Oxygen saturation or respiratory rate to improve risk stratification in hemodynamically stable patients with acute pulmonary embolism.

Essentials In acute pulmonary embolism (PE), risk stratification is essential to drive clinical management. Improving the 2014-ESC risk stratification strategy is crucial in hemodynamically stable patients. Oxygen saturation and respiratory rate improve risk stratification in hemodynamically stable PE. Simple and routine tests improve risk stratification of hemodynamically stable PE. SUMMARY: Background In patients with acute pulmonary embolism (PE), risk stratification for short-term death is recommended to drive clinical management. A risk stratification strategy combining the simplified Pulmonary Embolism Severity Index (PESI), echocardiography and troponin was proposed by the European Society of Cardiology (ESC) in 2014. The identification of hemodynamically stable patients at increased risk of death by this strategy needs improvement. Objective To assess whether further stratification by serial cut-off values of oxygen saturation or respiratory rate improves the accuracy of the ESC risk stratification strategy in hemodynamically stable PE patients. Methods Prospective cohorts of hemodynamically stable patients with PE were merged in a collaborative database. The accuracy of risk stratification for 30-day mortality by the original and a modified 2014 ESC strategy was assessed. Results Overall, 255 patients (27%) were categorized as low, 510 (54%) as intermediate-low and 181 (19%) as intermediate-high risk according to the original 2014 ESC strategy. Thirty-day mortality was 1.2% in low, 10% in intermediate-low and 11% in intermediate-high-risk patients. By adding oxygen saturation in air of < 88%, the discriminatory power of the 2014 ESC model improved for 30-day mortality (c-statistics, 0.71; 95% confidence interval [CI], 0.65-0.77 vs. 0.63, 95% CI, 0.56-0.69) and for PE-related death (c-statistics, 0.75; 95% CI, 0.69-0.81 vs. 0.63, 95% CI 0.56-0.69). Conclusions Simple and routine tests, such as oxygen saturation or respiratory rate, could be added to the 2014 ESC strategy for risk stratification to identify hemodynamically stable PE patients at increased risk of death who are potentially candidates for more aggressive treatment.

Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.

BACKGROUND AND AIM: To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). METHODS AND RESULTS: Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). CONCLUSION: Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Endobronchial primary large B-cell Non-Hodgkin lymphoma in HIV-infected patient in the Highly Active Antiretroviral Therapy era: Description of a case report.

We report an unusual case of endobronchial primary large B-cell Non Hodgkin Lymphoma in a HIV-infected patient in the course of effective Highly Active Antiretroviral Therapy (HAART). Diagnosis of large B-cell NHL was obtained by fibreoptic bronchoscopy (FOB) biopsies. Three cycles of R-CHOP chemotherapy (rituximab, vincristine, cyclophosphamide, hydroxydaunorubicin, prednisone) was performed and clinical and radiological remission was obtained after 3 cycles of therapy.

Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study.

The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: - 32±10 and - 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.

Effects of Sleeve Gastrectomy and Gastric Bypass on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients: a 2-Year Follow-up.

BACKGROUND: Bariatric surgery (BS) is known to favorably impact fasting lipid profile. Fasting and postprandial lipids were evaluated before and 2 years after BS in obese type 2 diabetic (T2DM) patients. METHODS: A prospective study was conducted in 19 obese T2DM patients: ten undergoing sleeve gastrectomy (SG) and nine undergoing Roux-en-Y gastric bypass (RYGB). Before and 2 years after BS, clinical parameters and the response of lipid and incretin hormones to a mixed meal (MM) were assessed. RESULTS: The two groups had similar characteristics at baseline. After BS, weight loss was similar in the two groups (p ≤ 0.01). Fasting glucose, insulin, and triglycerides decreased while HDL cholesterol increased in a similar way (p < 0.05); in contrast, fasting LDL cholesterol decreased only after RYGB (p < 0.05). Post-meal glucose concentrations decreased while early insulin response significantly improved after both procedures (p < 0.001 for both). Postprandial triglycerides decreased after both procedures (p < 0.05) while postprandial LDL cholesterol decreased only after RYGB (p < 0.05). Meal-GLP-1 increased postoperatively in both groups although to a greater extent after RYGB (p < 0.001 vs. SG). GIP decreased after both procedures, especially after RYGB (p = 0.003). At multivariate analysis, GLP-1 peak was the best predictor of LDL reduction (ß = -0.552, p = 0.039) while the improvement of HOMA-IR (ß = 0.574, p = 0.014) and weight loss (ß = 0.418, p = 0.036) predicted triglycerides reduction. CONCLUSIONS: Both surgical procedures markedly reduce fasting and postprandial triglycerides and increase HDL cholesterol levels. LDL cholesterol decreases only after RYGB through a mechanism likely mediated by the restoration of GLP-1.

