Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls (P = 0.003**). A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease (P = 0.0001***) and patient's age (P = 0.01*). There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients. Rheumatoid arthritis is a chronic inflammatory disease. Cardiovascular events are the most important cause of mortality and morbidity in patients with rheumatoid arthritis . PatientOne hundred and twelve patients with RA were included in the present study, 94 women and 18 men; their age ranged from 21 to 49 years and disease duration ranged from six months to fifteen years. Patients were diagnosed according to the American College of Rheumatology (ACR) 1987 revised criteria for the classification of rheumatoid arthritis [Exclusion Criteria. Control and RA patients with known atherosclerotic complications such as stroke and MI; those undergoing hemodialysis; patients with peripheral vascular disease, malignancy, or infections; hypertensive and diabetic patients; and smokers were excluded; patients complaining of any cardiac symptoms or signs  were also excluded.Forty age and sex matched healthy subjects were recruited as controls for laboratory investigations and duplex ultrasonographic evaluation.All patients underwent a complete history taking and clinical examination according to the standard protocol. General and locomotor examinations were done for all patients.Assessment of disability by the Health Assessment Questionnaire (HAQ) disability index: The Arabic version of disability index of the Stanford Health Assessment Questionnaire was used to assess disability  , using an automated cell counter, Sysmex NE; erythrocyte sedimentation rate (ESR) (by Westergren method); rheumatoid factor (RF); latex agglutination slide test for the qualitative and semiquantitative determination of rheumatoid factor in nondiluted serum ; liver fAnteroposterior radiographs of both hands and feet were done. Simple Erosion Narrowing Score (SENS) was used for X-ray scoring . It is aDuplex ultrasonography of both carotids;ultrasonography to right brachial artery to detect endothelial function.Evaluation is done as follows:(I) Carotid Ultrasound Measurements. Subclinical atherosclerosis was investigated in RA patients and in control subjects using carotid ultrasound evaluation. Briefly, individuals in the study population were investigated in the supine position, with the head turned away slightly from the sonographer. The common carotid arteries were carefully examined for wall changes in all subjects, obtaining different longitudinal and transverse views with the high-resolution B-mode ultrasound equipment Medison 9900 multibeam 30 UL (Korea) equipped by liner probe (7.5 MHz) with the use of a standardized protocol [protocol . A regioAll ultrasound measurements were performed by the same examiner who was unaware of subject characteristics.This evaluation aims to determine the intima media thickness (IMT) and to detect carotid plaques. The mean IMT (the mean of both right and left sides) was assessed. At the same time the maximum IMT  was also assessed. IMT is considered abnormal if >0.07 cm . Plaques(II) Endothelial Function. To assess endothelial function noninvasively with B-mode ultrasound, conduit vessel endothelium-dependent vasodilatation was induced by reactive hyperemia, while endothelium-independent vasodilatation was induced by administration of sublingual nitroglycerine  as described by Yim and his colleagues [lleagues . Measurelleagues .FMD, GTN, and dilatation were calculated as follows:*Student's t-test: The independent samples T test was used to compare the means of two groups of cases.  *The chi-squared (χ2) test: We used the χ2 test to test the significance of the differences between the two groups in categorical variables. Correlations: The bivariate correlations procedure computes Pearson's correlation coefficient with its significance levels. Pearson's correlation coefficient is a measure of linear association.Data were coded, entered, and analyzed by the statistical package for the Social Sciences (SPSS for windows version 11.0) . Two-taiThis study was carried out on 112 RA patients (group 1) and 40 age and sex matched healthy controls (group 11). Patients were classified by DAS28 scores into the following: patients in remission (defined as DAS28 score <2.4) was observed in six out of 112 (5.4%) cases; low disease activity (<3.2) was found in 14 (12.5%); moderate activity (3.2–5.1) in 28 (25%); and high disease activity (>5.1) in 64 (57.1%) RA patients.The demographic data of the RA patients and controls are shown in The mean disease duration was 6.03 ± 3.9 years (ranging from 6 months to 15 years) and 19.64% of our patients were of recent onset (<2 years). The DAS28 ranged between 1.2 and 7.81 with a mean of 5.21 ± 1.68. The visual analog scale of pain ranged between 20 and 80 with a mean of 55.71 ± 5.135, while the Health Assessment Questionnaire-Disability Index ranged between 0 and 1.77 with a mean of 0.742 ± 0.501. The body mass index ranged between 17.7 and 42.25 with a mean of 26.02 ± 6.42; also the waist circumferences ranged between 61 and 120 cm with a mean of 90.86 ± 11.94. Regarding deformities, they were present in 68 (60.71%) patients while rheumatoid nodules were present also in 18 (16.07%) patients. At the time of the study, 10 (8.93%) patients only were not using NSAIDs. 58 patients (51.8%) were using steroids. Ninety patients (80.4%) were using antimalarial drugs, while 98 patients (87.5%) were using MTX. Twenty patients (17.9%) were using Sulphasalazine. 44 (39.3%) patients were using Leflunomide.There were highly statistical significant difference between patients and controls as regarding the prevalence of subclinical atherosclerosis; thirty-five patients (31.3%) have thickened IMT and only 6 patients (5.4%) had atherosclerotic plaque; meanwhile, only two (5%) of controls had thickened intima with no detected plaque formation.P < 0.000***) and patient's age (P < 0.01*). There is a significant association between the cumulative doses of steroids and the thickened IMT (P < 0.005**). Also there is significant difference in Us-CRP (P < 0.000***), DAS28 (P < 0.002**). We must notice that cut-off value of IMT was different in different studies; some studies showed carotid artery IMT ≥0.60 mm was a marker of atherosclerosis; if we take this threshold in our mind, we found the same number of our patient had atherosclerosis. But another author showed carotid artery IMT >0.90 mm was a marker of atherosclerosis; the number of our patients who had IMT >0.90 mm was only four (3.6%).P < 0.0001***, P < 0.002**, resp.).The mean and standard deviation of disease duration of all patients was 6.4 ± 3.9. The mean of disease duration in patients with and without atherosclerosis was 10.5 ± 3.1 and 4.7 ± 2.9, respectively. The mean of disease activity index in patients was 5.2 ± 1.68 and the mean of disease activity index in patients with and without atherosclerosis was 5.8 ± 1.5 and 2.8 ± 1.3, respectively , FMD dilatation percent (P < 0.000***), and dilatation ratio (P < 0.000***) were significantly lower in patient than controls, even in group 1B.P < 0.04*), FMD dilatation percent (P < 0.03*), and dilatation ratio (P < 0.01*) were significantly lower in the first group than the second.Atherosclerosis and Steroid Use. There are 58 patients (51.8%) of current steroid users and 54 patients (48.2%) are nonsteroid users in RA patients, nearly similar prevalence of cases with increased mean IMT in patient using glucocorticoids  than nonusers . No significant differences were found in comparison of parameters which asses the endothelial function in RA patients and ultrasonographic duplex of their carotid arteries in patients who used steroids with patients who do not use steroids , and also it has a significant correlation with ultrasonographic duplex findings of carotid arteries maximum, left IMT, and mean IMT  (Tables ) Tables  and 16.P = 0.01*). In addition to the two markers of subclinical atherosclerosis; the mean right and left IMT were higher in patients compared to the controls. Plaques were also more frequently observed in RA (P = 0.02). And by comparison of parameters which asses the endothelial function in RA patients and controls. Only FMD (P = 0.043) and dilatation ratio (P = 0.001) were significantly lower in patient than controls. These result in agreement of other studies [In the present study there is an overall higher prevalence of premature atherosclerosis in RA patients than controls; in addition, the mean IMT was significantly higher in RA patients than our healthy controls  . This was in agreement with other authors  who showIn our study, there was no significant difference found between the two groups.As regarded the prevalence of traditional cardiovascular risk factors. In our study, obesity, as defined by BMI >30.0, was reported in 40 (35.7%) of our RA patients versus 12 (30%) of our healthy controls with no significant statistical differences between both groups. Our results were similar to other study . Most auP < 0.001) were detected in RA compared to healthy controls; this is in agreement with the previous study [Inflammation is considered to be an important risk factor for premature atherosclerosis in RA. This was a very consistent finding in the present study as measured by acute phase reactants including high level erythrocyte sedimentation rate and CRP. As expected, higher levels of ESR . Other authors saw that patients requiring GCs as part of their disease management are likely to have aggressive disease, which contributes to a reduction in mobility as a result of joint stiffness and damage. Therefore, GC use in this subset of patients may result in suppression of disease activity and allow patients to lead a more active lifestyle with a further beneficial effect on HDL levels as well as aggressive control of inflammatory disease activity with available means, including judicious usage of GCs [In this study the percentages of steroid user are 51.8% and nonusers are 48.2% in RA patients. No significant differences were found between the two groups in ultrasonographic duplex of their carotid arteries; and no significant differences were found in the endothelial function; but there is a significant association between the cumulative doses of steroids and the thickened IMT (e of GCs . Thus, aEgyptian asymptomatic RA patients exhibited increased carotid IMT and impaired FMD with increasing the frequency of atherosclerosis compared with general population. Thus carotid ultrasonography and endothelial function by flow mediated vasodilatation must be done in all RA patients, which could be simple noninvasive method of identifying preclinical atherosclerosis, in addition to the need for control of rheumatoid disease activity and its inflammatory burden because uncontrolled chronic inflammation is probably the major factor for premature atherosclerosis.


