The effects of antenatal glucocorticoid exposure on fetal and neonatal skin maturation

2017 ◽  
Vol 45 (8) ◽  
Author(s):  
Deanne August ◽  
Yogavijayan Kandasamy
Keyword(s):  
Animal Studies ◽  
Controlled Trial ◽  
Fetal Lung ◽  
Human Studies ◽  
Standard Clinical Practice ◽  
Antenatal Steroids ◽  
Improved Outcomes ◽  
Type Ii Pneumocytes ◽  
Neonatal Skin ◽  
And Function

AbstractAims:The use of antenatal glucocorticoids in women with preterm labor has dramatically improved outcomes for premature infants. The most commonly used antenatal glucocorticoids are betamethasone and dexamethasone. Glucocorticoids accelerate fetal lung growth by several mechanisms, including the maturation of type II pneumocytes enabling surfactant production. Furthermore, the lipids in the lung share similarity with those in the skin. Therefore, antenatal administration of glucocorticoids may have effects on the structure and function of the developing epidermal barrier in fetuses and neonates.Methods:We performed a systematic review to characterize these effects, identifying 11 studies (six animal and five human studies).Results:Five out of the six animal studies used a rodent model for investigating the effects of antenatally administered glucocorticoids, while the other used an ovine model. Antenatally administered glucocorticoids accelerated skin maturation in animal studies, but studies of human fetuses found conflicting results. None of the reviewed studies compared the effects of different types of glucocorticoids.Conclusions:More human studies are needed to fully understand the effects of antenatal steroids. However, as the antenatal use of glucocorticoids in preterm pregnancies has become part of standard clinical practice, it would be unethical to carry out a large randomized controlled trial. We may have to rely on animal models to improve our understanding of the effects of antenatal glucocorticoid exposure on the fetal and neonatal skin maturation.

scholarly journals Role of Factor XIa and Plasma Kallikrein in Arterial and Venous Thrombosis

2020 ◽  
Vol 120 (06) ◽  
pp. 883-993 ◽  
Author(s):  
Mayken Visser ◽  
Stefan Heitmeier ◽  
Hugo ten Cate ◽  
Henri M. H. Spronk
Keyword(s):  
Venous Thrombosis ◽  
Animal Studies ◽  
Vascular Occlusion ◽  
Coagulation Factors ◽  
Human Studies ◽  
Plasma Kallikrein ◽  
Contact Activation ◽  
Charged Surfaces ◽  
Factor Xia ◽  
And Function

AbstractCardiovascular disease, including stroke, myocardial infarction, and venous thromboembolism, is one of the leading causes of morbidity and mortality worldwide. Excessive coagulation may cause vascular occlusion in arteries and veins eventually leading to thrombotic diseases. Studies in recent years suggest that coagulation factors are involved in these pathological mechanisms. Factors XIa (FXIa), XIIa (FXIIa), and plasma kallikrein (PKa) of the contact system of coagulation appear to contribute to thrombosis while playing a limited role in hemostasis. Contact activation is initiated upon autoactivation of FXII on negatively charged surfaces. FXIIa activates plasma prekallikrein (PK) to PKa, which in turn activates FXII and initiates the kallikrein–kinin pathway. FXI is also activated by FXIIa, leading to activation of FIX and finally to thrombin formation, which in turn activates FXI in an amplification loop. Animal studies have shown that arterial and venous thrombosis can be reduced by the inhibition of FXI(a) or PKa. Furthermore, data from human studies suggest that these enzymes may be valuable targets to reduce thrombosis risk. In this review, we discuss the structure and function of FXI(a) and PK(a), their involvement in the development of venous and arterial thrombosis in animal models and human studies, and current therapeutic strategies.

