Prefrontal lesions impair the implicit and explicit learning of sequences on visuomotor tasks

OBJECTIVE: (1) To verify whether the prefrontal cortex (PFC) is specifically involved in visuomotor sequence learning as opposed to other forms of motor learning and (2) to establish the role of executive functions in visuomotor sequence learning. BACKGROUND: Visuomotor skill learning depends on the integrity of the premotor and parietal cortex; the prefrontal cortex, however, is essential when the learning of a sequence is required. METHODS: We studied 25 patients with PFC lesions and 86 controls matched for age and educational level. Participants performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task (perceptual learning) and a pattern tracking task (explicit motor sequence learning with learning indicated by the decrease in mean root square error across trial blocks), (2) a 12-item sequence version of a serial reaction time task (SRTT) with specific implicit motor sequence learning indicated by the rebound increase in response time when comparing the last sequence block with the next random block, and (3) a neuropsychological battery that assessed executive functions. RESULTS: PFC patients were impaired in sequence learning on the pattern tracking task of the PTT and on the SRTT as compared to controls, but performed normally on the PTT random tracking task. Learning on the PTT did not correlate with learning on the SRTT. PTT performance correlated with planning functions while SRTT performance correlated with working memory capacity. CONCLUSIONS: The PFC is specifically involved in explicit and implicit motor sequence learning. Different PFC regions may be selectively involved in such learning depending on the cognitive demands of the sequential task.     

Evaluation of four enrichment media for isolation of Campylobacter jejuni.

Diarrheal stool specimens were inoculated into the following media: alkaline peptone water (APW), Bruce-Zochowsky medium (BZ), Campylobacter enrichment broth (CEB), Campy-thio broth (CT), and Skirrow blood-agar (SK) plate. All media were incubated at 42 degrees C in microaerophilic conditions for 24 h. Afterwards, a new SK plate was inoculated from every liquid medium. Campylobacter jejuni was isolated from 43 of the 259 specimens when CT was used, from 45 when APW was used, from 46 when BZ was used, and from 46 when CEB was used; these totals include specimens that grew after enrichment only, on SK plates only, and both after enrichment and on SK plates. No significant differences were found between the isolates obtained with and without enrichment procedures.     

Racial and Workplace Disparities in Seroprevalence of SARS-CoV-2, Baton Rouge,Louisiana, USA

By using paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined point prevalence and seroprevalence in Louisiana, USA, during the second phase of reopening. Infections were highly variable by race and ethnicity, work environment, and ZIP code. Census-weighted seroprevalence was 3.6%, and point prevalence was 3.0%.     

Wakefulness-sleep modulation of EEG-EMG epileptiform activities: a quantitative study on a child with intractable epilepsia partialis continua

Continuous all night recordings of epileptiform EEG activities from right frontal scalp and thalamic Centromedian regions and EMG activities from left deltoid muscular region were performed on a child with intractable epilepsia partialis continua, with depth stimulating-recording electrodes used for neuroaugmentive seizure control. In addition, "normal" and "mature" sleep indicators in the same child were simultaneously recorded according to the International Procedures. During wakefulness (W), type B seizures consisted of isolated, high amplitude, negative-positive EEG sharp waves recorded from the right Centromedian region (RCM sharp) correlated with isolated bursts of high amplitude EMG potentials recorded from the left deltoid muscle (LEMG jerks). Type C seizures consisted of clusters of repetitive RCM sharp and LEMG jerks, where individual EEG-EMG activities showed poor correlations. Number and amplitude of type B RCM sharp and LEMG jerks significantly decreased when patient directly shifted from W to slow wave sleep I and II (SWSI and II). Number and amplitude of RCM sharp increased while those of LEMG jerks decreased directly from SWS I and II to slow wave sleep III (SWS III); all forms of EEG-EMG epileptiform type B activities significantly decreased directly or indirectly from W and SWS to paradoxical sleep (PS). Scalp EEG spikes from right frontal and central regions showed almost parallel changes to those of RCM sharp, except during SWS II, when amplitude increased in the former and decreased in the later. Occurrence of type C seizures only decreased during PS and duration decreased directly from SWS I to II and indirectly from SWS I to SWS II and PS; and from W to SWS II and III and PS.     

