Delayed onset Bickerstaff brainstem encephalitis overlapping Miller-Fisher Syndrome during SARS-CoV-2 infection.

Bickerstaff brainstem encephalitis (BBE) is a neuroimmunologic disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance, mostly subsequent to an infection. BBE is considered to be a variant of Miller-Fisher syndrome (MFS), which also exhibits external ophthalmoplegia and ataxia but not presenting consciousness alterations. Therefore, these two medical conditions are included in the clinical spectrum of the "Fisher-Bickerstaff syndrome" ( Shahrizaila and Yuki in J Neurol Neurosurg Psychiatry 84(5):576-583) [1]. With regard to the etiopathogenesis, increasing evidence worldwide suggests that SARS-CoV-2 infection-enhanced immune response is involved in a wide range of neurological complications such as Guillain-Barré syndrome (GBS), MFS, acute necrotizing encephalitis (ANE), myelitis, acute disseminated encephalomyelitis (ADEM), and, although very rarely, BBE either (Hosseini et al. in Rev Neurosci 32:671-691) [2]. We report a case of a patient affected by delayed onset BBE overlapping MFS during a mild SARS-CoV-2 infection. To the best of our knowledge, similar cases have never been reported.

Migraine with aura: which patients are most at risk of stroke?

The complex association between migraine (M) and ischemic stroke (IS) is discussed. Epidemiological studies and meta-analyses show that M with aura (MA) and not M without aura, doubles the risk of IS. The risk is higher for female gender, young age and higher headache attacks frequency. Smoking habit and oral contraceptives, especially if associated, increase stroke risk. The underlying pathogenetic mechanisms are not completely understood, but it is hypothesized that a particular brain susceptibility to cortical spread depression could explain the association between MA and IS. The absolute risk of IS in migraineurs is relatively low and an antithrombotic primary prevention is not indicated, but it is mandatory to investigate and treat associated risk factors for IS and, in young MA women, consider only progestinic oral contraceptives, if needed, and smoking cessation.

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth.

In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor (EGF) trigger association of the androgen receptor (AR)-estradiol receptor (ER) (alpha or beta) complex with Src. This interaction activates Src and affects the G1 to S cell cycle progression. In this report, we identify the sequence responsible for the AR/Src interaction and describe a 10 amino-acid peptide that inhibits this interaction. Treatment of the human prostate or mammary cancer cells (LNCaP or MCF-7, respectively) with nanomolar concentrations of this peptide inhibits the androgen- or estradiol-induced association between the AR or the ER and Src the Src/Erk pathway activation, cyclin D1 expression and DNA synthesis, without interfering in the receptor-dependent transcriptional activity. Similarly, the peptide prevents the S phase entry of LNCaP and MCF-7 cells treated with EGF as well as mouse embryo fibroblasts stimulated with androgen or EGF. Interestingly, the peptide does not inhibit the S phase entry and cytoskeletal changes induced by EGF or serum treatment of AR-negative prostate cancer cell lines. The peptide is the first example of a specific inhibitor of steroid receptor-dependent signal transducing activity. The importance of these results is highlighted by the finding that the peptide strongly inhibits the growth of LNCaP xenografts established in nude mice.

Electroclinical evolution in ring chromosome 20 epilepsy syndrome: a case with severe phenotypic features followed for 25 years.

Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20 syndrome [r(20)], while dysmorphic features, mental retardation and behavioural disturbances are widely variable. The clinical evolution of r(20) over time is not well defined as relatively few cases have been reported. Here we describe a patient with severe clinical features followed for a 25-year period. The patient was subjected to clinical, psychometric and EEG evaluation twice a year from the age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence in situ hybridization (FISH) and several immunological investigations were performed. Ring chromosome 20 was found in 50% of examined metaphases with the deletion of subtelomeric regions 20p and 20q. Our patient presented with marked dysmorphic features, severe mental retardation, tetraparesis, dysarthria and intractable epilepsy with onset during the first year of life. During follow up, EEG findings and clinical features progressively worsened: a progressive disorganization of background EEG activity occurred and mental and motor impairment evolved. The severity of clinical expression depended on the extent of chromosomal deletion and on the haploinsufficiency of other important related genetic loci due to ring instability. The progressive worsening of both clinical and EEG features over a long period, which has also been reported by other authors, further characterized this syndrome.