A study of internet searches for medical information in dermatology patients: The patient–physician relationship

BACKGROUND: The use of the Internet to search for medical information is considered by some physicians as an invasion of their medical domain and a reflection of a lack of trust in their advice and recommendations. OBJECTIVE: The main objective of this study was to estimate the amount of medical information gathered from the Internet and to establish whether these online searches reflect a lower degree of patient satisfaction. PATIENTS AND METHODS: A survey was conducted among 175 patients seen at the melanoma and psoriasis units of San Cecilio University Hospital in Granada, Spain between May 2010 and December 2011. RESULTS: Online searches for medical information were performed by 44.4% of patients who returned correctly completed questionnaires. The main reasons given for these searches were to complement appropriate information provided by the physician (67.3%) and to gather information before consultation with the physician (36.5%). Variables associated with the search for medical information on the Internet in the multivariate analysis were a higher educational level, a higher score on two items in the Need for Cognition Scale, and consultation of mass media other than the Internet. Limitations: Studies with larger numbers of patients and other diseases, however, are required to confirm these results. CONCLUSIONS: The search for medical information is a widespread reality among patients with psoriasis and melanoma and it is not associated with a poor relationship with the physician. Dermatologists can play a beneficial role by recommending trustworthy Internet sites during the patient's visit and by promoting the development of pages by scientific societies to provide high-quality information

ANTECEDENTES: La búsqueda de información médica en Internet es considerada por algunos médicos como una invasión y falta de confianza en su valor como profesional. OBJETIVO: El principal objetivo es estimar la cantidad de información médica proveniente de Internet, y establecer si la búsqueda de información médica en Internet implica un menor grado de satisfacción por parte del paciente. PACIENTES Y MÉTODOS: Fueron incluidos 175 pacientes provenientes de las unidades de melanoma y psoriasis del Hospital Clínico San Cecilio, Granada (España) de mayo de 2010 a diciembre de 2011. RESULTADOS: La búsqueda de información médica en Internet fue realizada por el 44,4% de los pacientes. La principal razón fue complementar la adecuada información aportada por el médico (67,3%) y obtener información antes de la consulta con el médico (36,5%). Las variables asociadas en el análisis multivariante con la búsqueda de información médica en Internet fueron un alto nivel educativo, alta puntuación en la escala «Necesidad de conocimiento» «NFC1 y NFC2» y consultar otros mass media distintos de Internet. Limitaciones: Son necesarios estudios con mayor número de pacientes y otras enfermedades dermatológicas para confirmar los resultados. CONCLUSIONES: La búsqueda de información médica es una realidad muy extendida entre los pacientes con soriasis y melanoma, y no está asociada con una peor relación con el médico. Los dermatólogos pueden desempeñar un papel beneficioso a 2 niveles: recomendando páginas de interés y promoviendo el desarrollo de páginas por sociedades científicas con el fin de proporcionar información de alta calidad

A study of Internet searches for medical information in dermatology patients: The patient-physician relationship.

BACKGROUND: The use of the Internet to search for medical information is considered by some physicians as an invasion of their medical domain and a reflection of a lack of trust in their advice and recommendations. OBJECTIVE: The main objective of this study was to estimate the amount of medical information gathered from the Internet and to establish whether these online searches reflect a lower degree of patient satisfaction. PATIENTS AND METHODS: A survey was conducted among 175 patients seen at the melanoma and psoriasis units of San Cecilio University Hospital in Granada, Spain between May 2010 and December 2011. RESULTS: Online searches for medical information were performed by 44.4% of patients who returned correctly completed questionnaires. The main reasons given for these searches were to complement appropriate information provided by the physician (67.3%) and to gather information before consultation with the physician (36.5%). Variables associated with the search for medical information on the Internet in the multivariate analysis were a higher educational level, a higher score on two items in the Need for Cognition Scale, and consultation of mass media other than the Internet. LIMITATIONS: Studies with larger numbers of patients and other diseases, however, are required to confirm these results. CONCLUSIONS: The search for medical information is a widespread reality among patients with psoriasis and melanoma and it is not associated with a poor relationship with the physician. Dermatologists can play a beneficial role by recommending trustworthy Internet sites during the patient's visit and by promoting the development of pages by scientific societies to provide high-quality information.

Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation.

AIMS: To evaluate the clinical efficacy of bariatric surgery vs medical therapy with liraglutide on weight loss, glycemic control and cardiovascular risk profile in patients with type 2 diabetes and severe obesity. METHODS: A retrospective evaluation was conducted in 31 patients with type 2 diabetes and severe obesity who had undergone bariatric surgery and in 31 patients with type 2 diabetes and comparable body weight who had added liraglutide to their background medical treatment in the period 2009-2013. Anthropometric parameters, glycemic control, treatment of diabetes and other comorbidities, safety and side effects before and 12 months after treatment were assessed. RESULTS: Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p < 0.001); body mass index before treatment was 44 ± 7 and 40 ± 4 kg/m(2) in bariatric surgery and medical treatment, respectively (p = 0.03). Twelve months after treatment, average weight loss was 38 ± 15 kg among bariatric surgery patients, and 5 ± 8 kg in medical treatment group (p < 0.001). Glycemic control improved in both groups with greater improvement in bariatric surgery patients. The UKPDS risk score decreased in both groups, although it remained higher in medical treatment than in bariatric surgery patients (p < 0.001). Of note, almost 60 % of patients on liraglutide met the target of glycated hemoglobin <7 % (53 mmol/mol) and lost ≥5 % of body weight. CONCLUSIONS: In severely obese type 2 diabetic patients, bariatric surgery reduced body weight and improved overall metabolic control to a greater extent than medical treatment. Randomized clinical studies are necessary.

C2238/αANP modulates apolipoprotein E through Egr-1/miR199a in vascular smooth muscle cells in vitro.

Subjects carrying the T2238C ANP gene variant have a higher risk to suffer a stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need to be fully clarified. In the present work we aimed at exploring the impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As a first step, an atherosclerosis gene expression macroarray analysis was performed in vascular smooth muscle cells (VSMCs) exposed to either T2238/αANP (wild type) or C2238/αANP. The major finding was that apolipoprotein E (ApoE) gene expression was significantly downregulated by C2238/αANP and it was upregulated by T2238/αANP. We subsequently found that C2238/αANP induces ApoE downregulation through type C natriuretic peptide receptor (NPR-C)-dependent mechanisms involving the upregulation of miR199a-3p and miR199a-5p and the downregulation of DNAJA4. In fact, NPR-C knockdown rescued ApoE level. Upregulation of miR199a by NPR-C was mediated by a reactive oxygen species-dependent increase of the early growth response protein-1 (Egr-1) transcription factor. In fact, Egr-1 knockdown abolished the impact of C2238/αANP on ApoE and miR199a. Of note, downregulation of ApoE by C2238/αANP was associated with a significant increase in inflammation, apoptosis and necrosis that was completely rescued by the exogenous administration of recombinant ApoE. In conclusion, our study dissected a novel mechanism of vascular damage exerted by C2238/αANP that is mediated by ApoE downregulation. We provide the first demonstration that C2238/αANP downregulates ApoE in VSMCs through NPR-C-dependent activation of Egr-1 and the consequent upregulation of miR199a. Restoring ApoE levels could represent a potential therapeutic strategy to counteract the harmful effects of C2238/αANP.

Early improvement of postprandial lipemia after bariatric surgery in obese type 2 diabetic patients.

BACKGROUND: Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1. METHODS: We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS. RESULTS: After BS, there was a significant reduction in body weight (p < 0.001), fasting plasma glucose (p < 0.001), fasting plasma insulin (p < 0.05), HOMA-IR (p < 0.001), and fasting plasma lipids (p < 0.05). The meal response of plasma triglycerides, total cholesterol, and HDL cholesterol was significantly lower compared to pre-intervention (p < 0.05, p < 0.001). In particular, the incremental area under the curve (IAUC) of plasma triglycerides decreased by 60% (p < 0.005). The meal-stimulated response of active GLP-1 increased, reaching a statistical significance (p < 0.001). CONCLUSIONS: BS leads to an early improvement of fasting and postprandial lipemia. The fall in fasting triglycerides is associated with an improvement of insulin resistance, while the reduction of postprandial lipemia is likely related to reduced intestinal lipid absorption consequent to bariatric surgery.

