bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocrine Bone Disease in Pregnancy
Authors: Cox Jeremy , Robinson Stephen
Published: January 2022

Fetal and neonatal calcium requirements are high. To meet this need requires marked changes in maternal calcium physiology and bone metabolism during pregnancy and lactation. The import of widespread vitamin D deficiency and low calcium diets has been difficult to ascertain in the context of these changes, despite extensive studies. The impact goes beyond simple calcium homeostasis, with associations of low Vitamin D levels to worse maternal, fetal, and neonatal outcomes, including neonatal hypocalcaemia and pre-eclampsia. Other less common disorders of calcium metabolism, such as diseases involving the parathyroid axis, that are stable outside of pregnancy are markedly affected both by pregnancy and lactation and may cause serious complications to mother and fetus, requiring much closer monitoring and possible intervention. The normal physiological changes in calcium control during pregnancy and lactation may themselves cause disease, particularly osteoporosis, but also rarer entities such as pseudohyperparathyroidism.
Short Stature in Children Born Small for Gestational Age
Authors: Hokken-Koelega Anita C.S.
Published: January 2022

Small-for-gestational-age (SGA) is defined as a birth weight and/or length <–2 SDS. As the aetiology of SGA is multifactorial and includes maternal lifestyle and obstetric factors, placental dysfunction, and numerous (epi)genetic abnormalities, SGA-born children comprise a heterogeneous group. The majority of SGA-born infants show catch-up growth to a normal stature, but 10% remains short. For more than 30 years, studies have been performed in short children after SGA birth, including children with Silver–Russell syndrome (SRS). Studies have generally excluded short SGA children with major dysmorphic features or a (suspected) syndrome, primordial dwarfism, or DNA repair disorder. Thus present knowledge and management, particularly on GH treatment, are based on the results in non-syndromic short SGA/SRS children. This chapter presents our current knowledge of the (epi)genetic causes of short stature for those born SGA, the health consequences of SGA, and the diagnostic approach and management of short SGA-born children, including the efficacy and safety of GH treatment.
Growth Disorders with No Defined Aetiology
Authors: George Minu , Chernausek Steven
Published: January 2022

Short stature is one of the most common conditions presenting to paediatric endocrinology clinics. After careful history, physical examination, and standard laboratory diagnosis, the majority are classified as having idiopathic short stature. The extent to which the condition is detrimental to the well-being of the child, as well as the effectiveness, benefit, and safety of treatments remain incompletely delineated. There is evidence that administration of human growth hormone stimulates skeletal growth and increases adult stature, however, the response is variable and so the challenge has been to identify those for whom treatment may be warranted. The chapter addresses these issues and describes a diagnostic strategy that incorporates newer genetic testing to identify the basis of the growth disorder for select patients. With such an approach a definitive diagnosis can be reached 25–40% of patients labelled as idiopathic short stature and thereby aid in their management.
Endocrine Treatment of Transgender Youth
Authors: Klink Daniel
Published: January 2022

Transgender adolescent healthcare is a relatively novel part of endocrine medicine. Treatment protocols have emerged since the late1990’s and outcome data have become available more recently. A multidisciplinary approach with psychology and endocrinology is required to accommodate the specific needs of developing transgender adolescents and their primary caretakers. Therefore, treatment is ideally provided by specialized centres. However, with a growing population in numbers, all physicians should be familiar with treatment protocols. The endocrine treatment of transgender youth differs from that of transgender adults. The first step of treatment is a phase of gonadal suppression using either gonadotropin hormone-releasing hormone analogues (GnRHa) or, alternatively, progestogens, or antiandrogens. Second step is the induction of sexual characteristics of the affirmed gender using synthetic sex steroids in increasing dosages to mimic a pubertal fase. These specific therapeutics approaches of the transgender adolescent are outlined in this chapter.
Hormone Therapy in Transgender Women
Authors: Tangpricha Vin , Sineath Craig
Published: January 2022

When a transgender woman decides to begin medical transition, she will meet with a physician to begin the steps of starting gender-affirmation therapy via hormone replacement. This process involves an initial evaluation that includes psychological evaluation, a complete history and physical exam, and baseline lab values. There are many medications available for transgender women to take for their transition; in general, a transgender woman will begin an oestrogen agent and a testosterone-lowering agent. This combination of medications has effects on the body including breast development, redistribution of body fat, dermatological effects, and changes to the genitalia and sexual desire. While these drugs are considered safe, there are some lab values that must be monitored longitudinally depending on which regiment the patient is taking. This chapter outlines the overall process of starting hormone therapy, what effects the therapy will have on the patient, and longitudinal monitoring.
Hormone Therapy in Transgender Men
Authors: T’Sjoen Guy , Defreyne Justine
Published: January 2022

Currently, transgender medicine is not a strong part of the medical curriculum, although a large number of transgender persons will search for some kind of gender-affirming care. As psychopathology is clearly reduced in transgender persons after the initiation of hormone therapy, we believe all endocrinologists should become familiar with endocrinological care for transgender persons. In transgender men, testosterone therapy is initiated, aimed at achieving cisgender male reference values of serum testosterone in order to induce virilization. Although gender-affirming hormonal therapy with testosterone is considered safe, endocrinological follow-up is advised in all transgender people receiving gender-affirming hormonal care and will be discussed in this chapter for transgender men.
Fertility Options for Transgender Persons
Authors: Roo Chloë De , T’Sjoen Guy
Published: January 2022

