Inappropriate Manipulation Research Articles

Experimental and theoretical model of microvascular network remodeling and blood flow redistribution following minimally invasive microvessel laser ablation.

Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling. The microvasculature was imaged non-invasively by bright-field and multi-photon laser microscopy, and optical coherencetomography pre-ablation and up to 30 days post-ablation. A theoretical model of network remodeling was developed to compute blood flow and intravascular pressure and identify vessels most susceptible to changes in flow direction. The skin microvascular remodeling patterns were consistent among the five specimens studied. Significant remodeling occurred at various time points, beginning as early as days 1-3 and continuing beyond day 20. The remodeling patterns included collateral development, venous and arterial reopening, and both outward and inward remodeling, with variations in the time frames for each mouse. In a representative specimen, immediately post-ablation, the average artery and vein diameters increased by 14% and 23%, respectively. At day 20 post-ablation, the maximum increases in arterial and venous diameters were 2.5× and 3.3×, respectively. By day 30, the average artery diameter remained 11% increased whereas the vein diameters returned to near pre-ablation values. Some arteries regenerated across the ablation sites via endothelial cell migration, while veins either reconnected or rerouted flow around the ablation site, likely depending on local pressure driving forces. In the intact network, the theoretical model predicts that the vessels that act as collaterals after flow disruption are those most sensitive to distant changes in pressure. The model results correlate with the post-ablation microvascular remodeling patterns.

Successful Extraction of Guidewire Entrapped in the Tricuspid Valve Leaflet Using a Laser Sheath

Right ventriculography is a necessary step for implantation of leadless pacemaker and is considered a safe procedure. However, an inappropriate manipulation of the guidewire can lead to serious complications. We present a case where the guide-wire was entrapped in the tricuspid valve, and its successful extraction using a laser sheath. (Level of Difficulty: Advanced.)

Retraction

Retraction: “KDM6B promotes ovarian cancer cell migration and invasion by induced transforming growth factor‐β1 expression,” by Shumei Liang, Qingmin Yao, Deying Wei, Ming Liu, Feng Geng, Qin Wang, and Yun‐shan Wang. Journal of Cellular Biochemistry 2019, 493‐506. The above article, published online on 11 September 2018 in Wiley Online Library (doi:10.1002/jcb.27405), has been retracted by agreement between the authors, the journal's Editor‐in‐Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed after the authors asked for a correction. An investigation revealed duplication and inappropriate manipulation in figure 7D. As a result, the experiments in this article are considered unreliable and to not sufficiently support the conclusions.

Liberal democracy: absolutist eu rule of law conditionality or pluralistic bargaining chip?

EU membership accentuates values. The current emphasis is a case of EU idealism, of stricter conditionality in response to political ideology and governance. Democracy is tantamount to liberal democracy, but at the same time pluralism is an integral part of the conditionality. This raises the question about the countryspecific maneuvering scope or – if EU candidate countries and Member States (are seen to) deviate from a non-negotiable ideal – inappropriate manipulation. While the authors do not address absolutism per se, they proceed on the premise that the “European perspective” disallows any value dilution, thereby maximizing theconflict and identity crisis which Poland and Hungary have caused and which have overshadowed accession talks for candidate countries. One intention is to contextualize the debate and dispute about values by incorporating interdisciplinary insights. Another is to challenge the (European perspective on the) rule of law cluster, inter alia, with the illiberal measures that Denmark has adopted.