Efficacy of topical cannabinoids in the management of pain: a systematic review and meta-analysis of animal studies

2022 ◽  
pp. rapm-2021-102719
Author(s):  
Lukas D Linde ◽  
Carey M Ogryzlo ◽  
Cassandra M Choles ◽  
Brian E Cairns ◽  
John L K Kramer
Keyword(s):  
Pain Management ◽  
Side Effects ◽  
Animal Studies ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Preliminary Evidence ◽  
Human Studies ◽  
Tail Flick ◽  
Major Barrier ◽  
Pain Ratings

Background/importanceCannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management.ObjectiveOur purpose was to systematically review the literature on the effectiveness of peripherally acting cannabinoids for pain management.Evidence reviewWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed databases. Included studies examined the effect of topical/peripherally administered cannabinoids on pain ratings in humans, as well as pain-related outcomes in animals (eg, paw withdrawal). Due to a lack of trials, human studies were summarized in a narrative synthesis. Separate meta-analyses were performed for animal studies using radiant tail flick or paw withdrawal outcomes.FindingsOur search yielded 1182 studies following removal of duplicates, with 46 studies (6 human, 40 animal) included. Human studies (one randomized controlled trial and five case studies/series) reported no adverse events to topical cannabinoids and preliminary evidence of decreased pain ratings. Animal studies reporting tail flick (5) (2.81, 95% CI 1.93 to 3.69, p<0.001) and mechanical withdrawal (11) (2.74, 95% CI 1.82 to 3.67, p<0.001) reported prolonged responses (analgesia) in peripheral cannabinoid groups compared with controls.ConclusionsPreclinical animal studies provided low-quality evidence for peripherally administered cannabinoids to provide regional, antinociceptive effects. The scarcity of high-quality human studies underscores the need to translate preclinical evidence into well-controlled human trials.

Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives

2020 ◽  
Vol 20 ◽  
Author(s):  
Suong N.T. Ngo ◽  
Desmond B. Williams
Keyword(s):  
Breast Cancer ◽  
Protective Effect ◽  
Animal Studies ◽  
Cancer Survival ◽  
Breast Cancer Survival ◽  
Human Studies ◽  
In Vitro Studies ◽  
Cochrane Library ◽  
Cruciferous Vegetables

Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their antibreast cancer effects. Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peerreviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways which promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemoresistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively smallest inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane appeared to display the greatest potential.

scholarly journals Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reperfusion Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Human Studies ◽  
Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

scholarly journals Nutrition-focused group intervention with a strength-based counseling approach for people with clinical depression: a study protocol for the Food for Mind randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Roponen ◽  
Anu Ruusunen ◽  
Pilvikki Absetz ◽  
Timo Partonen ◽  
Virpi Kuvaja-Köllner ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Diet Quality ◽  
Group Intervention ◽  
Controlled Trial ◽  
Treatment Of Depression ◽  
Strength Based ◽  
Behavioral Nutrition ◽  
And Function

Abstract Background Depression is a highly prevalent mental disorder with major public health effects globally. It impairs the quality of life and reduces the ability to work and function, leading to increasing costs of sick leaves and disability pensions. Current treatment strategies focus on biological and psychological pathways while understating the role of lifestyle factors. Epidemiological studies have shown convincing evidence of an inverse relationship between diet quality and depression. However, only limited data are available on the therapeutic effects of diet quality improvement on depression. Using a randomized controlled trial design, our primary aim is to investigate the effectiveness and cost-effectiveness of a behavioral nutrition group intervention compared to a social support intervention in the treatment of depression. Methods Participants (N=144, aged 20–65 years) with a diagnosis of moderate or severe depression recruited in collaboration with outpatient care units will be randomized into two arms: Food for Mind (FM) nutrition intervention (n=72) or Bring Good Mood (BGM) social support control group (n=72). Both arms will be provided with 6 group sessions over an 8-week period. FM involves improving diet quality by applying strength-based behavioral nutrition counseling and activities facilitated by a registered dietitian. The control arm comprises a befriending protocol. During the interventions, all participants will continue their treatment for depression as usual. Longitudinal data are collected at baseline, at 8 weeks, and at 6- and 12-month follow-ups. Depressive symptoms, diet quality, eating behavior, ability to work and function, and quality of life are assessed by self-reported questionnaires. A treatment expectancy questionnaire will be administered at baseline and an acceptability questionnaire at 8 weeks. The Center for Epidemiologic Studies Depression Scale is used as the primary endpoint at 1 year. The results will be analyzed with linear mixed-effects models. Economic evaluation includes both cost-effectiveness and cost-utility analysis. Two incremental cost-effectiveness ratios will be calculated to evaluate the incremental cost per QALY and the incremental cost per improvement in CES-D. Discussion If the intervention proves to be cost-effective and acceptable, it be can be implemented in healthcare to support the treatment of depression. Trial registration ClinicalTrials.gov NCT03904771. Retrospectively registered on 5 April 2019