Transgender persons inherently possess normal reproductive capacity, however, hormonal and surgical treatments for transgender people potentially impair the ability of these individuals to reproduce. Additionally, transgender people tend to start gender-affirming treatment at a young age, when reproductive wishes are not yet clearly defined nor fulfilled. The most recent Standards of Care of the World Professional Association for Transgender Health recommend to clearly inform patients on their future reproductive options prior to initiation of treatment. Where surgery definitely results in sterility, hormone therapy on the other hand also has an important, but partially reversible impact on fertility. However, thresholds for cross-sex hormone treatment to avoid permanent reproductive impairment have not been established. The current fertility preservation options for transgender men are embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. For transgender women, sperm cryopreservation, surgical sperm extraction, and testicular tissue cryopreservation are possible.
Endocrinology in the Critically Ill
Authors: Berghe Greet Van den , Langouche Lies
Published: January 2022

The neuroendocrine responses to acute and prolonged critical illness are substantially different. In the acute phase, the adaptations are probably beneficial in the struggle for short-term survival, whereas the chronic alterations may be maladaptive and participate in the general wasting syndrome of prolonged critical illness. Thorough understanding of the pathophysiology underlying these distinct neuroendocrine alterations during acute and prolonged critical illness is vital when considering new therapeutic strategies to correct these abnormalities and, as such, open perspectives to improve survival. Indeed, adequate choice of hormone and corresponding dosage are crucial and depend on such insights. The concomitant administration of presumed deficient (hypothalamic) releasing factors holds promise as an effective and safe intervention to jointly restore the corresponding axes and to counteract the hypercatabolic state of prolonged critical illness.
Endocrine Abnormalities in HIV Infection
Authors: Grinspoon Steven K. , Stanley Takara L.
Published: January 2022

Treated and untreated human immunodeficiency virus (HIV) infection is associated with perturbations in body composition and in the function of the endocrine axes. In advanced stages of disease, individuals with untreated HIV may have wasting, decreased lean mass, and abnormalities of multiple endocrine axes, including growth hormone (GH) resistance, androgen deficiency, oligo- or amenorrhea in women, and impaired adrenal function. By contrast, individuals with well-treated HIV often experience weight gain and ectopic fat accumulation. Whereas frank endocrine abnormalities are less common in people with well-treated HIV, cardiometabolic abnormalities such as insulin resistance, dyslipidaemia, and non-alcoholic fatty liver disease are relatively common. Finally, bone mineral density may be reduced, and cardiovascular risk is increased in individuals with HIV, in large part due to the immune dysregulation and persistent inflammation that accompanies even treated HIV. Appropriate care for individuals with HIV includes evaluation of any potential signs or symptoms of endocrine dysregulation as well as assessment and management of cardiovascular risk factors.
Endocrinology and Alcohol
Authors: Walter Marc , Proescholdt Margit G.
Published: January 2022

Alcohol has widespread effects on the endocrine system, potentially impairing endocrine function. Endocrine dysfunction observed in alcoholism, not only results from hepatic failure or chronic malnutrition, but also from direct, toxic actions of alcohol on the endocrine organs themselves as well as interferences with endocrine regulation at the hypothalamic–pituitary level. In the absence of liver disease, alcohol-induced endocrine impairment is mostly reversible upon cessation of alcohol consumption. The endocrine system itself may play a crucial role in the facilitation and maintenance of addictive behaviour. There is conflicting evidence that low to moderate alcohol consumption confers benefit on some endocrine diseases. The question as to whether low to moderate alcohol consumption has benefits on general health is unresolved. A better understanding of the impact of alcohol on the endocrine system is required to drive public health recommendations on alcohol consumption.
Dietary and Medical Management of Obesity
Authors: Wilding John P. , Lim Jonathan Z.M.
Published: January 2022

Lifestyle interventions that restrict energy intake, increase physical activity, and modify behaviour are the mainstay of most weight management programmes. Diets producing an intake of 500–600 kcal day below estimated total daily energy expenditure, combined with altered dietary macronutrient composition result in an average decrease of 3–5% initial body weight over 12 months. Use of meal replacements coupled with lifestyle support and gradual re-introduction of normal food can result in better weight loss than other dietary strategies, but weight regain is still common. Increasing physical activity through structured, gradual increments of intensity and frequency are predictors of success in weight maintenance at 1 year, 3 years, and beyond 5 years in combination with diet. Evidence from meta-analysis of behaviour modification therapy has further led clinicians to reconsider the types of messages, advice, and behaviour support offered to tackle the psychosocial aspects and stigma associated with obesity. Current pharmacological antiobesity agents include the intestinal lipase inhibitor orlistat, centrally acting drugs such as lorcaserin, naltrexone/bupropion, or phentermine alone or in combination with topiramate, and liraglutide, a GLP-1 receptor analogue also approved for use as glucose lowering agent. Future developments will likely target multiple pathways to optimize efficacy.
Classification and Diagnosis of Diabetes Mellitus
Authors: Colagiuri Stephen , Lee Crystal Man Ying
Published: January 2022