However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7’s role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission.Human genetic studies show that the voltage gated sodium channel 1.7 (Na Drugs were made up in 100% DMSO as a 10 mM stock, except for tetrodotoxin  which was dissolved in water. Final working concentrations were made on the day of the experiments in ECS.v1.7 (hNav1.7) channel resulted from iterative structure activity relationship—based refinement of a series of novel arylsulfonamide Nav channel inhibitors. Arylsulfonamide inhibitors of Nav1.7 . State-dependence of block was likewise assessed. In order to measure compound block at resting state, the original voltage protocol was modified to remove the conditioning step to the half-inactivation voltage, retaining all other aspects of the drug addition and voltage-control parameters  the natural molecular determinant for TTX sensitivity in domain 1    [26 [26v1.7 A-fibres  12] [1] [1]v1.7 A-fibres . Using Red to WT . Taken tv1.7 to both mouse and human sensory neuron action potential firing. In particular, the effects of Nav1.7 inhibitors on mouse DRG rheobase provide the first pharmacological evidence using a small molecule selective inhibitor that native Nav1.7 acts as the threshold channel. These data are consistent with recorded changes in rheobase following Nav1.7 silencing in cultured nodose sensory neurons . Co. Cov1.7 v1.7 inhibitor PF-05198007 in wild-type mouse, but this inhibitor had no effect on the Nav1.7Nav1.8Cre knock-out mouse at the same dose. These data suggest a key role of Nav1.7 in controlling neuropeptide release from peripheral terminals of peptidergic C-fibres and potentially a role in conduction associated with the axon reflex.TRPV1 expression has previously been shown to be limited to C-fibres in mouse  39] [13 [1339] , capsaicv1.7 in neurogenic flare, conduction and presynaptic release. However, peptidergic terminals in the dorsal horn consist of en passant varicosities . Th. Thv1.7 S1 Table(DOCX)Click here for additional data file.


Vertical human immunodeficiency virus (HIV) transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART). Moreover, we detect HIV antiretroviral (ARV) drug resistance among mother–infant pairs and identify subtypes and circulating recombinant forms (CRF) in Burkina Faso.In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer.In this study, 12.26%  of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388) overall vertical transmission of HIV, with rates of 1.75% (2/114) among mothers under prophylaxis and 0.00% (0/274) for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%), CRF02_AG (35.3%), and subtype G (5.9%).ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso. Globally, about 35.3 million people were living with HIV in 2012. Sub-Saharan Africa is the region most affected by the HIV epidemic with approximately 25 million people living with the virus  of HIV-1 in Burkina Faso.From October 2009 to June 2013, 3,215 pregnant women with less than 32 weeks of amenorrhea attended a prenatal consultation at Saint Camille Medical Centre  and agreed to answer a questionnaire and receive counseling for voluntary HIV testing. This medical center has high attendance, mostly from women with low incomes/assets and/or who already know their HIV serology, because the center delivers low cost medical care and laboratory analyses to HIV-positive pregnant women and their families. Pregnant women attended CMSC until delivery and those newborns positive for HIV-1 despite having followed the PMTCT protocol were included in this study. Pregnant women who did not consent to participate were not included in this study.Following WHO recommendations , pregnanVenous blood (6 mL) was collected at the laboratory of Saint Camille Medical Centre on two EDTA-treated tubes and plasma was collected after centrifugation at 4,000 g for 10 min; 1.5 mL aliquots were stored at −80°C. Molecular tests were conducted at the Biomolecular Research Center Pietro Annigoni (CERBA) in Ouagadougou.®  and SD Bioline . When the two tests had discordant results in an individual, a third confirmatory test was recommended immediately, according to the national algorithm, with another kit such as Immunocombs .Serology of HIV testing among women was determined using two rapid tests: DetermineInfants born to mothers infected with HIV were tested 6 months after birth through a PCR (polymerase chain reaction) of HIV diagnosis test on dried blood spot (DBS). Newborn samples detected as positive were immediately sent to another laboratory for confirmation. Meanwhile, children detected as negative for HIV were followed until the age of 18 months.For children diagnosed HIV-1 positive, sequencing was carried out from a venous blood sample after serological confirmation test at 18 months.CD4 cells were counted for mothers using FACSCount techniques and reagents . Patient whole blood was homogenized, 50 µL was collected and placed in each tube of the pair of reactive CD4/CD8. Once all the samples were distributed in pairs of reagents corresponding to each patient, they were incubated in the dark for 1 h. After incubation, 50 µL of a fixative solution was added to each tube and then passed through the FACScount machine.Women HIV Viral loads were determined using the ABBOTT kit and a Real Time PCR M2000 instrument (ABBOTT).DNA was extracted from DBS using the QIAamp DNA Blood Mini Kit  following the manufacturer's instructions.® PCR System 9700 using the kit ‘Generic HIV DNA Cell’  following the manufacturer's protocol.Detection of HIV-1 proviral DNA was carried out in the Applied Biosystems Gene AmpWe used 20 µL of extracted DNA and 50 µL of the Master Mix containing PCR water (2 µL), primers and probe (1 µL), 2×mix (25 µL). The amplification was carried out following these steps: Initial activation for 2 min at 50°C, 10 min at 95°C and a denaturation for 15 sec at 95°C, annealing for 1 min at 60°C during 50 cycles. Afterwards, 10 µL of the amplified DNA mixed with 2 µL of running buffer was migrated on electrophoresis . The UV revelation was done using the Gene Flash Sygene Bio Imaging device.Patients selected for the determination of possible resistance to ARV drugs were the women who, despite ARV treatment, had a CD4 count of <350 cells/µL, a high viral load, or who had transmitted HIV-1 to their children or the children tested positive for HIV-1.® Products, Inc., Cleveland Ohio, USA). After purification of sequence reactions with isopropanol, the sequencing process was started using the ABI PRISM 3,130 Genetic Analyzer .Ribonucleic acid (RNA) was extracted from plasma using the QIAamp Viral RNA Mini Kit  according to the manufacturer's instructions. Reverse transcription of RNA into cDNA, and DNA amplification and sequencing were performed using the complete ViroSeqTM Pack  according to the manufacturer's instructions. The reverse transcriptase (RT)/PCR product was quantified by electrophoresis on an agarose gel at 1% and purified with ExoSAP-IT . However, among HIV-negative pregnant women, many were in their first pregnancy (38.36% vs. 21.91%: p<0.0001).The pregnant women in this study were aged between 18 and 46, with an average age of 26.7±5.6. Among them, there were housewives (54.5%), women working in the informal sector such as trading activities (26.7%), employees (7.6%), high school students (6.8%), and university students (4.5%). Most of the seropositive pregnant women were in their fourth pregnancy or more .Among the 3,215 pregnant women who were tested for HIV, 394 (12.26%) were infected and among them 97.97% women had HIV-1, 1.78% had HIV-2, and 0.25% had coinfection of HIV-1/2. But from 2009 to 2013, HIV prevalence decreased (21.43% vs. 10.46%). Among the 394 pregnant women who tested HIV positive, six of them were lost to follow up and 388 babies were born. A total of 29.38% children were born to mothers under the WHO 2006 prophylactic protocol  and 70.62% were born to mothers on HAART (triple therapy combining AZT/3TC+NVP or D4T/3TC+NVP or 2NRTI+1NNRTI or 2NRTI+ 1PI). The median viral load of mothers whose children tested positive for HIV-1 was 161,231 copies per mL, with mean T CD4 cell counts of 185 cells per µL. The tests for the mothers in our study revealed that transmission was higher among women with low rate of CD4 count and high viral load . With reVertical transmission was very low in our study (0.52%). Among mothers under HAART, there were no cases of HIV transmission, but at the level of triprophylaxis, 1.75% cases of transmission have been reported .Sequencing was performed for 17 patients, including 11 mothers who had followed the PMTCT protocol and six of their children all infected with HIV-1: Four HIV-positive children were taken from the sample of a previous study, two were from mothers who transmitted HIV to their children in this study. These children's mothers were selected in addition to five other mothers with therapeutic failure.In this study, 17 samples were sequenced. Recombinant forms between subtypes A and G of HIV-1 were present in 94.1% cases with: 58.8% of CRF06_CPX and 35.3% CRF02_AG. Subtype G was also isolated in 5.9%. The detected subtypes were the same within each mother–child pair . The various subtypes obtained from the present study in comparison with those of later studies are described in The ratio of resistance to ARV drugs generated from the ViroSeq software  showed the presence of numerous mutations that can cause HIV resistances to ARV drugs . ImportaThe present research work was conducted at Saint Camille Medical Centre in Ouagadougou and is similar to those conducted by Simpore et al. , 14. TheRegarding the screening of HIV in this study, 12.26% of pregnant women 394/3,215) were diagnosed HIV positive. This rate, although high, is lower than 17.7% identified at the same site by Pignatelli et al.  were dia. An evenIn this study, despite the monitoring and treatment of these women during pregnancy, residual risk of transmission to infants born to mothers receiving PMTCT was very low, estimated at 0.52% in total, or 1.72% with prophylaxis and 0.00% with HAART. The global transmission rate obtained in this study is relatively low compared to rate of 4.6% obtained in Cameroon . In BurkLate treatment is also a factor which increases the risk of transmission . There iIn addition to coinfections , 22 and Many mutations can cause HIV-1 resistance to some ARV drugs, for example, the RT inhibitors used in the context of PMTCT in Burkina Faso. In fact, we have found the mutations to be M184V, K103N, and Y181C. Simpore et al.  showed tBeyond the toxicity and mutations induced by the combined use of ARVs, HAART has reduced not only the number of mutations and resistance but also the residual risk of HIV transmission to infants born to mothers receiving PMTCT.Moreover, the presence of 5.9% of HIV-1 subtype G was noted in this study, with a total lack of subtypes A or B. However, previous studies in Burkina Faso found subtype A at varying rates: 10.0% , 6.9% 1 Table 5Table 5. Thus, CRF06_CPX and CRF02_AG are responsible for a great number of infections in West Africa: In Mali : CRF02_AIn this study, it appears that pregnant women under HAART have no risk of vertical transmission of HIV-1. This provides evidence of the effectiveness of the new PMTCT program in Burkina Faso.The CRF CRF06_ CPX and CRF02_AG of HIV-1 are the main strains of infection in our study group. Certainly, ARV treatment significantly reduces vertical transmission of HIV-1. However, it causes mutations that induce resistance of HIV to ART and thus limits the available choice of best drug combination. The real fight against resistance to ARV therefore demands a permanent interaction between researchers, physicians, and pharmacists. Finally, the strengthening of a network of monitoring and surveillance of drug resistance in Burkina Faso is needed.