Inappropriate manipulation and drainage exacerbate post-operative pain and prolong the hospital stay after laparoscopic appendectomy for pediatric complicated appendicitis

BackgroundThis study examined whether drain placement or not is associated with the postoperative outcomes of pediatric patients following trans-umbilical single-port laparoscopic appendectomy (TUSPLA) for complicated appendicitis.Methods The medical records of pediatric patients undergoing TUSPLA for acute complicated appendicitis from January 2012 to September 2018 in Kaohsiung Chang Gung Memorial Hospital were reviewed retrospectively. They were classified according to whether they received passive drainage with a Penrose drain (Penrose group) (19), active drainage with a Jackson-Pratt drain with a vacuum bulb (JP group) (16), or no drain (non-drain group) (86). The postoperative outcomes of the three groups were compared.ResultsPostoperative visual analog scale pain score was significantly higher in the non-drain group than in either the JP group or Penrose group. Patients in the Penrose group had a significantly longer postoperative hospital stay than those in the non-drain group and a higher rate of intra-abdominal abscess, while patients in the JP group had a significantly shorter postoperative hospital stay; moreover, no patient in JP group developed a postoperative intra-abdominal abscess.ConclusionsCompared to passive drainage with a Penrose drain or no drain, active drainage with a JP drain shorter the postoperative hospital stay and decreased the risk of postoperative intra-abdominal abscess.

Estimated Manipulation of Tablets and Capsules to Meet Dose Requirements for Chinese Children: A Cross-Sectional Study.

Objectives: To estimate the frequency of manipulations of all tablets and capsules prescribed for children in a teaching and tertiary children's hospital in China over the course of 1 month. Moreover, hypothetical reduction of manipulation according to the availability of low-strength tablets/capsules licensed by the Chinese National Medical Products Administration (CNMPA) was evaluated.Methods: Information on all tablets and capsules prescribed in the hospital from March 17 to April 16, 2019 was collected. It was assumed that tablets or capsules were manipulated if the prescribed dose would have required only a proportion of the intact dose form. Manipulation typically includes splitting or crushing tablets, opening capsules and dispersing in water, or combinations of these method. Moreover, we defined an “avoidable manipulation,” when the dose could be rounded and/or when alternative products with a reduced strength or in liquid formulation were available in the hospital, and a “inappropriate manipulation,” which involved manipulated medications with a direct contraindication for any manipulation, such as those with a narrow therapeutic index or hazardous ingredients, or modified release dosage-forms. The frequencies of total, avoidable, and inappropriate manipulation were estimated, along with the hypothetical reduction of manipulation according to the availability of CNMPA-approved drug doses.Results: A total of 17,123 prescriptions for 142 medications were identified to have required a manipulation among 78,366 prescriptions administered during the study period, with 43 different proportions of subdivisions, ranging from a 19/20 to 1/180 product strength reduction. Half, quarter, and trisection were the most common subdivisions administered. Overall, 19% of the manipulated prescriptions were determined to be avoidable, and 19% of the manipulations involved medications with a clear recommendation to not manipulate. In addition, 21% of the manipulated prescriptions could have been potentially avoided if all of the approved preparations with the lowest strength would have been available at the hospital. Any manipulations undertaken were carried out by pharmacists and family care givers.Conclusions: More than 20% of tablets and capsules prescriptions need manipulated, included a high incidence of avoidable and inappropriate manipulation.

Retraction.

Retraction: "Role of RKIP in human hepatic stellate cell proliferation, invasion, and metastasis", by Quanfang Huang, Jinbin Wei, Ling Wei, Xiaolin Zhang, Facheng Bai, Shujuan Wen, Yuanyuan Wei, Shimei Tan, Zhongpeng Lu, and Xing Lin, J Cell Biochem. 2019; 6168-6177: The above article, published online on 10 October 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcb.27904) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. The investigation was conducted by several experts into the accuracy of the data acquisition and concluded that inappropriate manipulation had taken place during Western blotting. Specifically, inconsistencies and duplicated image elements were found in figures 1A, 1B, 1D, 2C, 5D, and 6A. The authors disagree with this decision.

Inappropriate Manipulation of Digital Images

Inappropriate Manipulation of Digital Images

Measuring the Appropriateness of Spinal Manipulation for Chronic Low Back and Chronic Neck Pain in Chiropractic Patients.