Molecular analysis of the heterogeneity region of the human ribosomal spacer.

The human ribosomal non-transcribed spacers are 30 X 10(3) base-pairs (or 30 kb) in length with a limited length heterogeneity localized in a specific region downstream from the 3' end of the transcribed region. Total DNA digested with EcoRI and BamHI and hybridized with a probe containing the 3' end of the 28 S ribosomal RNA coding region shows four major bands of 3.9 kb, 4.6 kb, 5.4 kb and 6.2 kb. The 5.4 kb band is the most abundant in every individual, followed by the 4.6 kb band. The longest and the shortest size classes are less well-represented and may even be absent. Every individual shows his own pattern of relative abundance of non-transcribed spacer length classes that can be followed through generations. We decided to investigate the molecular structure of the heterogeneity region, in order to cast light onto the mechanisms underlying the origin and maintenance of this length heterogeneity. Pertinent spacer regions of eight ribosomal clones from two human genomic libraries were subcloned and analyzed by restriction mapping and nucleotide sequencing. In the minimal length class, there is a sequence of 700 base-pairs that appears to be tandemly duplicated once, twice or three times in the other length classes. This repeated DNA module contains a region consisting of repetitions of simple pyrimidine groups like C-T, C-T-T-T or C-C-C-T. DNA module repeats may differ by the length of this pyrimidine-rich region. However, these length variations are not continuous, as revealed by Southern transfer analysis of several individuals and different cloned gene units: instead, the repeated modules fall into two discrete length classes of about 700 base-pairs and 800 base-pairs. An imperfect duplication of a short sequence of 86/89 base-pairs is present at the boundary between the heterogeneity region and the upstream flanking region, representing a very ancient duplication event.

Phosphorylation on tyrosine of in vitro synthesized human estrogen receptor activates its hormone binding.

Hormone binding controls the activity of estradiol receptor. The in vitro synthesized human receptor binds hormone with high affinity and low efficiency (1-4% of the maximal binding). We now report that phosphorylation on tyrosine of the synthetic receptor by an extensively purified calf uterus kinase increases hormone binding towards maximal levels without change in affinity. This is the first direct demonstration that a newly synthesized hormone receptor acquires ligand binding through phosphorylation. The use of in vitro synthesized proteins as substrates for enzymes which cause functional modifications of proteins is very promising because it is easy to identify the modified domains and residues by using deleted and point mutated proteins. Experiments with two estradiol receptor deletion mutants, one which lacks the N-terminal half of the receptor and binds hormone independently from the N-terminal half of the receptor, the other which lacks the C-terminal half of the receptor and contains the domain required to recognize the estradiol responsive elements, show that tyrosine phosphorylation occurs exclusively within or near the hormone binding domain of the receptor.

In vitro phosphorylation and hormone binding activation of the synthetic wild type human estradiol receptor.

A tyrosine kinase purified from calf uterus activates the hormone binding of endogenous estradiol receptor (ER) predephosphorylated and preinactivated by a nuclear phosphotyrosine phosphatase. The kinase also activates and phosphorylates the human estradiol receptor HEO synthesized in vitro, which differs from the wild type receptor HEGO because a glycine is replaced by a valine at position 400. Moreover, the kinase activates and phosphorylates a deletion mutant of HEO which consists almost exclusively of the hormone binding domain. Using HEGO and HEO in parallel and measuring both binding activation and phosphorylation of ER we now observe that the wild type receptor is a good kinase substrate, slightly better than HEO. Furthermore, HEGO like the calf uterus receptor in the presence of estradiol, stimulates the kinase. From present findings it appears that ER and uterus tyrosine kinase are functionally associated and that this association is abolished by glycine to valine substitution at position 400 of ER.

Sex steroid hormones act as growth factors.

