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Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗

Video-assisted thoracic surgery (VATS) for children with pulmonary metastases from osteosarcoma.

BACKGROUND: Video-assisted thoracic surgery (VATS) may complement open thoracotomy in children with osteosarcoma requiring pulmonary metastasectomy. METHODS: The records of children with metastatic pulmonary osteosarcoma considered for initial VATS intervention (n = 9) were reviewed. RESULTS: Two children did not have VATS exploration: one child with multiple bilateral nodules and another child with a deep parenchymal nodule. VATS provided diagnostic biopsy material in all cases when used (n = 7). Two children had benign inflammatory lesions; four children had VATS-directed wedge resections of solitary malignant lesions; and one child had VATS biopsy of diffuse parenchymal and pleural pulmonary disease not amenable to resection. The mean operative time and hospital length of stay were 1.78 +/- 0.54 h and 3.5 +/- 1.8 days, respectively. There were two complications of VATS: bleeding in a child, requiring a transfusion, and a latent pneumothorax in a patient after removal of the chest tube. CONCLUSION: VATS is safe, serves as an excellent diagnostic modality, complements the open thoracotomy, and may enable the surgeon to avoid more extensive procedures in selected cases.

Adolescent↗

Chronic diffuse interstitial fibrosis of the lung in uranium miners.

Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure.

Adult↗

Pyothorax-associated lymphoma: a lymphoma developing in chronic inflammation.

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin lymphoma of exclusively B-cell phenotype developing in the pleural cavity of patients after more than 20-year history of pyothorax resulting from an artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. The most common symptoms on admission are chest pain and fever. Serum neuron-specific enolase level suggesting a diagnosis of small cell lung cancer is occasionally elevated. Histologically PAL usually shows a diffuse proliferation of large cells of B-cell type (diffuse large B-cell lymphoma [DLBL]). In PAL cells, representative B-cell markers other than CD20 are frequently negative with aberrant expression of T-cell markers such as CD2. A gene expression profile of PAL is distinct from nodal DLBL in its higher expression level of interferon-inducible genes. PAL is strongly associated with Epstein-Barr virus (EBV) infection with expression of EBV latent genes such as EBNA-2, LMP-1, together with EBNA-1. Taken together, PAL is a distinct entity both in its clinicopathologic presentation as well as its gene expression profile. Use of an artificial pneumothorax, EBV infection, and cytokines and reactive oxygen species produced in longstanding pyothorax might be important factors for PAL development.

Aged↗

Effect of centrifugation on separation by aqueous two-phase partition of an early and late endosome model using inside-out plasma membrane vesicles from plants.

Inside-out vesicles of plasma membranes prepared from a plant source were used as models to investigate effects of centrifugal forces on separations of early and late endosome populations by aqueous two-phase partition. Endosome subpopulations were resolved readily by preparative free-flow electrophoresis where acidification of the interiors of late endosomes occurred upon addition of ATP to activate a proton translocating ATPase. The resultant increased diffusion potential provided for a surface difference between late and early endosomes to permit electrophoretic separation. With the plant membranes, unincubated inside-out plasma membrane vesicles modeled early endosomes, whereas inside-out vesicles incubated with 1 mM ATP modeled late endosomes. A latent, 2,4-dichlorophenoxyacetic acid (2,4-D)-(auxin)-stimulated NADH:protein disulfide reductase measured spectrophotometrically was used as an enzymatic marker for both populations of inside-out vesicles. Phase partition behavior of each population was quantitated using total protein as the parameter.

Adenosine Triphosphate↗

Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen.

A case of so-called inflammatory pseudotumor (IPT), occurring in the spleen of a 77-year-old woman, is reported. The spleen contained a well-circumscribed mass with central hemorrhage and necrosis. Histologically, spindle cells were dispersed in a background of abundant inflammatory cells, predominantly lymphocytes and plasma cells. The cells possessed enlarged, sometimes twisted or irregularly folded, nuclei that contained vesicular chromatin, and small but distinct, centrally located nucleoli. Immunohistochemically, the spindle cells were diffusely positive for vimentin, and focally positive for follicular dendritic cell (FDC) markers (Ber-MAC-DRC for CD35 and CNA.42). The Epstein-Barr virus (EBV) was exclusively detected in the spindle cells by in situ hybridization analysis. The cells also expressed the latent membrane protein-1 (LMP-1) of EBV, and polymerase chain reaction (PCR) analysis revealed that the LMP-1 gene had a 30-bp deletion and three point mutations, although their significance remains controversial. Inflammatory pseudotumor is a descriptive term that encompasses several different entities, and recent investigations have revealed the existence of neoplastic entities among IPT. One of the neoplastic IPT, recently designated 'IPT-like FDC tumor', is characterized by proliferation of EBV-positive FDC and commonly occurs in the liver and spleen. Because such tumors are capable of recurrence and metastasis, it is important to consider the possibility of an IPT-like FDC tumor when making a diagnosis of a hepatic/splenic IPT-like lesion.

Aged↗

Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside.

Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear. Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant. The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.

Adult↗

Physical and functional interaction of the Epstein-Barr virus BZLF1 transactivator with the retinoic acid receptors RAR alpha and RXR alpha.

Epstein-Barr virus (EBV) reactivation, indicated by induction of EBV early antigens from latently infected lymphoid cell lines by phorbol esters, is inhibited by retinoic acid (RA). Viral reactivation, which is triggered by the immediate-early BZLF-1 (Z) viral gene product, is repressed by retinoic acid receptors (RARs) RAR alpha and RXR alpha. These proteins negatively regulate Z-mediated transactivation of the promoter for an EBV early gene product, early antigen-diffuse (EaD). Here we confirm a direct physical interaction between the AP1-like protein Z and RXR alpha and map the domains of interaction in the Z protein and RXR alpha. The domain required for homodimerization of Z is separate from that required for its interaction with RXR alpha. Z also has the effect of repressing activation of an RAR-responsive cellular promoter (BRE). Point mutants in the dimerization domain of Z unable to interact with RXR alpha do not repress RXR alpha-mediated transactivation of BRE, the promoter for RAR beta, which suggests that interaction between the two proteins is required for this repressor effect. The domain of RXR alpha required for interaction with Z has been mapped, and is again separate from that required for homodimerization. These results indicate that a 'cross-coupling' or direct interaction between Z and RAR alpha and RXR alpha can modulate the reactivation of latent EBV infection and suggest that, reciprocally, the viral protein Z may influence cellular regulatory pathways.

Amino Acid Sequence↗

Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.

Antigens, CD↗

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus.

OBJECTIVES: Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. STUDY DESIGN: A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. RESULTS: Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. CONCLUSIONS: These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Adolescent↗

Latent carcinoma of the thyroid in Austria: a systematic autopsy study.

Data concerning the incidence of latent thyroid carcinoma (LTC) in populations with endemic goiter are scarce. Despite the introduction of iodine goiter prophylaxis in the early sixties, iodine supply is still insufficient in Austria and goiter remains endemic. This is the first detailed study dealing with epidemiological features of LTC at autopsy in Austria. A total of 118 thyroid glands were included in the study. The glands were serially sectioned at 2- to 3-mm intervals, embedded in paraffin and histologically examined for the presence of LTC. In addition, the incidence and severity of lymphocytic thyroiditis (LT) were evaluated. Ten thyroids were found to contain LTC (8.6%). All were of the papillary type. The mean tumor dimension was 4.9 mm +/- 3.2, the smallest lesion measuring 1 mm. Only the largest tumor slightly exceeded the extent of a microcarcinoma and measured 10.5 mm. Multifocal disease was present in three cases (30%). The prevalence of latent papillary thyroid carcinoma (LPTC) was 6.6% (n = 4) in females and 10.5% (n = 6) in males. The mean age of the subjects with LPTC was 67.7 +/- 14.4 yr, range 37 to 77 yr. Goitrous thyroids were seen in 33 cases (28%): One gland was diffusely enlarged and 32 (27.1%) enlarged glands were nodular goiters. The overall prevalence of LT was 30.5% (n = 36) and the only type of thyroiditis observed was focal lymphocytic thyroiditis (FLT). There was no correlation between the presence of LPTC and goiter, the presence of FLT and the subjects' age and sex. The incidence of LPTC in Austria is similar to that in nongoitrous regions. The adult population at large seems to be uniformly exposed to factors involved in the initiation and early growth of papillary thyroid carcinoma (PTC). This suggests that the levels of iodine intake only play a minor role in the early phase of the carcinogenesis of PTC, but may be of some importance in the progression of LPTC to clinically evident PTC.

Adolescent↗

A case of lupus nephritis showing rectal erosion with cytomegalovirus infection.

A case of lupus nephritis showing rectal erosion with cytomegalovirus infection is described. The patient revealed nephrotic syndrome. She complained of skin ulcer with livedo reticularis on the right breast, purpura with thrombocytopenia, hepatic dysfunction, and bloody stool. Renal biopsy demonstrated diffuse proliferative lupus nephritis with prominent wire loops. Intestinal fiberscopy showed rectal erosion which was a cause of bloody stool, and rectal biopsy revealed cytomegalic inclusions characteristic of cytomegalovirus infection. Immunosuppression due to combined therapy with prednisolone and mizoribine could have led to reactivation of latent cytomegalovirus infection, resulting in the rectal erosion with bloody stool.

Adult↗

[Total thyroidectomy to prevent recurrence of benign thyroid goiter].

