bluuebunny/crossref_metadata_2025 huggingface dataset:
Female Infertility
Authors: Oktay Kutluk , Taylan Enes
Published: January 2022

Fertility preservation is an emerging field which aims to develop and utilize effective treatment options for women under risk of ovarian insufficiency (OI) due to a wide range of conditions from chromosomal disorders to antineoplastic treatments and surgical interventions that can cause loss of ovarian follicle reserve. Irreversible loss of fertility and ovarian endocrine function can have a negative impact on women’s physiological and psychosocial health. Therefore, preservation of fertility in reproductive age women is a critical component of modern healthcare and improved quality of life. In this chapter, we will review the current status and future perspectives of the field of fertility preservation as an emerging branch of assisted reproductive technologies.
Hormonal Contraception
Authors: Chin Jennifer , Kaneshiro Bliss
Published: January 2022

The birth control pill, the first hormonal contraceptive method widely available to the public, transformed the way society viewed childbearing and sexuality. Since the 1960s, many different types of hormonal contraceptives have been developed and are now available to women. There are two main categories of hormonal contraceptives, combined hormonal contraceptives, which consist of oestrogen and progestin, and progestin-only contraceptives. Within each category, various methods and formulations exist, each with a different mechanism of action, efficacy, and side effect profile. Emergency contraception offers a post-coital method that can be used in cases where women did not use contraception at the time of intercourse or had a method failure (i.e. condom breakage). Several contraceptive methods have non-contraceptive benefits. Most methods decrease the risk of endometrial cancer and combined hormonal contraceptives decrease the risk of ovarian cancer. Many methods have been used in the treatment of abnormal uterine bleeding, dysmenorrhoea, premenstrual syndrome, and acne.
General Considerations Relating to Thyroid Disease in Pregnancy
Authors: Taylor Peter N. , Premawardhana L.D.K.E. , Lazarus John H.
Published: January 2022

Thyroid hormone is essential for maintaining a pregnancy and ensuring fetal development. Thyroid disorders are common in women of childbearing age and as pregnancy has a substantial impact on the hypothalamic–pituitary–thyroid axis, abnormal thyroid function is frequently encountered in antenatal clinics. It is also well established that overt thyroid disease is associated with adverse obstetric and offspring neuro-developmental outcomes. There is now growing concern that more marginal degrees of thyroid dysfunction particularly subclinical hypothyroidism (elevated TSH and normal fT4 concentration) and isolated hypothyroxinaemia (normal TSH and low fT4) are also associated with fetal loss, prematurity and impaired offspring cognitive function. In some studies, maternal thyroid autoimmunity has also been identified as a potential risk for fetal loss even in euthyroid women. Correction of overt hypothyroidism and hyperthyroidism dramatically reduces the risk of major adverse obstetric outcomes including fetal loss and premature birth.
Thyroid Disease During Pregnancy
Authors: Korevaar Tim I.M. , Peeters Robin P.
Published: January 2022

Thyroid physiology undergoes major changes during pregnancy, understanding of which improves the clinical assessment of thyroid function during pregnancy and the clinical decision-making process regarding the follow-up and treatment of gestational thyroid disease. Although thyroid function is frequently assessed before and during pregnancy, accurate clinical assessment, and interpretation of maternal (and fetal) thyroid function during pregnancy is complicated by the maternal–placental–fetal interaction. Given this complexity, it remains difficult how and when to evaluate for thyroid dysfunction, as well as if and how to treat (mild) thyroid disease during pregnancy. This chapter discusses current insights on physiology, diagnosis, risk of adverse outcomes, and treatment options.
Thyroid Disorders in Newborns
Authors: van Trotsenburg A.S. Paul , Zwaveling-Soonawala Nitash
Published: January 2022

Thyroid hormone is essential for normal brain development starting in the early embryonic period and continuing throughout the first years of life. Untreated congenital hypothyroidism leads to permanent intellectual and motor disabilities. Neonatal screening programmes have proven to be very successful in preventing brain damage by early detection and treatment of congenital hypothyroidism. Congenital hypothyroidism may be of thyroidal (primary) or of hypothalamic–pituitary (central) origin. Primary congenital hypothyroidism accounts for approximately 90–95% of all cases and may be due to abnormal thyroid gland formation (dysgenesis) or defective thyroid hormone syntheses by a structurally normal gland (dyshormonogenesis). Central congenital hypothyroidism has a reported incidence of up to one in 16 000 live births and may occur in isolation, but in the majority of cases is accompanied by additional pituitary hormone deficiencies. In this chapter the aetiology, diagnostics, and treatment of congenital hypothyroidism are discussed.
Sex Determination and Differentiation
Authors: Hiort Olaf , Werner Ralf
Published: January 2022

The biological sex of a human being is dependent on a genetic pathway starting from the chromosomal set that determines the differentiation of the gonads. In this chapter the current knowledge of the physiological genetic regulation of gonadal development, termed sex determination is described, followed by the endocrine differentiation into the usual phenotypes of male and female. The delicate complexity of these pathways is not only dependent on the genetic composition, but needs to occur in a stringent step-wise and time-dependent manner, therefore dependent on hitherto often unknown regulatory mechanisms. Deviations and disruptions of these pathways may lead to disorders or differences of sex development (DSD), demonstrating that the poles of female and male may be not robust, but are subject to high variability even within the usual sex development.
Recognizing Normal and Disordered Pubertal Development
Authors: Rogol Alan D. , Fuqua John S.
Published: January 2022

