bluuebunny/crossref_metadata_2025 huggingface dataset:
Other Disorders of the Pituitary and Hypothalamus in Pregnancy
Authors: Carroll Paul V. , Karavitaki Niki , Lithgow Kirstie
Published: January 2022

Pregnancy results in significant alteration of pituitary anatomy and hormone physiology. Prolactin-producing lactotroph cells undergo progressive and significant hyperplasia throughout pregnancy contributing to increase in size of the anterior pituitary. Changes in pituitary hormone production, binding protein levels and target hormone action occur during pregnancy. As a result of these alterations, the assessment of pituitary status in the pregnant woman is complex and differs from the non-pregnant state. Disorders of hormone function may be well established prior to pregnancy or less frequently develop during pregnancy. These conditions may impact on maternal and fetal outcomes and influence pregnancy management. The physiology of pregnancy may also influence behaviour of endocrine conditions. Several disorders are specifically associated with pregnancy, lymphocytic hypophysitis, and Sheehan’s syndrome being particular examples.
Imaging for Endocrine Diseases in Pregnancy
Authors: Lowe Sandra
Published: January 2022

Imaging for endocrine diseases in pregnancy requires a detailed understanding of the risks and benefits of the imaging options. As in the non-pregnant subject, non-ionizing radiation options such as ultrasound and magnetic resonance imaging should be considered first. In almost all cases, radiation and contrast risks are negligible and therefore the most sensitive and specific imaging should be performed at the most appropriate time, whether during or after pregnancy. For practical purposes, no specific counselling is required for women undergoing diagnostic imaging with a predicted fetal absorbed dose of less than 10 mGy. This includes all X-ray and CT scanning not involving the abdomen and most nuclear scans. Despite widely held concerns, even at an estimated fetal dose of 50 mGy, the additional risk of childhood cancer is at worst 1.1–3.0 cases per 1000 patient exposures.
Disorders of the GH-IGF Axis
Authors: Jorge Alexander A.L. , Correa Fernanda A. , Scalco Renata C.
Published: January 2022

Disorders of the GH-IGF axis include a large heterogeneous group of conditions with distinct phenotypes. Each of the defects identified in this axis is responsible for a rare and specific condition that endocrinologists need to be familiar with. Traditionally, clinical and hormonal evaluations are the cornerstones of their diagnosis but in recent years, molecular genetic tests are becoming an important tool for the investigation of GH-IGF axis disorders. In this chapter, we will focus on genetic causes and highlight their main characteristics and the diagnostic approaches for each of them. The expansion of our knowledge in this field may lead to treatment based on the molecular defect.
Precocious Puberty
Authors: Léger Juliane , Carel Jean-Claude
Published: January 2022

Precocious puberty (PP) is defined as the onset of clinical signs of puberty before the age of 8 years in girls and 9.5 years in boys. It may be caused by central or peripheral mechanisms. Central PP (CPP) results from premature reactivation of the hypothalamo–pituitary–gonadal axis, with a hormonal pattern similar to that of normal puberty. CPP may be due to hypothalamic lesions or idiopathic in most cases, particularly in girls. It may have consequences for growth and psychosocial development. Thorough evaluation is required to identify its cause and potential for progression. Gonadotropin-releasing hormone agonists are the standard treatment for progressive CPP. The available data indicate that this treatment does not seem to cause or aggravate obesity or have repercussions for body composition, bone mineral density and fertility. Recent studies have implicated a genetic cause for paternally transmitted familial CPP, but such defects do not underlie maternally transmitted CPP and are rarely involved in sporadic forms.
Management of Sexual Dysfunction
Authors: Rochira Vincenzo , Carani Cesare , Granata Antonio R.M.
Published: January 2022

Sexual dysfunction in men may be related to multiple factors according to the type of sexual problems (e.g. low desire, erectile, or ejaculatory disturbances). Organic and psychological factors both contribute to the development of male sexual dysfunction. Among organic causes, endocrine disorders (the most important of which is hypogonadism) may contribute to the occurrence of male sexual dysfunction, but are much less frequent than other organic causes (i.e. vascular, neurological, and drug-induced). Clinical assessment (including a sexual history) is important for identifying patients with hormonal (e.g. testosterone deficiency) or other disorders (e.g. vascular or neurological) who may present with symptomatic sexual dysfunction. The aetiology(ies) underlying the sexual dysfunction will guide the most appropriate treatment in individual cases. Management of male sexual dysfunction may include psychological counselling, pharmacological therapy (e.g. PDE5Is), surgery, and testosterone replacement therapy in cases of well-documented hypogonadism. Despite the recent improvements due to the use of PDE5Is, in the management of erectile dysfunction remains largely unsatisfactory for a significant proportion of patients so there is still a major treatment gap and challenge ahead.
Introduction to Transgender and Gender Diverse People
Authors: Arcelus Jon , Bouman Walter Pierre
Published: January 2022

