scholarly journals Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response

2021 ◽  
Vol 22 (22) ◽  
pp. 12605
Author(s):  
Francesca Antonelli ◽  
Arianna Casciati ◽  
Montserrat Belles ◽  
Noemi Serra ◽  
Maria Victoria Linares-Vidal ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Therapeutic Potential ◽  
Target Volume ◽  
Treatment Modalities ◽  
Prevention Measures ◽  
Long Term Effects ◽  
Brain Repair ◽  
Shh Pathway ◽  
Pathway Activation

Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (Ptch1+/−). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in Ptch1+/− mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.

scholarly journals The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome

2021 ◽  
Vol 118 (6) ◽  
pp. e2010217118
Author(s):  
B. Brett Finlay ◽  
Katherine R. Amato ◽  
Meghan Azad ◽  
Martin J. Blaser ◽  
Thomas C. G. Bosch ◽  
...  
Keyword(s):  
Human Health ◽  
Human Microbiome ◽  
Risk Groups ◽  
Hygiene Hypothesis ◽  
Control Measures ◽  
Prevention Measures ◽  
Long Term Effects ◽  
Substantial Impact ◽  
Future Challenges

The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19−induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome’s influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.

scholarly journals Hedgehog pathway permissive conditions allow generation of immortal cell lines from granule cells derived from cancerous and non-cancerous cerebellum

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180145 ◽  
Author(s):  
Constantin Heil
Keyword(s):  
Cell Lines ◽  
Hedgehog Pathway ◽  
Simple Method ◽  
Genetic Ablation ◽  
Neural Lineage ◽  
Shh Pathway ◽  
Pathway Activation

Cerebellar granule cell progenitors (GCPs) undergo proliferation in the post-natal cerebellum that is dependent on sonic hedgehog (SHH) signalling. Deregulated SHH signalling leads to type 2 medulloblastoma (MB). In this work, a novel cell culture protocol is described, which is suitable for the establishment and long-term maintenance of GCP-derived cells. This method is first applied to SHH pathway active MB cells from Atoh1 -cre; Ptch1 FL/FL tumours, which leads to the generation of neurosphere-like cell lines expressing GCP markers and an active SHH signalling pathway. These cells also show high sensitivity to the Smoothened inhibitor vismodegib, therefore recapitulating the SHH pathway requirement for survival shown by type 2 MB. Analysis of culture supplements reveals that bFGF and fetal bovine serum act as inhibitors of the SHH pathway and therefore preclude generation of cell lines that are relevant to the study of the SHH pathway. Consequently, these insights are transferred from the context of MB to non-transformed, post-natal day 7 cerebellum-derived cellular explants. In contrast to other, previously used methods, these GCP cultures proliferate indefinitely and depend on SHH pathway activation, either by means of the small molecule SAG or through genetic ablation of Ptch1 . This culture method therefore leads to the generation of immortal neurosphere-like cell lines, that are named murine SAG-dependent spheres (mSS). Despite long-term culture, mSS cells remain dependent on continuous stimulation of the SHH pathway. Further, mSS cells maintain their lineage after extensive periods in vitro, as demonstrated by their differentiation towards the neural lineage. Herein a simple method for the generation of immortal cell lines from murine cerebella is defined. These lines can be maintained indefinitely through hedgehog pathway activation and maintain the GCP lineage.

Long-Term Biological Damage: What is Known, and How Should that Influence Decisions on Response, Assessment, and Restoration?

2001 ◽  
Vol 2001 (1) ◽  
pp. 399-403 ◽  
Author(s):  
Mark G. Carls ◽  
Ron Heintz ◽  
Adam Moles ◽  
Stanley D. Rice ◽  
Jeffrey W. Short
Keyword(s):  
Oil Spill ◽  
Polyaromatic Hydrocarbons ◽  
Environmental Cost ◽  
Life Stages ◽  
Prevention Measures ◽  
Long Term Effects ◽  
Short Term ◽  
Exxon Valdez ◽  
Damage Scenarios

ABSTRACT Immediate damage from an oil spill is usually obvious (oiled birds, oiled shoreline), but long-term damage to either fauna or habitat is more subtle, difficult to measure, difficult to evaluate, and hence often controversial. The question is, are too many of response decisions such as dispersant use or shoreline cleanup based on short-term acute toxicity models? Have long-term damage scenarios been discounted because of the inherent difficulty in deriving definitive answers? Experience with the Exxon Valdez oil spill is shedding new light on the potential for long-term damage. Government-funded studies demonstrated that oil persists in certain habitats for extended periods of time, such as the intertidal reaches of salmon streams, in soft sediments underlying mussel beds, and on cobble beaches armored with large boulders. Observation of long-term persistence of oil in some habitats is not new, but an increasing number of studies indicate that fauna may be chronically and significantly exposed to oil in these habitats. The toxic components in oil responsible for much of the long-term effects are believed to be the larger 3- and 4-ring polyaromatic hydrocarbons (PAHs) that can induce cellular and genetic effects rather than the narcotic monoaromatic hydrocarbons (MAHs) responsible for acute mortalities. Observation of long-term persistence of Exxon Valdez oil, coupled with adverse effects on sensitive life stages, leads to the conclusion that strategies based on minimizing acute mortalities immediately following a spill probably do not provide adequate protection against long-term damage. When making environmental decisions in response to a spill (prevention measures or restoration measures), more weight should probably be given to long-term issues rather than discounting their significance. Total environmental cost is the sum of short-term damage and long-term damage, and long term-damage to habitats and sensitive life stages probably needs more consideration even though it is very difficult to evaluate and compare to the relatively obvious acute issues.

