Fatty Acid Oxidation Inhibition Improves Survival in Glioblastoma.

Glioblastoma (GBM) is the most aggressive adult glioma with a median survival of 14 months. While standard treatments (safe maximal resection, radiation, and temozolomide chemotherapy) have increased the median survival in favorable O(6)-methylguanine-DNA methyltransferase (MGMT)-methylated GBM (~21 months), a large proportion of patients experience a highly debilitating and rapidly fatal disease. This study examined GBM cellular energetic pathways and blockade using repurposed drugs: the glycolytic inhibitor, namely dicholoroacetate (DCA), and the partial fatty acid oxidation (FAO) inhibitor, namely ranolazine (Rano). Gene expression data show that GBM subtypes have similar glucose and FAO pathways, and GBM tumors have significant upregulation of enzymes in both pathways, compared to normal brain tissue (p < 0.01). DCA and the DCA/Rano combination showed reduced colony-forming activity of GBM and increased oxidative stress, DNA damage, autophagy, and apoptosis in vitro. In the orthotopic Gl261 and CT2A syngeneic murine models of GBM, DCA, Rano, and DCA/Rano increased median survival and induced focal tumor necrosis and hemorrhage. In conclusion, dual targeting of glycolytic and FAO metabolic pathways provides a viable treatment that warrants further investigation concurrently or as an adjuvant to standard chemoradiation for GBM.

Diagnostic and management considerations in incidental common peroneal intraneural haemangioma.

Intraneural haemangiomas are rare tumours that can affect peripheral nerves. We describe a case of a 10-year-old female with an incidental finding of a common peroneal nerve lesion following knee injury. MRI demonstrated avid heterogeneous enhancement and peri-lesional oedema, and an open biopsy was performed revealing haemangioma on histopathological analysis. The patient was managed with observation and remains intact at 24-month follow-up.

Idiopathic intradural dorsal thoracic arachnoid cysts: A case series and review of the literature.

BACKGROUND: Spinal intradural arachnoid cysts (SIAC) are cerebrospinal fluid (CSF) filled sacs formed by arachnoid membranes and may be either idiopathic or acquired. Idiopathic cysts represent a separate entity and their aetiology remains uncertain. By far the most difficult differential diagnosis is distinguishing between idiopathic anterior spinal cord herniation (IASCH) and dorsal thoracic intradural arachnoid cysts (TIAC), due to their similarity in radiological appearance. Cine-mode (SSFP) is emerging as a novel technique in the diagnosis and operative planning of SIAC. METHOD: Retrospective analysis of patients with idiopathic TIACs that were surgically managed at Royal North Shore Hospital and North Shore Private Hospital between November 2000 and November 2015. RESULTS: Ten patients were included in this study. Age ranged from 20 to 77years with a mean age of 60years and a female preponderance. The most common clinical features were progressive gait ataxia and lower limb myelopathy. Radicular pain tends to improve following surgery, however gait ataxia may not. DISCUSSION: While there are circumstances in which the distinction between dorsal thoracic intradural arachnoid cysts and idiopathic anterior spinal cord herniation are radiologically obvious, in cases where the appearances are less clear, cine-mode SSFP MRI imaging can provide an invaluable tool to differentiate these pathologies and lead the clinician towards the correct diagnosis and management. The mainstay of surgical management for dorsal TIACs is laminectomy and cyst excision or fenestration. Surgery for gait ataxia should be aimed towards preventing deterioration, while maintaining the potential for symptomatic improvement, whereas surgery for radicular pain should be curative.

Estimation of postmortem interval using vitreous potassium levels in cases of fatal road traffic collision

