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Objective: Obesity is related to the recurrence of breast cancer. In-person groups or individual telephone counseling currently comprise the behavioral weight loss (BWL) programs tested for cancer survivors. Group support via telehealth may be convenient and provide support from fellow survivors, but feasibility, acceptability, and efficacy testing are needed., Methods: A single-arm, 6-month BWL program was conducted for female breast cancer survivors with an ECOG performance 0 or 1, BMI > 25 kg/m 2 , and > 6 months from completion of adjuvant chemotherapy and/or radiation treatment. Participants attended 22 video group sessions over 6 months, completing acceptability ratings, weight measurements, Patient Health Questionnaire (PHQ-9), City of Hope Breast Cancer Quality of Life Scale (QOL), and International Physical Activity Questionnaire. Changes in survey scores and weight (last-observation carried forward) and differences in outcomes by patients' race were computed with paired t -tests, ANCOVAs and Chi-square tests., Results: Twenty-one (5 Black, 15 White, 1 Asian American; Mean (SD) = 60.7 (11.6) years; BMI 33.1 (5.9) kg/m 2 ) survivors enrolled with 90% retention and 81.3% of sessions attended. Acceptability ratings were high (all > 4 on a five-point scale). Mean (SD) weight loss was 5.9% (5.2%), with 60% losing ≥ 5% of baseline weight; White participants lost 7.5% and Black participants lost 1.9% ( p  = 0.04). Significant improvements were observed in mood (PHQ-9; p  = 0.01) and physical wellbeing QOL ( p  = 0.01). Physical activity did not change., Conclusion: This telehealth group BWL program was feasible and acceptable for breast cancer survivors, yielding a clinically significant weight loss. Future studies should test this intervention in larger, more diverse samples., Trail Registration: ClinicalTrials.gov identifier: NCT04855552, posted April 22, 2021., Competing Interests: Kelly C. Allison reports investigator‐initiated research funding from Novo Nordisk. Carmen E. Guerra reports grant support from the National Cancer Institute, the Breast Cancer Research Foundation, Genentech, and the Lazarex Foundation; compensated advisory board service for Guardant Health; and honoraria from the National Comprehensive Cancer Network for work outside the submitted work. The remaining authors declare no relevant financial or non‐financial interests to disclose., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

The growing interest in Diversity, Equity, and Inclusion (DEI) centred work in the field of Ergonomics and Human Factors (EHF) can greatly benefit from Iris Young's Five Faces of Oppression theory, which details how well-intentioned systems can perpetuate harm in a number of ways. We call for a greater focus on systems of oppression in EHF research and practice along with increased collaboration with social sciences to tackle important societal issues. This article reviews the current state of research in the child welfare domain and provides examples for how cognitive engineering approaches can take inspiration from the social sciences to help create a more equitable future. These examples outline the potential mutualism between social sciences and EHF and the way this collaboration might dismantle various oppressive systems.