Diabetes is a major contributor to the global disease burden. The first official recommendation on the diagnostic criteria and classification of diabetes was published in 1965. At the time measurement of 2-hour plasma glucose during an oral glucose tolerance test was the only recommended diagnostic test. Today, measures of fasting plasma glucose and glycated haemoglobin are recognized alternatives. Diagnostic criteria for diabetes are universally agreed but criteria for intermediate hyperglycaemia differ. Classification of diabetes has evolved with improved understanding of the aetiopathology of diabetes but remains challenging due to the overlap of diabetes phenotypes. While new classification systems have been proposed to address the limitations of the current system, lack of global access to diagnostic tests which might better characterize types of diabetes hinders their universal application.
Epidemiology and Public Health
Authors: Wild Sarah , Price Jackie
Published: January 2022

Epidemiological studies provide valuable information about the definition, incidence, and prevalence of diabetes and its complications and their risk factors. Prevalence of diabetes is increasing globally as a consequence of ageing populations and increasing urbanization and obesity. Incidence of type 2 diabetes is falling in some developed countries, but prevalence continues to increase as a consequence of increasing survival. Differences between populations in prevalence of diabetes have provided important information in understanding the aetiology of diabetes and in developing approaches to prevention and treatment. However, there are still considerable gaps in our knowledge of the epidemiology of diabetes and in how we apply existing knowledge about effective approaches to the prevention of diabetes and its complications at a population level. Complications of diabetes results in major costs to individuals, health systems, and societies.
Non-Insulin Glucose-Lowering Agents
Authors: Bailey Clifford J. , Davies Melanie J.
Published: January 2022

A selection of differently acting blood glucose-lowering agents can be used in the management of type 2 diabetes to address different aspects of disease pathogenesis and comorbidities. Key factors influencing choice of medication include extent and duration of hyperglycaemia, obesity, insulin resistance, and impairment of beta-cell function, risk of hypoglycaemia, and risk or presence of cardiovascular, renal, and other complications. Diet, other lifestyle measures, patient education, and empowerment are fundamental throughout. Metformin is still widely used as initial orally administered blood glucose-lowering therapy. Other orally administered agents include sulphonylureas and meglitinides which stimulate insulin secretion, sodium/glucose cotransporter-2 (SGLT2) inhibitors which increase glucose elimination in the urine, thiazolidinediones which improve insulin sensitivity, and alpha-glucosidase inhibitors which slow the rate of carbohydrate digestion. Dipeptidylpeptidase-4 (DPP4) inhibitors slow the degradation of endogenous incretins, particularly glucagon-like peptide-1 (GLP-1), potentiating prandial insulin secretion, and reducing excess glucagon secretion. GLP-1 receptor agonists, which are administered by subcutaneous injection further increase prandial insulin secretion, reduce hyperglucagonaemia, and facilitate weight loss.
Strategies for the Management of Type 1 Diabetes
Authors: Hammond Peter , Campbell Fiona
Published: January 2022

The management of type 1 diabetes depends on optimal administration of insulin based on measurement of blood glucose levels. In order for a person living with diabetes to do this effectively on a daily basis they require training through a structured education programme in insulin delivery using multiple daily insulin injections or insulin pump therapy, and adjusting insulin doses according to monitored glucose values from capillary blood glucose measurements or continuous interstitial glucose sensing. This strategy applies to children and adults alike, although the specifics of the training and dosing regimen will be tailored to the individual. National benchmarking and audit programmes set the standards that services should expect to meet to demonstrate that they are helping the persons living with diabetes under their care to effectively implement this management strategy.
Immunotherapy for Type 1 Diabetes
Authors: Dayan Colin , Tatovic Danijela
Published: January 2022

A period of several years from the appearance of multiple antibodies to beta-cell antigens to clinical presentation of type 1 diabetes represents a window of opportunity for immunological intervention in order to halt the autoimmune process and preserve beta-cell function. The most rapid loss of beta-cell function happens in the first 12 months after diagnosis, which provides a further opportunity for interventions leading to effective beta-cell preservation. This is important as even a small amount of residual beta-cell function markedly improves metabolic control. Low-risk immunotherapeutic options are now available and widely used in other autoimmune diseases, but no such therapies are licensed for use in type 1 diabetes. With multiple immuno-intervention approaches showing potential efficacy in type 1 diabetes, we are now on the brink of fundamentally changing the management of this burdensome disease by using immunotherapy to preserve endogenous beta-cell function and make metabolic control substantially easier. It seems likely that non-antigen-specific therapies will be licensed first, but antigen-specific therapy may follow, offering the possibility of treating type 1 diabetes in the preclinical phase and delaying or preventing the need for insulin therapy.
Transplantation (Islet and Solid Organ)
Authors: Flatt Anneliese , Drage Martin , Callaghan Chris , Senior Peter
Published: January 2022