Clonidine has sedative and analgesic properties. Randomized studies examining these properties in mechanically ventilated ICU patients are scarce. This study was designed to assess the impact of clonidine on sedative agent use in mechanically ventilated patients.In a prospective, randomized, double blind, placebo-controlled study in a general ICU of a university medical center in Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or more randomized into 2 equal groups of clonidine and placebo. Clonidine arm received usual sedation and enteral clonidine 0.1 mg TID and escalated to 0.2 mg TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was used to assess sedation.Opioids and midazolam were used in all patients. 10 patients in clonidine and 3 in placebo arms had history of drug abuse (P = 0.018). The mean of sedatives used in the clonidine/placebo arms (mg/day) were; MED  91.4 ± 97.9/112.1 ± 98.8 P=0.39, midazolam 7.1 ± 7.9/8.3 ± 9.2 P=0.66 and propofol 535.8 ± 866.7/139.1 ± 359.9 P=0.125. After adjusting for addiction and propofol, clonidine reduced MED use by 79.6 mg/day (P=0.005) and midazolam by 5.41 mg/day (P = 0.05).Opioids and midazolam need reduced by clonidine co-administration regardless of history of drug abuse. Acceptable side effect profile and the lower cost of clonidine could make it an attractive adjunct to sedative agents in ICU. Critically ill ICU patients, particularly those on mechanical ventilation are exposed to anxiety, pain and stress . SedatioCommonly used parenteral sedative agents in ICU are benzodiazepines such as midazolam, lorazepam and diazepam; opioids such as morphine, fentanyl, remifentanil, sufentanil and alfentanil; propofol and dexmedetomidine. However each of these drugshas their own problems with possible added adverse effects when they have to be used in combination .Benzodiazepines can be associated with respiratory depression and hypotension, especially if they are given in combination with other cardiopulmonary depressants. In addition, tolerance to benzodiazepines can develop in long-term administration. Propofol can cause dose-dependent respiratory depression, hypotension or in occasions propofol infusion syndrome (PRIS).Dexmedetomidine, a newer α2 receptor agonist that has been approved for short-term 24 h) ICU sedation, is one of the most favored agents. Patients sedated with dexmedetomidine respond to stimuli and arouse easily with minimal respiratory depression  on the assumption that 10 µg of fentanyl and 1 mg of parenteral and 2 mg of enteral methadone was considered equivalent to 1 mg of morphine . Doses oStatistical analysisStatistical analysis was performed using SPSS® 19 Software. Continuous variables in each group of subjects were expressed as mean values ± standard deviation (SD). Differences between mean of two groups were performed using Mann-Whitney u-test. Chi-square test to compare dichotomous variable were used. Linear regression model was applied for assessment of addiction and propofol effect on opioid and midazolam consumption. In all cases a p-value of less than 0.05 was considered to be statistically signiﬁcant.Patient populationFifty five patients, 30 in the intervention and 25 in control groups were enrolled in the study. Ten patients were excluded in the treatment arm; five due to extubation under 3 days, two for administration errors, two due to hypotension and one who died on the second day of enrolment.Five patients were withdrawn from the study in the control arm; three due to extubation under 3 days, one with decreased level of consciousness and one for hypotension. The overall methodology for the study has been presented in the flowchart shown in Basic patient characteristics, the severity of illness based on APACHI II scores measured in the first 24 hours of ICU admission and total duration of the study were not significantly different among two groups. Number of patients with drug abuse were 10 (50%) in intervention and 3 (15%) in the control group, P = 0.018 .Clonidine effect on consumption of sedative agentsOpioids and midazolam were administered to all patients in both groups. Propofol was used for eight and four patients in the treatment and control groups respectively.The mean MED (mg/day) used in the clonidine arm was 91.4 ± 97.9 and placebo arm was 112.1 ± 98.8(P = 0.39) and after excluding 12 patients who received propofol it was 47.4 ± 67 and 101.7 ± 98.7 in the treatment and placebo arms respectively (P = 0.063).The number of patients requiring 4 days of MED were 19 (95%) and 18 (90%) and 7 days of MED were 13 (65%) and 11 (55%) in the placebo and the clonidine arms respectively. Mean daily MED use (mg/day) during the study period reduced by 27.5 ± 14.36 in the clonidine arm and increased by 1.96 ± 18.78 in the placebo arm (P=0.006) .The mean doses (mg/day) of midazolam consumption were 7.1 ± 7.9 and 8.3 ± 9.2 in the intervention and placebo arms respectively (P = 0.66) .The number of patients requiring 4 days of midazolam were 19 (95%) and 19 (90%) and 7 days of midazolam were 13 (65%) and 13 (65%) in the placebo and the clonidine arms respectively. The mean daily midazolam use (mg/day) during the study period reduced by 1.87 ± 1.63 in the clonidine arm and increased by 0.41 ± 0.64 in the placebo arm respectively (P=0.005), .The mean doses (mg/day) of propofol used was 535.8 ± 866.7 in eight patients of intervention arm and 139.1 ± 359.9 in four patients in the control arm (P = 0.125).The effect of drug abuse on sedative requirementTen patients in the treatment arm and three in placebo had history of drug abuse (P=0.018).In patients without and with history of drug abuse the sedative requirements were; MED 64.1 ± 66.2 mg/day and 179.8 ± 108 mg/day (P=0.003), midazolam 5.6 ± 7.7 mg/day and 11.9 ± 8.7 mg/day (P=0.018) and propofol 276.7 ± 658.5 mg/day and 463.5 ± 748.7 mg/day (P=0.188).Linear regression adjustment for the effects of confounding variables such as history of drug abuse and higher propofol use in the intervention arm, 8 versus 4, indicated a reduction in opioid requirement in the clonidine arm by 79.6 mg/day (P=0.005). After similar adjustments for the study groups and propofol use opioid requirement was noted to be 143.4 mg/day lower in patients with no history of drug abuse (P = <0.001).Adjusting for clonidine and history of drug abuse did not indicate any significant effect of propofol on opioids use, P=0.24 .Adjustment for propofol and drug abuse indicated a reduction of midazolam use by 5.41 mg/day in the presence of clonidine (P = 0.05). Similar adjustments for the study groups and propofol use showed a reduction of midazolam by 7.9 mg/day (P=0.008) in patients with no history of drug abuse. Adjusting for clonidine and history of drug abuse did not indicate any significant effect of propofol on midazolam use (P=0.07) .Clonidine adverse effectThere were no significant differences between heart rate, systolic, diastolic and mean arterial blood pressure in the treatment and control group.In our randomized double blind placebo-controlled study, we evaluated the effects of clonidine as a sedative adjunct in mechanically ventilated ICU patients. Clonidine was started in doses of 0.1 mg three times daily via feeding tube. This dose was escalated to 0.2 mg three times daily on the following day if hemodynamics remained stable.The mean MED and midazolam requirement did not show any significant reduction in the clonidine arm in our initial analysis. However the analysis of daily changes in MED and midazolam use indicated a significant reduction of its requirement in the clonidine arm in subsequent days, particularly during the first four days of the study.Adjustments for confounding variables such as history of drug abuse and unequal number of patients receiving propofol in the treatment and placebo arms, revealed a significant reduction of MED and a near significant reduction in midazolam requirement in the clonidine arm.  and 4.The higher doses of midazolam used in day 6 were caused by an increased requirement for targeted sedation, by the 3 patients with history of drug abuse in the clonidine arm.Opium, based on surveys in our patient population, is the commonest drug of abuse. We observed a significantly increased opioid requirement in patients with history of drug abuse in both arms of the study which is most likely secondary to the increased tolerance to opioids in these patients. Higher mean doses of propofol used in the treatment arm, albeit statistically insignificant, was due to the larger number of patients on tis agent than the placebo arm. This in turn, could have been due to the significantly higher number of patients with history of drug abuse, in the clonidine arm, with generally greater requirement for the targeted sedation.Clonidine is a α2-adrenoceptor agonist introduced to the pharmaceutical market in 1960s for its antihypertensive effect . It has Controlled studies examining the place of clonidine as an ICU sedative agent or adjunct to other agents are limited in medical literature.The efficacy of clonidine for decreasing alcohol withdrawal symptoms in ICU patients on mechanical ventilation for over seven days was evaluated and published in an abstract form. In this study ten patients received clonidine intravenous infusion with fentanyl and midazolam infusion and 10 received fentanyl and midazolam infusion. Midazolam consumption was 34% lower in the treatment group. Sympathetic hyperactivity symptoms seen in 60% of placebo group were not observed in the clonidine arm. Forty multiple trauma patients on long-term mechanical ventilation with symptoms of sympathetic hyperactivity receiving fentanyl and