Background: The relationship between theoretically relevant psychosocial and behavioral variables and outcomes of metabolic and bariatric surgery remains unclear. Some studies have found that the presence of psychopathology, disordered eating, and impulsivity, either before surgery or during the early postoperative period, is associated with suboptimal postoperative weight loss. Other studies have not found these relationships., Objective: Examine the relationship between psychopathology, disordered eating, impulsivity, and weight loss 24 months postoperatively., Setting: Two large, urban university health systems., Methods: Participant characteristics were collected using validated interviews, patient-reported outcome measures, and computerized assessment methods. Linear mixed effect models were used to test the association of the variables of interest on percent weight loss (%WL)., Results: Three hundred participants were enrolled at baseline; weight data at 24 months were available for 227 participants; between 181 and 53 individuals completed other outcome measures. The mean %WL was 23.3 ± 9.9% at 24 months. Patients who underwent Roux-en-Y gastric bypass lost more weight than those who underwent sleeve gastrectomy. The presence of subjective binge episodes at baseline was related to a greater %WL at 24 months; there were no other baseline predictors. The presence of eating disorder diagnoses and disordered eating symptoms after surgery were associated with smaller weight losses over 24 months. Current and lifetime psychopathology and impulsivity were unrelated to %WL at 24 months., Conclusion: Disordered eating after bariatric surgery was associated with a smaller %WL at postoperative year 2. Additional monitoring of these symptoms in the early postoperative period is recommended. Psychotherapeutic and/or dietary interventions may promote more optimal weight loss outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Several computed tomographic studies have shown the presence of atherosclerosis in ancient human remains. However, while it is important to understand the development of atherosclerotic cardiovascular disease (ASCVD), genetic data concerning the prevalence of the disease-associated single nucleotide polymorphisms (SNPs) in our ancestors are scarce., Objective: For a better understanding of the role of genetics in the evolution of ASCVD, we applied an enrichment capture sequencing approach to mummified human remains from different geographic regions and time periods., Methods: Twenty-two mummified individuals were analyzed for their genetic predisposition of ASCVD. Next-generation sequencing methods were applied to ancient DNA (aDNA) samples, including a novel enrichment approach specifically designed to capture SNPs associated with ASCVD in genome-wide association studies of modern humans., Findings: Five out of 22 ancient individuals passed all filter steps for calculating a weighted polygenic risk score (PRS) based on 87 SNPs in 56 genes. PRSs were correlated to scores obtained from contemporary people from around the world and cover their complete range. The genetic results of the ancient individuals reflect their phenotypic results, given that the only two mummies showing calcified atherosclerotic arterial plaques on computed tomography scans are the ones exhibiting the highest calculated PRSs., Conclusions: These data show that alleles associated with ASCVD have been widespread for at least 5,000 years. Despite some limitations due to the nature of aDNA, our approach has the potential to lead to a better understanding of the interaction between environmental and genetic influences on the development of ASCVD., Competing Interests: Professor Jagat Narula is Executive Editor of the journal Annals of Global Health. None of the other authors have any conflicts of interest., (Copyright: © 2024 The Author(s).)

In South Tyrol (Eastern Italian Alps), during Late Antiquity-Early Middle Ages, archeological records indicate cultural hybridization among alpine groups and peoples of various origin. Using paleogenomics, we reconstructed the ancestry of 20 individuals (4 th -7 th cent. AD) from a cemetery to analyze whether they had heterogeneous or homogeneous ancestry and to study their social organization. The results revealed a primary genetic ancestry from southern Europe and additional ancestries from south-western, western, and northern Europe, suggesting that cultural hybridization was accompanied by complex genetic admixture. Kinship analyses found no genetic relatedness between the only two individuals buried with grave goods. Instead, a father-son pair was discovered in one multiple grave, together with unrelated individuals and one possible non-local female. These genetic findings indicate the presence of a high social status familia , which is supported by the cultural materials and the proximity of the grave to the most sacred area of the church., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background and Objectives: Pathogenic variants in STXBP1 are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control., Methods: We performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals with STXBP1 -related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System (GMFCS) scores and a speech impairment score and were compared within and across clinically defined subgroups., Results: We collected data of 71 individuals with STXBP1 -related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (interquartile range 3.5-9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including 2 individuals presenting with close to age-appropriate motor development. Twenty-nine of 61 individuals (48%) were able to walk unassisted, and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs 4, p < 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs 58%, p < 0.01). Individuals with early epilepsy onset had higher speech impairment scores ( p = 0.02) than individuals with later epilepsy onset., Discussion: We expand the spectrum of STXBP1 -related disorders and provide clinical features and developmental trajectories in individuals with and without a history of epilepsy. Individuals with epilepsy, in particular epileptic spasms, and neonatal or early-onset presented with less favorable motor and language functional outcomes compared with individuals without epilepsy. These findings identify children at risk for severe disease and can serve as comparator for future interventional studies in STXBP1 -related disorders., (© 2023 American Academy of Neurology.)