RAND/UCLA Appropriateness Method (RUAM) applied to chiropractic manipulation for patients with chronic low-back pain (CLBP) and chronic neck pain (CNP). Determine the rate of appropriate care provided by US chiropractors. Spinal manipulation has been shown effective for CLBP and CNP but may not be appropriate for all patients with these conditions. Ratings of the appropriateness of spinal and cervical manipulation previously developed by two RUAM expert panels were applied to data abstracted from random samples of patient charts from chiropractors in six US regions to determine the appropriateness of manipulation for each patient. Of 125 chiropractors sampled, 89 provided charts that could be abstracted. Of the 2128 charts received, 1054 were abstracted. Charts received but not abstracted included 460 that were unusable (e.g., illegible), and 555 did not have CLBP or CNP. Across the abstracted charts 72% had CLBP, 57% had CNP, and 29% had both; 84% of patients with CLBP and 86% with CNP received manipulation. Patients with CLBP who had minor neurologic findings, sciatic nerve irritation, or no joint dysfunction were significantly less likely to receive manipulation. Patients with CNP who had substantial trauma etiology, no joint dysfunction, or no radiographs were significantly less likely to receive manipulation. Most manipulation for CLBP (64%) was appropriate and most manipulation for CNP (93%) was for patients where appropriateness was uncertain or equivocal. The proportions of patients receiving inappropriate manipulation for either condition were low (1%-3%) as were the numbers of patients presenting to these chiropractors for which manipulation was inappropriate. Chiropractors in this US sample tend to provide manipulation to very few patients with CLBP or CNP for which it is inappropriate. However, more research is needed to determine which patients with CNP benefit from manipulation.Level of Evidence: 4.

RETRACTED: LncRNA GAS6-AS1 facilitates the progression of breast cancer by targeting the miR-324-3p/SETD1A axis to activate the PI3K/AKT pathway

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the current Editor in Chief, with the agreement of all authors. The article is being retracted due to inappropriate manipulation of the original data for presentation in Figures 2C, 5C and 6C. Upon further investigation and discussion with the authors, insufficient evidence was provided to support a reasonable explanation for these mistakes. In addition, the authors could not provide convincing original data supporting other figures of the manuscript, e.g. Figures 2G, 4 and 6A. Based on these findings, the Editor in Chief and the authors have decided to retract the study. The authors apologize for any inconvenience caused.

Retraction.

Retraction of 'Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression', by Yuan H, Zhang J, Li F, Li W1, Wang H. 2019;125(5):450-459: The above article, published online on 17 July 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13285), has been retracted by agreement between the journal Editor in Chief, Professor Kim Brøsen, the Nordic Association for the Publication of BCPT and John Wiley & Sons Ltd. The retraction has been decided following an investigation based on public allegations. The authors disagree with this decision. The investigation was conducted by several experts into the accuracy of the data acquisition, and concluded that inappropriate manipulation had taken place during Western blotting. REFERENCE Yuan H, Zhang J, Li F, Li W, Wang H. Sinomenine exerts anti-tumour effect in gastric cancer cells via enhancement of miR-204 expression. Basic Clin Pharmacol Toxicol. 2019;125(5):450-459. https://doi.org/10.1111/bcpt.13285.

Retraction statement: 'Identification, subcellular localization and some properties of a cysteine-rich suppressor of gene silencing encoded by peanut clump virus' by Patrice Dunoyer, Sébastien Pfeffer, Christiane Fritsch, Odile Hemmer, Olivier Voinnet and K. E. Richards (https://onlinelibrary.wiley.com/doi/full/10.1046/j.0960-7412.2001.01242.x) and 'Correction' by Dunoyer et al. (https://onlinelibrary.wiley.com/doi/10.1111/tpj.12884).