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

Src is an initial target of sex steroid hormone action.

Recent observations that steroids use pathways universally known to be regulated by growth factors and interleukins highlight the following points: (1) Steroid stimulation of the canonical pathway Src/Ras/Erk signaling from membrane to nuclei or its single members has been observed in different cell types including human cancer-derived cells, neurons, osteoblasts, osteocytes, and endothelial cells. This stimulation has been reconstituted and analyzed in transiently transfected cells. (2) Cellular context and intracellular localization of receptors are crucial in determining the biological effects evoked by this hormonal stimulation: proliferation, protection from apoptosis, and vasorelaxation. (3) Classical steroid receptors localized in the extranuclear compartment directly and, in some cases, simultaneously interact with Src. They are capable of unexpected cross talks responsible for the observed effects. (4) Other signaling pathways including P13K/AKT are also stimulated by steroids. The aim of future work will be to arrive at an integrated general view of the different signaling pathways activated by steroids and to analyze the concert between these pathways and the hormonal transcriptional action. This general view should be simultaneously verified in different cell contexts, under different physiologic and pathologic conditions. We expect that the new technologies, above all gene and protein microarray, will make this goal feasible.

Characterization and epitope mapping of a new panel of monoclonal antibodies to estradiol receptor.

A new panel of monoclonal antibodies to the calf uterus estrogen receptor was prepared. Thirteen antibodies were characterized for their isotype and for the affinity for the antigen. These antibodies recognize the human receptor and can be used in Western blot analysis. The location of the epitopes was mapped on the antigen structure using synthetic fragments of estrogen receptor, and it was possible to group the antibodies in five groups. Many antibodies were useful for the purification of estrogen receptor from tissue extracts by immunoaffinity chromatography. The reciprocal inhibition of the antibodies for the antigen binding was measured with an immunoadsorption assay. This was maximal and symmetrical for antibody pairs within the same group, but was incomplete and, in some instances, asymmetrical between pairs of antibodies from different groups. One antibody was able to inhibit the estrogen receptor-DNA interaction, whereas two others were unable to recognize the receptor-DNA complexes. This new panel of antibodies is a useful addition to the existing tools for studying structure and function of the estrogen receptor.

Cholecystoenteric fistula (CF) is not a contraindication for laparoscopic surgery.

BACKGROUND: Cholecystoenteric fistula (CF) is a rare complication of cholelithiasis. The aim of this study was to evaluate the safety and risk of complications when the laparoscopic approach is applied in patients with CF. METHODS: A questionnaire was mailed to all surgeons with experience of >100 cholecystectomies working in Naples, Italy, and the neighboring area. RESULTS: Between February 1990 and May 1999, 34 patients presented with cholecystoenteric fistula (0.2% of >15,000 laparoscopic cholecystectomies performed in the same period). These patients were allocated into two groups: the LT group (those who underwent laparotomic conversion after the diagnosis of CF), which consisted of 20 patients, four men and 16 women, with a mean age of 66.5 +/- 9.3 years (range, 46-85) and the LS group (laparoscopically treated patients), which consisted of 14 patients, three men and 11 women, with a mean age of 65.6 +/- 8.8 years (range, 51-74). They types of CF observed were as follows: in the former group of patients, cholecystoduodenal fistulas (n = 11, 55%), cholecystocolic fistulas (n = 5, 25%), cholecystojejunal fistulas (n = 3, 15%), and cholecystogastric fistulas (n = 1, 5%); in the latter group, cholecystoduodenal fistulas (n = 8, 5.1%), and cholecystocolic fistulas (n = 4, 28.6) and cholecystojejunal fistulas (n = 2, 14.3%). Stapler closure of CF was done in four LT patients and three LS patients with cholecystoduodenal fistula; it was also done in three LT patients and three LS patients with cholecystocolic fistula. Hand-sutured fistulectomy was performed in six LT patients and three LS patients with cholecystoduodenal fistula, in two LT patients with cholecystocolic fistula, and in all patients with cholecystojejunal or cholecystogastric fistula. There were no deaths or intraoperative complications in either group. One patient in the LT group developed a bronchopneumonia postoperatively. Postoperative hospital stay was significantly longer in LT patients-17 +/- 4 vs 3+/-1 days (p < 0.001). CONCLUSION: Cholecystoenteric fistula is an occasional intraoperative finding during laparoscopic cholecystectomy. The results of this study, which are based on the collective experiences of 19 surgeons, illustrate the growing success of the laparoscopic approach to this condition, including a decreasing rate of conversion to open surgery over the last 3 years.

