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Background: Electroconvulsive therapy (ECT) involves the induction of a generalized seizure with an electrical current and has been used worldwide when treating medically refractory psychiatric illness. Here we describe a patient with no prior history or risk factors for epilepsy who developed temporal lobe epilepsy after chronic treatment of ECT. Methods: A 16-year-old right-handed boy with severe refractory depression received ECT treatment every 10 days for 8 months. Six months into his ECT treatment, the patient developed seizures and was admitted to a pediatric epilepsy monitoring unit. Results: Initial clinical events included lightheadedness, diaphoresis, and nausea with associated kaleidoscopic vision changes. Seizures progressed to confusion, fear and paranoia by the time the patient was admitted for monitoring. Long-term video EEG captured many focal seizures with impaired awareness, all originating from both temporal lobes. MRI was normal. ECT was terminated and the patient started on carbamazepine. He has been seizure free for the past 2 years on medication Conclusions: While rare, we present a case of a patient with no prior risk factors for epilepsy who developed temporal lobe epilepsy after chronic ECT treatment. Although ECT is an indispensable treatment for many medically refractory psychiatric illnesses, we suggest caution in young patient undergoing ECT.
The feasibility of using X-ray diffraction methods to measure residual stresses in uranium and zirconium (Zircaloy-2) was investigated. A precision method was developed for the determination of diffraction peak positions and the precision associated therewith. The statistical tables of Fisher and Yates were used to determine what order polynomial provided the best least squares fit within the known precision of the observed data. It was found that a second-order polynomial provided an adequate regression. With the aid of a desk calculator less than 5 min calculation time is required to determine the peak position to a precision of ±0.01°.
The stress constant for uranium was determined to be 1308 ± 110 psi/0.01° shift in Δ2θ for copper radiation on the (116) planes at 2θ = 158.3°. The stress constant for Zircaloy-2 was determined to be 430 ± 1 psi/0.01° shift in Δ2θ for chromium radiation on the (10,4) planes at 2θ = 156.4°.
Background: Anti-NMDAR Encephalitis is an autoimmune disease of children and adults which most often presents with sub-acute psychiatric disturbance or seizures, but includes a broad group of potential clinical manifestations. Routine neuroimaging, such as cerebral MRI, is often nonspecific or normal. Methods: This study reports a series of retrospectively reviewed pediatric patients with AntiNMDAR encephalitis with emphasis on the evolution of clinical features over time, cerebral MRI, 18-FDG Positron emission tomography (PET) findings, and post illness neurocognitive features. Results: Four cases of Antibody confirmed AntiNMDAR encephalitis were included, two male and two female, of a mean of 13 years of age. Patients had a mean of three symptom categories by presentation, though many of these were subtle, progressing to 6.5 by the end of the first month. MRI, CSF and EEG were abnormal for one, three and all patients, respectively. All patients had abnormal cerebral PET scans, and all displayed some temporal lobe hypermetabolism on either initial or repeat cerebral PET Scan. Conclusions: Anti-NMDAR encephalitis is a variable disorder with an evolving clinical presentation in children. Temporal hypermetabolism on cerebral PET may be a time dependent feature of the disorder.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
Background: Stiff person syndrome (SPS) is a rare disorder presenting with progressive stiffness and spasms of the musculature of the trunk and limbs. SPS is reported very rarely in children and adolescents, with 5 cases over 25 years in a recent 99 patient cohort. Methods: Case Study Results: Herein we report a 15 year old female, presenting with acute onset of rapidly progressive spasticity of the lower extremities. Initial exam was remarkable for markedly limited left knee range of motion, in addition to asymmetrical knee spastic catch and hyper-reflexia. EMG revealed almost continuous motor unit activity which dissipated with voluntary muscle contraction. Diagnosis was confirmed by high titres of glutamate decarboxylase (GAD65) antibodies >25,000 units/ml. The patient was initially treated with IVIG, baclofen, and diazepam followed by IV methylprednisolone, with mild subjective improvements. One day following the first rituximab treatment, she achieved spontaneous knee flexion and regained the ability to ambulate independently. There is a residual spastic catch at the knees. Conclusions: This case highlights that SPS, albeit extremely rare, should be considered in the differential diagnosis of acquired spasticity in children. Also noteworthy is the relatively rapid resumption of function with aggressive immunomodulatory treatments in this historically devastating disorder.
Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.
<Nocte> tamen insequenti ipso pervigilante in eodem loco alia excitata turris prima luce miraculo hostibus fuit. Simul et oppidi turris quae maximum propugnaculum fuerat, subrutis fundamentis, dehiscere ingentibus rimis et tum [xvi litt.] ṭọ [iii litt.] igni coepit; incendiique simul et ruinae metu territi Contrebienses de muro trepidi refugerunt; et ut legati mitterentur ad dedendam urbem ab universa multitudine conclamatum est. Eadem virtus quae irritaverat oppugnantem victorem placabiliorem fecit. Obsidibus acceptis pecuniae modicam exegit summam armaque omnia ademit. Transfugas liberos vivos ad se adduci iussit; fugitivos, quorum maior multitudo erat, ipsis imperavit ut interficerent. Iugulatos de muro deiecerunt.
Cum magna iactura militum quattuor et quadraginta diebus Contrebia expugnata, relictoque ibi L. Insteio [xvi litt.] ipse ad Hiberum flumen copias reduxit. Ibi hibernaculis secundum oppidum quod Castra Aelia vocatur aedificatis ipse in castris manebat; interdiu conventum sociarum civitatium in oppido agebat. Arma ut fierent pro copiis cuiusque populi per totam provinciam edixerat; quibus inspectis referre vetera arma milites iussit, quae aut itineribus crebris aut oppu [c. xxx litt.] facta erant, novaque iis per centuriones divisit. Equitatum quoque novis instruxit armis, vestimentaque praeparata ante divisa, et stipendium datum.
Common genetic variants, such as the brain-derived neurotrophic factor
(BDNF) Val/66/Met polymorphism (rs6265), are known to interact with
environmental factors such as early adversity to increase the risk of
subsequent major depression. Much less is known about how they interact
with individual differences in cortisol, although these also represent a
risk for major depression.
To determine whether this BDNF variant moderated the risk represented by
higher levels of morning salivary cortisol in adult women.
We recruited 279 premenopausal women who were at high risk of major
depressive disorder because of either negative self-evaluation,
unsupportive core relationship or chronic subclinical symptoms of
depression or anxiety. Morning salivary cortisol was measured daily for
up to 10 days at entry. Participants were followed up for about 12 months
by telephone calls at 3–4 monthly intervals. Major depression and severe
life events were assessed through interviews at baseline and follow-up;
DNA was obtained from the saliva.
There were 53 onsets (19%) of depressive episodes during follow-up. There
was a significant U-shaped relationship between adjusted morning cortisol
levels at baseline and the probability of depression onset during
follow-up. In total, 51% experienced at least one severe life
event/difficulty, and this strongly predicted subsequent onsets of
depressive episodes. The BDNF Val/66/Met genotype was
not directly associated with onsets of depression or with cortisol
levels, but there was significant interaction between Val/66/Met and
cortisol: the association between baseline cortisol and depression was
limited to those with the Val/66/Val variant. There was no interaction
between life events and either this BDNF polymorphism or cortisol
Morning salivary cortisol interacts with the BDNF Val/66/Met polymorphism
in predicting new depressive episodes. This paper adds to the evidence
that single gene polymorphisms interact with endogenous factors to
Perovskite compositions are used to investigate the relationship between the minor components (i.e. LREE, Fe3+ and Nb) and the oxygen fugacity (fo2) of perovskite in four different kimberlite lithofacies from the Dutoitspan pipe, Kimberley, South Africa, which range from diamondiferous to barren. The perovskite textures and chemical variations provide insight into magmatic and eruptive processes. Some crystals display cores with rims separated by a sharp boundary. The cores contain larger Na and LREE contents relative to the rims, which show a large increase in Fe3+ and Al. The mid-grade and barren kimberlites have bi-modal cores, reflected in the mineral chemistry, signifying multiple batches of magma and magma mixing. The fo2 of the magma is determined by an Fe-Nb oxygen barometer. The most diamondiferous kimberlite has the greatest Fe3+ content and highest fo2 (NNO –3.6 to –1.1). The kimberlite containing large diamonds has the smallest Fe3+ content and lowest fo2 (NNO –5.2 to –3.0). The barren and mid-grade kimberlites display a wide range of fo2,(NNO –5.3 to –1.5) as a result of perovskites forming in different melts and subsequently mixing together. Chemical and petrological evidence suggests that the volatile content, degassing, decompression and rate of crystallization can influence the rate at which the magma is erupted. One possibility is that the most oxidized magma, containing the highest volatile content, is therefore erupted much more rapidly, preserving diamond as a consequence.