The limitations of insulin therapy as a means to manage glycaemia in type 1 diabetes are familiar to affected individuals and clinicians. Current therapies are burdensome and are unable to reliably achieve euglycaemia without substantial risk of hypoglycaemia and weight gain, while micro- and macrovascular complications remain major contributors to morbidity and mortality. Restoration of endogenous glucose-dependent insulin secretion by replacing beta cells through transplantation remains an intriguing option. Given the limited number of organ donors as well as the potential risks, including the present requirement for lifelong immunosuppression, identification of individuals for whom the risk benefit clearly favours transplantation is key. Rather than an alternative to insulin, transplantation may be better considered as an option when conventional therapy integrating technology and educational approaches has failed. This chapter aims to describe our current knowledge of the risks and benefits of islet and pancreas transplantation to help practitioners identify those most likely to benefit from beta-cell replacement.
Care of Diabetes in ICU and Perisurgery
Authors: Gunst Jan , Van den Berghe Greet
Published: January 2022

Critically ill patients and patients undergoing major surgery usually develop stress hyperglycaemia, which is associated with an increased morbidity and mortality risk. Randomized controlled trials interfering with elevated blood glucose during intensive care and the perioperative period have yielded mixed results, however. The optimal blood glucose target may depend on the context. Tight glucose control was shown to be effective and safe when performed with accurate glucose measurement tools and a reliable insulin infusion protocol in patients receiving early parenteral nutrition. Whether tight glucose control is beneficial in the absence of early parenteral nutrition, remains to be studied. In any case, hypoglycaemia and severe hyperglycaemia should be avoided. In patients with poorly controlled diabetes, the ideal blood glucose target may be higher than in non-diabetics.
Type 1 Diabetes and Psychiatry
Authors: Ismail Khalida , Garrett Chris , Stadler Marietta
Published: January 2022

There is a consistent pattern of association of several psychiatric disorders and type 1 diabetes (T1D) including depression, anxiety, eating disorders, and personality disorders. The presumption is that most psychiatric morbidity is accrued from the psychological burden per se of T1D or that individuals with subclinical pre-existing mental health difficulties are tipped into an overt psychiatric diagnosis. Elements of the T1D regime, namely the acute focus on food and the energy it contains, as well as heightened requirements of self-control can predispose to eating disorders, while others find the unrelenting requirements profoundly depressing, leading to clinical depression. Others acquire diabetes-specific anxieties, such as fear of hypoglycaemia or preoccupation with long-term complications. Psychiatric disorders impact diabetes self-management and there is an established association with acute and long-term complications including increased mortality. An underlying mental health problem should be a primary differential in certain clinical scenarios. such as persistent high HbA1c (>80 mmol/mol IFCC), particularly with recurrent diabetic ketoacidosis (rDKA) and also those with recurrent severe hypoglycaemia. This is particularly important in rDKA where subsequent all-cause mortality is in excess of 15% and closely linked to mental health disorders. Early recognition of psychiatric disorders is therefore vital for prognosis for both physical and mental health and diabetes clinicians should routinely monitor for psychiatric disorders.
Retinopathy
Authors: Scanlon Peter H.
Published: January 2022

Diabetic retinopathy is the leading cause of blindness in the working age population of most developed countries but has been shown to no longer be the leading cause in England and Wales. The introduction of the national screening programmes has been considered to be a major contributor to this achievement. The people with diabetes who still lose vision are often non-attenders who present late in the disease when treatment is more difficult. Tightening of control of glycaemia and blood pressure can slow the disease progression. When sight threatening retinopathy is detected, laser treatment and vascular endothelial growth factor (VEGF) inhibitor treatments reduce the risk of visual loss. When advanced retinopathy is detected, vitrectomy results have improved considerably over the last 20 years and a reasonable level of vision is often retained.
Diabetic Nephropathy
Authors: Gnudi Luigi , Marshall Sally M.
Published: January 2022

Diabetic nephropathy (DN) is the most feared diabetic chronic vascular complication. Characterized by progressive renal function decline, it eventually results in end-stage renal disease (ESRD) and is the major cause of ESRD (United States Renal Data System, 2016). In patients with type 1 diabetes (T1DM), DN presents initially with hyperfiltration and albuminuria which are then followed by a relentless decline in glomerular filtration rate; this classical presentation occurs in 30–40% patients and is always paralleled by the presence of retinopathy. The presentation of diabetic kidney disease (DKD) in patients with T2DM is not straightforward and often presents diagnostic difficulties: we are often unaware of the duration of diabetes and hypertension, and about the potential concomitant presence of other glomerular/tubular pathologies; the fact that only half of patients with T2DM with kidney disease have diabetic retinopathy highlights the heterogeneity of DKD in T2DM. All-cause mortality in individuals with DKD is 20–40 times higher than that in diabetic patients without nephropathy. Most patients with DKD die from cardiovascular disease before they reach ESRD. The prevention and management of diabetes and its chronic vascular complications and associated cardiovascular mortality and morbidity, is a global challenge and a significant social and economic burden.
Diabetic Neuropathy
Authors: Tesfaye Solomon , Wu Jing
Published: January 2022

