Contribution of family risk, emergent literacy and environmental protective factors in children’s reading difficulties at the end of second-grade

It is well established that emergent literacy is a strong predictor of later reading difficulties, and that the home literacy environment plays an important role in the development of children’s preschool emergent literacy and oral language. Furthermore, reading difficulties runs in families and children with a family risk of reading difficulties tend to show delays in emergent literacy and might experience a less advantageous home literacy environment. This study examined whether family risk predicts children’s second-grade reading difficulties in a multifactorial model including both emergent literacy and environmental protective factors such as home literacy environment and parental level of education. Children were assessed for emergent literacy at the beginning of first grade, and were identified as having reading difficulties at the end of second grade if they performed below the national threshold in at least three of the subtests in reading and spelling. The multifactorial model suggested that children with family risk showed reading difficulties that could not be explained in terms of individual differences in emergent literacy, gender, interest in literacy, years in kindergarten, home literacy environment or parental education level. These findings highlight the advantages of using multifactorial models of reading difficulties that encompass different domains of genetic, cognitive-based and environmental factors. In sum, not only did we find family risk is associated with children’s literacy outcomes after 2 years of formal reading instruction, but we also identified possible modifiable factors that may benefit from interventions and lessen the likelihood of developing reading difficulties

Comparing efficacy of montelukast versus doxycycline in treatment of moderate acne

Background: Treatment of acne is an important issue for reducing the cosmetic and psychological burden of disease. Regarding the inflammatory effect of LT-B4 in acne lesions and action mechanism of Montelukast, this study was performed to determine the efficacy of Montelukastin acne treatment comparison with doxycycline. Materials and Methods: In a randomized clinical trial that was performed in Dermatology Clinic in a Training Tertiary Health Care Center in Tehran, Iran since January 2012 to May 2014, 52 patients with moderate acne were evaluated. The included patients were randomly assigned to receive doxycycline 100 mg/day plus 1 Clindamycin solution (Group 1) or Montelukast 5 mg daily plus 1 clindamycin solution (Group 2). The acne severity index was measured and compared between two groups at baseline (on admission), 1-month and 3 months later. Independent-Sample-T, Chi-Square, and Repeated-Measure ANOVA tests were used and were considered statistically significant at P < 0.05. Results: The mean age was 26.8 ± 7.1 in Group 1 and25 ± 4.8 in Group 2 (P = 0.1). 73 women and 26.7 4 men in Group 1 and 86.7 women, and 13.3 men in Group 2 (P = 0.01). The mean acne severity index at baseline was 18.2 ± 6.1 and 19 ± 4.2 in Montelukast and doxycycline group, respectively (P = 0.679). The mean acne severity index after 1-month was 10.5 ± 6.2 and 12.9 ± 3.3 in Montelukast and doxycycline group, respectively (P = 0). Finally, the mean acne severity index after 3 months follow-up was 8.6 ± 4.8 and 8.2 ± 1.2 in Montelukast and doxycycline group, respectively (P = 0.01). There was no significant difference between two groups regarding the amount of decrease in acne severity index across the study (P = 0.186). However, each groups showed a significant reduction in the acne severity index, separately (P = 0.001). Conclusion: It may be concluded that Montelukast is an effective and safe medication for moderate-level acne treatment. © 2015, Isfahan University of Medical Sciences(IUMS). All rights reserved

Caon serum iron level, ferritin and total iron binding capacity level among nonpregnant women with and without melasma

Background: Melasma is a common acquired disorder characterized by symmetric, hyperpigmented patches with an irregular outline, occurring most commonly on the face. It is most prevalent among young to middle-aged women. Although iron overload affects skin pigmentation, effect of iron deficiency on skin is not clear. So, we evaluated serum iron level, ferritin and total iron binding capacity (TIBC) level among nonpregnant women with and without melasma. Materials and Methods: A cross-sectional case study was conducted in 2012 at university dermatologic department on 33 nonpregnant women with melasma (case) and 33 nonpregnant women without melasma (control). Serum iron level, TIBC and ferritin in the two groups was measured and compared. Results: Serum iron level was lower in the case group (85 ± 11) in comparison with control group (102 ± 9), but the difference was not significant (P: 0.9). Mean TIBC and Ferritin were higher in the case group (TIBC: 329.4 ± 29, ferritin: 6 ± 18) than the control group (TIBC: 329.3 ± 29, ferritin: 33 ± 6) without significant difference. Conclusion: Although the serum iron level was lower in nonpregnant women with mealsma, it was not significant compared with those without melasma. © 2015, Isfahan University of Medical Sciences(IUMS). All rights reserved

Preliminary report of a nationwide case-control study for identifying risk factors of tuberculosis following renal transplantation

