After extensive counseling as to the diagnosis of fetal CMV and t

After extensive counseling as to the diagnosis of fetal CMV and their options, including pregnancy termination, the couple chose to continue the pregnancy. After consultation with an infectious disease specialist, CMV immune globulin (200 U/kg, for a total Cisplatin cost dose of 10 g intravenous [IV]) was recommended starting at 25 weeks of gestation with subsequent doses of 5 g IV planned at monthly intervals. Fetal magnetic resonance imaging (MRI) at 25 weeks of gestation showed no evidence of intracranial calcifications or abnormalities. Figure 1 Representative perinatal ultrasound image showing fetal echogenic bowel. Fetal echogenic bowel refers to increased echogenicity or brightness of the fetal bowel noted on second trimester ultrasound examination. The diagnosis of echogenic bowel should …

At 30 weeks of gestation, following 2 doses of CMV immune globulin, the fetal heart-rate tracing was noted to have absent variability and repetitive late decelerations (category III). A biophysical profile was 2/10 (2 points for amniotic fluid volume only) and umbilical artery Doppler velocimetry showed reversed end-diastolic flow. A viable female infant was delivered by emergent cesarean weighing 920 g with Apgar scores of 2, 7, and 10 at 1, 5, and 10 minutes, respectively. Cord blood analysis showed an arterial pH of 7.16 and base excess of ?12.5 and venous of pH 7.29 and base excess of ?8.9. The neonate was intubated and admitted to neonatal intensive care. Chest radiography showed ground glass opacities consistent with congenital CMV pneumonia.

Hematologic abnormalities included thrombocytopenia, coagulopathy, elevated transaminase levels, and hyperbilirubinemia. CMV antigenemia was present in the infant��s blood, and CMV DNA was identified in urine and cerebrospinal fluid. Placental pathology showed diffuse fibrin deposition and villous edema. Specific immunostaining of the placenta was positive for CMV (Figure 2). Figure 2 Representative histologic images of a placenta with cytomegalovirus (CMV) infection. (A) Placental histology shows moderate villous edema, intervillous fibrin deposition, amnion hyperplasia, and grade I inflammation. (B) Specific immunostaining confirms … The infant was treated with IV gancyclovir (6 mg/kg twice daily) with subsequent resolution of laboratory and imaging abnormalities over a 10-day period.

Ultrasound examination of the head and abdomen showed no evidence of calcifications, ventriculomegaly, or hepatosplenomegaly prior to treatment. Ophthalmologic examination showed no evidence of retinitis. However, the infant failed multiple newborn hearing screens and appeared to have Cilengitide profound bilateral deafness. Antiviral therapy was continued for 6 weeks. The infant was discharged home in stable condition on day of life 55. Discussion CMV infection is very common in the United States, with 50% to 80% of reproductive-age women showing serological evidence of previous infection.

The residents were asked to state factors that could promote rese

The residents were asked to state factors that could promote research. Most of them (66%) admitted that guidance from senior faculty was essential. Forty-six percent thought that reduction of working hours ARQ197 of residency could lead to more research involvement and 40% felt that financial assistance would help to promote research. Forty-four percent considered that a system of extra credit points for research-related presentations and publications would be helpful. DISCUSSION Postgraduate students are introduced to the concept of designing and conducting research during residency. Medical research carried out by undergraduate and postgraduate students in India is disappointing compared to developed countries. To date research has not become a mandatory part of the curriculum of undergraduate medical education in India.

In Germany, where research is an integral part of undergraduate medical curriculum; medical students were involved in 28% of the publications in a particular institution.[11] A study reported that in a European country, Croatia, 23% of the undergraduate students were involved in research projects.[12] We carried out this study to assess the awareness of residents toward research and to find out whether the current methods of training and facilities are adequate to foster a research culture in postgraduate students. This study showed various key findings that would be of interest to medical educators and policy makers. It was found that knowledge about the need and prerequisites of research was fairly good among resident doctors.

