Male Rejuvenation: Injectables.

The use of injectables can effectively treat the areas of greatest facial esthetic concern in males. Due to significant differences in the facial anatomy of men compared to women, treatment strategy, dosage, and technique differs. This article will review the pharmacology, preparation, pertinent anatomy, technique, risks, and adverse events associated with injectable agents emphasizing unique differences in male anatomy and esthetics.

Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism.

Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP). D-VITylation of PTH caused no reduction in activity at the PTHR1 receptor, and resulted in a plasma elimination half-life of 7-15 h in rats and 24-32 h in cynomolgus monkeys. Analysis of steady-state pharmacokinetics as a function of dose showed flat profiles with smaller peak:trough ratios at low doses, indicative of slower subcutaneous absorption. In thyroparathyroidectomized (TPTx) rats, PTH(1-34)-vitamin D conjugates restored serum calcium and phosphate levels into the normal range over the 24 h dosing period, and increased bone turnover markers and reduced bone mineral density. Urinary calcium was initially elevated, but normalized by the end of treatment on day 27. In healthy monkeys, a single dose of PTH(1-34)-vitamin D conjugates elevated serum calcium levels above the normal range for a period of 24-48 h while simultaneously reducing urinary calcium. Therefore, the lead compound, EXT608, is a promising candidate as a therapeutic that can truly mimic the endogenous activity of PTH and warrants further study in patients with hypoparathyroidism.

The Association between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare Supplement plans. METHODS: We conducted a retrospective analysis of the MerativeTM MarketScan® Medicare Supplement Database (2017-2019) in Medigap enrollees (≥ 65 years) with hypertension. Proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥ 0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs was associated with a 0.06 (95% Confidence intervals [CI]: -0.09 - -0.03) lower probability of adequate adherence, or a 5% (95% C.I.: 4% - 7%) decrease in PDC. Compared to comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (O.R.: 0.69, 95%C.I.: 0.62 - 0.77), but higher among those with preferred provider organization (PPO) plans (O.R.: 1.08, 95%C.I.: 1.01 - 1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

A Pilot Study Characterizing Real Time Exposures to Particulate Matter and Carbon Monoxide from Cookstove Related Woodsmoke in Rural Peru.

Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to unvented cooking fires. We aimed to use PM2.5 and CO measurements to characterize exposure to cookstove generated woodsmoke in real time among control (n=10) and intervention (n=9) households in San Marcos, Cajamarca Region, Peru. Real time personal particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), and personal and kitchen carbon monoxide (CO) samples were taken. Control households used a number of stoves including open fire and chimney stoves while intervention households used study-promoted chimney stoves. Measurements were categorized into lunch (9am - 1pm) and dinner (3pm - 7pm) periods, where applicable, to adjust for a wide range of sampling periods (2.8- 13.1hrs). During the 4-h time periods, mean personal PM2.5 exposures were correlated with personal CO exposures during lunch (r=0.67 p=0.024 n=11) and dinner (r=0.72 p=0.0011 n=17) in all study households. Personal PM2.5 exposures and kitchen CO concentrations were also correlated during lunch (r=0.76 p=0.018 n=9) and dinner (r=0.60 p=0.018 n=15). CO may be a useful indicator of PM during 4-h time scales measured in real time, particularly during high woodsmoke exposures, particularly during residential biomass cooking.

Carbon monoxide exposures and kitchen concentrations from cookstove-related woodsmoke in San Marcos, Peru.

BACKGROUND: Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to biomass-fueled fires. OBJECTIVE: We compare CO exposures and concentrations among study promoted intervention stove users and control stove users in San Marcos Province, Cajamarca region, Peru. METHODS: Passive CO diffusion tubes were deployed over a 48-hour sampling period to measure kitchen CO concentrations and personal mother and child CO exposures in 197 control and 182 intervention households. RESULTS: Geometric means (95% CI) for child, mother, and kitchen measurements were 1.1 (0.9-1.2), 1.4 (1.3-1.6), and 7.3 (6.4-8.3) ppm in control households, and 1.0 (0.9-1.1), 1.4 (1.3-1.6), and 7.3 (6.4-8.2) ppm among intervention households, respectively. CONCLUSION: With no significant differences between control and intervention CO measurements, results suggest that intervention stove maintenance may be necessary for long-term reductions in CO exposures.

Racial and ethnic differences in patterns of use and discontinuation of long-acting injectable antipsychotics using Medicaid claims data.

Introduction: In general, racial and ethnic differences exist in antipsychotic prescription practices. However, little is known about such differences between individual long-acting injectable (LAI) antipsychotic formulations, specifically. This study's primary objective was to determine racial and ethnic differences among LAI antipsychotic use. Secondary objectives were to identify if discontinuation rates differed between agents and by race or ethnicity. Methods: International Classification of Diseases, 10th edition (ICD-10) codes were used to identify patients with schizophrenia and related disorders (18-64 years) who received an LAI antipsychotic between 2016 and 2020 using Merative Multi-State Medicaid databases. Using National Drug Code numbers for LAI antipsychotics, pharmacy claims were identified and data analyzed. Cochran-Mantel-Haenszel tests and odds ratio estimators were used to investigate conditional association between race or ethnicity and medication, while controlling for age, sex, health plan, and prescription year. Kaplan-Meier survival curves were examined, and stratified log-rank tests were conducted to compare the time until discontinuation distributions by race or ethnicity. Results: The analysis included 37 712 patients. Blacks received an LAI first-generation antipsychotic more often than Whites (OR: 1.64, 95% CI: [1.56, 1.73], Hispanics (OR: 1.46, 95% CI: [1.21, 1.75]) and others (OR: 1.44, 95% CI: [1.20, 1.73]). Aside from fluphenazine decanoate showing earlier discontinuation rates for Whites over Blacks (P = .02), no significant differences in discontinuation across race or ethnicity were identified. Discussion: Despite no significant differences in second-generation antipsychotic LAI discontinuation rates between Blacks and other racial or ethnic groups, Blacks received second-generation antipsychotic LAIs significantly less often than other groups. Further studies are needed to determine why differences may be occurring.

Utilization of Counseling Services by Pediatric Patients With Obesity Using MarketScan Data (2017-2019).

The United States has implemented policy efforts for public and private insurance to cover counseling services related to the treatment of obesity. However, no research has yet studied counseling service utilization among pediatric patients with obesity. We used 3 years (2017-2019) of IBM MarketScan Commercial Claims and Encounters Database and IBM MarketScan Multi-State Medicaid Data to examine such utilization patterns. We found the proportion of patients receiving any counseling services to be low among both privately insured (7.06%-7.97%) and Medicaid patients (9.51%-11.61%) within 6 months from diagnosis of obesity. This underutilization is concerning as many pediatric patients go undiagnosed, as evidenced in this research. Among the utilized services, nutrition counseling and face-to-face counseling were utilized the most by privately and Medicaid-insured patients over 6- and 12-month follow-ups. Our study underscores the need for implementing policies and programs to promote the utilization of counseling services among pediatric patients.

Early growth, development and allometry of glyphosate-resistant and susceptible Amaranthus palmeri in response to current and elevated temperature and CO2.

