Association of Eating and Sleeping Intervals With Weight Change Over Time: The Daily24 Cohort.

Background We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort. Methods and Results This is a multisite prospective cohort study of adults recruited from 3 health systems. Over the 6-month study period, 547 participants downloaded and used a mobile application to record the timing of meals and sleep for at least 1 day. We obtained information on weight and comorbidities at each outpatient visit from electronic health records for up to 10  years before until 10 months after baseline. We used mixed linear regression to model weight trajectories. Mean age was 51.1 (SD 15.0) years, and body mass index was 30.8 (SD 7.8) kg/

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization

Background: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. Methods: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. Results: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. Conclusion: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Data on the early oxidation of SiO2-coated pure Ti and bulk Ti5Si3 at 800 °C

Oxidation of pure Ti sputtered with a 250 nm layer of amorphous SiO2 and bulk Ti5Si3 was conducted at 800 °C for 2 or 32 h in a 1 standard cubic centimeter per minute (SCCM) O2/4 SCCM Ar environment (approximately pO2 = 0.2 atm/20.3 kPa). Specimens were characterized using transmission electron microscopy, scanning transmission electron microscopy, and energy dispersive spectroscopy. The data in this article accompanies research article “Early oxidation behavior of Si-coated titanium” [1], which contains further discussion. The data for this article is hosted at the Materials Commons data repository and is available for download at https://materialscommons.org/mcapp/#/data/dataset/b8bc8038-a735-4cb9-9a9e-a0fb912b248c

Peptidoglycan hydrolysis is required for assembly and activity of the transenvelope secretion complex during sporulation inBacillus subtilis

Sporulating Bacillus subtilis cells assemble a transenvelope secretion complex that connects the mother cell and developing spore. The forespore protein SpoIIQ and the mother-cell protein SpoIIIAH interact across the double membrane septum and are thought to assemble into a channel that serves as the basement layer of this specialized secretion system. SpoIIQ is absolutely required to recruit SpoIIIAH to the sporulation septum on the mother-cell side, however the mechanism by which SpoIIQ is localized has been unclear. Here, we show that SpoIIQ localization requires its partner protein SpoIIIAH and degradation of the septal peptidoglycan (PG) by the two cell wall hydrolases SpoIID and SpoIIP. Our data suggest that PG degradation enables a second mother-cell-produced protein to interact with SpoIIQ. Cells in which both mother-cell anchoring mechanisms have been disabled have a synergistic sporulation defect suggesting that both localization factors function in the secretion complex. Finally, we show that septal PG degradation is critical for the assembly of an active complex. Altogether, these results suggest that the specialized secretion system that links the mother cell and forespore has a complexity approaching those found in Gram-negative bacteria and reveal that the sporulating cell must overcome similar challenges in assembling a transenvelope complex

A highly coordinated cell wall degradation machine governs spore morphogenesis in Bacillus subtilis

How proteins catalyze morphogenesis is an outstanding question in developmental biology. In bacteria, morphogenesis is intimately linked to remodeling the cell wall exoskeleton. Here, we investigate the mechanisms by which the mother cell engulfs the prospective spore during sporulation in Bacillus subtilis. A membrane-anchored protein complex containing two cell wall hydrolases plays a central role in this morphological process. We demonstrate that one of the proteins (SpoIIP) has both amidase and endopeptidase activities, such that it removes the stem peptides from the cell wall and cleaves the cross-links between them. We further show that the other protein (SpoIID) is the founding member of a new family of lytic transglycosylases that degrades the glycan strands of the peptidoglycan into disaccharide units. Importantly, we show that SpoIID binds the cell wall, but will only cleave the glycan strands after the stem peptides have been removed. Finally, we demonstrate that SpoIID also functions as an enhancer of SpoIIP activity. Thus, this membrane-anchored enzyme complex is endowed with complementary, sequential, and stimulatory activities. These activities provide a mechanism for processive cell wall degradation, supporting a model in which circumferentially distributed degradation machines function as motors pulling the mother cell membranes around the forespore

Recognizing the reversible nature of child-feeding decisions: Breastfeeding, weaning, and relactation patterns in a shanty town community of Lima, Peru

Researchers have normally considered weaning to be a non-reversible event. To determine the validity of this assumption, we interviewed 36 mothers of toddlers who were living in a poor shanty town of Lima, Peru. Data from 32 women were complete and used in this analysis. Mothers described their beliefs, practices, and decisions about breastfeeding, weaning, and relactation (the reintroduction of breastfeeding after weaning). We recorded attempted weaning events if the mother reported (1) purposefully not breastfeeding with the intention to wean, or (2) carrying out an action that was believed to cause the child to stop breastfeeding. Using a constant comparative approach, references to child-feeding decisions were coded, categorized, and analyzed. All mothers breastfed for at least 12 months; the median duration of breastfeeding was 25 months. There were several different patterns of child-feeding. Thirteen women never attempted to wean their children or had weaned on the first attempt. The majority (n=19) of women, however, attempted to wean their children - some as early as 3 months of age - but relactated between less than 1 day and 3 months later. Factors that influenced feeding decisions were primarily related to maternal and child health, and maternal time commitments. Children were weaned when there was a perceived problem of maternal health or time commitments and child health was not at risk of deterioration. Mothers postponed weaning because of poor child health. The primary reason for relactation was a child's negative reaction to weaning (e.g., incessant crying or refusal to eat). Personalities of the mother and child were important determinants of feeding decisions. These results demonstrate that maternal and child factors jointly influence child-feeding decisions and that these decisions are easily reversed. As relactation is culturally acceptable, health practitioners should consider recommending relactation when children have been prematurely weaned and human milk would improve their nutritional and health status.breastfeeding weaning relactation toddlers decision-making Peru