Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice.

Binge alcohol consumption induces discrete social and arousal disturbances in human populations that promote increased drinking and accelerate the progression of Alcohol Use Disorder. Here, we show in a mouse model that binge alcohol consumption disrupts social recognition in females and potentiates sensorimotor arousal in males. These negative behavioral outcomes were associated with sex-specific adaptations in serotonergic signaling systems within the lateral habenula (LHb) and the bed nucleus of the stria terminalis (BNST), particularly those related to the receptor 5HT2c. While both BNST and LHb neurons expressing this receptor display potentiated activation following binge alcohol consumption, the primary causal mechanism underlying the effects of alcohol on social and arousal behaviors appears to be excessive activation of LHb5HT2c neurons. These findings may have valuable implications for the development of sex-specific treatments for mood and alcohol use disorders targeting the brain's serotonin system.

[Multiple extraneural metastasis of glioblastoma multiforme].

INTRODUCTION: Glioblastoma multiforme is the most frequent primary tumor in the brain. Despite improvements in its surgical, chemotherapy and radiotherapy treatment, prognosis remains poor. Extracranial metastases of glioblastoma are a rare complication in this disease. Its appearance has been described in lung, liver, bone or lymph nodes. CASE REPORT: We describe the case of a 20 year-old patient who complained of a subacute-onset headache. In the MRI an enhancing right temporal lesion was detected suggesting a high grade glioma as first diagnosis. Surgery was performed, obtaining a gross total resection of the lesion. Our patient underwent adjuvant radiotherapy and chemotherapy treatment, according to our hospital's protocol. Five months after initial surgery our patient complained of chest pain and a hacking cough. A thoracic-abdominal-pelvic CT scan was obtained, which showed bilateral lung infiltrates with pleural effusion, a pancreatic nodule and several vertebral lytic lesions. The lung lesions were biopsied. The pathologic diagnosis was metastatic glioblastoma multiforme. The patient died eight months after initial diagnosis. CONCLUSION: Extracranial metastases of glioblastoma remain a rare event although its incidence is increasing, probably due to the improvement in survival among these patients and better imaging techniques. The mechanisms for extracranial dissemination of glioblastoma are not entirely known, as several theories exist in this regard. Physicians must be aware of this complication and keep it in mind as a differential diagnosis to improve the quality of life of our patients.

Multiple extraneural metastasis of glioblastoma multiforme / Metástasis extraneurales múltiples de glioblastoma multiforme

Introduction: Glioblastoma multiforme is the most frequent primary tumor in the brain. Despite improvements in its surgical, chemotherapy and radiotherapy treatment, prognosis remains poor. Extracranial metastases of glioblastoma are a rare complication in this disease. Its appearance has been described in lung, liver, bone or lymph nodes. Case report: We describe the case of a 20 year-old patient who complained of a subacute-onset headache. In the MRI an enhancing right temporal lesion was detected suggesting a high grade glioma as first diagnosis. Surgery was performed, obtaining a gross total resection of the lesion. Our patient underwent adjuvant radiotherapy and chemotherapy treatment, according to our hospital’s protocol. Five months after initial surgery our patient complained of chest pain and a hacking cough. A thoracicabdominal-pelvic CT scan was obtained, which showed bilateral lung infiltrates with pleural effusion, a pancreatic nodule and several vertebral lytic lesions. The lung lesions were biopsied. The pathologic diagnosis was metastatic glioblastoma multiforme. The patient died eight months after initial diagnosis. Conclusion: Extracranial metastases of glioblastoma remain a rare event although its incidence is increasing, probably due to the improvement in survival among these patients and better imaging techniques. The mechanisms for extracranial dissemination of glioblastoma are not entirely known, as several theories exist in this regard. Physicians must be aware of this complication and keep it in mind as a differential diagnosis to improve the quality of life of our patients (AU)

