Electroencephalographic functional connectivity is altered in persons with Down syndrome and Alzheimer's disease.

BACKGROUND: Persons with Down syndrome (DS) are at increased risk of developing Alzheimer's dementia (DS-AD). Due to heterogeneity in the functioning in persons with DS, it is difficult to use cognitive testing to assess whether a person with DS has developed dementia due to AD. Electroencephalography (EEG) functional connectivity has shown promising results as a diagnostic tool for AD in persons without DS. In the current exploratory study, we investigated whether EEG functional connectivity could be used as a diagnostic marker of AD in persons with DS and the association with symptoms. METHODS: Electroencephalography from 12 persons with DS and 16 persons with DS-AD were analysed, and both coherence and weighted phase lag index were calculated. In addition, we calculated the average coherence for fronto-parietal and temporo-parietal connections. Lastly, we investigated the correlation between the informant-based Dementia Screening Questionnaire in Intellectual Disability (DSQIID) and total alpha coherence. RESULTS: Decreased alpha and increased delta coherence and weighted phase lag index were observed in DS-AD as compared with DS. The decrease in alpha coherence was more marked in the fronto-parietal connections as compared with the temporo-parietal connections. No significant correlation was found between DSQIID and total alpha coherence (P value = 0.095, rho = -0.335). CONCLUSION: The decreased alpha coherence and weighted phase lag index have previously been found in AD. The increased delta coherence and weighted phase lag index may indicate a different initial neurophysiological presentation as compared with patients with AD or may be a sign of more advanced disease. Larger studies are needed to confirm the current findings.

Associations between electroencephalography power and Alzheimer's disease in persons with Down syndrome.

BACKGROUND: It is complicated to diagnose dementia in persons with Down syndrome (DS). Older studies have, however, demonstrated low-frequency activity in electroencephalography (EEG) in persons with concurrent DS and Alzheimer's disease (DS-AD). The aim of this study was to examine whether it was possible to identify AD-associated changes (increased high-frequency power and decreased low-frequency power) in persons with DS-AD compared with DS. METHODS: We included 21 persons with DS-AD and 16 with DS without cognitive deterioration assessed by the informant-based Dementia Screening Questionnaire in Intellectual Disability. EEG was recorded for all participants. Absolute power for each electrode and global power were calculated for all frequency bands for both eyes open and eyes closed. RESULTS: For global power in the eyes closed condition, we found an increased global slow-frequency activity and a decreased global high-frequency activity in DS-AD compared with DS. In addition, we found a significant difference in the global alpha/delta ratio with the largest difference found for global alpha power in DS-AD compared with DS. CONCLUSIONS: In the current study, we found that changes known to be associated with AD could also be identified when comparing DS-AD with DS using quantitative EEG. In general, these findings suggest that EEG might be a useful tool in diagnosing AD in persons with DS, but larger studies are needed.

Subjective cognitive complaints included in diagnostic evaluation of dementia helps accurate diagnosis in a mixed memory clinic cohort.

OBJECTIVE: Our objective was to examine the quantity and profile of subjective cognitive complaints in young patients as compared with elderly patients referred to a memory clinic. METHODS: Patients were consecutively recruited from the Copenhagen University Hospital Memory Clinic at Rigshospitalet. In total, 307 patients and 149 age-matched healthy controls were included. Patients were classified in 4 diagnostic groups: dementia, mild cognitive impairment, affective disorders and no cognitive impairment. Subjective memory was assessed with subjective memory complaints (SMC) scale. Global cognitive functions were assessed with the Mini-mental state examination (MMSE) and Addenbrooke's cognitive examination (ACE), and symptoms of depression were rated with Major Depression Inventory (MDI). All interviews and the diagnostic conclusion were blinded to the SMC score. RESULTS: We found that young patients with dementia have a significantly higher level and a different profile of subjective cognitive complaints as compared with elderly patients with dementia. Furthermore, young patients, diagnosed with an affective disorder, had the highest level of subjective cognitive complaints of all patients in a memory clinic. The age of the patients and MDI score (but not MMSE or ACE) had significant impact on the level of subjective cognitive complaints. CONCLUSIONS: We have established that young patients with dementia have a different profile of subjective cognitive complaints than elderly patients, and further studies are needed to clarify possible relation to specific subtypes of dementia. Altogether, a systematic interview on subjective cognitive complaints may contribute to the diagnostic evaluation of patients referred to a memory clinic.