midazolam for sedation, were studied by the same authors. Clonidine infusion led to decreased heart rate to lessthan 120/min in 90% of patients within 24 hours with reduction of fentanyl and midazolam requirement by 38% ± 19% within 24 hours .In another work, clonidine administration significantly decreased the withdrawal symptoms after sedation interruption in mechanically ventilated patients. This resulted in reduced respiratory, metabolic and hemodynamic demands and facilitated patient cooperation with the ventilator and weaning process .In a small retrospective study of thirteen patients, clonidine was shown to reduce the opioid and benzodiazepine needs in ICU patients. In nine patients on opioids, the average daily dose was 44.7 mg morphine before and 28.2 mg after clonidine administration. In the eleven patients on lorazepam the daily dose was 14.6 mg pre and 3.9 mg post clonidine administration and six of seven patients receiving concomitant clonidine and propofol showed reduction in the requirement for propofol .To our knowledge our study is the first randomized, placebo-controlled trial, examining the effects of predefined doses of clonidine co-administrated with other sedative agents in mechanically ventilated ICU patients.Small sample size and simple randomization, which could not allow us better stratification of subgroups such as patients with history of drug abuse, are the main limitations of our study. Larger multicenter trials are needed to further elucidate our findings.Clonidine administration reduced opioids and benzodiazepines requirement significantly in mechanically ventilated ICU patients with or without history of drug abuse. However clonidine co-administration did not change propofol requirement. We did not observe any important adverse reactions of clonidine in the doses administered in our study.Cost constraint and difficulties to access drugs such as dexmedetomidine, particularly in the third world countries and FDA current approval of this agent for only 24 hours could make clonidine a relatively safe and attractive adjunct to other ICU sedative agents.


The aim of the study is to compare efficacy of IvIg versus PE in treatment of mechanically ventilation adults with GBS in intensive care unit.It is a prospective, non randomized study, realized in a medical ICU from 2006 to 2010. We included all patients with GBS who required mechanical ventilation (MV). We defined two groups: group 1 (group treated by IvIg: 0.4 g/kg/day for 5 days) and group 2 (group treated by PE: 4 PE during 10-14 days). We collected demographic characteristics, clinical and therapeutic aspects and outcome. Statistical analysis used: The quantitative variables are expressed on mean ± standard derivation and compared by Student test. The statistic analysis has been based on SPSS for windows. P < 0.05 is considered as significant.Forty-one patients (21 in group 1 and 20 in group 2) were enrolled. The mean age was 37.4 ± 9.2 years, with a masculine predominance (75.4%). Electromyogram in all patients found acute inflammatory demyelinating polyradiculoneuropathy in 80.5% of patients. The mean length of hospitalization was 45.3 ± 9.2 days. The length of hospitalization of the IvIg group is less long than PE group (p = 0.03). The weaning of the MV was more precocious in IvIg group than PE group (p = 0.01). Also, the beginning of motility recuperation was precocious at IvIg group than PE group (p = 0.04).Our work reveals a meaningful difference for the MV weaning and precocious recovery in IvIg group compared to PE group. Guillain-Barré syndrome (GBS) is a demyelinating polyradiculoneuropathy with an acute paralysing disorder, typically symmetric and ascending and areflexia. Incidence varies between 0.66 and 1.79 cases per 100 000 persons in general population . Our aim2 less than 90% in room air requiring increasing FiO2, or showed clinical symptoms of CO2 retention. When patients were able to trigger spontaneous breathing, they were changed to a pressure-support spontaneous ventilation mode. Pressure support was gradually decreased to 10 cmH2O. If secretions were manageable with good airway reflexes, a daily spontaneous breathing trial (SBT) was performed using a T-piece for 12 to 24 hours. Patients were extubated if SBT was successful. SBT was declared successful if there was no increased work of breathing or apnea, symptoms of hypercapnia, tachycardia and if SpO2 remained well compared to pre-SBT value. The quantitative variables are expressed on mean ± standard derivation and compared with Student tes. The statistic analysis has been based on SPSS 10.0 for windows. P < 0.05 is considered as significant.It is a prospective, monocentric non randomized study, realized in a medical ICU in Ibn Rochd university hospital of Casablanca which is a tertiary referring medical centre, during 5 years. We included all patients with GBS who required mechanical ventilation (MV). The diagnosis was according to clinical criteria . We defiBetween January 2006 and December 2010, 41 patients were enrolled, 21 in group 1 (IvIg group) and 20 in group 2 (PE group). No medical history was found in all patients. The mean age was 37.4 ± 9.2 years, with a masculine predominance (75.4%). There was a statistically insignificant age between the two groups, 35.4 ± 8.4 years for IvIg group versus 39.3 ± 5.2 years for PE group. Symptoms preceding the onset of GBS were fatigue in all patients, gastro-intestinal infections in 13 (32%) patients and nasopharyngitis in 21 (51.2%). The main initial sign was limb weakness followed by muscle pain in all patients and paresthesia in 20 (49%) patients. The mean time from the onset to the maximum of illness in all patients was 8.3 ± 4.2 days. There was no involvement of the cranial nerves in all patients. Autonomic dysfunction was reported in 20 (49%) during hospitalisation such hypotension-hypertension and/or bradycardia and/or excessive sweating. The reason for admission in the ICU was respiratory impairment. Twenty eight patients were admitted from the emergency department, 13 patients were transferred from the department of neurology. Lumbar puncture was performed on all patients; the mean of CSF protein was elevated (0.95 ± 0.1 g/l) in 29% of patients without CSF cell change. Based on electrophysiological findings, in 33 (80.5%) patients had acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) in 8 (19.5%) patients. The mean length of hospitalization was 45.3 ± 9.2 days (range 30 to 118 days). The ICU stay was significantly shorter (p = 0.03) in the IvIg group than PE group. Patients receiving IvIg were early weaned of MV (p = 0.01) compared to those receiving PE with a statistical significance. Also, the beginning of motility recuperation was significantly precocious (p = 0.04) in IvIg group than PE group . Both grOur results suggest that IvIg is more benefit for our patients than PE. For the IvIg group, the ICU stay was shorter, weaned earlier of MV and the beginning of motility recuperation was precocious than PE group. According to two reviews published in the Cochrane library 2012, patients treated within two weeks from onset with IvIg had recovery as much as PE ; and comAlthough the results of the literature are not conclusive, our work of which the most important slant is the absence of randomization, reveals that there is a meaningful difference for the MV weaning and a precocious recovery in IvIg group compared to the PE group. These encouraging results would merit to be confirmed by controlled and randomized works.


Monotherapy against HIV has undoubted theoretical advantages and has good scientific fundaments. However, it is still controversial and here we will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r) on patients who have received this treatment in our hospitals.Observational retrospective study that includes patients from 10 Andalusian hospitals that have received DRV/r in MT and that have been followed over a minimum of 12 months. We carried out a statistical descriptive analysis based on the profile of patients who had been prescribed MT and the efficacy and safety that were observed, paying special attention to treatment failure and virological evolution.3 at 24 weeks.DRV/r was prescribed to 604 patients, of which 41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had received an average of five lines of previous treatment and had a history of treatment failure to analogues in 33%, to non-analogues 22 and protease inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The simplification was the main criteria for the instauration of MT in the 81.5% and the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6% additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three genotypes were performed after failure without findings of resistance mutations to DRV/r or other IPs. Only 23.7% of patients presented some blips during the period of exposition to MT. Eighty seven percent of all determinations of VL had <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of voluntary decision. Although the average of total and LDL cholesterol increases 10 mg/dL after 2 years of follow-up, so did HDL cholesterol in 3mg/dL and the values of triglycerides (−14 mg/dL) and GPT (−6 UI/mL) decreased. The average count of CD4 lymphocytes increased from 642 to 714/mmIn a very broad series of patients obtained from clinical practice, data from clinical trials was confirmed: MT with DRV as a de-escalation strategy is very safe, it's associated to a negligible rate of adverse effects and maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL) is always under 10% and in any case without consequences.