Pubertal maturation is a time of dramatic physical, reproductive, and psychological changes, including the development of secondary sex characteristics and changes in body composition. It requires a complex series of hormonal changes initiated by alterations in hypothalamic regulatory mechanisms that are incompletely understood, culminating in gonadal sex steroid secretion and associated maturation. While genetics play a major role in the timing and progression of pubertal maturation, other inputs such as nutrition, environmental factors, and social milieu yield individualized variations in the maturational pattern. It is likely that these factors are in part responsible for changes in timing and tempo of pubertal maturation noted over the last few decades. When a child begins to mature at the earliest or latest extremes of the normal ranges, the clinician must determine if the child is undergoing normal puberty, a non-pathologic variation, or a medically concerning condition that requires further investigation or treatment.
Pubertal Delay and Hypogonadism
Authors: Rogol Alan D. , Fuqua John S.
Published: January 2022

Delayed puberty occurs when no signs of pubertal maturation are seen by 14 years of age in boys or 13 years in girls. Although constitutional delay of growth and puberty is commonly seen and is often regarded as benign, there are many other causes of pubertal delay that ultimately result in permanent hypogonadism, and these must be differentiated from self-limited delays in maturation. Causes of hypogonadism include disorders affecting the gonads (primary hypogonadism) and abnormalities of pituitary or hypothalamic function (hypogonadotropic hypogonadism). Hypogonadotropic hypogonadism may be part of a more global set of pituitary deficiencies or may be the only endocrine axis affected. A rapidly growing array of genetic disorders accounts for isolated hypogonadotropic hypogonadism. Treatment of delayed puberty often consists of short-term administration of sex steroids to those with constitutional delay, while individuals with permanent hypogonadism require long-term testosterone or oestradiol replacement.
Transition in Endocrinology
Authors: Gleeson Helena K. , Wright Rohana J.
Published: January 2022

Healthcare professionals are increasingly aware that the transition from childhood to adulthood requires special consideration, in terms of meeting the needs of young people with any long-term condition, both through healthcare design and delivery and the need for a specific skill and behaviour set in order to do this effectively. Young people can be a forgotten group, not adequately considered in paediatric or adult service development strategies resulting in disrupted care. This phase of life is key, as it is when a young person develops their ideas about, and relationships with the healthcare system and their own health condition, thus setting the scene for future interactions. Young people with endocrine conditions, whether onset is in early childhood or during adolescence, often require lifelong care, and therefore both paediatric and adult healthcare professionals require knowledge about: biopsychosocial development and how it can both affect and be affected by having an endocrine condition; key aspects of adolescent health; developmentally appropriate healthcare; effective transition between paediatric and adult services; endocrine-specific care during adolescence and young adulthood.
Paraneoplastic Endocrine Syndromes
Authors: Ray David W.
Published: January 2022

Hormone production from non-endocrine glands poses a diagnostic and management challenge. With improvements in hormone assay precision, and diagnostic imaging, the clinician is better equipped now to manage the patient. Here, we review the underlying biology of ectopic hormone production, and aberrant regulation. Ectopic adrenocorticotrophic hormone (ACTH) syndrome is a prevalent disorder, but in most cases remains undiagnosed, and is managed as part of treatment for small cell undifferentiated cancer. Humoral hypercalcaemia of malignancy is also commonly encountered, but with PTHrP assay, and bisphosphonate therapy can be effectively managed. SIADH is a frequent diagnosis in medical inpatients, here the danger is frequently overtreatment. Hormone-dependent cancers are primarily managed by oncology services, but the role of hormones in breast and prostate development, and the hormonal manipulations used in their management are important. Here, we review the state of the art in hormone-dependent cancers.
Hormonal Therapy for Prostate Cancer
Authors: Vasilevskaya Irina A. , Schiewer Matthew J. , Knudsen Karen E.
Published: January 2022

First-line therapy for metastatic prostate cancer (PCa) is targeted at the androgen receptor (AR), which governs gene expression programmes that impact pro-tumorigenic phenotypes, including proliferation, survival, and DNA repair. As is the case for many cancers, ageing is one of the most significant risk factors for PCa. PCa develops mainly in older men, with a significantly higher frequency in African-American men. Diagnosis rarely occurs in men younger than 40 years old, with the majority of new cases diagnosed between the ages of 65 and 79. Current data suggest that only up to 10% of PCa cases are hereditary, especially in early onset disease, while other risk factors proposed in some studies, such as smoking and excess body weight, have not been universally accepted. This chapter will outline the mechanistic underpinnings of response and resistance to AR-directed therapy, including androgen deprivation therapy (ADT) and AR antagonists.
Obesity as a Public Health Problem
Authors: Bauman Adrian
Published: January 2022