The value of 18F-FDG PET/CT for assessing the response to neoadjuvant therapy in locally advanced rectal cancer.

PURPOSE: Neoadjuvant radiochemotherapy (RCT) is an accepted treatment for locally advanced rectal cancer (LARC) that improves surgical outcomes. If a pathological complete response is achieved, conservative surgery can be considered. The objective of our study was to assess the reliability of (18)F-FDG PET/CT for evaluating the response to neoadjuvant RCT in LARC. METHODS: We prospectively studied 41 patients diagnosed with LARC and candidates for neoadjuvant RCT. PET/CT was performed before RCT and again 7 weeks later. A visual and semiquantitative analysis was carried out. The pathological response was classified according to the Mandard tumour regression grade (TRG). We analysed: (a) the relationship between TRG and the result of the posttreatment PET/CT scan, and (b) the correlation between the percentage of pathological response and the percentage decrease in SUVmax according to the response index (RI). RESULTS: The mean SUVmax of the rectal lesions at diagnosis was 13.6 and after RCT 3.96. The mean RI was 65.32 %. Sensitivity was 88.88 %, specificity 92.86 %, positive predictive value 96 %, negative predictive value 81 %. Of the 41 patients, 8 had TRG I (all negative PET/CT); 6 had TRG II (5 negative, 1 positive PET/CT); 16 had TRG III (13 positive, 3 negative PET/CT); 9 had TRG IV (all positive PET/CT); 2 had TRG V (all positive PET/CT). Of the 14 patients classified as responders (TRG I, II), 13 (92.86 %) had negative PET/CT. Of the 27 patients classified as nonresponders (TRG III-V), 24 (88.88 %) had positive PET/CT. Differences were statistically significant (p < 0.0001). The RI in responders was 79.9 % and in nonresponders was 60.3 %. Differences were statistically significant (p < 0.037). CONCLUSION: PET/CT is a reliable technique for assessing response to neoadjuvant RCT in LARC, with a view to considering more conservative surgical treatment. The combination of the visual and semiquantitative analysis increases the diagnostic validity of PET/CT.

Radiation-induced lattice relaxation in [Formula: see text]-Fe[Formula: see text]O[Formula: see text] nanorods.

We report radiation-induced lattice relaxation of the [Formula: see text]-Fe[Formula: see text]O[Formula: see text] and its associated alteration of particle morphology. The [Formula: see text]-Fe[Formula: see text]O[Formula: see text] was grown in solution by microwave hydrothermal synthesis technique in which more than half of the synthesized material was nanorods with axis along the (001) direction. Five sets of the synthesized [Formula: see text]-Fe[Formula: see text]O[Formula: see text] samples were irradiated using gamma-ray from [Formula: see text]Co cell with doses of 600 kGy, 700 kGy, 800 kGy, 900 kGy, and 1 MGy. The investigation of the pristine and gamma-irradiated samples was carried out using X-ray powder diffraction, transmission electron microscope, and electron paramagnetic resonance methods. Results showed that continuous alternation of radiation-induced lattice compression and expansion causes lattice relaxation. The morphology of the [Formula: see text]-Fe[Formula: see text]O[Formula: see text] nanorods was found to change with absorbed dose into buckyball-shaped particles in response to the alternation of the compression and expansion strain. The EPR results showed a correlation between distortion in the [Formula: see text]-[Formula: see text] octahedron structure and the relaxation of the lattice. The synthesis, growth, and relaxation are discussed in detail.

Overdiagnosis of dementia in young patients - a nationwide register-based study.

BACKGROUND: Little is known about the quality of the diagnostic evaluation and the validity of dementia diagnoses in young patients established in routine clinical practice. The aim of this study was to investigate the validity of the diagnosis of dementia registered in the Danish nationwide hospital registers in young patients. METHODS: Two hundred patients were randomly selected from 891 patients <65 years registered with a dementia diagnosis for the first time in 2008. The patients' medical records were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and current clinical criteria for specific dementia subtypes. RESULTS: A registered diagnosis was found to be correct in only 59%. A misdiagnosis of dementia occurred primarily in patients with depression or alcohol abuse. CONCLUSION: Our results suggest that dementia is overregistered and overdiagnosed in young patients. This may be due to a different symptom profile of dementia in young patients, lack of knowledge among clinical physicians and the wide range of conditions which may be misinterpreted as dementia.

