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In Europe, an increasing number of human milk banks (HMBs) collect donor human milk to feed preterm infants when their mother’s milk is not available or not enough. Moreover, donor milk is a bridge to breastfeeding, with positive clinical and psychological advantages for both mother and infant. Italy, with 41 HMBs actively operating in 2022, has the highest number of HMBs in Europe. The process of human milk donation is complex, so activity of HMBs must be regulated according to well-established rules. The present recommendations have been prepared as a tool to standardize the organization, management, and procedures of HMBs operating in Italy and to determine the minimal essential requirements to establish new HMBs. This article covers all the aspects of human milk donation and human milk banking, including general recommendations, donor recruitment and screening, expression, handling and storage of donor human milk, milk screening, and milk treatment (pasteurization). A pragmatic approach was taken to drafting the recommendations. Items for which there was consensus or robust published evidence on which to base recommendations were included. When there were differences that could not be resolved by reference to published research, a statement of explanation based on the expert opinion of the authors (all members of the Italian Association of Human Milk Banks) was included. Implementation of these recommendations can contribute to promotion of breastfeeding.

Background The use of so-called “red flags” may be beneficial in identifying patients with metastatic spinal disease. This study examined the utility and efficacy of these red flags in the referral chain of patients surgically treated for spinal metastases. Methods The referral chains from the onset of symptoms until surgical treatment for all patients receiving surgery for spinal metastases between March 2009 and December 2020 were reconstructed. The documentation of red flags, as defined by the Dutch National Guideline on Metastatic Spinal Disease, was assessed for each healthcare provider involved. Results A total of 389 patients were included in the study. On average, 33.3% of red flags were documented as present, 3.6% were documented as absent, and 63.1% were undocumented. A higher rate of red flags documented as present was associated with a longer time to diagnosis, but a shorter time to definitive treatment by a spine surgeon. Moreover, red flags were documented as present more often in patients who developed neurological symptoms at any point during the referral chain than those who remained neurologically intact. Conclusions The association of red flags with developing neurological deficits highlights their significance in clinical assessment. However, the presence of red flags was not found to decrease delays prior to referral to a spine surgeon, indicating that their relevance is currently not sufficiently recognized by healthcare providers. Raising awareness of symptoms indicative of spinal metastases may expedite timely (surgical) treatment and thus improve treatment outcome.

How can we definitively determine which biomedical choices are morally correct and which engage in seriously wrongful acts? Depending on whom one asks, one is informed that choices such as abortion, euthanasia, and significant body modification involve real moral harm (either as forms of murder or as denying the goodness of the body that God has provided), or that disallowing such “medical care” violates the basic rights of persons (where abortion, active euthanasia, and body modification are appreciated as positive expressions of personal autonomy). Secular bioethics appears no longer able to appreciate what could possibly be wrong with such activities, provided that the individuals involved consent in some fashion. Indeed, many actions that were once openly and easily recognized as sinful have become so commonplace, as well as politically desirable, as to appear as if they were obviously good. As the authors in this issue of Christian Bioethics explore, fully to appreciate the serious moral issues raised by modern medicine requires a foundational orientation to the Christian God.

For the sake of consistency with settled principles from other theological and ethical questions, there is a need for a Christian reexamination of in vitro fertilization (IVF). Both Old and New Testaments demonstrate that human personal life begins at conception or fertilization. Additionally, the Bible teaches that human beings are persons in the image of God from the very beginning of their existence. Thus, it can be concluded that the embryos created via IVF are persons in God’s image. Applying this to the destruction and freezing of embryos, several limitations or restrictions present themselves—embryos should not be purposefully destroyed or wasted, all embryos ought to be implanted, and embryos should not be frozen. Ultimately, however, due to the immense quantity of embryo wastage, it is concluded that Christians should avoid this form of assisted reproductive technology and consider it a pro-life issue.

While the traditional Christian teaching opposing abortion has been relatively unanimous until the twentieth century, it has been claimed in more recent decades that certain Biblical passages support the view that the fetus, or unborn child, has a lesser moral status than a born child, in a way that might support the permissibility of abortion. In this paper, I address the foremost three texts used to argue this point: Genesis 2:7; Exodus 21:22–25; and Numbers 5:11–31. I argue that interpreting the former in the literal way necessary to support abortion leads to untenable moral and exegetical conclusions, indeed straightforwardly contradicting other Biblical texts. I then demonstrate that the most plausible readings of the other passages—on textual and contextual grounds—do not support a lesser moral status, one of the passages plausibly even supporting full moral status, for the unborn child.

In writing The Way of Medicine: Ethics and the Healing Profession, Farr Curlin and Christopher Tollefsen have provided a helpful, accessible resource for clinicians seeking to conscientiously practice medicine in pursuit of health. These authors identify a major threat to such a practice, which they call the provider of services model (PSM), and compare it to a historic way of practicing that they seek to recover, called the Way of Medicine. Throughout the book, they contrast the PSM and the Way in ways that are helpful. However, the process of continual contrasts and the reliance on controversial cases presents several counter-productive drawbacks that weaken their project.

Issues pertaining to sex and gender continue to be some of the most hotly debated topics of our time. While many of the most heated disputes occur at the level of politics and public policy, metaphysics, too, has a crucial role to play in these debates. In this essay, I explore several key metaphysical debates concerning sex and gender through the lenses of two important areas in contemporary metaphysics: the metaphysics of essence and the ontology of the human person. The goal here is not to advocate any particular position on these issues, but to show how the tools of contemporary metaphysics can help to offer a more comprehensive map of the conceptual terrain, indicating where major areas of agreement can be found and where the most important disagreements really lie.