Public health approaches to obesity are distinctly different, but complementary, to clinical management. The history of describing obesity as a public health problem is lengthy, preceding the 1990s high-income country ‘obesity epidemic’. Overweight and obesity now affect half to two-thirds of developed country populations, and rates are still increasing in middle-income countries. Patterns and socioeconomic correlates of obesity differ across countries at different stages of industrial development. In relation to health outcomes, obesity is consistently related to non-communicable disease, especially diabetes. Risk increases across all levels of obesity, but increases exponentially for extreme obesity. Population-wide increases are likely due to a complex system of environmental, societal, economic, and cultural factors, and these need to be addressed in implementing upstream primary prevention solutions. Working outside of the health sector will be required, posing challenge to the implementation of national obesity prevention plans.
Epidemiology and Public Health
Authors: Mayer-Davis Elizabeth J. , Igudesman Daria
Published: January 2022

Diabetes mellitus is a collection of endocrine disorders that involve insufficient or dysfunctional insulin production. Their causes include genetic and environmental factors that vary from one individual to another, and across populations. Trends in incidence and prevalence of diabetes and its complications also vary by geographic region, and by demographic factors such as gender, race, and ethnicity. While type 1 and type 2 diabetes onset tend to occur more frequently in children and adults, respectively, relative proportions of the two may be difficult to measure accurately in middle- and low-income countries. Gestational diabetes is a third diabetes type that is on the rise, partially due to increases in obesity among women of childbearing age. Prevention and treatment efforts should include a combination of pharmacologic and lifestyle interventions, and should be targeted based upon resource availability and feasibility. Economic impact is discussed both nationally and internationally.
Presentation and Natural History of Type 2 Diabetes
Authors: Taylor Roy
Published: January 2022

Clinical presentation of type 2 diabetes are described. The natural history of the three phases of type 2 diabetes—prediabetes, diabetes itself, and the post-diabetic state—are presented in terms of clinical features and underlying pathophysiology. The dangerous, asymptomatic phase of prediabetes is a high risk state for cardiovascular disease. This is also true for type 2 diabetes, with the additional microvascular complication risks. If weight loss is not achieved and maintained after diagnosis, the diabetic state steady progresses, requiring sequential addition of antidiabetic agents. In the past decade clear information on the potential reversibility of the processes underlying diabetes has become available. It is now possible to describe the post-diabetic state. Provided that substantial weight loss is achieved and maintained, non-diabetic glycaemic control can be stable for several years. Longer-term observation is required of cardiovascular outcomes, although risk indices indicate return to background levels.
Monogenic Forms of Diabetes Resulting from Beta-Cell Dysfunction
Authors: Hattersley Andrew , Patel Kashyap A. , Besser Rachel
Published: January 2022

Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing beta-cell dysfunction, which accounts for the majority of cases. Patients can usually be divided into three clinical categories; maturity-onset diabetes of the young (MODY) which is dominantly inherited familial diabetes, neonatal diabetes diagnosed under the age of 6 months and monogenic diabetes syndromes which are characterized by multiple non-pancreatic features. In each clinical category there are several aetiological genes, which usually result in a discrete clinical phenotype. Genetic diagnosis is now possible in >80% of cases and is crucial in determining appropriate management, predicting clinical course, screening affected relatives, and genetic counselling of unaffected family members. Importantly, in many of the most common causes of monogenic beta-cell diabetes, making a diagnosis can result in greatly improved treatment. However diagnosis can be challenging because of low prevalence rates in a diabetes clinic (1–3%) and the majority of patients are therefore misdiagnosed as having type 1 (T1D) or type 2 diabetes (T2D). Features that distinguish these disorders are discussed.
Pathogenesis of Microvascular Complications
Authors: Shore Angela
Published: January 2022

The microvascular complications of diabetes, seen clinically as diabetic retinopathy, nephropathy, and neuropathy are preceded by subclinical microvascular dysfunction and abnormalities in other cells in the neurovascular units. Once microvascular complications are established both structural (e.g. thickened capillary basement membrane, acellular capillaries, pericyte loss, tissue remodelling, fibrosis, mesangial expansion) and functional changes (e.g. reduced perfusion, impaired endothelial function, leukocyte sticking and migration, increased vascular permeability) occur. The mechanisms underlying the formation and progression of microvascular complications are complex, and vary both with the stage of disease and an individual’s susceptibility to complications due to both their genetic risk and environmental factors.
Management of Idiopathic Male Infertility
Authors: Tournaye Herman , Popovic-Todorovic Biljana
Published: January 2022

Male reproductive deficiency may result from factors that affect sperm production, sperm quality and function, or sperm transport. However, in about 30–40% of men the cause for these impairments remain unexplained, but increasingly, genetic causes are being discovered. In general, although largely unproven, a healthy lifestyle may improve sperm quality. Currently, there is no evidence of beneficial effect of food supplements and oral antioxidant preparations in management of idiopathic male infertility. Empiric hormonal treatment has no role in unexplained male infertility. Assisted reproduction technologies (ART) are relatively successful and increasingly used as the management of choice in the idiopathic male infertility.
Hypothalamo–Pituitary–Testicular Axis Function in Systemic Diseases and Effects of Medications
Authors: Wittert Gary , Yeap Bu B. , Grossmann Mathis
Published: January 2022

