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By: James L. Zehnder, MD

  • Professor of Pathology and Medicine, Pathology Department, Stanford University School of Medicine, Stanford

https://profiles.stanford.edu/james-zehnder

An eighty-year-outdated man is increasingly forgetful buy 400mcg pulmicort visa, and his flexes that enhance the guts rate buy generic pulmicort pills. Of the possible preexisting situations listed pupil at therapeutically appropriate doses. The alternative of route of administration plays an imaggravate asthma, further weaken A-V conduction, portant function in the actions of instantly performing choliand risk perforation of the bowel if an obstruction nomimetics. Hypotension, which can be life threatening, can route of administration is: be averted by stopping the entry of instantly act(A) Bradycardia ing cholinomimetics into the circulatory system. A sensible information to energy, the dose of neostigmine is too high, borthe recognition and management of myasthenia dering on the manufacturing of a depolarizing block of gravis. Muscarinic acetylcholine receptors: Signal agonist, will only very transiently enhance the transduction via multiple effectors. Pharmacological therapy cholinoreceptor agonist that will stimulate nicotinic for glaucoma: a evaluate. Physostigmine will enhance the energy of the Medical purposes of neurochemical ideas. She is sweating the extra difficult question is whether oxime treatprofusely, vomiting, and having difficulty respiration. Certainly a that the lady had threatened suicide 2 hours earquick inquiry to see if the product can be identified lier. It quate ventilatory assist is out there, it could be appears that the ingestion occurred in the past 2 higher to treat the affected person symptomatically. At least seven amino the best identified of the muscarinic blocking drugs are the acids from 4 transmembrane helices have been imbelladonna alkaloids, atropine (Atropine) and scopolplicated in agonist binding to the muscarinic receptors. They are tertiary amines that conSome of these residues, significantly a negatively tain an ester linkage. Although the tertiary amine and quaand some artificial compounds with little structural simternary ammonium groups of antimuscarinic drugs bind ilarity to the belladonna alkaloids are also in use. Finally, some Tissue or different courses of drugs can act partly as muscarinic ansystem Effects tagonists. For instance, the antipsychotics and antideSkin Inhibition of sweating (hyperpyrexia may pressants produce antimuscarinic unwanted effects. Therefore, the magnitude of pancreatic, intestinal, and biliary secretions the response produced by muscarinic antagonists deUrinary Urinary retention (leisure of the depends on the present degree of cholinergic activity or on trusor muscle); leisure of ureter the presence of muscarinic agonists. At these places, block of the activation of musCentral nervous Decreased focus and reminiscence; carinic receptors can enhance the tone provided by the system drowsiness; sedation; excitation; ataxia; adrenergic enter. The tissues or systems affected will rely upon the dose administered, the drug’s pharmacokinetic properties. Blood Vessels Heart Atropine and different muscarinic antagonists produce Intravenous administration of low doses of atropine or minimal effects on the circulation in the absence of cirscopolamine often produces slight bradycardia, whereas culating muscarinic agonists. This reflects the comparatively larger doses produce tachycardia by instantly blocking minor function of cholinergic innervation in determining the parasympathetic enter to the sinoatrial node. Atropine can produce Although it has been instructed that the bradycardia reflushing in the blush space owing to vasodilation. The inhibition of Antagonism of these presynaptic muscarinic receptors salivation by low doses of atropine ends in a dry prevents feedback inhibition and will increase the release mouth and difficulty in swallowing. Relatively large hibitors of secretions throughout the respiratory sysdoses of atropine are required to inhibit acid secretion, tem, from the nose to the bronchioles. Although the antimuscarinic drugs are normally selective for muscarinic cholinergic receptors, high concentrations of brokers with a quaternary ammonium group Bladder. The active isomer, nevertheless, can doses of 10 mg or extra are used, the affected person may exundergo dealkylation, oxidation, and hydrolysis. Large doses of scopolamine quantities of these compounds are eradicated in the feces can produce the entire responses seen with atropine. The blood-brain barrier Other tertiary amine compounds with muscarinic reprevents quaternary ammonium muscarinic blockers ceptor blocking activity have similar central effects. This ends in dilation of the pupil (mydriasis) and paralysis of lodging (cycloplegia), responses Atropine