Theory of photochemical reactions.

Although the great number of electronic states available to an excited molecule might seem to preclude a coherent picture of photochemical reaction mechanisms, it is possible to bring out some basic features common to a great many reactions. The electronic states of the primary diradical intermediates, surface crossings, topicity, and avoided surface crossings have been shown to be essential components of the electronic theory of photochemical reactions. Diradicals have four important electronic states. Knowing these states, and making a simple electron count, it is possible to draw state correlation diagrams. Some diagrams show a typical surface crossing of the ground singlet state with the lowest (singlet, triplet) pair of excited states, with clear-cut consequences of quantum yields under various conditions. In other reactions the surfaces stay apart. The critical discriminating feature that determines the type of correlation diagram is the topicity. Photochemical reactions can be classified according to topicity, which is useful in interpreting their mechanisms (53). Avoided surface crossings can also be classified into different types. Figure 7, which illustrates the interplay of a covalent and an ionic surface responsible for photochemical electron transfer, is a typical multidimensional representation of a photochemical reaction. The chemical behavior of the excited zwitterionic states of common intermediates, such as twisted ethylene or diallyl, reflects the quantum mechanical nature of photochemical processes. In these states, for perfectly symmetric systems, charge oscillates back and forth between two symmetry-equivalent sites. Slight geometric perturbations can create a sudden polarization of the excited molecule, with localization of almost a full charge at one end of the molecule. A photon is transformed into an electrical signal thanks to an appropriate molecular distortion. Nature may have used this simple process in the N-retinylidene visual chromophore to trigger an electrical response to vision.

Influence of vitamin D supplementation on glycemic control in type 2 diabetics.

INTRODUCTION: Several studies have suggested a benefic impact of vitamin D supplementation on glycemic control and insulin resistance among patients with type 2 diabetes mellitus. The aims of our study were to assess vitamin D status in individuals with type 2 diabetes mellitus and to investigate the effects of vitamin D supplementation on glycemic measures in patients having vitamin D deficiency. METHODS: We conducted a comparative prospective study involved 100 Tunisian patients with type 2 diabetes followed at the National Institute of Nutrition and Food Technology of Tunis. Glycemic control and insulin resistance were evaluated in the beginning of the study and three months after supplementation. RESULTS: Baseline mean 25-Hydroxy vitamin D  (25(OH)D) level was 17.5±9.8 ng/ml. Vitamin D status was deficient in 60%, insufficient in 26% and sufficient in 14% patients. After vitamin D supplementation, mean serum 25(OH)D concentration increased significantly (p˂10-3). We observed a negative correlation between the variation of plasma 25(OH)D level and the waist circumference's variation (r=-0.266 and p=0.018). This correlation persisted after adjustment for therapeutic management. Vitamin D supplementation did significantly improve neither glycemic control nor insulin resistance parameters. CONCLUSION: Vitamin D deficiency is frequent in patients with type 2 diabetes mellitus. The metabolic effects of supplementation are controversial, hence the need of expanding studies to better demonstrate these effects.

[Growth hormone deficiency and pituitary stalk interruption in Fanconi anemia]. / Déficit en GH par interruption de la tige pituitaire dans l'anémie de Fanconi.

Fanconi anemia is a rare disorder inherited by recessive autosomic transmission belonging to the group of chromosomal instability syndromes. It is characterized by progressively developing medullary aplasia, various congenital malformations and especially a high risk of cancer, particularly acute myeloblastic leukemia and certain solid tumors. The association is quite common in patients with endocrine disease which constitutes an additional factor of morbidity and must be diagnosed and treated. We report a case of Fanconi anemia revealed by severe delay in statural growth and primary amenorrhea with a 21-year-old girl. The diagnosis was suggested by asymptomatic pancytopenia caused by a medullary hypoplasia and confirmed by a cytogenetic investigation using cross-linking agents that showed a large number of chromosomal breaks. Hormonal exploration revealed hypopituitarism with complete growth hormone (GH) deficiency and hypogonadotrophic hypogonadism caused by interruption of the pituitary stalk. The aim of this case report is to illustrate the importance of early exploration of retarded growth which, in some patients, can reveal potentially serious, and treatable, disease.