‘Pathological hypogonadism’, reflecting disease within the hypothalamo–pituitary–testicular (HPT) axis occurs in under 2.5% of men. However, low serum testosterone (T) concentrations, which affect up to 40% of middle-aged and elderly men in some populations, are more frequently attributable to acute and chronic disease, medication use, and lifestyle behaviours external to the HPT axis, i.e. ‘functional hypogonadism’. Undernutrition, obesity, type 2 diabetes, cardiovascular disease, chronic airways disease, inflammatory disorders, severe infections, and depression are associated with reduced T and low or inappropriately normal gonadotrophin concentrations. In chronic liver disease low T is associated with increased sex-hormone-binding-globulin (SHBG). Hyper- and hypothyroidism result in marked increases and decreases in SHBG concentrations in respectively. In chronic kidney disease the predominant effect is failure of Leydig cell function with elevated gonadotropin levels. In any of these circumstances the effects are modulated by concomitant comorbidities and/or medication use.
Active Duty Service Members, Primary Managers, and Administrators’ Perspectives on a Novel Sleep Telehealth Management Platform in the U.S. Military Healthcare System
Authors: Wickwire Emerson M , Abdelwadoud Moaz , Collen Jacob , Edwards Hillary , Labra Christian , Capaldi Vincent F , Williams Scott G , Manber Rachel , Assefa Samson Z , Drake Christopher L , Albrecht Jennifer S , Bevan Jeffrey , Mahoney Alexandra , Tatum Eileen D , Pierre Elysse , Mantua Janna , Grandner Michael A , Mullins C Daniel
Published: January 2022

Introduction

Sleep disorders are common in the military, and there is a gross shortage of sleep specialists in the military health system. The purposes of the present study were to (1) understand perceptions and expectations surrounding sleep telehealth approaches and (2) solicit feedback to optimize and refine a proposed novel sleep telehealth management platform. To accomplish these objectives, we investigated the perceptions, expectations, and preferences of active duty service members (ADSMs) with sleep disorders, primary care managers (PCMs), and administrative stakeholders regarding sleep telehealth management.

Materials and Methods

Using convenience sampling, we conducted five focus groups with 26 ADSMs and 11 individual interviews with PCMs from two military treatment facilities in the U.S National Capital Region and 11 individual interviews with administrative sleep stakeholders (9 military and 2 civilian).

Results

Active duty service members, PCMs, and administrative stakeholders provided insight regarding expectations for sleep telehealth as well as suggestions to optimize the novel sleep telehealth platform. In terms of outcomes, ADSMs expected sleep telehealth to improve sleep and convenience. Primary care managers expected improved sleep and other comorbidities, enhanced operational readiness, and reduced mortalities among their patients. Administrators expected increased access to care, optimized utilization of health services, realized cost savings, reduced accidents and errors, and improved military performance. In terms of the platform, for ADSMs, desired characteristics included delivery of timely clinical reports, improved patient–provider communication, and enhanced continuity of care. For PCMs and administrators,an ideal sleep telehealth solution will improve the diagnosis and triage of sleep patients, save PCM time, be easy to use, and integrate with the electronic health record system.

Conclusion

The proposed sleep telehealth platform appealed to nearly all participants as a significant force multiplier to enhance sleep disorder management in the military. Stakeholders offered valuable recommendations to optimize the platform to ensure its successful real-world implementation.
Dust models for the extinction of Type IIn supernova SN 2010jl
Authors: Li Jun , Gao Jian , Jiang Biwei , Lin Zesen
Published: January 2022

The unusual extinction curves of SN 2010jl provide an excellent opportunity to investigate the properties of dust formed by core-collapse supernovae. By using a series of dust models with different compositions and grain size distributions, we fit the extinction curves of SN 2010jl and find that a silicate–graphite mixture dust model characterized by exponentially cut-off power-law size distributions can well reproduce its unusual extinction curves. The best-fitting results show that the extinctions derived from the dust models are consistent with the observed values at all epochs. However, the total-to-selective extinction ratio RV is ∼2.8–3.1, which is significantly smaller than the value of RV ≈ 6.4 derived by Gall et al. The best-fitting models indicate that the dust grains around SN 2010jl are possibly composed of small-sized astronomical silicate grains and micron-sized graphite grains. In addition, by fitting the optical to mid-infrared spectral energy distribution, we find that the dust mass around SN 2010jl increases with time, up to $0.005\, \mathrm{ M}_{\odot }$ around 1300 d after peak brightness, which is consistent with previous estimates (Gall et al.; Sarangi et al.).
Itching in dialysis patients: impact on health-related quality of life and interactions with sleep problems and psychological symptoms—results from the RENINE/PROMs registry
Authors: van der Willik Esmee M , Lengton Robin , Hemmelder Marc H , Hoogeveen Ellen K , Bart Hans A J , van Ittersum Frans J , ten Dam Marc A G J , Bos Willem Jan W , Dekker Friedo W , Meuleman Yvette
Published: January 2022

Background

Itching (pruritus) is common in dialysis patients, but little is known about its impact on health-related quality of life (HRQOL), sleep problems and psychological symptoms. This study investigates the impact of itching in dialysis patients by looking into the persistence of itching, the effect of itching on the course of HRQOL and the combined effect of itching with sleep problems and with psychological symptoms on HRQOL.