Diabetic neuropathy is a major complication of diabetes and a cause of considerable morbidity and mortality. Classification of the various syndromes of diabetic neuropathy is also difficult: it is not a single entity as such, but includes several neuropathic syndromes. In clinical practice, the commonest presentation of neuropathy is chronic distal symmetrical polyneuropathy (DSP) also known as diabetic peripheral neuropathy (DPN). The neuropathic syndromes depicted have varied presentations and pathogenesis. This chapter will cover these syndromes although the main focuses will be: (1) DPN, which is the main initiating factor for foot ulceration and a cause of troublesome painful neuropathic symptoms and (2) autonomic neuropathy.
Mechanisms of Macrovascular Disease in Diabetes
Authors: Kearney Mark T. , Patel Peysh A. , Cubbon Richard M.
Published: January 2022

Insulin resistance describes defective metabolic and signalling responses to insulin, which may manifest clinically as prediabetes or frank diabetes. The spectrum of insulin resistance is associated with accelerated development of cardiovascular disease, ranging from endothelial dysfunction to advanced atherosclerosis, and also impedes endogenous vascular repair. Systemic insulin resistance encompasses a cluster of inter-related pro-atherosclerotic factors such as dyslipidaemia, hyperglycaemia, oxidative stress, and chronic inflammation. Perturbed insulin signalling within the vascular wall is also emerging as an important contributor to the macrovascular complications of diabetes. Insulin-resistant disorders remain a risk factor for developing cardiovascular disease and its fatal complications, necessitating the development of new therapeutic approaches.
Modern Management of Diabetes-Related Foot Disease
Authors: Bowling Frank Lee , Boulton Andrew J.M.
Published: January 2022

Diabetic foot problems are preventable but still account for a high number of hospital admissions in developed countries. In 2005, The International Diabetes Federation (IDF) focused on the diabetic foot. The ‘Put Feet First’ campaign highlighted the high prevalence of amputations within the diabetic population worldwide. Parallel to this World Diabetes Day launch, The Lancet dedicated a large proportion of its issue to the diabetic foot: a first for any major non-specialist journal focusing on this global challenge. Armstrong et al. concluded that 34% of people with diabetes will develop a foot ulcer during the course of their life; thus the overall treatment and healthcare management of diabetic foot complications can be sustained and time-consuming requiring the involvement of a multidisciplinary team (MDT) dedicated to foot health. It has recently been suggested that those with a previous foot ulcer history should be described as being in ‘remission’ rather than ‘healed’, emphasizing the seriousness of a foot ulcer history. A non-healing lesion complicated by gross infection is estimated to precede 85% of all major lower limb amputations.
Sex Steroid Actions in the Male
Authors: Vanderschueren Dirk , Antonio Leen , Kim Na Ri , Claessens Frank
Published: January 2022

Testosterone (T) is the principal circulating androgen in men. T can be converted to the more potent androgen dihydrotestosterone (DHT) by 5a-reductase enzymes and to oestradiol (E2) by the aromatase enzyme. Growing evidence suggests that not only androgen-, but also oestrogen-mediated pathways are important in male physiology. In this chapter, we will discuss sex steroid metabolism and transport in the circulation and the molecular mechanisms of sex steroid actions via the androgen and oestrogen receptor. Furthermore, we will review androgen and oestrogen actions throughout the male lifespan and the differential effects of T, DHT, and E2 in adult male physiology.
Plagiarism and the Napoleonic Potpourri
Authors: Weitz Shaena B
Published: January 2022

This article presents the modern rediscovery of the potpourri, a genre of music that appeared in France around 1787 and was banned by Napoleonic copyright law in 1810. While potpourris have been dismissed as mere medleys, this article shows that in its original form, the potpourri used musical excerpts for an intriguing game: to make pointed musical commentary about the politics of musical resemblance. As a genre, the potpourri reveals various conclusions about musical creation, setting into relief tensions between older ideas about the primacy of imitation and newer ideas about creativity ex nihilo—tensions that were not sufficiently resolved when the new intellectual property law privileging the ‘rights of genius’ was enacted in 1793. Potpourris provide, from the viewpoint of working musicians, previously unexamined commentary on the philosophical discourse and legal action that defined and protected certain creative practices and delegitimized others around the turn of the nineteenth century.
Evolution of Gene Expression across Species and Specialized Zooids in Siphonophora
Authors: Munro Catriona , Zapata Felipe , Howison Mark , Siebert Stefan , Dunn Casey W
Published: January 2022