Introduction: Identifying eating behaviors associated with suboptimal weight loss following bariatric surgery remains important. This study assessed the relationship between eating behaviors and weight loss following bariatric surgery in a racially diverse sample., Methods: Participants were assessed before surgery and 6 and 12 months postoperatively, with the Structured Clinical Interview for DSM-5, the Eating Disorder Examination-Bariatric Surgery Version, and validated measures assessing a range of eating behaviors. Linear mixed effect models were used to test the impact of eating behaviors on percent weight loss (%WL) at 6 and 12 months., Results: We enrolled 300 participants (mean age 40.1 years; BMI 45.9 kg/m 2 ; 87% women; 62% Black and 30% White). The majority (82%) underwent sleeve gastrectomy (SG). Mean %WL was 23.0 ± 5.1% at 6 months and 26.2 ± 7.6% at 12 months. Subjective binge episodes prior to surgery predicted greater %WL over the first 12 postoperative months (p = 0.028). Postoperative disinhibition, hunger, night eating symptoms, objective binge episodes, global disordered eating attitudes and behaviors, and snacks per day were associated with smaller %WL over 12 months (all p's < 0.01). The presence of picking/nibbling and addictive-like eating behaviors was not associated with %WL at the end of the first postoperative year., Conclusion: Among a diverse participant sample, problematic eating behaviors following surgery were associated with smaller %WL over 12 months. Postoperative assessment and treatment of eating behaviors are needed to address these issues as they arise and to prevent attenuation of early weight loss in some patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case., Results: Although we could not detect any molecular signs of the syphilis-causing pathogen Treponema pallidum subsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy's bone lesion and high mercury concentrations., Conclusions: The study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly., (© 2023. The Author(s).)

Introduction: Pharmacogenetic testing is proposed to minimize adverse effects when considered in combination with pharmacological knowledge of the drug. As yet, limited studies in clinical settings have investigated the predictive value of pharmacokinetic (pk) gene variation on therapeutic drug levels as a probable mechanism of adverse effects, nor considered the combined effect of pk gene variation and drug level on antidepressant treatment response., Methods: Two depression cohorts were investigated for the relationship between pk gene variation and antidepressant serum concentrations of amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment response. For the analysis, 519 patients (49% females; 46.6±14.1 years) were included., Results: Serum concentration of amitriptyline was associated with CYP2D6 (higher concentrations in poor metabolizers compared to normal metabolizers), of venlafaxine with CYP2C19 (higher concentrations in intermediate metabolizers compared to rapid/ultrarapid metabolizers) and CYP2D6 (lower metabolite-to-parent ratio in poor compared to intermediate and normal metabolizers, and intermediate compared to normal and ultrarapid metabolizers). Pk gene variation did not affect treatment response., Discussion: The present data support previous recommendations to reduce starting doses of amitriptyline and to guide dose-adjustments via therapeutic drug monitoring in CYP2D6 poor metabolizers. In addition, we propose including CYP2C19 in routine testing in venlafaxine-treated patients to improve therapy by raising awareness of the risk of low serum concentrations in CYP2C19 rapid/ultrarapid metabolizers. In summary, pk gene variation can predict serum concentrations, and thus the combination of pharmacogenetic testing and therapeutic drug monitoring is a useful tool in a personalized therapy approach for depression., Competing Interests: J. Deckert is the co-recipient of a grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy (BayMED, MED-1604-0010) and an investigator in a European grant (Horizon 2020 SME programme of the European Union ref 696802) to P1Vital. A. Menke has given educational lectures for the health insurance company AOK, Servier, Recordati, Neuraxpharm, and Medice. K. Domschke is a member of the Janssen Pharmaceuticals, Inc. Steering Committee Neurosciences. M. Scherf-Clavel, H. Weber, C. Wolf, S. Stonawski, C. Wurst, L. Hommers, S. Unterecker, N. Rost, T. Brückl, S. Lucae, M. Uhr and E. Binder have no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Studies comparing individuals with loss of control (LOC) eating who do and do not have objectively large binge episodes have found that degree of LOC is more important than binge size to psychological and behavioral outcomes. However, the relative importance of these characteristics has not