Breastfeeding and cognitive development of children: assessment at one year of age

Breastfeeding is the fundamental component of child survival strategy. It significantly influences neurological development of children. The study was conducted to assess whether exclusive and prolonged breastfeeding improves children's cognitive development, including low birth weight (LBW) babies, in a developing country setting like Bangladesh. This observational study was done on a cohort of newborn infants who were discharged from the special care baby unit of Dhaka Shishu Hospital during January 2006 to December 2008 with proper counseling about exclusive and prolonged breastfeeding. Their neuro-developmental follow-up was started at 4 weeks postnatal age and continued at 3-monthly intervals up to 1 year of age. At each visit, cognitive development was assessed using the Bayley Scales of Infant Development (BSID II). Cognitive development was compared between the babies of exclusive vs. non exclusive breastfeeding, normal weight vs. low birth weight and male vs. female babies. A total of 105 cases were successfully followed-up during this period. Out of these 47(44.8%) babies were exclusively breastfed up to 6 month of age and 58(55.2%) were in nonexclusive group. Overall Psychomotor Development Index (PDI) was slightly more (108.40 ± 23.06 vs. 103.23 ± 19.87) in the exclusive breast fed babies in comparison to nonexclusive breast fed babies, but was significantly more in babies having birth weight >2.5 kg in comparison to those having birth weight of <2.5 kg. Other parameters of cognitive development were more or less same in both normal and LBW groups. Mental and motor development was same in both boys and girls. In behavior ratings, cooperation was significantly high (5.89 ± 2.54 vs. 4.71 ± 3.13, p=0.05) and vocalization (5.89 ± 1.07 vs. 4.58 ± 1.16) was also high, though not significant, in girls than boys.     

Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring

In the United States, marijuana is one of the drugs most abused by adolescents, with females representing a growing number of users. In previous studies, treatment of adolescent female rats with morphine significantly altered brain reward systems in future offspring. As both cannabinoid and opioid systems develop during adolescence, it was hypothesized that early exposure to cannabinoids would induce similar transgenerational effects. In the current study, female rats were treated with the cannabinoid receptor (CB1/CB2) agonist WIN 55,212-2 or its vehicle for three consecutive days during adolescent development (30 days of age), and were subsequently mated in adulthood (60 days of age). The adolescent and adult male offspring of these WIN 55,212-2 (WIN-F1)- or vehicle (VEH-F1)-treated females were tested for their response to morphine using the conditioned place preference (CPP) paradigm. Both adolescent and adult WIN-F1offspring exhibited greater sensitivity to morphine CPP than their VEH-F1 counterparts. Collectively, the findings provide additional evidence of transgenerational effects of adolescent drug use.     

Diallyl trisulfide as an inhibitor of benzo(a)pyrene-induced precancerous carcinogenesis in MCF-10A cells

Diallyl trisulfide (DATS) is a garlic organosulfide that is toxic to cancer cells, however, little is known about its effect in the initiation phase of carcinogenesis. We sought to determine whether DATS could inhibit the carcinogen, benzo(a)pyrene (BaP), from inducing precancerous activity, in vitro. MCF-10A cells were either pre-treated (PreTx) or concurrently treated (CoTx) with 1 μM BaP, and 6 or 60 μM DATS for up to 24 h. The DATS 6 and 60 μM CoTx inhibited BaP-induced cell proliferation by an average of 71.1% and 120.8%, respectively, at 6 h. The 60 μM DATS pretreatment decreased BaP-induced G2/M cell cycle transition by 127%, and reduced the increase in cells in the S-phase by 42%; whereas 60 μM DATS CoTx induced a 177% increase in cells in G1. DATS effectively inhibited (P < 0.001) BaP-induced peroxide formation by at least 54%, which may have prevented the formation of BaP-induced DNA strand breaks. In this study, we reveal mechanisms involved in DATS inhibition of BaP-induced carcinogenesis, including inhibition of cell proliferation, regulation of cell cycle, attenuation of ROS formation, and inhibition of DNA damage. At the doses evaluated, DATS appears to be an effective attenuator of BaP-induced breast carcinogenesis, in vitro.     

Genetic Association of DLG5 R30Q with Familial and Sporadic Inflammatory Bowel Disease in Men

Background: The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania. Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex™ Genotyping System in 473 samples. Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p=0.006), and separately with CD (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p=0.015 vs 0.241 (IBD), p=0.024 vs 0.190 (CD), and p=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p=0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families. Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.     

Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary and pancreatic disorders

Little is known about the role of fat-soluble vitamins K and D in liver function and bone metabolism in biliary and pancreatic diseases associated with cholestasis and/or fat malabsorption. The aim of this study was to determine vitamin K of bone, vitamin D and parathyroid hormone status in patients with biliary and pancreatic disorders. In 90 consecutive patients (mean ± SD age, 65.5 ± 17.7 years; 45 females) undergoing endoscopic retrograde cholangiopancreatography (68 with choledocholithiasis, 14 with other benign condition, and 8 with cholangiopancreatic cancers) fasting concentrations of carboxylated (cOC) and undercarboxylated osteocalcin (ucOC), 25-hydroxyvitamin D, calcium, phosphorus, magnesium, prothrombin time, liver function tests, lipase, and creatinine were measured. Vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was found in 45.6% of patients and elevated parathyroid hormone levels in 27.8%. The ratio ucOC/cOC (index of vitamin K deficiency) was above 20% in 50.6% of patients, above 30% in 31%, and above 50% in 18.4%. Hyperbilirubinemia was a significant independent predictor of low cOC (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.9-59.4; P = .07). The ratio ucOC/cOC positively correlated with alanine aminotransferase levels (r = 0.410; P < .001). Elevated γ-glutamyltransferase (>180 U/L) and international normalized ratio (>1.1) levels were significant independent predictors of ucOC/cOC greater than 30% after adjustment for other covariants (OR, 5.5; 95% CI, 1.2-25.2; P = .027, and OR, 3.1; 95% CI, 1.1-8.8; P = .036, respectively). This study demonstrates that vitamin K and vitamin D deficiencies are common in patients undergoing endoscopic retrograde cholangiopancreatography. Liver dysfunction is associated with and predictive of vitamin K deficiency of bone and decreased production of osteocalcin, indicating the need for appropriate supplementation.     

The clinical outcome of small (<20 mm) arterially enhancing nodules on MRI in the cirrhotic liver

OBJECTIVES: To evaluate the outcome of arterially enhancing nodules (AENs) measuring <20 mm detected on MRI in patients with cirrhosis. METHODS: Prospective analysis of 54 patients with a total of 161 AENs <20 mm on MRI. Inclusion criteria included a minimum of 12 months of MRI follow-up or histological evaluation of the AEN. Key exclusions were patients with an AEN >20 mm or prior diagnosis of HCC. Two radiologists blinded to the clinical and pathological data reviewed serial MRIs and classified the AENs as no longer visible, stable, increasing, or decreasing in size. RESULTS: A total of 161 AENs were identified and were followed by serial MRI for a mean of 24 months. Eighty (50%) AENs were no longer visible on repeat imaging, 42 (26%) remained stable, 1 of which was diagnosed as HCC on short-term follow-up, 8 (5%) increased in size and were subsequently diagnosed as HCC, and 24 (15%) decreased in size. In addition, 7 AENs (4%) were diagnosed on biopsy immediately following the initial MRI. Overall MR characteristics diagnostic of HCC were growth > or =2 mm and peripheral rim enhancement on initial MRI. CONCLUSIONS: The majority (90%) of AENs <20 mm in cirrhosis are benign. The presence of rim enhancement or interval growth of an AEN are suggestive of HCC.     

Reduced eye gaze explains "fear blindness" in childhood psychopathic traits

ObjectiveDamage to the amygdala produces deficits in the ability to recognize fear due to attentional neglect of other people's eyes. Interestingly, children with high psychopathic traits also show problems recognizing fear; however, the reasons for this are not known. This study tested whether psychopathic traits are associated with reduced attention to the eye region of other people's faces.MethodAdolescent males (N = 100; age mean 12.4 years, SD 2.2) were stratified by psychopathic traits and assessed using a Tobii eye tracker to measure primacy, number, and duration of fixations to the eye and mouth regions of emotional faces presented via the UNSW Facial Emotion Task.ResultsHigh psychopathic traits predicted poor fear recognition (1.21 versus 1.35; p < .05) and lower number (1.85 versus 2.51; p < .001) and duration (375 versus 620 ms; p < .001) of eye fixations, and fewer first foci to the eye region (1.01 versus 2.01; p < .001). There were no differences in gaze indices to the mouth region. All indices of gaze to the eye region correlated positively with accurate recognition of fear for the high psychopathy group, especially the number of times that subjects looked at the eyes first (r = .50; p < .01).ConclusionsAttention to other people's eyes is reduced in young people with high psychopathic traits, thus accounting for their problems with fear recognition, and is consistent with amygdala dysfunction failing to promote attention to emotional salience in the environment.     

Abeta-globulomers are formed independently of the fibril pathway

Soluble A beta-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the beta-amyloid cascade hypothesis was extended by A beta-oligomers and their central neuropathogenic role in AD. However, the molecular structure of A beta-oligomers and their relation to amyloid fibril formation remains elusive. Previously we demonstrated that incubation of A beta(1-42) with SDS or fatty acids induces the formation of a homogeneous globular A beta-oligomer termed A beta-globulomer. In this study we investigated the role of A beta-globulomers in the aggregation pathway of A beta-peptide. We used in vitro assays such as thioflavin-T binding and aggregation inhibitors like Congo red to reveal that A beta-peptide in its A beta-globulomer conformation is a structural entity which is independent from amyloid fibril formation. In addition, cellular Alzheimer's-like plaque forming assays show the resistance of A beta-globulomers to deposition as amyloid plaques. We hypothesize that a conformational switch of A beta is decisive for either fibril formation or alternatively and independently A beta-globulomer formation.