Figure 9 (a–j): Right frontal tuberculoma in a 50-year-old male patient on antituberculous therapy with follow-up every 4 months for a total period of 1 year.
TBI is an injury to the brain caused by a blow or jolt to the head from blunt or penetrating trauma.
Concussion is a mild head injury that can cause a brief loss of consciousness and usually does not cause permanent brain injury. Diffuse axonal injury (DAI) is a shearing and stretching of the nerve cells at the cellular level. Traumatic Subarachnoid Hemorrhage (tSAH) is bleeding into the space that surrounds the brain. Contusion is a bruise to a specific area of the brain caused by an impact to the head; also called coup or contrecoup injuries.
Although described as individual injuries, a person who has suffered a TBI is more likely to have a combination of injuries, each of which may have a different level of severity. Secondary brain injury occurs as a result of the body's inflammatory response to the primary injury. Diffuse injuries (such as a concussion or diffuse axonal injury) will typically cause an overall decreased level of consciousness. Every patient is unique and some injuries can involve more than one area or a partial section, making it difficult to predict which specific symptoms the patient will experience.
Common causes include falls, car or motorcycle crashes, vehicular accidents involving pedestrians, athletics, and assaults with or without a weapon. Approximately 1.5 to 2 million adults and children suffer a traumatic brain injury (TBI) each year in the United States.
When a person is brought to the emergency room with a head injury, doctors will learn as much as possible about his or her symptoms and how the injury occurred.
The Glasgow Coma Score (GCS) is a 15-point test used to grade a patient's level of consciousness.
Computed Tomography (CT) is a noninvasive X-ray that provides detailed images of anatomical structures within the brain.
Magnetic Resonance Imaging (MRI) is a noninvasive test that uses a magnetic field and radiofrequency waves to give a detailed view of the soft tissues of the brain. The goals of treatment are to resuscitate and support the critically ill patient, minimize secondary brain injury and complications, and facilitate the patient's transition to a recovery environment. Neurocritical care is the intensive care of patients who have suffered a life-threatening brain injury. Surgery is sometimes necessary to repair skull fractures, repair bleeding vessels, or remove large blood clots (hematomas). Craniotomy involves cutting a hole in the skull to remove a bone flap so that the surgeon can access the brain.
Tracheotomy involves making a small incision in the neck to insert the breathing tube directly into the windpipe. Percutaneous Endoscopic Gastrostomy Tube (PEG) is a feeding tube inserted directly into the stomach through the abdominal wall. Clinical trials are research studies in which new treatmentsa€”drugs, diagnostics, procedures, and other therapiesa€”are tested in people to see if they are safe and effective. When a patient is in a coma, his or her eyes are closed and they show minimal reaction when spoken to or stimulated.
As patients recover, they need help understanding what has happened to them during this a€?lost period of time.a€? Keep in mind that the recovery of consciousness is a gradual process a€“ not just a matter of waking up. Most patients are discharged from the hospital when their condition has stabilized and they no longer require intensive care. A long-term acute care (LTAC) facility is a place for patients who have stabilized from their initial injury but who still require a ventilator or frequent nursing care. A rehabilitation facility is a place for patients who do not require a ventilator but who still require help with basic daily activities. Recovering from a brain injury relies on the brain's plasticitya€”the ability for undamaged areas of the brain to take over functions of the damaged areas. A physical therapist helps patients rebuild and maintain strength, balance, and coordination. An occupational therapist helps patients to perform activities of daily living, such as dressing, feeding, bathing, toileting, and transferring themselves from one place to another. A speech therapist helps patients by monitoring their ability to safely swallow food and helping with communication and cognition. A neuropsychologist helps patients relearn cognitive functions and develop compensation skills to cope with memory, thinking, and emotional needs.
Always wear your helmet when riding a bicycle, motorcycle, skateboard, or all-terrain vehicle. Always wear your seat belt and ensure that children are secured in the appropriate child safety seats. Avoid falls in the home by keeping unsecured items off the floor, installing safety features such as non-slip mats in the bathtub, handrails on stairways, and keeping items off of stairs. Support groups provide an opportunity for patients and their families to share experiences, receive support, and learn about advances in treatments and medications. Mayfield’s neurotrauma patients receive the most highly skilled care available anywhere in the United States.
For support groups in the Greater Cincinnati area, contact the Brain Injury Association of Ohio Support Group at (513) 542-2704. We will be provided with an authorization token (please note: passwords are not shared with us) and will sync your accounts for you. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at time of review. Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI.
The Centers for Disease Control estimate that every year in the United States approximately 2.5 million people sustain a Traumatic brain injury (TBI). The lack of effective pharmacological treatments for TBI patients despite the many clinical trials in the past two decades suggests that the development of improved therapies for the treatment of TBI will depend upon a better understanding of the underlying mechanisms that drive secondary neuronal injury during the acute phase of TBI. For analysis of cerebrovascular permeability after TBI, mice were injected with 100 microliters of 4% EB (intravenous, Sigma-Aldrich) in lactated Ringer’s solution 1 h before the animals were sacrificed by transcardial perfusion with phosphate buffered saline (PBS) for 8 min.
For the data analysis, Image J software (NIH) was used to calculate the lesion volume from T2 scan, and Matlab software (MathWorks, Natick, MA, USA) was used to calculate the apparent diffusion coefficient from DWI scan. Deeply anaesthetized mice were perfused transcardially 21 days after TBI with PBS for 2 min and followed by 4% paraformaldehyde for 5 min. This study was conducted in accordance with the National Health and Medical Research Council of Australia National Statement on Ethical Conduct in Research Involving Humans and approved by Human Ethics Committees of the Alfred Hospital and Austin Hospital, Melbourne, Australia. Brain edema, defined as an increase of brain tissue volume resulting from an increase in its fluid content, is an important pathological process in many central nervous system diseases, such as cerebral ischemia, traumatic brain injury, and epilepsy. Transient focal cerebral ischemia was induced by MCAO as previously described (Li et al., 2013).
The extent of post-ischemic brain edema was determined by the wet- and dry-weight (wt) at 48 h post-MCAO.
At 48 h post-MCAO or on day 3 after GSK1016790A-injection, the mice were perfused transcardially with ice-cold phosphate-buffered saline under anesthesia.
Brain edema began to develop as early as 3 h after MCAO and progressed rapidly to a maximum on the second and third day, and gradually regressed thereafter (Gotoh et al., 1985).
During stroke, MMP-2 and MMP-9 are up-regulated, leading to increased BBB permeability through degradation of endothelial matrix proteins. During the cerebral ischemica, cytotoxic cell swelling develops shortly after the occlusion of cerebral artery and is caused by energy failure.
The BBB is formed by brain endothelia cells lining the microvascular system that is sealed by tight junction (TJ). Brain edema, either a cause or a consequence, disturbs physiological neuronal function and amplifies tissue damage.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Science, Technology and Medicine open access publisher.Publish, read and share novel research. Sudlow CL, Warlow CP (1997) Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. Fogelholm R, Murros K, Rissanen A, Avikainen S (2005) Long term survival after primary intracerebral haemorrhage: a retrospective population based study.
Ardizzone TD, Zhan X, Ander BP, Sharp FR (2007) SRC kinase inhibition improves acute outcomes after experimental intracerebral hemorrhage. Oda H, Kumar S, Howley PM (1999) Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination. Biscardi JS, Ishizawar RC, Silva CM, Parsons SJ (2000) Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and c-Src interactions in breast cancer. Morse WR, Whitesides JG, 3rd, LaMantia AS, Maness PF (1998) p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory pathway.
Rouer E (2010) [Neuronal isoforms of Src, Fyn and Lck tyrosine kinases: A specific role for p56lckN in neuron protection].
Stein PL, Vogel H, Soriano P (1994) Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Ali DW, Salter MW (2001) NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity.
Sharp F, Liu DZ, Zhan X, Ander BP (2008) Intracerebral hemorrhage injury mechanisms: glutamate neurotoxicity, thrombin, and Src.
Hossain MI, Kamaruddin MA, Cheng HC (2012) Aberrant regulation and function of Src family tyrosine kinases: their potential contributions to glutamate-induced neurotoxicity.
Yang M, Leonard JP (2001) Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src. Zheng F, Gingrich MB, Traynelis SF, Conn PJ (1998) Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Kohr G, Seeburg PH (1996) Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family. Liu DZ, Ander BP, Sharp FR (2010) Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases. Novak B, Tyson JJ, Gyorffy B, Csikasz-Nagy A (2007) Irreversible cell-cycle transitions are due to systems-level feedback.
Liu DZ, Ander BP (2012) Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of aberrant cell cycle diseases: an update. Nagy Z, Esiri MM, Cato AM, Smith AD (1997) Cell cycle markers in the hippocampus in Alzheimer's disease. McShea A, Harris PL, Webster KR, Wahl AF, Smith MA (1997) Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Nagy Z, Esiri MM (1998) Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy.
Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. O'Hare M, Wang F, Park DS (2002) Cyclin-dependent kinases as potential targets to improve stroke outcome. Lefevre K, Clarke PG, Danthe EE, Castagne V (2002) Involvement of cyclin-dependent kinases in axotomy-induced retinal ganglion cell death. Jordan-Sciutto KL, Dorsey R, Chalovich EM, Hammond RR, Achim CL (2003) Expression patterns of retinoblastoma protein in Parkinson disease.
Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. Ranganathan S, Bowser R (2003) Alterations in G(1) to S phase cell-cycle regulators during amyotrophic lateral sclerosis.
Herrup K, Neve R, Ackerman SL, Copani A (2004) Divide and die: cell cycle events as triggers of nerve cell death. Yang Y, Varvel NH, Lamb BT, Herrup K (2006) Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. Rao HV, Thirumangalakudi L, Desmond P, Grammas P (2007) Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons.
Zhang J, Herrup K (2011) Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death in post-mitotic neurons.
Liu DZ, Ander BP (2011) Cell cycle phase transitions: signposts for aberrant cell cycle reentry in dying mature neurons. Mishra R, Wang Y, Simonson MS (2005) Cell cycle signaling by endothelin-1 requires Src nonreceptor protein tyrosine kinase. Self-monitoring of blood glucose (SMBG) is important in evaluating the efficacy of prescribed anti-hyperglycaemic therapies and can help the patient better understand the importance of achieving glycaemic control. Several instruments for measurement of blood pressure have been validated by important medical societies involved in hypertension, and much effort has been given to compliance and patient comfort. A literature search on PubMed using the term “self-measurement of blood glucose (SMBG) and pain” retrieved only two publications, demonstrating a general lack of interest of the medical community. Another problem of significant importance concerns the reproducibility and accuracy of blood glucose measurements.
Unfortunately, by pricking the fingertip at this depth, numerous tactile corpuscles in the dermis are also touched, causing the unpleasant sensation of pain.
The objective of the present study is to compare alternative sites of puncture using a new semi-rigid lancet and determine if blood glucose values are similar to those obtained using traditional methods. The present study enrolled 5 general practitioners and 70 patients with diabetes and without diabetes-related (micro-albuminuria, retinopathy, arterial disease of the lower limbs) complications. Semi-rigid lancets were provided by Terumo Corporation (Tokyo, Japan) and consisted in a 23-gauge needle that was remodelled to permit less painful puncture than a traditional lancet (Fig. Using a periungual puncture site, pain was not referred by any subject, although a bothersome sensation was noted by some. The present study evaluated the use of alternative puncture sites that are associated with less pain. In conclusion, it is our belief that a new type of finger lancet that decreases or eliminates pain associated with lancing merits additional consideration.
Tumefactive Multiple Sclerosis (MS) is a rare variant of MS that is extremely difficult to diagnose.
We present a rare case of Tumefactive MS that exhibited a clinical picture identical to brain metastasis. A 48-year-old African American female was brought in by emergency medical services after falling with a brief loss of consciousness.
On physical examination the patient was afebrile, normotensive and tachycardic with an oxygen saturation of 89% on room air.
Due to a non-focal neurological examination, she was discharged on Levetiracetam 500 mg for seizure prophylaxis and Dexamethasone 4 mg for perilesional oedema. The imaging studies for this patient established a concern for metastasis, infection or primary malignancy. We would like to acknowledge Dashartha Harsewak MD for interpreting radiological scans, Musarat Shareeff MD for valuable guidance and Anna Lucia Giannone for input on figure design.
JOANN COLEMAN DNP, ANP, ACNP, AOCN, Acute Care Nurse Practitioner & Clinical Program Coordinator, Sinai Center for Geriatric Surgery, Baltimore, MD, USA. Methamphetamine abuse is associated with various cardiac complications like acute coronary syndrome, cardiomyopathy and sudden cardiac death.
Methamphetamine and related compounds are the most widely abused drugs in the world after cannabis 1. Methamphetamine intoxication causes various systemic complications like sympathetic over activity, agitation, seizure, stroke, rhabdomyolysis and cardiovascular collapse.
Here we present a case of methamphetamine overdose, which presented with cardiomyopathy and severe systolic heart failure whose cardiac function was normalized after treatment. A 38-year-old male presented with shortness of breath, chest tightness and sweating which started after he used intravenous crystal meth the day before presentation. Subsequently the patient became tachypnoeic and hypoxic, was intubated, put on a mechanical ventilator, and sedated with versed, fentanyl and propofol. This patient used intravenous crystal meth after which his problem started, so the most likely culprit was methamphetamine. ASHOK RAJ DEVKOTA, MD, Resident, Department of Internal medicine, Interfaith medical Center, Brooklyn, NY. ALIX DUFRENSE, MD, Chair, Department of Cardiology, Interfaith Medical Center, Brooklyn, NY. PREMRAJ PARAJULI, MD, Resident, Department of Medicine, Interfaith Medical Center, Brooklyn, NY.
ASHOK RAJ DEVKOTA, MD, Resident, Department of Internal medicine, Interfaith medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213.
Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. Here we present a case of Acute Oesophageal Necrosis, a rare but increasingly recognised endoscopic finding.
A 79 year old lady presented to the accident and emergency department with severe abdominal pain. She had multiple co-morbidities, including ischaemic heart disease, hypertension and chronic kidney disease. Three days into her admission she had a single episode of hematemesis and a gastroscopy was arranged.
The images seen at endoscopy demonstrate a region of oesophageal ulceration progressing to a diffuse, circumferential, black discoloration of the distal esophageal mucosa, with an abrupt transition to normal mucosa at the gastro-esophageal junction (Figs.
AON was first described in 1990 by Goldberg et al, since which over one hundred cases have been reported in the literature1.
The aetiology of this condition is not entirely clear; however case reports to date suggest that this is almost exclusively observed in those who are systemically unwell, usually in the context of multi-organ dysfunction5-7. The most common indication for the gastroscopy that makes the diagnosis of AON is hematemesis and melena, accounting for over 75% of cases6.
Whilst AON has no specific treatment, its presence is indicative of significant systemic compromise and predicts a poor prognosis. SABINA BEG, Lister Hospital, North East Hertfordshire NHS trust, Correy Mill lane, Hertfordshire, SG1. Angiogenesis is pivotal component of many normal biological programmes as well as of pathogenetic processes involved in tumour growth and progression and of inflammatory and autoimmune diseases such as multiple sclerosis (MS), a demyelinating disease of the CNS. Angiogenesis is an integral process in biological programmes of embryonic development, tissue damage and regeneration, tumour growth and progression and pathogenesis of inflammatory and autoimmune diseases.
Multiple sclerosis is an autoimmune inflammatory condition and so immunomodulators have been used in treatment.
Thalidomide was introduced over four decades ago to treat respiratory infections and to combat morning sickness in pregnant women. Most of the work on the efficacy of thalidomide and the analogues has been carried out in preclinical models. This report describes a case of secondary syphilis represented by generalized lymphadenopathy . As syphilis is a notable clinical and pathological imitator, its diagnosis remains challenging.
We report the case of a seventy-year old woman with a medical history of arterial hypertension.
On initial examination, the patient was thin with generalised lymphadenopathy: she had an axillary adenopathy that measured 4 cm in diameter in the right axilla and one measuring 3 cm in the left axilla.
A CT scan of the patient’s neck and chest showed a marked anterior mediastinal mass of about 50 mm diameter with multiple calcifications. According to these clinical and pathological findings, the most common granulomatous diseases are mycobacterial diseases such as tuberculosis, hence why the diagnosis of tuberculous lymphadenitis was highly suspected, and the patient was given anti-TB drugs. Additional histological stains, including Ziehl-Nielsen, were performed and returned negative, excluding the diagnosis of tuberculosis.
The patient received intramuscular injections of 2.4 million units of benzathine penicillin every three weeks. Syphilis is predominantly a sexually-transmitted disease with both local and systemic manifestations.
Syphilis has many non-specific signs and symptoms that may be overlooked by the physician, because in some cases it may simply be indistinguishable from other more common diseases.
Several older methods can be used to confirm syphilis diagnosis such as direct identification of TP by dark-field microscopy or direct fluorescent antibody tests, but such tests are not practical in a routine clinical setting and these methods can only be performed on lesion exudate or tissue 3. Lymphadenitis is the most common extra-pulmonary manifestation of tuberculosis but its diagnosis is difficult, often requiring biopsy.
In the case of tuberculosis infection, demonstration of the mycobacteria can be done with Ziehl-Neelsen staining or by immunofluorescence using auramine-rhodamine. NAZIHA KHAMMASSI, ASMA GARGOURA, HAYKEL ABDELHEDI, YOUSSEF KORT, MANEL MABROUK and OUAHIDA CHERIF, Department of Internal Medicine, Razi Hospital, 2010- Manouba, Tunisia. NAZIHA KHAMMASSI, Doctor, Department of Internal Medicine, Razi Hospital, 2010- Manouba, Tunisia.
Hernandez-Pando R, Bornstein QL, Aguilar Leon D, Orozco EH, Madrigal VK, Martinez Cordero E.
