Early, regular breast-milk pumping may lead to early breast-milk feeding cessation

Objective To estimate the effect of early, regular breast-milk pumping on time to breast-milk feeding (BMF) and exclusive BMF cessation, for working and non-working women.Design Using the Infant Feeding Practices Survey II (IFPS II), we estimated weighted hazard ratios (HR) for the effect of regular pumping (participant defined) compared with non-regular/not pumping, reported at month 2, on both time to BMF cessation (to 12 months) and time to exclusive BMF cessation (to 6 months), using inverse probability weights to control confounding.Setting USA, 2005-2007.Subjects BMF (n 1624) and exclusively BMF (n 971) IFPS II participants at month 2.Results The weighted HR for time to BMF cessation was 1·62 (95 % CI 1·47, 1·78) and for time to exclusive BMF cessation was 1·14 (95 % CI 1·03, 1·25). Among non-working women, the weighted HR for time to BMF cessation was 2·05 (95 % CI 1·84, 2·28) and for time to exclusive BMF cessation was 1·10 (95 % CI 0·98, 1·22). Among working women, the weighted HR for time to BMF cessation was 0·90 (95 % CI 0·75, 1·07) and for time to exclusive BMF cessation was 1·14 (95 % CI 0·96, 1·36).Conclusions Overall, regular pumpers were more likely to stop BMF and exclusive BMF than non-regular/non-pumpers. Non-working regular pumpers were more likely than non-regular/non-pumpers to stop BMF. There was no effect among working women. Early, regular pumpers may need specialized support to maintain BMF

Genetics of tension-type headache

The objective of this study was to investigate the importance of genetics in tension-type headache. A MEDLINE search from 1966 to December 2006 was performed for “tension-type headache and prevalence” and “tension-type headache and genetics” The prevalence of tensiontype headache varies from 11 to 93%, with a slight female preponderance. Co-occurrence of migraine increases the frequency of tension-type headache. A family study of chronic tension-type headache suggests that genetic factors are important. A twin study analysing tension-type headache in migraineurs found that genetic factors play a minor role in episodic tension-type headache. Another twin study analysing twin pairs without co-occurrence of migraine showed a significantly higher concordance rate among monozygotic than same-gender dizygotic twin pairs with no or frequent episodic tension-type headache, while the difference was minor in twin pairs with infrequent episodic tensiontype headache. Frequent episodic and chronic tension-type headache is caused by a combination of genetic and environmental factors, while infrequent episodic tensiontype headache is caused primarily by environmental factors

The nutritional phenotype in the age of metabolomics

The concept of the nutritional phenotype is proposed as a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. The nutritional phenotype integrates the effects of diet on disease/wellness and is the quantitative indication of the paths by which genes and environment exert their effects on health. Advances in technology and in fundamental biological knowledge make it possible to define and measure the nutritional phenotype accurately in a cross section of individuals with various states of health and disease. This growing base of data and knowledge could serve as a resource for all scientific disciplines involved in human health. Nutritional sciences should be a prime mover in making key decisions that include: what environmental inputs (in addition to diet) are needed; what genes/proteins/metabolites should be measured; what end-point phenotypes should be included; and what informatics tools are available to ask nutritionally relevant questions. Nutrition should be the major discipline establishing how the elements of the nutritional phenotype vary as a function of diet. Nutritional sciences should also be instrumental in linking the elements that are responsive to diet with the functional outcomes in organisms that derive from them. As the first step in this initiative, a prioritized list of genomic, proteomic, and metabolomic as well as functional and behavioral measures that defines a practically useful subset of the nutritional phenotype for use in clinical and epidemiological investigations must be developed. From this list, analytic platforms must then be identified that are capable of delivering highly quantitative data on these endpoints. This conceptualization of a nutritional phenotype provides a concrete form and substance to the recognized future of nutritional sciences as a field addressing diet, integrated metabolism, and health

Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome

Purpose: Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data. Methods: The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes’ rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants. Results: The genetic screen-derived variants established that the two-component classification procedure displays high sensitivities and specificities. Moreover, these inactivating variants enabled the direct reclassification of human variants of uncertain significance (VUS) as (likely) pathogenic. Conclusion: The two-component classification procedure and the genetic screens provide complementary approaches to rapidly and cost-effectively classify the large majority of human MSH6 variants. The approach followed here provides a template for the classification of variants in other disease-predisposing genes, facilitating the translation of personalized genomics into personalized health care

A "critical" climatic evaluation of last interglacial (MIS 5e) records from the Norwegian Sea

Sediment cores from the Norwegian Sea were studied to evaluate interglacial climate conditions of the marine isotope stage 5e (MIS 5e). Using planktic forminiferal assemblages as the core method, a detailed picture of the evolution of surface water conditions was derived. According to our age model, a step-like deglaciation of the Saalian ice sheets is noted between ca. 135 and 124.5 Kya, but the deglaciation shows little response with regard to surface ocean warming. From then on, the rapidly increasing abundance of subpolar forminifers, concomitant with decreasing iceberg indicators, provides evidence for the development of interglacial conditions sensu stricto (5e-ss), a period that lasted for about 9 Ky. As interpreted from the foraminiferal records, and supported by the other proxies, this interval of 5e-ss was in two parts: showing an early warm phase, but with a fresher, i.e., lower salinity, water mass, and a subsequent cooling phase that lasted until ca. 118.5 Kya. After this time, the climatic optimum with the most intense advection of Atlantic surface water masses occurred until ca. 116 Kya. A rapid transition with two notable climatic perturbations is observed subsequently during the glacial inception. Overall, the peak warmth of the last interglacial period occurred relatively late after deglaciation, and at no time did it reach the high warmth level of the early Holocene. This finding must be considered when using the last interglacial situation as an analogue model for enhanced meridional transfer of ocean heat to the Arctic, with the prospect of a future warmer climate

Formal ratification of subseries for the Pleistocene Series of the Quaternary System

The Pleistocene Series/Epoch of the Quaternary System/ Period has been divided unofficially into three subseries/ subepochs since at least the 1870s. On 30th January, 2020, the Executive Committee of the International Union of Geological Sciences ratified two proposals approved by the International Commission on Stratigraphy formalizing: 1) the Lower Pleistocene Subseries, comprising the Gelasian Stage and the superjacent Calabrian Stage, with a base defined by the GSSP for the Gelasian Stage, the Pleistocene Series, and the Quaternary System, and currently dated at 2.58 Ma; and 2) the term Upper Pleistocene, at the rank of subseries, with a base currently undefined but provisionally dated at ~129 ka. Defining the Upper Pleistocene Subseries and its corresponding stage with a GSSP is in progress. The Middle Pleistocene Subseries is defined by the recently ratified GSSP for the Chibanian Stage currently dated at 0.774 Ma. These ratifications complete the official division of the Pleistocene into three subseries/ subepochs, in uniformity with the similarly subdivided Holocene Series/Epoch.</p

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review

Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab