We estimate life expectancy and average years of life lost (AYLL) after an HIV diagnosis using population-based surveillance data from 25 states that have had name-based HIV surveillance since 1996.
...We used US national HIV surveillance data (cases > or = 13 years old) to model life expectancy after an HIV diagnosis using the life table approach. We then compared life expectancy at HIV diagnosis with that in the general population of the same age, sex, and race/ethnicity in the same calendar year using vital statistics data to estimate the AYLL due to an HIV diagnosis.
Average life expectancy after HIV diagnosis increased from 10.5 to 22.5 years from 1996 to 2005. Life expectancy (years) was better for females than for males but improved less for females (females: 12.6-23.6 and males: 9.9-22.0). In 2005, life expectancy for black males was shortest, followed by Hispanic males and then white males. AYLL for cases diagnosed in 2005 was 21.1 years (males: 19.1 and females: 22.7) compared with 32.9 years in 1996.
Disparity in life expectancy for females and both black and Hispanic males, compared with males and white males, respectively, persists and should be addressed.
Intermuscular adipose tissue (IMAT) is negatively related to insulin sensitivity, but a causal role of IMAT in the development of insulin resistance is unknown. IMAT was sampled in humans to test for ...the ability to induce insulin resistance in vitro and characterize gene expression to uncover how IMAT may promote skeletal muscle insulin resistance. Human primary muscle cells were incubated with conditioned media from IMAT, visceral (VAT), or subcutaneous adipose tissue (SAT) to evaluate changes in insulin sensitivity. RNAseq analysis was performed on IMAT with gene expression compared with skeletal muscle and SAT, and relationships to insulin sensitivity were determined in men and women spanning a wide range of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Conditioned media from IMAT and VAT decreased insulin sensitivity similarly compared with SAT. Multidimensional scaling analysis revealed distinct gene expression patterns in IMAT compared with SAT and muscle. Pathway analysis revealed that IMAT expression of genes in insulin signaling, oxidative phosphorylation, and peroxisomal metabolism related positively to donor insulin sensitivity, whereas expression of macrophage markers, inflammatory cytokines, and secreted extracellular matrix proteins were negatively related to insulin sensitivity. Perilipin 5 gene expression suggested greater IMAT lipolysis in insulin-resistant individuals. Combined, these data show that factors secreted from IMAT modulate muscle insulin sensitivity, possibly via secretion of inflammatory cytokines and extracellular matrix proteins, and by increasing local FFA concentration in humans. These data suggest IMAT may be an important regulator of skeletal muscle insulin sensitivity and could be a novel therapeutic target for skeletal muscle insulin resistance.
It is now widely understood that ADHD can be feigned easily and convincingly. Despite this, almost no methods exist to assist clinicians in identifying when such behavior occurs. Recently, new ...validity indicators specific to feigned ADHD were reported for the Personality Assessment Inventory (PAI). Derived from a logistic regression, these algorithms are said to have excellent specificity and good sensitivity in identifying feigned ADHD. However, these authors compared those with genuine ADHD only to nonclinical undergraduate students (asked to respond honestly or asked to simulate ADHD); no criterion group of definite malingerers was included. We therefore investigated these new validity indicators with 331 postsecondary students who underwent assessment for possible ADHD and compared scores of those who were eventually diagnosed with ADHD (n
=
111) to those who were not Clinical controls (66), Definite malingerers (36); No diagnosis (117). The two proposed PAI algorithms were found to have poor positive predictive value (.19 and .17). Self-report validity measures from the Connors' Adult Attention Rating Scale, and the Negative Impression Management scale on the PAI returned more positive results. Overall, more research is needed to better identify noncredible ADHD presentation, as the PAI-based methods proposed by Aita et al. appear inadequate as symptom validity measures.
B lymphocytes are compartmentalized within lymphoid organs. The organization of these compartments depends upon signaling initiated by G-protein linked chemoattractant receptors. To address the ...importance of the G-proteins Gαi2 and Gαi3 in chemoattractant signaling we created mice lacking both proteins in their B lymphocytes. While bone marrow B cell development and egress is grossly intact; mucosal sites, splenic marginal zones, and lymph nodes essentially lack B cells. There is a partial block in splenic follicular B cell development and a 50-60% reduction in splenic B cells, yet normal numbers of splenic T cells. The absence of Gαi2 and Gαi3 in B cells profoundly disturbs the architecture of lymphoid organs with loss of B cell compartments in the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B cells are poorly responsive to antigen receptor engagement. Gαi2 and Gαi3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells.