[Vaccination and celiac disease: results of a retrospective study]. / Vaccinazioni e malattia celiaca: risultati di uno studio retrospettivo.

AIM: Human leucocyte antigen (HLA) system plays an essential role in the human immune system activity and the expression of some specific HLA antigens could modify the immune response to vaccinations. Celiac disease is included among the diseases associated to specific HLA profiles, principally characterized by the expression of the HLA DQ2 antigen. METHODS: Our study was a retrospective study, leaded on a group of celiac children, with the object to evaluate their immunological response to both obligatory and recommended vaccinations in childhood. It was a retrospective study, including 66 patients affected by celiac disease, between 3 and 15 years of age, and a control group of 50 children of the same age. All patients performed both obligatory and recommended vaccinations as indicated in the Italian standard regimen for vaccinations. The immunologic response to each vaccine was analysed and compared in the two groups. Moreover, authors also studied the immunologic response to vaccines in celiac children comparing patients whose diagnosis was made before 18 months of age with those whose disease was diagnosed after 18 months of age. RESULTS: Our results showed that in celiac patients the immunological response to vaccine is similar to that one found in general population, except for HBV vaccine. CONCLUSION: The evaluation of immunological response to HBV vaccine should be regularly effectuated in celiac children and revaccination should be recommended.

Impact of sleeve gastrectomy on weight loss, glucose homeostasis, and comorbidities in severely obese type 2 diabetic subjects.

This study was undertaken to assess medium-term effects of laparoscopic sleeve gastrectomy (LSG) on body weight and glucose homeostasis in severely obese type 2 diabetic (T2DM) subjects. Twenty-five obese T2DM subjects (10 M/15 F, age 45 ± 9 years, BMI 48 ± 8 kg/m(2), M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9-15 months after LSG. Mean BMI decreased from 48 ± 8 kg/m(2) to 40 ± 9 kg/m(2) (P < .001) at 3 months and 34 ± 6 kg/m(2) (P < .001) at 9-15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL and HbA1c < 6.5% in the absence of hypoglycemic treatment) occurred in all patients but one. There was a remarkable reduction in the percentage of patients requiring antihypertensive and hypolipidemic drugs. Our study shows that LSG is effective in producing a significant and sustained weight loss and improving glucose homeostasis in severely obese T2DM patients.

Trains of sleep sequences are indices of learning capacity in rats.

In previous work dealing with the identification of four sleep sequences (SS-->W, SS-->PS, SS-->TS-->W and SS-->TS-->PS) in the baseline session of adult male Wistar rats [Mandile P, Vescia S, Montagnese P, Romano F, Giuditta A. Characterization of transition sleep episodes in baseline EEG recordings of adults rats, Physiol Behav 1996;60:1435-1439], we have shown that those containing an intervening episode of transition sleep (TS) strongly correlate with the number of avoidances scored the following day [Vescia S, Mandile P, Montagnese P, Romano F, Cataldo G, Cotugno M, Giuditta A. Baseline transition sleep and associated sleep episodes are related to the learning ability of rats, Physiol Behav 1996;60:1513-152]. More recently, clusters of sleep sequences (trains) separated by waking intervals longer than 60 s have been identified in the baseline session of the same rats [Piscopo S, Mandile P, Montagnese P, Cotugno M, Giuditta A, Vescia S. Identification of trains of sleep sequences in adult rats, Behav Brain Res, this volume], and distinguished in homogeneous or mixed trains according to the presence of a single sleep sequence or more than one sequence. Mixed trains have been further separated into trains containing the SS-->TS-->W sequence (+TSW trains) and trains lacking it (-TSW trains). Analysis of the distribution of variables of baseline trains (and of their sleep sequences and components) among fast learning (FL), slow learning (SL), or non-learning (NL) rats, indicates that variables of +TSW trains prevail in FL rats, while variables of -TSW trains prevail in NL rats. In addition, variables of +TSW trains correlate with the number of avoidances of the training session, while variables of -TSW trains do not significantly correlate, or show inverse correlations. Interestingly, sleep sequences such as SS-->W or SS-->TS-->W show direct or inverse correlations with avoidances depending on whether they are included in +TSW trains or in -TSW trains. The data are interpreted to suggest that the outcome of brain operations performed during a sleep sequence may selectively condition the appearance of later sequences within a time interval shorter than a given threshold. An analogous mechanism may be responsible for the aggregation of sleep components in sleep sequences.

