Abstract
Background
While antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH ...receiving ART, thereby contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, underlying mechanisms remain elusive.
Methods
Our cohort consisted of PWH with ART adherence and viral suppression ( < 50 copies/mL; N = 173). Measurements included immune cell markers of overall immune health (CD4/CD8 T-cell ratio) and myeloid inflammation (CD16+ monocytes), plasma markers of inflammatory status (soluble CD163 and CD14), and structural and functional neuroimaging (volume and cerebral blood flow CBF, respectively).
Results
Decreased CD4/CD8 ratios correlated with reduced brain volume, and higher levels of inflammatory CD16+ monocytes were associated with reduced brain volume in total cortex and gray matter. An increase in plasma soluble CD14—a marker of acute peripheral inflammation attributed to circulating microbial products—was associated with reduced CBF within the frontal, parietal, temporal, and occipital cortices and total gray matter.
Conclusions
CD4/CD8 ratio and number of CD16+ monocytes, which are chronic immune cell markers, are associated with volumetric loss in the brain. Additionally, this study shows a potential new association between plasma soluble CD14 and CBF.
Solution Structure of Poly(UG) RNA Escobar, Cristian A; Petersen, Riley J; Tonelli, Marco ...
Journal of molecular biology,
12/2023, Letnik:
435, Številka:
24
Journal Article
Recenzirano
Poly(UG) or "pUG" RNAs are UG or GU dinucleotide repeat sequences which are highly abundant in eukaryotes. Post-transcriptional addition of pUGs to RNA 3' ends marks mRNAs as vectors for gene ...silencing in C. elegans. We previously determined the crystal structure of pUG RNA bound to the ligand N-methyl mesoporphyrin IX (NMM), but the structure of free pUG RNA is unknown. Here we report the solution structure of the free pUG RNA (GU)
, as determined by nuclear magnetic resonance spectroscopy and small and wide-angle x-ray scattering (NMR-SAXS-WAXS). The low complexity sequence and 4-fold symmetry of the structure result in overlapped NMR signals that complicate chemical shift assignment. We therefore utilized single site-specific deoxyribose modifications which did not perturb the structure and introduced well-resolved methylene signals that are easily identified in NMR spectra. The solution structure ensemble has a root mean squared deviation (RMSD) of 0.62 Å and is a compact, left-handed quadruplex with a Z-form backbone, or "pUG fold." Overall, the structure agrees with the crystal structure of (GU)
bound to NMM, indicating the pUG fold is unaltered by docking of the NMM ligand. The solution structure reveals conformational details that could not be resolved by x-ray crystallography, which explain how the pUG fold can form within longer RNAs.
Nanocoatings have numerous potential applications in the indoor environment, such as flooring finishes with increased scratch- and wear-resistance. However, given concerns about the potential ...environmental and human health effects of nanomaterials, it is necessary to develop standardized methods to quantify nanomaterial release during use of these products. One key choice for mechanical wear studies is the abrasion wheel. Potential limitations of different wheels include the release of fragments from the wheel during abrasion, wearing of the wheel from the abrasion process, or not releasing a sufficient number of particles for accurate quantitative analysis. In this study, we evaluated five different wheels, including a typically used silicon oxide-based commercial wheel and four wheels fabricated at the National Institute of Standards and Technology (NIST), for their application in nanocoating abrasion studies. A rapid, nondestructive laser scanning confocal microscopy method was developed and used to identify released particles on the abraded surfaces. NIST fabricated a high performing wheel: a noncorrosive, stainless-steel abrasion wheel containing a deep cross-patch. This wheel worked well under both wet and dry conditions, did not corrode in aqueous media, did not release particles from itself, and yielded higher numbers of released particles. These results can be used to help develop a standardized protocol for surface release of particles from nanoenabled products using a commercial rotary Taber abraser.
Controversies exist as to whether one should rely on the 'scoop and run' or 'stay and play' approach in the case of penetrating trauma in the prehospital setting. Optimal prehospital care is much ...debated and the extent to which advanced life support (ALS) measures should be performed remains unclear. This study aimed to report the outcome of penetrating torso trauma in relation to the on-scene time and ALS procedures performed prehospitally. It was hypothesised that a longer on-scene time could predict a higher mortality after penetrating torso trauma.
This was an observational cohort study of penetrating trauma patients treated by the Mobile Emergency Care Unit in Copenhagen with a 30-day follow-up. Between January 2002 and September 2009, data were prospectively registered regarding the anatomical location of the trauma, time intervals and procedures performed in the prehospital setting. Follow-up data were obtained from a national administrative database. The primary end point was 30-day survival.