During impact to the head, the soft brain crashes back and forth against the inside of the hard skull causing bruising, bleeding, and shearing of the brain. Symptoms can include confusion, disorientation, memory loss, headache, and brief loss of consciousness. It occurs when the brain quickly moves back and forth inside the skull, tearing and damaging the nerve axons. This space is normally filled with cerebrospinal fluid (CSF), which acts as a floating cushion to protect the brain.
In coup injuries, the brain is injured directly under the area of impact, while in contrecoup injuries it is injured on the side opposite the impact. This makes answering questions like a€?what part of the brain is hurt?a€? difficult, as more than one area is usually involved. Whereas, focal injuries (such as an ICH or a contusion) will have symptoms based on the brain area affected (Fig.
The table lists the lobes of the brain and their normal functions as well as problems that may occur when injured. Most people who experience a head injury, about 1.1 million, will have a mild injury that does not require an admission to the hospital. Doctors assess the patient's ability to 1) open his or her eyes, 2) ability to respond appropriately to orientation questions, (a€?What is your name?
CT scan shows a blood clot (hematoma) collecting under the bone (red arrows) and displacing brain (yellow arrow) to the other side of the skull. A CT scan of the head is taken at the time of injury to quickly identify fractures, bleeding in the brain, blood clots (hematomas) and the extent of injury (Fig.
The numbers generated from this scan provide a general prognosis about the patient's ability to recover from the injury. Despite significant research, doctors only have measures to control brain swelling, but do not have a way to eliminate swelling from occurring. It is possible that your loved one's appearance will be altered because of facial injury and equipment that is used for monitoring. A brain oxygen and cerebral blood flow monitor is inserted into the brain tissue and secured to the skull with a bolt. A catheter is placed through a small hole in the skull and positioned inside the ventricle (fluid-filled area deep within the brain) to measure pressure inside the head (Fig. A catheter is placed through a small hole in the skull and positioned within the brain tissue. When patients are on a ventilator or have a decreased level of alertness, they may not be able to eat or get sufficient nutrition to meet their needs. Patients who've had a moderate to severe traumatic brain injury are at higher risk of having seizures during the first week after their injury. A large decompressive craniectomy is removed and the dura is opened to allow the brain to expand. This is typically performed when extremely high intracranial pressure becomes life threatening. The ventilator will then be connected to this new location on the neck and the old tube is removed from the mouth.
A small camera is placed down the patient's throat into the stomach to aid with the procedure and to ensure correct placement of the PEG tube (see Surgical Procedures for Accelerated Recovery). Movements that may be seen at this time are basic reflexes or automatic responses to a stimulus.
Patients at this stage will move away from any stimulus or tend to pull at items attached to them in an attempt to remove anything that is uncomfortable or irritating. They may look at a person and follow them around the room with their eyes, or follow simple commands such as a€?Hold up your thumb.a€? Patients tend to be confused and may have inappropriate or agitated behaviors. A social worker will work closely with the family as preparations are made for a return home or for transfer to a long-term care or rehabilitation center. Physical and occupational therapists work with patients to help them achieve their maximum potential for recovery. For information about Neurocritical Care at the University of Cincinnati Neuroscience Institute, call 866-941-8264.
There are four ventricles: two lateral ventricles (one on each side of the brain), the third ventricle, and the fourth ventricle. Our Neuroscience Intensive Care Unit at The University of Cincinnati Medical Center provides a full spectrum of advanced neuroscience treatment, while the nearby Drake Center offers state-of-the-art rehabilitation care. However, this immunosuppressed condition can predispose the patient to opportunistic infections like tuberculosis.
Intracerebral calcification in a case of systemic lupus erythematosus with neurological manifestations.
Brain white-matter lesions in celiac disease: A prospective study of 75 diet-treated patients. This means that you will not need to remember your user name and password in the future and you will be able to login with the account you choose to sync, with the click of a button. This page doesn't support Internet Explorer 6, 7 and 8.Please upgrade your browser or activate Google Chrome Frame to improve your experience. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. There are approximately 53,000 TBI related deaths and 283,000 hospitalizations annually, with many patients suffering permanent disability (Frieden et al., 2014). One of the most serious and difficult to control secondary effects of TBI is the development of cerebral edema. Our data suggest that PDGF signaling contributes to the development of vasogenic edema by increasing BBB opening after TBI and that both vasogenic edema and cognitive impairment can be reduced by Imatinib treatment.
The brains were removed and separated into hemispheres ipsilateral and contralateral to the TBI.
To calculate volumetric tissue loss 21 days after TBI, ROIs from MRI slices corresponding to the hippocampal region were calculated by Image J.


The pool was 1.2 meters in diameter and filled with water made opaque with white non-toxic paint. CSF (30 μl of undiluted CSF) were subjected to SDS-PAGE electrophoresis under denaturing conditions and transferred to nylon membranes using standard conditions. Activation of transient receptor potential vanilloid 4 (TRPV4) causes an up-regulation of matrix metalloproteinases (MMPs) in lung tissue. TRPV4 can be activated by diverse stimulation, including cell swelling-induced mechanical stimulation, modest heat, hypotonic stimulation, endogenous and synthetic ligands (Vincent and Duncton, 2011). All experimental procedures were conformed to Guidelines for Laboratory Animal Research of Nanjing Medical University and were approved by Institutional Animal Care and Use Committee of Nanjing Medical University. In brief, the mice were placed in a stereotaxic device (Kopf Instruments, Tujunga, CA, USA) after they were anesthetized.
Sham-operated animals were treated identically, except that the middle cerebral artery was not occluded after neck incision. After the mice were decapitated under anesthesia, the olfactory bulb, cerebellum and brainstem were removed. The cerebral hemispheres were collected, followed by homogenization with 50% trichloracetic acid and centrifugation. Therefore, we examined the effect of HC-067047, a specific TRPV4 antagonist, on the brain water content at 48 h post-MCAO.
It is the earliest morphological change that cannot be avoided, but this cellular morphology change indeed facilitates the activation of TRPV4. Src family kinases (SFKs) participate in mitogenic signaling pathways that play critical roles in blood-brain barrier (BBB) disruption and self-repair after intracerebral hemorrhage (ICH).
Pain related to puncture of the fingertip, needed for determination of blood glucose, can notably reduce compliance of patients using self-monitoring devices.
In the traditional method, blood samples for self-monitoring are taken from the fingertip of any finger using a lancing device with a semi-rigid prick (Figs. In a recent study by Koschinsky1 on around 1000 patients with type 1 (T1D) and type 2 diabetes (T2D), about one-half (51%) referred that they normally pricked themselves on the side of the fingertip because it is less painful. These encouraging results undoubtedly warrant further investigation in a larger cohort, but nonetheless suggest that compliance with SMBG can be optimised. Due to the possibility to select a minimal depth of only 0.3 mm, it can be used at alternative sites that allow a reduction in the frequency of samples taken from the fingertip. It can resemble malignancy and perplex the clinician until all diagnostic tests are exhausted.
This was diagnosed with surveillance MRI and CSF analysis in the absence of a brain biopsy.
Initial lumbar puncture with CSF analysis was not completed secondary to possible complications that could be incurred while on necessary PE anticoagulation. Over subsequent months the patient did well without headaches, vision changes or seizure like activity. Repeat MRI of the head (Figure 4 A-C) showed predominantly T1 hypointense and T2 hyperintense (A-B) lesions with significant decrease in size from MRI done three months ago. MRI of brain showing axial T1-weighted (A-C) hypodense lesions of the left centrum semiovale(A), left basal ganglia(B) and left occipital lobe(C).
MRI of abdomen showing coronal T2-weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE) hyperdense lesion. MRI of brain (3 month after initial scans) showing axial T-2 weighted (A-B) hyperdense lesions of the left centrum semiovale(A) and left basal ganglia(B).
Increased accumulations of N-isopropyl-p-[123I]- iodoamphetamine related to tumefactive multiple sclerosis. Tumefactive multiple sclerosis requiring emergent biopsy and histological investigation to confirm the diagnosis: a case report.
Distinguishing tumefactive demyelinating lesions from glioma or central nervous system lymphoma: added value of unenhanced CT compared with conventional contrast-enhanced MR imaging. We report a case of patient who presented with cardiomyopathy and acute heart failure due to intravenous methamphetamine abuse. Methamphetamine is a synthetic stimulant which acts both on central and peripheral nervous system.
Acute cardiac complications of methamphetamine like chest pain, hypertension, arrhythmias, aortic dissection, acute coronary syndrome, cardiomyopathy, and sudden cardiac death have been reported 4, 5. He was an active poly substance abuser and used different drugs like marijuana, alprazolam, amphetamine, cocaine, percocet (oxycodone and acetaminophen) and clonazepam regularly. Although he used multiple drugs including cocaine and amphetamine, which have acute and chronic effects on the heart, his cardiac function was normal before. It has been postulated that necrosis most commonly occurs as a consequence of hypo-perfusion caused by a low flow state in those with underlying vascular disease. It is therefore likely that AON is significantly under reported as endoscopy is often precluded in those who are clinically unstable. This diagnosis should alert physicians that close monitoring and aggressive treatment is required to optimise patient outcomes. The severity of the underlying clinical condition appears to be the most important factor in determining prognosis. Many angiogenic factors are expressed in MS and in the animal model of MS known as experimental autoimmune encephalomyelitis. It is recognised that aberrant activation of the immune system and the associated network of its regulation are important events in the pathogenesis of the disease. Quite understandably, in the clinical setting very little effort is seen to check whether thalidomide or the analogues provide any beneficial effects in MS or neuro-inflammation.