Methods

Data were obtained from the RENINE/PROMs registry and included 2978 dialysis patients who completed patient-reported outcome measures between 2018 and 2020. Itching, sleep problems and psychological symptoms were assessed with the Dialysis Symptom Index (DSI) and HRQOL with the 12-item Short Form Health Survey. Effects of itching on HRQOL and interactions with sleep problems and psychological symptoms were investigated cross-sectionally and longitudinally using linear regression and linear mixed models.

Results

Half of the patients experienced itching and in 70% of them, itching was persistent. Itching was associated with a lower physical and mental HRQOL {−3.35 [95% confidence interval (CI) −4.12 to −2.59) and −3.79 [95% CI −4.56 to −3.03]}. HRQOL remained stable during 2 years and trajectories did not differ between patients with or without itching. Sleep problems (70% versus 52%) and psychological symptoms (36% versus 19%) were more common in patients with itching. These symptoms had an additional negative effect on HRQOL but did not interact with itching.

Conclusions

The persistence of itching, its impact on HRQOL over time and the additional effect on HRQOL of sleep problems and psychological symptoms emphasize the need for recognition and effective treatment of itching to reduce symptom burden and improve HRQOL.
Comparable Impairment of Vascular Endothelial Function by a Wide Range of Electronic Nicotine Delivery Devices
Authors: Rao Poonam , Han Daniel D , Tan Kelly , Mohammadi Leila , Derakhshandeh Ronak , Navabzadeh Mina , Goyal Natasha , Springer Matthew L
Published: January 2022

Introduction

Electronic nicotine delivery systems (ENDS; ie, vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, their cardiovascular effects are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices, including a new ultrasonic vaping device, impairs endothelial function.

Aims and Methods

We measured arterial flow-mediated dilation (FMD) in rats (n = 8/group) exposed to single session of 10 cycles of pulsatile 5-second exposure over 5 minutes to aerosol from e-liquids with and without nicotine generated from a USONICIG ultrasonic vaping device, previous generation e-cigarettes, 5% nicotine JUUL pods (Virginia Tobacco, Mango, Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls. We evaluated nicotine absorption and serum nitric oxide levels after exposure, and effects of different nicotine acidifiers on platelet aggregation.

Results

Aerosol/smoke from all conditions except air significantly impaired FMD. Serum nicotine varied widely from highest in the IQOS group to lowest in USONICIG and previous generation e-cig groups. Nitric oxide levels were not affected by exposure. Exposure to JUUL and similarly acidified nicotine salt e-liquids did not affect platelet aggregation rate. Despite lack of heating coil, the USONICIG under airflow conditions heated e-liquid to ~77°C.

Conclusions

A wide range of ENDS, including multiple types of e-cigarettes with and without nicotine, a heated tobacco product, and an ultrasonic vaping device devoid of heating coil, all impair FMD after a single vaping session comparably to combusted cigarettes.

Implications

The need to understand the cardiovascular effects of various ENDS is of timely importance, as we have seen a dramatic increase in the use of these products in recent years, along with the growing assumption among its users that these devices are relatively benign. Our conclusion that a single exposure to aerosol from a wide range of ENDS impairs endothelial function comparably to cigarettes indicates that vaping can cause similar acute vascular functional impairment to smoking and is not a harmless activity.
Antiretroviral Refill Histories as a Predictor of Future Human Immunodeficiency Virus Viremia
Authors: Sokpa Darryl , Lyden Elizabeth , Fadul Nada , Bares Sara H , Havens Joshua P
Published: January 2022

Background

The use of adherence measures as markers for virologic failure (VF) has been studied. Yet, there is currently no single adherence metric recommended for VF. Antiretroviral prescription refill histories, for people living with human immunodeficiency virus (HIV), are readily accessible and can be easily quantified to an estimated adherence level.

Methods

Participants from a Midwestern US HIV clinic were retrospectively evaluated from 2018 to 2020. Refill histories (RH) and last HIV RNA for each participant were abstracted for each study year. RH were quantified as a percentage of days covered (PDC) and VF was defined as HIV RNA >200 copies/mL. PDC values were matched with subsequent year HIV RNA (matched pair). Sample t test were used to compare mean PDC level by viral suppression status and generalized estimating equations models were used to determine the predictability of PDC level for VF. An optimal PDC threshold for VF was determined using receiver operating characteristic curve analysis and Youden index.

Results

A total of 1056 participants contributed to 1923 matched pairs (PDC/HIV RNA); mean age was 48.3 years, 24% women, and 30.6% Black. PDC levels differed significantly based on dichotomized HIV RNA (2018–2019: >200: 40% [95% confidence interval {CI}, 33%–46%] vs ≤200: 85% [95% CI, 84%–87%], P < .0001; 2019–2020: >200: 45% [95% CI, 38%–51%] vs ≤200: 87% [95% CI, 86%–89%], P < .0001). Based on the Youden index value of 0.66 (sensitivity 0.77, specificity 0.89), the optimal PDC threshold predictive of VF was 52%.