This study aimed to evaluate the influence of CO2 and temperature on glyphosate-resistant and susceptible biotypes of Amaranthus palmeri (Palmer amaranth) in terms of morphological development. Height (cm), stem diameter (cm), leaf area (cm2), number of leaves, leaf, stem, and root dry matter, plant volume (m3), as well as shoot-to-root allometry were evaluated. The Palmer amaranth biotypes were grown under four different scenarios: 1-low temperature (23/33 °C) and CO2 (410 ± 25 ppm); 2-low temperature (23/33 °C) and high CO2 (750 ± 25 ppm); 3-high temperature (26/36 °C) and low CO2 (410 ± 25 ppm); and 4-high temperature (26/36 °C) and CO2 (750 ± 25 ppm). Between CO2 and temperature, the majority of differences observed were driven by CO2 levels. Palmer amaranth grown under 750 ppm of CO2 was 15.5% taller, displayed 10% more leaf area (cm2), 18% more stem dry matter, and had a 28.4% increase in volume (m3) compared to 410 ppm of CO2. GA2017 and GA2020 were 18% and 15.5% shorter, respectively. The number of leaves was 27% greater for GA2005. Plant volume decreased in GA2017 (35.6%) and GA2020 (23.8%). The shoot-to-root ratio was isomeric, except at 14 and 21 DAT, where an allometric growth towards shoot development was significant. Palmer amaranth biotypes responded differently to elevated CO2, and the impacts of temperature need further investigation on weed physiology. Thus, environmental and genetic background may affect the response of glyphosate-resistant and susceptible populations to climate change scenarios.

EXT418, a novel long-acting ghrelin, mitigates Lewis lung carcinoma induced cachexia in mice.

BACKGROUND: Ghrelin is a potential therapy for cachexia due to its orexigenic properties and anabolic effects on muscle and fat. However, its clinical use is limited by the short half-life of active (acylated) ghrelin (~11 min in humans). EXT418 is a novel long-acting, constitutively active ghrelin analog created by covalently linking it to a vitamin D derivative. Here, we evaluated the effects and mechanisms of action of EXT418 on Lewis lung carcinoma (LLC)-induced cachexia in mice. METHODS: Male C57BL/6J mice (5- to 7-month-old) were implanted with 1 × 106 heat-killed (HK) or live LLC cells. When the tumour was palpable, mice were injected with vehicle (T + V) or EXT418 daily (T + 418 Daily, 0.25 mg/kg/day) or every other day (T + 418 EOD, 0.5 mg/kg/EOD) for up to 14 days, whereas HK-treated mice were given vehicle (HK + V). Subsets of T + 418 Daily or EOD-treated mice were pair-fed to the T + V group. Body composition and grip strength were evaluated before tumour implantation and at the end of the experiment. Molecular markers were probed in muscles upon termination. RESULTS: In tumour-bearing mice, administration of EXT418 daily or EOD partially prevented weight loss (T + V vs. T + 418 Daily, P = 0.030; and vs. T + 418 EOD, P = 0.020). Similar effects were observed in whole body fat and lean body mass. Grip strength in tumour-bearing mice was improved by EXT418 daily (P = 0.010) or EOD (P = 0.008) administration compared with vehicle-treated mice. These effects of EXT418 on weight and grip strength were partially independent of food intake. EXT418 daily administration also improved type IIA (P = 0.015), IIB (P = 0.037) and IIX (P = 0.050) fibre cross-sectional area (CSA) in tibialis anterior (TA) and EXT418 EOD improved CSA of IIB fibres in red gastrocnemius (GAS; P = 0.005). In skeletal muscles, tumour-induced increases in atrogenes Fbxo32 and Trim63 were ameliorated by EXT418 treatments (TA and GAS/plantaris, PL), which were independent of food intake. EXT418 administration decreased expression of the mitophagy marker Bnip3 (GAS/PL; P ≤ 0.010). Similar effects of EXT418 EOD were observed in p62 (GAS/PL; P = 0.039). In addition, EXT418 treatments ameliorated the tumour-induced elevation in muscle Il6 transcript levels (TA and GAS/PL), independently of food intake. Il-6 transcript levels in adipose tissue and circulating IL-10 were elevated in response to the tumour but these increases were not significant with EXT418 administration. Tumour mass was not altered by EXT418. CONCLUSIONS: EXT418 mitigates LLC-induced cachexia by attenuating skeletal muscle inflammation, proteolysis, and mitophagy, without affecting tumour mass and partially independent of food intake.

Personal exposure to PM(2.5) and urinary hydroxy-PAH levels in bus drivers exposed to traffic exhaust, in Trujillo, Peru.