been investigated in a population with binge eating disorder (BED), who by definition all have objectively large binge episodes. Persons with BED and higher weight (N = 34) were enrolled in a BED treatment trial and completed the Loss of Control Over Eating Scale, the Eating Disorder Examination, and measures of eating behavior, mood, and quality of life. Body mass index (BMI) was calculated from measured height and weight. The size of the largest binge episode (measured in kilocalories) and degree of LOC were entered into multiple regression equations to determine their relationships with disordered eating symptoms, depression, quality of life, and BMI in this pilot study. Greater LOC had a stronger independent association than binge size with higher total eating psychopathology, shape dissatisfaction, hunger, food cravings and food addiction symptoms. Larger binge size had a stronger independent association than LOC with higher weight concern and lower general and social quality of life. Both characteristics were associated with higher eating concern and neither were associated with depression or BMI. Both binge size and degree of LOC are associated with important psychosocial treatment targets in patients with BED. Future research should validate the largest binge episode measurement method and replicate the present findings in a larger sample., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess the efficacy of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, for binge eating disorder (BED)., Methods: Adults with a body mass index (BMI) ≥ 27 kg/m 2 enrolled in a pilot, 17-week double-blind, randomized controlled trial of liraglutide 3.0 mg/day for BED. The primary outcome was number of objective binge episodes (OBEs)/week. Binge remission, weight change, and psychosocial variables were secondary outcomes. Mixed effect models were used for continuous variables, and generalized estimating equations were used for remission rates., Results: Participants ( n  = 27) were 44.2 ± 10.6 years; BMI = 37.9 ± 11.8 kg/m 2 ; 63% women; and 59% White and 41% Black. At baseline, the liraglutide group ( n  = 13) reported 4.7 ± 0.7 OBEs/week, compared with 3.0 ± 0.7 OBEs/week for the placebo group, p  = 0.07. At week 17, OBEs/week decreased by 4.0 ± 0.6 in liraglutide participants and by 2.5 ± 0.5 in placebo participants ( p  = 0.37, mean difference = 1.2, 95% confidence interval 1.3, 2.0). BED remission rates of 44% and 36%, respectively, did not differ. Percent weight loss was significantly greater in the liraglutide versus the placebo group (5.2 ± 1.0% vs. 0.9 ± 0.7%, p  = 0.005)., Conclusion: Participants in both groups reported reductions in OBEs, with the liraglutide group showing clinically meaningful weight loss. A pharmacy medication dispensing error was a significant limitation of this study. Further research on liraglutide and other GLP-1 agonists for BED is warranted., Competing Interests: Ariana M. Chao reports grant funding from Eli Lilly and Company and WW International, Inc., outside the submitted work. Robert I. Berkowitz has received research grant support from Novo Nordisk and Eisai Inc. and has served as a scientific consultant to WW International. Thomas A. Wadden serves on scientific advisory boards for Novo Nordisk and WW International and has received grant support from Novo Nordisk and Epitomee Medical. Jena S. Tronieri has received consulting fees/honoraria from Novo Nordisk., (© 2022 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

The identity of the mummified Lady from the Barfüsser Church in Basel, Switzerland has been unsolved for decades, despite the prominent location of the burial place in front of the choir screen. A recent multidisciplinary research approach came up with a possible candidate, Anna Catharina Bischoff who died in Basel in 1787 with an age of 69 years (1719-1787). To verify the identity of the mummy, genealogists of the Citizen Science Basel discovered three living individuals of the maternal lineage of two different family branches, separated from Anna Catharina Bischoff by up to 22 generations. In this study we compare the ancient mitochondrial DNA of the mummy recovered from a premolar to the mitochondrial DNA of these three candidates. Initially the mitochondrial hypervariable regions I and II of the living individuals were screened using the Sanger sequencing method. This was followed by a mitochondrial capture approach and next generation sequencing to enrich for the whole mitochondrial genome of the mummy and one living person. A full mitochondrial genome has been recovered of both individuals sharing an identical haplotype. The sequence was assigned to the mitochondrial haplogroup U5a1+!16192 including two private mutations 10006G and 16293C. Only by using an interdisciplinary approach combining ancient DNA analysis and genealogy a maternal