The above original article, first published online on 01 March 2002 in Wiley Online Library (wileyonlinelibrary.com), and in volume 29, pp. 555-567, has been retracted by agreement between the following authors: Patrice Dunoyer, Sébastien Pfeffer, Christiane Fritsch, Odile Hemmer, Olivier Voinnet and K. E. Richards, the journal Editor-in-Chief, Lee Sweetlove, and John Wiley & Sons Ltd. This notice updates and replaces the article and its correction notice, published on 10 June 2015 and in volume 82, pp. 1076-1077. In the correction notice, updated versions of Figures 2, 3 and 6 were published. It has since come to light that an image provided for the correction notice (Fig 2C) contained evidence of inappropriate manipulation. Additional inconsistencies in the representation of the data shown in Figures 3 and 4 have also become apparent. Patrice Dunoyer and Sébastien Pfeffer take full responsibility for the described manipulation and inconsistencies that were made without the consent or knowledge of any of the other co-authors. The authors consider that the integrity of the paper has been compromised and that the most appropriate course of action is a retraction of the article.

Photodynamic therapy in wound healing in vivo: a systematic review

Wounds constitute severe problems in public health. Inappropriate manipulation to promote wound healing and indiscriminate use of antibiotics may contribute to failure in wound treatment, leading to bacterial growth and resistance. Appropriate and correct approaches to wound treatment are crucially important. Further, the development of new and effective treatment modalities is important to decrease infection-related mortality and to reduce patient suffering and side effects. Photodynamic therapy (PDT) could be a promising approach to ameliorate this global health problem. We researched articles that used PDT in wound healing in vivo. The systematic review included articles that investigated the effect of PDT on wound healing in animals, published from May 2008 through 2018, in the databases PubMed and Web of Science. The main types of wounds described in the selected articles were burns, abrasions, and excisional wounds. Most of the studies tested PDT in wounds infected by methicillin-resistant Staphylococcus aureus, S. aureus standard strain, or Pseudomonas aeruginosa. The studies demonstrated that PDT contributes in several ways to the wound healing process, such as killing bacterial cells and stimulating the proliferation of fibroblasts and consequently of collagen and elastin. Based on these studies, PDT provided excellent results for the wound healing process, acting in several steps and accelerating tissue repair. PDT has proven to be a promising therapeutic modality, able to inhibit bacterial regrowth or kill bacteria, contributing significantly to accelerate the wound healing process.

Prescribing, dispensing and administration indicators to describe rational use of oral dosage forms of medicines given to children.

Owing to lack of indicators, researchers are compelled to use non-specific indicators to assess rational use of medicines in children. Thus, paediatric-specific issues are poorly described. This study aims to develop a set of indicators to describe rational use of oral dosage forms of medicines given to children. A modified RAND/UCLA Appropriateness Method was used. A comprehensive draft list of 40 indicators was compiled, based on the results of a literature review. Twelve experts rated these indicators in two rounds, using a nine-point Likert scale, first in an online survey, for clarity, necessity and scientific merit, and secondly in a face-to-face meeting, for necessity, feasibility and predictive value. An overall panel median score of ≥7 and agreement within the experts were used in indicators. The indicators were ranked independently by the research team and a final list of indicators was prepared. These indicators were pilot-tested for acceptability and interrater reliability. Nine prescribing indicators, such as weight, appropriate dose and age-appropriate dosage form; five dispensing indicators, such as adequacy of labelling and inappropriate manipulation by pharmacists; and five administration indicators, such as inappropriate manipulation by parents and full completion of dose, were finalized in the second round. This novel approach has provided a set of indicators to describe the use of oral dosage forms of medicines given to children, which can be used by researchers as a supplement to the World Health Organization's drug use indicators when investigating rational use of medicines in children.