This chapter provides an introduction to transgender health. It starts with a brief historical and cultural overview concerning those people who identify as transgender or gender diverse, followed by a description of current language and terminology in transgender health with a glossary of transgender-related nomenclature. The classification of transgender and gender-diverse identifying people is described in the context of the International Classification of Diseases of the World Health Organization (WHO) and the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (APA). This is followed by a description of prevalence studies in clinical populations, as well as in the general population, regarding transgender and gender-diverse identifying people. The chapter further discusses transgender health services, including assessment and gender-affirming medical treatments, and concludes with a short presentation of mental health problems in the transgender population.
The Endocrinology of Liver Disease
Authors: George Jacob , Eslam Mohammed
Published: January 2022

Liver and endocrine diseases are common in the general population and intimately linked, such that diseases of both organ systems frequently coexist. Thus, disease in one can modulate the phenotypic manifestations or progression of the other and share pathogenic mechanisms. The common liver diseases, non-alcoholic fatty liver disease, viral hepatitis and haemochromatosis have unique extrahepatic endocrine manifestations, including diabetes mellitus, thyroid dysfunction, osteoporosis, and gonadal dysfunction. Conversely, the liver is frequently a target of a variety of endocrinopathies, including hypothyroidism, hypercortisolaemia, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency, and hypogonadism. It is therefore incumbent on both gastroenterologists and endocrinologists to consider these reciprocal interrelationships in daily practice, to provide better clinical care. Prospective studies are required to reveal if we need to change current guidelines on screening for endocrine disease in patients with liver dysfunction and vice versa, at least in high risk groups. In the following chapter, we summarize this bidirectional relationship.
Effect of Opioids on Adrenal and Reproductive Endocrinology
Authors: Armeni Eleni , Grossman Ashley B. , Khoo Bernard
Published: January 2022

Endogenous opioids and opioid receptors play key neuroendocrinological roles in regulating the body’s response to stress and pain. As part of this function, endogenous opioids regulate the hypothalamo–pituitary–adrenal (HPA), hypothalamo—pituitary–gonadal axes (HPG) axes and posterior pituitary function. Exogenous opioids have been used from ancient times as analgesics but have a well-known addictive potential. Opiate dependency is now a widespread global problem, driven by the easy availability of both prescribed and illegal opiates. As a consequence, the endocrine complications from opiates are becoming more common and chronic opiate users are at high risk of developing hypoadrenalism and hypogonadism. A robust screening protocol for these endocrinopathies, in collaboration between pain specialists and endocrinologists, is essential for appropriate replacement treatment and the prevention of morbidities and possibly mortality, especially from hypoadrenalism.
The Breast
Authors: Clarke Robert , Greenhalgh Alice
Published: January 2022

Breast cancer is the most common form of cancer in women. In order to fully understand the molecular causes of breast cancer, it is critical to understand the underlying mechanisms which regulate and dictate normal breast development. Both pituitary and ovarian steroid hormones are required to regulate and govern breast development. Progesterone is an ovarian steroid hormone and is considered to be a major risk factor for the development of breast cancer, since it controls proliferation of stem and progenitor cells. The human breast is organized as an epithelial network of ducts opening at the nipple and these form a tree-like structure ending in lobuloalveolar glands located within the collagenous and adipose tissue of the mammary gland. Upon pregnancy, specialized luminal cells develop in the alveoli which go on to secrete milk proteins and lipids during lactation. Breast development occurs in three well-defined stages: embryonic, pubertal, and reproductive.
The Physiology of Bodyweight Regulation
Authors: Coll Anthony P.
Published: January 2022

Mammalian body weight is highly regulated. An understanding of the processes governing body weight is closely relevant to clinical practice as disorders of energy homeostasis are common, cause significant morbidity and mortality and can be challenging to treat. Detailed clinical observation of extreme phenotypes, both human and model organism, coupled with significant advances in molecular biology have led to the identification of a host of endocrine pathways that control appetitive behaviour, body composition, and energy expenditure. Compelling data show the central nervous system, in particular regions such as the hypothalamus and brainstem, have primacy in sensing a multitude of humoral and neuronal signals from the periphery, integrating them into a coordinated output that aims to maintain weight in the face of a changing environment. This understanding not only gives a biological basis for interindividual variation in body weight, but has opened up new avenues for rational therapeutic interventions.
Metabolic Surgery
Authors: Rubino Francesco , Anastasiou Vivian , Ferraro Luca , Qanaq Dalal , Chamseddine Ghassan
Published: January 2022

Despite constantly evolving drugs, many patients with type 2 diabetes have suboptimal glycaemic control and excess illness and mortality. Widely adopted guidelines from the 2nd Diabetes Surgery Summit (DSS-II) recommend consideration of bariatric/metabolic surgery as a standard treatment option for patients with obese type II diabetes. Studies in animals and humans have shown that gastrointestinal operations can induce weight-independent effects on glucoregulatory physiology, while randomized trials have shown that surgery achieves better glycaemic control than lifestyle and available pharmaceutical interventions. The exact mechanisms of action of surgery remain unclear, but it provides compelling evidence for a critical role of the gastrointestinal system in glucose homeostasis. Further elucidation of the mechanisms of action of surgery and the role of the gut in metabolic regulation may identify novel targets for prevention and therapy of diabetes and obesity. To capitalize fully on this opportunity, however, addressing of common misperceptions and misconceptions that impede appropriate use of metabolic surgery will be required. This chapter reviews biological, clinical, and economic evidence supporting a surgical approach to type 2 diabetes and discusses current evidence-based indications.
Assessment of Obesity in Children
Authors: Farooqi I. Sadaf
Published: January 2022