lineage of a non-noble family spanning 22 generations could be confirmed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3 + regulatory T-cell frequencies among CD4 + T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4 + Foxp3 + regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3 + regulatory T cell among human CD4 + T cells in vitro . In an observational prospective clinical study with patients suffering from major depression, we observed that acid sphingomyelinase-inhibiting antidepressants induced a stronger relative increase in the frequency of CD4 + Foxp3 + regulatory T cells in peripheral blood than acid sphingomyelinase-non- or weakly inhibiting antidepressants. This was particularly true for CD45RA - CD25 high effector CD4 + Foxp3 + regulatory T cells. Mechanistically, our data indicate that the positive effect of acid sphingomyelinase inhibition on CD4 + Foxp3 + regulatory T cells required CD28 co-stimulation, suggesting that enhanced CD28 co-stimulation was the driver of the observed increase in the frequency of Foxp3 + regulatory T cells among human CD4 + T cells. In summary, the widely induced pharmacological inhibition of acid sphingomyelinase activity in patients leads to an increase in Foxp3 + regulatory T-cell frequencies among CD4 + T cells in humans both in vivo and in vitro ., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Fear conditioning and generalization are well-known mechanisms in the pathogenesis of anxiety disorders. Extinction of conditioned fear responses is crucial for the psychotherapeutic treatment of these diseases. Anxious depression as a subtype of major depression shares characteristics with anxiety disorders. We therefore aimed to compare fear learning mechanisms in patients with anxious versus non-anxious depression. Fear learning mechanisms in patients with major depression (n = 79; for subgroup analyses n = 41 patients with anxious depression and n = 38 patients with non-anxious depression) were compared to 48 healthy participants. We used a well-established differential fear conditioning paradigm investigating acquisition, generalization, and extinction. Ratings of valence, arousal and probability of expected threat were assessed as well as skin conductance response as an objective psychophysiological measure. Patients with major depression showed impaired acquisition of conditioned fear. In addition, depressed patients showed impaired extinction of conditioned fear responses after successful fear conditioning. Generalization was not affected. However, there was no difference between patients with anxious and non-anxious depression. Results differed between objective and subjective measures. Our findings show altered fear acquisition and extinction in major depression as compared to healthy controls, but they do not favor differential fear learning and extinction mechanisms in the pathogenesis of anxious versus non-anxious depression. The results of impaired extinction warrant future studies addressing extinction learning elements in the treatment of depression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Most patients who undergo bariatric surgery experience significant weight loss and improvements in obesity-related co-morbidities in the first 6-18 months after surgery. However, 20%-30% of patients experience suboptimal weight loss or significant weight regain within the first few postoperative years. Psychosocial functioning may contribute to suboptimal weight loss and/or postoperative psychosocial distress., Objective: Assess psychosocial functioning, eating behavior, and impulsivity in patients seeking bariatric surgery., Setting: Two university hospitals., Methods: Validated interviews and questionnaires. Impulsivity assessed via computer program., Results: The present study included a larger (n = 300) and more racially diverse (70% non-White) sample than previous studies of these relationships. Forty-eight percent of participants had a current psychiatric diagnosis and 78% had at least 1 lifetime diagnosis. Anxiety disorders were the most common current diagnosis (25%); major depressive disorder was the most common lifetime diagnosis (44%). Approximately 6% of participants had a current alcohol or substance use disorder; 7% had a positive drug screen before surgery. A current psychiatric diagnosis was associated with greater symptoms of food addiction and night eating. Current diagnosis of alcohol use disorder or a lifetime diagnosis of anxiety disorders was associated with higher delay discounting., Conclusion: The study identified high rates of psychopathology and related symptoms among a large, diverse sample of bariatric surgery candidates. Psychopathology was associated with symptoms of disordered eating and higher rates of delay discounting, suggesting impulse control issues., (Copyright © 2020. Published by Elsevier Inc.)