Pollution of Surface and Ground Water by Sources Related to Agricultural Activities

The objective of this study was to monitor the quality of ground water supplied to animal farms and 2 villages and of surface water (rivers) in the same area (Kosice basin, eastern Slovakia) with the aim to assess contamination of water by potential sources in this area. Samples for physico-chemical and microbiological examination were collected at 12 sampling points (6 – surface water; 6 – ground water) from May 2014 up to March 2015, covering all four seasons. The examination and evaluation of individual parameters was carried out according to relevant Slovak legislation compatible with EU Drinking water directive. The physico-chemical evaluation focused on parameters that indicate pollution of water resulting from human activities and farming. Microbiological examination included determination of counts of bacteria cultivated at 22°C and 37°C (BC22 and BC37), total coliforms, E. coli and faecal streptococci. Ground water intended for mass consumption (farms, villages) is abstracted from wells, collected in storage reservoirs and disinfected before brought to consumers. Some families in the villages use their own wells. Water for individual consumption (individual households) originates directly from individual wells. Examination of potable water used on agricultural farms showed some possibility of contamination of sources by runoff and inappropriate manipulation with excrements. Surface water in in the area close to both farms was polluted with organic substances (CODMn), however they did not exceed the limit set for surface water. At many samplings we detected in surface water presence of total coliforms, E. coli and occasionally also faecal enterococci indicating faecal pollution that could eventually affect ground water in individual wells. Our investigations showed that protection zones of water sources were not always sufficient. There were considerable variations in the quality of surface water during the year but no clear relationship between microbial contamination and seasons was observed. Quality of ground water supplied for mass consumption complied with legislative regulations except for BC 22 (heterotrophic count at 22°C) in summer and autumn). Water from individual wells contained occasionally presence of total coliforms, E.coli and enterococci and higher heterotrophic counts.

The Use of Photo-Essay to Report Advances in Applied Science and Health

Background: In the applied health and science disciples there is an expectation that project work is reported through a publication. The conventional papers written to do this follow a structure that includes sections providing background, methods, results and a discussion or conclusion, supported by figures and tables. Sometimes photographs are included, and with more on-line publications the opportunities have increased for these to be available in full color. Borrowing from the field of photojournalism photo-essays are now a publication option where a series of images are used to tell the story; these are often related to health and well-being.Aims: To summarize the methodology used to effectively combine a series of images with a brief text, and short reference list to create a visually engaging and informative short report.Guidelines: Images are taken throughout the project with consent obtained from those whose images will be recognisable. Creative licence is used to compile representative images into a sequence that conveys the background, method, results and outcome(s) of the project. Images need to be of high resolution; editing for light, colour and contrast, and cropping is allowed to increase their clarity and relevance. The ethics of photojournalism apply making inappropriate manipulation of images or erroneous captions unacceptable.Conclusions: Photo-essays are a novel and informative way to report on an applied health, social or scientific topic. The format is an excellent one to use for a brief report, or to prepare a research presentation for a scientific meeting.Keywords: Photograph, Photojournalism, Photo-manipulation.

Salmonella in Sausage, Frankfurter and Meat Sausage, Not Only in Raw or Undercooked but Also Found in Smoked and Cooked Ones: An Alert for Public Health and Travelerʼs Health Problem, Including Aerospace Medicine?