SHERBET, DSc, FRSC, FRCPath, Institute for Molecular Medicine, Huntington Beach CA, USA and University of Newcastle upon Tyne UK.
SHERBET, Institute for Molecular Medicine, Huntington Beach CA, USA and University of Newcastle upon Tyne UK.
Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter.
Physicians should be vigilant to suspect syphilis in cases of non-specific signs, such as lymphadenopathies, even in patients with no apparent risk for sexually transmitted infections or a history of primary syphilis. She had neither smoked cigarettes nor drunk alcohol and she had no significant medical family history. She also had two cervical lymph nodes that were less significant, and one enlarged right inguinal lymph node of about 3 cm in diameter. The remaining results of her full blood count, electrolytes, liver enzymes, lactate dehydrogenase and urine analysis were within normal limits. However, other differential diagnoses were considered, including bacterial infections like syphilis or actinomycosis, protozoal infections such as toxoplasmosis, and miscellaneous diseases such as sarcoidosis, Crohn's disease and Wegener's granulomatosis. Additional clinical and laboratory examinations were performed for both the patient and her family. The causative organism is the spirochete Treponema Pallidum (TP) which was first demonstrated on the 17th of May 1905 1. In fact, syphilis can share clinical manifestations with other treponemal and non-treponemal diseases, and it may be asymptomatic in some stages.
This case presented diagnostic difficulties because of its clinical and histopathological resemblance to other pathological conditions. In such granulomatous disease, and in cases of persisting doubts, it is necessary to identify the specific etiological agent by further investigations such as special stains, culture methods and molecular techniques like polymerase chain reaction (PCR) and serological tests, as in the case of syphilis.
A definitive diagnosis cannot be made on the basis of the history and physical examination alone, confirmatory testing should be performed in order to identify the specific etiologic agent correctly.
Inflammatory cytokine production by immunological and foreign body multinucleated giant cells. The hyperintense portion of the lesion is cellular with a very small necrotic fraction appearing hypointense on the MT T1W images. While an injury may occur in a specific area, it is important to understand that the brain functions as a whole by interrelating its component parts. Another 235,000 individuals will be hospitalized with a moderate to severe head injury, and approximately 50,000 will die. What is the date today?a€?), and 3) ability to follow commands (a€?Hold up two fingers, or give a thumbs upa€?).
Their care is overseen by a neurointensivist, a specialty-trained physician who coordinates the patient's complex neurological and medical care. Numerous tubes, lines, and equipment may be used to closely monitor his or her heart rate, blood pressure, and other critical body functions. A catheter is inserted into the ventricle of the brain to monitor intracranial pressure (ICP). A nasal-gastric feeding tube may be inserted through the patient's nose and passed down the throat into the stomach. Approximately 24% of patients who suffer a TBI will have a seizure that is undetected unless they are monitored by an electroencephalogram (EEG). These medications can be turned off quickly in order to awaken the patient and check their mental status. It works by drawing the extra water out of the brain cells into the blood vessels and allowing the kidneys to filter it out of the blood.
Patients are given an anti-seizure medication (levetiracetam or phenytoin) to prevent seizures from occurring. The bone flap is replaced in its normal position and secured to the skull with plates and screws.
At that time the patient is taken to the operating room where a large portion of the skull is removed to give the brain more room to swell (Fig. Information about current clinical trials, including eligibility, protocol, and locations, are found on the Web.
The brain wave activity in a comatose person is very different from that of a sleeping person.
His or her eyes may be open more often, but they may not be aware of their behavior or be able to interact in a meaningful way. It is difficult to determine at what point a patient will start understanding and interacting with their caregivers or family in a meaningful way.
You can most effectively convey your concern by sitting quietly and holding your loved one's hand. Once off the ventilator, they can be moved to a rehabilitation or skilled nursing facility. Rehab facilities are either Acute Inpatient Rehab that require patients to participate in 3 hours or more of rehab a day or a Skilled Nursing Facility (SNF) that provide 1-3 hours of rehab a day depending on what the patient can tolerate. And most importantly, on the patient's hard work to relearn and compensate for lost abilities. This information is not intended to replace the medical advice of your health care provider.
Our neurointensivists work one-on-one with patients and families, and our dedicated nurses are trained to help you understand your loved one’s condition and gain access to available resources.
In these patients, tuberculosis can affect different systems and can have uncommon clinical presentations. Cerebral edema leads to brain swelling and increased intracranial pressure (ICP), which in severe cases can result in cistern compression, brain herniation, and even death. These findings identify novel targets for TBI treatment and contribute to our understanding of the relationship between BBB leakage and the downstream secondary injuries associated TBI. For the unilateral TBI experiments, a 3.5 mm craniotomy was made over the right parietotemporal cortex with an electric drill (Harvard Apparatus) and the bone flap was removed. Each hemisphere was then homogenized in N, N-dimethylformamide (Sigma-Aldrich) and centrifuged for 45 min at 25,000 rcf. Brains were cut in 14 μm-thick coronal sections with a sliding microtome and stained with hematoxylin and eosin.
The escape platform consisted of a 10 cm platform that was submerged 0.5 cm below the surface of the water in the center of one of the quadrants. The mouse was then placed into the water facing the wall of the pool and allowed to search for the platform. Patients who required an external ventricular drain (EVD) for monitoring ICP were included.
To detect PDGF-CC, membranes were hybridized with a polyclonal goat anti-human PDGF-C antibody (RnD Systems, AF1560) diluted 1:200.
MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema.
Our recent study reveals that the protein level of TRPV4 increases during ischemia-reperfusion (Jie et al., 2014). Left (contralateral) and right (ipsilateral) hemispheres were separated and then the wet weight was determined immediately. The amount of EB in the cerebral hemispheres was quantified at 620 nm by spectrofluorophotometry as previously described (Wang et al., 2014).
Hippocampal samples were collected from the hemisphere of three mice as a set of western blot analysis. Our unpublished data find that application of TRPV4 agonist decreases the protein of claudin-5 in hippocampus, indicating that, besides ZO-1 and occludin, activation of TRPV4 may result in the loss of other TJ protein.
Inhibition of MMP-9 by a selective gelatinase inhibitor protects neurovasculature from embolic focal cerebral ischemia.
Panels A-C show rats following sham operations labeled for BrdU, bromodeoxyuridine (A), RECA-1, rat endothelial antigen-1 (B) and the overlay or Merged image (C).
Panels A-C show rats with sham operation labeled for BrdU (A), GFAP (B), and Merged image (C). IntroductionIntracerebral hemorrhage (ICH), which accounts for 2 million (10–15%) of about 15 million strokes worldwide each year [1], has very high mortality rates of 31% at 7 days, 59% at 1 year, 82% at 10 years, and greater than 90% at 16 years [2,3]. The use of glycated haemoglobin, while providing a measure of glycaemic control over the past 2-3 months, is an average of pre- and post-prandial glycaemia and does not take into account glycaemic variability, which is an important cardiovascular risk factor that can be assessed by SMBG. Just as measurement of arterial blood pressure has become an important tool in follow-up of patients with hypertension by the GP, SMBG has become a valuable tool to evaluate glycaemic control. In particular, little consideration has been given to patient compliance, and SMBG is often perceived as an agonising experience. Pain related to skin pricks on the fingertip, needed for determination of glucometric blood glucose, can significantly reduce compliance to SMBG, thus depriving the physician of a useful tool for monitoring the efficacy of anti-hyperglycaemic therapy and glycaemic control. However, almost one-third (31%) used the centre of the fingertip, which is the site associated with the most pain.
The sensation associated with puncture (with or without pain) was used to compare the two groups.
The use of the area close to the nail bed allowed high quality blood samples to be obtained for measurement of blood glucose, with an accuracy that was the same as that seen using the fingertip.
In theory, compared to traditional lancets, this would allow less perception of pain even at traditional sites as well as at periungual zones, and it was our intention to compare the different types of lancets to reinforce this idea. If validated, this would enable patients with diabetes - especially those who need to take several daily blood glucose samples - to perform SMBG with greater peace of mind and less distress. These aggressive variants are more likely to present with symptoms similar to neoplasm such as motor impairments and seizures. On subsequent visits to the clinic, she had no evidence of focal neurological deficits except for mild bilateral symmetric hyperreflexia. These lesions demonstrated no enhancement to incomplete ring enhancement, with diminished vasogenic oedema (A).