[Reticulosarcoma of the stomach. Apropos of 3 cases]. / Sul reticolosarcoma dello stomaco. A proposito di tre osservazioni.

The authors report 3 cases of gastric reticulum cell sarcoma upon 58 tumours of stomach observed in the period 1975-1978. They examine the anatomopathological aspects in conformity with the last classification, they dispute about the clinical aspects and they accentuate the difficulty whether clinical or instrumental to succeed in an early diagnosis but they confirm also the opinion a surgical therapy extremely aggressive in sole possible. This therapy aggressive, eventually associated with the irradiation therapy and sometimes with the chemotherapy, makes the prognosis of types of tumours remarkably better than forms carcinomatous.

[Study of suprarenal cysts. Apropos of a case of cystic lymphagioma of the adrenal glands]. / Contributo allo studio delle cisti del surrene. A proposito di un caso di linfangioma cistico del surrene.

Following a review of the literature on the incidence and characteristics of suprarenal cysts, the case of a young woman who was suffering from bland urinary symptomatology is reported. On the basis of anatomopathological study, the case was classified as a cystic lymphangioma of the suprarenal gland arising on a malformative base.

[Asthma and covert toxocariasis]. / Asma y toxocarosis encubierta.

The relationship between asthma and covert toxocariasis was studied in 38 patients with asthma and 44 control individuals (without asthma). Inclusion/exclusion criteria were determined. An ELISA test based on the detection of Anti-Toxocara canis (E/S antigen) serum immunoglobulin G (Ig G) and E (Ig E) was determined in both groups. Ordinary allergens and E/S antigen of T. canis injections were used to evaluate cutaneous reactivity. The seroprevalence in patients with asthma was 68.42%, and in the control individuals was 13.63%. This difference was significant. The percentage of asthmatic patients with two antitoxocara antibodies was 26.31% and 4.54% in control individuals. All asthmatic patients with antitoxocara IgE had cutaneous reactivity to Ag E/S. We conclude that the asthmatic patients with IgE and IgG antitoxocara suffer a covert toxocarosis.

Atopic dermatitis guideline. Position paper from the Latin American Society of Allergy, Asthma and Immunology.

As in other regions, the incidence of atopic dermatitis in Latin America has been increasing in recent years. Although there are several clinical guidelines, many of their recommendations cannot be universal since they depend on the characteristics of each region. Thus, we decided to create a consensus guideline on atopic dermatitis applicable in Latin America and other tropical regions, taking into account socio-economic, geographical, cultural and health care system characteristics. The Latin American Society of Allergy Asthma and Immunology (SLAAI) conducted a systematic search for articles related to the pathophysiology, diagnosis and treatment of dermatitis using various electronic resources such as Google, Pubmed, EMBASE (Ovid) and Cochrane data base. We have also looked for all published articles in Latin America on the subject using LILACS (Latin American and Caribbean Literature on Health Sciences) database. Each section was reviewed by at least two members of the committee, and the final version was subsequently approved by all of them, using the Delphi methodology for consensus building. Afterward, the final document was shared for external evaluation with physicians, specialists (allergists, dermatologists and pediatricians), patients and academic institutions such as universities and scientific societies related to the topic. All recommendations made by these groups were taken into account for the final drafting of the document. There are few original studies conducted in Latin America about dermatitis; however, we were able to create a practical guideline for Latin America taking into account the particularities of the region. Moreover, the integral management was highlighted including many of the recommendations from different participants in the health care of this disease (patients, families, primary care physicians and specialists). This practical guide presents a concise approach to the diagnosis and management of atopic dermatitis that can be helpful for medical staff, patients and their families in Latin America.