can be useful in sufferers with carotid sinus that trigger photophobia and inability to give attention to nearby syncope. Ocular effects are produced only after larger of afferent neurons whose stretch receptors are in the parenteral doses. By reflex mechanisms, this excessive afferresponses lasting a number of days when utilized on to ent enter to the medulla oblongata causes pronounced the eyes. Under cerpathetic innervation of respiratory smooth muscle is tain situations, atropine could also be useful in the therapy most plentiful in large airways, the place it exerts a domiof acute myocardial infarction. In settlement with this innervaoccurs after acute myocardial infarction, particularly in tion pattern, muscarinic antagonists produce their the first few hours, and this in all probability results from exgreatest bronchodilator effect at large-caliber airways. The increased tone and bradycardia 13 Muscarinic Blocking Drugs 137 facilitate the development of ventricular ectopy. To miniwithout hazard, as a result of cardiac work can be increased mize this possibility, pressure must be utilized to the with out improved perfusion, and ventricular arrhythlacrimal sac for a few minutes after topical software mias may happen. Shorter-performing drugs, similar to cyclopentolate and tropicamide, are now favored for this Uses in Anesthesiology software as a result of complete restoration of accommodaAt one time, atropine or scopolamine was routinely adtion happens inside 6 to 24 hours and a couple of to 6 hours, reministered before the induction of general anesthesia to spectively. High been used as adjunctive therapy in the therapy of irserum ranges of drugs with antimuscarinic activity can ritable bowel syndrome. Glycopyrrolate brocrease the ache associated with postprandial spasm of mide (Robinul) has also been given intramuscularly as intestinal smooth muscle by blocking contractile rea preanesthetic medication with passable results. Some of the brokers used for this disorthis agent is a quaternary ammonium compound and der have only antimuscarinic activity. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic conUse With Cholinesterase Inhibitors centrations primarily have a direct smooth muscle reDuring reversal of competitive neuromuscular blocklaxant effect with little antimuscarinic motion.

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Silent studying can also be impaired (deep dyslexia) as reflected by poor textual content comprehension; The terms ‘small Broca’s aphasia’ cheap 400 mcg pulmicort with visa, ‘mini-Broca’s aphasia’ buy pulmicort 400mcg mastercard, and ‘Broca’s space aphasia’ have been reserved for a more circumscribed clinical and neuroanatomical deficit than Broca’s aphasia, whereby the injury is restricted to Broca’s space or its subjacent white matter. There is a mild and transient aphasia or anomia which can share some of the characteristics of aphemia/phonetic disintegration. Broca’s aphasia is typically associated with a proper hemiparesis, particularly affecting the arm and face; there can also be bucco-lingual-facial dyspraxia. Classically Broca’s aphasia is associated with a vascular lesion of the third frontal gyrus in the inferior frontal lobe (Broca’s space), but in apply such a circumscribed lesion is seldom seen. Cross References Agrammatism; Agraphia; Alalia; Alexia; Aphasia; Aphemia; Aprosodia, Aprosody; Paraphasia; Recurrent utterances; Wernicke’s aphasia Brown-Séquard Syndrome the Brown-Séquard syndrome is the consequence of anatomical or, more usually, practical hemisection of the spinal cord (spinal hemisection syndrome), producing the following sample of clinical findings:. Motor: Ipsilateral spastic weakness, because of corticospinal tract involvement; Segmental lower motor neurone signs at the stage of the lesion, because of root and/or anterior horn cell involvement. Cross References Dissociated sensory loss; Myelopathy; Proprioception; Spasticity; Weakness Brudzinski’s (Neck) Sign Brudzinski described a variety of signs, however the one most frequently utilized in clinical apply is the neck signal, which is typically evident in circumstances of meningeal irritation, for example, because of meningitis. Passive flexion of the neck to bring the head onto the chest is accompanied by flexion of the thighs and legs. As with nuchal rigidity and Kernig’s signal, Brudzinski’s signal may be absent in aged or immunosuppressed patients with meningeal irritation. Brueghel’s syndrome must be distinguished from different syndromes of cranial dystonia that includes blepharospasm and oromandibular dystonia, better termed Meige’s syndrome. Cross References Blepharospasm; Dystonia Bruit Bruits arise from turbulent blood flow causing arterial wall vibrations that are audible at the body surface with the unassisted ear or with a stethoscope (diaphragm rather than bell, better for detecting greater