Conclusions

Lower antiretroviral therapy (ART) adherence levels were predictive of future VF when PDC ≤52%.
Factors Associated With SARS-CoV-2 Attack Rates in Aged Care—A Meta-analysis
Authors: Kunasekaran Mohana , Quigley Ashley , Rahman Bayzidur , Chughtai Abrar A , Heslop David J , Poulos Christopher J , MacIntyre C Raina
Published: January 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality in aged-care facilities worldwide. The attention of infection control in aged care needs to shift towards the built environment, especially in relation to using the existing space to allow social distancing and isolation. Physical infrastructure of aged care facilities has been shown to present challenges to the implementation of isolation procedures. To explore the relationship of the physical layout of aged care facilities with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack rates among residents, a meta-analysis was conducted.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P), studies were identified from 5 databases using a registered search strategy with PROSPERO. Meta-analysis for pooled attack rates of SARS-CoV-2 in residents and staff was conducted, with subgroup analysis for physical layout variables such as total number of beds, single rooms, number of floors, number of buildings in the facility, and staff per 100 beds.

Results

We included 41 articles across 11 countries, reporting on 90 657 residents and 6521 staff in 757 facilities. The overall pooled attack rate was 42.0% among residents (95% CI, 38.0%–47.0%) and 21.7% in staff (95% CI, 15.0%–28.4%). Attack rates in residents were significantly higher in single-site facilities with standalone buildings than facilities with smaller, detached buildings. Staff-to-bed ratio significantly explains some of the heterogeneity of the attack rate between studies.

Conclusions

The design of aged care facilities should be smaller in size, with adequate space for social distancing.
A tale of many families: calcium channels in plant immunity
Authors: Xu Guangyuan , Moeder Wolfgang , Yoshioka Keiko , Shan Libo
Published: January 2022

Plants launch a concerted immune response to dampen potential infections upon sensing microbial pathogen and insect invasions. The transient and rapid elevation of the cytosolic calcium concentration [Ca2+]cyt is among the essential early cellular responses in plant immunity. The free Ca2+ concentration in the apoplast is far higher than that in the resting cytoplasm. Thus, the precise regulation of calcium channel activities upon infection is the key for an immediate and dynamic Ca2+ influx to trigger downstream signaling. Specific Ca2+ signatures in different branches of the plant immune system vary in timing, amplitude, duration, kinetics, and sources of Ca2+. Recent breakthroughs in the studies of diverse groups of classical calcium channels highlight the instrumental role of Ca2+ homeostasis in plant immunity and cell survival. Additionally, the identification of some immune receptors as noncanonical Ca2+-permeable channels opens a new view of how immune receptors initiate cell death and signaling. This review aims to provide an overview of different Ca2+-conducting channels in plant immunity and highlight their molecular and genetic mode-of-actions in facilitating immune signaling. We also discuss the regulatory mechanisms that control the stability and activity of these channels.
Genetic characterization and curation of diploid A-genome wheat species
Authors: Adhikari Laxman , Raupp John , Wu Shuangye , Wilson Duane , Evers Byron , Koo Dal-Hoe , Singh Narinder , Friebe Bernd , Poland Jesse
Published: January 2022

A-genome diploid wheats represent the earliest domesticated and cultivated wheat species in the Fertile Crescent and include the donor of the wheat A sub-genome. The A-genome species encompass the cultivated einkorn (Triticum monococcum L. subsp. monococcum), wild einkorn (T. monococcum L. subsp. aegilopoides (Link) Thell.), and Triticum urartu. We evaluated the collection of 930 accessions in the Wheat Genetics Resource Center (WGRC) using genotyping by sequencing and identified 13,860 curated single-nucleotide polymorphisms. Genomic analysis detected misclassified and genetically identical (>99%) accessions, with most of the identical accessions originating from the same or nearby locations. About 56% (n = 520) of the WGRC A-genome species collections were genetically identical, supporting the need for genomic characterization for effective curation and maintenance of these collections. Population structure analysis confirmed the morphology-based classifications of the accessions and reflected the species geographic distributions. We also showed that T. urartu is the closest A-genome diploid to the A-subgenome in common wheat (Triticum aestivum L.) through phylogenetic analysis. Population analysis within the wild einkorn group showed three genetically distinct clusters, which corresponded with wild einkorn races α, β, and γ described previously. The T. monococcum genome-wide FST scan identified candidate genomic regions harboring a domestication selection signature at the Non-brittle rachis 1 (Btr1) locus on the short arm of chromosome 3Am at ∼70 Mb. We established an A-genome core set (79 accessions) based on allelic diversity, geographical distribution, and available phenotypic data. The individual species core set maintained at least 79% of allelic variants in the A-genome collection and constituted a valuable genetic resource to improve wheat and domesticated einkorn in breeding programs.
Identification and characterization of a set of monocot BAHD monolignol transferases
Authors: Smith Rebecca A , Beebe Emily T , Bingman Craig A , Vander Meulen Kirk , Eugene Alexis , Steiner Alexander J , Karlen Steven D , Ralph John , Fox Brian G
Published: January 2022