Siphonophores are complex colonial animals, consisting of asexually produced bodies (zooids) that are functionally specialized for specific tasks, including feeding, swimming, and sexual reproduction. Though this extreme functional specialization has captivated biologists for generations, its genomic underpinnings remain unknown. We use RNA-seq to investigate gene expression patterns in five zooids and one specialized tissue across seven siphonophore species. Analyses of gene expression across species present several challenges, including identification of comparable expression changes on gene trees with complex histories of speciation, duplication, and loss. We examine gene expression within species, conduct classical analyses examining expression patterns between species, and introduce species branch filtering, which allows us to examine the evolution of expression across species in a phylogenetic framework. Within and across species, we identified hundreds of zooid-specific and species-specific genes, as well as a number of putative transcription factors showing differential expression in particular zooids and developmental stages. We found that gene expression patterns tended to be largely consistent in zooids with the same function across species, but also some large lineage-specific shifts in gene expression. Our findings show that patterns of gene expression have the potential to define zooids in colonial organisms. Traditional analyses of the evolution of gene expression focus on the tips of gene phylogenies, identifying large-scale expression patterns that are zooid or species variable. The new explicit phylogenetic approach we propose here focuses on branches (not tips) offering a deeper evolutionary perspective into specific changes in gene expression within zooids along all branches of the gene (and species) trees.
Biomarkers of dietary patterns: a systematic review of randomized controlled trials
Authors: Liang Shuang , Nasir Reeja F , Bell-Anderson Kim S , Toniutti Clémence A , O’Leary Fiona M , Skilton Michael R
Published: January 2022

Context

Most methods for assessing dietary intake have considerable measurement error. Dietary biomarkers are objective tools for dietary assessment. Dietary biomarkers of dietary patterns have not been well described, despite modern dietary guidelines endorsing dietary patterns.

Objective

This systematic review sought to describe the dietary biomarkers commonly used to assess dietary patterns, and the novel biomarkers of dietary patterns identified by exploratory studies.

Data Sources

MEDLINE, Embase, Cochrane Central, PreMEDLINE, and CINAHL databases were searched.

Data Extraction

Data extraction and bias assessment were undertaken in duplicate.

Data Analysis

A qualitative approach was applied, without statistical analysis.

Conclusion

In controlled settings, dietary biomarkers of single nutrients or of individual foods or food groups are commonly used to assess compliance with dietary patterns. However, currently, there are no dietary biomarkers or biomarker profiles that are able to identify the specific dietary pattern that has been consumed by an individual. Future work should seek to validate novel dietary biomarkers and biomarker profiles that are indicative of specific dietary patterns and their characteristics. A dietary biomarker panel consisting of multiple biomarkers is almost certainly necessary to capture the complexity of dietary patterns.

Systematic Review Registration

PROSPERO registration no. CRD42019129839.
lncRNA7 and lncRNA2 modulate cell wall defense genes to regulate cotton resistance to Verticillium wilt
Authors: Zhang Lin , Liu Jinlei , Cheng Jieru , Sun Quan , Zhang Yu , Liu Jinggao , Li Huimin , Zhang Zhen , Wang Ping , Cai Chaowei , Chu Zongyan , Zhang Xiao , Yuan Youlu , Shi Yuzhen , Cai Yingfan
Published: January 2022

In plants, long noncoding RNAs (lncRNAs) regulate disease resistance against fungi and other pathogens. However, the specific mechanism behind this regulation remains unclear. In this study, we identified disease resistance-related lncRNAs as well as their regulating genes and assessed their functions by infection of cotton (Gossypium) chromosome segment substitution lines with Verticillium dahliae. Our results demonstrated that lncRNA7 and its regulating gene Pectin methylesterase inhibitor 13 (GbPMEI13) positively regulated disease resistance via the silencing approach, while ectopic overexpression of GbPMEI13 in Arabidopsis (Arabidopsis thaliana) promoted growth and enhanced resistance to V. dahliae. In contrast, lncRNA2 and its regulating gene Polygalacturonase 12 (GbPG12) negatively regulated resistance to V. dahliae. We further found that fungal disease-related agents, including the pectin-derived oligogalacturonide (OG), could downregulate the expression of lncRNA2 and GbPG12, leading to pectin accumulation. Conversely, OG upregulated the expression of lncRNA7, which encodes a plant peptide phytosulfokine (PSK-α), which was confirmed by lncRNA7 overexpression and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) experiments. We showed that PSK-α promoted 3-Indoleacetic acid (IAA) accumulation and activated GbPMEI13 expression through Auxin Response Factor 5. Since it is an inhibitor of pectin methylesterase (PME), GbPMEI13 promotes pectin methylation and therefore increases the resistance to V. dahliae. Consistently, we also demonstrated that GbPMEI13 inhibits the mycelial growth and spore germination of V. dahliae in vitro. In this study, we demonstrated that lncRNA7, lncRNA2, and their regulating genes modulate cell wall defense against V. dahliae via auxin-mediated signaling, providing a strategy for cotton breeding.
Affective Dysregulation Precedes Emergence of Psychosis-Like Experiences in a Community Sample of Young Adults
Authors: Bornheimer Lindsay A , Martz Meghan E , Suzuki Takakuni , Tso Ivy F , Burton Cynthia Z , Li Verdugo Juliann , Grove Tyler , Heitzeg Mary M , Taylor Stephan F
Published: January 2022