Firearm-related injuries are among the five leading causes of death for people aged 1-44 years in the U.S. The immediate and long-term harms of firearm injuries pose an economic burden on society. ...Fatal and nonfatal firearm injury costs in the U.S. were estimated providing up-to-date economic burden estimates.
Counts of nonfatal firearm injuries were obtained from the 2019-2020 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Data on nonfatal injury intent were obtained from the National Electronic Injury Surveillance System - Firearm Injury Surveillance System. Counts of deaths (firearm as underlying cause) were obtained from the 2019-2020 multiple cause-of-death mortality data from the National Vital Statistics System. Analyses were conducted in 2023.
The total cost of firearm related injuries and deaths in the U.S. for 2020 was $493.2 billion, a 16 percent increase compared with 2019. There are significant disparities in the cost of firearm deaths in 2019-2020, with non-Hispanic Black people, males, and young and middle-aged groups being the most affected.
Most of the nonfatal firearm injury-related costs are attributed to hospitalization. These findings highlight the racial/ethnic differences in fatal firearm injuries and the disproportionate cost burden to urban areas. Addressing this important public health problem can help ameliorate the costs to our society from the rising rates of firearm injuries.
Adverse and positive childhood experiences have a profound impact on lifespan health and well-being. However, their incorporation into ongoing population-based surveillance systems has been limited. ...This paper outlines critical steps in building a comprehensive approach to adverse and positive childhood experiences surveillance, provides examples from the Preventing Adverse Childhood Experiences: Data to Action cooperative agreement, and describes improvements needed to optimize surveillance data for action. Components of a comprehensive approach to adverse and positive childhood experiences surveillance include revisiting definitions and measurement, including generating and using uniform definitions for adverse and positive childhood experiences across data collection efforts; conducting youth-based surveillance of adverse and positive childhood experiences; using innovative methods to gather and analyze near real-time data; leveraging available data, including from administrative sources; and integrating data on community- and societal-level risk and protective factors for adverse childhood experiences, including social and health inequities such as racism and poverty, as well as policies and conditions that create healthy environments for children and families. Comprehensive surveillance data on adverse and positive childhood experiences can inform data-driven prevention and intervention efforts, including focusing prevention programming and services to populations in greatest need. Data can be used to evaluate progress in reducing the occurrence of adverse childhood experiences and bolstering the occurrence of positive childhood experiences. Through expansion and improvement in adverse and positive childhood experiences surveillance-including at federal, state, territorial, tribal, and local levels-data-driven action can reduce children's exposure to violence and other adversities and improve lifelong health and well-being.
We examined the association between socioeconomic position (SEP) and HIV diagnosis rates in the United States and whether racial/ethnic disparities in diagnosis rates persist after control for SEP.
...We used cases of HIV infection among persons aged 13 years and older, diagnosed 2005 through 2009 in 37 states and reported to national HIV surveillance through June 2010, and US Census data, to examine associations between county-level SEP measures and 5-year average annual HIV diagnosis rates overall and among race/ethnicity-sex groups.
The HIV diagnosis rate was significantly higher for individuals in the low-SEP tertile than for those in the high-SEP tertile (rate ratios for low- vs high-SEP tertiles range = 1.68-3.38) except for White males and Hispanic females. The SEP disparities were larger for minorities than for Whites. Racial disparities persisted after we controlled for SEP, urbanicity, and percentage of population aged 20 to 50 years, and were high in the low-SEP tertile for males and in low- and high-SEP tertiles for females.
Findings support continued prioritization of HIV testing, prevention, and treatment to persons in economically deprived areas, and Blacks of all SEP levels.
Accumulation of diacylglycerol (DAG) and sphingolipids is thought to promote skeletal muscle insulin resistance by altering cellular signaling specific to their location. However,the subcellular ...localization of bioactive lipids in human skeletal muscle is largely unknown.
We evaluated subcellular localization of skeletal muscle DAGs and sphingolipids in lean individuals (n = 15), endurance-trained athletes (n = 16), and obese men and women with (n = 12) and without type 2 diabetes (n = 15). Muscle biopsies were fractionated into sarcolemmal, cytosolic, mitochondrial/ER, and nuclear compartments. Lipids were measured using liquid chromatography tandem mass spectrometry, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamp.
