Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Brooke-Spiegler Syndrome - an underrecognized cause of multiple familial scalp tumors: report of a new germline mutation

BACKGROUND: Brooke-Spiegler syndrome (BSS) is probably an underdiagnosed genodermatosis that predisposes for the development of cylindromas, spiradenomas and trichoepitheliomas mainly of the head and neck. Wide phenotypic variability regarding the number and type of lesions can be observed within a family. Mutations of the CYLD gene are identified in the vast majority of cases and play a key role in BSS pathogenesis. MAIN OBSERVATIONS: Two first degree relatives with numerous erythematous telangiectatic nodules of the scalp present for decades, with recurring tendency regardless the multiple previous excisions. Histopathological review of the lesions revealed predominantly "spiradenocylindromas" in the proband and cylindromas in her sister. The suspicion of BSS was confirmed after detection of a new nonsense germline mutation of CYLD (c.1783C>T pGln 595*) in the proband. CONCLUSIONS: BSS diagnosis can be challenging and is based on clinical-pathological correlation, positive familial association and identification of CYLD mutations. CYLD exerts antineoplastic effects by downregulating intracellular NF-κB signalling pathways. The reported mutation affecting the ubiquitin-specific protease domain leads to a truncated and catalytically inactive enzyme. Despite the expanding list of CYLD mutations no firm genotype-phenotype correlation is known so far. Early recognition and treatment of BSS avoid disfiguring changes like "turban tumor".

Les représentations de la femme dans le discours religieux du XIIIe au XVe siècle : une cause de la chasse aux sorcières?

[…] Le regard que nous porterons sur le discours religieux et ses représentations de la femme nous permettra de déterminer quel rôle il a joué dans la conception de la femme comme symbole et source du mal dans la société du temps et, par le fait même, dans le phénomène de la chasse aux sorcières. Comme nous le verrons, plusieurs causes peuvent être attribuées à ce phénomène, causes d'autant plus déterminantes que le discours religieux sur les femmes vient les renforcer. La démarche d'exposition de la problématique se déploiera dans quatre chapitres. Le premier chapitre nous permettra de dégager les sources d'influence des représentations de la femme dans le discours religieux du XIIIe au XVe siècle. Nous tenterons de démontrer que les théologiens médiévaux ont puisé dans ces sources, des citations virulentes qu'ils ont utilisées hors de leur visée contextuelle afin d'appuyer par des autorités reconnues leur thèse d'une nature inférieure chez la femme et de démontrer sans conteste qu'elle est un être destiné au mal. Avec le chapitre deux nous poserons notre regard sur le discours religieux; soit le discours théologique et les sermons populaires sur la femme à l'époque en cause. Nous découvrirons, qu'il révélé ses sources d'influence, et de surcroît qu'il reflète plus que jamais auparavant une profonde misogynie. La femme est désormais, et cela sans l'ombre d'un doute, l'incarnation du mal. Au chapitre trois, nous tenterons de démontrer quelle influence a eu ce discours, particulièrement les sermons populaires, dans l'intégration sociale des représentations de la femme. Comme nous le verrons, cette société a elle aussi participé à décrier la femme, à faire d'elle un être destiné au mal. Le dernier chapitre, le quatrième, vise à déterminer quel rôle a joué le discours religieux dans le phénomène de la chasse aux sorcières du XIIIe au XVe siècle. Cela en tenant compte d'un ensemble de facteurs, tous plus plausibles les uns que les autres. Certes, il nous faut remplir notre engagement. Pour ce faire, il nous faut surtout éviter de tomber dans la tentation de l'anachronisme, c'est-à-dire, de juger une Église, une société, une culture au nom d'une autre, à partir de la nôtre. Cet écueil nous estimons l'avoir évité. Certes, notre intérêt pour la promotion des femmes nous a guidé dans le choix de notre sujet, mais dans l'analyse de nos sources nous avons privilégié l'impartialité.

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015 : a systematic analysis for the Global Burden of Disease Study 2015

Arterial entrapment syndrome in the cubital fossa: a rare cause of acute stress-related arterial thrombosis in a patient with brachial artery duplication

Arterial entrapment syndrome (AES) at elbow level is very rare and to our knowledge no case of AES by lacertus fibrosus in the cubital fossa in presence of brachial artery duplication has been described to date. We describe a rare case of acute arterial thrombosis of one of two brachial arteries highlighted in the cubital fossa which developed after strenuous right elbow flexor muscle activity and hyper-extensions presumably related to AES by lacertus fibrosus at elbow level. A 43-year-old right-handed woman, experienced paleness, coldness and numbness of the right hand, after 8 consecutive hours of gardening. As she worked, her ipsilateral flexor elbow muscles remained in prolonged and inappropriate tension. Clinical examination evidenced the absence of radial artery pulse in the wrist and mild hypothermia in the second and third finger. During surgical exploration two anastomosed brachial arteries were detected in the cubital fossa under the lacertus fibrosus. The lateral superficial brachial artery was occluded. Intraoperative arteriography evidenced brachial artery duplication at the third superior of the arm and normal vascular pattern at the forearm level. In cases of unexplained atypical intermittent upper extremity claudication or acute ischemic symptoms an AES should always be ruled out, particularly when symptoms are exacerbated by strenuous upper extremity activity or when upper limb muscular hypertrophy is evident. In these cases a thorough dynamic clinical and instrumental examination is mandatory to confirm a diagnosis of AES and to avoid possible future ischemic complications.

Rice-Infecting Pseudomonas Genomes Are Highly Accessorized and Harbor Multiple Putative Virulence Mechanisms to Cause Sheath Brown Rot

Sheath rot complex and seed discoloration in rice involve a number of pathogenic bacteria that cannot be associated with distinctive symptoms. These pathogens can easily travel on asymptomatic seeds and therefore represent a threat to rice cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been associated with sheath brown rot disease in several rice growing areas around the world. The appearance of a similar Pseudomonas population, which here we named P. fuscovaginae-like, represents a perfect opportunity to understand common genomic features that can explain the infection mechanism in rice. We showed that the novel population is indeed closely related to P. fuscovaginae. A comparative genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous genomes and a high number of strain-specific genes. The genomes of P. fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI) and other important pathogenicity machinery that could probably facilitate rice colonization. We identified 123 core secreted proteins, most of which have strong signatures of positive selection suggesting functional adaptation. Transcript accumulation of putative pathogenicity-related genes during rice colonization revealed a concerted virulence mechanism. The study suggests that rice-infecting Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a variable set of metabolic capabilities as a potential strategy to occupy a range of environments.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

Brooke-Spiegler Syndrome - an underrecognized cause of multiple familial scalp tumors: report of a new germline mutation

BACKGROUND: Brooke-Spiegler syndrome (BSS) is probably an underdiagnosed genodermatosis that predisposes for the development of cylindromas, spiradenomas and trichoepitheliomas mainly of the head and neck. Wide phenotypic variability regarding the number and type of lesions can be observed within a family. Mutations of the CYLD gene are identified in the vast majority of cases and play a key role in BSS pathogenesis. MAIN OBSERVATIONS: Two first degree relatives with numerous erythematous telangiectatic nodules of the scalp present for decades, with recurring tendency regardless the multiple previous excisions. Histopathological review of the lesions revealed predominantly "spiradenocylindromas" in the proband and cylindromas in her sister. The suspicion of BSS was confirmed after detection of a new nonsense germline mutation of CYLD (c.1783C>T pGln 595*) in the proband. CONCLUSIONS: BSS diagnosis can be challenging and is based on clinical-pathological correlation, positive familial association and identification of CYLD mutations. CYLD exerts antineoplastic effects by downregulating intracellular NF-κB signalling pathways. The reported mutation affecting the ubiquitin-specific protease domain leads to a truncated and catalytically inactive enzyme. Despite the expanding list of CYLD mutations no firm genotype-phenotype correlation is known so far. Early recognition and treatment of BSS avoid disfiguring changes like "turban tumor".