Affective dysregulation (AD) among persons with schizophrenia spectrum disorders, involving the tendency to exhibit sensitivity to minor stress and negative affective states, is an important diagnostic feature and relates to poorer functional and clinical outcomes. Studies of persons with elevated risk for psychosis demonstrate similar AD to those with schizophrenia, and literature suggest a potential influence of AD in the transition from psychosis-like symptoms (PLEs) to disorder. Cross-sectional investigations to date have supported the link between AD and psychosis, and longitudinal studies have mostly yielded mixed findings without demonstration of potential causal relationships between AD and psychosis. This study examined the concurrent and predictive relationships between AD and PLE in a community sample of youth (n = 630) with attention to distinct facets of AD as a latent construct, including low resiliency, low reactive control, and negative emotionality, using structural equation to estimate a longitudinal cross-lagged and autoregressive model across 3 study waves from 15 to 24 years of age. As hypothesized, AD in the mid-teen years predicted subsequent PLE 3 years later. In addition, we found that increasing PLE in the end of the teen years related to a subsequent increase in AD in the early 20s. A cross-sectional relationship between AD and PLE in the mid-teen years was also supported. Findings overall describe important relationships between AD and PLE that appear to vary with developmental stage, implicating various factors to inform approaches for identifying youth who may be at risk for subsequent PLE or other mental health conditions.
The Effects of Organophosphate Esters Used as Flame Retardants and Plasticizers on Granulosa, Leydig, and Spermatogonial Cells Analyzed Using High-Content Imaging
Authors: Wang Xiaotong , Luu Trang , Beal Marc A , Barton-Maclaren Tara S , Robaire Bernard , Hales Barbara F
Published: January 2022

The replacement of regulated brominated flame retardants and plasticizers with organophosphate esters (OPEs) has led to their pervasive presence in the environment and in biological matrices. Further, there is evidence that exposure to some of these chemicals is associated with reproductive toxicity. Using a high-content imaging approach, we assessed the effects of exposure to 9 OPEs on cells related to reproductive function: KGN human granulosa cells, MA-10 mouse Leydig cells, and C18-4 mouse spermatogonial cells. The effects of OPEs were compared with those of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a legacy brominated flame retardant. Alterations in several important cell features, including cell survival, mitochondrial dynamics, oxidative stress, lysosomes, and lipid droplets, were analyzed. Most of the OPEs tested displayed higher cytotoxicity than BDE-47 in all 3 cell lines. Effects on phenotypic parameters were specific for each cell type. Several OPEs increased total mitochondria, decreased lysosomes, increased the total area of lipid droplets, and induced oxidative stress in KGN cells; these endpoints were differentially affected in MA-10 and C18-4 cells. Alterations in cell phenotypes were highly correlated in the 2 steroidogenic cell lines for a few triaryl OPEs. Potency ranking using 2 complementary approaches, Toxicological Prioritization Index analyses and the lowest benchmark concentration/administered equivalent dose method, revealed that while most of the OPEs tested were more potent than BDE-47, others showed little to no effect. We propose that these approaches serve as lines of evidence in a screening strategy to identify the potential for reproductive and endocrine effects of emerging chemicals and assist in regulatory decision-making.
An observational assessment of the safety of mass drug administration for trachoma in Ethiopian children
Authors: Ciciriello Allan M , Addiss David G , Teferi Tesfaye , Emerson Paul M , Hooper P J , Seid Mohammed , Tadesse Girma , Seife Fikre , Sormolo Mohammed-Aman Jemal , Kebede Fikreab , Kiflu Genet , West Sheila K , Alemu Menbere , LaCon Genevieve , Gebre Teshome
Published: January 2022

Background

The International Trachoma Initiative (ITI) provides azithromycin for mass drug administration (MDA) to eliminate trachoma as a public health problem. Azithromycin is given as tablets for adults and powder for oral suspension (POS) is recommended for children aged <7 y, children <120 cm in height (regardless of age) or anyone who reports difficulty in swallowing tablets. An observational assessment of MDA for trachoma was conducted to determine the frequency with which children aged 6 mo through 14 y received the recommended dose and form of azithromycin according to current dosing guidelines and to assess risk factors for choking and adverse swallowing events (ASEs).

Methods

MDA was observed in three regions of Ethiopia and data were collected on azithromycin administration and ASEs.

Results

A total of 6477 azithromycin administrations were observed; 97.9% of children received the exact recommended dose. Of children aged 6 mo to <7 y or <120 cm in height, 99.6% received POS. One child experienced choking and 132 (2%) experienced ≥1 ASEs. Factors significantly associated with ASEs included age 6–11 mo or 1–6 y, non-calm demeanor and requiring coaxing prior to drug administration.

Conclusions

There is a high level of adherence to the revised azithromycin dosing guidelines and low incidence of choking and ASEs.
Physician Training for Electrocardiogram Interpretation: A Systematic Review and Meta-Analysis
Authors: Oh So-Young , Cook David A. , Van Gerven Pascal W.M. , Nicholson Joseph , Fairbrother Hilary , Smeenk Frank W.J.M. , Pusic Martin V.
Published: January 2022

Purpose

Using electrocardiogram (ECG) interpretation as an example of a widely taught diagnostic skill, the authors conducted a systematic review and meta-analysis to demonstrate how research evidence on instruction in diagnosis can be synthesized to facilitate improvement of educational activities (instructional modalities, instructional methods, and interpretation approaches), guide the content and specificity of such activities, and provide direction for research.