Surgical approach of benign nodules and goiters in euthyroid patients is not yet well definite concerning the latent of the resection: has it to be large (for avoiding recurrence) of thrifty (in the aim of decreasing the necessity of postoperative thyroid replacement therapy)? We reviewed the results of 338 surgical thyroidectomies in patients followed at least 7 years. 87.36% of them had diffuse pathological abnormalities. Recurrence level was 1.68% in this group, occurring in an average delay of 10 years after the first thyroidectomy. Another study group concerned 47 patients operated for a recurrence in an average of 13.9 years after the first thyroidectomy (mean age at the first thyroidectomy: 35 years). Post operative sequellae after one thyroidectomy or after a second for recurrence seemed not statistically different. Recurrence rate is not important, but it is probably underevaluated by the frequent absence of long-term follow-up. Total thyroidectomy avoids it, and its sequellae are comparable with those observed after reoperation for recurrence. The surgical choice is between the acceptation of a possible recurrence and the necessity of an indefinite thyroid replacement therapy.

Adolescent↗

Large B-cell lymphoma with Hodgkin's features.

AIMS: To describe the features of a series of nine cases of diffuse large B-cell lymphoma (DLBCL) showing morphological and immunophenotypic features that are intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9) presented as mediastinal tumours affecting young males, while the other three cases arose in extramediastinal locations. Histopathologically, tumours showed diffuse large cell areas in a polymorphous background, with pleomorphic cytology and the common presence of Hodgkin's and Reed-Sternberg cells. Immunophenotypically, tumours shared features of DLBCL and classical HL, with expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20, CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found in 2/9 cases. The majority of tumours had immunohistochemical features consistent with activation of the NF-(kappa)B pathway, including nuclear location of the c-REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6) rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.

Adult↗

[Differential diagnosis of delayed encephalopathy induced by anthelmintic imidazoles].

Anthelmintic imidazoles induced delayed encephalopathy (AIIDE) is frequently encountered and has usually been misdiagnosed as sporadic encephalitis of unknown cause (SEU). This study was carried out to facilitate differentiation of the two diseases. The records of 202 cases of AIIDE were reviewed and the clinical features analyzed. As a results, 7 diagnostic criteria for AIIDE were proposed as follows: (1) history of exposure to anthelmintic before the onset; (2) presence of a latent period of of 2 to 5 weeks; (3) onset of the disease acute or subacute; (4) presence of neuropsychiatric symptoms and signs resulted from multifocal cerebral damage; (5) Fulfillment of two of the following conditions; (a) subinflammatory change in CSF with elevation of IgG; (b) diffuse slow waves in EEG during early stage; (c) characteristics of acute demyelinating encephalopathy in brain biopsy; (6) good therapeutic effect of adrenal corticosteroids; (7) exclusion of other neuropsychiatric disorders in a fallow-up period of one year. AIIDE is a new disease entity and its diagnosis is mainly based on the clinical features. EEG, CT or MRI are important diagnostic measures, but history of exposure to anthelmintic is the most important criterion. Multifocal hemorrhagic leukoencephalopathy is its main pathologic feature.

Adult↗

Hodgkin's lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate.

We describe the occurrence of malignant lymphoma as a possible complication of immunosuppression associated with low dose methotrexate (MTX) therapy for juvenile rheumatoid arthritis (JRA). A 6-year-old girl with systemic onset JRA who had received low dose MTX therapy for 16 months developed diffuse peripheral lymphadenopathy and enlargement of the lymph nodes in the mediastinum, hilum of the lungs, and liver. Lymph node histology disclosed mixed cellularity Hodgkin's lymphoma; the neoplastic cells were positive for CD30 and CD15, but negative for Epstein-Barr virus RNA or EBV latent membrane protein. After chemotherapy, the girl had complete remission of her disease lasting for 18 months; however, the disease relapsed and autologous peripheral stem cell transplantation was performed. Although the occurrence of lymphoma may be associated with autoimmune diseases, our observations suggest that in pediatric patients, the increasing use of low dose MTX therapy for JRA may be an additional factor for the development of lymphoproliferative disease.

Arthritis, Juvenile↗

Toxoplasmosis in immunosuppression and AIDS.

Reactivation of chronic, latent infection of Toxoplasma gondii has been observed previously in transplant patients and malignancies treated with immunosuppressive drugs. Recently it has emerged as the most common recognized central nervous system infection in acquired immunodeficiency syndrome (AIDS) patients, seen in 6-20% of all AIDS cases. It produces diffuse encephalopathy or space-occupying and necrotic lesions. Contrary to classical toxoplasmosis, the serological diagnosis is unreliable and the therapeutical response in most cases is poor.

Acquired Immunodeficiency Syndrome↗

[Familial hypobetalipoproteinaemia and diabetes mellitus (author's transl)].

In a 60-year-old patient with manifest diabetes mellitus and in his 63-year-old brother with latent diabetes mellitus hypobeta-lipoproteinaemia was diagnosed. Cholesterol values were around 1,8 mmol/1 in whole serum samples. The LDL-cholesterol fraction was 1,04 mmol/1. The beta-lipoprotein band in the lipoprotein electrophoresis was markedly reduced. Apolipoprotein B measured by radial immuno-diffusion was about 30% of the normal for age. The components of LDL were normal. Values of hepatic triglyceride lipase and lipoprotein lipase in heparinised plasma were within the normal range. The simultaneous occurrence of hypobetalipoproteinaemia and diabetes mellitus is described here for the first time.

Adult↗