[Correlations between insulin sensitivity with anthropometric and metabolic parameters in type 2 diabetics]. / Étude de la corrélation entre la sensibilité à l'insuline et les paramètres anthropométriques et métaboliques dans le diabète de type 2.

AIM: The aim of the study was to evaluate correlations between insulin sensitivity and insulinosecretion with anthropometric and metabolic parameters in type 2 diabetics. MATERIALS AND METHODS: We conducted a cross-sectional study among patients with type 2 diabetes mellitus treated with oral antidiabetic medications. The evaluation of insulin resistance and insulinosecretion was based on the calculation of the HOMA-IR and HOMA-ß indices. RESULTS: The mean age for the 100diabetes recruited was 56.4±8.4years. The mean body mass index (BMI) and waist circumference (WC) were 30.5±5.7kg/m2 and 101.2±11.9cm respectively. The HOMA-IR and HOMA ß indices were respectively 3.5±2.8 and 48.9±45.5. We have found a significantly positive correlation between HOMA-IR index and weight (r=0.406, p<10-3), BMI (r=0.432, p<10-3) and WC (r=0.412, p<10-3). We noticed a significant negative correlation between HOMA ß index and fasting glucose (r=-0.457, p<10-3) and A1C (r=-0.399, p<10-3). A positive statistically significant correlation was noted between HOMA-IR and HOMA-ß (r=0.400, p<10-3). CONCLUSION: Insulin resistance is very related to overweight, especially the android distribution of fat hence the need for adequate management of this android obesity. It would also be interesting to evaluate the effects of weight loss on insulin resistance parameters.

[Experimental determination of correction factors of four detectors used in small field radiotherapy]. / Détermination expérimentale des facteurs de correction de quatre détecteurs actifs utilisés pour la dosimétrie des minifaisceaux utilisés en radiothérapie.

PURPOSE: The aim of this work is to determine experimentally the correction factors [Formula: see text] for four active commercial dosimeters: two microchambers and two diode detectors based on the output factor measured with radiochromic film for a radiotherapy linear accelerator equipped with circular cones. MATERIALS AND METHODS: Initially, a radiochromic film dosimetry measurement protocol with an accuracy of 2% was developed to approach the "reference output factor". Afterwards, the corrective factors of four detectors were determined for two ionization chambers (PinPoint PTW 31016 3D, Micropoint Extradin A16) and two diodes (PTW T60017 Diode, PTW-60019 Micro-Diamond). These measurements were carried out under conical BrainLAB® collimators defining circular fields with diameters equal to 7.5mm, 10mm, 12.5mm, 15mm, 17.5mm, 20mm, 25mm, 30mm, 35mm and 45mm of a 6MV X-ray beam generated by the ClinaciX linear accelerator (Varian®). These factors are weakly dependent on the type of accelerator, whether the model and the collimation type. This allowed their comparisons with those published for the same type of detector and for an accelerator with the same index of beam quality. RESULTS: The correction factors obtained experimentally were comparable in maximum deviation of 1.9% with published ones of the works using the same type of detector (mark and model) and an accelerator delivering the same beam quality for the same field size at the measurement point. CONCLUSION: The measurement protocol using the EBT3 film, which was used as a passive dosimeter to determine the "reference output factor", was validated by comparing measured and published data of active detector correction factors.

The global diabetes pandemic: the Tunisian experience.

OBJECTIVE: The prevalence of diabetes mellitus is known to be increasing rapidly worldwide, but few population-based surveys have been undertaken in Africa or the Middle East. The aims of this study are to report the prevalence of diabetes mellitus and impaired fasting glucose (IFG) in Tunisia, to compare the prevalence to previous studies and to analyse the relationship between diabetes and age, sex, area of residency and body mass index (BMI). SUBJECTS AND SETTING: We have used data from the Tunisian National Nutrition Survey, a cross-sectional health study providing a large nationally representative sample of the Tunisian population including 3729 adults. We used the American Diabetes Association diagnostic criteria to determine the prevalence of diabetes mellitus and IFG. RESULTS: The overall diabetes prevalence was 9.9% (9.5% in men and 10.1 in women) giving age-adjusted prevalence of diabetes of 8.5% (7.3% in men and 9.6% in women). Step-wise logistic regression showed age of more than 40 years, urban residency and high BMI to each be significantly and independently related to diabetes prevalence. The prevalence of diabetes mellitus has more than doubled in Tunisia over a 15-year period. CONCLUSIONS: Our study has demonstrated a high prevalence of diabetes in the adult population with a wide difference among the rural and urban areas with an increased prevalence compared to previous studies. The results underline the need to increase public awareness and to emphasize the benefit of lifestyle modification in order to prevent type II diabetes.