Breast cancer: contribution of molecular biology to the management of the disease

The possible applications of molecular biology to cancer research obviously surpass the confines of exclusively scientific knowledge, making available solid tools for the management of the disease. Breast cancer patients can be considered one of the populations that has most benefited from current research, both clinical and basic, probably as a consequence of the clinical epidemiological relevance of this malignancy. The applications of the knowledge contributed by molecular biology to the study of breast cancer can be grouped according to their mechanisms and the aspect of the disease for which they have been designed: as information complementary to pathologic diagnosis, as prognostic markers of the disease, as possible predictors of treatment response, as a rational basis for developing new treatment strategies, and as the molecular basis for establishing groups of hereditary cancers.     

Rapid Resolution of Nitrofurantoin-Induced Interstitial Lung Disease

We report the case of a 40-year-old woman diagnosed with interstitial lung disease due to long-term nitrofurantoin therapy. Despite severely distorted bronchiolar architecture and honeycombing confirmed by computed tomography of the thorax, transbronchial biopsy showed a pattern of acute/subacute interstitial pneumonitis and the symptoms and radiographic findings disappeared within 1 month after administration of prednisone. This case shows that nitrofurantoin-induced lung disease may run a benign course and respond favorably to corticosteroids, even when there is radiographic evidence of established lung fibrosis. Transbronchial biopsy might be useful for assessing the reversibility of pulmonary lesions associated with nitrofurantoin.     

Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF‐κB/Rel proteins via the p38 mitogen‐activated protein kinase pathway,and of the MEK‐1/ERK pathway

Objective

Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL). In patients with primary APS, expression of tissue factor (TF) on the surface of monocytes is increased, which may contribute to thrombosis in these patients. However, the intracellular mechanisms involved in aPL‐mediated up‐regulation of TF on monocytic cells are not understood. This study was undertaken to investigate the intracellular signals induced by aPL that mediate TF activation in monocytes from APS patients.

Methods

We analyzed, both in vivo and in vitro, aPL interactions with proteins that have signaling functions, including mitogen‐activated protein kinases (MAP kinases) and NF‐κB/Rel proteins.

Results

In vivo studies demonstrated significantly higher levels of both TF messenger RNA and TF protein in monocytes from APS patients compared with controls. At the molecular level, increased proteolysis of IκBα and activation of NF‐κB were observed. Constitutive activation of both p38 and ERK‐1 MAP kinases was also found. Treatment of normal monocytes with aPL activated ERK‐1 and p38 MAP kinases, as well as the IκB/NF‐κB pathway, in a dose‐dependent manner. NF‐κB activation and IκBα degradation induced by aPL were inhibited by the NF‐κB inhibitor SN50 and the p38 MAP kinase inhibitor SB203580, thus suggesting crosstalk between these pathways. However, the MEK‐1/ERK inhibitor PD98059 did not affect aPL‐induced NF‐κB binding activity. TF expression induced by aPL was significantly inhibited by combined treatment with the 3 inhibitors.

Conclusion

Our results suggest that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK‐1/ERK proteins, and the p38 MAP kinase–dependent nuclear translocation and activation of NF‐κB/Rel proteins.

     

Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures.

The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian-thalamic nucleus (ESCM) for control of generalized tonic-clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike-wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic-clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient's subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory.     

Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP.

Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway.     

Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2--deficient mice.

Angiogenesis and enhanced microvascular permeability are hallmarks of a large number of inflammatory diseases. Although up-regulation of proangiogenic factors such as vascular endothelial growth factor and interleukin-8 have been previously reported in inflamed tissue, the biologic role of endogenous inhibitors of angiogenesis in inflammation has remained unclear. To investigate the biologic role of the potent angiogenesis inhibitor thrombospondin-2 (TSP-2) in the control of cutaneous inflammation, delayed-type hypersensitivity reactions were elicited in the ear skin of wild-type and TSP-2-deficient mice by topical sensitization and challenge with oxazolone. Cutaneous TSP-2 expression was up-regulated in the inflamed skin of wild-type mice, predominantly in dermal fibroblasts and microvessels. Lack of TSP-2 resulted in a significantly enhanced inflammatory response with increased angiogenesis, edema formation, and inflammatory infiltration. Ear swelling and inflammation persisted for more than 2 weeks in TSP-2-deficient mice, as compared with 1 week in wild-type mice. Although baseline vascular permeability was unchanged, significantly enhanced microvascular leakage was found in the inflamed skin of TSP-2-deficient mice. Moreover, the fraction of rolling leukocytes was significantly increased in the untreated skin of TSP-2-deficient mice. These results reveal an important role of TSP-2 in limiting the extent and the duration of edema formation, angiogenesis, and inflammatory cell infiltration during acute and chronic inflammation.