scholarly journals Metformin reduces 12-month change in body weight among people newly commenced on clozapine: a retrospective naturalistic cohort study

2021 ◽  
Vol 11 ◽  
pp. 204512532110006
Author(s):  
Jessica Spokes ◽  
Samantha Hollingworth ◽  
Karl Winckel ◽  
Steve Kisely ◽  
Andrea Baker ◽  
...  
Keyword(s):  
Cohort Study ◽  
Weight Gain ◽  
Tobacco Smoking ◽  
Digital Health ◽  
Controlled Trial ◽  
Bodyweight Gain ◽  
Metabolic Effects ◽  
Secondary Outcome ◽  
Standard Clinical Practice ◽  
Randomised Controlled

Background: People with schizophrenia have a 15–20-year reduction in life expectancy, driven in part by the metabolic effects of antipsychotics. Clozapine is associated with the highest rates of weight gain. As clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), identifying treatments to ameliorate clozapine-induced weight gain (CIWG) is urgently needed to reduce this morality gap. Methods: We retrospectively analysed digital health records of patients with TRS aged 18–65 newly initiated on clozapine at four tertiary hospitals in south-east Queensland from 1 March 2017 to 30 June 2019. Our primary outcome was the effect of metformin on change in percentage bodyweight at 12 months after clozapine initiation, with secondary outcome being proportion with >5% or >7% bodyweight change. We also explored impact on bodyweight change of other variables including sex, tobacco smoking, type 2 diabetes (T2DM), age, clozapine level and dose and clozapine/norclozapine ratio. Results: Among 90 patients initiated on clozapine, metformin use ( n = 48) was associated with a smaller increase in percentage bodyweight (1.32% versus 5.95%, p = 0.031), lower rates of >7% gain in bodyweight (37.8% versus 63.0%, p = 0.025) but not >5% gain in bodyweight. Age below the median (32.0 years) was associated with greater bodyweight gain (5.55% versus 1.22%, p = 0.046). Sex, tobacco smoking, T2DM, clozapine dose and level and clozapine/norclozapine ratio were not associated with differences in change in bodyweight. Conclusion: In this small retrospective cohort study, use of metformin within 12-months of clozapine initiation was associated with a statistically and clinically significant reduction in CIWG. Although there is increasing evidence for the role of metformin to ameliorate bodyweight gain at time of clozapine initiation, our findings need replication and testing in a randomised controlled trial before recommending metformin co-commencement with clozapine as standard clinical practice.

scholarly journals Combined Hip Abductor and External Rotator Strengthening and Hip Internal Rotator Stretching Improves Pain and Function in Patients With Patellofemoral Pain Syndrome: A Randomized Controlled Trial With Crossover Design

2021 ◽  
Vol 9 (4) ◽  
pp. 232596712198972
Author(s):  
Anis Jellad ◽  
Amine Kalai ◽  
Mohamed Guedria ◽  
Mahbouba Jguirim ◽  
Sana Elmhamdi ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Pain Syndrome ◽  
Patellofemoral Pain Syndrome ◽  
Patellofemoral Pain ◽  
Level Of Evidence ◽  
Randomized Controlled ◽  
Group Standard ◽  
Hip Muscle ◽  
And Function

