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Κυριακή 6 Νοεμβρίου 2022

Testing different sources of environmental unpredictability on adolescent functioning: ancestral cue versus statistical learning and the role of temperament

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Background

The dimensional model of environmental adversity highlighted the effects of an unpredictable environment in promoting risky development. Toward gaining greater specificity in understanding, this multimethod, longitudinal study investigated the role of two sources of environmental unpredictability—ancestral cues versus statistical learning, and their interaction with dove temperament conceptualized within the evolutionary model of temperament, in shaping adolescent functioning.

Methods

Participants were 192 families with an adolescent (M age = 12.4) followed for two annual waves. We measured unpredictability within the ancestral-cue approach as incidents of disruptive family events, and statistical-learning unpredictability as the random variability in observed moment-to-moment maternal hostility during parent–child interaction. We focused on dove temperament, which characterizes strategies of cautious and inhibited behavior in novel contexts and persistence and intrinsic engagement in benign contexts.

Results

Findings indicated unique effects of ancestral-cue versus statistical-learning unpredictability—in interaction with dove temperament—in association with adolescent functioning. Ancestral-cue unpredictability interacted with dove temperament in association with vagal stress reactivity, and the interactive effects of statistical-learning unpredictability were only associated with set-shifting. Furthermore, the family instability-x-dove temperament interaction was linked to adolescent adjustment via vagal reactivity. Adolescents with lower dove temperament showed dampened vagal reactivity within the more unpredictable environments, which was in turn associated with a greater decrease in social withdrawal over time.

Conclusions

The findings highlighted the specificity in different sources of environmental unpredictability in shaping adolescent development.
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Update of the classification of midpalatal suture behaviour after surgically assisted rapid maxillary expansion using computed tomography

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The aim of this study was to update the midpalatal suture classification after surgically assisted rapid maxillary expansion (SARME) using computed tomography (CT). Thirty-five patients with a transverse maxillary deficiency and unilateral or bilateral posterior crossbite underwent SARME with osteotomy of the pterygoid apophysis of the sphenoid. CT was performed before installation of the Hyrax expander appliance and after the final activation. Opening of the midpalatal suture was classified into three types: type I, total midpalatal suture opening from anterior nasal spine (ANS) to posterior nasal spine (PNS); type II, partial midpalatal suture opening from ANS to the transverse palatine suture, with partial or non-existent opening of the midpalatal suture posterior to the transverse pala...
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Transcriptional analysis of the mfa‐cluster genes in Porphyromonas gingivalis strains with one and two mfa5 genes

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Abstract

The Porphyromonas gingivalis Mfa1 fimbria is composed of the Mfa1 to Mfa5 proteins, encoded by the mfa1 to mfa5 genes, respectively, which are tandemly arranged on chromosomes. A recent study discovered that many P. gingivalis strains possess two mfa5 genes (called herein mfa5-1 and mfa5-2), which are also in tandem. This study examined the transcriptional unit and activity of mfa-cluster genes in strains with one (the ATCC 33277 and TDC60 strains) and two (the HG66 and A7436 strains) mfa5 genes. Complementary DNA was prepared from the total RNA extracted from the bacterial cells in the logarithmic growth phase using a random primer. PCR analysis for the intergenic regions from mfa1 to mfa5 or mfa5-2 showed that mfa1 to mfa5 or mfa5-2 formed a polycistronic gene cluster. Quantitative real-time PCR showed that the mfa1 transcription was 5–10 times higher than tha t of mfa2 in all the strains. However, mfa2 to mfa5 mostly showed a comparable expression. Both mfa5 genes were comparably transcribed in HG66 and A7436 strains. The transcriptional levels were almost consistent with the respective protein expression levels. In silico analysis identified a transcriptional terminator structure in the intergenic region between mfa1 and mfa2 that was probably responsible for the decreased transcription rate of mfa2 and the downstream genes.