Plant BAHD acyltransferases perform a wide range of enzymatic tasks in primary and secondary metabolism. Acyl-CoA monolignol transferases, which couple a CoA substrate to a monolignol creating an ester linkage, represent a more recent class of such acyltransferases. The resulting conjugates may be used for plant defense but are also deployed as important “monomers” for lignification, in which they are incorporated into the growing lignin polymer chain. p-Coumaroyl-CoA monolignol transferases (PMTs) increase the production of monolignol p-coumarates, and feruloyl-CoA monolignol transferases (FMTs) catalyze the production of monolignol ferulate conjugates. We identified putative FMT and PMT enzymes in sorghum (Sorghum bicolor) and switchgrass (Panicum virgatum) and have compared their activities to those of known monolignol transferases. The putative FMT enzymes produced both monolignol ferulate and monolignol p-coumarate conjugates, whereas the putative PMT enzymes produced monolignol p-coumarate conjugates. Enzyme activity measurements revealed that the putative FMT enzymes are not as efficient as the rice (Oryza sativa) control OsFMT enzyme under the conditions tested, but the SbPMT enzyme is as active as the control OsPMT enzyme. These putative FMTs and PMTs were transformed into Arabidopsis (Arabidopsis thaliana) to test their activities and abilities to biosynthesize monolignol conjugates for lignification in planta. The presence of ferulates and p-coumarates on the lignin of these transformants indicated that the putative FMTs and PMTs act as functional feruloyl-CoA and p-coumaroyl-CoA monolignol transferases within plants.
Schnitzler syndrome and Schnitzler-like syndromes
Authors: Chu Cong-Qiu
Published: January 2022

Schnitzler syndrome is a rare disease of adult-onset with main features including chronic urticarial rash, recurrent fever, arthralgia or arthritis, monoclonal gammopathy of undetermined significance (MGUS), and marked systemic inflammation. Schnitzler syndrome is often underdiagnosed. Patients with Schnitzler syndrome may present to dermatologists and allergists for urticaria, hematologists for MGUS, or rheumatologists for arthritis. It is important to recognize Schnitzler syndrome for its remarkable response to interleukin (IL)-1 blockade. Besides, many cases of Schnitzler-like syndromes do not meet the diagnostic criteria of classical Schnitzler syndrome but display excellent response to IL-1 inhibitors. The overly produced IL-1 is the result of a somatic mosaic gain of function mutation of NLRP3 (nucleotide-binding oligomerization domain [NOD]-like receptor [NLR] family pyrin domain containing 3) gene in some patients with Schnitzler-like syndromes. Inflammasome activation is evident in patients with classical Schnitzler syndrome although no NLRP3 gene mutation is identified. Collectively, Schnitzler syndrome and Schnitzler-like syndromes represent a spectrum of IL-1 mediated adult-onset autoinflammatory diseases.
Endotracheal Tube Cuff Pressure Management
Authors: Kebapci Ayda , Ozkaynak Mustafa
Published: January 2022

Introduction

The aim of the rigorous endotracheal tube cuff pressure (ETTCP) management is to maintain cuff pressures within the recommended values during the mechanical ventilation period. However, hyperinflation or hypoinflation of cuff has been reported because of inconsistent clinical practices in intensive care unit (ICU) settings. Furthermore, there is no available best evidence for clinical decision-making regarding the ETTCP management provided by international institutes.

Purpose

The aim of this study was to examine the ETTCP management work system in ICU settings in urban hospitals of Turkey and the United States using the Systems Engineering Initiative for Patient Safety model.

Methods

This was a direct observational, prospective field study, in which the COREQ (Consolidated Criteria for Reporting Qualitative Research) tool was used. The direct observations and follow-up interviews were conducted, and the results were reported using the Systems Engineering Initiative for Patient Safety model.

Results

We identified important characteristics of the ETTCP management work system in each of the 4 ICU and differences across the settings.

Conclusion

Common use of the evidence-based and internationally used protocols may standardize the management of ETTCP, improve communication among ICU staff, and promote desired patient outcomes.

Relevance to Clinical Practice

There is a need for developing strategies to provide standardized ETTCP management and to improve patient's quality of care. To improve the patient outcomes and quality of care, ICU managers should consider clear expectations for ETTCP management in each job description, structured and evidence-based protocols, and effective communication among disciplines and provide teaching opportunities to encourage physicians, nurses, and respiratory therapists to meet their educational needs.
Shifting Nursing Care Models as a Solution for the Increasing Demand on Intensive Care Unit Beds During a Pandemic
Authors: Geltmeyer Klara , Dehennin Laurence , Vanacker Tom , Goedertier Hilde , Verhaeghe Rik , Benoit Dominique , Malfait Simon
Published: January 2022

Aim

An option appraisal of different nursing care delivery models was presented, which were made in between the first and second COVID-19 waves. The authors wanted to inform colleagues on involving nursing care delivery models in the problem-solving process during a pandemic.

Local Problem

In the pre–COVID-19 hospital practice, the nursing care delivery model of primary nursing was applied in the intensive care unit (ICU). However, during the COVID-19 pandemic, this situation could not be upheld because of the increased need for ICU beds and the shortages of available ICU nurses.

Methods

This study used the literature of an ongoing systematic review on nursing care delivery models and expert meetings between the authors and nursing staff.