Background High-dose methotrexate (HDMTX) is a mainstay of primary central nervous system lymphoma (PCNSL) treatment. Transient hepatotoxicity from HDMTX has been characterized in pediatric patients but not in adults. We sought to characterize hepatotoxicity in adult PCNSL patients undergoing HDMTX treatment. Methods Retrospective study of 65 PCNSL patients treated at the University of Virginia from 02/01/2002 to 04/01/2020 was performed. Hepatotoxicity was defined using National Cancer Institute Common Toxicity Criteria (CTC) for adverse events, fifth version. High-grade hepatotoxicity was defined as a bilirubin or aminotransferase CTC grade of 3 or 4. Relationships between clinical factors and hepatotoxicity were assessed with logistic regression. Results Most patients (90.8%) had a rise of at least one aminotransferase CTC grade during HDMTX treatment. 46.2% had high-grade hepatotoxicity based on aminotransferase CTC grade. No patients developed high-grade bilirubin CTC grades during chemotherapy. Liver enzyme test values decreased to low CTC grade or normal in 93.8% of patients after the conclusion of HDMTX treatment without treatment regimen changes. Prior ALT elevation (P = .0120) was a statistically significant predictor of high-grade hepatotoxicity during treatment. Prior history of hypertension was associated with increased risk of toxic serum methotrexate levels during any cycle (P = .0036). Conclusions Hepatotoxicity develops in the majority of HDMTX-treated PCNSL patients. Transaminase values decreased to low or normal CTC grades in almost all patients after treatment, without modification of MTX dosage. Prior ALT elevation may predict patients’ increased hepatotoxicity risk, and hypertension history may be a risk factor for delayed MTX excretion.

Background Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

Background While therapeutically effective, chemoradiotherapy treatment for high-grade glioma (glioblastoma) is often accompanied by side effects. Exercise has been demonstrated to alleviate the adverse effects of such treatments in other cancers. We aimed to evaluate the feasibility and preliminary efficacy of supervised exercise incorporating autoregulation. Methods Thirty glioblastoma patients were recruited, five declined exercise and 25 were provided with a multimodal exercise intervention for the duration of their chemoradiotherapy treatment. Patient recruitment, retention, adherence to training sessions and safety were evaluated throughout the study. Physical function, body composition, fatigue, sleep quality, and quality of life were evaluated before and after the exercise intervention. Results Eight of the 25 participants commencing exercise withdrew prior to completion of the study (32%). Seventeen patients (68%) demonstrated low to high adherence (33%–100%) and exercise dosage compliance (24%–83%). There were no reported adverse events. Significant improvements were observed for all trained exercises and lower limb muscle strength and function with no significant changes observed for any other physical function, body composition, fatigue, sleep, or quality of life outcomes. Conclusions Only half of glioblastoma patients recruited were willing or able to commence, complete or meet minimum dose compliance for the exercise intervention during chemoradiotherapy indicating the intervention evaluated may not be feasible for part of this patient cohort. For those who were able to complete the exercise program, supervised, autoregulated, multimodal exercise was safe and significantly improved strength and function and may have prevented deterioration in body composition and quality of life.

Background Interpretive front-of-pack labels (FoPLs) are supported by World Health Organization as an important policy tool to promote healthy diets. At present, various FoPLs formats co-exist in the European Union (EU). However, as part of the Farm to Fork strategy published in 2020, the European Commission stated that it would propose a single mandatory FoPL. The aim of this study was to analyze Spanish consumers’ preference and objective understanding of Nutri-Score and NutrInform, two FoPLs that are currently the subject of debate in the EU. Methods In a representative sample of 1026 Spanish adults (50% women, mean age ± SD = 46 ± 14 years), objective understanding was assessed by asking participants to identify the healthiest food products in three food categories (breakfast products, breakfast cereals and added fats). The preference dimensions were tested by asking participants about the perceived helpfulness of the FoPL in discriminating the nutritional quality of food products (subjective understanding) and their overall assessment of the FoPL’s ease of use, informativeness, trust and liking (perception). Results In terms of objective understanding, Nutri-Score was significantly associated with an increase in consumers’ ability to identify healthier food products across all food categories compared with NutrInform [OR (odds ratio) = 19.1 [14.2–25.7], P Conclusions This study provides new evidence to support Nutri-Score in comparison with NutrInform in Spanish consumers, on both objective understanding and preference aspects.

Background Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs—in light of the diverse selected treatment regimes. Methods A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed. Results Divergent initial histological diagnoses were encountered in 40.7%. There was no significant difference in local progression-free (PFS) and overall survival (OS) following gross total or subtotal resection. Postoperative radiotherapy was completed in 81% (22/27) following surgical intervention. Local PFS was 54.4% (95% CI: 35.3–84.0%) and OS was 81.3% (95% CI: 63.8–100%) after 3 years following postoperative radiotherapy. Initial relapses post-radiotherapy were primarily located in the previous tumor location and/or the planning target volume (PTV) (12/13). All patients in our cohort demonstrated the prognostically favorable pTERT-wildtype mcPXA. Conclusion Our study demonstrated that adult patients with mcPXAs display a worse progression-free survival compared to the reported WHO grade 2 PXAs. Future matched-pair analyses are required with a non-irradiated cohort to elucidate the benefit of postoperative radiotherapy in adult patients with mcPXAs.

