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Abstract Background The aim of the investigation was to evaluate if the inclination of the lower anterior teeth can be controlled reliably after lower premolar extraction for Class III camouflage treatment with completely customized lingual appliances (CCLAs). Treatment outcome was tested against the null hypothesis that lower premolar extractions for non-surgical camouflage treatment of a Class III malocclusion will lead to further compensation by retroclining mandibular incisors during CCLA treatment. Methods This retrospective study included 25 patients (f/m 12/13; mean age 20.7 years, SD 9.5 years) with uni- or bilateral Class III molar relationship and a Wits value of ≤ -2 mm. In all consecutively debonded patients, lower premolars were extracted to correct the sagittal relationship with a non-surgical camouflage approach. Lateral head films prior to (T1) and at the end of lingual orthodontic treatment (T2) were used to evaluate skeletal and dentoalveolar effects. A paired t-test with alpha = 5% was used to define differences between the endpoints. The linear correlation between the inclination of the mandibular incisors at T1 and the achieved correction was measured with the Pearson correlation coefficient (PCC). A Schuirmann’s TOST equivalence test was used to check if the final lower incisor inclination was within the defined norms. Results The null hypothesis was rejected as the mean lower incisor inclination was improved by 1.8° despite lower premolar extractions (T1: 86.8°/ T2: 88.6°). There was a strong correlation (-0.75) between the lower incisor inclination at T1 and the achieved correction indicating a controlled correction towards the norm regardless of the initial incisor position. At T2, the interincisal angle as well as the lower incisor inclination were within the norm. Conclusion Lower premolar extractions for non-surgical camouflage treatment of a Class III malocclusion will not lead to undesired retroclining of mandibular incisors during CCLA treatment even in severe cases.

Abstract Two-pore domain K+ (K2P) channel activity was previously thought to be controlled primarily via a selectivity filter (SF) gate. However, recent crystal structures of TASK-1 and TASK-2 revealed a lower gate at the cytoplasmic pore entrance. Here, we report functional evidence of such a lower gate in the K2P channel K2P17.1 (TALK-2, TASK-4). We identified compounds (drugs and lipids) and mutations that opened the lower gate allowing the fast modification of pore cysteine residues. Surprisingly, stimuli that directly target the SF gate (i.e., pHe., Rb+ permeation, membrane depolarization) also opened the cytoplasmic gate. Reciprocally, opening of the lower gate reduced the electric work to open the SF via voltage driven ion binding. Therefore, it appears that the SF is so rigidly locked into the TALK-2 protein structure that changes in ion occupancy can pry open a distant lower gate and, vice versa, opening of the lower gate concurrently promote SF gate opening. This concept might extent to other K+ channels that contain two gates (e.g., voltage-gated K+ channels) for which such a positive gate coupling has been suggested, but so far not directly demonstrated.

Abstract Background and aim The study investigated the effects of a 14-day social media abstinence on various mental health factors using an experimental design with follow-up assessment. Hypotheses included positive associations between problematic smartphone use (PSU) and depression, anxiety, fear of missing out (FoMO), and screentime. Decreases in screentime, PSU, depression and anxiety, and increases in body image were assumed for the abstinence group. Additionally, daily changes in FoMO and loneliness were explored. Methods Participants completed different questionnaires assessing PSU, FoMO, depression and anxiety, loneliness and body image and were randomized into control and social media abstinence groups. Daily questionnaires over 14 days assessed FoMO, loneliness, screentime, and depression and anxiety. 14 days after the abstinence, a follow-up questionnaire was administered. Multilevel models were used to assess changes over time. Results PSU was positively associated with symptoms of depression, anxiety and FoMO, but not with screentime. Spline models identified decreased screentime and body image dissatisfaction for the intervention group. Depression and anxiety symptoms, PSU, trait and state FoMO, and loneliness, showed a decrease during the overall intervention time but no difference between the investigated groups could be observed (hence this was an overall trend). For appearance evaluation and body area satisfaction, an increase in both groups was seen. Daily changes in both loneliness and FoMO were best modelled using cubic trends, but no group differences were significant. Discussion Results provide insights into effects of not using social media for 14 days and show that screentime and body image dissatisfaction decrease. The study also suggests areas for future studies to better understand how and why interventions show better results for some individuals.

Objective: Improper use and poor understanding of asthma medications can lead to poorly controlled asthma, emergency department visits, and hospitalizations for children with asthma. Pharmacists play a critical role in improving asthma medication adherence through education on asthma self-management. The use of color-coded labels applied at pharmacies to help patients differentiate between rescue and maintenance inhalers has not been explored. Methods: Pharmacies were recruited to join a community pharmacy asthma coalition. Pharmacists provided patient education and labeled inhalers with two types of color-coded stickers. A red sticker labeled “RESCUE” was used for short-acting β-2 agonist medication inhalers. A green sticker labeled “USE EVERY DAY” was used for inhaled corticosteroids (ICS) or combination ICS/long-acting β-2 agonist medication inhalers. Results: During the two years of the pilot program, 25 pharmacy locations participated. Pharmacies labeled over 6000 rescue and 9000 controller medications using color-coded labels. Over 1000 children and 7000 adults were served by the coalition. Conclusion: Color-coded asthma medication labels can be successfully utilized by pharmacies. This low-cost tool provides vital information regarding the proper use of asthma medications. Innovation: The color-coded labeling of asthma medications is a novel innovation that can be successfully used by pharmacists to improve asthma self-management education.