Background: Active rehabilitation has an important role in the management of patellofemoral pain syndrome (PFPS). Although some studies have shown the benefit of hip-muscle strengthening, the effect of combining hip-muscle stretching with strengthening has not yet been defined. Purpose: To evaluate the effect of combined strengthening of the hip external rotators and abductors and stretching of the hip internal rotators on pain and function in patients with PFPS. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 109 patients with PFPS (75 female and 34 male; mean age, 31.6 ± 10.8 years) were first randomly assigned to protocol A (n = 67) of the A-B arm (AB group; standard rehabilitation) or protocol B (n = 42) of the B-A arm (BA group; standard rehabilitation with strengthening of the hip external rotators and abductors and stretching of the hip internal rotators). Each protocol consisted of 3 sessions a week for 4 weeks. After a washout period, corresponding to a symptom-free period, rehabilitation programs were crossed over. A visual analog scale (VAS) evaluating perceived pain, the Functional Index Questionnaire (FIQ), and the Kujala score were administered at baseline, the end of each rehabilitation protocol, and 12 weeks after the completion of the second protocol for each group. Results: Until the final follow-up, VAS, FIQ, and Kujala scores were significantly improved in both the A-B and B-A arms ( P < .05 for all). Compared with protocol A, protocol B provided significant improvement in terms of pain and function in both the BA (VAS and Kujala; P < .001) and AB (VAS and Kujala; P < .001) groups. Conclusion: Combined strengthening of the hip abductors and external rotators with stretching of the hip internal rotators provided better outcomes, which were maintained for at least 12 weeks, in terms of pain and function in patients with PFPS.

scholarly journals Baseline Characteristics of Participants in a Randomized Controlled Trial of Metformin for Frailty Prevention

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 130-131
Author(s):  
Tiffany Cortes ◽  
Nicolas Musi ◽  
Chen-pin Wang ◽  
Joel Michalek ◽  
Sara Espinoza
Keyword(s):  
Randomized Controlled Trial ◽  
Glucose Tolerance ◽  
Physical Performance ◽  
Controlled Trial ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Randomized Controlled ◽  
Insulin Clamp ◽  
And Function

Abstract We are conducting a double-blind, randomized controlled trial of metformin for frailty prevention. Participants are adults aged 65+ years with pre-diabetes assessed by 2-hour oral glucose tolerance test (OGTT). Those who are frail (Fried criteria) are excluded. Participants are randomized to metformin (maximum dose of 2,000 mg/day) vs. placebo and followed for 2 years. The primary outcome is frailty (category and score); secondary outcomes are physical performance and function (short physical performance battery, 6-minute walk, lower extremity strength), systemic and skeletal muscle tissue inflammation, muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (OGTT), and body composition (dual-energy x-ray absorptiometry). Safety assessments occur every 3 months; frailty, systemic inflammation, and OGTT are assessed at baseline and every 6 months, and insulin clamp with muscle biopsies are assessed at baseline and every 12 months. To date, 85 subjects have been randomized; 120 completers are planned. Mean age is 72.8 ± 5.7 years, 55.3% are male, and 43.5% were Hispanic. Mean BMI is 30.2±5.8 kg/m2, waist circumference is 104.4 ±15.5 cm, fasting glucose is 102.3 ± 10.0 mg/dL, Hemoglobin A1c is 5.8 ±0.3, and glucose at 2 hours during OGTT is 167.3 ± 17.8 mg/dL. Metformin is being examined in this study as a potential therapeutic agent to prevent frailty in older adults with pre-diabetes. Findings from this trial may have future implications for the screening and potential treatment of pre-diabetes in older patients with metformin for the prevention of frailty.

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