Method

The authors searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, PsycInfo, CINAHL, ERIC, and Web of Science databases through February 21, 2020, for empirical investigations of ECG interpretation training enrolling medical students, residents, or practicing physicians. They appraised study quality with the Medical Education Research Study Quality Instrument and pooled standardized mean differences (SMDs) using random effects meta-analysis.

Results

Of 1,002 articles identified, 59 were included (enrolling 17,251 participants). Among 10 studies comparing instructional modalities, 8 compared computer-assisted and face-to-face instruction, with pooled SMD 0.23 (95% CI, 0.09, 0.36) indicating a small, statistically significant difference favoring computer-assisted instruction. Among 19 studies comparing instructional methods, 5 evaluated individual versus group training (pooled SMD −0.35 favoring group study [95% CI, −0.06, −0.63]), 4 evaluated peer-led versus faculty-led instruction (pooled SMD 0.38 favoring peer instruction [95% CI, 0.01, 0.74]), and 4 evaluated contrasting ECG features (e.g., QRS width) from 2 or more diagnostic categories versus routine examination of features within a single ECG or diagnosis (pooled SMD 0.23 not significantly favoring contrasting features [95% CI, −0.30, 0.76]). Eight studies compared ECG interpretation approaches, with pooled SMD 0.92 (95% CI, 0.48, 1.37) indicating a large, statistically significant effect favoring more systematic interpretation approaches.

Conclusions

Some instructional interventions appear to improve learning in ECG interpretation; however, many evidence-based instructional strategies are insufficiently investigated. The findings may have implications for future research and design of training to improve skills in ECG interpretation and other types of visual diagnosis.
The Optimized Oxford Hip Skeletal Maturity System Proves Resilient to Rotational Variation
Authors: Castillo Tafur Julio C. , Furdock Ryan J. , Sattar Abdus , Liu Raymond W.
Published: January 2022

Background:

The recently described optimized Oxford skeletal maturity system utilizes anteroposterior (AP) hip radiographs to accurately, rapidly, and reliably estimate skeletal maturity. However, in the real-world setting, significant positional variation in AP hip radiographs may influence the accuracy of optimized Oxford skeletal age estimates. We sought to evaluate the consistency of skeletal age estimations using the optimized Oxford system between differently rotated radiographs.

Methods:

Thirty normal computerized tomography scans of males (15 children, 9 to 15 y) and females (15 children, 8 to 14 y) were obtained retrospectively, converted into 3D reconstructions, and then used to produce simulated hip radiographs in five different rotational positions. The optimized Oxford system was applied to the 150 simulated AP hip radiographs (5 differently rotated views of 30 hips) to produce a skeletal age estimate for each.

Results:

Rotational position did not have a statistically significant effect on the skeletal age (P=0.84) using 1-way repeated measures analysis of variance. Of the 5 radiographic parameters in the optimized Oxford system, only greater trochanter height showed significant rotational variation after Greenhouse-Geisser correction (F2.58, 74.68=5.98,P<0.001). However, post hoc analyses showed that the greater trochanter height obtained at the most centered position was not different from the other 4 rotational positions (P>0.05 for all).

Conclusion:

The optimized Oxford skeletal maturity system is resilient to rotational variation. Mildly to moderately rotated radiographs obtained in the modern clinical setting can be used for skeletal age estimation by this method, broadening the clinical usage of this system.

Level of Evidence:

Level III—diagnostic study.
The Use of Physical Restraints in Italian Intensive Care Units: Results From a Multicenter Observational Study
Authors: Mattiussi Elisa , Piani Tommaso , De Marco Alice , Portolan Camilla , Castriotta Luigi , Danielis Matteo
Published: January 2022

Background

The use of physical restraints (PRs) varies across countries and clinical settings, with intensive care units having the highest frequency. Although many investigations on the use of PRs have been conducted worldwide, few studies are reported in the Italian context.

Objectives

The aims of this study were to describe PR rates and types and to observe the factors associated with PR use.

Methods

In this observational study, 2 methods were used to collect data: direct observation and review of patients' documentations.

Results

We performed 328 observations on 146 critically ill patients. Physical restraints were applied in 56.7% (n = 186) of these observations. Bilateral wrist ties were used for most PR episodes (n = 135, 72.6%), followed by unilateral wrist ties (12.9%). The most documented reasons were preventing patients from self-extubation (n = 93, 50.0%) and preserving indwelling lines and tubes (n = 60, 32.2%). In the multivariate logistic regression analysis, patients who were cared for during the night shift were almost 4 times more likely to be restrained than patients in the morning shifts (odds ratio, 3.84; P = .001) and patients with endotracheal tube were 3.5 times more likely to be restricted than spontaneously breathing patients (odds ratio, 3.59; P < .001).

Discussions

Physical restraints are commonly used among critically ill patients in Italian intensive care units. There is a need to share the metrics for an efficient and accurate measurement of PR usage and trends and to document the reason for restraints, type of restraints, timeframe, and decision-making criteria.