It is becoming increasingly important for physicians to have a systematic approach to the assessment of children with severe obesity. While a small proportion of severely obese children have features associated with classical genetic obesity syndromes such as Prader–Willi syndrome, there is increasing recognition that genetic disorders can present as severe obesity alone without developmental delay, dysmorphology, or other clinical signs. The diagnosis of a genetic obesity syndrome is of value for families and may help both children and families deal with the social stigma around severe childhood obesity. The finding of a genetic cause for a patient’s obesity sometimes leads to specific therapy. Exome and genome sequencing have accelerated discovery of genes and mechanisms that explain a variety of previously unrecognized childhood obesity syndromes.
Lipoprotein Metabolism
Authors: Angelin Bo , Parini Paolo
Published: January 2022

Lipids are a heterogeneous group of substances with a myriad of structural and regulatory functions. The realization that changes in plasma lipids, particularly elevated cholesterol in apolipoprotein B-containing lipoproteins, are associated with an increased risk of cardiovascular disease has given great impetus to the study of factors regulating plasma lipid metabolism. With the use of increasingly refined methodology, understanding of normal plasma lipoprotein metabolism and its derangements in the face of genetic and/or environmental factors is continuously expanding. This chapter summarizes current concepts regarding normal plasma lipoprotein synthesis, transport, and interconversion in humans, forming a basis for subsequent discussions of pathogenesis, diagnosis, and treatment of dyslipidaemia.
Autoimmune Hypoglycaemia
Authors: Gorden Phillip , Malandrino Noemi
Published: January 2022

Insulin autoimmune syndrome and type B insulin resistance are rare causes of autoimmune hypoglycaemia. Insulin autoimmune syndrome is due to autoantibodies against endogenous insulin, and typically presents with episodes of postprandial hyperinsulinaemic hypoglycaemia. Type B insulin resistance is caused by autoantibodies against the insulin receptor, and may present with severe insulin resistance and hyperglycaemia, hypoglycaemia following a period of hyperglycaemia, or hypoglycaemia alone. The combination of clinical manifestations and positive insulin or insulin-receptor antibodies in the blood confirm the diagnosis of autoimmune hypoglycaemia. However, in rare cases, insulin treatment in patients with positive insulin antibodies and frequent episodes of hypoglycaemia can complicate the diagnosis of insulin autoimmune syndrome. In this chapter, the clinical characteristics, pathophysiology, diagnosis, and management of autoimmune hypoglycaemia syndromes will be described, and the challenges in identifying those insulin antibodies which may significantly affect insulin kinetics in insulin-treated diabetes discussed.
Physiology of Glucose Homeostasis
Authors: Persaud Shanta J. , Jones Peter M.
Published: January 2022

This chapter provides an overview of the physiological mechanisms underlying appropriate control of blood glucose levels. In particular, it focuses on the anatomy and cellular composition of islets of Langerhans; regulation of synthesis and storage of the anabolic hormone insulin in secretory granules of islet beta-cells; cellular mechanisms by which elevations in blood glucose levels stimulate insulin release from beta-cells by a process known as exocytosis; modulation of glucose-stimulated insulin secretion by hormones and neurotransmitters; and the physiological signal transduction pathways used by insulin to stimulate storage of fuels in adipose tissue, liver, and skeletal muscle. It also reviews the deleterious effects of chronic hyperglycaemia that are responsible for diabetic complications.
Pathogenesis
Authors: Bashir Ayat , Oram Richard A. , Wong F. Susan
Published: January 2022

Multiple genes encode susceptibility factors for the development of type 1 diabetes. These interact with environmental factors, the exact nature of which are, as yet unknown, and this leads to activation of autoimmune B and T lymphocytes. The pathogenesis of type 1 diabetes results from complex interactions between these immune cells and the insulin-producing beta-cells of the pancreatic islets of Langerhans, causing damage and destruction, ultimately leading to insufficient production of insulin. In this chapter, the evidence for autoimmunity will be discussed, and currently unanswered questions relating to pathogenesis of type 1 diabetes will be highlighted, among other important aspects.
Hypoglycaemia in the Treatment of Diabetes Mellitus
Authors: Amiel Stephanie A.
Published: January 2022