frequency sounds). Examination for carotid bruits in asymptomatic people might be finest averted, apart from in the clinical trial -67 B Brushfield Spots setting, because the optimum management of asymptomatic carotid artery stenosis has yet to be totally defined. Brushfield Spots Brushfield spots are small gray-white specks of depigmentation that can be seen in the irides of some (90%) patients with Down’s syndrome; they might additionally happen in normal people. Dysfunction of efferent and/or afferent thalamic and striatopallidal tracts has been suggested as the neural substrate. If necessary, a rubber gum protect or bite may be worn in the mouth to defend the enamel. Cross References ‘Bon-bon signal’; Dyskinesia Bulbar Palsy Bulbar palsy is weakness of bulbar musculature of lower motor neurone origin. This may be differentiated clinically from bulbar weakness of upper motor neurone origin (pseudobulbar palsy). Brainstem disorders affecting cranial nerve motor nuclei (intrinsic): Motor neurone disease (which can additionally cause a pseudobulbar palsy); Poliomyelitis; Glioma; Syringobulbia. A myogenic bulbar palsy may be seen in oculopharyngeal muscular dystrophy, inclusion body myositis, and polymyositis. Cross References Cauda equina syndrome; Reflexes Buphthalmos Buphthalmos, literally ox-eye, consists of a large and bulging eye brought on by raised intraocular pressure because of congenital or secondary glaucoma. Cross Reference Diamond on quadriceps signal Calf Hypertrophy Calf enlargement has many causes; it may reflect true hypertrophy (enlargement of muscle fibres) or, more commonly, pseudohypertrophy, because of infiltration with tissue elements apart from muscle. Calf (and different muscle) hypertrophy is also a characteristic of limb girdle muscular dystrophy kind 2I. Dystrophinopathies (Duchenne muscular dystrophy, Becker dystrophy), because of extra connective tissue; Head flexion to 30◦ above the horizontal permits most stimulation of the horizontal semicircular canals, whereas 60◦ below horizontal maximally stimulates the lateral semicircular canals. Induced nystagmus is then timed both with and with out visual fixation (in the dead of night, Frenzel glasses). Normally, the eyes show conjugate deviation in the direction of the ear irrigated with chilly water, with corrective nystagmus in the opposite direction; with heat water the alternative sample is seen. A decreased period of induced nystagmus is seen with canal paresis; enhancement of the nystagmus with removal of visual fixation suggests this is peripheral in origin (labyrinthine, vestibulocochlear nerve), whereas no enhancement suggests a central lesion. In coma the deviation may be present but with out corrective saccades, even at a time when the oculocephalic responses elicited by the doll’s head manoeuvre are misplaced. As coma deepens even the caloric reflexes are misplaced as brainstem involvement progresses. Cross References Coma; Nystagmus; Oculocephalic response; Vertigo; Vestibulo-ocular reflexes Camptocormia Camptocormia, or ‘bent spine syndrome’, was first described as a psychiatric phenomenon in males dealing with armed conflict (a ‘struggle neurosis’). It has subsequently been realized that reducible lumbar kyphosis can also end result from neurological disorders, together with muscle disease (paravertebral myopathy, nemaline myopathy), Parkinson’s disease, dystonia, motor neurone disease, and, probably, as a paraneoplastic phenomenon. Cross References Dropped head syndrome; Dystonia Camptodactyly Camptodactyly, literally ‘bent finger’, is a flexion deformity at the proximal interphalangeal joint, particularly affecting the little fingers; this can be unilateral or bilateral. The term streblomicrodactyly has generally been used to designate isolated crooked little fingers. Camptodactyly might happen as a part of a developmental disorder with different dysmorphic features or in isolation. It is necessary to differentiate camptodactyly, a non-neurogenic reason for clawing, from neurological diagnoses corresponding to:. Awareness of the condition is necessary to avoid pointless neurological investigation. Cross Reference Claw hand Capgras Syndrome this is one of the classical delusional syndromes of psychiatry, by which patients acknowledge a close household relative, or different liked object, but believe them to be have been replaced by an exact alien or ‘double’ (phantasm of doubles). Initially described in patients with psychiatric disorders, it may additionally happen in traumatic, metabolic, and neurodegenerative disorders. Neurologists have encompassed this phenomenon under the term reduplicative paramnesia. Capgras syndrome may be envisaged as a Geschwindian disconnection syndrome, by which the visual recognition system is disconnected from the limbic system, hence faces could be recognized but no emotional significance ascribed to them.

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Selection elements can embrace the pharmacodynamic responsiveness of the mannequin cheap pulmicort line, pharmacokinetic profile buy pulmicort canada, species, strain, gender and age of the experimental animals, the susceptibility, sensitivity, and reproducibility of the test system and available background knowledge on the substance. The time points for the measurements must be based on pharmacodynamic and pharmacokinetic concerns. Justification must be provided for the selection of the actual animal mannequin or test system. Data from unrestrained animals that could be chronically instrumented for telemetry, other appropriate instrumentation strategies for aware animals, or animals conditioned to the laboratory surroundings are preferable to knowledge from restrained or unconditioned animals. In the usage of unanesthetized animals, the avoidance of discomfort or ache is a foremost consideration. Thus, the number of animals or isolated preparations must be enough to reveal or rule out the presence of a biologically significant impact of the test substance. Appropriate adverse and optimistic management teams must be included within the experimental design. In properly-characterized in vivo test systems, optimistic controls will not be necessary. Regardless of the route of administration, exposure to the parent substance and its major metabolites must be just like or greater than that achieved in humans when such info is available. Assessment of results by more than one route could also be applicable if the test substance is meant for clinical use by more than one route of administration. Generally, the doses eliciting the adverse impact must be compared to the doses eliciting the first pharmacodynamic impact within the test species or the proposed therapeutic impact in humans, if possible. It is recognized that there are species differences in pharmacodynamic sensitivity. Therefore, doses ought to embrace and exceed the first pharmacodynamic or therapeutic vary. In the absence of an adverse impact on the safety pharmacology parameter(s) evaluated within the examine, the very best examined dose must be a dose that produces reasonable adverse results in this or in other studies of similar route and length. These adverse results can embrace dose-limiting pharmacodynamic results or other toxicity. Testing of a single group on the limiting dose as described above could also be enough within the absence of an adverse impact on safety pharmacology endpoints within the test species. The vary of concentrations used must be selected to enhance the probability of detecting an impact on the test system. The higher restrict of this vary could also be influenced by physico-chemical properties of the test substance and other assay particular elements. In the absence of an impact, the vary of concentrations selected must be justified. When pharmacodynamic results happen only after a certain length of remedy, or when outcomes from repeat dose non-clinical studies or outcomes from use in humans give rise to issues about safety pharmacological results, the length of the safety pharmacology studies to handle these results must be rationally based. Evaluation of major metabolites is commonly completed through studies of the parent compound in animals. If the main human metabolite(s) is (are) discovered to be absent or current only at comparatively low concentrations in animals, assessment of the effects of such metabolite(s) on safety pharmacology endpoints must be considered. Additionally, if metabolites from humans are identified to substantially contribute to the pharmacological actions of the therapeutic agent, it may be essential to test such lively metabolites. In vitro or in vivo testing of the person isomers must also be considered when the product contains an isomeric mixture. Safety pharmacology studies with the finished product formulation(s) must be carried out only for formulations that substantially alter the pharmacokinetics and/or pharmacodynamics of the lively substance in comparison to formulations beforehand examined. In this regard, the cardiovascular, respiratory and central nervous systems are normally considered the very important organ systems that must be studied within the core battery. In some instances, based on scientific rationale, the core battery must be supplemented (see part 2. The exclusion of certain test(s) or exploration(s) of certain organs, systems or functions must be scientifically justified. Motor activity, behavioral adjustments, coordination, sensory/motor reflex responses and physique temperature must be evaluated. In vivo, in vitro and/or ex vivo evaluations, together with strategies for repolarization and conductance abnormalities, must also be