scholarly journals Short and Long-Term Effects of Growth Hormone in Children and Adolescents With GH Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael B. Ranke
Keyword(s):  
Gh Deficiency ◽  
Child Growth ◽  
Treatment Modalities ◽  
Diagnostic Process ◽  
Childhood And Adolescence ◽  
Long Term Effects ◽  
Childhood Onset ◽  
Gh Secretion ◽  
Number Of Patients

The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit via replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored.

scholarly journals Sub-acute and long-term effects of ayahuasca on mental health and well-being in healthy ceremony attendants: A replication study

2021 ◽  
Author(s):  
Kim I. van Oorsouw ◽  
Malin V. Uthaug ◽  
Natasha L. Mason ◽  
Nick J. Broers ◽  
Johannes G. Ramaekers
Keyword(s):  
Mental Health ◽  
Therapeutic Potential ◽  
Well Being ◽  
Altered States Of Consciousness ◽  
Altered States ◽  
Long Term Effects ◽  
States Of Consciousness ◽  
First Time ◽  
Health And Well Being

Abstract Background and aims There is a growing body of evidence suggesting that the psychedelic plant tea, ayahuasca, holds therapeutic potential. Uthaug et al. (2018) demonstrated that a single dose of ayahuasca improved mental health sub-acutely and 4-weeks post-ceremony in healthy participants. The present study aimed to replicate and extend these findings. A first objective was to assess the sub-acute and long-term effects of ayahuasca on mental health and well-being in first-time and experienced users. A second aim was to extend the assessment of altered states of consciousness and how they relate to changes in mental health. Method Ayahuasca ceremony attendants (N = 73) were assessed before, the day after, and four weeks following the ceremony. Results We replicated the reduction in self-reported stress 4-weeks post ceremony, but, in contrast, found no reduction in depression. Also, increased satisfaction with life and awareness the day after the ceremony, and its return to baseline 4 weeks later, were replicated. New findings were: reduced ratings of anxiety and somatization, and increased levels of non-judging 4-weeks post-ceremony. We replicated the relation between altered states of consciousness (e.g., experienced ego dissolution during the ceremony) and mental health outcomes sub-acutely. The effects of ayahuasca did not differ between experienced and first-time users. Conclusion Partly in line with previous findings, ayahuasca produces long-term improvements in affect in non-clinical users. Furthermore, sub-acute mental health ratings are related to the intensity of the psychedelic experience. Although findings replicate and highlight the therapeutic potential of ayahuasca, this needs to be confirmed in placebo-controlled studies.

scholarly journals Metabolic Effects of Oxytocin

2019 ◽  
Vol 41 (2) ◽  
pp. 121-145 ◽  
Author(s):  
Shana E McCormack ◽  
James E Blevins ◽  
Elizabeth A Lawson
Keyword(s):  
Weight Loss ◽  
Therapeutic Potential ◽  
Model Systems ◽  
Metabolic Effects ◽  
Long Term Effects ◽  
Controlled Clinical Trials ◽  
Mineral Density ◽  
Future Studies ◽  
The Impact

Abstract There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader–Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX – XX, 2020)

scholarly journals Update in pediatric nasopharyngeal undifferentiated carcinoma

2019 ◽  
Vol 92 (1102) ◽  
pp. 20190107 ◽  
Author(s):  
Line Claude ◽  
Emmanuel Jouglar ◽  
Loig Duverge ◽  
Daniel Orbach
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Systemic Treatment ◽  
Young Patients ◽  
Undifferentiated Carcinoma ◽  
Treatment Modalities ◽  
Long Term Effects ◽  
Chemotherapy Induction ◽  
Undifferentiated Nasopharyngeal Carcinoma

Many of the principles established in adults with undifferentiated nasopharyngeal carcinoma (NPC) apply to children, adolescents and young adults. However, NPC in young patients should be distinguished from the adult form by several points. This review focuses mainly on differences between adult and pediatric NPC. The role of biology and genetics in pediatric NPC is discussed. Systemic treatment modalities including type of chemotherapy induction, timing of treatment, role of immunotherapy as adjuvant treatment, or in relapsing/ metastatic diseases are reported. Radiation modalities (doses, techniques…) in children are also reviewed. Long-term effects including secondary cancers are finally be discussed in this young NPC population.

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