Identification of trains of sleep sequences in adult rats.

In previous studies based on high resolution EEG analyses of the 7 h baseline session of 18 adult male Wistar rats [6,14], we have identified four sleep sequences initiating with slow wave sleep (SS) and terminating with waking (W) or paradoxical sleep (PS). Two of these sequences contained an intervening episode of transition sleep (TS). Several variables of these sequences (SS-->W, SS-->TS-->W, SS-->TS-->PS, and SS-->PS) were selectively correlated with the capacity of rats to learn a two-way active avoidance task the following day, and were differently distributed in fast learning, slow learning and non learning rats [21]. The temporal organization of different sleep components in sequences suggested that a comparable temporal organization might concern the different sleep sequences, albeit on a longer time scale. We have now used waking periods longer than 60 s to separate clusters of baseline sleep sequences (trains) in the same rats. Trains containing the same sleep sequence (homogeneous trains) have been distinguished from trains containing different sleep sequences (mixed trains). In addition, mixed trains including the SS-->TS-->W sequence (+TSW trains) have been separated from mixed trains lacking that sequence (-TSW trains). Mixed trains of the +TSW type were longest and most numerous, while homogeneous trains were shortest and least abundant. Mixed trains of the -TSW type displayed intermediate values. Several variables of sleep sequences and sleep components differed within mixed trains and among mixed and homogeneous trains. The data indicate that baseline sleep sequences aggregate in relatively long strings in a non random fashion. The mechanism of this association is discussed.

Post-trial sleep sequences including transition sleep are involved in avoidance learning of adult rats.

High resolution computerized EEG analyses, and behavioral observations were used to identify slow wave sleep (SS), paradoxical sleep (PS) and transition sleep (TS) in adult male Wistar rats exposed to a session of two-way active avoidance training. Of the four sleep sequences that could be identified, two included TS (SS-->TS-->W and SS-->TS-->PS), while the other two did not (SS-->W and SS-->PS). Comparison of post-trial sleep variables between fast learning rats (FL, reaching criterion in the training session), slow learning rats (SL, reaching criterion in the retention session the following day), and non learning rats (NL, failing to reach criterion) indicated that the total amounts of SS, TS and PS of the SS-->TS-->PS sequence was markedly higher in FL rats than in SL rats. In addition, in comparison with the corresponding baseline period, the average duration and total amount of SS and TS episodes of the SS-->TS-->PS sequence increased in FL rats, while the number of SS-->TS-->W sequences decreased. On the other hand, the average duration of SS episodes increased in the SS-->TS-->W and SS-->W sequences of SL rats, and in the SS-->W and SS-->TS-->PS sequences of NL rats. Correlative analyses between number of avoidances and post-trial sleep variables demonstrated that avoidances were directly correlated with the duration of SS episodes of the SS-->TS-->PS sequence and with the duration of TS episodes of the SS-->TS-->W sequence, but inversely correlated with the number and amount of SS episodes of the SS-->W sequence and with the duration and amount of SS episodes of the SS-->PS sequence. On the whole, the data supported the view that TS-containing sleep sequences are involved in long-term storage of novel adaptive behavior, while sleep sequences lacking TS are involved in the maintenance of innate behavioral responses.

Baseline transition sleep and associated sleep episodes are related to the learning ability of rats.