Childhood trauma as well as severe events occurring later in life have been associated with the development of major depressive disorder (MDD). However, the interaction of early and later occurring adverse events in patients with MDD is understudied. This study aims to disentangle this interaction by investigating the effects on two of the main stress-response systems of the body, the hypothalamic-pituitaryadrenal (HPA-) axis and the immune system in depressed patients. The function of the HPA-axis was assessed by measuring FKBP5, SGK1 and NR3C1 mRNA-expression in peripheral blood after an in vivo glucocorticoid receptor (GR) challenge with 1.5 mg dexamethasone in 150 depressed in-patients (47.4% females). Childhood trauma was evaluated using the Childhood Trauma Questionnaire (CTQ), severe life events occurring one year prior to hospital admission were assessed with the List of Threatening Experiences (LTE). Multiple childhood traumata, i.e. ≥ 3, were present in 68 (45.5%) patients, 59 (39.3%) experienced ≥ 3 severe recent life events. The history of ≥ 3 severe recent life events was associated with an impaired GR-induction of SGK1 (F = 10.455; df = 1; p = 0.002) and FKBP5 mRNA expression (F = 8.720; df = 1; p = 0.004), and with elevated measures of the immune system such as CRP and lymphocyte count. In addition, severe recent life events were associated with a substantially impaired treatment response to antidepressants (F = 7.456; df = 1; p = 0.008). These effects could not be observed in relation to childhood trauma. Severe life events occurring prior to MDD development substantially impaired the stress-response systems and the response to treatment with antidepressants. This finding may indicate the need to employ additional treatment options such as psychotherapy right at the beginning of treatment or immune-modulating approaches., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although malaria is one of the oldest and most widely distributed diseases affecting humans, identifying and characterizing its presence in ancient human remains continue to challenge researchers. We attempted to establish a reliable approach to detecting malaria in human skeletons using multiple avenues of analysis: macroscopic observations, rapid diagnostic tests, and shotgun-capture sequencing techniques, to identify pathological changes, Plasmodium antigens, and Plasmodium DNA, respectively. Bone and tooth samples from ten individuals who displayed skeletal lesions associated with anaemia, from a site in southern Egypt (third to sixth centuries AD), were selected. Plasmodium antigens were detected in five of the ten bone samples, and traces of Plasmodium aDNA were detected in six of the twenty bone and tooth samples. There was relatively good synchronicity between the biomolecular findings, despite not being able to authenticate the results. This study highlights the complexity and limitations in the conclusive identification of the Plasmodium parasite in ancient human skeletons. Limitations regarding antigen and aDNA preservation and the importance of sample selection are at the forefront of the search for malaria in the past. We confirm that, currently, palaeopathological changes such as cribra orbitalia are not enough to be certain of the presence of malaria. While biomolecular methods are likely the best chance for conclusive identification, we were unable to obtain results which correspond to the current authentication criteria of biomolecules. This study represents an important contribution in the refinement of biomolecular techniques used; also, it raises new insight regarding the consistency of combining several approaches in the identification of malaria in past populations., Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-021-01350-z., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Background: The therapeutic reference range for venlafaxine in antidepressant treatment has been defined as 100 to 400 ng/mL. However, in an everyday setting active moiety concentrations above the therapeutic reference range were often reported., Aim: The aim of this study was to re-evaluate the therapeutic reference range of venlafaxine., Methods: In-patients (⩽60 years) with major depressive episodes receiving antidepressant monotherapy with venlafaxine during routine clinical treatment were included in this observational study. Depressive symptom severity was evaluated on a weekly basis using the Hamilton Depression Rating Scale (HAMD-21), and therapeutic drug monitoring analyses were performed. Resting electrocardiograms were analyzed in week 3, week 5 and week 7 of study participation., Results: Clinical improvement from baseline to week 4 was significantly associated with increasing serum concentrations of the active moiety of venlafaxine ( N = 23, Pearson correlation, p = 0.009), but not with the dose of venlafaxine. Patients achieving remission showed significantly higher serum concentrations than patients achieving response/non-response (Kruskal-Wallis test, p = 0.019). Moreover, in patients with serum concentrations above 400 ng/mL time to remission and time to response was significantly shorter than in patients with concentrations below 400 ng/mL (Mantel-COX test, p = 0.001; p = 0.010). QTc time was below the upper limit of a normal QTc time (450 ms) for all patients., Conclusion: The serum concentration of the active moiety and not the dose determined the effect of venlafaxine. Shorter remission times without ECG alterations in patients with serum concentrations above the therapeutic reference range suggest a re-evaluation of the therapeutic reference range for venlafaxine in larger studies.