Hypoglycaemia (blood glucose concentration below the normal range) is a common and feared complication of exogenous insulin and insulin secretagogue treatments for diabetes. Severe hypoglycaemia is defined as an episode in which third-party intervention is required because of cognitive impairment secondary to the glucose lack. Even non-severe episodes can be unpleasant, as the body mounts a symptomatic stress response to the glucose fall. These protective, counterregulatory responses are impaired in diabetes, increasingly so with increasing diabetes duration, increasing the risk of severe hypoglycaemia. Much can be done to reduce individual risk of severe hypoglycaemia, starting with adjustment of medications and, for insulin users, structured education in how to use insulin flexibly; through use of technologies such as analogue insulins, insulin infusion, and continuous glucose monitoring, with β cell replacement a final step. Technological solutions should be accompanied by support for psychological issues of having diabetes and hypoglycaemia, which are challenging for patients and families. This chapter discusses the epidemiology of hypoglycaemia in diabetes, explores the pathogenesis of impaired awareness and severe hypoglycaemia and discusses the treatment pathway.
Psychological and Behavioural Aspects of Type 1 Diabetes Management
Authors: Hendrieckx Christel , Speight Jane
Published: January 2022

Type 1 diabetes is a demanding, complex lifelong condition. Optimal self-care involves repetitive behavioural tasks, undertaken ‘24/7’: administering multiple daily insulin doses, adjusted for food/activity and monitoring glucose levels to avoid hyper- and hypoglycaemia. This requires a comprehensive understanding of diabetes, as well as healthy coping, resilience, problem-solving, and risk reduction skills. It is unsurprising that many experience emotional distress as a consequence of living with type 1 diabetes, which impacts not only on their well-being but also on self-management and outcomes. Clinical guidelines acknowledge that diabetes affects both physical and emotional health. However, the misguided perception persists that the psychosocial care is separate from the diabetes care, and that it requires mental health specialists to assist. A paradigm shift is needed. Diabetes health professionals need to enhance their consultation skills to identify and address psychological needs, if they are to support people to live well with this challenging condition.
Management of the Inpatient with Diabetes Mellitus
Authors: Rayman Gerry
Published: January 2022

The previous edition of this textbook lamented on the general lack of interest in inpatient diabetes care. Since then there has been a significant change, partly brought about by increasing recognition of the significant financial burden of inpatient diabetes, increased lengths of stay, worryingly high levels of patient harms associated with poor control (both hyperglycaemia and hypoglycaemia), and poor patient experience. In England and Wales, the National Diabetes Inpatient Audit (NaDIA—vide infra), the world’s first national diabetes audit was partially instrumental in highlighting the levels of patient harms and patient dissatisfaction as well revealing the paucity of inpatient diabetes specialists. Additionally, recognizing the need to improve inpatient diabetes care the Joint British Diabetes Societies (JBDS) for inpatient care was formed to produce evidence and consensus based national guidelines to promote better care and reduce variation in practice. Similarly, in 2013, diabetes specialists in the United States formed a consortium for Planning Research in Inpatient Diabetes (PRIDE) to improve inpatient diabetes care. Thus, driven by evidence of suboptimal management and the associated high costs, inpatient diabetes care has now become a major focus for funders, hospital management, clinicians, and patients. The goal should be to ensure that the outcomes for people with diabetes admitted to hospital are no different from those without diabetes by prevention of inpatient hyperglycaemia, hypoglycaemia, and hospital acquired foot lesions and ensuring early and safe discharge.
Lipodystrophies and Severe Insulin Resistance Syndromes
Authors: Stears Anna , Savage David B. , O’Rahilly Stephen
Published: January 2022

Severe insulin resistance syndromes are rare disorders which may be inherited or acquired. They can be classified into three groups: (1) defects in insulin signalling (including insulin receptoropathies); (2) defects in adipocyte triglyceride storage (lipodystrophies); and (3) complex syndromes. All three groups are associated with clinical features including acanthosis nigricans, hyperandrogenism in women, and metabolic abnormalities including diabetes. Diabetes may be relatively resistant to standard therapies, and disabling hypoglycaemia may precede it. Lipodystrophies predispose to severe hypertriglyceridaemia which may be complicated by pancreatitis; therefore, management involves strict dietary calorie and fat restriction. Acquired insulin receptoropathies may be successfully be treated with immunosuppression. Accurate diagnosis is key so that appropriate management can be put into place and genetic counselling can be undertaken where required. Biochemical and genetic study of patients with rare syndromes of severe insulin resistance also provides insights into the pathogenesis of the insulin resistance associated with obesity and type 2 diabetes.
Macrovascular Disease in Type 1 Diabetes
Authors: Petrie John R.
Published: January 2022

Even young adults with type 1 diabetes are affected by accelerated atherosclerosis. This manifests as a premature onset of angina, myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, or a combination of these. The development of subclinical renal disease (microalbuminuria) is an early marker of especially high risk. Current management focuses on prevention, aiming for: (i) intensive glucose control and smoking avoidance from diagnosis; and (ii) blood pressure and cholesterol control with longer disease duration. With the exception of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, a post-randomization follow-up of the Diabetes Control and Complications Trial (DCCT), there are very few long-term data to guide cardiovascular risk management in type 1 diabetes. Current thresholds and targets for treatments are therefore largely extrapolated from type 2 diabetes, even although the underlying pathophysiology is very different.
Health Economics of Diabetes Care and Prevention
Authors: Clarke Philip , Lung Thomas
Published: January 2022