The EEGs of 18 adult male Wistar rats were recorded during a baseline session lasting 7 h (day 1). The following day, rats were trained for a 2-way active avoidance task in an automated shuttle-box. A retention test was scheduled on the third day. On the basis of the number of avoidances scored during the training and retention sessions, rats were assigned to a fast-learning group (FL; achieving criterion during the training session), a slow-learning group (SL; achieving criterion in the retention test session), and a nonlearning group (NL; failing to achieve criterion). Vigilance states were determined by analyzing EEG data in 5-s epochs and calculating EEG power spectra of consecutive time intervals as short as 1 s. This high-resolution method led to the identification of transition sleep episodes that followed slow-wave sleep (SS) and were followed by waking (TS-->W) or by paradoxical sleep (TS-->PS). Comparison of the baseline sleep variables of the 3 behavioral groups revealed the presence of several significant differences. These observations were confirmed by the results of correlative analyses between baseline sleep variables and number of avoidances scored during the training and retention sessions. The most reliable indices of the capacity to learn the avoidance task were the amounts of SS preceding the TS-->W or the TS-->PS sequence, and the amounts of either component of the latter sequence. These variables displayed markedly higher values in FL rats. In addition, the amount of SS preceding TS-->W and the amount of TS-->(W) were significantly correlated with the number of avoidances scored during the training session. On the other hand, 1' SS-->(PS) and (SS)-->PS episodes were longer in NL rats than in SL or FL rats, respectively; and 2, the duration of SS-->(PS) episodes was inversely correlated with the number of avoidances of the first training period. The data are interpreted to suggest that TS and associated sleep episodes may predict the acquisition of the avoidance task, and the episodes of SS-->PS not associated with TS may predict the retention of innate responses, such as freezings or escapes.

Implantation of an EEG telemetric transmitter in the rat.

We describe a method of implanting a telemetric transmitter of EEG signals in the laboratory rat. The transmitter is available commercially and may be implanted in a subcutaneous pocket prepared in the hindermost dorsal region of the animal. The two stainless steel electrodes connected to the transmitter are led to the cranium through a subcutaneous tunnel, and are fixed to the cranium bones. EEG signals are collected by a receiver placed under the cage; reception of the signals is improved by suitably placed antennae. The method allows recording of EEG data from a free-moving rat during the expression of behavioral tasks in a limited space.

The sequential hypothesis of the function of sleep.

In addition to modulatory roles concerning bodily functions, sleep is assumed to play a main processing role with regard to newly acquired neural information. Elaboration of memory traces acquired during the waking period is assumed to require two sequential steps taking place during slow wave sleep (SWS) and eventually during paradoxical sleep (PS). This view is suggested by several considerations, not the least of which concerns the natural sequence of appearance of SWS and PS in the adult animal. While the involvement of PS in memory processing is well documented, the involvement of SWS is supported by the results of baseline and post-trial EEG analyses carried out in rats trained for a two-way active avoidance task or a spatial habituation task. Together with control analyses, these data indicate that the marked increase in the average duration of post-trial SWS episodes does not reflect the outcome of non-specific contingent factors, such as sleep loss or stress, but is related to memory processing events. Several considerations have furthermore led to the proposal that, during SWS, after a preliminary selection step, the first processing operation consists in the weakening of non-adaptative memory traces. The remaining memory traces would then be stored again under a better configuration during the ensuing PS episode. This view is in agreement with several relevant features of sleep, including the EEG waveforms prevailing during SWS and PS, as well as the ontogenetic sequence of appearance of SWS and PS. Some theoretical considerations on the role of sleep are also in agreement with the sequential hypothesis. More recent data indicate that the learning capacity of rats is correlated with several baseline EEG features of sleep and wakefulness. They include the average duration of PS episodes and of SWS episodes followed by wakefulness (longer in fast learning rats), and the waking EEG power spectrum of fast learning rats whose output is more balanced in the frequency range below 10 Hz than in slow learning and in non-learning rats. Additional EEG data suggest that fast learning rats may accomplish 'on line' processing of newly acquired information according to a sequence of events not dissimilar from the one proposed by the sequential hypothesis.

Effective antibody response in newborn babies living in Maldives to simultaneous vaccination against hepatitis B, poliomyelitis, diphtheria and tetanus.

The antibody responses of Maldivian infants early in their life to simultaneous immunization against hepatitis B virus, poliomyelitis, diphtheria and tetanus were investigated. The vaccines were given at 6, 10 and 14 weeks of age. Among 243 newborn babies from HBsAg-negative mothers, 103 received three doses of oral poliomyelitis (OPV) and diphtheria and tetanus (DTV) vaccines; 105 were similarly immunized but received in addition the recombinant hepatitis B vaccine (HBV); 35 were immunized with the HBV recombinant vaccine alone. The antibody response to all of the vaccines was effective. No significant differences among the groups were observed. Hepatitis B vaccination of infants neither affected nor was affected by the contemporary administration of OPV and DTV vaccines.