Public transport vehicle drivers, especially in highly polluted or trafficked areas, are exposed to high levels of air pollutants. In this study, we assessed the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within-shift changes in the urinary whole weight and creatinine-corrected concentrations of the PAH metabolites. We measured personal PM(2.5) as a proxy of exposure to traffic emission. Urine samples were collected daily from two bus drivers and three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured in the urine samples. Drivers were also monitored for exposure to PM(2.5) (n = 41). Daily work shift (mean = 13.1 ± 1.3 hr) integrated PM(2.5) was measured in the breathing zones of the drivers for an average of 10.5 days per driver. The differences across shift in OH-PAH concentrations were not statistically significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4-hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4-hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (ρ = 0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM(2.5) (geometric mean = 64 µg/m(3); 95% confidence limits = 52 µg/m(3), 78 µg/m(3)) is similar to those measured in many other studies of traffic exposure. There was significant change across work shift for concentrations of only two of the OH-PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited time for clearance of PAH exposure from the body between work shifts. Comparisons of the concentrations of creatinine-corrected hydroxy-PAH to those reported in other studies indicate that exposure of public transport drivers to PAH could be similar. By following the subjects over multiple days, this study gives an indication of appropriate exposure situations for the use of hydroxy-PAHs and will be beneficial in designing future occupational studies of PAH exposure.

D-VITylation: Harnessing the biology of vitamin D to improve the pharmacokinetic properties of peptides and small proteins.

Peptides have great potential to be potent and specific therapeutics, yet their small size leads to rapid glomerular filtration, which severely limits therapeutic applications. Although conjugation of small proteins to large polymers typically results in longer residence times, these conjugates often have a significant loss of biological activity due to steric hindrance. Here, we improve the pharmacokinetics (PK) of peptide therapeutics by harnessing the biology of vitamin D. Attachment of a small vitamin D-based molecule (D-VITylation) protects the conjugated peptide or protein from renal clearance by virtue of reversible binding to the serum-circulating vitamin D binding protein (DBP), without compromising bioactivity. Varying the conjugation site on vitamin D affects the binding to DBP, with higher affinity corresponding to a longer plasma half-life. We also demonstrate the important contribution of the peptide to the overall PK, likely due to alternative clearance mechanisms such as protease degradation and receptor-mediated cellular uptake. With a Fab antibody fragment, for which these alternate clearance mechanisms are not significant, D-VITylation increases the half-life of elimination from 14 to 61 h in rats. The PK profile in minipigs and projected lifetime in humans suggest that D-VITylation is a viable strategy to achieve once-weekly dosing of peptide therapeutics in humans.

Comparisons of trabecular and cortical bone in late adolescent black and white females.

Few childhood studies have investigated racial differences in volumetric bone mineral density (vBMD), bone geometry, and bone strength indices measured by three-dimensional bone imaging. The purpose of this study was to compare trabecular and cortical bone parameters at the radius and tibia between late adolescent white and black females using peripheral quantitative computed tomography (QCT). White (n = 25) and black females (n = 25), 18-19 years of age, were pair-matched for age, height, and fat-free soft tissue mass. Peripheral QCT scans were obtained at the 4% (trabecular bone), 20% (cortical bone), and 66% [muscle cross-sectional area (CSA)] sites from the distal metaphyses. Bone strength was determined from vBMD and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength-strain index (SSI; cortical site). Radial SSI was not different between groups; however, blacks had greater radial BSI (P = 0.02) than whites. After adjustment for the longer forearm in blacks, the greater radial BSI in blacks no longer remained. At the tibia, blacks versus whites had greater bone strength at the trabecular and cortical bone sites (BSI, P = 0.03; SSI, P = 0.04, respectively). When controlling for differences in tibial length and muscle CSA, the higher estimates of bone strength persisted in blacks versus whites (BSI, P = 0.01; SSI, P = 0.02). Our data suggest that when differences in body size are considered, late adolescent black versus white females have a stronger bone profile, due to greater bone geometry and vBMD, at the trabecular and cortical regions of the tibia but not at the radius.