La incidencia de dermatitis atópica en Latinoamérica muestra un incremento constante, si bien existen muchas guías clínicas de dermatitis atópica, muchas de las recomendaciones no pueden ser válidas de manera universal debido a las particularidades de cada región. Por ello, nos propusimos crear una guía de consenso de dermatitis atópica válida para Latinoamérica y otras regiones tropicales, que tome en cuenta las características socioeconómicas, geográficas, culturales y de los sistemas de salud. La Sociedad Latinoamericana de Alergia, Asma e Inmunología (SLAAI) realizó una búsqueda sistemática de artículos relacionados con la fisiopatología, el diagnóstico y el tratamiento de la dermatitis atópica usando diversas fuentes electrónicas, como Google, Pubmed, EMBASE (Ovid) y Cochrane. También realizamos una búsqueda extensa de las publicaciones realizadas en Latinoamérica utilizando el buscador LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). Cada sección fue revisada por al menos dos miembros del comité y luego una versión final fue aprobada por todos los participantes, utilizando la metodología Delphi para la construcción de consensos. Finalmente, el documento final fue compartido para la evaluación externa por médicos, otros especialistas (alergólogos, dermatólogos, pediatras), pacientes e instituciones académicas, como universidades y sociedades científicas relacionadas con el tema. Todas las recomendaciones dadas por estos grupos se tomaron en cuenta y se incluyeron en la versión final del documento. Existen pocos estudios realizados en Latinoamérica acerca de dermatitis; sin embargo, fue posible crear una guía que considera las particularidades de la región tropical. Además, destacó el tratamiento integral porque se consideraron muchas de las recomendaciones ofrecidas por los diferentes participantes en el tratamiento de esta enfermedad (pacientes, familiares, médicos de atención primaria, especialistas). atópica, muchas de las recomendaciones no pueden ser válidas de manera universal debido a las particularidades de cada región. Por ello, nos propusimos crear una guía de consenso de dermatitis atópica válida para Latinoamérica y otras regiones tropicales, que tome en cuenta las características socioeconómicas, geográficas, culturales y de los sistemas de salud. La Sociedad Latinoamericana de Alergia, Asma e Inmunología (SLAAI) realizó una búsqueda sistemática de artículos relacionados con la fisiopatología, el diagnóstico y el tratamiento de la dermatitis atópica usando diversas fuentes electrónicas, como Google, Pubmed, EMBASE (Ovid) y Cochrane. También realizamos una búsqueda extensa de las publicaciones realizadas en Latinoamérica utilizando el buscador LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). Cada sección fue revisada por al menos dos miembros del comité y luego una versión final fue aprobada por todos los participantes, utilizando la metodología Delphi para la construcción de consensos. Finalmente, el documento final fue compartido para la evaluación externa por médicos, otros especialistas (alergólogos, dermatólogos, pediatras), pacientes e instituciones académicas, como universidades y sociedades científicas relacionadas con el tema. Todas las recomendaciones dadas por estos grupos se tomaron en cuenta y se incluyeron en la versión final del documento. Existen pocos estudios realizados en Latinoamérica acerca de dermatitis; sin embargo, fue posible crear una guía que considera las particularidades de la región tropical. Además, destacó el tratamiento integral porque se consideraron muchas de las recomendaciones ofrecidas por los diferentes participantes en el tratamiento de esta enfermedad (pacientes, familiares, médicos de atención primaria, especialistas).

Tyrosine phosphorylation of estradiol receptor by Src regulates its hormone-dependent nuclear export and cell cycle progression in breast cancer cells.