Background Most primary brain tumor patients rely on family caregivers for support. Caregiving can be rewarding, but also leads to significant burden from unmet needs. We aimed to: (1) identify and characterize caregivers’ unmet needs; (2) determine associations between unmet needs and wish for support; (3) evaluate acceptability of the Caregiver Needs Screen (CNS) and perceived feasibility in clinical practice. Methods Family caregivers of primary brain tumor patients were recruited from outpatient clinics and asked to complete an adapted version of the CNS consisting of 33 common issues caregivers report (item scale 0–10), and the wish for support (yes/no). Participants ranked acceptability and feasibility (item scale 0–7; higher scores being positive) of the adapted CNS. Descriptive and non-parametric correlational analyses were applied. Results Caregivers (N = 71) reported 1–33 unmet caregiving needs (M = 17.20, sd = 7.98) but did not always wish for support (range 0–28, M = 5.82, sd = 6.96). A weak correlation was found between total number of unmet needs and wish for support (r = 0.296, P = .014). Most distressing items were patients’ changes in memory/concentration (M = 5.75, sd = 3.29), patients’ fatigue (M = 5.58, sd = 3.43), and signs of disease progression (M = 5.23, sd = 3.15).Caregivers most often wished support with recognizing disease progression (N = 24), and least often with managing spiritual issues (N = 0). Caregivers evaluated acceptability and feasibility of the CNS tool positively (mean scores ranged 4.2–6.2). Conclusions Family caregivers experience distress resulting from many neuro-oncology specific needs, but this is not directly related to wish for support. Family caregiver needs screening could be useful to tailor support to suit their preferences in clinical practice.

Background and objectivesIt is well documented that college student populations are vulnerable to food insecurity and other adverse environmental conditions. Additionally, exposure to environmental adversity can have deleterious, long-term effects on physical and mental health. This study applies evolutionary life history theory to examine the relationship between environmental adversity, mental distress and diet among resource insecure university students during the COVID-19 pandemic.MethodologyStructured and semi-structured surveys were used to assess perceptions of environmental adversity (including mortality risk, food insecurity and resource availability; and changes in these factors over the course of COVID-19), mental distress, diet and use of campus support services. Participants included 51 college students recruited through an economic crisis center located at a large public university in southern California.ResultsMost students were experiencing mental distress and food insecurity, and food insecurity and other components of adversity increased during COVID-19. Food insecurity was significantly associated with both perceived extrinsic mortality risk and mental distress, whereas mental distress was significantly associated with reduced dietary quality and caloric intake. Use of two or more campus support resources and/or living with family or rent free disrupted the associations of food insecurity with extrinsic mortality risk and mental distress.Conclusion and ImplicationThis study contributes to a growing body of applied evolutionary frameworks concerned with the health and wellbeing of economically vulnerable populations. It also provides novel insights informed by life history theory into interventions and recommendations for improving support services for financially insecure college students.

Good hygiene, in both health care and the community, is central to containing the rise of antibiotic resistance, as well as to infection control more generally. But despite the well-known importance, the ecological mechanisms by which hygiene (or other transmission control measures) affect the evolution of resistance remain to be elucidated. Using metacommunity ecology theory, we here propose that hygiene attenuates the effect of antibiotic selection pressure. Specifically, we predict that hygiene limits the scope for antibiotics to induce competitive release of resistant bacteria within treated hosts, and that this is due to an effect of hygiene on the distribution of resistant and sensitive strains in the host population. We show this in a mathematical model of bacterial metacommunity dynamics, and test the results against data on antibiotic resistance, antibiotic treatment, and the use of alcohol-based hand rub in long-term care facilities. The data are consistent with hand rub use attenuating the resistance promoting effect of antibiotic treatment. Our results underscore the importance of hygiene, and point to a concrete way to weaken the link between antibiotic use and increasing resistance.

Racial health disparities are a pervasive feature of modern experience and structural racism is increasingly recognized as a public health crisis. Yet evolutionary medicine has not adequately addressed the racialization of health and disease, particularly the systematic embedding of social biases in biological processes leading to disparate health outcomes delineated by socially defined race. In contrast to the sheer dominance of medical publications which still assume genetic ‘race’ and omit mention of its social construction, we present an alternative biological framework of racialized health. We explore the unifying evolutionary-ecological principle of niche construction as it offers critical insights on internal and external biological and behavioral feedback processes environments at every level of the organization. We Integrate insights of niche construction theory in the context of human evolutionary and social history and phenotype-genotype modification, exposing the extent to which racism is an evolutionary mismatch underlying inequitable disparities in disease. We then apply ecological models of niche exclusion and exploitation to institutional and interpersonal racial constructions of population and individual health and demonstrate how discriminatory processes of health and harm apply to evolutionarily relevant disease classes and life-history processes in which socially defined race is poorly understood and evaluated. Ultimately, we call for evolutionary and biomedical scholars to recognize the salience of racism as a pathogenic process biasing health outcomes studied across disciplines and to redress the neglect of focus on research and application related to this crucial issue.