Prevalence of metabolic abnormalities in the Tunisian adults: a population based study.

AIMS: To estimate the prevalence of individual metabolic abnormalities and the cluster of metabolic abnormalities in a representative sample of the Tunisian adult population and to identify their relationship with gender, age and residency. The definition used is an adaptation of the NCEP ATP III definition, using total cholesterol>or=5.2 mmol/l instead of HDL-cholesterol. MATERIALS AND METHODS: We used a sample of the Tunisian National Nutrition Survey (TNNS), a cross-sectional health survey conducted in 1996, to estimate the nutritional status of the population. The TNNS included 2 927 adults aged 20 years or older who had measurements of height, body weight, waist circumference, blood pressure, fasting plasma glucose, total cholesterol and triglycerides. The cluster of metabolic abnormalities was defined as the presence of three or more metabolic abnormalities. RESULTS: The prevalence of abdominal obesity, hypertriglyceridemia, high total cholesterol, high blood pressure and high fasting plasma glucose was, respectively, 9%, 23%, 24%, 45% and 15% in men and 33%, 19%, 29%, 44% and 15% in women. The prevalence of the cluster was more frequent in women than in men (18% versus 13%, P<0.001) and in those living in urban communities (21% in women, 16% in men) rather than rural communities (11% in women, 8% in men) (P<0.001). The prevalence also increased significantly with age (P<0.001). CONCLUSION: The cluster of metabolic abnormalities and its components are common in the Tunisian adult population and prevalence increases significantly with female sex, urban residency and age.

[Ramadan fasting in type 2 diabetes mellitus]. / La pratique du jeûne du mois de Ramadan chez le diabétique de type 2.

This study was designed to assess the effects of fasting during Ramadan on weight, blood pressure, metabolic control and plasma lipoproteins in diabetic patients. This study was conducted in December 2000 (Ramadan 1421) when the length of fasting was 12 hours a day. It included 38 type 2 diabetic patients (20 males and 18 females). Mean patient age was 51.410.5 years and mean body mass index (BMI) 28.94.7kg/m2. Three patients were treated with diet and 35 with oral hypoglycemic agents. Clinical and biochemical parameters were evaluated during three periods: three weeks before Ramadan (T0), at the fourth week of Ramadan (T1) and three weeks after the end of Ramadan (T2). During the month of Ramadan, a decrease in weight (0.52kg) and no change in blood pressure were observed. No metabolic complication occurred in our patients. A significant effect of Ramadan fasting was observed on glycemic control and lipoprotein levels. In patients whose fructosamine level before Ramadan was higher than 340micromol/l, plasma fasting glucose and serum fructosamine increased during Ramadan (p<0.003) and returned to initial levels at the end of Ramadan T2; in these patients also, a decrease of HDL-cholesterol (p<0.01) associated with an increase of LDL-cholesterol (p<0.003) were observed at T1 and disappeared at T2. But, in patients whose fructosamine level at T0 was lower than 340micromol/l, no effect on glycemic control and no significant effect on serum lipoprotein levels were found during Ramadan month. Ramadan fasting in type 2 diabetic patients seems to cause slight effects on glycemia and lipoprotein levels when previous metabolic control is quite good; but fasting induces more deterioration when previous control is poor.

Suppressor analysis of the Saccharomyces cerevisiae gene REC104 reveals a genetic interaction with REC102.