The metropolitan area of Barcelona is the most densely populated metropolitan area on the Mediterranean coast. Several studies have reported the presence of canine heartworm disease in this region; however, there are no published epidemiological data regarding feline heartworm in this region and the prevalence in this species remains unknown.D.immitis and anti-Wolbachia antibody detection were used while a commercial ELISA test kit was used to detect circulating D.immitis antigens.Serum samples from 758 cats living in the metropolitan area of Barcelona (Spain) were collected between 2012 and 2013. To establish the seroprevalence of heartworm infection in cats, serological techniques for anti-D.immitis and Wolbachia surface protein antibodies and 0.26% were positive to D.immitis antigens. The higher antibody seroprevalences were found in the areas that follow the courses of the rivers Llobregat and Anoia  where humidity and vegetation favour the development of the mosquito vectors. High antibody seroprevalences were also found in the urban areas , which demonstrates that city cats are also at risk from D.immitis infection.Of these samples, 11.47% were positive to Generally, in Spain cats do not receive prophylactic treatment and therefore the risk of infection is higher in this species than in dogs. Adequate prophylactic plans should be implemented in the feline population. This is the first epidemiologic study on feline heartworm infection to be carried out in continental Spain. Dirofilaria immitis (heartworm) is a vector-borne zoonotic parasite. Transmission occurs through different species of culicid mosquitoes belonging to the genera Culex, Aedes and Anopheles, among others [D. immitis is the causative agent of pulmonary dirofilariosis characterized by the development of benign pulmonary nodules that mimic malignant pulmonary nodules [g others . The domg others . Further nodules .Cats are inherently resistant to heartworm infection. This is reflected by relatively low adult worm burden, the lack of microfilaremia and their short life span, which complicates the diagnosis of this disease in the feline patient. The non-specific clinical signs, generally of a respiratory or digestive nature, are usually confused with other diseases, as well as the frequent asymptomatic course of feline dirofilariosis in which the sudden death of the animal is sometimes the only clinical sign shown All the afore mentioned contribute to the difficulty of the diagnosis in this species .Recently feline heartworm disease has been increasingly diagnosed due to heightened awareness of the disease in cats, improved diagnostic methods and the increasing number of cases reported in the last few years. It is now generally accepted that heartworm disease may occur in cats in any area where dogs are infected, with a prevalence rate of infections in cats between 5% and 20% of that for dogs in the same geographical area .In Europe, heartworm disease is endemic in Mediterranean countries ,8, althoD. immitis in cats from the metropolitan area of Barcelona.Despite the numerous studies that have been carried out in canine heartworm, there are no published epidemiological data regarding feline heartworm in this region. In fact, no data on feline heartworm in continental Spain have been published to the authors’ knowledge. So far, this subject has only been studied in the Canary Islands . The aimThe present study included 758 client-owned cats presented to veterinary clinics. Of these, 56.5% were males and 43.5% were females. By breed, 77.2% were domestic shorthair, 12.3% were Persian, 6.7% were Siamese and 3.8% other breeds. The age ranged from 6 months to 18 years, with a mean range of 6.8 years. 56% of the cats were indoor , 28% was outdoor  and 16% for cats that spent at least 1–50% of their time outdoors (indoor/outdoor).The samples were collected at 27 veterinary centres located in the studied area, from cats presented to veterinary clinics between September 2012 and September 2013. The animals lived in 6 of the 7 regions which form the metropolitan area of Barcelona: Alt Penedés, Baix Llobregat, Barcelonés, Maresme, Vallés Occidental and Vallés Oriental , clinical history, and demographic data. All owners gave their consent to participate in the study. The study was approved by the ethical committee of Veterinary Medicine Service of Las Palmas de Gran Canaria University and was carried out in accordance with the current European legislation on animal protection.D.immitis and anti-Wolbachia antibody detection were used, as described by Morchón et al. [D. immitis somatic antigen and Wolbachia surface protein (WSP). Serum samples were prepared at 1/100 for anti-D.immitis serum antibodies and 1/40 for anti-WSP antibody detection. Anti-feline IgG antibody, horseradish peroxidase-labelled , was applied at 1/4000 dilution. The optical densities were measured in an Easy-Reader  at 492 nm. Cut-off points of ELISA D. immitis 0.8 and ELISA WSP 0.6 were obtained as arithmetic mean optical density ±3 standard deviations of serum of clinically healthy cats. The cats were considered seropositive when anti-D.immitis and anti-WSP antibodies presented jointly [Blood samples were collected from the cephalic or jugular vein, placed in 3 ml serum tubes and centrifuged. Serum was kept at –20°C until tests were performed. To establish the seroprevalence of heartworm infection in cats, serological techniques for anti-n et al.  with som jointly ,17.D.immitis antigens using a commercial immunochromatographic test kit  according to manufacturer’s instructions.All feline serum samples were tested for circulating χ2 and Fischer exact tests to compare proportions were performed. In all cases, the significance level was established at p < 0.05.Data were analyzed using SPSS Base 20.0 software for Windows . Descriptive analysis of the considered variables was carried out considering the proportions of the qualitative variables. D.immitis and WSP antibody seropositivity, of these 62.1% were males and 37.9% were females (p < 0.001)., Seroprevalence by age was 8.1% (<1 year), 9.7% (1-3 years), 13.7% (3-6 years), 13% (6-9 years), 9.5% (9-12 years), 10.8% (12-15 years) and 12% (>15 years), with no significant differences between groups. By breed, the higher prevalences were observed in Siamese cats (19.6%), mixed breed cats (18.2%) and domestic shorthair cats (11.3%), followed by Persian cats (9.7%), while the seroprevalence in the other studied breeds was 0%. Seroprevalence for outdoor cats was 21.2%, compared with 7.05% for indoor cats and 9.9% for indoor/outdoor cats (p < 0.001). Of the seropositive cats, 24.1% (21/87) showed respiratory signs (p < 0.001). By regions, the higher seroprevalences were found in cats living in Vallés Occidental 13.2% (14/106), Barcelonés 11.7% (28/239) and Baix Llobregat 11.5% (42/366). Lower seroprevalences were found in Maresme 9.1% (1/11) and Alt Penedés 6.4% (2/31). Vallés Oriental showed a seroprevalence of 0% (0/5). There were no statistically significant differences between regions except Vallés Oriental. In Sabadell  15.5% of the cats studied were seropositive (9/58) (p < 0.001) while in the urban area of Barcelona (located within Barcelonés) there were 13.1% seropositive cats (16/199) (p < 0.001).11.47% (87/758) of cats showed D.immitis antigens. Of the 2 cats that tested positive, one lived in the urban area of Barcelona (Barcelonés) and the other one in Baix Llobregat. Both cats were outdoors and tested positive to antibodies tests.0.26% (2/758) of the cats tested positive to D. immitis in cats in Barcelona and in continental Spain, previously only having been reported in the Canary Islands and in the North of Portugal [D. immitis in the distal pulmonary arteries in cats, this has been previously reported in seropositive cats from Barcelona [The present study is the first epidemiological report of seroprevalence of Portugal ,17. 11.4Portugal . AntibodPortugal . Of the arcelona ,20.D.immitis antigens. The sensibility of antigen testing is relatively low in cats, and because these tests only detect adult and female worms a negative result does not rule out an infection from male worms or pre-adult worms, most of which are common in cats [Only 0.26% of cats were positive to  in cats . Further in cats ,22. Henc in cats . It is eThe particular climatic conditions (Mediterranean climate) in Barcelona make it an endemic area for heartworm. These conditions are favourable for the development of the mosquito vectors. The results showed that the higher antibody seroprevalences are mainly found following the courses of rivers and streams Figure , where vMeanwhile, higher antibody seroprevalences were present in the urban areas of Vallés Occidental  and Barcelonés . Furthermore, one of the cats that tested positive to the antigen test lived in the urban area of Barcelona, close to an urban park. These results demonstrate that city cats are also at risk from heartworm infection. It has been described that building construction and human activity increase the density of potential hosts and develop a suitable environment for the proliferation of certain species of mosquitoes due to an increase in the provision of water sources and vegetation ,25. BesiD.immitis in cats living outdoor was observed when compared with cats living indoor or outdoor/indoor. Although an indoor lifestyle does not protect cats from infection, a higher prevalence is to be expected in outdoor cats, and our results are similar to those reported in previous studies [A higher rate of positivity for  studies .In the light of previous studies carried out in canine heartworm disease, with a prevalence of 2-2.5% [