There is an ever-increasing demand for healthcare. While clinical studies determine an intervention’s efficacy or effectiveness, limited resources mean that choices need to be made when deciding which healthcare interventions should be funded. Health economics focuses on how to make these choices to fund healthcare interventions that will maximize health benefits. This chapter introduces the ideas of key drivers in healthcare costs and issues around sustainability of funding for diabetes-specific programmes. It will then focus on the concept and different types of economic evaluation, measuring quality-adjusted life-years, and its use in identifying diabetes interventions that provide value for money, providing specific examples.
Types of Treatment
Authors: Rastrelli Giulia , Maggi Mario , Corona Giovanni
Published: January 2022

Several therapeutic options are available in the treatment of adult hypogonadism, the choice of which depend on the clinical situation, availability/costs of medications, patient expectations, and preferences. The induction or restoration of both fertility and testosterone (T) production are potentially achievable, in patients with secondary hypogonadism, whereas only T substitution is effective when the testes are damaged (i.e. primary hypogonadism). When fertility is desired, the use of gonadotrophins in secondary hypogonadism is the most appropriate treatment allowing sperm production to be achieved in about 50% of cases. In all other patients, T substitution is the treatment of choice as it is cheaper and easier to administer when compared to gonadotropins. The use of transdermal T preparations and long-acting injectable T undecanoate are currently the most popular forms of the treatment worldwide. They generally achieve a high level of efficacy with limited side effects.
Endocrine and Local Regulation of Testicular Hormone and Sperm Production
Authors: Huhtaniemi Ilpo , Toppari Jorma
Published: January 2022

The testis has two main functions, that is, androgen production and spermatogenesis, and the key role in their endocrine regulation is played by the two pituitary gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates Leydig cells of testicular interstitial tissue in the production of testosterone (T). T, secreted into the peripheral circulation, regulates the function of an array of androgen-responsive non-gonadal target tissues. Within the testis, T regulates indirectly spermatogenesis through stimulation of Sertoli cells in the seminiferous tubules. FSH promotes spermatogenesis, also indirectly, through actions on Sertoli cells. A plethora of local paracrine signals and metabolites between Sertoli and germ cells underlie the intricate regulatory mechanisms of spermatogenesis. This chapter summarizes the main hormonal regulation of the testis, that is, the hypothalamic–pituitary–testicular axis, and the main events in the process of spermatogenesis and its regulation.
Clinical Evaluation
Authors: Anawalt Bradley D.
Published: January 2022

The evaluation of the man with suspected hypogonadism and/or infertility begins with a directed history and physical examination on specific elements that help to determine the likely onset and possible causes of the androgen deficiency or infertility. Determination of the onset and possible causes of androgen deficiency or infertility is essential for determination of a rational diagnostic evaluation. For example, in the adult man who has testes are very small (≤6 cc each) has prepubertal onset of male hypogonadism. Congenital causes of hypogonadism such as Klinefelter syndrome and Kallmann syndrome become much more likely as aetiologies whereas acquired causes such as sellar masses and metabolic disorders such as hemochromatosis more commonly present postpubertally (because they take time to progress to hypogonadism) or there are clues to the acquired causes such as major testicular or hypothalamic disease or surgery when they occur pre- or peripubertally. Finally, the history and physical examination is indispensable in determining the potential benefits and risks of therapy for man with suspected androgen deficiency or infertility. This chapter introduces the reader into the rationale approach history taking and the physical examination of the man with possible hypogonadism.
Klinefelter’s Syndrome
Authors: Gravholt Claus H.
Published: January 2022

Klinefelter syndrome (KS) is a frequent genetic condition caused by the presence of an extra X chromosome with the resultant karyotype being 47,XXY. The condition is in males and results in hypergonadotropic hypogonadism, small testis, and infertility, although recent research has shown that some KS males harbour sparse amounts of spermatocytes that can be retrieved by testicular sperm extraction. Other characteristics include cognitive impairment, dyslexia, tall stature, gynaecomastia, a range of medical conditions, including the metabolic syndrome, type 2 diabetes, hyperlipidaemia, cardiovascular disease, extragonadal germ cell tumours, and breast cancer. Although the estimated prevalence of KS is 150 per 100 000 liveborn males, diagnosis poses several problems. Most KS are only diagnosed during adulthood, and only about 10% are diagnosed during childhood and adolescence. Studies from different countries indicate that only 25–50% of the expected number are ever diagnosed. Mortality and morbidity are high and the socioeconomic status is low. Medical therapy is directed towards hypogonadism and consists of testosterone replacement therapy, although no formal randomized clinical trial has been conducted in KS, and the prevention of lifestyle diseases. Comprehensive multidisciplinary care needs to be in place throughout life in order also to alleviate the neurocognitive problems encountered by many with KS and facilitate extra scholastic help and speech therapy, etc. The genetic background for KS is not thoroughly understood, but recent developments show global epigenetic and RNA expression changes that are likely tied with the phenotype.
Aetiology
Authors: Matsumoto Alvin M. , Narla Radhika
Published: January 2022