REC104 is a gene required for the initiation of meiotic recombination in Saccharomyces cerevisiae. To better understand the role of REC104 in meiosis, we used an in vitro mutagenesis technique to create a set of temperature-conditional mutations in REC104 and used one ts allele (rec104-8) in a screen for high-copy suppressors. An increased dosage of the early exchange gene REC102 was found to suppress the conditional recombinational reduction in rec104-8 as well as in several other conditional rec104 alleles. However, no suppression was observed for a null allele of REC104, indicating that the suppression by REC102 is not "bypass" suppression. Overexpression of the early meiotic genes REC114, RAD50, HOP1, and RED1 fails to suppress any of the rec104 conditional alleles, indicating that the suppression might be specific to REC102.

Coordination of the initiation of recombination and the reductional division in meiosis in Saccharomyces cerevisiae.

Early exchange (EE) genes are required for the initiation of meiotic recombination in Saccharomyces cerevisiae. Cells with mutations in several EE genes undergo an earlier reductional division (MI), which suggests that the initiation of meiotic recombination is involved in determining proper timing of the division. The different effects of null mutations on the timing of reductional division allow EE genes to be assorted into three classes: mutations in RAD50 or REC102 that confer a very early reductional division; mutations in REC104 or REC114 that confer a division earlier than that of wild-type (WT) cells, but later than that of mutants of the first class; and mutations in MEI4 that do not significantly alter the timing of MI. The very early mutations are epistatic to mutations in the other two classes. We propose a model that accounts for the epistatic relationships and the communication between recombination initiation and the first division. Data in this article indicate that double-strand breaks (DSBs) are not the signal for the normal delay of reductional division; these experiments also confirm that MEI4 is required for the formation of meiotic DSBs. Finally, if a DSB is provided by the HO endonuclease, recombination can occur in the absence of MEI4 and REC104.

Celiac disease in adult patients with type 1 diabetes mellitus in Tunisia.

OBJECTIVE: Type1 diabetes mellitus may be associated with celiac disease. The prevalence of celiac disease as determined by screening among adult patients with type 1 diabetes is high with rates of 1.07.8% in Europe and U.S.A. The aims of the study are to determine the prevalence of celiac disease in adults with type 1 diabetes in Tunisia. METHODS: 348 consecutive adult patients with type1 diabetes were investigated prospectively and screened for celiac disease. The mean age was 28.45+/-10.74 years old. There were 176 females and 172 males. For the screening of celiac disease, we used immunoglobulin A (IgA) anti-endomysium (EMA) antibodies determined by an indirect immunofluorescence method. Anti-transglutaminase (tTG) antibodies were determined by an ELISA method. Those patients with positive results for anti EMA and or tTG were proposed for duodenal biopsy. RESULTS: 14 patients were positive for anti EMA and had high or a weak positive level of tTG antibodies. One patient from this group was already known to have celiac disease. Only 8 patients consented to biopsy and morphological changes were consistent with celiac disease in all cases. Prevalence of biopsy-proven celiac disease was 2.3% (95% CI=1.0-4.5%). CONCLUSION: The present study confirms that celiac disease of adults is prevalent in type 1 diabetic patients in Tunisia. Serological screening for celiac disease in type 1 diabetes is important because many patients are asymptomatic and most are detected by the screening.

Slow-wave sleep in daytime and nocturnal sleep: an estimate of the time course of "Process S".

Daan et al. (1984) have proposed that sleep and wakefulness are regulated, in part, by a "Process S" that increases during wakefulness and declines during sleep. Data derived from several studies were taken to determine the time course of Process S during both wakefulness and sleep. As required by the model, slow-wave-sleep (SWS; an index of Process S) was found to increase exponentially as a function of prior wake time (equation 1) and to decline exponentially as a function of time asleep (equation 2). The equations accounted for 91% and 96% of the variance, respectively. In addition, equation 1 accurately predicted the amount the amount of SWS in the first hour of nocturnal sleep.

The influence of prior wakefulness on REM sleep.

Data from studies of naps and of shifted sleep were used to determine the relationship between two measures of rapid eye movement (REM) sleep (percentage of REM in the first 2 hr of sleep and REM latency) and prior wakefulness. For each sample, we calculated the difference between the observed value and that predicted by a cosine function that estimated the circadian rhythm of REM sleep propensity. The difference values were found to correlate reliably with hours and log hours of prior wakefulness. We conclude that while REM sleep is regulated in part by an endogenous circadian oscillator, it is also influenced by the duration of prior wakefulness.