This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI) to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB. Hepatitis B virus (HBV) infection is a major cause of chronic liver disease. Globally, there are over 400 million people infected with HBV, and infection-related complications such as severe liver failure have become a significant global health problem . It is wEighty-eight HBeAg-positive patients who met the inclusion criteria were selected from our hospitals between July 2007 and July 2013. The patient population included 57 males and 31 females, with an average age of 8.9 ± 5.6 years (range: 1 to 18). The following inclusion criteria were applied: CHB diagnosis conforms to the relevant criteria based on the Viral Hepatitis Prevention and Treatment Programs as previously reported [Hepatic function, routine blood tests, hepatitis B surface markers, and HBV DNA quantification were evaluated within 1 day before liver biopsy. Liver samples with the length of over 15 mm were taken twice from the region of interest by a Bard Magnum biopsy gun with diameter 1.4 mm. Two passages of hepatic tissue samples obtained from every patient were then sliced, stained, and observed under a microscope. The Scheuer scheme was adopted as the pathological diagnostic standard , 4, 15. An automatic biochemistry analyzer and an automated hematology analyzer measured the aspartate transaminase (AST) and platelet (PLT) levels just one day before the liver biopsy. The APRI was calculated as follows: AST (ULN)/PLT (109/L) .X ± S, an independent-samples t-test was used for comparison between two groups, and an ANOVA was used for comparison between more than two groups. Qualitative information R × C table was expressed by χ2 test. Spearman correlation analysis was used to inspect the degree of correlation between the APRI and liver fibrosis and inflammation. Logistic regression analysis was used for the prediction of risk indicator of liver fibrosis and inflammation. The result of pathological examination was taken as the “gold standard” to calculate sensitivity (Se) and specificity (Sp) of liver fibrosis and inflammation that were corresponding with each diagnostic cut-off value of the APRI and to make the receiver operating characteristic (ROC) curve. The area under the receiver operating characteristic curve (AUROC) was calculated by Hanley-McNeil nonparameter, calculating the corresponding positive predictive value (PPV) and negative predictive value (NPV). Differences were considered statistically significant at P < 0.05.SPSS16.0 statistical software was used for statistical analysis. Quantitative data was expressed as P < 0.01). The basic patient characteristics of the groups with mild and significant fibrosis are shown in Table S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2015/906026. Logistic regression analysis of those indicators that were significantly different revealed that albumin (ALB) (P = 0.036), PLT (P = 0.044), and APRI (P = 0.005) were predictive indices of the risk of liver fibrosis, with an OR of 0.85 (95% CI: 0.73–0.99), 0.99 (95% CI: 0.98–1.00), and 2.85 (95% CI: 1.38–5.89), respectively.In our cohort of 88 adolescent patients with CHB, 45 cases had mild liver fibrosis , and 43 had significant liver fibrosis , including 11 cases with S3 fibrosis and one with S4 fibrosis. The APRI value (0.86 ± 0.58) for patients with mild liver fibrosis was significantly lower than the patients with significant fibrosis . Logistic regression analysis revealed that ALB (P = 0.010), cholinesterase (CHE) (P = 0.000), and APRI (P = 0.005) were predictive indices of the risk of liver inflammation, with an OR of 0.82 (95% CI: 0.70–0.95), 0.99 (95% CI: 0.99–1.00), and 4.16 (95% CI: 1.55–11.18), respectively.With regard to liver inflammation, 31 patients had mild liver inflammation , and 57 patients had significant liver inflammation , including five cases with G3 inflammation and one with G4. The basic patient characteristics of the groups with mild and significant liver inflammation are shown in Table S2. Statistical analysis revealed that the APRI value (0.75 ± 0.46) in the patients with mild liver inflammation was significantly lower than the group with significant inflammation  and inflammation stages , respectively.If an APRI value of 0.5 and 1.5 was taken as the cut-off value to divide patients into three groups , the percentage of patients with significant liver fibrosis (≥S2) in each group was 22.2% (4/18), 51.9% (27/54), and 75% (12/16) and that with significant liver inflammation (≥G2) was 38.9% (7/18), 64.8% (35/54), and 94.1% (15/16), respectively. These values were significantly different (P < 0.05). Using an APRI of 0.40 as a cut-off point to judge patients who developed liver fibrosis (≥S1), the corresponding PPV and NPV were 98.7% and 18.2%, respectively (P < 0.05). Using an APRI of 0.83 as a cut-off point to judge patients who developed significant liver fibrosis (≥S2), the corresponding PPV and NPV were 71.7% and 76.2% . Using an APRI of 0.85 as a cut-off point to judge patients who developed significant liver inflammation (≥G2), the corresponding PPV and NPV were 82.2% and 53.5%, respectively (P < 0.05)  .In order to evaluate the correlation between age and liver fibrosis or inflammation using the APRI, we divided our patient population into three age groups, including those patients that were ≤6 years old, between 6 and 12 years old, and >12 years old. Based on the results described above, a cut-off value for the APRI to predict liver fibrosis and inflammation was set at 0.83 and 0.85, respectively. The diagnostic value of this index is shown in Tables The APRI may be the most accurate and simple marker for predicting significant fibrosis in CHB and CHC. Although clinical significance of this index in WHO guideline of prevention and treatment of HBV infection is recommended for assessing the degree of liver fibrosis –3, its pWith regard to the relationship between APRI and inflammation, several studies have shown that the APRI is associated with liver necroinflammation in the patients with CHB and CHC , 7. HoweIt is worthy of our attention that only few patients with S4 fibrosis and G4 inflammation were enrolled in this study, and patients with S3 fibrosis and G3 inflammation also represented a minor fraction of our study population. This distribution of disease severity reflects the fact that severe necroinflammation and cirrhosis are rarely detected in adolescent patients. However, this population cannot remove HBV infection and it is known that persistent viral infection can lead to persistent occult development of liver diseases and the occurrence of irreversible cirrhosis. Thus, we think the diagnostic usefulness of the APRI to indicate significant fibrosis (≥S2) or inflammation (≥G2) is important to identify disease progression in this young patient population, thereby facilitating timely treatment. A diagnostic tool is considered as a good tool if the AUROC is greater than 80%, excellent if the AUROC is greater than 90%, and perfect if the AUROC is 100%. According to these results, the APRI may not be considered as a good tool for predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis. However, APRI is a simple and cheap method and is suitable to monitor the dynamics status of some liver diseases –18.Conclusively, this study supported that the APRI model can predict significant liver fibrosis and (the cut-off point for prediction of significant liver fibrosis was 0.83) and inflammation (the cut-off point for prediction of significant liver inflammation was 0.85). The clinical significance of this index predictive of liver fibrosis and inflammation seemed advantageous in CHB patients with age of 6–12 y compared with age of ≤6 y or ≥12 y. Our data suggested that this index should be an important tool for auxiliary diagnosis. However, clinical significance of APRI in adolescent HBeAg-negative patients is still to be demonstrated.Answer: Table S1: Univariate analysis of variables associated with significant liver fibrosis in 88 adolescent patients with CHB. In this table, the clinical indicators including ALB, PLT, gender, age, total bilirubin (TBIL), APRI, Prothrombin time activity(PTA),ALB, Log10(HBV DNA), cholinesterase (CHE) were investigated with univariate analysis between 45 cases with mild liver fibrosis (S1) and 43 with significant liver fibrosis (≥ S2).Table S2: Univariate analysis of variables associated with significant liver inflammation in 88 adolescent patients with CHB. In this table, the clinical indicators including ALB, PLT, gender, age, total bilirubin (TBIL), APRI, Prothrombin time activity(PTA), ALB, Log10(HBV DNA), cholinesterase (CHE) were investigated with univariate analysis between 31 patients with mild liver inflammation (G1) and 57 patients with significant liver inflammation (≥ G2).