AIM OF THE STUDY: To produce a formula that can accurately predict postmortem interval (PMI) based on vitreous potassium levels using road traffic collision fatalities. MATERIAL AND METHODS: Vitreous humour samples were taken from 78 individuals who had died following road traffic collisions between 2010 and 2015. Samples were obtained from both eyes and were sent for on-site analysis. Measurement of potassium was by an indirect ion-specific electrode Siemens diagnostics ADVIA 2400 chemistry system. Exact time of death was known from police reports, the time of postmortem was recorded and the postmortem interval was calculated. Linear regression was then used to analyse the relationship between the two. The impact of age was also assessed. RESULTS: PMI was between 6 and 162 hours. As vitreous potassium increases, the PMI also increases; exhibiting a linear relationship. This is illustrated by a regression equation of PMI = 6.42[K+] - 40.94, R = 0.67 (p < 0.001). This produced a formula closely comparable with three other studies proposed in previous literature and produces estimates that may exceed one calendar day. When both age and medical intervention are accounted for there is an insignificant improvement in prediction. CONCLUSIONS: Validated methods have been used to produce a formula for prediction of PMI using vitreous potassium. Although this is specific to road traffic collisions, the methods are transferable and can be seen to be comparable with other recently published methods. Nonetheless, if greater levels of accuracy are required it is suggested that biomarkers delivering a higher level of precision should still be sought.

Has protest increased since the 1970s? How a survey question can construct a spurious trend.

The literature on political participation asserts that protest has increased over the last four decades, all over the world. This trend is derived from surveys asking questions about participation in various forms of protest, including demonstrations, boycotts, and unofficial strikes. The latter question made sense in the context in which it was formulated, Britain in the early 1970s, and with regard to the original methodological aim, measuring 'protest potential'. The absence of a generic question on strikes, however, distorts our understanding of protest. Two sources of data on Britain in the 1980s and 1990 s - a population survey and an event catalogue - comprehensively measure strikes. They show that strikes greatly outnumbered demonstrations and other forms of protest. Another claim in the literature, that protesters are highly educated, no longer holds once strikes are properly counted. Strikes in Britain, as in many countries, have dramatically declined since the 1980s. This decline more than offsets any increase in demonstrations and boycotts, meaning that the total volume of protest has decreased. The episode illustrates how survey questions, when replicated without scrutiny, can misconstrue social trends.

The role of histology in forensic autopsies: is histological examination always necessary to determine a cause of death?

In England and Wales there is a conflict between the law and advice from regulatory bodies in relation to the sampling of human tissue for histological examination following medico-legal post-mortem examinations. Considering the results of previous publications, we performed a specific study to investigate the role of histology in determining the cause of death in cases at a forensic unit. A retrospective study of 500 adult forensic cases was performed. Cases were categorized by the role the histological examination played in determining a cause of death and its contributory factors. Furthermore, cause of death, manner of death, organ systems involved, and discrepancies were assessed. Of the 500 cases, histology was undertaken in 287 cases (58 %). Microscopic examination provided the cause of death in 2 % of cases where histology had been undertaken, and it added to the cause of death in 8 %. In 61 % of cases microscopy confirmed the macroscopic findings, and in 30 % it did not influence the medical cause of death. Histological examination of all organs in all forensic cases for the purpose of providing a medical cause of death is not supported. Practice guidance should be adjusted to reflect that, while histological examination is essential in certain circumstances, the decision to retain material for histology should be made on a case by case basis at the pathologist's discretion.

Motor cortex neuroplasticity following brachial plexus transfer.

In the past decade, research has demonstrated that cortical plasticity, once thought only to exist in the early stages of life, does indeed continue on into adulthood. Brain plasticity is now acknowledged as a core principle of brain function and describes the ability of the central nervous system to adapt and modify its structural organization and function as an adaptive response to functional demand. In this clinical case study we describe how we used neuroimaging techniques to observe the functional topographical expansion of a patch of cortex along the sensorimotor cortex of a 27-year-old woman following brachial plexus transfer surgery to re-innervate her left arm. We found bilateral activations present in the thalamus, caudate, insula as well as across the sensorimotor cortex during an elbow flex motor task. In contrast we found less activity in the sensorimotor cortex for a finger tap motor task in addition to activations lateralized to the left inferior frontal gyrus and thalamus and bilaterally for the insula. From a pain perspective the patient who had experienced extensive phantom limb pain (PLP) before surgery found these sensations were markedly reduced following transfer of the right brachial plexus to the intact left arm. Within the context of this clinical case the results suggest that functional improvements in limb mobility are associated with increased activation in the sensorimotor cortex as well as reduced PLP.

The impact of molecular and clinical factors on patient outcome in oligodendroglioma from 20 years' experience at a single centre.