Male hypogonadism is diagnosed in patients who have symptoms and signs of androgen deficiency, and repeatedly low serum testosterone concentrations and decreased sperm production. The aetiology of hypogonadism may be due to disorders of the testes (primary hypogonadism) or hypothalamus or pituitary gland (secondary hypogonadism), or combined disorders. Primary and secondary hypogonadism are distinguished by gonadotropin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations. Either primary or secondary hypogonadism may be caused by a structural or congenital disorder of the hypothalamic–pituitary–testicular (HPT) axis that is usually permanent and necessitates testosterone treatment (organic hypogonadism) or a disorder that results in suppressed function of an intact HPT axis that is potentially reversible with treatment of the etiologic condition or discontinuing the offending medication (functional hypogonadism). The benefits and risks of testosterone treatment in men who have functional hypogonadism have not been evaluated fully in randomized, double-blind, placebo-controlled trials, while managing the underlying conditions may reverse the hypogonadism and confer other health benefits. Given that clinical management of primary and secondary hypogonadism due to organic or functional aetiologies vary, it is important to evaluate and establish the aetiology of hypogonadism prior to initiating testosterone treatment.
Benefits of Testosterone Treatment
Authors: Basaria Shehzad , Gagliano-Jucá Thiago
Published: January 2022

Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal concentrations of sperm, or both. Hypogonadism may result from disease or dysfunction of the testes (primary hypogonadism) or hypothalamic–pituitary unit (secondary hypogonadism). In young men with organic (classic) hypogonadism that results from diseases of the hypothalamus, pituitary, or testes, testosterone replacement therapy results in beneficial effects, which include induction and maintenance of secondary sexual characteristics, improvement in sexual function, increase in lean mass and improvement of bone mass and quality. In these young androgen-deficient men, testosterone therapy is generally safe and associated with few adverse effects. In contrast to the organic hypogonadism, the relatively low incidence of which has remained unchanged for decades, symptomatic older men with low circulating serum testosterone concentrations are increasingly being seen in clinical practice and commonly referred to as ‘late-onset’ or ‘age-related’ hypogonadism. This age-related decline in testosterone levels is generally small compared to men with organic hypogonadism. The evidence for clinical benefits of testosterone treatment in older men is limited and long-term risks (mainly prostate and cardiovascular) remain unknown. In this chapter, we will review efficacy of testosterone replacement therapy in men with organic hypogonadism as well as in men with age-related decline in testosterone.
Serum total IgE may be a biomarker among chronic pulmonary aspergillosis patients with elevated serum total IgE levels: A cohort study with pathological evaluations
Authors: Watanabe Shizuka , Suzuki Junko , Suzukawa Maho , Takeda Keita , Imoto Sahoko , Kitani Masashi , Fukami Takeshi , Sasaki Yuka , Hebisawa Akira , Matsui Hirotoshi
Published: January 2022

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients’ serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P < .0001). The median rate of change was 1.76 times (quartile 1.41–3.25). In addition, we used surgical specimens of CPA cases with high serum total IgE levels, normal serum total IgE CPA cases, and control surgical specimens and performed immunofluorescence staining with IgE, mast cell tryptase, CD138, and 4,6-diamidino-2-phenylindole. We observed multiple mast cells and plasma cells in the CPA cases regardless of the serum total IgE level. In contrast, multiple IgE-positive cells co-stained with tryptase were observed in CPA cases with high serum total IgE levels. This finding suggested that serum total IgE could serve as a biomarker for evaluating disease severity. Immunofluorescence staining suggested that IgE may play a role in pathogenesis through activation of mast cells by cross-linking in cases of CPA with high serum total IgE levels.

Lay summary

High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.
Invasive mold infection of the gastrointestinal tract: A case series of 22 immunocompromised patients from a single academic center
Authors: Quintero Orlando , Allard Libby , Ho Dora
Published: January 2022

Invasive mold infection (IMI) of the gastrointestinal (GI) tract is a rare complication in immunocompromised patients that carries a high mortality rate. It is most often described in the setting of disseminated disease. Early diagnosis and treatment are critical in its management, but this is rarely obtained, leading to delayed therapy. To describe the clinical characteristics, treatment and outcomes of this infection, we reviewed all the cases of adult patients with histopathological findings from autopsy or surgical specimens that demonstrated fungal invasion into the GI tract at Stanford Hospital & Clinics from January 1997 to August 2020. Twenty-two patients that met criteria were identified and they were all immunocompromised, either due to their underlying medical conditions or the treatments that they received. The most common underlying disease was hematological malignancies (63.6%) and the most common symptoms were abdominal pain, GI bleeding and diarrhea. A majority of patients (72.7%) had disseminated invasive mold infection, while the rest had isolated GI tract involvement. In 2/3 of our cases, the fungal genus or species was confirmed based on culture or PCR results. Given the very high mortality associated with GI mold infection, this diagnosis should be considered when evaluating immunocompromised patients with concerning GI signs and symptoms. A timely recognition of the infection, prompt initiation of appropriate antifungal therapy as well as surgical intervention if feasible, are key to improve survival from this devastating infection.