Fundamento: Los glioblastomas multiformes son los tumores cerebrales primarios más frecuentes. A pesar de los avances en su tratamiento quirúrgico, quimioterápico y radioterápico su pronóstico sigue siendo pobre. Las metástasis extracraneales de glioblastoma multiforme suponen una rara complicación dentro del curso de la enfermedad y ha sido descrita su aparición en distintas localizaciones como pulmón, hígado, hueso o ganglios linfáticos. Caso clínico: Presentamos el caso de una paciente de 20 años que consultó por un cuadro de evolución subaguda. Se obtuvo una RMN cerebral que demostró la presencia de una lesión temporal derecha, que sugería un glioma de alto grado como primera posibilidad diagnóstica. Se intervino a la paciente, realizando una resección macroscópicamente completa de la lesión. Se administró tratamiento radioterápico y quimioterápico adyuvante, de acuerdo con el protocolo de nuestro centro. Cinco meses después de la cirugía la paciente consultó por dolor torácio y tos seca. Se realizó un TAC toraco-abdomino-pélvico, que mostró la presencia de infiltrados pulmonares bilaterales con derrame pleural asociado, un nódulo pancreático y varias lesiones vertebrales líticas. Las lesiones pulmonares fueron biopsiadas. El diagnóstico anatomopatológico fue de metástasis de glioblastoma multiforme. La paciente falleció ocho meses después del diagnóstico inicial. Conclusiones: Las metástasis extracraneales de glioblastoma multiforme son un suceso poco frecuente, aunque su incidencia está aumentando en posible relación con el aumento de la supervivencia de nuestros pacientes. La aparición de esta complicación se asocia a un estado terminal de la enfermedad. A pesar de su baja frecuencia se debe mantener un alto nivel de sospecha en su diagnóstico para poder mejorar la calidad de vida de estos pacientes (AU)

Scaling perceived saturation.

Two psychophysical experiments were conducted at North Carolina State University (NCSU) and Rochester Institute of Technology (RIT) to obtain replicated perceived saturation data from color normal observers on the order of one unit of saturation. The same 37 Munsell sample sheets, including up to four references that had similar perceived saturation but different hue, were used in both experiments. Different assessment methods included presenting either four references simultaneously or only one reference at a time to observers and obtaining judged saturation magnitudes for the given Munsell samples. Four saturation models comprising Sab*, Suv*, CIECAM02, as well as Richter/Lübbe, were tested. CIECAM02 gave the best prediction of saturation for data obtained at NCSU while Sab* outperformed other models for the RIT data. For the combined dataset, Sab*, the Richter/Lübbe, and CIECAM02-based saturation models exhibited comparable performances. The Standardized Residual Sum of Squares index was used to measure the inter- and intra-observer variability and goodness of fit. Inter- and intra-observer variability of assessments was smaller than or comparable to those reported for the typical color difference evaluation experiments.

[Remote cerebellar haemorrhage after lumbar arthrodesis: case report and literature review]. / Hematoma cerebeloso como complicación de artrodesis lumbar. A propósito de uncaso y revisión de la literatura.

Remote cerebellar haemorrhage (RCH) is a rare complication of spinal surgery, less frequent than the RCH observed after an intracranial surgery. The patients principally complained of headache or were presented with deterioration in mental status. We report a case of RCH in a 55 years old woman that underwent lumbar arthrodesis with occult dural defect. We review the literature, analysing its causes and therapeutic implications.

Hematoma cerebeloso como complicación de artrodesis lumbar. A propósito de un caso y revisión de la literatura / Remote cerebellar haemorrhage after lumbar arthrodesis: Case report and literature review

El hematoma cerebeloso (HCD) como complicación en cirugía de raquis, es menos frecuente que el hematoma a distancia secundario a la cirugía intracraneal. Se manifiesta principalmente con cefalea o deterioro del nivel de consciencia y se ha asociado a la pérdida de LCR intra o postoperatoria. Presentamos un caso de HCD en una paciente de 55 años tras cirugía instrumentada de columna lumbar con fístula de LCR oculta, además de una revisión de la literatura con análisis de sus posibles causas, así como las implicaciones terapéuticas (AU)

Remote cerebellar haemorrhage (RCH) is a rare complication of spinal surgery, less frequent than the RCH observed after an intracranial surgery. The patients principally complained of headache or were presented with deterioration in mental status. We report a case of RCH in a 55 years old woman that underwent lumbar arthrodesis with occult dural defect. We review the literature, analysing its causes and therapeutic implications (AU)

A survey of oysters (Crassostrea gigas) in New Zealand for Vibrio parahaemolyticus and Vibrio vulnificus.

