The D o Acidity Function for Aqueous Sodium Hydroxide Solutions

The H o acidity function developed by Hammett and Deyrup is well known, and values for this function are established for solutions of various acids

Building on the past, shaping the future: The environmental mutagenesis and genomics society

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97167/1/em21765.pd

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Tensiomyography Derived Parameters Reflect Skeletal Muscle Architectural Adaptations Following 6-Weeks of Lower Body Resistance Training

Measurement of muscle specific contractile properties in response to resistance training (RT) can provide practitioners valuable information regarding physiological status of individuals. Field based measurements of such contractile properties within specific muscle groups, could be beneficial when monitoring efficacy of training or rehabilitation interventions. Tensiomyography (TMG) quantifies contractile properties of individual muscles via an electrically stimulated twitch contraction and may serve as a viable option in the aforementioned applications. Thus, aims of this study were; (i) to investigate the potential use of TMG to quantify training adaptations and differences, in response to exercise specific lower limb RT; and (ii) investigate any associations between TMG parameters and accompanying muscle architectural measures. Non-resistance trained male participants (n = 33) were randomly assigned to 1 of 3 single-exercise intervention groups (n = 11 per group); back squat (BS), deadlift (DL), or hip thrust (HT). Participants completed a 6-week linearized training program (2× per week), where the assigned exercise was the sole method of lower body training. Pre- and post-intervention testing of maximal dynamic strength was assessed by one repetition maximum (1RM) of BS, DL, and HT. Radial muscle belly displacement (Dm) and contraction time (Tc) were obtained via TMG from the rectus femoris (RF) and vastus lateralis (VL) pre- and post-intervention, alongside muscle architectural measures (pennation angle and muscle thickness). All three groups displayed significant increases all 1RM strength tests (p < 0.001; pη2 = 0.677–0.753). Strength increases were accompanied by significant overall increases in RF muscle thickness (p < 0.001, pη2 = 0.969), and pennation angle (p = 0.007, pη2 = 0.220). Additionally, an overall reduction in RF Dm (p < 0.001, pη2 = 0.427) was observed. Significant negative relationships were observed between RF Dm and pennation angle (p = 0.003, r = −0.36), and with RF Dm and muscle thickness (p < 0.001, r = −0.50). These findings indicate that TMG is able to detect improved contractile properties, alongside improvements in muscle function within an untrained population. Furthermore, the observed associations between Dm and muscle architecture suggest that TMG contractile property assessments could be used to obtain information on muscle geometry

Assessment of Systemic Genetic Damage in Pediatric Inflammatory Bowel Disease.

The etiology of distal site cancers in inflammatory bowel disease (IBD) is not well understood and requires further study. We investigated whether pediatric IBD patients' blood cells exhibit elevated levels of genomic damage by measuring the frequency of mutant phenotype (CD59-/CD55-) reticulocytes (MUT RET) as a reporter of PIG-A mutation, and the frequency of micronucleated reticulocytes (MN-RET) as an indicator of chromosomal damage. IBD patients (n = 18 new onset disease, 46 established disease) were compared to age-matched controls (constipation or irritable bowel syndrome patients from the same clinic, n = 30) and young healthy adults age 19 - 24 (n = 25). IBD patients showed no indication of elevated MUT RET relative to controls (mean ± std. dev. = 3.1 ± 2.3 x 10-6 versus 3.6 ± 5.6 x 10-6 , respectively). In contrast, of 59 IBD patients where %MN-RET measurements were obtained, 10 exceeded the upper bound 90% tolerance interval derived from control subjects (i.e., 0.42%). Furthermore, each of the 10 IBD patients with elevated MN-RET had established disease (10/42), none were new onset (0/17) (p = 0.049). Interestingly, each of the subjects with increased chromosomal damage was receiving anti-TNF based monotherapy at the time blood was collected (10/10, 100%), whereas this therapy was less common (20/32, 63%) among patients that exhibited ≤ 0.42% MN-RET (p = 0.040). The results clearly indicate the need for further work to understand whether the results presented herein are reproducible, and if so, to elucidate the causative factor(s) responsible for elevated MN-RET frequencies in some IBD patients

Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.

Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila

The prevalence of giant cell arteritis and polymyalgia rheumatica in a UK primary care population

Background: To update community-based prevalence values for Polymyalgia Rheumatic (PMR) and Giant Cell Arteritis (GCA) using case record review supplemented by population survey and subsequent clinical review. Methods: Clinical data were obtained from case records of a large primary care practice in Norfolk, UK and reviewed for diagnoses of GCA and PMR. In addition postal survey was carried out to capture potentially undiagnosed cases within the practice population. Those screening positive for potential diagnoses of GCA and PMR were invited for clinical review. A cumulative prevalence estimate was subsequently calculated on those diagnosed within the GP practice and subsequently on those fulfilling the various published classification criteria sets. The date of the database lock and mail merge was March 2013. Results: Through detailed systematic review of 5,159 GP case records, 21 patients had a recorded diagnosis of GCA and 117 had PMR . No new cases were identified among 2,227 completed questionnaires returned from the population survey of a sample of 4,728. The resulting cumulative prevalence estimate in those aged ≥55 years meeting the ACR classification criteria set for GCA was 0.25% (95% CI 0.11% to 0.39%) and for five published criteria sets for PMR ranged from 0.91% to 1.53% (95% CI ranges 0.65%, 1.87%). The prevalence of both conditions was higher in women than in men and in older age groups. Conclusion: This study provides the first UK prevalence estimate of GCA and PMR in over 30 years and is the first to apply classification criteria sets

Deprived children or deprived neighbourhoods? A public health approach to the investigation of links between deprivation and injury risk with specific reference to child road safety in Devon County, UK

BACKGROUND: Worldwide, injuries from road traffic collisions are a rapidly growing problem in terms of morbidity and mortality. The UK has amongst the worst records in Europe with regard to child pedestrian safety. A traditional view holds that resources should be directed towards training child pedestrians. In order to reduce socio-economic differentials in child pedestrian casualty rates it is suggested that these should be directed at deprived children. This paper seeks to question whether analysis of extant routinely collected data supports this view. METHODS: Routine administrative data on road collisions has been used. A deprivation measure has been assigned to the location where a collision was reported, and the home postcode of the casualty. Aggregate data was analysed using a number of epidemiological models, concentrating on the Generalised Linear Mixed Model. RESULTS: This study confirms evidence suggesting a link between increasing deprivation and increasing casualty involvement of child pedestrians. However, suggestions are made that it may be necessary to control for the urban nature of an area where collisions occur. More importantly, the question is raised as to whether the casualty rate is more closely associated with deprivation measures of the ward in which the collision occurred than with the deprivation measures of the home address of the child. CONCLUSION: Conclusions have to be drawn with great caution. Limitations in the utility of the officially collected data are apparent, but the implication is that the deprivation measures of the area around the collision is a more important determinant of socio-economic differentials in casualty rates than the deprivation measures of the casualties' home location. Whilst this result must be treated with caution, if confirmed by individual level case-controlled studies this would have a strong implication for the most appropriate interventions

IMI 2021 Yearly Digest

PURPOSE. The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers. METHODS. A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered. RESULTS. One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologicmyopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss. CONCLUSIONS. Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.Peer reviewe