Background and objectives Birth is a critical event in women’s lives. Since humans have evolved to give birth in the context of social support, not having it in modern settings might lead to more complications during birth. Our aim was to model how emotional factors and medical interventions related to birth outcomes in hospital settings in Poland, where c-section rates have doubled in the last decade. Methodology We analysed data from 2363 low-risk primiparous women who went into labor with the intention of giving birth vaginally. We used a model comparison approach to examine the relationship between emotional and medical variables and birth outcome (vaginal or c-section), including sociodemographic control variables in all models. Results A model with emotional factors better explained the data than a control model (ΔAIC = 470.8); women with continuous personal support during labor had lower odds of a c-section compared to those attended by hospital staff only (OR = 0.12, 95% CI = 0.09 − 0.16). A model that included medical interventions also better explained the data than a control model (ΔAIC = 133.6); women given epidurals, in particular, had increased odds of a c-section over those who were not (OR = 3.55, 95% CI = 2.95 − 4.27). The best model included variables for both the level of personal support and the use of epidural (ΔAIC = 598.0). Conclusions and implications Continuous personal support during childbirth may be an evolutionarily informed strategy for reducing complications, including one of the most common obstetrical complications in modern hospital settings, the c-section.

Background and objectives Virtual teaching tools have gained increasing importance in recent years. In particular, the COVID-19 pandemic has reinforced the need for media-based and self-regulated tools. What is missing are tools that allow us to interlink highly interdisciplinary fields such as evolutionary medicine and, at the same time, allow us to adapt content to different lectures. Methodology We designed an interactive online teaching tool, namely, the Mummy Explorer, using open-access software (Google Web Designer), and we provided a freely downloadable template. We tested the tool on students and lecturers of evolutionary medicine using questionnaires and improved the tool according to their feedback. Results The tool has a modular design and provides an overview of a virtual mummy excavation, including the subfields of palaeopathology, paleoradiology, cultural and ethnographic context, provenance studies, paleogenetics, and physiological analyses. The template allows lecturers to generate their own versions of the tool for any topic of interest by simply changing the text and pictures. Tests undertaken with students of evolutionary medicine showed that the tool was helpful during their studies. Lecturers commented that they appreciated having a similar tool in other fields. Conclusions and implications Mummy Explorer fills a gap in the virtual teaching landscape of highly interdisciplinary fields such as evolutionary medicine. It will be offered for free download and can be adapted to any educational topic. Translations into German and possibly other languages are in progress.

Background and objectives Childbirth fear, which has been argued to have an adaptive basis, exists on a spectrum. Pathologically high levels of childbirth fear is a clinical condition called tokophobia. As a chronic stressor in pregnancy, tokophobia could impact birth outcomes. Many factors associated with tokophobia, including inadequate labor support, were exacerbated by the COVID-19 pandemic. Methodology We used longitudinally collected data from a convenience sample of 1775 pregnant persons in the USA to evaluate the association between general and COVID-19 pandemic-related factors and tokophobia using the fear of birth scale. We also assessed associations between tokophobia, low birth weight and preterm birth when adjusting for cesarean section and other covariates among a subset of participants (N = 993). Results Tokophobia was highly prevalent (62%). Mothers who self-identified as Black (odds ratio (OR) = 1.90), had lower income (OR = 1.39), had less education (OR = 1.37), had a high-risk pregnancy (OR = 1.65) or had prenatal depression (OR = 4.95) had significantly higher odds of tokophobia. Concerns about how COVID-19 could negatively affect maternal and infant health and birth experience were also associated with tokophobia (ORs from 1.51 to 1.79). Tokophobia was significantly associated with increased odds of giving birth preterm (OR = 1.93). Conclusions and implications Tokophobia increases the odds of preterm birth and is more prevalent among individuals who are Black, have a lower income, and have less education. Tokophobia may, therefore, be an underappreciated contributor to inequities in US birth outcomes. The COVID-19 pandemic likely compounded these effects.

Background Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens. With increasing prevalence of autoimmune disease and development of new immunosuppressants, a genetically distinct entity known as iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD) has emerged. Many of these cases arise following methotrexate use, challenging feasibility of standard HD-MTX regimens. The aim of this study was to further characterize this disorder and determine the optimal management strategy. Methods We describe a case of a 76-year-old female with iatrogenic immunodeficiency-associated PCNSL successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency-associated LPD involving the CNS. We used a linear probability statistical model to determine correlations with outcome. Results Natalizumab was associated with EBV negative tumors (P = .023), and EBV positive tumors were associated with improved outcomes (P = .016). Surgical resection was associated with improved outcomes (P = .032), although limited by potential confounding effect. Antiviral treatment (P = .095), rituximab (P = .111), and stem cell transplant (SCT) (P = .198) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. Conclusion We propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency-associated LPD of the CNS. Further study through prospective cohort studies or randomized clinical trials is warranted.

Routine cognitive assessment for adults with brain cancers is seldom completed but vital for guiding daily living, maintaining quality of life, or supporting patients and families. This study aims to identify cognitive assessments which are pragmatic and acceptable for use in clinical settings. MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane were searched to identify studies published in English between 1990 and 2021. Publications were independently screened by two coders and included if they: (1) were peer-reviewed; (2) reported original data relating to adult primary brain tumor or brain metastases; (3) used objective or subjective assessments; (4) reported assessment acceptability or feasibility. The Psychometric And Pragmatic Evidence Rating Scale was used. Consent, assessment commencement and completion, and study completion were extracted along with author-reported acceptability and feasibility data. PROSPERO Registration: CRD42021234794. Across 27 studies, 21 cognitive assessments had been assessed for feasibility and acceptability; 15 were objective assessments. Acceptability data were limited and heterogeneous, particularly consent (not reported in 23 studies), assessment commencement (not reported in 19 studies), and assessment completion (not reported in 21 studies). Reasons for non-completion could be grouped into patient-factors, assessment-factors, clinician-factors, and system-factors. The three cognitive assessments with the most acceptability and feasibility data reported were the MMSE, MoCA, and NIHTB-CB. Further acceptability and feasibility data are needed including consent, commencement and completion rates. Cost, length, time, and assessor burden are needed for the MMSE, MoCA, and NIHTB-CB, along with potentially new computerized assessments suited for busy clinical settings.