Axial T2-weighted (D-F) views show multiple hyperdense lesions corresponding to the same locations. Since all tumor markers were negative a baseline PET scan was considered however, was not done secondary to insurance denial. It causes the release and blocks the reuptake of dopamine, norepinephrine, epinephrine and serotonin in neuronal synapse. Chronic methamphetamine use is associated with coronary artery disease, chronic hypertension and cardiomyopathy 6. The patient was in cardiogenic shock and dopamine drip was started and intravenous Lasix was given. Different mechanisms for cardiac injury due to methamphetamine have been proposed which include catecholamine excess, coronary vasospasm and ischaemia, increase in reactive oxygen species, mitochondrial injury, changes in myocardial metabolism, and direct toxic effects 3.Methamphetamine use is known to cause acute and chronic cardiomyopathy and the reversal of cardiac failure has been documented after discontinuing the drug. Ambrose, Methamphetamine-associated acute left ventricular dysfunction: a variant of stress-induced cardiomyopathy.
This condition is associated with a poor prognosis and therefore diagnosis should prompt aggressive correction of abnormal physiology. Blood tests demonstrated raised inflammatory markers and white count, but were otherwise unremarkable. These endoscopic features, in the absence of a history of ingestion of caustic substances, are diagnostic of Acute Oesophageal Necrosis (AON), also known as ‘Black Oesophagus’. There is a male preponderance, with an incidence four times greater than that for women and a peak incidence during the sixth decade of life5, 6. This is likely to account for the predilection for the distal third of the esophagus, which is relatively less vascular5.
Further it is not clear whether hematemesis is a universal symptom of this condition; it is conceivable that AON may go undiagnosed in those in whom this is not a feature. There is no clear role for the use of anti-acid therapy, however this is commonly used in management due to patient symptoms, which usually includes hematemesis. Inhibition of angiogenesis by suppressing these angiogenic effectors or inhibiting the elements of angiogenic signalling might provide a viable way to target therapy to manage MS.
The teratogenic effects are a result of the binding of thalidomide to cereblon, a protein found in both embryonic and adult tissues.
Clinically orientated investigations so far relate mainly to multiple myeloma and some other forms of haematological malignancies but not solid tumours5. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions.
To distinguish disease processes and make a definitive diagnosis, further investigations, such as special stains, culture methods and serologic tests, were indicated. As a result, the diagnosis of secondary syphilis was confirmed and tuberculosis treatment was ceased.
Unfortunately, undiagnosed and untreated syphilis may lead to life-threatening complications such as hepatitis, stroke and neurological damage 2. In fact, the presence of generalised lymphadenopathy and the finding of granulomatous lesions with epithelioid cells in the biopsy were highly suggestive of tuberculosis.
Since the growth of mycobacterium in culture requires a long time, additional histological stain with Ziehl-Nielsen was performed, but returned negative in the case of our patient. Diagnosis of the disease in the initial stages would be beneficial not only to allow the patients to receive early treatment, but also to prevent the spread of the disease to others. The cellular and total volumes of the lesion are seen to gradually decrease over 1 year on serial imaging. The consequences of a brain injury can affect all aspects of a person's life, including physical and mental abilities as well as emotions and personality. Widespread axonal injury disrupts the brain's normal transmission of information and can result in substantial changes in a person's wakefulness.
However, brain inflammation can be dangerous because the rigid skull limits the space available for the extra fluid and nutrients. If unconscious or unable to follow commands, his or her response to painful stimulation is checked. CT scans are used throughout recovery to evaluate the evolution of the injury and to help guide decision-making about the patient's care. However, there are times when a patient does not require surgery and can be safely monitored by nurses and physicians in the neuroscience intensive care unit (NSICU).
Patients are monitored and awakened every hour for nursing assessments of their mental status or brain function.
Some equipment may take over certain functions, such as breathing, nutrition, and urination, until the patient's body is able to do these things on its own.
The ICP monitor allows the NSICU team to intervene quickly if the pressure becomes too high. Adjustments in the amount of oxygen given to the patient are often made to maximize the brain's oxygen level.
Because patients often have other injuries, pain medication is given to keep them comfortable.
It is common for a patient to respond to each stimulus (hearing, seeing, or touching) in the same way. It is important to have patience; recovery from a brain injury can take weeks, months, or even years. A case of a young female of lupus (on steroids) with suprasellar tuberculoma is described here.
In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib.
The causes of edema in TBI patients are complex but it is well appreciated that the loss of the blood brain barrier (BBB) is a significant factor in the development of vasogenic edema (Chodobski et al., 2011). In addition, we demonstrate the potential effectiveness of Imatinib, an existing FDA approved inhibitor of the PDGFRα pathway, for the treatment of acute TBI, suggesting the possibility of rapid translation of these results. Vertically directed CCI was performed using a pneumatic impactor (Precision Systems and Instrumentation, VA) with a 3 mm flat-tip.
The supernatants were collected and quantitation of EB extravasation performed as described (Yepes et al., 2003).
Images were visualized using Nikon Eclipse TE-2000e and captured with a digital camera (Q-Imaging Micropubliser RTV version 5.0). After washing, membranes were hybridized with HRP tagged secondary rabbit anti-goat IgG antibody (1:5000 dilution). Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO) mice.
The dry weight was determined after drying the tissue to a constant weight at 100°C. After centrifugation, the supernatants were collected, and total protein concentration was determined using the Bradford assay (Bio-Rad, Hercules, CA, USA). We then studied the effect of TRPV4-blockage on the expression of zonula occludens-1 (ZO-1) and occludin, two major proteins involved in the tight junctions of BBB. Here, application of HC-067047 decreased the water content and EB leakage in the ipsilateral hemisphere of MCAO mice (Figure 1A) and this effect of closing TRPV4 is more likely due to the inhibition of vasogenic edema.
Here, the increase of MMP-9 protein expression and activity at 48 h post-MCAO was markedly blocked by TRPV4 antagonist. As is known that aquaporin-4 (AQ4) plays an important role in the formation of brain edema during stroke. This work was supported by National Natural Science Foundation of China (31271206), Qing Lan Project of Jiangsu province (2014–2017), and Research Award Fund for Outstanding Young Teachers in Nanjing Medical University (JX2161015033) to LC. Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture.
Representative Hematoxylin-Eosin stained section shows that 20U of thrombin causes brain injury, including hematoma and edema.
Administration of PP2 (src family kinase inhibitor) at day 0 blocked the increase in brain water content observed at 1 day after thrombin injection, whereas delayed PP2 administration (days 2-6) prevented the resolution of brain water content at 7 days post-thrombin injection.
ICH is associated with increased intracranial pressure, hematoma, blood brain barrier (BBB) disruption, brain edema, neuron loss, motor deficits, cognitive impairment and high mortality in humans. The search for sites as an alternative to the fingertip that are associated with less pain and good reproducibility and accuracy of blood glucose measurements is an area of growing interest. In particular, self-monitoring of both blood pressure and glycaemia are important to assess the efficacy of prescribed therapies, and can help the patient to better understand the importance of control of blood pressure and blood glucose.
Moreover, hourly pre-visit glucose curves for glycaemic control, even if important, do not have the same value as a standard control over 2 to 3 months between visits.
Moreover, HbA1c has clear limitations, even if it provides a good idea of glycaemic control over the past 2-3 months, as it is a mean value of pre- and post-prandial blood glucose.
Other sites of puncture on the fingers are used much less frequently (5%), while 12% used other places on the body.
The study was carried out according to the standards of Good Clinical Practice and the Declaration of Helsinki. In addition, a novel puncture site was used, namely the area proximal to the nail bed of each finger (Figs.
The VAS is a unidimensional tool that quantifies the subjective sensation such as pain felt by the patient and considers physical, psychological and spiritual variables without distinguishing the impact of the different components.
Differences in blood glucose with the two methods were analysed using Wilcoxon matched pairs signed ranks test.
All subjects who performed puncture in the central zone of the fingertip referred a painful sensation. The design of the lancet used herein was also associated with a lower perception of pain, which is composed of a hypodermic needle in a rigid casing that prevents accidental needle sticks both before and after use.
No puncture-related complications were reported, and another fundamental aspect that is not reported in other studies comparing traditional and alternative puncture sites is that no differences in blood glucose were observed.
Newer diagnostic tests are available that allow diagnosis to be attained and treated presumptively. CT of the abdomen and pelvis revealed a 2.6 cm indeterminate hypodense lesion in the left lobe of the liver (Figure 3A) along with an enlarged fibroid uterus (17x 7 x 14 cm).
Given that the metastatic work up remained negative, we considered obtaining a baseline Positron emission tomography (PET) scan to ensure we were not missing any possible metastasis. These findings suggested an inflammatory demyelinating process so a lumbar puncture was obtained after anticoagulation was held. Due to the asymptomatic presentation of her disease, a primary differential diagnosis of brain metastasis and anticoagulation therapy for PE, a CSF analysis was not considered until much later. This was likely the effects of steroids that the patient was on due to her vasogenic oedema. The definitive diagnostic test for MS is a brain biopsy but this is not preferred due to the invasiveness of the procedure. In one case report, a patient with chronic methamphetamine-associated cardiomyopathy did not demonstrate late gadolinium enhancement, consistent with an absence of significant fibrosis, and had left ventricular function recovered with 6 months of medical therapy and decreased drug abuse 7. Her treatment was optimised with a two-week course of fluconazole with the dose adjusted for her renal function and parenteral nutrition, with good clinical response. Whilst histology confirming necrosis is not necessary to make the diagnosis, it is confirmatory.