The increased chemosensitivity of oligodendroglial tumours has been associated with loss of heterozygosity (LOH) of the p arm of chromosome 1 and the q arm of chromosome 19 (LOH 1p/19q). Other clinical and molecular factors have also been identified as being prognostic and predictive of treatment outcome. We reviewed 105 patients with oligodendroglioma treated at a single centre over 20 years. Median survival in oligodendroglioma patients with LOH 1p/19q was significantly longer (10.9 vs. 2.0 years). In the anaplastic oligodendroglioma group, univariate analysis demonstrated decreased patient age, presentation with seizures, use of adjuvant chemotherapy and LOH 1p/19q as predictors of improved survival. Multivariate analysis confirmed LOH 1p/19q as a significant predictor of improved survival (hazard ratio, 3.4; p=0.015). Median survival in patients with anaplastic oligodendroglioma with LOH 1p/19q was 15.4 years vs. 1.2 years for those without LOH 1p/19q. This study confirms the utility of LOH 1p/19q as a prognostic marker in oligodendroglioma.

miR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion.

Glioblastoma (GBM) represents a formidable clinical challenge for both patients and treating physicians. Due to better local treatments and prolonged patient survival, remote recurrences are increasingly observed, underpinning the importance of targeting tumour migration and attachment. Aberrant expression of microRNA (miRNA) is commonly associated with cancer and loss of miR-124a has previously been implicated to function as a tumour suppressor. The assessment of miR-124a in clinical specimens has been limited and a potential role in migration and invasion has been unexplored until now. We measured the expression levels of mature miR-124a in a retrospective series of 119 cases of histologically confirmed GBM and found its expression was markedly lower in over 80% of the GBM clinical specimens compared to normal brain tissue. The level of reduction in the clinical cohort varied significantly and patients with lower than the average miR-124a expression levels displayed shorter survival times. Endogenous miR-124a expression and the protein expression of three of its targets; IQ motif containing GTPase activating protein 1 (IQGAP1), laminin γ1 (LAMC1) and integrin ß1 (ITGB1) were significantly reciprocally associated in the majority of the clinical cases. We confirmed this association in our in vitro model. Functionally, the ectopic expression of mature miR-124a in a GBM cell line resulted in significant inhibition of migration and invasion, demonstrating a role for miR-124a in promoting tumour invasiveness. Our results suggest that miR-124a may play a role in GBM migration, and that targeted delivery of miR-124a may be a novel inhibitor of GBM invasion.

Schwannomatosis, sporadic schwannomatosis, and familial schwannomatosis: a surgical series with long-term follow-up. Clinical article.

OBJECT: The aim of this study was to provide disease-specific information about schwannomatosis in its different forms and to present 2 particular cases of malignant schwannomas in the context of familial schwannomatosis (FS). METHODS: The authors analyzed patients with pathologically defined schwannomas and identified those with varied forms of schwannomatosis. Each case was retrospectively analyzed for patient sex and age, number of operations and tumors excised, symptoms, location and size of tumors, extent of resection, nerve function pre- and postoperatively, complications, other nonsurgically treated tumors, malignancy, results of brain MR imaging, and follow-up data. RESULTS: One hundred fifty-eight patients underwent the excision of 216 schwannomas. One hundred forty-two patients presented with solitary schwannomas, 2 had neurofibromatosis Type 2 (NF2), and 14 presented with schwannomatosis. The average follow-up was 52 months. Six individuals had sporadic schwannomatosis, whereas 8 had the familial form of the disease. These 14 patients had an average age of 28.3 years at the time of disease onset (median 27.5 years) and 35.4 years at the time of the first operation (median 37 years) Thirteen of the 14 patients with schwannomatosis experienced pain as the first symptom. Eight (57%) of the 14 patients presented with at least 1 tumor in the spinal canal or attached to the spinal nerve roots. Malignant schwannomas developed in 2 patients from the same family during the follow-up. CONCLUSIONS: Patients suffering from schwannomatosis tend to be younger than those presenting with solitary schwannomas. Therefore, individuals presenting at a young age with multiple schwannomas but not meeting the criteria for NF2 should prompt the physician to suspect schwannomatosis. Patients with schwannomatosis who report pain should be exhaustively examined. The spine is affected in the majority of patients, and MR imaging of the spine should be part of the routine evaluation. Rapid enlargement of schwannomas in the context of FS should raise suspicion of malignant transformation.