Lung function changes in wildland firefighters working at prescribed burns.

CONTEXT: Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. OBJECTIVES: We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season. MATERIALS AND METHODS: We measured forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow from 25% to 75% of FVC (FEF25₋75), and peak expiratory flow (PEF) of wildland firefighters before and after their workshifts. In all, 501 pre-shift and 488 post-shift measurements were collected over 22 prescribed burn days and 43 non-burn days from 24 non-smoking wildland firefighters during the dormant winter burn seasons of 2003 and 2004. We compared changes in the spirometry measures across the workshift on burn days to those observed on non-burn days. We also assessed the effect of cumulative exposure during the burn season on the spirometry measures. RESULTS: There were no significant differences in the across workshift changes on burn days compared to those on non-burn days for all the spirometry measures. However, for a given point in time during the season, each additional day of exposure was estimated to be associated with declines of 24 ml in pre-shift FVC and 24 ml in pre-shift FEV1 (p <0.01). DISCUSSION AND CONCLUSION: Cumulative exposure to woodsmoke was associated with slight decrements in lung function among the wildland firefighters.

Personal PM(2.5) exposure among wildland firefighters working at prescribed forest burns in Southeastern United States.

This study investigated occupational exposure to wood and vegetative smoke in a group of 28 forest firefighters at prescribed forest burns in a southeastern U.S. forest during the winters of 2003-2005. During burn activities, 203 individual person-day PM(2.5) and 149 individual person-day CO samples were collected; during non-burn activities, 37 person-day PM(2.5) samples were collected as controls. Time-activity diaries and post-work shift questionnaires were administered to identify factors influencing smoke exposure and to determine how accurately the firefighters' qualitative assessment estimated their personal level of smoke exposure with discrete responses: "none" or "very little," "low," "moderate," "high," and "very high." An average of 6.7 firefighters were monitored per burn, with samples collected on 30 burn days and 7 non-burn days. Size of burn plots ranged from 1-2745 acres (avg = 687.8). Duration of work shift ranged from 6.8-19.4 hr (avg = 10.3 hr) on burn days. Concentration of PM(2.5) ranged from 5.9-2673 µg/m(3) on burn days. Geometric mean PM(2.5) exposure was 280 µg/m(3) (95% CL = 140, 557 µg/m(3), n = 177) for burn day samples, and 16 µg/m(3) (95% CL = 10, 26 µg/m(3), n = 35) on non-burn days. Average measured PM(2.5) differed across levels of the firefighters' categorical self-assessments of exposure (p < 0.0001): none to very little = 120 µg/m(3) (95% CL = 71, 203 µg/m(3)) and high to very high = 664 µg/m(3) (95% CL = 373, 1185 µg/m(3)); p < 0.0001 on burn days). Time-weighted average PM(2.5) and personal CO averaged over the run times of PM(2.5) pumps were correlated (correlation coefficient estimate, r = 0.79; CLs: 0.72, 0.85). Overall occupational exposures to particulate matter were low, but results indicate that exposure could exceed the ACGIH®-recommended threshold limit value of 3 mg/m(3) for respirable particulate matter in a few extreme situations. Self-assessed exposure levels agreed with measured concentrations of PM(2.5). Correlation analysis shows that either PM(2.5) or CO could be used as a surrogate measure of exposure to woodsmoke at prescribed burns.

Particulate matter (PM2.5) and carbon monoxide from secondhand smoke outside bars and restaurants in downtown Athens, Georgia.