Individual cases have occurred in association with bacterial, viral and fungal infections, whilst malnutrition, malignancy and immune-compromise appear to be important factors3, 5, 6. Similarly, candidiasis may occur in conjunction with AON, whilst it is not thought to be causative, treatment is considered prudent given the poor prognosis associated with this condition. The current body of experience suggests aggressive management of abnormal physiology optimises outcomes5, 6. The focus of this article is on the ability of thalidomide and its analogues to inhibit angiogenic signalling systems. Among immunomodulators of note are Fingolimod which prevents infiltration of auto-destructive lymphocytes into the CSF, Teriflunomide which reduces lymphocyte infiltration of the CNS, axonal loss and inflammatory demyelination, and dimethyl fumarate, which modulates the immune system by many mechanisms. As illustrated by this case, syphilis should also be considered as a possible cause of generalized lymphadenopathy.


Both human immunodeficiency virus screening and the serological tests for hepatitis B and C were negative.
As a matter of fact, tuberculosis tops the list of aetiological causes of granulomatous infections5.
Histopathology is characterized by the presence of epitheloid granuloma with Langerhans giant cells and central caseous necrosis 7. As a consequence, the diagnosis of tuberculosis was excluded and syphilis was considered as a definitive diagnosis. While treatment for mild TBI may include rest and medication, severe TBI may require intensive care and life-saving emergency surgery. During the impact of an accident, the brain crashes back and forth inside the skull causing bruising, bleeding, and tearing of nerve fibers (Fig. A cerebral blood flow monitor, called a Hemedex, is a newer monitor that is placed with the Licox and helps the NSICU team evaluate blood flow through the brain.
The tube allows the machine to push air into and out of the lungs, thereby helping the patient breathe.
Because these seizures are serious, all patients with a severe TBI are monitored with continuous EEG for 24 to 72 hours after injury. Responses may include increased rate of breathing, moaning, moving, sweating, or a rise in blood pressure. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. Over the past two decades our understanding of the complex pathobiology of TBI has improved significantly. The walls surrounding the pool were adorned with high-contrast posters for use as distal cues.
Non-TBI control CSF samples obtained from 4 patients recruited to the Alfred hospital for elective neurosurgery, or via lumbar puncture from 5 patients recruited to the Austin Hospital (Melbourne) suspected of having multiple sclerosis. PDGF-CC signals were revealed using enhanced chemiluminescence (SuperSignal West Pico; Thermo Scientific, Rockford, IL, USA). All neuropathology experiments were repeated at least two independent times and n indicates the number of individual mice used in the study. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047.
BBB permeability is increased by activation of TRPV4 and TRPV2 complex (Brown et al., 2008). Prepared protein samples were loaded and separated by 10% Tris-glycine gel with 0.1% gelatin as substrate. By contrast, only the increased activity of MMP-9 was markedly blocked by HC-067047 treatment. These results indicate that activation of TRPV4 may facilitate the activation of MMP-9 to decrease the protein of ZO-1 and occludin. Consistently, MMP-9 protein level and activity in hippocampus were higher in GSK1016790A-injected mice.
TRPV4 and AQ4 co-expressed in the astrocytic endfeet and it acts as an important structural and functional partner of AQ4 (Benfenati et al., 2011). GSK1016790A-induced the increase of MMP-9 protein level and activity (A), and the decrease of ZO-1 and occludin protein levels (B) were blocked completely by HC-067047. Regulation of blood–brain barrier permeability by transient receptor potential type C and type V calcium-permeable channels.
Panels D to F show BrdU (D), RECA-1 (E) and the Merged image (F) at 1 day after thrombin injections.
Panels D-F show BrdU (D), GFAP (E) and the Merged image (F) at 1 day after thrombin injection. The major challenges immediately after ICH are re-bleed, hematoma induced brain injury, brain edema and neurological deficits [4]. In addition, after an initial period of "enthusiasm" the fear and hassle of pricking oneself and the unpleasant feeling of pain often cause the patient to abandon SMBG. It does not, therefore, measure glycaemic variability, which is an important cardiovascular risk factor. It is also interesting to see how many times patients reused the lancet: 10% once, 19% for 2-4 times, 22% for 5-7 times, 25% for 8-10 times and 21% for more than 11 times. Thanks to the needle point that was made using a triple-bevel cut, epidermal penetration is less traumatic and as a consequence less painful. Liver biopsy was considered but a repeat MRI and ultrasound showed the lesion to be cystic, so this was deferred following surgical oncology recommendations (Figure 3B). We were able to use surveillance MRI and CSF analysis to see some resolution of these lesions and confirm the diagnosis. Here an evolution in time and space is demonstrated which excluded brain metastasis and infection.
With the advent of newer diagnostic tests such as SPECT, MR Spectroscopy, surveillance MRI and CSF analysis, diagnosis can be attained and treated presumptively.
Urine toxicology was positive for opiate, methadone, amphetamine, benzodiazepine, cocaine and cannabinoid. Echocardiogram showed left ventricular dilatation with diffuse hypokinesis and depressed systolic function.
Another case of a female 42 year old methamphetamine user who had transient left ventricular dysfunction and wall motion abnormalities and an index ventriculogram showed apical ballooning consistent with Takotsubo cardiomyopathy; her left ventricular function significantly improved after 3 days of medical treatment 8. Antibiotics, antifungals and nutritional support should be considered on an individual basis. Thalidomide is a highly toxic drug but its analogues, lenalidomide and pomalidomide, show reduced toxicity and greater efficacy of growth suppression and inhibition of angiogenesis.
Furthermore, much attention has been devoted to the immunomodulatory properties of MSCs (mesenchymal stem cells) 4,5. Awareness by the clinician of such a presentation would make it easy to diagnose syphilis at an earlier stage. There was a history of occasional low-grade fever and weight loss, but no cough or night sweats.
After a nine-month follow-up, the patient had no clinical or laboratory evidence of syphilis. Worldwide it is considered the leading cause of contagious disease leading to approximately 1.4 million deaths per year 6. Color-coded fractional anisotropy (FA) map (e) shows gradual recovery of FA values with time in white matter regions. Most people who suffer moderate to severe TBI will need rehabilitation to recover and relearn skills. A clot that forms between the skull and the dura lining of the brain is called an epidural hematoma.
The score ranges from 3 to 15 and helps doctors classify an injury as mild, moderate, or severe.
This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Mice were given 6 trials per day (in blocks of two trials, 1 min inter-trial intervals and 1 h inter-block intervals) for 4 days, with the starting position chosen pseudo-randomly among 6 start positions. The relative amount of PDGF-CC in each sample was estimated from the intensity of the PDGF-CC band in each lane and assigned a value from 0 to 10, with 0 being undetected and 10 being the most intense.
P values less than 0.05 were considered statistically significant and are indicated in the figures by an asterisk.
In lung tissues, application of TRPV4 agonist increases the level of activated MMPs (Villalta et al., 2014). These results indicate that blockage of TRPV4 could inhibit the activated MMP-9 level and rescue the loss of ZO-1 and occludin in MCAO mice, which may benefit for the integrity of BBB. Although the protein level of MMP-2 was increased by application of TRPV4 agonist, the activity was nearly unaffected (Figures 1B, 2A). Therefore, TRPV4 is likely a potential target for treating brain edema during cerebral ischemia and other pathological process.
Compared with the sham group, RECA-1+cells tend to lose their tube-shape at 1 day following thrombin injections (arrows in panel F) and there were no BrdU+cells co-labeled with RECA-1 at one day (panel F).
Compared with the sham group, there is decreased GFAP immunoreactivity around brain vessels. Thus, more research is needed into puncture sites as an alternative to the fingertip that are associated with less pain, which could favour greater use of SMBG. Pricking oneself 2 several times daily for years is not only troublesome for patients, but also leads to the formation of scars and callouses, and reduces fingertip perception and tactile sensitivity.
In this area of the finger, blood flow is abundant and it is easy to obtain a blood sample. The past medical history included hypertension with no previous surgeries and family history included breast cancer of the mother diagnosed at age 47. For the hypertrophic uterus found on imaging, gynecology felt no further workup was necessary as they attributed the findings to a fibroid uterus. This revealed a normal myelin basic protein but with eight oligoclonal bands restricted to the CSF. This brings into discussion the diagnostic value of surveillance MRI, which in our case was helpful and appropriate as the patient did not have clinical symptoms. A repeat gastroscopy 10 weeks later showed complete resolution of endoscopic features with no evidence of perforation or stricture formation. Thalidomides are also capable of modulating the function of key element of the immune system related to the pathogenesis of MS, but this brief article is intended to emphasise the potential of thalidomide and its analogues as potent inhibitors of angiogenesis and the latent possibility of their use as a therapeutic agent in the control of MS.