Furthermore, they also showed a positive attitude toward medical research. However, there was disparity found with regard to their attitude toward medical research and actual participation. Although a majority of the postgraduate medical residents wished to get involved in research, very few had Drug_discovery participated in research work, other than the mandatory dissertation project. Moreover, very few had presented research papers at conferences or had publications. Discrepancy between attitude and practice was also highlighted in a study done in Faisalabad, in India. Although a large majority of postgraduate trainees of the Allied Hospital in Faisalabad appreciated the importance of reading current literature, only a few actually read journals and were actively involved in presenting research papers and making scientific contributions to the literature.[13] Similar selleckchem Brefeldin A results were obtained in a study done in Madison, in USA. Out of 143 postgraduate students, 85% felt that research experience was desirable, 48% were interested in pursuing research during residency, and only 8% were active in research.

Changes in CSF tau, MRI volume and cerebral metabolism may occur

Changes in CSF tau, MRI volume and cerebral metabolism may occur slightly later than changes in CSF A?? [41,49,51]. Amyloid PET imaging studies have yielded inhibitor Tipifarnib results similar to those from autopsy and CSF studies. Studies using 11C-PIB have reported amyloid-positive scans in 14 to 47% of cognitively normal elderly volunteers [40,43,52-55], and 55 to 72% of subjects with MCI [51,54-57]. Where data from both 11C-PIB PET scans and CSF A?? have been available, strong correlations between these measures have generally been reported [49,57]. Results with 18F-labeled imaging agents are similar to those for 11C-PIB. The proportion of A??-positive scans in cognitively normal subjects has ranged from 7% and 12% with flutametamol [29,30], to 13% with florbetapir [26], and 20% with florbetaben [28].

In MCI subjects the proportion of positive scans was about 50% for flutametamol [30] and florbetaben [58] and about 38% in the studies with florbetapir [59]. The difference across PET studies, which are similar to the difference in the pathological studies of cognitively normal controls and MCI, could easily be related to difference in subject age and inclusion criteria rather than difference in sensitivity of the different tracers. Consistent with findings in the autopsy literature [45,60], the proportion of cognitively healthy control subjects that are A??-positive by PET scan increases with age [26,30,44,49,53]. The mean age of cognitively healthy subjects varied by more than 10 years across the studies above [29,55]. Additionally, the florbetapir trial [58] was designed to evaluate early stage MCI patients, diagnosed within the past year.

These subjects may be more difficult to diagnose and thus more heterogeneous, leading to inclusion of a greater number of subjects with non-amyloid/AD-related impairments. Batimastat Jagust and colleagues [40], reporting on 11C-PIB subjects from the ADNI study, further evaluated quantitative values (cortical to cerebellar SUVR) for the A??-positive and A??-negative subjects by diagnostic presentation group (cognitively healthy, MCI and AD). Interestingly, there was no apparent difference in SUVR between A??-positive MCI and A??-positive AD, but SUVR in A??-positive MCI and AD both appeared greater than SUVR in A??-positive healthy controls.

These results are consistent with histopathology findings [47], indicating that the relative proportion of patients with high versus moderate levels of A?? pathology at autopsy (definite versus probable AD by CERAD criteria) does not increase from MCI to AD patients, and suggests that A?? accumulation reaches asymptote at now early stages of disease. Together with the image-autopsy results described above [27], these results suggest that PET imaging can detect the presence of A?? aggregates sufficient to support a pathological diagnosis of AD in upwards of 15% of cognitively healthy elderly subjects (prevalence increasing with age) as well as in 40 to 70% of subjects with MCI.

White matter and cognitive reserve White matter atrophy was highl

White matter and cognitive reserve White matter atrophy was highlighted in 1989 when, in a quantitative neuropathological study of elderly brains, it was found that people without cognitive decline but with some AD pathology had atrophy of white matter but not of grey matter, whereas those with dementia and more extensive AD pathology had both grey and white matter atrophy. It was suggested that selleck chemicals llc white matter atrophy may precede whole brain atrophy in ageing brains [27]. Neuroimaging has taken this concept further. O’Sullivan and colleagues [28] described reduced diffusional anisotropy, a measure of white matter integrity, and higher mean diffusivity in elderly people with normal cognitive performance for age compared with young control subjects.