A microbiological survey was conducted to determine the levels of total and pathogenic Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) in Pacific oysters (Crassostrea gigas) collected from commercial growing areas in the North Island, New Zealand. The survey was intended to be geographically representative of commercial growing areas of Pacific oysters in New Zealand, while selecting the time frame most likely to coincide with the increased abundance of pathogenic vibrio species. Vp was detected in 94.8% of oyster samples examined (n=58) with a geometric mean concentration of 99.3 MPN/g, while Vv was detected in 17.2% of oyster samples examined with a geometric mean concentration of 7.4 MPN/g. The frequency of Vp positive samples was 1.7 fold greater than reported in a study conducted three decades ago in New Zealand. Potentially virulent (tdh positive) Vp was detected in two samples (3.4%, n=58) while no trh (another virulence marker) positive samples were detected. 16S rRNA genotype could be assigned only to 58.8% of Vv isolates (8:1:1 A:B:AB ratio, n=10). There was a good agreement [98.2% of Vp (n=280) and 94.4% of Vv (n=18) isolates] between molecular tests and cultivation based techniques used to identify Vibrio isolates and there was a significant (R(2)=0.95, P<0.001, n=18) linear relationship between the MPN estimates by real-time PCR and cultivation. There was no significant correlation between any of the environmental parameters tested and Vp or Vv concentrations.

Malignant transformation of high-grade anal intraepithelial neoplasia.

BACKGROUND: The natural history of anal intraepithelial neoplasia (AIN) is uncertain. This makes management problematic as treatment options to eradicate the condition carry morbidity. The authors report their 10-year experience with conservative management of this condition, highlighting the lessons learnt. METHODS: All patients were diagnosed with high-grade AIN (AIN III) between 1994 and 2003. Diagnosis was by full-thickness biopsy and histopathological examination. Excision of localized lesions was undertaken, and all patients underwent follow-up every 6 months. Prospective data were collected regarding recurrence, postoperative complications and progression to invasive carcinoma. RESULTS: Thirty-five patients were followed for a median of 63 (range 14-120) months. Excision of localized high-grade AIN was carried out in 28 patients with minimal morbidity. Six patients were systemically immunosuppressed at diagnosis, all of whom had multifocal perianal lesions. Three immunosuppressed patients developed invasive anal squamous carcinoma during follow-up. By contrast, no invasive carcinomas were identified among immunocompetent patients with either localized or multifocal perianal disease. CONCLUSION: AIN III appears to have a relatively low potential for malignant transformation in the immunocompetent patient. However, immunosuppressed patients are more likely to have extensive AIN III and a greater risk of malignant change.

Autonomic brainstem nuclei are linked to the hippocampus.

Vagal nerve stimulation has been reported to enhance memory in both rats and humans, and to be an effective treatment for epilepsy in some patients, but the underlying neuroanatomical substrate(s) responsible for these effects remains unknown. Since there is no direct anatomical projection from the nucleus tractus solitarius, the main vagal relay site of the brain, to the hippocampus, we tested whether a multisynaptic pathway exists. Pseudorabies virus, a pig herpesvirus that can be used as a retrograde transneuronal tracer, was injected into the ventral CA1 hippocampus of rats, and after 4 days, pseudorabies virus infected neurons were identified in the general visceral portion of the nucleus tractus solitarius, with the majority being localized in the A2 noradrenergic cell group. Other autonomic brainstem nuclei, including the parabrachial nucleus, locus coeruleus, A1 and A5 noradrenergic cell groups, and C1 adrenergic cell group, were labeled. In order to identify some of the potential relay sites of the nucleus tractus solitarius-->hippocampal pathway, immunotoxin lesions of the ventral CA1 region were made that selectively destroyed either the noradrenergic or cholinergic fibers. After 2 weeks' recovery, pseudorabies virus was injected in this same CA1 area, and 4 days later, the transneuronal labeling in the nucleus tractus solitarius was reduced by approximately 65%. These findings suggest that the noradrenergic neurons of the locus coeruleus and cholinergic neurons of the medial septum/diagonal band are likely to be relay sites for this pathway. Other potential linkages are discussed. In summary, this is the first anatomical report to show that the general visceral region of nucleus tractus solitarius is linked via multisynaptic relays to the hippocampus.