We report that in breast cancer cells, tyrosine phosphorylation of the estradiol receptor alpha (ERalpha) by Src regulates cytoplasmic localization of the receptor and DNA synthesis. Inhibition of Src or use of a peptide mimicking the ERalpha p-Tyr537 sequence abolishes ERalpha tyrosine phosphorylation and traps the receptor in nuclei of estradiol-treated MCF-7 cells. An ERalpha mutant carrying a mutation of Tyr537 to phenylalanine (ER537F) persistently localizes in nuclei of various cell types. In contrast with ERalpha wt, ER537F does not associate with Ran and its interaction with Crm1 is insensitive to estradiol. Thus, independently of estradiol, ER537F is retained in nuclei, where it entangles FKHR-driving cell cycle arrest. Chromatin immunoprecipitation analysis reveals that overexpression of ER537F in breast cancer cells enhances FKHR interaction with cyclin D1 promoter. This mutant also counteracts cell transformation by the activated forms of Src or PI3-K. In conclusion, in addition to regulating receptor localization, ERalpha phosphorylation by Src is required for hormone responsiveness of DNA synthesis in breast cancer cells.

LGI1 microdeletion in autosomal dominant lateral temporal epilepsy.

OBJECTIVES: To characterize clinically and genetically a family with autosomal dominant lateral temporal epilepsy (ADLTE) negative to LGI1 exon sequencing test. METHODS: All participants were personally interviewed and underwent neurologic examination. Most affected subjects underwent EEG and neuroradiologic examinations (CT/MRI). Available family members were genotyped with the HumanOmni1-Quad v1.0 single nucleotide polymorphism (SNP) array beadchip and copy number variations (CNVs) were analyzed in each subject. LGI1 gene dosage was performed by real-time quantitative PCR (qPCR). RESULTS: The family had 8 affected members (2 deceased) over 3 generations. All of them showed GTC seizures, with focal onset in 6 and unknown onset in 2. Four patients had focal seizures with auditory features. EEG showed only minor sharp abnormalities in 3 patients and MRI was unremarkable in all the patients examined. Three family members presented major depression and anxiety symptoms. Routine LGI1 exon sequencing revealed no point mutation. High-density SNP array CNV analysis identified a genomic microdeletion about 81 kb in size encompassing the first 4 exons of LGI1 in all available affected members and in 2 nonaffected carriers, which was confirmed by qPCR analysis. CONCLUSIONS: This is the first microdeletion affecting LGI1 identified in ADLTE. Families with ADLTE in which no point mutations are revealed by direct exon sequencing should be screened for possible genomic deletion mutations by CNV analysis or other appropriate methods. Overall, CNV analysis of multiplex families may be useful for identifying microdeletions in novel disease genes.

Multiple cerebral aneurysms associated with atrial myxoma. A case report.

Cardiac myxoma is a tumor of mesenchymal origin accounting for half of all primary cardiac neoplasms. Intracranial involvement by atrial myxoma is a rare cause of neurologic deficit. When the myxoma arises in the left atrium, systemic emboli from a cardiac myxoma can lead to infarction, cerebral hemorrhage and aneurysm formation. In the light of the potentially preventable nature of these lesions, the diagnosis of myxomatous aneurysms should be considered in any patient with neurologic symptoms and a history of cardiac myxoma. Because aneurysms are often stable over several years, conservative management with careful clinical and radiological follow-up with MRI and angiography seems sensible. We describe a case in which MR imaging and angiography were used to diagnose multiple cerebral aneurysms caused by left atrial myxoma.

First results on angular distributions of thermal dileptons in nuclear collisions.

The NA60 experiment at the CERN Super Proton Synchrotron has studied dimuon production in 158A GeV In-In collisions. The strong excess of pairs above the known sources found in the complete mass region 0.2

Unawareness of "illnesses": a case of right-sided hemiballism.

The Authors describe a non-demented patient who, after a left subthalamic haemorrhage causing hemiballism, was completely unaware of both neurological (i.e., dyskinesias) and non-neurological (i.e., cough) symptoms occurring after the stroke. In contrast, he was perfectly able to acknowledge pathological conditions affecting him before the brain damage. Neuropsychological assessment showed no cognitive defects, but revealed the presence of frontal behaviours (e.g., perseverations and utilization behaviours). This unusual clinical picture was ascribed to damage of frontal-subcortical circuits involved in conscious representation of current bodily states.