Background and Objectives Testosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men. Methodology Relationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer’s disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries. Results Results of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality—which included deaths from any known disease—also revealed greater general risk for those with lower testosterone levels. For most disease categories, the hazard associated with low testosterone was especially evident at older ages when mortality from that particular ailment was already elevated. Notably, testosterone levels were not related to mortality risk for deaths unrelated to chronic disease (i.e. accidents and injuries). Conclusions and Implications While the causal direction of relationships between testosterone and mortality risk remains unclear, these results may reflect the decline in testosterone that accompanies many disease states. Accordingly, the relationship between testosterone and male mortality may be indirect; ill individuals are expected to have both lower testosterone and higher mortality risk.

AO_SCPLOWBSTRACTC_SCPLOWNon-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, have been widely implemented during the COVID-19 pandemic. In addition to playing an important role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply and altering the strength of selection for novel variants. However, it is unclear how NPIs might affect the emergence of novel variants of concern that are able to escape pre-existing immunity (partially or fully), are more transmissible, or cause greater mortality. Here, we analyse a stochastic two-strain epidemiological model to determine how the strength of NPIs affects the emergence of variants with similar or contrasting life-history characteristics to the wildtype. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross immunity to have a greater probability of emerging at intermediate levels of NPIs. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be implementation of strong, timely NPIs. AO_SCPLOWUTHORC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSUMMARYC_SCPLOWDuring the COVID-19 pandemic, a wide range of non-pharmaceutical interventions, including mask wearing, quarantine, isolation, and lockdowns, have been used by governments around the world to suppress virus transmission. Although considerable efforts have been made to understand how such interventions affect transmission, much less attention has been paid to their effects on pathogen evolution. While vaccines are well-known to affect virus evolution, non-pharmaceutical interventions also influence mutation supply and the strength of selection, and hence play a key role in the emergence of novel variants. Here, we use a relatively simple mathematical model to explore how non-pharmaceutical interventions during an epidemic affect the emergence of a novel variant of a pathogen. We show that in general, it is important to implement effective transmission-reducing public health measures in a timely manner to prevent the emergence of novel variants, which may be more transmissible, more deadly, or able to escape immunity.

Recent research has characterized the behavioral defense against disease. In particular the detection of sickness cues, the adaptive reactions (e.g. avoidance) to these cues and the mediating role of disgust have been the focus. A presumably important but less investigated part of a behavioral defense is the immune system response of the observer of sickness cues. Odors are intimately connected to disease and disgust, and research has shown how olfaction conveys sickness cues in both animals and humans. This study aims to test whether odorous sickness cues (i.e. disgusting odors) can trigger a preparatory immune response in humans. We show that subjective and objective disgust measures, as well as TNFα levels in saliva increased immediately after exposure to disgusting odors in a sample of 36 individuals. Altogether, these results suggest a collaboration between behavioral mechanisms of pathogen avoidance in olfaction, mediated by the emotion of disgust, and mechanisms of pathogen elimination facilitated by inflammatory mediators. Disgusting stimuli are associated with an increased risk of infection. We here test whether disgusting odors, can trigger an immune response in the oral cavity. The results indicate an increase level of TNFα in the saliva. This supports that disease cues can trigger a preparatory response in the oral cavity.

Background Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival. Methods A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS). A historical control population of 737 patients with brain metastases was used to assess similarities and differences between the long-term survivor population and the general population treated with SRS. Results A total of 98 patients with brain metastases were found to have survived over 60 months. No differences between long-term survivors and controls were identified with regards to the age at first SRS (P = .19), primary cancer distribution (P = .80), and the number of metastases at first SRS (P = .90). Cumulative incidence of neurologic death at 6, 8 and 10 years for the long-term survivor cohort was 4.8%, 16%, and 16% respectively. In the historical controls, cumulative incidence of neurologic death reached a plateau at 40% after 4.9 years. A significant difference in the distribution of burden of disease at the time of the first SRS was found between the 5-year survivors and the control (P = .0049). 58% of 5-year survivors showed no evidence of clinical disease at the last follow-up. Conclusion Five-year survivors of brain metastases represent a diverse histologic population, suggesting a small population of oligometastatic and indolent cancers exist for each cancer type.

Does the idea of human enhancement presuppose a goal or an ideal to direct technological modifications? In the absence of such an agreed ideal in today’s culture, can Christian theology help clarify the goal or the meaning of “perfection” when applied to human beings? A theological perspective rooted in scripture and in the writings of theologians such as Irenaeus, Athanasius, and Gregory of Nyssa suggests that theology instead of offering its own definition of the human ideal, theology rejects the possibility of any defined human goal. An analysis of the biblical word teleios (“mature” or “perfect”), along with Gregory’s view of infinite ascent, leads to the conclusion that the human goal is found in relationship to the triune God and not in any anthropologically-definable status.

With the godlike powers of modern technology, just one bad actor can unleash hell on Earth. In the face of this threat posed by technology, some have proposed moral bioenhancement as a solution. Although moral bioenhancement may at first seem like something Christian should support, it is my contention in this paper that there is at least one significant reason for Christians to be cautious in their appropriation of moral bioenhancement technology: it can at best give us a false apatheia, which runs the ironic risk of destroying our ability to make moral progress.

Taking a cue from Teilhard de Chardin's Christologically inflected speculation, the key question in this issue is whether the project of transhumanism is compatible with Christianity and the Incarnation of Christ. Two articles focus on theological anthropology and the limits, if any, of human perfection in light of Christ's perfection. Another article examines the ontological claims about human nature in transhumanism and its incompatibility with a Christian ontology. The last two turn from more abstract concerns to consider how the use of technology can inhibit or help human moral and spiritual development.

Transhumanism’s ideology is marked by a commitment to the “progress” or “perfection” of the human species through technological means. What transhumanists are after is not just therapeutic intervention or optimization of current human capabilities, but an ontological change from human to posthuman. In this article, I critique transhumanist ideology on the grounds that it fundamentally misunderstands human moral perfection as resulting from forces acting upon us (i.e., technological interventions), rather than an internal change of character. This misunderstanding reflects an impoverished view of the concept of motion brought about by the rise of modern science, which entails certain ontological commitments that are not Christian in nature. I conclude transhumanism is untenable because it rests on a shaky foundation of Newtonian physics, and reduces the world to mere matter and forces. Furthermore, Christian transhumanism is especially flawed, because it is complicit in this severing of creation from its sacramental ontology, from the Being of God.

This essay argues that a Christian incarnational response to posthumanism must recognize that what is at stake isn't just whether belief systems align. It seeks to relocate the interaction between the church and posthumanism to how the practices of posthumanism and Christianity perform the bodies, affections and dispositions of each. Posthuman practices seeks to habituate: (1) A preference for informational patterns over material instantiation; (2) that consciousness and the self are extended and displaced rather than discrete and localized; (3) that the body is merely a tool, the original prosthesis we learn to manipulate and (4) that human life is organized such that it is seamless with intelligent machines. The Christian performance of embodied life, on the other hand, has Christ as template and, in the Eucharist, Christians are marked by offering, sacrifice and celebration in a community that affirms the integrity of our common incarnate life.

Background The Brain Tumor Registry of Canada was established in 2016 to enhance infrastructure for surveillance and clinical research on Central Nervous System (CNS) tumors. We present information on primary CNS tumors diagnosed among residents of Canada from 2010 to 2015. Methods Data from 4 provincial cancer registries were analyzed representing approximately 67% of the Canadian population. Age-standardized incidence rates (ASIR) and 95% confidence intervals (CI) were calculated using the 2011 Canadian population age distribution. Net survival was estimated using the Pohar-Perme method. Results A total of 31 644 primary tumors were identified for an ASIR of 22.8 per 100 000 person-years. Nonmalignant tumors made up 47.1% of all classified tumors, with mixed behaviors present in over half of histology groupings. Unclassified were 19.5% of all tumors. The most common histological subtypes are meningiomas (ASIR = 5.5 per 100 000 person-years); followed by glioblastomas (ASIR 4.0 per 100 000 person-years). The overall 5-year net survival rate for CNS tumors was 65.5%; females 70.2% and males 60.4%. GBMs continue to be the most lethal CNS tumors for all sex and age groups. Conclusions The low annual frequency of most CNS tumor subtypes emphasizes the value of population-based data on all primary CNS tumors diagnosed among Canadians. The large number of histological categories including mixed behaviors and the proportion of unclassified tumors emphasizes the need for complete reporting. Variation in incidence and survival across histological groups by sex and age highlights the need for comprehensive and histology-specific reporting. These data can be used to better inform research and health system planning.

Background and objectives Sleep is a vulnerable state in which individuals are more susceptible to threat, which may have led to evolved mechanisms for increasing safety. The sentinel hypothesis proposes that brief awakenings during sleep may be a strategy for detecting and responding to environmental threats. Observations of sleep segmentation and group sentinelization in hunter-gatherer and small-scale communities support this hypothesis, but to date it has not been tested in comparisons with industrial populations characterized by more secure sleep environments. Methodology Here, we compare wake after sleep onset (WASO), a quantitative measure of nighttime awakenings, between two nonindustrial and two industrial populations: Hadza hunter-gatherers (n = 33), Malagasy small-scale agriculturalists (n = 38), and Hispanic (n = 1,531) and non-Hispanic White (NHW) (n = 347) Americans. We compared nighttime awakenings between these groups using actigraphically-measured sleep data. We fit linear models to assess whether WASO varies across groups, controlling for sex and age. Results We found that WASO varies significantly by group membership and is highest in Hadza (2.44 h) and Malagasy (1.93 h) and lowest in non-Hispanic Whites (0.69 h). Hispanics demonstrate intermediate WASO (0.86 h), which is significantly more than NHW participants. After performing supplementary analysis within the Hispanic sample, we found that WASO is significantly and positively associated with increased perception of neighborhood violence. Conclusions and implications Consistent with principles central to evolutionary medicine, we propose that evolved mechanisms to increase vigilance during sleep may now be mismatched with relatively safer environments, and in part responsible for driving poor sleep health.

Background There is no consensus on the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors remains to be illuminated. Methods We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9 years) harboring 68 tumors. Clinical and radiological data were obtained every 6 months for 2 years, annually until 5 years, then every second year. Results The natural progression of incidental meningiomas during 12 years of monitoring was growth (P Conclusion Active monitoring seems a safe and appropriate first-line management of incidental meningiomas. Intervention was avoided in > 40% with indolent tumors in this cohort. Treatment was not compromised by tumor growth. Clinical follow-up seems sufficient beyond 5 years if self-limiting growth is established. Steady or accelerating growth warrant monitoring until they reach a stable state or intervention is initiated.

Background Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Methods Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. Results There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Conclusions Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Context There is still controversy over the effect of vitamin D3 supplementation on bone health. Objective The effects of vitamin D3 supplementation on bone mineral density (BMD) and markers of bone turnover, as well as the dose-response relationship between vitamin D3 and bone health in adults, were evaluated. Data Sources The PubMed, Scopus, Cochrane, Web of Science, and AGRIS databases were searched for articles published through April 30, 2022. Thirty-nine of the 6409 records identified met the inclusion criteria Data Extraction Data were extracted from articles by 2 authors, and data extraction was cross-checked independently. A random-effects model was used to estimate the pooled effect size and the associated 95%CI for the effect of vitamin D3 for each outcome. A one-stage random-effects dose-response model was used to estimate the dose-response relationship between vitamin D3 supplementation and BMD. Data Analysis Results of meta-analysis showed a beneficial effect of vitamin D3 at the lumbar spine (standardized mean difference [SMD] = 0.06; 95%CI, 0.01–0.12) and femoral neck (SMD = 0.25; 95%CI, 0.09–0.41). Dose-response analysis revealed a linear relationship between vitamin D3 supplementation doses and BMD at the femoral neck, lumbar spine, and total hip sites. No significant effect of vitamin D3 supplementation on whole-body or total hip BMD was observed (P > 0.05). Vitamin D3 supplementation significantly decreased BMD at both proximal and distal forearm (SMD = −0.16; 95%CI, −0.26 to −0.06). The variables of ethnicity, age, baseline 25-hydroxyvitamin D (25[OH]D), menopause status, vitamin D3 dosing frequency, and bone health status (P interaction = 0.02) altered the effect of vitamin D3 supplementation on BMD. Additionally, a nonlinear relationship between vitamin D3 supplement doses and markers of bone turnover was found. Conclusion A protective effect of vitamin D3 supplementation on BMD of the lumbar spine, femoral neck, and total hip is implicated. Systematic Review Registration PROSPERO registration number CRD42017054132.

Background Childhood brain tumor survivors are at high risk of late effects, especially neurocognitive impairment. Limited data are available examining neurocognitive function and associations with quality of life (QoL) in childhood brain tumor survivors. Our aim was to examine neurocognitive function in childhood brain tumor survivors, and associations with QoL and symptom burden. Methods Five–year survivors of brain tumors over the age of 15 were identified in the Danish Childhood Cancer Registry (n = 423). Eligible and consenting participants completed neuropsychological tests and questionnaires assessing QoL, insomnia, fatigue, anxiety, and depression. Survivors treated with radiation (n = 59) were statistically compared with survivors not treated with radiation (n = 102). Results In total, 170 survivors participated (40.2% participation rate). Sixty-six percent of the survivors who completed neurocognitive tests (n = 161) exhibited overall neurocognitive impairment. Survivors treated with radiation, especially whole-brain irradiation, exhibited poorer neurocognitive outcomes than survivors not treated with radiation. Neurocognitive outcomes for survivors treated with surgery were below normative expectations. Furthermore, a number of survivors experienced significant fatigue (40%), anxiety (23%), insomnia (13%), and/or depression (6%). Survivors treated with radiation reported lower quality of life (QoL) and higher symptom burden scores than survivors not treated with radiation; particularly in physical functioning, and social functioning with symptoms of fatigue. Neurocognitive impairment was not associated with QoL or symptom burden. Conclusions In this study, a majority of the childhood brain tumor survivors experienced neurocognitive impairment, reduced QoL, and high symptom burden. Although not associated with each other, it is apparent that childhood brain tumor survivors experience not only neurocognitive dysfunction but may also experience QoL impairments and significant symptom burden.

Context Depression is the most common causes of disease burden worldwide (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–1858). Objective An umbrella review has been performed to assess the strength and validity of the available observational and trial evidence for the association between a variety of dietary patterns and depression. Data Sources MEDLINE/PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and Cochrane Database were searched. Data Extraction The Joanna Briggs Institute Umbrella Review Methodology was used. Data Analysis The review included 19 articles, covering a relatively wide range of dietary patterns: healthy dietary patterns (n = 8), Mediterranean diet (MedDiet) (n = 6), Dietary Inflammatory Index (DII) (n = 5), Western diet (n = 4), Dietary Approaches to Stop Hypertension (DASH) (n = 2), vegetarian diets (n = 4), and other dietary interventions (n = 2). The methodological quality of the included meta-analyses was generally low or critically low. The strength of the evidence was generally weak, although convincing or suggestive evidence was found for an inverse relationship between MedDiet/DII and depression. Higher adherence to the MedDiet and lower DII score were significantly associated with lower risk of depression. Conclusion Considering the generally high heterogeneity and low quality of the available evidence, further studies adopting more coherent and uniform methodologies are needed. Systematic Review Registration PROSPERO registration no. CRD42020223376.