Review article: The rationale for antidepressant therapy in functional gastrointestinal disorders.

The rationale for antidepressants in the treatment of functional gastrointestinal disorders (FGDs) has been the subject of much interest. However, because of our incomplete understanding of FGDs, this rationale remains unclear. A key point is whether the high degree of psychiatric co-morbidity associated with FGDs (40-90%) represents a shared pathophysiology or the ascertainment bias of tertiary referral patients. Our aims were four-fold: (i) to review the current rationale for antidepressant therapy in FGDs; (ii) to review the studies comparing the characteristics of FGDs with both organic gastrointestinal disease and psychiatric disorders; (iii) to propose a model of FGDs which explains the high psychiatric co-morbidity; (iv) to compare the treatment regimes and effectiveness of antidepressants in FGDs and psychiatric illnesses. The review highlights two important observations. Firstly, the characteristics of FGDs are similar to those of affective disorders and dissimilar to those of organic disease. Secondly, although antidepressants benefit FGD sufferers, their benefits in psychiatric illnesses are greater. We conclude that, in view of the degree of similarity between FGDs and affective disorders, FGDs could be considered as affective disorders in their own right and, if the prescription of antidepressants conformed to their use in affective disorders, FGD morbidity would be reduced.

Expression of cellular prion protein (PrPc) in the rat central nervous system / Expresión de la proteína priónica celular (PrPc) en el sistema nervioso central de la rata

The localization of cellular prion protein in the central nervous system of adult rats is an important step not only for understanding its biology, but also to gain a better understanding of the propagation of pathogenic prion protein within the central nervous system in spongiform encephalopathies. Here, the expression of cellular prion protein is studied by immunocytochemistry and Western blotting techniques. The presence of the protein varied in the rostrocaudal direction: it was less abundant in the brainstem than in prosencephalon. PrPc-positive cells were especially abundant in the cerebral cortex. The immunoreaction was present in areas projecting to the intermediate band of the mediodorsal thalamic nucleus and the anteroventral nucleus of the thalamus. Some immunopositive neurons, glial cells, and fibres were located around vessels in areas where nitrergic activity is well documented. Our findings lead us again to propose a retrograde propagation of altered prion proteins in human spongiform encephalopathies such as fatal familial insomnia, followed by an alteration of the nitrergic systems. Moreover, destruction of the mediodorsal thalamic nucleus in fatal familial insomnia may unleash an alteration of prion and nitrergic physiology (AU)

El estudio de la localización de la proteína priónica celular en el sistema nervioso central de la rata es un importante paso no sólo para la mejor comprensión de la biología de PrPc, sino para aportar más información sobre la propagación de la proteína priónica patógena dentro del sistema nervioso central en las encefalotías espongiformes transmisibles. En el presente trabajo se estudia la expresión de la proteína priónica celular mediante técnicas inmunocitoquímicas y western blot. La presencia de la proteína varía en dirección rostrocaudal, siendo menos abundante en el tronco de encéfalo que en el prosencéfalo. Especialmente abundantes fueron las células positivas para PrPc en la corteza cerebral. El marcaje apareció en áreas que proyectan a la banda intermedia del núcleo dorsomedial del tálamo y núcleo anteroventral del tálamo. Algunas neuronas, células de la glía y fibras inmunopositivas se localizaban alrededor de vasos en áreas donde la actividad nitrérgica es bien conocida. Nuestros hallazgos nos llevan a proponer una propagación retrógrada de la proteína priónica alterada en las encefalopatías espongiformes que afectan a humanos, como por ejemplo en el caso del insomnio familiar fatal, seguida de una alteración de los sistemas nitrérgicos encefálicos. Además, por trabajos previos, sospechamos que la destrucción del núcleo dorsomedial del tálamo supone una alteración en la fisiología priónica y nitrérgica, lo cual podría ser aplicable a la comprensión de la fisiopatología del insomnio familiar fatal (AU)

A comparison of patients with chronic fatigue syndrome attending separate fatigue clinics based in immunology and psychiatry.

Hospital clinics for patients with chronic unexplained fatigue are held in departments of various disciplines. This causes difficulties for referrers in choosing the appropriate clinic and for researchers in generalizing findings from one type of clinic to others. We randomly selected 37 outpatients attending an immunology fatigue clinic and 36 outpatients attending a psychiatry fatigue clinic, all of whom had chronic fatigue syndrome. We compared demographic factors, symptoms, disability, quality of life, psychological distress and illness attributions. The patients from the two clinics were closely similar in their specific symptoms, disability, quality of life, psychological distress and previous attendance to mental health professionals. Psychological distress was high and equal in the two samples. The proportion of men was greater among patients attending the immunology clinic. In a post-hoc analysis, 64% of immunology attenders attributed their fatigue to physical factors, compared with 31% of psychiatry clinic attenders (chi(2)=6.35, 1 d.f., P=0.01). These findings suggest that research data from one type of chronic fatigue clinic can be generalized to others. Clinically similar patients are referred to different clinics, and the choice of clinic may be influenced by the patients' illness beliefs. The high levels of emotional distress suggest that psychosocial management is as important as physical management in hospital outpatients with chronic fatigue syndrome, irrespective of its aetiology.

A sequential protocol combining dual neuroanatomical tract-tracing with the visualization of local circuit neurons within the striatum.

We describe here an experimental approach designed to aid in the identification of complex brain circuits within the rat corpus striatum. Our aim was to characterize in a single section (i) striatal thalamic afferents, (ii) striatopallidal projection neurons and (iii) striatal local circuit interneurons. To this end, we have combined anterograde tracing using biotinylated dextran amine and retrograde neuroanatomical tracing with Fluoro-Gold. This dual tracing protocol was further implemented with the visualization of different subpopulations of striatal interneurons. The subsequent use of three different peroxidase substrates enabled us to unequivocally detect structures that were labeled within a three-color paradigm.

Cardiac involvement in patients with acute neurologic disease: confirmation with cardiac troponin I.

BACKGROUND: Patients with acute neurologic illness often manifest findings suggestive of cardiac injury. Their proper interpretation is unclear. Accordingly, we conducted a blinded evaluation to assess the incidence of cardiac injury determined by elevations of cardiac troponin I (cTnI) in patients presenting within 24 hours of a neurologic event and to determine their short- and long-term prognostic effect. METHODS: Blood samples for measurement of cTnI levels were obtained on hospital admission and daily for 3 days and were run by immunoassay. Extensive clinical evaluations including electrocardiograms and echocardiograms were obtained from all patients; daily follow-up evaluations were performed. The clinical electrocardiographic, echocardiographic, and biochemical data were analyzed independently by blinded observers. RESULTS: Peak levels of cTnI were elevated (> or =0.4 microg/L) in 17 patients (19%) (mean + SD, 2.5 + 2.7 microg/L). All patients with elevated cTnI levels had clinical, electrocardiographic, or echocardiographic evidence of cardiac injury except those (n = 5) with minor elevations. One-year mortality was 29% (23/80). Early death (< or =30 days) accounted for 44% of total mortality (n = 10) and was significantly higher in patients with elevated cTnI levels (Wilcoxon P =.01; odds ratio, 6. 4). This difference was less marked by 1 year (Wilcoxon P =.07). CONCLUSIONS: There is a substantial prevalence of myocardial injury in patients with acute neurologic illness. Cardiac injury in this population, as in others, seems to adversely affect prognosis.

An ikaros-containing chromatin-remodeling complex in adult-type erythroid cells.