Staphylococcus aureus in patients with psoriasis and in healthy persons. Patients and methods: a comparative study that include 33 patients with psoriasis and 33 healthy persons. Samples were taken from lesional and non lesional psoriatic skin and from healthy skin of control group. For S. aureus nasal carriage, we used sterile cotton tipped swabs. Out of165 samples , 26 S. Aureus strains were isolated in 26 persons, 57.69% in the control group and 42.3% in the psoriasisgroup. S. aureus skin colonization was found in one case (3%) inlesional psoriatic skin vs 9 cases (27.3%) in control skin OR=0.08 IC 95% (0.01-0.70) p=0.02 and in 12,1% in non lesional soriatic skin vs 27, 3% in control skin . This colonization was less important in lesional psoriatic skin (3%) than in non lesional psoriatic skin (12.1%) p= 0.20. Nasal screening identified (7/33) 21, 21% S. aureus carriers in psoriasis group and in control group. Our results are in consensus withliterature findings. They have confirmed the importance of antimicrobial peptides in Innateimmunity of human skin. These peptides are normally produced bykeratinocytes in response to inflammatory stimuli such as psoriasis. Their high expression in psoriasis skin reduces the risk of skin infection and skin colonization with S. Aureus.Psoriatic lesions are rarely complicated by recurrent infections. The aim of our study is to determine skin colonisation and nasal carriage of  S. Aureus which usually resides on the skin, has also been implicated in the pathogenesis of psoriasis [S. aureus in patients with psoriasis vulgaris and in healthy persons.Psoriasis is a chronic inflammatory skin disease which is thought to affect up to 5% of the world's population . In the soriasis . The plasoriasis . Few stusoriasis . The aimPatients: this is a comparative study performed in a university outpatient setting for 6 months. The study participants included 33 patients with psoriasis vulgaris and 33 healthy subjects. The inclusion criteria were patients with chronic plaque psoriasis aged over 16 years. None of the patients had received ultraviolet light or systemic therapies previously and none had received topical corticosteroids or antibacterial treatment for at least two weeks before enrollment. The study got approval from the Research and Ethical Committee of the Faculty of Medicine and Pharmacy of Casablanca, Hassan II University. The patients and healthy persons signed a written consent after being informed about the study.S. aureusCollection of : S. aureus skin colonization was obtained using Count-Tact Agar plates . Specimens were collected in the psoriasis group from the psoriasis plaques and from non lesional skin of the back and in the control group from healthy skin of the back. For S. aureus nasal carriage, we used sterile cotton tipped swabs. The specimens were obtained by 5 rotations in each anterior nare of patients and healthy persons. All samples were quickly sent to the bacteriological laboratory.S. aureusIsolation and identification of : the studywasconductedat the Laboratory of Molecular Bacteriology of the Pasteur institute, Casablanca, Morocco. The Count-Tact Agar plates were incubatedaerobicallyat 36°C for 24 to 48 h. The nasal swabs were inoculated on Chapman agar , and incubated at the same conditions. After incubation, The colonies were identified on the basis of their morphologies, mannitol fermentation, catalase test and Gram staining, coagulase activity on rabbit plasma , production of clumping factor  and biochemical features using theApi Staph Bio-Mérieux France microorganism identification test kit. The homogeneous strains were stored at 4°C in nutrient agar until use, and at -20°C in glycerol stocks using commercial Cryobilles .Antimicrobial resistance: Antibiotic sensitivity of S. aureus strains was obtained using the agar disc diffusion method on M-H medium  according to the recommendations given by the CA-SFM (2012). The following antimicrobial agents  were tested: cefoxitin (30 μg), penicillin G (6 μg), tetracycline (30 μg), erythromycin (15 μg), lincomycin (15 μg), pristinamycin (15 μg), kanamycin (30 μg), tobramycin (30 μg), gentamicin (10 μg), chloramphenicol (30 μg), rifampicin (5 μg), fosfomycin (50 μg), pefloxacin (5 μg), trimethoprim/sulfamethoxazole (1.25/23.75 μg), fusidic acid (10 μg) and vancomycin (30 μg). S. aureus isolates were considered as multidrug resistant (MDR) when they were resistant to 3 or more of the antibiotics listed above.Methicillin sensitivity: Methicillin susceptibility was studied by using agar screen plates on Muller-Hinton (M-H) agar  with 30 μg/ml of cefoxitin disc as recommended by the French Microbiological Society Antibiogram Committee (CA-SFM 2012). Inhibition diameter around cefoxitin disks less than 27 mm after incubation at 36°C for 18-24 h. reflects MRSA suspicion. MRSA U2A1593 and methicillin-susceptible S. aureus U2A1594 provided by Pasteur Institute  were used as controls.Statistical Analysis: Data was analyzed using SPSS statistical software, version 16.0 . Chi-Square test was used to assess the differences between proportions of S. aureus strains isolated in psoriasis lesional skin, psoriasis non-lesional skin and control skin. Odds Ratio was calculated to assess the association between S. aureus skin colonization and psoriasis. A  was considered as statistically significant.S. aureus strains was isolated in 26 persons, 15/26 (57. 69%) in the control group and 11/26 (42. 3%) in the psoriasis group (Out of 33 psoriasis patients 10 were women (30. 3%) and their mean age at the time of enrollment was 43. 21(SD=15.80). Of the 33 control individuals, 14 were women  and their mean age at the time of enrollment was 38. 94 (SD=14. 35). Diabetes was found in 3 patients in the psoriasis group versus 2 persons in the control group. In the 165 samples  obtained from 66 subjects, a total of 26 is group .Cutaneous colonization: S. aureus skin colonization was found in one case (3%) in lesional psoriatic skin versus 9 cases (27.3%) in control skin OR=0.08 IC95% (0.01-0.70) (p=0.02) and in 4 cases (12.1%) in non lesional psoriatic skin versus 9 cases (27. 3%) in control skin OR=0.37 IC95% (0.10-1.34) (p =0.13). This colonization was less prevalent in lesional psoriatic skin (3%) than in non lesional psoriatic skin (12.1%) OR=0.23 IC95% (0.02-2.15) p= 0.20. Bacterial load of S. aureus was more important in control skin. Intense bacterial load of S. aureus (> 300 colonies) was not found in lesional psoriatic skin however it was found in 3% in non lesional psoriatic skin and in 9.1% in control skin, but these associations were not significant too.Nasal carriage: Nasal screening identified 21, 21% S. aureus carriers in psoriasis group and 21, 21% S. aureus carriers in control group.Antibiotic susceptibility: A total of 10 various resistance phenotypes were found for the 26 S. aureus strains isolated  was found in one nasal carriage in the psoriasis group and Methicillin resistant S. aureus (MRSA) was found in three cases (12%) in control skin. Multi-resistance to three antibiotic classes or more was not observed in lesional psoriatic skin isolates while 1 (3%) and 2 (6.1%), Multi-resistant S. aureus were found respectively in non lesional psoriatic skin and in control skin. The difference was not statistically significant.isolated . The conisolated . Wild-tyS. aureus colonization was significantly higher in the control skin than in the lesional psoriatic skin (27.3% vs 3%) OR=0.08 IC95% (0.01-0.70) (p=0.02). Thus, the psoriasis is a protective factor against skin S. aureus colonization. This difference was already reported by Fahlen et al [S. aureus infection and antimicrobial peptides in patients with atopic dermatitis, psoriasis and in normal subjects; the authors highlighted the role of antimicrobial peptides in innate immunity of human skin and in the ability of the skin to resist bacterial infection. They explained that Cathelicidins (LL-37) and defensins (HBD-2) belonging to this antimicrobial peptides family contribute to hostdefense against S. aureus.In our study, we have revealed that the percentage of S. aureus. They concluded that a deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus. The antimicrobial peptides HBD-2 and LL-37 are normally produced by keratinocytes in response to inflammatory stimuli such as psoriasis or injury [S. aureus [S. aureus colonization was less important in non lesional psoriatic skin (12.1%) than in control skin (27.3%) however the difference was not significant (p= 0.13). It has recently been reported that the skin flora varies depending on the site from which the samples are taken [S. aureus skin colonization in non lesional psoriatic skin and control skin is not related to the site of skin biopsy, but rather to antimicrobial peptides production. These results are in consensus with findings by Peck and al [The results of this study showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions . The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing r injury . Their hre taken , 12. There taken , 13. Howk and al , 13.S. aureus in non lesional psoriatic skin (12.1%) compared with control skin (27.3%) and in lesional psoriatic skin (3%) compared with non lesional psoriatic skin(12.1%). Moreover, intense bacterial load was more important in control skin followed by non lesional psoriatic skin then by lesional psoriatic skin. This difference may be related to a local production of antimicrobial peptides which is more important in psoriatic skin [S. aureus nasal carriage rate in the present study was found to be 21, 21% in both psoriasis group and control group. These findings are consistent with figures that usually quoted for S. aureus nasal carriage of 20-40% [S. aureus strains, the control group showed the highest number of resistance. MRSA was found in 12% of isolates, all originating in control group skin. Multi-resistance to three antibiotic classes or more was not observed in lesional psoriatic skin isolates compared with 3% and 6.1% multi-resistant S. aureus respectively in non lesional psoriatic skin and in control skin. The difference was not statistically significant. Further studies are required to determine genetic characteristics of S. aureus strains isolated.Thus in our study, HBD-2 and LL-37 could be present in non lesional psoriatic skin since psoriasis is an inflammatory disease with a production of systemic inflammatory cytokines. These cytokines could lead to increased synthesis of antimicrobial peptides by keratinocytes even in non lesional psoriatic skin but in low rates. This hypothesis could explain the poor colonization with tic skin . S. auref 20-40% . When asS. aureus colonization from control and psoriasis groups shows some differences. However, the number of samples was very limited and further work is needed to investigate these possible differences and to compare the expression of antimicrobial expression in different sites.Our study suggests that skin Psoriasis lesions are rarely complicated by recurrent infections.S. aureus colonization was more important in normal skin of control group compared with psoriatic skin.S. aureus colonization was more important in non lesional psoriatic skin compared with lesional psoriatic skin of the same patients.