In the study described in this article, the authors' objective was to measure particles < or = 2.5 microm in aerodynamic diameter (PM2.5) and carbon monoxide (CO) in outdoor waiting areas and patios of restaurants and bars in downtown Athens, Georgia, where indoor smoking is banned. The authors also wanted to investigate whether the measured concentrations are directly associated with the number of cigarettes lit in these settings. Real-time PM2.5 and CO were monitored on four summer weekend afternoons/evenings in outdoor waiting areas or patios at five locations in Athens. In addition, smokers and pedestrians present or passing and motorized vehicles passing each sampling location were counted. PM2.5 levels were significantly higher than levels at the control location (all p-values > .001). Carbon monoxide levels outside the restaurant and bar sites did not differ significantly from the control. The results of the authors' study indicate that (1) secondhand smoke (SHS) leads to significant increases in PM2.5 outside of restaurants and bars; and (2) although CO can be used as a proxy for SHS in these outdoor environments, its levels remain relatively low.

The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes.

Ribosomal protein (RP) genes in eukaryotes are coordinately regulated in response to growth stimuli and environmental stress, thereby permitting cells to adjust ribosome number and overall protein synthetic capacity to physiological conditions. Approximately 50% of RNA polymerase II transcription is devoted to RP genes. The transcriptional regulator Rap1 binds most yeast RP promoters, and Rap1 sites are important for coordinate regulation of RP genes. However, Rap1 is not the specific regulator that controls RP transcription because it also functions as a repressor, and many Rap1-activated promoters are not coordinately regulated with RP promoters. Here we show that the transcription factors Fhl1 and Ifh1 associate almost exclusively with RP promoters; association depends on Rap1 and (to a lesser extent) a DNA element at many RP promoters. Ifh1 is recruited to promoters via the forkhead-associated (FHA) domain of Fhl1; the level of Ifh1 associated with RP promoters determines the level of transcription; and environmental stress causes a marked reduction in the association of Ifh1, but not Fhl1 or Rap1. Thus, Ifh1 association with promoters is the key regulatory step for coordinate expression of RP genes.

An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae.

HMG proteins are architectural proteins that bind to DNA with low sequence specificity, but little is known about their genomic location and biological functions. Saccharomyces cerevisiae encodes 10 HMG proteins, including Hmo1, which is important for maximal transcription of rRNA. Here we use chromatin immunoprecipitation coupled with microarray analysis to determine the genome-wide association of Hmo1. Unexpectedly, Hmo1 binds strongly to the promoters of most ribosomal protein (RP) genes and to a number of other specific genomic locations. Hmo1 binding to RP promoters requires Rap1 and (to a lesser extent) Fhl1, proteins that also associate with RP promoters. Hmo1, like Fhl1 and Ifh1, typically associates with an IFHL motif in RP promoters, but deletion of the IFHL motif has a very modest effect on Hmo1 binding. Surprisingly, loss of Hmo1 abolishes binding of Fhl1 and Ifh1 to RP promoters but does not significantly affect the level of transcriptional activity. These results suggest that Hmo1 is required for the assembly of transcription factor complexes containing Fhl1 and Ifh1 at RP promoters and that proteins other than Fhl1 and Ifh1 also play an important role in RP transcription. Lastly, like mammalian UBF, Hmo1 associates at many locations throughout the rRNA gene locus, and it is important for processing of rRNA in addition to its role in rRNA transcription. We speculate that Hmo1 has a role in coordinating the transcription of rRNA and RP genes.

Characterization of htrB and msbB mutants of the light organ symbiont Vibrio fischeri.

Bacterial lipid A is an important mediator of bacterium-host interactions, and secondary acylations added by HtrB and MsbB can be critical for colonization and virulence in pathogenic infections. In contrast, Vibrio fischeri lipid A stimulates normal developmental processes in this bacterium's mutualistic host, Euprymna scolopes, although the importance of lipid A structure in this symbiosis is unknown. To further examine V. fischeri lipid A and its symbiotic function, we identified two paralogs of htrB (designated htrB1 and htrB2) and an msbB gene in V. fischeri ES114 and demonstrated that these genes encode lipid A secondary acyltransferases. htrB2 and msbB are found on the Vibrio "housekeeping" chromosome 1 and are conserved in other Vibrio species. Mutations in htrB2 and msbB did not impair symbiotic colonization but resulted in phenotypic alterations in culture, including reduced motility and increased luminescence. These mutations also affected sensitivity to sodium dodecyl sulfate, kanamycin, and polymyxin, consistent with changes in membrane permeability. Conversely, htrB1 is located on the smaller, more variable vibrio chromosome 2, and an htrB1 mutant was wild-type-like in culture but appeared attenuated in initiating the symbiosis and was outcompeted 2.7-fold during colonization when mixed with the parent. These data suggest that htrB2 and msbB play conserved general roles in vibrio biology, whereas htrB1 plays a more symbiosis-specific role in V. fischeri.