We have previously described a SWI/SNF-related protein complex (PYR complex) that is restricted to definitive (adult-type) hematopoietic cells and that specifically binds DNA sequences containing long stretches of pyrimidines. Deletion of an intergenic DNA-binding site for this complex from a human beta-globin locus construct results in delayed human gamma- to beta-globin switching in transgenic mice, suggesting that the PYR complex acts to facilitate the switch. We now show that PYR complex DNA-binding activity also copurifies with subunits of a second type of chromatin-remodeling complex, nucleosome-remodeling deacetylase (NuRD), that has been shown to have both nucleosome-remodeling and histone deacetylase activities. Gel supershift assays using antibodies to the ATPase-helicase subunit of the NuRD complex, Mi-2 (CHD4), confirm that Mi-2 is a component of the PYR complex. In addition, we show that the hematopoietic cell-restricted zinc finger protein Ikaros copurifies with PYR complex DNA-binding activity and that antibodies to Ikaros also supershift the complex. We also show that NuRD and SWI/SNF components coimmunopurify with each other as well as with Ikaros. Competition gel shift experiments using partially purified PYR complex and recombinant Ikaros protein indicate that Ikaros functions as a DNA-binding subunit of the PYR complex. Our results suggest that Ikaros targets two types of chromatin-remodeling factors-activators (SWI/SNF) and repressors (NuRD)-in a single complex (PYR complex) to the beta-globin locus in adult erythroid cells. At the time of the switch from fetal to adult globin production, the PYR complex is assembled and may function to repress gamma-globin gene expression and facilitate gamma- to beta-globin switching.

Lethal effects of apidaecin on Escherichia coli involve sequential molecular interactions with diverse targets.

Apidaecins, short proline-arginine-rich peptides from insects, are highly bactericidal through a mechanism that includes stereoselective elements but is completely devoid of any pore-forming activity. The spectrum of antibacterial activity, always limited to Gram-negatives, is further dependent on a small number of variable residues and can be manipulated. We show here that mutations in the evolutionary conserved regions result in a more general loss of function, and we have used such analogs to probe molecular interactions in Escherichia coli. First, an assay was developed to measure selectively chiral association with cellular targets. By using this method, we find that apidaecin uptake is energy-driven and irreversible and yet can be partially competed by proline in a stereospecific fashion, results upholding a model of a permease/transporter-mediated mechanism. This putative transporter is not the end point of apidaecin action, for failure of certain peptide analogs to kill cells after entering indicates the existence of another downstream target. Tetracycline-induced loss of bactericidal activity and dose-dependent in vivo inhibition of translation by apidaecin point at components of the protein synthesis machinery as likely candidates. These findings provide new insights into the antibacterial mechanism of a unique group of peptides and perhaps, by extension, for distant mammalian relatives such as PR-39.

The impact of patient experience on practice: the acceptability of emergency contraceptive pills in inner-city clinics.

OBJECTIVES: This article reports on a study of 119 women who sought and used emergency contraceptive pills (ECPs) at Planned Parenthood of New York City (PPNYC) clinics between June 1996 and May 1997. It focuses on their satisfaction with the method, their attitudes toward ECPs, their reactions to the service, and the impact their perceptions had on changing the provision of care. METHOD: The PPNYC clinical protocol employed the Yuzpe method and fairly conservative procedures, including restrictive screening, a pelvic examination for all new patients, and limited appointment slots. A two-part survey captured information on patient experience with ECPs. RESULTS: The largest group of respondents (40%) found out about ECPs from friends. Almost 90% of the women were using contraception before their visit to the clinic. Sixty-eight percent reported that they sought ECPs because the condom failed. In the follow-up, a majority (57%) reported that they intended to change or had changed their method of contraception--more than three-quarters to a hormonal contraceptive. While generally satisfied with the service, many respondents were cautious of more extensive distribution of ECPs. CONCLUSION: The survey results had a profound impact on services: PPNYC revised the ECP protocol, developed a staff training package, expanded its service, and planned a multidimensional public media campaign. Further research, including a closer examination of participants' cautious attitude toward unrestricted distribution of ECPs, will be needed as PPNYC expands access to ECP.