Introduction:Salmonella sp is one of the most common causes of food poisoning responsible for hospitalizations and deaths worldwide.This is related to bad hygiene and poor basic sanitary conditions. It is more prevalent in underdeveloped countries.The consumption of contaminated food is the major factor that predisposes the disease,including the ingestion of raw meat.Some authors reported the presence of Salmonella sp in the intestinal tract of poultry and pigs used in the production of sausages. Usually,food poisoning with this bacteria is due to raw or under-cooked food.However,it can be found in meat sausage,which goes through cooking or smoking at high temperatures. Our aim was to analyze the presence of Salmonella sp in sausage and meat sausage. Methods: A retrospective study was done in the following databases:PubMed, SciELO, Bireme, BMJ using as keywords “Salmonella sp”, “sausages”,“frankfurter”, “pork sausages”, “meat sausage” between years of 2006 and 2016. Results: Some Brazilian authors analyzed samples of homemade sausages,and industrial ones including, of poultry,swine,smoked chorizo,goats and fish. The presence of Salmonella sp was detected in all samples with the exception of goat chorizo and tilapia sausage.Although raw meat favors the growth of pathogenic microorganisms,much of the contamination of the product is due to inappropriate manipulation,lack of hygiene,use of contaminated water in the manufacture,inadequate packaging,storage at inappropriate temperatures and undue consumption.This explains the health authorities' concerns about transportation,feeding on board of aircraft and entry permission into foreign territories.Regarding transportation,refrigerated trucks and packages are necessary.Food poisoning on board can occur in all air crew as well as passengers.It can present severe cases of diarrhea,nauseas and vomiting,bringing about dehydration.Moreover,toillets number are limited. Passengers can get off bringing an infectious acute diarrhea.Minister of Agriculture has strict rules because of bacteria contamination in food. Conclusion: Although,there is a great probability of the presence of Salmonella sp in meat sausages and homemade frankfurter,any failure in the production axis of the food until final consumption,including transportation may predispose the contamination to the pathogens.Therefore, it can be a public health problem and/or Traveller's Health problem,including Aerospace Medicine.

Retracted: Mice lacking the Raf-1 kinase inhibitor protein exhibit exaggerated hypoxia-induced pulmonary hypertension, by I Morecroft, B Doyle, M Nilsen, W Kolch, K Mair and MR MacLean. British Journal of Pharmacology, volume 163(5): 948-963, published in June 2011; DOI 10.1111/j.1476-5381.2011.01305.x.

The above article, published by the British Journal of Pharmacology in June 2011 (http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01305.x/full), has been retracted by agreement between the authors, the Journal Editor in Chief and John Wiley & Sons Ltd. Formal internal investigations by the British Journal of Pharmacology have concluded that inappropriate manipulation of western blots depicted in Figures 1, 8 and 9 has occurred. The non-corresponding authors (M MacLean, B Doyle, K Mair, M Nilsen, W Kolch) wish to state that they had no knowledge that the figures in question had been manipulated. These issues are currently being investigated by the University of Glasgow. The retraction statement has also been approved by The University of Glasgow Research Integrity Council. Reference Morecroft I, Doyle B, Nilsen M, Kolch W, Mair K and MacLean MR (2011). Mice lacking the Raf-1 kinase inhibitor protein exhibit exaggerated hypoxia-induced pulmonary hypertension. Brit J Pharmacol 163: 948-963. doi: 10.1111/j.1476-5381.2011.01305.x.

Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom

Background: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. Objective: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. Study Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. Methods: Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 – 1.5 – 2 mA) was applied to the right “Shousanli” (LI10) and “Quchi” (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. Results: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. Limitations: Limitations include the fact that there was demyelination of the cervical cord (C8- T1) in the control group because of inappropriate manipulation. Conclusion: Repeated EA contributes significant analgesic effects in the treatment of BPN. Key words: Electroacupuncture, brachial plexus neuralgia, cobra venom, cervical cord, ultrastructural alterations

The critical importance of the fetal hypothalamus-pituitary-adrenal axis.

The fetal hypothalamus-pituitary-adrenal (HPA) axis is at the center of mechanisms controlling fetal readiness for birth, survival after birth and, in several species, determination of the timing of birth. Stereotypical increases in fetal HPA axis activity at the end of gestation are critical for preparing the fetus for successful transition to postnatal life. The fundamental importance in fetal development of the endogenous activation of this endocrine axis at the end of gestation has led to the use of glucocorticoids for reducing neonatal morbidity in premature infants. However, the choice of dose and repetition of treatments has been controversial, raising the possibility that excess glucocorticoid might program an increased incidence of adult disease (e.g., coronary artery disease and diabetes). We make the argument that because of the critical importance of the fetal HPA axis and its interaction with the maternal HPA axis, dysregulation of cortisol plasma concentrations or inappropriate manipulation pharmacologically can have negative consequences at the beginning of extrauterine life and for decades thereafter.