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Psychiatry

Maternal Antibodies May Trigger up to 25% of Autism Cases

Judy Van de Water, PhD, and colleagues have coined the term "maternal autoantibody–related," or MAR, autism

Maternal antibodies that interfere with fetal brain proteins during pregnancy may be responsible for roughly one quarter of cases of autism spectrum disorder (ASD), a new study suggests.

Critical Role in Brain Development
The antigens include the following: lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2), and Y-box-binding protein.
In 246 mothers of children with ASD and 149 mothers of typically developing children, maternal reactivity to any of these antigens, individually or in combination, was statistically significantly associated with having a child with ASD (odds ratio, 3.26; 95% confidence interval, 1.92 - 5.53), the researchers found.
Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of children with ASD and in only 1% of mothers of typically developing children.
Behaviorally, the researchers found that children with ASD whose mothers have autoantibodies targeting a subset of these antigens had greater overall impairment compared with children with ASD whose mothers lack these particular antibodies.
This study, coupled with several prior studies, provides "compelling evidence" that placental transfer of maternal antibodies could alter fetal neurodevelopment and could play a role in autism, they note.
"Each of the target autoantigens...is known to have a critical role in the developing brain and interference with the level or function of more than one of them could act synergistically to change the trajectory of brain development," the investigators write.
"The effect of MAR autoantibodies could occur through a direct antigen–antibody interaction, thereby either decreasing the abundance of or causing functional interference of the target proteins. Alternatively, the presence of these maternal antibodies may merely serve as a biomarker of cell destruction," they point out.
Clinical Implications
Dr. Van de Water told Medscape Medical News that their new findings have potential implications for diagnosis and treatment.
"We can work toward the development of a clinical test to determine the risk of having a child with autism preconception or during the early postnatal period, which would be especially important in the high-risk population of those women who already have at least 1 child on the spectrum," she said.
"It's important to note that this would be a rule-in test, as a negative result would not necessarily mean that you would have a typically developing child, but if you are positive, your risk of having a child with ASD is greater than 99%," she added.
"The second implication is that we can explore a target therapeutic approach in the future through a better understanding of the specific antibody targets," Dr. Van de Water said.
She said her group is now working on identifying the specific sites on the protein targets that are recognized by the MAR antibodies (the epitopes), "which will allow us to build a more specific animal model. We will use this model to determine the mechanism through which these antibodies affect neurodevelopment, or their true pathologic significance."

source from 

Medscape Medical News by M.Madan Mohan. Librarian, VMMC.

'Caution' Warranted if Consuming Artificial Sweeteners

Consumption of noncaloric, artificially sweetened beverages (ASBs) is associated with an increased risk for disease variety of chronic diseases, according to an opinion article by Susan E. Swithers, PhD, a professor of behavioral neuroscience at Purdue University in West Lafayette, Indiana, published online July 10 in Trends in Endocrinology & Metabolism.

"Frequent consumers of these sugar substitutes may...be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease,"

The prospective studies Dr. Swithers reviewed found an elevated risk for weight gain and obesity, metabolic syndrome, type 2 diabetes, coronary heart disease, and hypertension in those who consumed ASBs. No decreased risk for weight gain or increased body fat percentage was associated with ASB intake.

 "In [the] short-term, ASBs is preferable to the use of SSBs. For those who want to kick the habit of drinking sugary soda, diet soda may be the beverage equivalent of a nicotine patch: it can be used in small amounts, for a short time. For most people, plain water and unsweetened coffee or tea are more healthy alternatives to either SSBs or ASBs,"
Hormones, Brain Response Altered

Dr. Swithers reviewed 2 interventional studies. The first found that children of normal weight who consume ASBs may have decreased weight gain compared with those who consume SSBs. In the second study, overweight and obese adults who substituted water or ASBs for SSBs had no greater weight loss at 6 months than an attentional control group.

Brain responses are altered in those who consume artificial sweeteners compared with those who consume caloric sweeteners. In imaging studies of the human brain, sucrose activates dopaminergic midbrain areas involved with reward, but sucralose does not. Sucralose also reduces activation in other pathways related to taste when compared with sucrose.

 Dr. Swithers concludes "Current findings suggest that caution about the overall sweetening of the diet is warranted, regardless of whether the sweetener provides energy directly or not,"

Source from Medscape Medical News  by M.Madan Mohan. Librarian VMMC.

AVIAN INFLUENZA

Human infection with avian influenza A H7N9 virus: an assessment of clinical severity Hongjie Yu MD a †, Benjamin J Cowling PhD

Summary

Background

Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013.

Methods

We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk.

Findings

Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26—45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60—77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76—90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63—460) and 2800 (1000—9400) per 100 000 symptomatic cases.

Interpretation

Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human 

This article available The Lancet Journal 2013. Further details Contact: Librarian. VMMC

JOURNAL OFCLINICAL ORTHOPAEDICS AND TRAUMA

JOURNAL OF CLINICAL ORTHOPAEDICS AND TRAUMA AVAILABLE PRINT COPY MONTH OF JUNE 2013. VOLUME 4 NO.2.

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HEPATIC ARTERY DOPPLER INDICES:

HEPATIC ARTERY DOPPLER INDICES:

DEFINATION:

Hepatic Artery Resistive Index: (HARI): Peak systolic velocity minus end-diastolic velocity divided by the peak systolic velocity.

The Early Systolic Acceleration (ESA) in the hepatic artery is the slope of tangent of the initial systolic upsweep of the arterial waveform i.e. duration of upstroke from end-diastolic to peak systole, measured using calipers. The time corresponding to ESA was computed and this was referred to as the Hepatic Artery Acceleration Time (HAAT) in sec. The Value used in this study was obtained by taking an average of three measurements.

The Hepatic Artery Acceleration Index (HAAI) is the ratio between the acceleration of the Doppler special waveform and the relative peak systolic velocity. The systolic acceleration was calculated as a change in the distance between the beginning of systolic flow and the peak systolic velocity (cm/sec), divided by the acceleration time. The acceleration index is expressed in frequency units as KHz/sec or in velocity units as cm/sec^{2 .}

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