A prospective analysis of plasma 25-hydroxyvitamin D concentrations in white and black prepubertal females in the southeastern United States.

BACKGROUND: Little is known regarding changes in vitamin D status among children living in the southern United States and whether these changes are race-dependent. OBJECTIVES: The aims were to prospectively assess plasma 25-hydroxyvitamin D [25(OH)D] concentrations in prepubertal black and white girls (n = 83) living in northeast Georgia and to determine whether 25(OH)D concentrations change with increasing age. DESIGN: Plasma samples were obtained annually over a time frame of 1-7 y, and 25(OH)D concentrations were assessed by using radioimmunoassay. Percentage body fat (%BF) and fat-free soft tissue (FFST) mass were measured by using dual-energy X-ray absorptiometry. Linear mixed-effects models were used with height, weight, body mass index percentile, %BF, FFST, pubertal stage, dietary intake, physical activity, and socioeconomic status as covariates. RESULTS: Plasma 25(OH)D values < 80 nmol/L were observed in 75% of the participants. Plasma 25(OH)D values (analyzed on the natural logarithm scale) decreased with increasing age (P = 0.02), independent of race. Plasma 25(OH)D values were higher in whites than in blacks (P < 0.0001), and the amount of this difference depended on season (P < 0.001 for all seasons). A significant negative association between FFST and 25(OH)D, beyond the effects of age, race, and season (P = 0.007), was observed. The effects of age, race, and season on 25(OH)D remained significant when dietary calcium, vitamin D, and physical activity were used as covariates; however, after adjustment for FFST, only the effects of race and season remained. CONCLUSIONS: White girls living in the southeastern United States have higher 25(OH)D concentrations than do black girls, and the magnitude of this difference depends on the season. Decreases in 25(OH)D with age are associated with increases in FFST. Whether FFST requires additional vitamin D during growth remains to be determined.

Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females.

BACKGROUND: Whereas excess adiposity is presumed to be advantageous for the skeleton, studies investigating relations between bone strength and fat during youth have been equivocal. OBJECTIVES: Relations of percentage body fat (BF) and bone strength indexes were assessed in late adolescent females, taking into consideration surrogates of muscle force [ie, muscle cross-sectional area (MCSA) and bone length]. Bone measurements in the normal- and high-fat groups were also compared. DESIGN: Late adolescent females (n = 115; aged 18.2 +/- 0.4 y) participated in this cross-sectional study. Fat-free soft tissue mass, fat mass, and percentage BF were measured with the use of dual-energy X-ray absorptiometry. Tibial and radial peripheral quantitative computed tomography measurements were taken at the 4% (trabecular bone), 20% (cortical bone), and 66% (for measurement of MCSA) sites from the distal metaphyses. RESULTS: Percentage BF was inversely related to radial cortical bone area, total bone cross-sectional area (CSA), cortical bone mineral content (BMC), periosteal circumference, and strength-strain index (SSI) (20% site; all P < 0.05). After control for MCSA and limb length, negative relations remained between percentage BF and radial measurements and were also observed at the tibia (20% site). Unadjusted bone measures were not different between groups. After control for MCSA, the high- compared with the normal-fat group had lower bone measures at the 20% site (cortical bone area and cortical BMC at the tibia, total bone CSA at the radius, and SSI at both the tibia and radius; P < 0.05 for all). CONCLUSION: Excess weight in the form of fat mass does not provide additional benefits, and may potentially be negative, for adolescent bone.