Association of body mass index in midlife with morbidity burden in older adulthood and longevity

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P \u3c .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95$10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to$28 319]) participants compared with those with a normal BMI (P \u3c .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Specifics of the Elemental Excitations in "True One-Dimensional" MoI3_3 van der Waals Nanowires

We report on the temperature evolution of the polarization-dependent Raman spectrum of exfoliated MoI$_3$, a van der Waals material with a "true one-dimensional" crystal structure that can be exfoliated to individual atomic chains. The temperature evolution of several Raman features reveals anomalous behavior suggesting a phase transition of a magnetic origin. Theoretical considerations indicate that MoI$_3$ is an easy-plane antiferromagnet with alternating spins along the dimerized chains and with inter-chain helical spin ordering. The calculated frequencies of the phonons and magnons are consistent with the interpretation of the experimental Raman data. The obtained results shed light on the specifics of the phononic and magnonic states in MoI$_3$ and provide a strong motivation for future study of this unique material with potential for spintronic device applications.Comment: 28 page

Allelic Lineages of the Ficolin Genes (FCNs) Are Passed from Ancestral to Descendant Primates

The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species

A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses.

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy\u27s potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe 1-(2-fluorophenyl)-2-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,2-dihydrochromeno[2,3

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects