Higher Dietary Calcium Intakes Are Associated With Reduced Risks of Fractures,Cardiovascular Events,and Mortality: A Prospective Cohort Study of Older Men and Women

The aim of this population‐based, prospective cohort study was to investigate long‐term associations between dietary calcium intake and fractures, non‐fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (～99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD‐related deaths (n = 557), cerebrovascular disease‐related deaths (n = 139), incident non‐fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non‐fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ～13 years after baseline. Quartiles of baseline energy‐adjusted calcium intake from food were estimated using a food‐frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy‐adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all‐cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76–0.98, p_trend = 0.01); for non‐fatal CVD and stroke, the OR was 0.84 (95% CI 0.70–0.99, p_trend = 0.04) and 0.69 (95% CI 0.51–0.93, p_trend = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54–0.92, p_trend = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non‐fatal CVD, stroke, and all‐cause mortality. © 2015 American Society for Bone and Mineral Research.     

Kinase domain of the muscle-specific receptor tyrosine kinase (MuSK) is sufficient for phosphorylation but not clustering of acetylcholine receptors: Required role for the MuSK ectodomain?

Formation of the neuromuscular junction (NMJ) depends upon a nerve-derived protein, agrin, acting by means of a muscle-specific receptor tyrosine kinase, MuSK, as well as a required accessory receptor protein known as MASC. We report that MuSK does not merely play a structural role by demonstrating that MuSK kinase activity is required for inducing acetylcholine receptor (AChR) clustering. We also show that MuSK is necessary, and that MuSK kinase domain activation is sufficient, to mediate a key early event in NMJ formation—phosphorylation of the AChR. However, MuSK kinase domain activation and the resulting AChR phosphorylation are not sufficient for AChR clustering; thus we show that the MuSK ectodomain is also required. These results indicate that AChR phosphorylation is not the sole trigger of the clustering process. Moreover, our results suggest that, unlike the ectodomain of all other receptor tyrosine kinases, the MuSK ectodomain plays a required role in addition to simply mediating ligand binding and receptor dimerization, perhaps by helping to recruit NMJ components to a MuSK-based scaffold.     

End of life in the intensive care unit: knowledge and practice of clinicians from Karachi, Pakistan

Background:  With improvements in the care of critically ill, physicians are faced with obligations to provide quality end-of-life care. Barriers to this include inadequate understanding of the dying patient and withdrawal or limitation of care. The objectives of this study were to document the comprehensions of physicians and nurses regarding the recognition and practice of end-of-life care for critically ill patients placed on life support in the intensive care unit.
Methods:  This was a cross-sectional study carried out at three hospitals in Karachi. Chi-squared analysis and one-way anova were used to compare differences in response between the groups.
Results:  One hundred and thirty-seven physicians and critical care nurses completed the survey. 'Brain death' was defined as an ' irreversible cessation of brainstem function' by 85% respondents, with 50% relying on specialty consultation. Withdrawal of life support is practised by 83.2%; physicians are more likely (Chi square test P -value < 0.001) to withdraw mechanical ventilation, compared with nurses who would withdraw vasopressors ( P -value 0.006). In a do not resuscitate patient, 72.3% use vasopressors, 83% initiate haemodialysis and 17.5% use non-invasive ventilation; 72.6% consult Hospital Ethics Committees; 16% respondents never withdraw life support; 28.3% considered it their responsibility to 'sustain life at all costs' and only 8% gave religious beliefs as a reason.
Conclusions:  There are confusions in the definition of brain death, end-of-life recognition and indications and processes of withdrawal of life support. There are discrepancies between physicians' and nurses' perceptions and attitudes. Clearly, teaching programmes will need to incorporate cultural and religious differences in their ethics curricula.     

Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination

Immune responses in serum and saliva were studied in Pakistani children by enzyme-linked immunosorbent assay after natural exposure to poliovirus and vaccination with live or inactivated poliovirus vaccines. Swedish children unexposed to wild poliovirus who had almost 100% vaccination coverage with inactivated vaccine at 8, 9, and 18 months and at 5 years of age were analyzed for comparison. Natural exposure induced secretory IgA (SIgA) antibodies to poliovirus in the saliva of Pakistani infants at one month of age that reached adult levels at six months. No difference in levels of salivary antibody at eight months was observed between groups vaccinated with either live or inactivated vaccines. Vaccination with live or inactivated vaccine starting at 2 or 3 months of age resulted in high titers of IgG antibody to poliovirus in serum, the highest of which occurred after four doses of live vaccine. In Sweden, an increase of antibody in serum was observed after the third vaccination. IgA antibodies continued to increase subsequently, whereas IgG antibodies reached a plateau. The SIgA response in saliva initially appeared on the third vaccination, with a significant increase after the fourth. Repeated vaccination with inactivated poliovirus vaccine induces specific SIgA antibodies. Adults all had SIgA antibodies to poliovirus in saliva.     

Complete nucleotide sequence of a soybean actin gene

Soybean contains a small multigene family of actin-related sequences. We have determined the complete nucleotide sequence of a soybean actin gene carried on the recombinant plasmid pSAc3. As deduced from the nucleotide sequence, this soybean actin is composed of 376 amino acids. Compared to other eukaryotic actins, pSAc3 actin has a deletion of one amino acid between residues 118 and 122. The initiator methionine is followed by alanine, which is not found at this position in other eukaryotic actins. pSAc3 actin differs, in primary sequence, more from fungal and animal actins than any of the known nonplant actins differ from each other. pSAc3 actin appears to be related to both cytoplasmic and muscle specific actins in the location of specific NH₂-terminal amino acids. The coding sequence is interrupted by three small introns, each less than 90 base pairs long. The splice junctions are similar to those found in other eukaryotic genes, suggesting the presence of a similar splicing apparatus in higher plants. Introns 1 and 3 interrupt the reading frame after codons 20 and 355, respectively. Intron 2 splits a glycine codon at position 151. None of these intron positions is conserved relative to the positions of introns in other actin genes examined.