An analysis of two recent epidemiologic reports in the New England Journal of Medicine associating breast cancer in women with moderate alcohol consumption

Two cohort studies showed an association between moderate alcohol consumption and breast cancer, with an apparent relative risk of 1.50. Drinkers and nondrinkers already differed in important ways at the initiation of these two studies, precluding a causal interpretation of the associations found. Women in need of the relaxing effect of alcohol may indeed be the group at higher risk for breast cancer. Inasmuch as the studies did not inquire into other cancers, morbidities, mortalities, or total mortality, they leave open the possibility that, on balance, moderate alcohol consumption is beneficial.     

Fetal motility and chronic exposure to antiepileptic drugs.

The potential influence of antiepileptic drugs (AEDs) on fetal CNS function was studied with respect to motility patterns. Quantitative and qualitative aspects of spontaneous fetal activity were investigated for chronic AED-exposed fetuses and controls at three intervals during pregnancy: i.e. 20, 32 and 38 weeks. Movements were observed applying real-time ultrasound. Third trimester rest-activity cycles were determined according to the fetal behavioural state concept. Quantitative analysis revealed no marked differences in gross fetal motility between AED-exposed fetuses and controls. Both groups demonstrated the same developmental trend from midterm towards the third trimester. The number of trunk movements decreased, while their median duration increased. The incidence of fetal eye movements during C2F was lower for AED-exposed fetuses than for controls (significant for 38 weeks). In qualitative analysis, general movements of AED-exposed fetuses were more often labeled as suspect or abnormal than those of control fetuses (respectively, 8 out of 31 and 1 out of 20; P = 0.06). Future studies concerning chronic fetal AED-exposure and fetal CNS function should focus on qualitative rather than quantitative aspects of motility.     

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey

Summary Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4–20 A, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 A, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 A. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 A respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different muscle fields. The merits of STA and ICMS for exploring cortical organisation are discussed.     

The role of recombination signal sequences in the preferential joining by deletion in DH-JH recombination and in the ordered rearrangement of the IgH locus

The bias favoring deletion over inversion in DH-JH rearrangement has been known for years, but the underlying mechanism has yet to be fully defined. It has been suggested that the ratio of deletion/inversion is determined by the combined effect of two factors: (i) the relative strengths of 5' and 3' recombination signal sequences (RSS) of a DH segment, and (ii) the efficiency with which the deletional product (one joint) forms relative to the inversional product (two joints). In this study, we analyzed for the first time the effect of factor 1 alone on the biased 3' RSS utilization in DH-JH joining by using deletional plasmids in an extrachromosomal substrate V(D)J recombination assay. It was found that the 3' RSS and associated coding end (12 bp) mediate recombination more efficiently than the 5' RSS/coding end DH-JH plasmids. These results demonstrate that the effect of the RSS/coding end alone can account, at least partially, for the predominant deletion in DH-JH recombination. The potential effect of the relative strength of RSS and associated coding end on the ordered rearrangement of DH-JH followed by VH to DH-JH was also assessed. When recombination frequencies of D-->J (3' DH to J3) were compared with frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found that V-->D joining was, if anything, more efficient than D-->J joining. Therefore, if all three segments were accessible, RSS/coding end effects would not contribute to the ordered rearrangement of the IgH locus.      

Automated analysis of near-term antepartum fetal heart rate in relation to fetal behavioral states: the Sonicaid System 8000.

Fetal heart rate and fetal movements were recorded in 16 uncomplicated near-term pregnancies. The recordings were used to evaluate a system for automated fetal heart rate analysis (Sonicaid System 8000). Fetal rest-activity patterns were considered in the analysis. The mean duration of C2F periods "active sleep," 33 minutes) was significantly greater than that of C1F periods ("quiet sleep," 19 minutes) (p less than 0.001). The incidence of accelerations and decelerations and the overall fetal heart rate variations were greater during C2F than during C1F (p less than 0.001). In 11 of 16 C1F periods, the system classified the fetal heart rate variation as "questionable" or "abnormal." Episodes of high variation were identified in only 3 of 16 C1F periods, but they were found in all 18 C2F periods. Episodes of low variation were identified in 14 of the 16 C1F periods but were not found in any C2F periods. During C2F periods, the system's criteria of normality were met in all cases but one; they were not met during any of the C1F periods. Thus the diagnosis of fetal distress should not be based merely on the absence of accelerations, low fetal heart rate variation, or absence of episodes of high variation in recordings with a duration of less than 45 minutes.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

FISSURE SEALANT IN A NUTSHELL. EVIDENCE-BASED META-EVALUATION OF SEALANTS’ EFFECTIVENESS IN CARIES PREVENTION AND ARREST

ObjectiveThis meta-evaluation aimed to summarize all available evidence regarding different fissure sealants on occlusal caries prevention, arrest, retention rate, adverse effect, and cost-effectiveness; when compared with no intervention, other preventive or minimally-invasive procedures.Materials and MethodsThe systematic reviews and meta-analyses were identified via four electronic databases and manual searching. Two independent reviewers performed study selection, data extraction, quality assessment with AMSTAR-2.ResultsAmong the 366 records yielded, 38 systematic reviews were identified as eligible 24 of them included meta-analyses. Moderate evidence has supported the efficacies of resin-based sealants (RBS) in occlusal caries prevention, arrest and cost-effectiveness compared to no interventions. Low to very low certainty of evidence suggested similar effectiveness of glass-ionomer cements in caries prevention with RBS and more superior performance of resin infiltration in arresting non-cavitated occlusal lesions.ConclusionThis meta-evaluation supports the use of RBS on permanent molars to reduce occlusal caries occurrence, arrest lesion progression and alleviate oral health inequalities between individuals of different socioeconomic status. This meta-evaluation also advocates further research on glass-ionomer cements and resin infiltration with respect to their efficacies in caries prevention and arrest.