Lay summary

Patients with a weakened immune system can suffer from mold infections in the bowel, which are difficult to diagnose and have very high death rate. We examined such cases in our institution in order to learn about their clinical and microbiological features. This study can further improve our understanding of these infections in order to improve patient outcome.
Paeonol enhances treatment of fluconazole and amphotericin B against oropharyngeal candidiasis through HIF-1α related IL-17 signaling
Authors: Pan Min , Wang Qirui , Liu Yulong , Xiao Nan , Niu Xiaojia , Wu Daqiang , Wang Tianming , Yan Guiming , Shao Jing
Published: January 2022

Oropharyngeal candidiasis (OPC) is an oral infection mainly caused by Candida albicans, a dimorphic human opportunistic pathogen that can proliferate and invade the superficial oral epithelium using its hyphae. The filamentation of C. albicans is a hallmark of biofilm formation, accompanied by the occurrence of a hypoxic microenvironment. Paeonol (PAE) is a traditional medicine with multiple properties. In a previous study, we demonstrated the synergism of PAE plus Fluconazole (FLU) or Amphotericin B (AmB) against C. albicans in vitro and in vivo. This study aimed to explore the therapeutic mechanisms of drug combinations on OPC. In an established OPC mouse model, the culture of hypoxia was observed by calcofluor white and hypoxyprobe staining. The expression and levels of IL-17 signaling-associated genes and proteins (IL-17A and IL-23) were evaluated in tissue homogenates and EC109 cells. The results show that compared with the single therapy, PAE plus FLU or AmB can decrease fungal burden, restore mucosal integrity, and reduce the hypoxic microenvironment and inflammation in the OPC mice. Relative to infected mice, the drug combinations can also rectify the abnormal expression of hypoxia inducible factor (hif)-1α, il-17a, and il-23 mRNA. Meanwhile, compared with the infected EC109 cells treated with a single drug, PAE plus FLU or AmB significantly inhibited the mRNA and protein expression of HIF-1α, IL-17A, and IL-23. Taken together, the possible mechanism of PAE plus FLU or AmB can be attributed to the regulation of hypoxia-associated IL-17 signaling in OPC treatment.
Compact object mergers in hierarchical triples from low-mass young star clusters
Authors: Trani Alessandro A , Rastello Sara , Carlo Ugo N Di , Santoliquido Filippo , Tanikawa Ataru , Mapelli Michela
Published: January 2022

A binary star orbited by an outer companion constitutes a hierarchical triple system. The outer body may excite the eccentricity of the inner binary through the von Zeipel-Lidov-Kozai (ZLK) mechanism, triggering the gravitational wave (GW) coalescence of the inner binary when its members are compact objects. Here, we study a sample of hierarchical triples with an inner black hole (BH) – BH binary, BH – neutron star (NS) binary, and BH – white dwarf (WD) binary, formed via dynamical interactions in low-mass young star clusters. Our sample of triples was obtained self-consistently from direct N-body simulations of star clusters which included up-to-date stellar evolution. We find that the inner binaries in our triples cannot merge via GW radiation alone, and the ZLK mechanism is essential to trigger their coalescence. Contrary to binaries assembled dynamically in young star clusters, binary BHs merging in triples have preferentially low mass ratios (q ≃ 0.3) and higher primary masses ($m_{\rm p} \gtrsim 40 {\, \rm M_\odot }$). We derive a local merger rate density of 0.60, 0.11 and $0.5 {-1} \, \rm Gpc^{-3}$ for BH-BH, BH-NS and BH-WD binaries, respectively. Additionally, we find that merging binaries have high eccentricities across the GW spectrum, including the LIGO-Virgo-KAGRA (LVK), LISA, and DECIGO frequencies. About 7 per cent of BH-BH and 60 per cent of BH-NS binaries will have detectable eccentricities in the LVK band. Our results indicate that the eccentricity and the mass spectrum of merging binaries are the strongest features for the identification of GW mergers from triples.
Thethesanproject: properties of the intergalactic medium and its connection to reionization-era galaxies
Authors: Garaldi E , Kannan R , Smith A , Springel V , Pakmor R , Vogelsberger M , Hernquist L
Published: January 2022

The high-redshift intergalactic medium (IGM) and the primeval galaxy population are rapidly becoming the new frontier of extragalactic astronomy. We investigate the IGM properties and their connection to galaxies at z ≥ 5.5 under different assumptions for the ionizing photon escape and the nature of dark matter, employing our novel thesan radiation-hydrodynamical simulation suite, designed to provide a comprehensive picture of the emergence of galaxies in a full reionization context. Our simulations have realistic ‘late’ reionization histories, match available constraints on global IGM properties, and reproduce the recently observed rapid evolution of the mean free path of ionizing photons. We additionally examine high-z Lyman-α transmission. The optical depth evolution is consistent with data, and its distribution suggests an even-later reionization than simulated, although with a strong sensitivity to the source model. We show that the effects of these two unknowns can be disentangled by characterizing the spectral shape and separation of Lyman-α transmission regions, opening up the possibility to observationally constrain both. For the first time in simulations, thesan reproduces the modulation of the Lyman-α flux as a function of galaxy distance, demonstrating the power of coupling a realistic galaxy formation model with proper radiation hydrodynamics. We find this feature to be extremely sensitive on the timing of reionization, while being relatively insensitive to the source model. Overall, thesan produces a realistic IGM and galaxy population, providing a robust framework for future analysis of the high-z Universe.
Siloxyl radical initiated HCN polymerization: computation of N-heterocycles formation and surface passivation
Authors: Fioroni Marco , DeYonker Nathan J
Published: January 2022