It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virusinfected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0·001) and Hib (P < 0·01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.
In birds, the nucleus of the basal optic root (nBOR) of the accessory
optic system (AOS) and the pretectal nucleus lentiformis mesencephali (LM)
are involved in the analysis of optic flow and the generation of the
optokinetic response. In several species, it has been shown that the AOS
and pretectum receive input from visual areas of the telencephalon.
Previous studies in pigeons using anterograde tracers have shown that both
nBOR and LM receive input from the visual Wulst, the putative homolog of
mammalian primary visual cortex. In the present study, we used retrograde
and anterograde tracing techniques to further characterize these
projections in pigeons. After injections of the retrograde tracer cholera
toxin subunit B (CTB) into either LM or nBOR, retrograde labeling in the
telencephalon was restricted to the hyperpallium apicale (HA) of the
Wulst. From the LM injections, retrograde labeling appeared as a discrete
band of cells restricted to the lateral edge of HA. From the nBOR
injections, the retrograde labeling was more distributed in HA, generally
dorsal and dorso-medial to the LM-projecting neurons. In the anterograde
experiments, biotinylated dextran amine (BDA) was injected into HA and
individual axons were reconstructed to terminal fields in the LM and nBOR.
Those fibers projecting to the nBOR also innervated the adjacent ventral
tegmental area. However, tracing of BDA-labeled axons revealed no evidence
that individual neurons project to both LM and nBOR. In summary, our
results suggest that the nBOR and LM receive input from different areas of
the Wulst. We discuss how these projections may transmit visual and/or
somatosensory information to the nBOR and LM.
We demonstrate a close analogy between a viscoelastic medium and an electrically
conducting fluid containing a magnetic field. Specifically, the dynamics of the
Oldroyd-B fluid in the limit of large Deborah number corresponds to that of a
magnetohydrodynamic (MHD) fluid in the limit of large magnetic Reynolds number.
As a definite example of this analogy, we compare the stability properties of differentially
rotating viscoelastic and MHD flows. We show that there is an instability
of the Oldroyd-B fluid that is physically distinct from both the inertial and elastic
instabilities described previously in the literature, but is directly equivalent to the
magnetorotational instability in MHD. It occurs even when the specific angular momentum
increases outwards, provided that the angular velocity decreases outwards;
it derives from the kinetic energy of the shear flow and does not depend on the curvature
of the streamlines. However, we argue that the elastic instability of viscoelastic
Couette flow has no direct equivalent in MHD.
This volume of the second edition of the Cambridge Ancient History traces the history of Rome from its origins to the eve of the Second Punic War. Although the period covered is essentially the same as in the undivided Volume VII of the first edition, the treatment of the material is completely fresh and is much more extensive. Account is taken of new scholarly insights and of the considerable amount of new evidence, much of it archaeological, which has become available since the first edition was published. After a survey of the sources of our information the origins of Rome are discussed, beginning with the first discernible traces of the bronze Age settlement and going on to an assessment of the regal period. The complex and often controversial history of the early Republic is examined with reference to its internal development, the evolution of its relationships with the Latins, and the remorseless, if occasionally erratic, advance of Roman power in parts of Italy less immediately adjacent to the city. These developments are traced further in relation to the intervention of Pyrrhus and its aftermath, leading to consideration of Rome's relationships with Carthage, the First Punic War, and the beginnings of overseas empire. Rome is considered from a different perspective in a chapter on society and religion.