scholarly journals Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

2021 ◽  
Author(s):  
Livia H. Morais ◽  
Anna V. Golubeva ◽  
Sophie Casey ◽  
Karen A. Scott ◽  
Ana Paula Ramos Costa ◽  
...  
Keyword(s):  
Caesarean Section ◽  
Early Life ◽  
Gastrointestinal Transit ◽  
Postnatal Period ◽  
High Dose ◽  
Mediated Effects ◽  
Mouse Behaviour ◽  
Wide Range ◽  
Caesarean Section Delivery ◽  
Mode Of Birth

AbstractThe oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

scholarly journals Dysbiosis in Children Born by Caesarean Section

2018 ◽  
Vol 73 (Suppl. 3) ◽  
pp. 24-32 ◽  
Author(s):  
Mariana C. Salas Garcia ◽  
Alyson L. Yee ◽  
Jack A. Gilbert ◽  
Melissa Dsouza
Keyword(s):  
Risk Factors ◽  
Caesarean Section ◽  
Early Life ◽  
Infant Development ◽  
The United States ◽  
Microbial Risk ◽  
Microbial Dysbiosis ◽  
Caesarean Section Delivery ◽  
The Impact

The rate of Caesarean-section delivery in the United States has increased by 60% from 1996 through to 2013 and now accounts for > 30% of births [CDC, 2017]. The purpose of this review is to present the current understanding of both the microbial risk factors that increase the likelihood of a Caesarean-section delivery and the microbial dysbiosis that is thought to result from the Caesarean section. We provide examples of research into the impact of early-life microbial dysbiosis on infant development and long-term health outcomes, as well as consider the efficacy and the long-term implications of microbiome-based therapies to mitigate this dysbiosis. The steep rise in the Caesarean-section delivery rate makes it imperative to understand the potential of microbiota modulation for the treatment of dysbiosis.

Infeksi Herpes Simpleks Dalam Kehamilan

2017 ◽  
Vol 10 (1) ◽  
pp. 1
Author(s):  
Fauzia Andrini Djojosugito
Keyword(s):  
Herpes Simplex ◽  
Caesarean Section ◽  
Sexually Transmitted Diseases ◽  
Recurrent Infection ◽  
Neonatal Infection ◽  
Sexually Transmitted ◽  
Caesarean Section Delivery ◽  
Common Causes ◽  
Pregnancy And Delivery ◽  
Simplex Virus

Herpes simplex virus is one the most common causes of sexually transmitted diseases. This infection is common inreproductive age women and can cause severe sequealae for fetus and neonates because this virus can be transmittedto the fetus during pregnancy and the newborn. Infection of Herpes simplex can occurs as first or primary infectionand recurrent infection. Most of the case is asymptomatic. Rarely during intrauterine, the risk of transmission ofmaternal-fetal can be increased during the last trimester of pregnancy and delivery. Based on type of infection,primary or recurrent, performing a treatment with antiviral drugs or caesarean section delivery can decrease the riskof neonatal infection

Protector and Casualty

2019 ◽  
pp. 495-522
Author(s):  
Meg Dennison ◽  
Katie McLaughlin
Keyword(s):  
Early Life ◽  
Positive Emotion ◽  
Positive Emotions ◽  
Protective Factor ◽  
Mental Health Problems ◽  
Positive Emotionality ◽  
Early Life Adversity ◽  
Adverse Experiences ◽  
Wide Range ◽  
Positive Valence

Early-life adversity is associated with elevated risk for a wide range of mental disorders across the lifespan, including those that involve disruptions in positive emotionality. Although extensive research has evaluated heightened negative emotionality and threat processing as developmental mechanisms linking early-life adversity with mental health problems, emerging evidence suggests that positive emotions play an integral, but complex, role in the association of early-life adversity with psychopathology. This chapter identifies two pathways through which positive emotion influences risk for psychopathology following early-life adversity. First, experiences of early-life adversity may alter the development of the “positive valence system”, which in turn increases risk for psychopathology. Second, the association between adversity and psychopathology may vary as a function of individual differences in positive emotionality. We consider how the development of positive emotionality—measured at psychological, behavioral and neurobiological levels—may be altered by early-life adversity, creating a diathesis for psychopathology. We additionally review evidence for the role of positive emotion, measured at multiple levels, as a protective factor that buffers against the adverse impacts of adversity. In integrating these two roles, it is proposed that characteristics of environmental adversity, including developmental timing, duration, and type of adversity, may differentially impact the development of positive emotionality, leading to a better understanding of risks associated with specific adverse experiences. Methodological issues regarding the measurement of adverse environments as well as implications for early intervention and treatment are discussed.

scholarly journals Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Zhanying Zheng ◽  
Sharon Shui Yee Leung ◽  
Raghvendra Gupta
Keyword(s):  
Dry Powder Inhaler ◽  
Research Direction ◽  
Particle Methods ◽  
Future Research ◽  
High Dose ◽  
Dry Powder ◽  
Multi Scale ◽  
Wide Range ◽  
Computational Fluid Dynamics Cfd ◽  
Discrete Element Methods