In this work, by means of quantum chemistry (Density Functional Theory (DFT), PW6B95/def2-TZVPP; DLPNO-CCSD(T)/CBS), HCN polymerization [(HCN)1 − 4] initiated and catalysed by a siloxyl radical (Si-O•) on a model silica surface is analysed. Linear HCN polymers (pHCN) are obtained by a radical initiated mechanism at a SiO• site and are characterized by a -(HC-N)- skeleton due to radical localization on the terminal N atom and radical attack on the C centre. NC heterocycles are formed by cyclization of the linear SiO-(HCN)3 − 4 and are always thermodynamically preferred over their linear counterparts, acting as thermodynamic sinks. Of particular interest to the astrochemistry community is the formation of the N-heterocycle 1,3,5-triazine that can be released into the gas phase at relatively low T (ΔG† = 23.3 kcal/mol). Full hydrogenation of SiO-(HCN•) follows two reaction channels with products: (a) SiO-CH3 + •NH2 or (b) amino-methanol + Si•, though characterized by slow kinetics. Nucleophilic addition of H2O to the electron-rich SiO-(HCN•) shows an unfavourable thermodynamics as well as a high-activation energy. The cleavage of the linear (HCN)1−4 from the SiO• site also shows a high thermodynamic energy penalty (ΔG≥82.0 kcal/mol). As a consequence, the silicate surface will be passivated by a chemically active ‘pHCN brush’ modifying the surface physico-chemical properties. The prospect of surface-catalysed HCN polymers exhibiting a high degree of chemical reactivity and proposed avenues for the formation of 1,3,5-triazine and amino-methanol opens exciting new chemical pathways to Complex Organic Matter formation in astrochemistry.
The RapidXMM upper limit server: X-ray aperture photometry of the XMM-Newton archival observations
Authors: Ruiz A , Georgakakis A , Gerakakis S , Saxton R , Kretschmar P , Akylas A , Georgantopoulos I
Published: January 2022

This paper presents the construction of the RapidXMM database that is available through the XMM-Newton Science Archive and offers access to upper limits and aperture photometry across the field of view of the XMM-Newton Pointed and Slew Survey observations. The feature of RapidXMM is speed. It enables the fast retrieval of X-ray upper limits and photometry products in three energy bands (0.2–2, 2–12, and 0.2–12 keV) for large numbers of input sky positions. This is accomplished using the Hierarchical Equal Area Iso Latitude pixelation of the sphere (HEALPix). The pre-calculated upper-limits and associated X-ray photometry products are reprojected into the HEALPix grid of cells before being ingested into the RapidXMM database. This results in tables of upper limits and aperture photometry within HEALPix cells of size ≈3 arcsec (Pointed observations) and 6 arcsec (Slew Survey). The database tables are indexed by the unique integer number of the HEALPix cells. This reduces spatial nearest-neighbour queries by sky position to an integer-matching exercise and significantly accelerates the retrieval of results. We describe in detail the processing steps that lead from the science products available in the XMM-Newton archive to a database optimized for sky queries. We also present two simple show-case applications of RapidXMM for scientific studies – searching for variable X-ray sources and stacking analysis of X-ray faint populations.
NGC 2004 #115: a black hole imposter containing three luminous stars
Authors: El-Badry Kareem , Burdge Kevin B , Mróz Przemek
Published: January 2022

NGC 2004 #115 is a recently identified black hole (BH) candidate in the Large Magellanic Cloud (LMC) containing a B star orbiting an unseen companion in a 2.9 d orbit and a Be star tertiary. We show that the unseen companion is not a 25 M⊙ BH, but a $(2\!-\!3)\, {\rm M}_{\odot }$ luminous star. Analysing the Optical Gravitational Lensing Experiment (OGLE) and MAssive Compact Halo Object (MACHO) light curves of the system, we detect ellipsoidal variability with amplitude 10 times larger than would be expected if the companion were a 25 M⊙ BH, ruling out the low inclination required for a massive companion. The light curve also shows a clear reflection effect that is well modelled with a $2.5\, {\rm M}_{\odot }$ main-sequence secondary, ruling out a lower mass BH or neutron star companion. We consider and reject models in which the system is a binary containing a stripped star orbiting the Be star: only a triple model with an outer Be star can explain both the observed light curve and radial velocities. Our results imply that the B star, whose slow projected rotation velocity and presumed tidal synchronization were interpreted as evidence for a low inclination (and thus a high companion mass), is far from being tidally synchronized: despite being in a 2.9 d orbit that is fully or nearly circularized (e < 0.04), its surface rotation period appears to be at least 20 d. We offer cautionary notes on the interpretation of dormant BH candidates in binaries.