Another early diffusion tensor imaging study identified reduced white matter integrity in the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum whereas the pyramidal tracts were spared [29]. Bartzokis and colleagues [30] found, using the transverse relaxation rate, that people who were ApoE4-positive, and therefore at increased risk to develop AD (though they performed cognitively normally when examined), had a reduced cognitive processing speed, which was significantly correlated with myelin breakdown in late myelinating white matter regions. Presymptomatic carriers of familial AD mutations have altered diffusion tensor imaging signal in white matter throughout the brain and particularly in the perforant pathways, the fornix, and orbito-frontal white matter [31].

It was suggested that the changes in the fornix in particular may provide a biomarker for early disease in sporadic AD. Andrews-Hanna and colleagues [32] used functional MRI signal correlations between regions within large-scale brain systems in young and old cognitively normal subjects (mean Mini-Mental State Examination in the elderly score of 28.8) and showed marked reductions with age in normally present functional correlations within two higher order brain systems. The Anacetrapib worst affected system was the anterior to posterior components within the default network. Reduced correlations were associated with loss of white matter integrity. Abnormalities in the default mode network were also detected selleck kinase inhibitor using resting state paradigms in mild cognitively impaired subjects [33]. The level of deactivation differed in the anterior frontal, precuneus and posterior cingulate in AD when compared to controls, and the level of deactivation was intermediate in mild cognitive impairment. Both studies suggest activity in the default mode network may provide a marker for early changes and indicate continuity between normal ageing and so-called pathological ageing.

Most non-converters retain high functioning over the duration He

Most non-converters retain high functioning over the duration. Hence, therefore cognitive flexibility can be useful for discriminating future conversion outcomes, but does not appear as informative as episodic memory level 2. Finally, in Figures ?Figures8a8a and ?and8b,8b, for perceptual motor speed, note that there appears to be a subset of converters for whom perceptual motor speed becomes more impaired. While there are non-converters who also have low probability values, this number is outweighed by the converters over the duration. Moreover, as Table ?Table55 indicates, these converters are likely to also be relatively more impaired with episodic memory level 2 than the non-converters. This allows us to identify this particular combination of lower level functioning as being specifically associated with high risk for conversion.

Multivariate prediction using logistic regression models A multivariate model was fit that recognized the above findings, and included other variables such as gender, age, and educational level. The presence of an APOE4 allele was viewed as a binary variable, as well as whether or not a subject had attended college. Also, probability values for performing at a relatively high level for episodic memory level 2, cognitive flexibility, and perceptual motor speed were viewed as continuous explanatory variables. After an initial fit of a full model, gender, age, and educational level were clearly not significant predictors in the model (respective P-values were 0.96, 0.65, and 0.81; Wald’s test).

Using goodness-of-fit tests based on the test statistic of -2 times the difference in log-likelihood values to compare nested models, it appears the best fit is when episodic Drug_discovery memory level 2, perceptual motor speed, and APOE4 status are included in the model. Results are given in Table ?Table6.6. Note that episodic memory level 2, perceptual motor speed, and APOE4 status all are significant predictors (P-value <0.05; Wald's test). When cognitive flexibility is included with these variables, it is not significant (P-value = 0.26). Table 6 Multivariate logistic regression model with outcome as conversion to Alzheimer's disease (AD) from mild cognitive impairment (MCI) within 24 months from baseline Using the model-based estimated probabilities of converting to AD as a predictor, and for instance, using a cutoff value of 0.

55 or higher, classification accuracy is 66.8%, with positive predictive value of 61.5% (32 out of 52). Figure ?Figure99 displays receiver operating characteristic (ROC) curves for these logistic regression probabilities, as well as for the probabilities for episodic memory selleck kinase inhibitor level 2, perceptual motor speed, and cognitive flexibility. Values for the area under the curve (AUC) are 0.710, 0.678, 0.655, and 0.644, respectively. Using a multivariate approach can thus apparently improve prediction.