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

scholarly journals A Novel Benzopyrane Derivative Targeting Cancer Cell Metabolic and Survival Pathways

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2840
Author(s):  
Dana M. Zaher ◽  
Wafaa S. Ramadan ◽  
Raafat El-Awady ◽  
Hany A. Omar ◽  
Fatema Hersi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Mitochondrial Metabolism ◽  
High Dose ◽  
Anticancer Effect ◽  
Safety Margins ◽  
Wide Range

(1) Background: Today, the discovery of novel anticancer agents with multitarget effects and high safety margins represents a high challenge. Drug discovery efforts indicated that benzopyrane scaffolds possess a wide range of pharmacological activities. This spurs on building a skeletally diverse library of benzopyranes to identify an anticancer lead drug candidate. Here, we aim to characterize the anticancer effect of a novel benzopyrane derivative, aiming to develop a promising clinical anticancer candidate. (2) Methods: The anticancer effect of SIMR1281 against a panel of cancer cell lines was tested. In vitro assays were performed to determine the effect of SIMR1281 on GSHR, TrxR, mitochondrial metabolism, DNA damage, cell cycle progression, and the induction of apoptosis. Additionally, SIMR1281 was evaluated in vivo for its safety and in a xenograft mice model. (3) Results: SIMR1281 strongly inhibits GSHR while it moderately inhibits TrxR and modulates the mitochondrial metabolism. SIMR1281 inhibits the cell proliferation of various cancers. The antiproliferative activity of SIMR1281 was mediated through the induction of DNA damage, perturbations in the cell cycle, and the inactivation of Ras/ERK and PI3K/Akt pathways. Furthermore, SIMR1281 induced apoptosis and attenuated cell survival machinery. In addition, SIMR1281 reduced the tumor volume in a xenograft model while maintaining a high in vivo safety profile at a high dose. (4) Conclusions: Our findings demonstrate the anticancer multitarget effect of SIMR1281, including the dual inhibition of glutathione and thioredoxin reductases. These findings support the development of SIMR1281 in preclinical and clinical settings, as it represents a potential lead compound for the treatment of cancer.

Distribution, feeding behaviour, and condition of Cape horse mackerel early life stages, Trachurus capensis, under different environmental conditions in the northern Benguela upwelling ecosystem

2014 ◽  
Vol 72 (2) ◽  
pp. 543-557 ◽  
Author(s):  
S. J. Geist ◽  
A. Kunzmann ◽  
H. M. Verheye ◽  
A. Eggert ◽  
A. Schukat ◽  
...  
Keyword(s):  
Dissolved Oxygen ◽  
Feeding Ecology ◽  
Environmental Conditions ◽  
Early Life ◽  
Early Life History ◽  
Horse Mackerel ◽  
Larval Phase ◽  
Recruitment Success ◽  
Wide Range ◽  
Variable Recruitment

Abstract Early life history (ELH) traits are key to understand variable recruitment success and hence the stock size of marine fish. One of the currently most puzzling ecosystems in this regard is the northern part of the Benguela Current upwelling system off Namibia. Here, populations of the formerly dominant pelagic species, sardine and anchovy, failed to recover during the last three decades after a dramatic decline. In contrast, Cape horse mackerel, Trachurus capensis, maintained a constant population size. Warming of the system and shoaling of hypoxic zones together with feedback loops within an altered foodweb are discussed to be responsible for this regime shift. In this study, we address the role of larval traits for the successful performance of the T. capensis population under the present environmental conditions with the focus on feeding ecology. We investigated seasonal variations of the geographical distribution, growth rate, feeding ecology, and nutritional condition of their ELH stages and examined relationships with water temperature, dissolved oxygen concentration, and micro-zooplankton composition. T. capensis' ELH stages showed a wide spatial and seasonal distribution, a preference for higher water temperatures (18–21°C) and presence over a wide range of dissolved oxygen concentrations (0.13–6.35 ml O2 l−1). Feeding success was high and mainly different groups of Copepoda were targeted, which were strongly size selected. The high dietary importance of micro-copepods during large parts of the larval phase indicates successful exploitation of this food source, which has increased in abundance during the last decade. It also explains observed best nutritional conditions at temperatures between 18 and 21°C, since these small copepods are commonly associated with warmer temperatures. Altogether, these traits enhance the species' probability to encounter suitable environments for the survival of their ELH stages, which is likely to lead to their high recruitment success in the northern Benguela ecosystem.