To evaluate the feasibility of using pseudo-continuous arterial spin labeling (pCASL) perfusion in a geriatric population at 1.5-Tesla.In 17 participants (mean age 78.8±1.63 years) we assessed; 1) inter-session repeatability and reliability of resting state perfusion in 27 brain regions; 2) brain activation using finger-tapping as a means to evaluate the ability to detect flow differences; 3) reliability by comparing cerebral blood flow (CBF) with pCASL to CBF with phase contrast (PC-MR).B) was larger than the SDw for all regions. Comparison of CBF at rest and activation on a voxel level showed significantly higher perfusion during finger tapping in the motor- and somatosensory regions. The mean CBF for whole brain GM was 40.6±8.4 ml/100g/min at rest and 42.6±8.6 ml/100g/min during activation. Finally the reliability of pCASL against the reference standard of PC-MR was high (ICC = 0.80). The mean CBF for whole brain measured with PC-MRI was 54.3±10.1 ml/100g/min and 38.3±7.8 ml/100g/min with pCASL.The CBF (mean±standard deviation (SD)) for the whole brain grey matter (GM) was 40.6±8.4 and 41.4±8.7 ml/100g/min for the first and second scan respectively. The within-subject standard deviation (SDw), the repeatability index (RI) and intra-class correlation coefficient (ICC) across the 27 regions ranged from 1.1 to 7.9, 2.2 to 15.5 and 0.35 to 0.98 respectively. For whole brain GM the SDw, RI and ICC were 1.6, 3.2 and 0.96 respectively. The between-subject standard deviation (SDThe results demonstrate moderate to high levels of repeatability and reliability for most brain regions, comparable to what has been reported for younger populations. The performance of pCASL at 1.5-Tesla shows that region-specific perfusion measurements with this technique are feasible in studies of a geriatric population. Arterial spin labeling (ASL) can be used to visualize and quantify cerebral blood flow (CBF), an important physiological parameter used in the diagnosis and assessment of neurological disorders as well as for an examination of brain function . SeveralHowever, ASL techniques are emerging as a tool for clinical use and the availability of systems at field strength of 1.5-Tesla are more widely available. Further, most extant studies are limited to young subjects. There is a need for reliability studies in older persons where there are specific issues that need to be accounted for when aiming for reliable measures. Older persons are at high risk for neurodegenerative disorders, and more detailed assessment of localized brain regions is needed. Motion artifacts in MR images that degrade their quality and clinical utility may be more likely to occur in older compared to younger adults. Imaging with ASL of older persons is also challenging due to age related morphological alterations of vasculature such as increased vessel tortuosity and damage of arteriole walls  shown toThe objective of this study was to evaluate the feasibility of using pseudo-continuous arterial spin labeling (pCASL) in very old individuals with a commercial 1.5-Tesla MRI system. To our knowledge, there is no other study in the current literature that has assessed pCASL reproducibility in localized brain regions in a geriatric population at 1.5-Tesla.We assessed the following; 1) inter-session repeatability and reliability of resting state perfusion in template driven brain regions including GM and WM with and without white matter hyperintensities (WMH); 2) task-driven brain activation in GM regions as a way to assess the ability of pCASL to detect flow changes; and 3) reliability of pCASL by comparing whole brain CBF values generated with pCASL to whole brain CBF values generated with phase contrast -MRI as a reference standard.The volunteers for this study were recruited from participants in the prospective population based Age Gene/Environment Susceptibility-Reykjavik Study . RepeateAll scans were acquired on a 1.5-Tesla Signa system , Waukesha, WI). In the first session when subjects were at rest, imaging with pCASL was followed with phase contrast (PC)-MRI for quantification of total CBF (tCBF). Anatomical imaging was acquired for brain tissue segmentation. The pCASL imaging was performed with the product sequence from GE , which af is the perfusion, S is the signal on the control- (Sctrl), label- (Slbl) or reference image (Sref), λ is the blood brain partition coefficient (0.9 ml/g), α is the labeling efficiency (assumed to be 0.80), T1b is the T1 of blood (assumed to be 1400 msec). The same T1 of blood was assumed for men and women [g of 1200 msec (assumed T1 of GM), tsat is the saturation time (2000 msec), w is the post-labeling delay and τ is the labeling duration.The quantitative CBF maps were generated using software v16, M4) on the GE scanner console computer with a method proposed by Wang et al [, M4 on tWhole brain tissue segmentation of GM, WM, WMH and cerebral-spinal-fluid (CSF) was done on intensity normalized and non-uniformity corrected anatomical images in MNI Talairach space, using a trained classifier . RegionaFor assessing the ability of pCASL to detect flow differences, statistically significant differences in perfusion between brain activation and rest were determined voxel-wise within MNI-space. Testing for significance was performed by permutation testing using the FSL software randomize with 5000 permutations . The perThe PC-MR images were processed using the software package FLOW  . The sofw), a measure of measurement error was calculated as the square root of the residual mean square within subjects using one-way ANOVA [B) was calculated in the same way as SDW but from residual between subjects mean square. Third, the repeatability index (RI), defined as the 95% confidence limits for the difference between repeated measurements was calculated using [w with the overall mean of CBF for both scans [The repeatability and reliability of pCASL was assessed by comparing the CBF measurements from the two scans at rest in the 27 ROIs. Several statistical parameters were included in these assessments that individually or all together have commonly been used in previous studies addressing ASL perfusion repeatability including Bland-Altman plot demonstrating the agreement between the first and second scan at rest for whole brain CBF , 21. Theay ANOVA . The beted using :RI=2x1.th scans . Lastly,th scans .For assessing the ability of pCASL to detect flow differences, statistically significant differences in perfusion between brain activation and rest were determined voxel-wise after correcting for multiple comparisons.For the assessment of reliability of pCASL compared to PC-MRI, the ICC was calculated and a paired t-test used to assess difference between whole brain resting mean CBF values generated with the two techniques. Level of significance for all analyses was set to <0.05. All statistical analyses were performed with SAS/STAT®9.2 (SAS Institute Inc).B for the two pCASL scans acquired at rest, and the measures of repeatability and reliability. There was no statistically significant difference between the two resting scans for any of the 27 ROIs except for the occipitotemporal gyrus (p = 0.04). The SDB was larger than SDw in all regions. There was a significant negative correlation between regional volume and SDw . Small ROIs had generally greater within-subject variability compared to large ROIs.Study sample characteristics are summarized in The CBF (mean±SD) for the whole brain GM was 40.6±8.4 and 41.4±8.7 ml/100g/min for the first and second scan respectively. The corresponding CBF values for normal WM were 35.2±7.1 and 35.1±6.3 ml/100g/min and for total WM 34.6±7.2 and 34.5±6.5 ml/100g/min . The GM/Women had higher CBF values than men for whole brain (42.3±7.4 vs. 35.8±7.2), whole brain GM (45.2±8.1 vs. 38.0±7.7), whole brain normal WM (37.8±6.5 vs. 33.3±6.4) and whole brain total WM (37.5±6.5 vs. 32.5±6.5). This difference was not statistically significant for any of these regions.w, RI, CoV) for whole brain GM were 1.62 ml/100g/min, 4.50 ml/100g/min and 4.10% respectively, for whole brain normal WM 1.34 ml/100g/min, 3.71 ml/100g/min and 3.9% respectively and for whole brain WMH 2.16 ml/100g/min, 5.98 ml/100g/min and 9.11% respectively . As with pCASL, women showed on average higher mean whole brain CBF with PC-MRI than men . Measurements of CBF using pCASL showed high level of reliability when considering CBF using PC-MRI as a reference standard; the ICC between PC-MRI and pCASL was 0.80.The aim of this study was to evaluate the feasibility of using perfusion imaging with pCASL on a 1.5-Tesla MRI system in an elderly population. The motivation of the study was the increasing clinical use of ASL and great promises of ASL for the assessment of neurodegenerative disorders as evidenced by fast growing literature , 25, 26.The mean CBF estimates at rest for whole brain GM of this study are consistent with values reported in the PET and ASL MRI literature for healthy elderly individuals , 27, 28,The mean CBF for total WM were significantly lower than mean CBF in normal WM. Hypoperfusion in areas of WMH is consistent with findings in two other studies , 36 and Women had on average higher CBF values than men for whole brain regions although this difference was not statistically significant. Higher CBF in women compared to men is in accordance with other ASL perfusion studies , 11, 27 The estimates of inter-session reproducibility and reliability in this study do not suggest increased variability in perfusion of healthy elderly subjects when compared to other ASL studies of younger subjects. In a study by Wang et al , reproduW for all 27 regions, there was no statistically significant difference between the two scans at rest for 26 of the 27 regions and the ICC reflected moderate to high reliability for 24 out of the 27 regions  and the sensory receptive area for the sense of touch  have been well established in the literature . The meaThe reliability of pCASL was also tested by comparing it to PC-MRI as a reference standard. Flow quantification with PC-MRI is a well-established, robust method  that hasThis study has several limitations. Small sample size may explain lack of statistical significance in perfusion sex differences. The non-triggered PC-MRI scan used as a reference standard may contain noise and ghosting due to cardiac pulsation and physiologic fluctuations resulting in inaccuracies in the flow quantification. Further, averaging flow information over the cardiac cycle compared to trigger the scan to the cardiac cycle has been shown to give rise to a loss of information in the periphery of the vessels, resulting in artificially high flow values . The assIn conclusion, the overall results of this study demonstrate moderate to high level of repeatability and reliability for majority of regions, comparable to what has been reported in younger populations with 3.0 Tesla MRI systems. The performance of pCASL on a 1.5-Tesla system in this study shows that perfusion measurements in brain regions of very old individuals are feasible.