Sarcolemmal 1,2-DAGs were not significantly related to insulin sensitivity. Sarcolemmal ceramides were inversely related to insulin sensitivity, with a significant relationship found for the C18:0 species. Sarcolemmal sphingomyelins were also inversely related to insulin sensitivity, with the strongest relationships found for the C18:1, C18:0, and C18:2 species. In the mitochondrial/ER and nuclear fractions, 1,2-DAGs were positively related to, while ceramides were inversely related to, insulin sensitivity. Cytosolic lipids as well as 1,3-DAG, dihydroceramides, and glucosylceramides in any compartment were not related to insulin sensitivity. All sphingolipids but only specific DAGs administered to isolated mitochondria decreased mitochondrial state 3 respiration.
These data reveal previously unknown differences in subcellular localization of skeletal muscle DAGs and sphingolipids that relate to whole-body insulin sensitivity and mitochondrial function in humans. These data suggest that whole-cell concentrations of lipids obscure meaningful differences in compartmentalization and suggest that subcellular localization of lipids should be considered when developing therapeutic interventions to treat insulin resistance.
National Institutes of Health General Clinical Research Center (RR-00036), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK089170), NIDDK (T32 DK07658), and Colorado Nutrition Obesity Research Center (P30DK048520).
•Longitudinal ischemic volume positively correlated to primate neurological assessment.•Specific gray and white matter regions correlated to overall neurological assessment.•Behavioral recovery index ...was most strongly associated to stroke magnitude and volumetric recovery index.•There is a close relationship between the size and location of the stroke and the behavioral outcome.•There are significant correlations in areas that could represent therapeutic targets for novel neuroprotective strategies.
Stroke is the second leading cause of death worldwide. Brain imaging data from experimental rodent stroke models suggest that size and location of the ischemic lesion relate to behavioral outcome. However, such a relationship between these two variables has not been established in Non-Human Primate (NHP) models. Thus, we aimed to evaluate whether size, location, and severity of stroke following controlled Middle Cerebral Artery Occlusion (MCAO) in NHP model correlated to neurological outcome. Forty cynomolgus macaques underwent MCAO, after four mortalities, thirty-six subjects were followed up during the longitudinal study. Structural T2 scans were obtained by magnetic resonance imaging (MRI) prior to, 48 h, and 30 days post-MCAO. Neurological function was assessed with the Non-human Primate Stroke Scale (NHPSS). T2 whole lesion volume was calculated per subject. At chronic stages, remaining brain volume was computed, and the affected hemisphere parceled into 50 regions of interest (ROIs). Whole and parceled volumetric measures were analyzed in relation to the NHPSS score. The longitudinal lesion volume evaluation showed a positive correlation with the NHPSS score, whereas the remaining brain volume negatively correlated with the NHPSS. Following ROI parcellation, NHPSS outcome correlated with frontal, temporal, occipital, and middle white matter, as well as the internal capsule, and the superior temporal and middle temporal gyri, and the caudate nucleus. These results represent an important step in stroke translational research by demonstrating close similarities between the NHP stroke model and the clinical characteristics following a human stroke and illustrating significant areas that could represent targets for novel neuroprotective strategies.
Germinal centers (GCs) are microanatomic structures that develop in secondary lymphoid organs in response to antigenic stimulation. Within GCs B cells clonally expand and their immunoglobulin genes ...undergo class switch recombination and somatic hypermutation. Transcriptional profiling has identified a number of genes that are prominently expressed in GC B cells. Among them is Rgs13, which encodes an RGS protein with a dual function. Its canonical function is to accelerate the intrinsic GTPase activity of heterotrimeric G-protein α subunits at the plasma membrane, thereby limiting heterotrimeric G-protein signaling. A unique, non-canonical function of RGS13 occurs following translocation to the nucleus, where it represses CREB transcriptional activity. The functional role of RGS13 in GC B cells is unknown. To create a surrogate marker for Rgs13 expression and a loss of function mutation, we inserted a GFP coding region into the Rgs13 genomic locus. Following immunization GFP expression rapidly increased in activated B cells, persisted in GC B cells, but declined in newly generated memory B and plasma cells. Intravital microscopy of the inguinal lymph node (LN) of immunized mice revealed the rapid appearance of GFP(+) cells at LN interfollicular regions and along the T/B cell borders, and eventually within GCs. Analysis of WT, knock-in, and mixed chimeric mice indicated that RGS13 constrains extra-follicular plasma cell generation, GC size, and GC B cell numbers. Analysis of select cell cycle and GC specific genes disclosed an aberrant gene expression profile in the Rgs13 deficient GC B cells. These results indicate that RGS13, likely acting at cell membranes and in nuclei, helps coordinate key decision points during the expansion and differentiation of naive B cells.
PDF
