Glutamate in dopamine neurons: synaptic versus diffuse transmission

There is solid electron microscopic data demonstrating the existence of dopamine (DA) axon terminals (varicosities) with or without synaptic membrane specializations (junctional complexes) in many parts of the CNS, and notably in neostriatum and nucleus accumbens. The dual morphological character of these DA innervations has led to the suggestion that the meso-telencephalic DA system operates by diffuse (or volume) as well as by classical synaptic transmission. In the last decade, electrophysiological and neurochemical evidence has also accumulated indicating that monoamine neurons in various parts of the CNS, and particularly the mesencephalic DA neurons, might release glutamate as a co-transmitter. Following the identification of the vesicular transporters for glutamate (VGluT), in situ hybridization and RT-PCR studies carried out on isolated neurons or standard tissue cultures, and more recently in vivo, have shown that VGluT2 mRNA may be expressed in a significant proportion of mesencephalic DA neurons, at least in the ventral tegmental area. A current study also suggests that the co-expression of tyrosine hydroxylase (TH) and VGluT2 by these neurons is regulated during embryonic development, and may be derepressed or reactivated postnatally following their partial destruction by neonatal administration of 6-hydroxydopamine (6-OHDA). In both 15 day-old and adult rats subjected or not to the neonatal 6-OHDA lesion, concurrent electron microscopic examination of the nucleus accumbens after dual immunocytochemical labeling for TH and VGluT2 reveals the co-existence of the two proteins in a significant proportion of these axon terminals. Moreover, all TH varicosities which co-localize VGluT2 are synaptic, as if there was a link between the potential of DA axon terminals to release glutamate and their establishment of synaptic junctions. Together with the RT-PCR and in situ hybridization data demonstrating the co-localization of TH and VGluT2 mRNA in mesencephalic neurons of the VTA, these observations raise a number of fundamental questions regarding the functioning of the meso-telencephalic DA system in healthy or diseased brain.     

Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses

A longstanding paradox in the activation of cytotoxic T lymphocytes (CTL) arises from the observation that CTL recognize and rapidly destroy target cells with exquisite sensitivity despite the fact that cytokine production requires sustained signaling at the immunological synapse. Here we solve this paradox by showing that CTL establish sustained synapses with targets offering strong antigenic stimuli and that these synapses persist after target cell death. Simultaneously, CTL polarize lytic granules toward different cells without discrimination regarding antigenic potential. Our results show that spatiotemporal uncoupling of immunological synapse and lytic granule secretion allows multiple killing and sustained signaling by individual CTL. This unique mechanism of responding to multiple contacts provides remarkable efficiency to CTL function.     

Hepatic tuberculosis: case report of pseudotumoral form

Inflammatory pseudo-tumors of the liver are rare and difficult to diagnose, mimicking malignant tumors. We report a patient, 42 year old with hepatic pseudo-tumor who was suspected to have pseudotumoral hepatic tuberculosis without immunodepression and treated by major hepatic surgery because no sure diagnosis. Therapeutic approach of hepatic inflammatory pseudotumors is often medical and surgical and may need major hepatic surgery in case of sure etiologic diagnosis.     

Sigmoid lipoma as an exceptional cause of intussusception and bowel obstruction in adults: A case report and review of literature

Acute intestinal intussusception in adults is a rare condition, most often secondary to an organic lesion (tumor or inflammation), representing 1%-5% of intestinal obstructions. Pure colic intussusception on lipoma rectal causing bowel obstruction is an exceptional situation. A 60-year-old man presented to the emergency department for acute abdominal pain with marked abdominal distention and red rectal bleeding. A contrast-enhanced abdominal CT scan was performed, which revealed a recto-sigmoid intussusception on lipoma, causing mechanical intestinal obstruction. The patient underwent a partial reduction of the intussusception with partial sigmoid resection and end colostomy. Colonic lipomas of the recto-sigmoid region represent a very rare condition and a subsequent etiology for intussusception and bowel obstruction in adults. However, it should be considered in the differential diagnosis of such situations.     

Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR = 1.03), Medicare insurance (OR = 2.21) and having a primary care physician (PCP) (OR = 4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR = 1.04) and having a PCP (OR = 2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR = 4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.     

Unusual cause of binocular diplopia: Cavernous sinus hemangioma

Cavernous hemangiomas are rare account representing 5%-13% of the intracranial vascular malformations and occur in approximately 0.5%-1% of the population. We report the case of 34-years-old woman, having a medical history of seizure, admitted for headache with binocular diplopia. The radiology investigation and operatory piece has shown an association of cavernous sinus hemangioma and frontal focal cortical dysplasia. This study highlights clinical, radiological and therapeutic features of this entity.     

A homozygous missense variant in the PLCB4 gene causes severe phenotype of auriculocondylar syndrome type 2

Auriculocondylar syndrome (ARCND) is a rare craniofacial birth defect characterized by malformations in the mandible and external ear (Question Mark Ear). Genetically, three distinct subtypes of ARCND (ARCND1, ARCND2, and ARCND3) have been identified. ARCND2 is linked to pathogenic variants in the PLCB4 gene (phospholipase C β4). PLCB4 is a key effector of the EDN1-EDNRA pathway involved in craniofacial development via the induction, migration, and maintenance of neural crest cells. ARCND2 is typically inherited in an autosomal dominant pattern, with recessive inheritance pattern being rare. In this study, we report the first homozygous missense variant (NM_000933.4: c.2050G>A: p.(Gly684Arg)) in the PLCB4 gene causing ARCND in a 3-year-old patient with a severe clinical phenotype of the syndrome. The patient presented with typical craniofacial ARCND features, in addition to intestinal transit defect, macropenis, and hearing loss. These findings further delineate the phenotypic spectrum of ARCND associated with autosomal recessive PLCB4 loss of function variants. Notably, our results provide further evidence that these variants can result in a more severe and diverse manifestations of the syndrome. Clinicians should consider the rare features of this condition for better management of patients.