Hashimoto’s Encephalopathy: An Unusual Cause of Autoimmune Encephalopathy in a Clinically and Biochemically Euthyroid Patient

Objectives: To highlight the occurrence of Hashimoto’s encephalopathy – a steroid-responsive encephalopathy associated with elevated antithyroid antibodies. Material and methods: We describe a clinically and biochemically euthyroid patient with an encephalopathy presenting with headache, mild confusion and personality changes for 6 weeks and tonic–clonic seizures upon admission Results: There was no obvious infective or metabolic cause. The patient had a high titre of antithyroid antibodies and responded to steroid therapy. Conclusion: This uncommon disease needs to be considered in patients presenting with neurological symptoms that remain unexplained after routine standard investigations, even when the patient is euthyroid. Early diagnosis is important, as this is a treatable condition.

Non-acute Transient Reversible Adrenal Insufficiency in a Survivor of Critical Illness: A Lesser-known Cause of Primary Adrenal Insufficiency

Objectives: Primary adrenal insufficiency AI is regarded as a progressive disease needing lifelong replacement therapy, but this may not always be the case. Material and methods: A non-acute presentation of AI following a hypotensive episode caused by blood loss was investigated. Results: Adrenal function fully recovered without treatment. Conclusions: There should be a high index of suspicion and a low threshold for performing tests of adrenal function in survivors of critical illness and severe hypotensive episodes.

A Rare Cause of Chronic Low Back Pain

Objectives: Autosomal dominant osteopetrosis (ADO) is a rare genetic disease characterized by increased bone mass and density due to defective bone resorption. The aim of this case study is to present the clinical and radiographic features of a 22-year-old male patient with ADO and to serve as a reminder that this rare disease should be considered in the differential diagnosis of chronic low back pain. Materials and methods: A 22-year-old patient with ADO is presented in this case report. Results: Clinical and radiographic features of the patient were consistent with ADO. Conclusions: ADO should be taken into consideration in differential diagnosis of low back pain.

“Saved by the Pacing Catheter”: Gigantic Right Atrial Thromboembolus as a Cause of Pulmonary Embolism

Pulmonary embolism (PE) related to the presence of right heart thromboemboli entails a higher mortality rate than PE alone. Furthermore, right heart thromboemboli are often associated with deep venous thrombosis. The most effective therapy for haemodynamically stable patients remains unknown, although recent data suggest that thrombolytic therapy is associated with a better outcome. We describe the case of an 83-year-old woman, hospitalized with PE consequent to right heart thrombus-in-transit, in whom investigation revealed a concomitant deep venous thrombosis. She required thrombolysis, given the high mortality risk that is traditionally associated with this clinical entity.

A Rare Cause of Confusion: Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis

An 81-year-old female patient required numerous admissions for symptoms of confusion, visual hallucinations, myoclonus and seizures, which were treated as stroke, infections and viral encephalitis with some improvement after treatment but with recurrence that caused her to be readmitted to hospital. On the last admission, she was found to have very high antithyroid antibodies and a diagnosis of Hashimoto’s encephalopathy was made, with an overwhelming response to steroids.

Deep Venous Thrombosis (DVT) in Lower Extremity Amputation as Cause of Pulmonary Embolism

The authors describe the case of a 43-year-old man with a right-leg knee amputation performed 14 years prior. He presented to hospital with dyspnea. A pulmonary embolism was detected. A Doppler ultrasound test showed deep vein thrombosis (DVT), which affected the stump of the amputated limb. When a pulmonary embolism is detected in a patient with an amputated lower limb, an exploration of the stump should be performed to rule out this uncommon complication.

An Unexpected Cause of Marked Weight Loss Associated with Vomiting in an Adult Man: Gastric Phytobeozar

Objectives: We present the case of an edentulous 47-year-old farmer referred to our Department of Internal Medicine because of postprandial vomiting, hyporexia, asthenia and weight loss. He ate a mostly vegetarian diet. Materials and methods: An oesophagogastroduodenoscopy revealed the presence of a phytobezoar at the level of the fundus and body of the stomach. Endoscopic fragmentation and removal of the phytobezoar were unsuccessful and the patient had to undergo open surgery. Results: Recovery was uneventful and free of complications. Conclusion: Phytobezoars should be taken into account in the differential diagnosis of unexplained vomiting and weight loss.