Results

One standard nursing care delivery model and 3 alternative nursing care delivery models were discussed and compared in this case study. Theoretically, a modular system of team nursing seemed the better model to use during a pandemic. This model leads to an equal distribution of expertise and social distancing between experts. Compared with the other models, a strategic reserve can be created.

Conclusion

This case study should be primarily considered as an example on how rethinking and reorganizing the nursing care delivery model could contribute to an enlarged, qualitative capacity, which needs to be organized in a short time span.
Modeling Benefits, Costs, and Affordability of a Novel Gene Therapy in Hemophilia A
Authors: ten Ham Renske M.T. , Walker Simon M. , Soares Marta O. , Frederix Geert W.J. , Leebeek Frank W.G. , Fischer Kathelijn , Coppens Michiel , Palmer Stephen J.
Published: January 2022

The objective was to undertake an early cost-effectiveness assessment of valoctocogene roxaparvovec (valrox; Roctavian) compared to factor (F)VIII prophylaxis or emicizumab (Hemlibra; Roche HQ, Bazel, Switzerland) in patients with severe Hemophilia A (HA) without FVIII-antibodies. We also aimed to incorporate and quantify novel measures of value such as treatment durability, maximum value-based price (MVBP) and break-even time (ie, time until benefits begin to offset upfront payment). We constructed a Markov model to model bleeds over time which were linked to costs and quality-of-life decrements. In the valrox arm, FVIII over time was estimated combining initial effect and treatment waning and then linked to bleeds. In FVIII and emicizumab arms, bleeds were based on trial evidence. Evidence and assumptions were validated using expert elicitation. Model robustness was tested via sensitivity analyses. A Dutch societal perspective was applied with a 10-year time horizon. Valrox in comparison to FVIII, and emicizumab showed small increases in quality-adjusted life years at lower costs, and were therefore dominant. Valrox’ base case MVBP was estimated at €2.65 million/treatment compared to FVIII and €3.5 million/treatment versus emicizumab. Mean break-even time was 8.03 years compared to FVIII and 5.68 years to emicizumab. Early modeling of patients with HA in The Netherlands treated with valrox resulted in estimated improved health and lower cost compared to prophylactic FVIII and emicizumab. We also demonstrated feasibility of incorporation of treatment durability and novel outcomes such as value-based pricing scenarios and break-even time. Future work should aim to better characterize uncertainties and increase translation of early modeling to direct research efforts.
Bowman Layer Onlay Graft for Recurrent Corneal Erosions in Map–Dot–Fingerprint Dystrophy
Authors: Mulders-Al-Saady Rana , van der Star Lydia , van Dijk Korine , Parker Jack S. , Dapena Isabel , Melles Gerrit R. J.
Published: January 2022

Purpose:

The purpose of this study was to describe a case with recurrent corneal erosions who was treated with a Bowman layer (BL) onlay graft.

Method:

BL onlay transplantation was performed.

Results:

In a 79-year-old female patient who presented with bilateral map–dot–fingerprint dystrophy and a history of recurrent painful corneal erosions, BL onlay grafting was performed to restore the corneal surface. At 1 month postoperatively, the epithelium was smooth over the graft, and until 1.5 years postoperatively, the patients had no complaints and no recurrence of the epithelial corneal erosion.

Conclusions:

In the described case, the transplantation of an isolated BL graft as an onlay proved to be an effective treatment for painful chronic recurrent erosions in the context of map–dot–fingerprint dystrophy in a patient who had undergone numerous unsuccessful previous treatments.
Diabetes Is Not Associated with Increased 10-week Mortality Risk in Patients with Cryptococcal Meningitis
Authors: Xu Lijun , Chen Ying , Zhou Minghan , Tao Ran , Guo Yongzheng , Lou Fangyuan , Yang Zongxing
Published: January 2022

Background:

Diabetes is a risk factor for acquisition of cryptococcal meningitis (CM). However, the effects of diabetes on outcomes of CM patient have not been fully studied.

Methods:

In this retrospective study, 49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method (1:2). Demographic characteristics, symptoms, and clinical assay parameters between the two groups were compared. Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.

Results:

The mean age of diabetic patients was 58.2 ± 13.8 years; 71.4% (35/49) were more than 50 years old and 46.9% were male. No difference in symptoms was found between diabetic and non-diabetic CM patients. The Charlson comorbidity score was higher in the diabetic group (1.9 vs. 0.7, P < 0.001). CM patients with diabetes had higher white blood cells count (×106 /L, 111.0 (18.0– 242.5) vs. 50.0 (10.0–140.0), P = 0.034) in cerebrospinal fluid (CSF), lower CSF India ink positivity (40.8% vs. 60.2%, P = 0.039), and Cryptococcus culture positivity (42.9% vs. 60.2%, P = 0.047). The overall 10-week survival rate was 79.7% in diabetic patients vs. 83.2% in non-diabetic patients (log-rank P = 0.794).

Conclusion:

Diabetic CM patients have higher CSF glucose and Charlson comorbidity score, but lower CSF India ink and culture positivity than non-diabetic CM patients. No difference in 10-week mortality was found between patients with and without diabetes. Other comorbidities may have a greater effect on prognosis.