Of the 467 patients registered, 442 (94.6%) were identified at the 30-day follow-up, of whom 40 (9%) were dead. A higher mortality was found among patients treated on-scene for more than 20 min (p=0.0001), although on-scene time was not a significant predictor of 30-day mortality in the multivariate analysis; OR 3.71, 95% CI 0.66 to 20.70 (p=0.14). The number of procedures was significantly correlated to a higher mortality in the multivariate analysis.
On-scene time might be important in penetrating trauma, and ALS procedures should not delay transport to definite care at the hospital.
Objectives This study compares prescription patterns between young adults and elderly with bipolar disorder who achieved a recovery status during the Systematic Treatment Enhancement Program for ...Bipolar Disorder (STEP-BD). Design STEP-BD is a multicenter National Institute of Mental Health-funded project designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD study involved extensive assessment across multiple domains including demographic data, diagnosis, symptom severity, treatment, and clinical status. Patients achieved “recovered” status when they experienced eight consecutive weeks without significant symptoms. Participants The authors analyzed data of all subjects who achieved a recovered status at least once in their participation. Measurements The authors compared treatment regimes and doses among young participants with middle age (N = 3,364), 20–59 years old, and older participants 60 and above (N = 246). Results Of the 3,615 STEP-BD participants who had a lifetime diagnosis of bipolar subtypes I or II, 67.6% (N = 2442) achieved a recovered status during their participation. A total of 78.5% (N = 193) of older patients recovered compared with 66.8% of the younger cohort. On average, participants who reached a recovered status took 2.05 medications with no difference between age groups. Lithium was prescribed to 37.8% of younger patients compared with only 29.5% of older participants. The mean dosages taken by younger and older patients differed significantly only for lithium, valproate, and risperidone with elderly individuals prescribed lower daily dosages. Significant reduction in lithium dosing was observed among individuals aged 50 and older and among individuals 60 and older for valproate. Although valproate was more often prescribed, 42.1% of recovered bipolar elder achieved recovery with lithium alone compared with only 21.3% of the younger cohort. Conclusion This data shows recovery is achievable in the elderly though more than one medication is often needed regardless of age.
Atopic dermatitis (AD) often develops in infancy as the first manifestation of the atopic phenotype. Wheezing is also common in infancy, but it is less clear whether infant wheezing should be ...considered as an atopic phenotype. If infant wheeze and AD share a common aetiology, this would indicate that infant wheezing is an atopic phenotype.
To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes, indicating a common etiology.
A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, and prenatal, perinatal, and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation, at 6 and 18 months of age, and by linkage to the Danish Medical Birth Register. Data were analyzed by binary and polytomous logistic regression models.
The following variables had significantly differential effects on infant wheezing and AD: parental hay fever, parental asthma, parental AD, sex, maternal age, maternal occupation, smoking during pregnancy, season of birth, birth weight, gestational age, head circumference, breast-feeding, number of older siblings, day care attendance, and pets in the home.
The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology. Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease, and infant wheezing should not be used as an indicator of the atopic phenotype.
Background
Lower semen quality is associated with increased mortality and morbidity, which may include osteoporosis.
Objective
To assess whether infertile men have a lower bone mineral density (BMD) ...compared with fertile men at the time of fertility workup.
Methods
A total of 146 men from infertile couples with unexplained impaired semen quality, characterized by sperm concentration < 20 million/mL, progressive motility < 50% or < 12% morphologically normal spermatozoa. Men with infertility due to a genetic etiology or a condition that could cause testicular damage were excluded. A total of 271 men from couples with an ongoing naturally conceived pregnancy served as a control group. Lumbar, femoral, and total body BMD were measured by dual X‐ray absorptiometry.
Results
Infertile men had similar BMD compared with fertile men (Beta coefficient (g/cm2) and 95% confidence interval for the difference between the two groups: −0.02 (−0.05; 0.01) for lumbar BMD, −0.02 (−0.05; 0.01) for femoral neck BMD, −0.01 (−0.04; 0.02) for total femur BMD, and −0.01 (−0.03; 0.01) for total body BMD). Semen parameters were not associated with BMD measurements. Furthermore, BMD did not differ between infertile men with the lowest semen quality vs. infertile men with better semen quality nor between infertile men with low testosterone vs. fertile men with normal testosterone levels.
Conclusion
Bone mineral density is preserved in men with unexplained infertility at the time of fertility workup.
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