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Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C

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Abstract
Background
The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.
Methods
An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for two years (arm B). The primary endpoint was overall survival (OS).
Results
Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, two-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95 to 4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.
Conclusions
This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
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Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients

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Journal of Human Genetics, Published online: 07 November 2022; doi:10.1038/s10038-022-01095-0

Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients
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Πέμπτη 3 Νοεμβρίου 2022

The effect of changing to Bictegravir on lipids using real world data: A brief report

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The effect of changing to Bictegravir on lipids using real world data: A brief report

Analysis of variance for change in lipid subfractions in patients switching to bictegravir.


Abstract

What is known and objective

Cardiovascular disease is of increasing concern in patients living with HIV. The significant advancement in antiretroviral treatment has ensured that patients are now succumbing to traditional diseases of ageing. First generation antiretroviral therapy caused multiple side effects including significant dyslipidaemia. Despite the advancement and improving safety profile of treatment concerns remain about antiretroviral induced dyslipidaemia. We sought to investigate the real-world effect on lipids in patients switching to a Bictegravir based regime.

Methods

We conducted a retrospective analysis in patients switching therapy to Biktarvy at the Royal Liverpool University Hospital. Data was collected from the HIV database that is established for clinical use, as an electronic patient record, and audit purposes. Lipid data was cross checked with the Trust electronic reporting system. Participants were included if they were HIV-positive, >18 years and had switched to Biktarvy Patients were also required to have a lipid profile available 52 weeks prior to switching and 100 weeks post switching. Summary statistic were calculated and multiple regressions models were constructed to assess the independent predictors of lipid change. We also performed one way analysis of covariance (ANCOVA) to assess the impact of switching therapy on each quartile of the baseline lipid panel.

Results and discussion

There were 135 patients included in the analysis with a mean age of 47. The majority of the population were male (80%). At a mean follow up of 42 weeks post switch there was no significant difference in total cholesterol (p = 0.64), triglyceride (p = 0.64) or high density lipoprotein (HDL) cholesterol (p = 0.08). In the regression analysis the highest quartile of baseline total cholesterol and triglyceride were independently associated with improvement in lipid markers. Switching from protease inhibitor therapy was also significantly associated with improvement in triglyceride. In addition, the ANCVOA demonstrated that the highest quartiles of total cholesterol, triglyceride and the lowest quartile of HDL were associated with significant improvement in lipid markers after switching to Bictegravir.

What is new and conclusion

We demonstrated that patients with the most adverse lipid profiles at baseline had significant improvements in lipid profiles. In addition, patient switching away from protease inhibitor therapy also had significant improvements in triglyceride.
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International variations in germ cell tumours incidence in children and adolescents

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In order to compare the subtype distribution of germ cell tumours in children and adolescents between Japan and other countries, we extracted information on cancer incidence in children and adolescents from the third volume of the International Incidence of Childhood Cancer series (IICC-3) (1). The IICC-3 reports the number or incidence rates of cancers diagnosed in childhood and adolescence, from cancer registries (regional or national) worldwide. We analysed germ cell tumours incidence in four countries in Asia (Japan, China, the Republic of Korea and Thailand), two countries in Africa (Egypt and Uganda), four countries in the Americas (North: USA and Canada, Latin and Caribbean: Brazil and Colombia), three countries in Europe (the UK, France and Germany) and two countries in Oceania (Australia and New Zealand). Information from the Republic of Korea, USA , UK, Australia and New Zealand was obtained at the national level, and that from the other countries was extracted from one or multiple regional cancer registries. The years of incidence included in the analyses varied from country to country, ranging from 1990 to 2014, with the shortest being 12 years (Egypt: 1999–2010, UK: 2000–11) and the longest being 24 years (Japan and China: both 1990–2013). In this study, we compared the incidence and proportional distribution of soft tissue sarcoma subtypes in children (0–14 years old) and adolescents (15–19 years old) between these countries.
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