Thalidomide possesses immunomodulatory, anti-inflammatory, anti-angiogenesis and cell proliferation inhibitory properties and this has suggested its use in the treatment of cancer5. In this context one should emphasise that pre-clinical exploration of the potential synergy between the thalidomides and the acknowledged modulators of the signalling pathways would be worthwhile. All her family members were well, with no contributory medical history, and none of them had similar symptoms. Its prevalence is still extremely high in certain populations especially in low-and middle-income countries such as Tunisia where the disease is endemic. Immediately after the accident the person may be confused, not remember what happened, have blurry vision and dizziness, or lose consciousness. One to 3 months after the swelling has resolved and the patient has stabilized from the injury, the bone flap is replaced in another surgery, called cranioplasty. She was diagnosed with systemic lupus erythematosus one year ago by clinical and laboratory criteria (ACR) with nephropathy grade three.
Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. The pathophysiology of TBI is complex and involves both primary and secondary insults (Hemphill and Phan, 2013b; Finnie, 2014). To generate a larger bilateral injury, a previously described TBI model was used where the CCI is delivered to the midline (Liu et al., 2013). The average for all the samples at each extended glasgow outcome scale (GOSE) score was plotted against the GOSE score. The loss of zonula occludens-1 (ZO-1) and occludin protein in MCAO mice was also attenuated by HC-067047. HC-067047 was injected beginning at 4 h after MCAO and then injected every 8 h until 48 h post-MCAO using a 26-G stainless steel needle. After developing, the gel was stained with 0.5% Coomassie Blue R-250 for 30 min and then destained appropriately. Here, we also found that GSK1016790A-induced modulation of MMP-9 protein expression and activity was blocked by application of TRPV4 antagonist HC-067047 (Supplementary Figure 1).
Activation of MMP opens the BBB by degrading TJ and increases BBB permeability after stroke, and an MMP inhibitor prevents the degradation of TJ and attenuates BBB disruption (Cui et al., 2012).
Panels G-I show the staining for BrdU (G), RECA-1 (H) and the Merged image (I) 1 day after thrombin plus PP2 injections. Notwithstanding, alternative sites of puncture such as the arm, forearm and abdomen have not been evaluated in a systemic manner. Moreover, the area has fewer tactile and pain receptors than the fingertip, and thus when lanced less pain is produced. This allows the use of a larger transversal section using a puncture with less depth, and less involvement of nerves present in skin. The imaging suggested a differential diagnosis which included metastasis, infection or primary CNS malignancy. He had moderate diastolic dysfunction, mild mitral regurgitation and tricuspid regurgitation with a pulmonary artery pressure of 38mmHg.
It is not clear how long it takes for cardiomyopathy to revert to normal after discontinuing the drug, or at what stage cardiac damage is irreversible. Here a postulate is presented that the perceived potential synergy between the thalidomides and modulators of angiogenic signalling might deliver benefits of thalidomides more effectively and at lower dosages compatible with greater safety of administration. This has led to the suggestion that inhibition of angiogenesis by suppressing these effectors or inhibiting the elements of angiogenic signalling pathways might provide a viable way to target therapy to manage MS. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα.
Primary injury to the brain can be induced by numerous mechanisms, such as brain contusion, hematoma, and shearing or stretching of the brain tissue caused by motion of the brain structures relative to the skull. During the probe trial, the escape platform was removed and mice were placed in the pool at the start location directly opposite of where the platform was previously located and allowed to swim for 60 s. Proteolytic bands in the zymography were quantified by scanning densitometry (Quantity one, Bio-Rad).
The above results indicate that blockage of TRPV4 inhibits the formation of brain edema following ischemic insult. PP2 administration at day 0, immediately after thrombin injection, blocks the thrombin-induced loss of tube-shape of RECA-1+cells. Panels G-I show the staining for BrdU (G), GFAP (H) and the Merged image (I) 1 day after thrombin plus PP2 injections.
In addition, the characteristics of the novel lancing device (Fine Touch, Terumo Corporation, Tokyo, Japan) allows adjusting the depth of puncture to the characteristics of each patient (e.g.
After the initial impact occurs, the brain undergoes a delayed trauma a€“ it swells a€“ pushing itself against the skull and reducing the flow of oxygen-rich blood.
These latter studies suggest that blocking PDGFRα signaling may provide benefit in diverse CNS pathologies through protection of the BBB. After the impact, the circular bone fragment from the craniotomy was glued back to the cranial window. To control for motivation and sensory deficits mice were also examined in the visible-platform version of the MWM 24 h after the probe trial. Finally, ZO-1 and occludin protein expression was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. Moreover, GSK1016790A-induced the loss of ZO-1 and occludin was completely blocked by HC-067047 (Supplementary Figure 1). Panels J-L show the staining of BrdU (J), RECA-1 (K) and the Merged image (L) 7 days after thrombin injection. PP2 administration at day 0, immediately after thrombin injection, blocks the thrombin-induced reductions in GFAP immunoreactivity.
At the acute stage, glutamine, thrombin, TNF-?, VEGF and other endogenous molecules are rapidly released following ICH.
It is unclear to what extent the use of multiple drugs play synergistic role in the cardiac complications that occur. Recently, many studies have elucidated the signalling pathways which thalidomides inhibit and thereby suppress cell proliferation, promote apoptosis and inhibit angiogenesis. Consistent with this suggestion our recent work indicates that tPA can promote post-traumatic cerebrovascular damage including increased BBB leakage (Sashindranath et al., 2012).
For the unilateral TBI experiments, animal group sizes were n = 10 for the Evans blue (EB) Assays, n = 6 in the T2 and apparent diffusion co-efficient (ADC) analysis, and n = 5 for volumetric tissue loss after 21 days. The visible-platform version consisted of a single day of training with 6 trials during which the platform was moved to a new location and marked with a distinct local cue. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein.
SB-3CT is the selective gelatinase inhibitor and can inhibit MMP-9 activity in vivo (Gooyit et al., 2012). The pathological changes in a stroke may facilitate the activation of TRPV4 and moreover, an increased TRPV4 protein level is found during ischemia-reperfusion (Jie et al., 2014). Our data suggested that during cerebral ischemia, activation of TRPV4 may increase the activated MMP-9 level, leading to the loss of ZO-1 and occludin.
Panels J-L show the staining for BrdU (J), GFAP (K) and the Merged image (L) 7 days after thrombin injection. Among patients who present with cardiomyopathy and cardiogenic shock, the usage of drugs like methamphetamine and co-ingestion of other drugs should be considered. These have led to the suggestion of combining the modulators of these signalling pathways to synergise with thalidomides to deliver the suppressor effects with enhanced efficacy and at lower concentrations thus reducing the side effects5 (Figure 1). However, it is not known whether the PDGFRα pathway also plays a role in TBI-related injuries. In the bilateral TBI experiments, animal group sizes were n = 5 in the T2 and ADC analysis, n = 5 for volumetric tissue loss after 21 days, and n = 7–9 in the Morris water maze (MWM) studies. In the future study, TRPV4 knockout mice will be needed to further clarify TRPV4-induced the above action and its involvement in the brain edema formation during cerebral ischemia.
He became haemodynamically stable and dopamine was discontinued; aspirin, clopidogrel and carvedilol were started.
Further study is needed to recommend treatment for methamphetamine and related drugs induced cardiomyopathy. She also had no prior visual problems.After admission, the patient developed low grade fever and her dimness of vision progressed.
Separate groups of animals were used in each experiment and were not overlapped with the exception that the T2 and ADC analysis at 24 h and 7 days were performed on the same mice. Images from the digital camera were processed and stored on a desktop PC using Actimetrics WaterMaze Software (Actimetrics, Wilmette, IL). This dose was used because it antagonized the increase of activated MMP-9 and exerted neuroprotection in transient focal cerebral ischemia (Cui et al., 2012). Therefore, it is proposed that during stroke, the over- or hyper-activation of TRPV4 aggravates the increase of [Ca2+]i, helping to increase the activated MMP-9. For sham surgeries, all animals underwent the same surgical procedures except the craniotomy and CCI. Proximity measurements were calculated by the tracking software at a rate of 1 Hz as the instantaneous distance (in centimeters) from the designated platform location. Briefly, mice were kept on a 37°C warming pad overnight during recovery and were monitored daily for any distress behavior until the end of the study, receiving analgesics after surgery as needed. His repeat echocardiogram one week later showed normal left ventricular systolic and diastolic function with an ejection fraction of 70%. All animal experiments were approved by the University Committee on Use and Care of Animals at the University of Michigan, and conducted in accordance with the United States Public Health Service’s Policy on Humane Care and Use of Laboratory Animals. Panels N to P show the staining for BrdU (M), RECA-1 (N) and the Merged image (P) 14 days after thrombin injection. Panels N-P show the staining for BrdU (N), GFAP (O) and the Merged image (P) 14 days after thrombin injection. Cumulative proximity is the sum of all of the instantaneous distance measurements minus the distance calculated as a perfect swim path which is represented as a straight line between the start location and the platform location.