Lifestyle intervention strategies in early life to improve pregnancy outcomes and long-term health of offspring: a narrative review

2018 ◽  
Vol 10 (3) ◽  
pp. 314-321 ◽  
Author(s):  
Romy Gaillard ◽  
John Wright ◽  
Vincent W.V. Jaddoe
Keyword(s):  
Health Outcomes ◽  
Pregnancy Outcomes ◽  
Early Life ◽  
Observational Studies ◽  
Postnatal Period ◽  
Modifiable Risk Factors ◽  
Lifestyle Interventions ◽  
Randomized Controlled ◽  
Offspring Health

AbstractAdverse exposures during fetal life and the postnatal period influence physical, cognitive and emotional development, and predispose to an increased risk of various chronic diseases throughout the life course. Findings from large observational studies in various populations and experimental animal studies have identified different modifiable risk factors in early life. Adverse maternal lifestyle factors, including overweight, unhealthy diet, sedentary behavior, smoking, alcohol consumption and stress in the preconception period and during pregnancy, are the most common modifiable risk factors leading to a suboptimal in-utero environment for fetal development. In the postnatal period, breastfeeding, infant growth and infant dietary intake are important modifiable factors influencing long-term offspring health outcomes. Despite the large amount of findings from observational studies, translation to lifestyle interventions seems to be challenging. Currently, randomized controlled trials focused on the influence of lifestyle interventions in these critical periods on short-term and long-term maternal and offspring health outcomes are scarce, have major limitations and do not show strong effects on maternal and offspring outcomes. New and innovative approaches are needed to move from describing these causes of ill-health to start tackling them using intervention approaches. Future randomized controlled lifestyle intervention studies and innovative observational studies, using quasi-experimental designs, are needed focused on the effects of an integrated lifestyle advice from preconception onwards on pregnancy outcomes and long-term health outcomes in offspring on a population level.

scholarly journals 2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Specific Population ◽  
Gram Negative ◽  
Wide Range

Abstract Background The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population. Methods We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected. Results Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%). The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively. Conclusion Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population. Disclosures All authors: No reported disclosures.

scholarly journals Combatting Vitamin A deficiency

2017 ◽  
Vol 8 (2) ◽  
pp. 151 ◽  
Author(s):  
Ted H Greiner
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Economic Benefits ◽  
Point Of View ◽  
Preschool Age ◽  
High Dose ◽  
Sample Sizes ◽  
Sweet Potatoes ◽  
Target Groups ◽  
Wide Range

Food-based approaches to combat vitamin A deficiency (VAD) continue to be largely ignored by governments and donor agencies. This review deals with common misperceptions as well as constraints that may lay behind this reality. First, high-dose vitamin A capsules provided to preschool age children are no solution for VAD. Second, researchers may assume that it is not possible to standardize foods adequately to study their efficacy in controlled trials. This review summarizes the results of 57 such trials, providing an overview that may assist researchers in making decisions on target groups to study, types of food supplements to provide, quantities, supplementation periods, impacts that are realistic to expect, and sample sizes. Even more complex is to design efficacy trials or impact evaluations of interventions. Again, the paper reviews 40 such trials, providing summary information on approaches, target groups, sample sizes, periods of intervention, and impacts measured using a variety of indicators. There are a number of barriers or constraints that must be planned for and overcome if food-based approaches are to work. This paper reviews several of the most important ones, briefly touching on many of the most effective ways that have been found to overcome them. Food-based approaches can reach all members of the community, are safe for pregnant women, tend to be at least partially sustainable, and confer a wide range of nutritional and other benefits in addition to improving vitamin A status. Food-based approaches are sometimes described as expensive, but this is based on a narrow view. For example, biofortification and dissemination of sweet potatoes cost $9 to $30 per disability-life-year (DALY) gained, while that from VAS was estimated at the estimated cost effectiveness of VAS is $73 per DALY gained. From the community point of view, the economic benefits of food based approaches are likely to subsidize or outweigh their costs.

scholarly journals Efficacy and Toxicity of Treatments for Primary Central System Lymphoma: Review of the Recent Literature

2019 ◽  
Vol 9 (1) ◽  
pp. 61-67
Author(s):  
Mohammad Jay ◽  
David. A. MacDonald
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Benefit ◽  
Radiation Treatment ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Wide Range

Primary Central Nervous system lymphoma (PCNSL) is an uncommon type of central nervous system lymphoma, most commonly presenting as hemiparesis and headache. Currently, there is a wide range of treatments for PCNSL, consisting of various permutations between chemotherapy, radiation and autologous stem cell transplant (ASCT). Although the backbone of PCNSL treatment consists of High-dose Methotrexate (HD-MTX), the role of combination versus single agent chemotherapy, combined modality (chemotherapy + radiation) versus chemotherapy or radiation alone, and the use of consolidative ASCT are contested. Surgery does not have a role in the treatment of PCNSL although stereotactic biopsies tend to help with symptomatic relief. Radiation monotherapy is generally reserved for patients with contraindications to chemotherapy or as a palliative measure. Combined chemotherapy and radiation treatment has been shown to have a great efficacy, although its increased neurotoxicity compared to chemotherapy alone is a major drawback. A growing body of research is focused on comparing the efficacy of various chemotherapeutic regimens. Currently, the MATRix regimen comprising of HD-MTX(3.5g/m2)-cytarabine/rituximab/thiotepa is widely used. The additional survival benefit of ASCT is contested although its role in the treatment of refractory or relapsed PCNSL is generally agreed upon. Finally, intrathecal HD-MTX has been shown to have added survival benefit when added to the standard therapies. Further retrospective and prospective studies are required to compare the efficacy and toxicity of various treatment options, with a focus on different chemotherapeutic agents and ASCT.

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