Background. Tuberculosis (TB) is an important infection encountered posttransplantation, especially among patients in developing countries, where there are high incidences of morbidity and mortality. Materials and Methods. One hundred and twenty subjects (1) from 15 major kidney transplantation centers in Iran from 1984 to 2003 were compared with 440 controls who were matched for operative time, treatment center, and surgical team. Results. Mean ages of research subjects and controls were 38.6 and 36.6 years (P = .04), respectively. The mean duration of pretransplantation hemodialysis was 29 months (range, 2 to 192 months) in research subjects and 20 months (range, 1 to 180 months) in controls (P = .003). Positive past history of tuberculosis was detected in 4 (3.3) research subjects and in 7 (1.5) controls (P = .2). Fifty-two research subjects (43.3) and 241 controls (54.8) had pretransplantation purified protein derivative of tuberculin less than 5 mm (P = .02). Mean dosages of initial and maintenance immunosuppressive drugs in research subjects and in controls were not significantly different. Sixty research subjects (50) and 152 controls (34.5) had rejection prior to diagnosis of TB (P = .03). Conclusion. To our knowledge, this is the first study that demonstrates an increased risk of posttransplant TB by prolonged duration of pretransplant hemodialysis and number of posttransplant rejection episodes. Further study is needed to clarify these findings specifically with respect to various immunosuppressive regimens. © 2005 by Elsevier Inc. All rights reserved

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A second update on mapping the human genetic architecture of COVID-19

Matters Arising From: COVID-19 Host Genetics Initiative. Nature https://doi.org/10.1038/s41586-021-03767-x (2021)Data availability: Summary statistics generated by the COVID-19 HGI are available online, including per-ancestry summary statistics for African, admixed American, East Asian, European and South Asian ancestries (https://www.covid19hg.org/results/r7/). The analyses described here used the data release 7. If available, individual-level data can be requested directly from contributing studies, listed in Supplementary Table 1. We used publicly available data from GTEx (https://gtexportal.org/home/), the Neale laboratory (http://www.nealelab.is/uk-biobank/), the Finucane laboratory (https://www.finucanelab.org), the FinnGen Freeze 4 cohort (https://www.finngen.fi/en/access_results) and the eQTL catalogue release 3 (http://www.ebi.ac.uk/eqtl/).Code availability: The code for summary statistics lift-over, the projection PCA pipeline including precomputed loadings and meta-analyses (https://github.com/covid19-hg/); for heritability estimation (https://github.com/AndrewsLabUCSF/COVID19_heritability); for Mendelian randomization and genetic correlation (https://github.com/marcoralab/MRcovid); and subtype analyses (https://github.com/mjpirinen/covid19-hgi_subtypes) are available at GitHub.Reporting summary: Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article online at: https://www.nature.com/articles/s41586-023-06355-3#MOESM2 .Supplementary information is available online at: https://www.nature.com/articles/s41586-023-06355-3#Sec4 .Copyright © The Author(s) 2023. Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development1,2. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release2. The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

The effects of carvedilol, metoprolol and propranolol on cisplatin-induced kidney injury

The β-adrenoceptor blockers may have anti-oxidant properties or induce β-arrestin recruitment beyond classical desensitization of receptor/G protein coupling, offering potential therapeutic benefits. Here, we investigated the effects of carvedilol, metoprolol and propranolol in an animal model of cisplatin-induced nephrotoxicity. Rats received the β-blockers (3 or 12 mg/kg/day) with or without cisplatin, and kidney function was investigated using renal scintigraphy, histopathology, and serum variables. Metoprolol and propranolol as well as low-dose carvedilol did not alter kidney function, per se. Meanwhile, high-dose carvedilol reduced renal accumulation of Technetium-99m (99mTc)–labeled dimercaptosuccinic acid (99mTc-DMSA) without significant effect on other variables. Furthermore, low-dose carvedilol prevented cisplatin-induced reduction of tracer uptake, but high-dose of this drug aggravated the situation. In this regard, both low and high -doses of carvedilol significantly inhibited cisplatin effects on kidney histology, BUN and creatinine levels. Also, high-dose propranolol inhibited cisplatin adverse effects on radiotracer uptake, histological manifestations, BUN and creatinine levels, while metoprolol failed to cause a notable effect. Taken together, carvedilol and high-dose propranolol may offer potential benefits in cisplatin nephrotoxicity

Impact of extremely low-frequency electromagnetic field (100 Hz, 100 G) exposure on human glioblastoma U87 cells during Temozolomide administration

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an extremely dismal prognosis, a median survival is12 months. Temozolomide (TMZ) is an alkylating agent widely used to treat cancer, resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. Therefore, the present study was carried out to evaluate the potential synergistic effect of 100 µM TMZ and EMF (100 Hz, 100 G) on human glioma cell line U87 U87 cells with four experimental groups (I�IV) were exposed to ELF-EMF and TMZ for 120 and 144 h, as follows: (I) control; (II) ELF-EMF; (III) TMZ; (IV) ELF-PEMFs / TMZ. mRNA expression of genes such as (Nestin,CD133, Notch4 and GFAP) were investigated by Real-time PCR and western blot. We also evaluated, SOD activity, MDA and calcium concentration by ELISA assay. Co-treatment synergistically decreased the expression of Nestin,CD133, and Notch4 and increased the GFAP genes. We also observed an increase in Superoxide dismutase (SOD) activity, Malondialdehyde (MDA) and Ca2+concentration in comparison to controls.TMZ prevents cancer progression not only through the induction of cell death, but also by inducing differentiation in cancer cells. In addition, our data demonstrate ELF-EMF (100 Hz, 100 G) can significantly enhance the effects of TMZ on human glioblastoma U87 cell. These findings may open new window for future studies. © 2019, © 2019 Taylor & Francis Group, LLC