Compared to 7 days, BrdU+cells are decreased, but some BrdU+cells (N) remain co-labeled with RECA-1 (arrow in panel P), and more and more brain capillaries regained the tube-shape 14 days after the thrombin injection. Tissue specificity, structure and activity regulation of SFKsSFKs are a family of non-receptor protein tyrosine kinases, include nine family members Src, Fyn, Lck, Lyn, Yes, Hck, Blk, Fgr, and Yrk [10-12], of which Src, Fyn, Yes and Yrk widely expressed whereas the rest members are expressed in specific tissues [13]. Ophthalmologists opined that the pathology was not intra-ocular; neurologists were of the opinion that there was a vascular event in cranium.
They were lethargic in the first few hours after surgery, and mice with the bilateral injury took longer to recover from anesthesia than mice in the unilateral model and remained lethargic for a longer period of time during the first day.
Some BrdU+cells (N, arrow) remain co-labeled with GFAP (arrow in panel P) 14 days after the thrombin injection. In addition, one tissue can express multiple SFK members, for example, Src, Fyn, Yes, and Lck have been examined in brain [13-19].
Immediate imaging was advised.Routine laboratory tests showed mild anemia and thrombocytopenia. There were no deaths or other complications with the unilateral model, but there was 1 death out of 52 mice subjected to the bilateral injury. Average proximity is the average of all of the instantaneous distance measurements recorded during the probe trial with lower values reflecting a more selective search strategy.
Importantly, the different SFK family members often compensate for one another [20], which are supported by the evidence that the mice deficient in Src can survive though Src plays vital role in cell signaling transduction [20]. SFKs share a conserved domain structure consisting of consecutive SH3 (polyproline type II helix for protein-protein interaction), SH2 (phosphotyrosine recognition), and SH1 (tyrosine kinase catalytic activity) [12]. Due to the presence of papilledema, we did a CT scan of brain [Figure 1] which showed a calcified mass in suprasellar region with perilesional edema (black arrow) with obstructive hydrocephalous. All SFK family members also contain an membrane-targeting region at their N-terminus that is followed by a unique domain of 50–70 residues, and the unique region is divergent among family members [12]. Although it still remains incompletely clear, Src activity is regulated by tyrosine phosphorylation at two sites (one is at Tyr416 in the SH1 domain, the other at Tyr527 in the short C-terminal tail), but with opposing effects. The Mantoux test of the patient was negative (she was on steroids), sputum did not show any acid-fast bacilli and chest X-Ray was also normal.
While phosphorylation at Tyr416 activates Src, phosphorylation at Tyr527 inactivates Src [13,21].3.
SFKs modulate NMDA receptor for brain injury after ICHNMDA receptors are ionotropic glutamate receptors, comprise NR1, NR2 and NR3 subunits, which form the central conductance pathway [22,23]. In the physiological conductions, activation of NMDA receptors results in the opening of an ion channel that allows the flow of Na+ and small amounts of Ca2+ into the cell and K+ out of the cell [22,23]. Following ICH there is a transient increase of glutamate release and local cerebral glucose utilization in the region surrounding the ICH, and the antagonists of NMDA receptors reverse the glucose hyper-metabolism produced by ICH [6]. However, glutamate alone could not explain the hypermetabolism since glutamate injected directly into brain did not produce hypermetabolism [6]. In view of the emergent nature of the illness, we started her on oral anti tubercular drugs with an increased dose of oral steroids. It has been proved that phosphorylation by Src at Tyr-1292, Tyr-1325 and Tyr-1387 in NR2A subunit increases activity of NMDA receptors, and phosphorylation of tyrosine residues by Src in the C-terminal of the subunits prevents a Zn2+-dependent inhibition of the NMDA receptors and thus increases channel conductivity [28-30].
Subsequently, after 1 month, a brain biopsy was done and the lesion was found to be calcified granuloma with aggregates of epitheloid cells, calcifications, necrosis, blood vessel destructions, and few scattered caseations [Figure 2]. We have demonstrated that either NMDA receptor inhibitors (MK-801) or SKF inhibitors (PP2) can attenuate brain injury at the acute stage after ICH (Fig. The lesion did not show any acid fast bacilli, but overall features were suggestive of tuberculosis. Repeat CT scan [Figure 3] showed only a mild decrease in the size of the edema; calcified mass size was the same.
In cases like ours, with no extra cranial manifestations of tuberculosis, diagnosis can be difficult and only suggested by CT scans.
Tuberculosis of central nervous system can have different forms like meningitis, abscess, tuberculoma, subdural collection or miliary form.
In resource-limited settings, and when the patient is severely ill, often diagnosis is not possible and empirical treatment is needed. However, there is no direct report showing the mechanism by which SFKs participate in NMDA receptors mediated neurogenesis after brain injury.4. SFKs regulate cell cycle for mitogenic toxicity and cell proliferation after ICHThe cell cycle is an irreversible, ordered set of events that normally leads to cellular division [32-36]. The release of cells from a quiescent state (G0) results in their entry into the first gap phase (G1), during which the cells prepare for DNA replication in the synthetic phase (S).
Also, lesions with an infective cause should be differentiated from calcified tumors and aneurysms because drug treatment is helpful in tuberculoma, whereas in other cases prompt surgery is the only option.
Mature neurons normally maintain themselves in G0 resting phase; however, a mature neuron that re-enters the cell cycle can neither advance to a new G0 quiescent state nor revert to its earlier G0 state. The idea of presenting this case is to draw attention on the catastrophic effects of long-term steroids.
This presents a critical dilemma to the neuron from which death may be an unavoidable, but necessary, outcome for adult neurons attempting to complete the cell cycle [32,37]. Although tuberculosis is a known complication of long-term immunosuppression, tuberculomas are rare and suprasellar tuberculoma causing visual impairment is indeed very rare. Increasing evidence have revealed that aberrant cell cycle re-entry leads to neuronal death [8,32,37-64], and cell cycle inhibition via blocking SFKs can protect neurons from death post-ICH [8].Apart from post-mitotic neurons, SFKs play critical roles in the process of cell cycle in dividable cells, by regulating mitogen-activated protein kinases (MAPKs) and cell cycle proteins such as cyclin-dependent kinases (Cdks) [65-69]. Although mitogenic signaling is necessary to initiate the cell cycle for normal cell division and proliferation, massive mitogenic signaling can also produce neurotoxicity and cell death [9,32,37,70]. Cell death and cell proliferation seem contradictory to each other, but these two seemingly different cellular processes share some common mitogenic molecules and signaling pathways (Fig.
Very rarely, tuberculomas are found near optic chiasm, but when they occur, they can cause these catastrophic consequences. In addition, many other molecules, including Ca2+, ROS, NO and MMPs can directly or indirectly activate or increase mitogenic signaling [54,71-77].There are two stages (acute and recovery) after ICH (Fig. However, fortunately, that case was diagnosed before the calcification stage and the patient responded favorably to drugs.Also, intracranial calcification is a vexing problem in a resource limited settings. This peaks within the first hour to a day in the acute stage after ICH, and then resolves gradually in the recovery stage after ICH. In a resource limited setting, anti-tubercular drug, even on empirical basis can be life saving and should be used without delay. Newer diagnostic methods like PET scan can also help in distinguishing these lesions (tuberculosis has lower FDG uptake than lymphoma). 1, thrombin (a potent mitogen) triggers mitosis after ICH by modulating mitogenic intracellular molecules such as SFKs. SFKs participate in mitogenic signaling activation via regulating mitogen-activated protein kinases (MAPKs) and other molecules [64-69] that play critical roles not only in brain injuries during the acute stage in ICH, but in brain self-repair during the recovery stage in ICH.
Acute inhibition of SFKs is beneficial, that attenuates hematoma, BBB breakdown, vasogenic edema, MAPK activation in the acute stage (0-24h) after ICH (Fig. In contrast, delayed and lasting inhibition of SFKs is detrimental, and prolongs BBB repair and brain edema resolution in the recovery stage (7-14 days) after ICH [9], presumably because SFKs mediate population of NPCs that exist in the “neurovascular niche”. Since delayed and chronic inhibition of SFKs may impair neurogenesis and prolong BBB self-repair during recovery stage post-ICH, the acute and transient inhibition of SFKs should be pursued in treatment of ICH. The nanoparticle-based siRNA transfection system allows transient knockdown of target gene(s) and highly efficient delivery of siRNA in vivo with low cytotoxicity [80,81]. This could present a novel therapy for treating ICH patients as the nanoparticle-based siRNA approach provides heightened specificity for specific SFK gene(s) with less off target effects and this approach has been used in humans [82-85].6. AcknowledgementsThe authors acknowledge the support of AHA Beginning Grant-in-Aid 12BGIA12060381 (DZL) and NIH grant NS054652 (FRS).



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