considered. Clinical observation of animals is usually not enough to assess respiratory operate, and thus these parameters must be quantified by utilizing applicable methodologies. Additionally, issues might arise from the safety pharmacology core battery, clinical trials, pharmacovigilance, experimental in vitro or in vivo studies, or from literature reports. When such potential adverse results elevate concern for human safety, these must be explored in follow-up or supplemental safety pharmacology studies, as applicable. The following subsections present lists of studies to additional consider these organ systems for potential adverse pharmacodynamic results. In some circumstances, it may be extra applicable to handle these results in the course of the conduct of other non-clinical and/or clinical studies. For instance, urinary volume, particular gravity, osmolality, pH, fluid/electrolyte balance, proteins, cytology, and blood chemistry determinations corresponding to blood urea nitrogen, creatinine and plasma proteins can be utilized. For instance, binding to receptors related for the autonomic nervous system, useful responses to agonists or antagonists in vivo or in vitro, direct stimulation of autonomic nerves and measurement of cardiovascular responses, baroreflex testing, and heart price variability can be utilized. For instance, gastric secretion, gastrointestinal injury potential, bile secretion, transit time in vivo, ileal contraction in vitro, gastric pH measurement and pooling can be utilized. For instance, dependency potential or skeletal muscle, immune and endocrine functions may be investigated. Safety pharmacology studies previous to the first administration in humans will not be needed for cytotoxic agents for remedy of finish-stage cancer sufferers. However, for cytotoxic agents with novel mechanisms of action, there could also be value in conducting safety pharmacology studies.

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Many neuropathies generic pulmicort 200mcg fast delivery, significantly polyneuropathies within the aged purchase pulmicort with a visa, remain idiopathic or cryptogenic, despite intensive investigation. If these different signs are absent, then isolated nuchal rigidity could suggest a foraminal strain cone. It may occur in syndromes causing predominantly axial (versus limb) rigidity. Cross References Brudzinski’s (neck) signal; Kernig’s signal; Meningism; Parkinsonism Nuchocephalic Reflex In a standing topic, speedy turning of the shoulders to both left or right (eyes closed to keep away from fixation) is associated with bilateral contraction of the cervical musculature in order that the pinnacle is held within the original place. This nuchocephalic -241 N Nyctalopia reflex is current in infants and kids up to the age of about 4 years. Beyond this age the reflex is inhibited, such that the pinnacle is actively turned within the path of shoulder motion after a time lag of about half a second. Cross References Age-related signs; Primitive reflexes Nyctalopia Nyctalopia, or night time blindness, is an impairment of visible acuity specific to scotopic imaginative and prescient, implying a loss or impairment of rod photoreceptor function. Patients could spontaneously complain of a disparity between daytime and nocturnal imaginative and prescient, by which case acuity should be measured in different ambient illumination. Cancer-related retinopathy: most commonly associated with small cell lung cancer (antirecoverin antibodies may be detected), although gynaecological malignancy and melanoma have additionally been related (with antibipolar retinal cell antibodies within the latter). The nature of the nystagmus could allow inferences about the precise location of pathology. Observations should be made within the 9 cardinal positions of gaze for path, amplitude, and beat frequency of nystagmus. The intensity of jerk nystagmus may be classified by a scale of three levels: 1st diploma: current when trying within the path of the quick part; 2nd diploma: current within the impartial place; 3rd diploma: current when trying within the path of the sluggish part. Pendular or undulatory nystagmus: In which the actions of the eyes are more or less equal in amplitude and velocity (sinusoidal oscillations) a couple of central (null) point. When studied utilizing oculography, the sluggish part of jerk nystagmus could present a uniform velocity (‘noticed-toothed’), indicative of imbalance in vestibulo-ocular -243 N Nystagmus reflex exercise. A sluggish part with exponentially lowering velocity (unfavorable exponential sluggish part) is ascribed to ‘leakiness’ of a hypothetical neural integrator, a construction which converts eye or head velocity alerts into approximations of eye or head place alerts (thought to lie within the interstitial nucleus of Cajal within the midbrain for vertical eye actions and within the nucleus propositus hypoglossi for horizontal eye actions). A sluggish part with exponentially growing velocity (high-achieve instability, runaway actions) may be seen in congenital or acquired pendular nystagmus. The pathophysiology of acquired pendular nystagmus is thought to be deafferentation of the inferior olive by lesions of the pink nucleus, central tegmental tract, or medial vestibular nucleus. Nystagmus of peripheral vestibular origin is typically decreased by fixation (hence these patients maintain their heads nonetheless) and enhanced by removing of visible fixation (in the dead of night, with Frenzel’s lenses). Central vestibular: unidirectional or multidirectional, 1st, 2nd or 3rd diploma; usually sustained and protracted. Cerebellar/brainstem: commonly gaze-evoked as a result of a failure of gaze-holding mechanisms. Congenital: often horizontal, pendular-sort nystagmus; worse with fixation, attention, and nervousness. It could seem with blindness of childhood onset or be acquired with neurological illness (multiple sclerosis, mitochondrial illness, Whipple’s illness, Pelizaeus–Merzbacher illness). Ataxic/dissociated: in abducting >> adducting eye, as in internuclear ophthalmoplegia and pseudointernuclear ophthalmoplegia. Many pathologies could cause nystagmus, the commonest being demyelination, vascular illness, tumour, neurodegenerative disorders of cerebellum and/or brainstem, metabolic causes. Wernicke–Korsakoff’s syndrome), paraneoplasia, medication (alcohol, phenytoin, barbiturates, sedative-hypnotic medication), toxins, and epilepsy. Pendular nystagmus could respond to anticholinesterases, according to its being a result of cholinergic dysfunction. Periodic alternating nystagmus responds to baclofen, hence the importance of making this diagnosis. These signs are thought to reflect important compromise of optic nerve head perfusion and are invariably associated with the finding of papilloedema. Obscurations mandate urgent investigation and remedy to stop permanent visible loss. Cross Reference Papilloedema Obtundation Obtundation is a state of altered consciousness characterised by decreased alertness and a lessened curiosity within the setting, sometimes described as psychomotor retardation or torpor. An elevated proportion of time is spent asleep and the patient is drowsy when awake. Cross References Coma; Psychomotor retardation; Stupor Ocular Apraxia Ocular apraxia (ocular motor apraxia) is a disorder of voluntary saccade initiation; reflexive saccades and spontaneous eye actions are preserved. Ocular apraxia may be overcome through the use of dynamic head thrusting, with or without blinking (to suppress vestibulo-ocular reflexes): the specified fixation point is achieved via reflex contraversive tonic eye actions to the midposition following the overshoot of the eyes caused by the pinnacle thrust. Ocular apraxia could occur as a congenital syndrome (within the horizontal aircraft only: Cogan’s syndrome), or may be acquired in ataxia telangiectasia (Louis–Bar syndrome), Niemann–Pick illness (mainly vertical aircraft affected), and Gaucher’s illness (horizontal aircraft only). Cross References Apraxia; Saccades Ocular Bobbing Ocular bobbing refers to intermittent abnormal vertical eye actions, often conjugate, consisting of a fast downward motion followed by a sluggish return to the preliminary horizontal eye place. The signal has no precise localizing value, but is most commonly associated with intrinsic pontine lesions. It has additionally been described in encephalitis, Creutzfeldt–Jakob illness, and poisonous encephalopathies. Its pathophysiology is uncertain but could involve mesencephalic and medullary burst neurone centres. Inverse ocular bobbing: sluggish downward motion, quick return (also called quick upward ocular bobbing or ocular dipping); Converse ocular bobbing: sluggish upward motion, quick down (also called sluggish upward ocular bobbing or reverse ocular dipping). Cross Reference Ocular dipping Ocular Dipping Ocular dipping, or inverse ocular bobbing, consists of a sluggish spontaneous downward eye motion with a fast return to the midposition.

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References:

  • http://www.oecd.org/education/school/48727127.pdf
  • https://www.medicine.wisc.edu/sites/default/files/diagnosis_manage_rhinosinusitis_wald.pdf
  • https://www.iasp-pain.org/files/Content/ContentFolders/Publications2/FreeBooks/Guide_to_Pain_Management_in_Low-Resource_Settings.pdf
  • https://www.marchofdimes.org/toward-improving-the-outcome-of-pregnancy-iii.pdf
  • https://ecrsh.eu/mm/conference_folder.pdf
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