Background There are no effective treatments for brain tumor-related fatigue. We studied the feasibility of two novel lifestyle coaching interventions in fatigued brain tumor patients. Methods This phase I/feasibility multi-center RCT recruited patients with a clinically stable primary brain tumor and significant fatigue (mean Brief Fatigue Inventory [BFI] score ≥ 4/10). Participants were randomized in a 1–1–1 allocation ratio to: Control (usual care); Health Coaching (“HC”, an eight-week program targeting lifestyle behaviors); or HC plus Activation Coaching (“HC + AC”, further targeting self-efficacy). The primary outcome was feasibility of recruitment and retention. Secondary outcomes were intervention acceptability, which was evaluated via qualitative interview, and safety. Exploratory quantitative outcomes were measured at baseline (T0), post-interventions (T1, 10 weeks), and endpoint (T2, 16 weeks). Results n = 46 fatigued brain tumor patients (T0 BFI mean = 6.8/10) were recruited and 34 were retained to endpoint, establishing feasibility. Engagement with interventions was sustained over time. Qualitative interviews (n = 21) suggested that coaching interventions were broadly acceptable, although mediated by participant outlook and prior lifestyle. Coaching led to significant improvements in fatigue (improvement in BFI versus control at T1: HC=2.2 points [95% CI 0.6, 3.8], HC + AC = 1.8 [0.1, 3.4], Cohen’s d [HC] = 1.9; improvement in FACIT-Fatigue: HC = 4.8 points [−3.7, 13.3]; HC + AC = 12 [3.5, 20.5], d [HC and AC] = 0.9). Coaching also improved depressive and mental health outcomes. Modeling suggested a potential limiting effect of higher baseline depressive symptoms. Conclusions Lifestyle coaching interventions are feasible to deliver to fatigued brain tumor patients. They were manageable, acceptable, and safe, with preliminary evidence of benefit on fatigue and mental health outcomes. Larger trials of efficacy are justified.

Optimal hydration is required for all physiologic functions and cognition. Children, especially younger ones, are particularly susceptible to dehydration, given their physiological specificities, in particular, their renal immaturity and relatively large skin surface in early life, but also their dependence on adults and their greater propensity to develop digestive diseases leading to fluid losses. Mild dehydration consequences are dominated by their impact on cognitive functions, whereas more severe dehydration may endanger the health outcome. Studies on this subject in children are scarce; in particular, the long-term consequence on renal function remains questionable. This review considers how children’s water intake including fluid intake and water content of food, are worrying. The findings show that, worldwide, most children do not meet adequate water intake recommendations. The main problems likely to explain insufficient water intake are access to safe water, availability of drinking water at school, and healthy-hydration education, which are all points that need to be improved within health policy.

Millet is consumed as a staple food, particularly in developing countries, is part of the traditional diet in a number of relatively affluent countries, and is gaining popularity throughout the world. It is a valuable dietary energy source. In addition to high caloric value, several health-promoting attributes have been reported for millet seeds. This review describes many nutritional characteristics of millet seeds and their derivatives that are important to human health: antioxidant, antihypertensive, immunomodulatory or anti-inflammatory, antibacterial or antimicrobial, hypocholesterolemic, hypoglycemic, and anti-carcinogenic potential, and their role as modulators of gut health. There are several varieties, but the main focus of this review is on pearl millet (Cenchrus americanus [synonym Pennisetum glaucum]), one of the most widely eaten millet crops grown in India, though other millet types are also covered. In this article, the health-promoting properties of the natural components (ie, proteins, peptides, polyphenols, polysaccharides, oil, isoflavones, etc.) present in millet seeds are discussed. Although many of these health benefits have been demonstrated using animal models in vitro studies, human intervention-feeding trials are required to confirm several of the potential health benefits of millet seeds. Based on the nutritional and health-promoting attributes known for pearl millet (discussed in this review), finger millet and foxtail millet are suggested as good candidates for use in future nutritional interventions for improved human health.

Context Changes in body weight and composition (fat and lean mass) are prominent side effects of cancer treatment. Nutrition and exercise interventions are both key strategies to protect against these adverse effects, yet their impact when combined has not been comprehensively reviewed in adults with cancer. Objective This systematic review and meta-analysis aims to assess the effects of combined nutrition and exercise interventions on body weight and composition in adults with cancer. Data Sources Four databases were searched until January 2021. Combined nutrition and exercise randomized controlled trials that detailed the nutrition and exercise prescription and reported body weight and composition outcomes were eligible. Data Extraction Risk of bias was assessed through the Cochrane Collaboration tool. The number of participants, mean values, and standard deviations of the outcome variables were extracted. Mean differences (MDs) were pooled using random-effects models. Predetermined subgroup analyses included cancer type, intervention intent, exercise modality, and use of behavior change strategies. Data Analysis Twenty-three RCTs were included. Nutrition plus exercise interventions significantly reduced body weight (MD − 2.13 kg; 95%CI, − 3.07 to − 1.19), fat mass (MD − 2.06 kg; 95%CI, − 3.02 to − 1.09), and lean mass (MD − 0.43; 95%CI, − 0.82 to − 0.04). Subgroup analyses in women with breast cancer showed that weight loss interventions and interventions incorporating behavior change strategies significantly reduced body weight and fat mass but also reduced lean mass. Interventions aiming to maintain body weight showed no changes in body weight, as intended. Conclusion Combined nutrition and exercise interventions successfully reduce body weight and fat mass in adults with cancer but also reduce lean mass. In contrast, weight loss–focused interventions are associated mostly with reduced lean mass. Systematic Review Registration PROSPERO registration number CRD42020161805.