The polar regions are the fastest warming places on earth. Accelerated glacial melting causes increased supply of nutrients such as metal oxides (i.e., iron and manganese oxides) into the surrounding environment, such as the marine sediments of Potter Cove, King George Island/Isla 25 de Mayo (West Antarctic Peninsula). Microbial manganese oxide reduction and the associated microbial communities are poorly understood in Antarctic sediments. Here, we investigated this process by geochemical measurements of in situ sediment pore water and by slurry incubation experiments which were accompanied by 16S rRNA sequencing. Members of the genus Desulfuromusa were the main responder to manganese oxide and acetate amendment in the incubations. Other organisms identified in relation to manganese and/or acetate utilization included Desulfuromonas, Sva1033 (family of Desulfuromonadales) and unclassified Arcobacteraceae. Our data show that distinct members of Desulfuromonadales are most active in organotrophic manganese reduction, thus providing strong evidence of their relevance in manganese reduction in permanently cold Antarctic sediments.

IntroductionPast research into the effectiveness of multi-agency public protection arrangements (MAPPA) in reducing reoffending it limited. Thus, the current study aimed to evaluate proven reoffending patterns for MAPPA managed individuals.MethodsProven reoffending for 39,501 MAPPA managed individuals was investigated by (1) examining patterns in the timing and frequency of proven reoffending for MAPPA managed individuals; (2) examining 1-, 3-, and 5-year proven reoffending patterns of MAPPA managed individuals by MAPPA category, age, and gender; and (3) comparing crime harm levels and recall to custody for MAPPA managed individuals pre- and post-MAPPA adoption.ResultsTaken together, our findings show that proven reoffending rates for individuals managed under MAPPA are substantially lower than those reported in proven reoffending statistics for England and Wales.DiscussionOur results suggest that MAPPA is making a positive contribution to a managing individuals convicted of sexual and violent offenses. Additionally, our findings provide the best evidence to date that MAPPA management may also be effective at reducing less serious offenses which do not typically involve immediate removal from society. These findings are considered in light of their theoretical and practical implications while potential limitations and avenues for future research are outlined.

In the context of the ongoing transformation in education, new learning methods, as well as new technologies, and therefore new forms of interactions are challenging higher education. This challenge can be addressed through ambient learning management systems that adapt to the student in the presentation and preparation of course materials. For educational games offered in such systems, this means that the game mechanics should be adapted to the student. To narrow down the sum of mechanics to the amount that is relevant for students, player types can be identified. This paper investigates the player types among students at the University of Lübeck. The characteristics of all player types of Marczewski’s Gamification User Types Hexad Framework are considered using a clustering method for the analysis. The result is three profiles with different characteristics of player types. For each of the profiles, mechanics are suggested which can be used for the respective profile. Thus, educational games can be more easily and automatically adapted to player type.

The digital transformation associated with the Fourth Industrial Revolution is having an impact on the way we teach. Under the term Education 4.0, new teaching methods, new technologies, as well as a student-centered approach, are expected to be used in teaching. One established method of teaching is the use of Serious Games, as it has various positive effects in terms of motivation and engagement. This paper deals with the question of how the transformation towards Education 4.0 influences the way Serious Games are designed and used in the context of higher education. To this end, a systematized literature review was conducted. Out of 550 publications, 28 were included. This revealed works on the general conception as well as studies on Serious Games in various areas of university teaching. The results show different concepts of Serious Games, with the structure often being adapted to learning content and not to students. In terms of technical implementation, Serious Games are mostly web- or desktop-applications instead of new technologies such as VR. As a result, new concepts seem necessary to adapt Serious Games to Education 4.0. In the future, we want to design Serious Games that respond flexibly to students’ needs and make it easy to integrate new technologies.

Hybrid nanoparticles (HNPs) were designed by combining a PLGA core with a lipid shell that incorporated PEG–Lipid conjugates with various functionalities (-RGD, -cRGD, -NH2, and -COOH) to create targeted drug delivery systems. Loaded with a neutral lipid orange dye, the HNPs were extensively characterized using various techniques and investigated for their uptake in human monocyte-derived macrophages (MDMs) using FC and CLSM. Moreover, the best-performing HNPs (i.e., HNP-COOH and HNP-RGD as well as HNP-RGD/COOH mixed) were loaded with the anti-inflammatory drug BRP-201 and prepared in two size ranges (dH ~140 nm and dH ~250 nm). The HNPs were examined further for their stability, degradation, MDM uptake, and drug delivery efficiency by studying the inhibition of 5-lipoxygenase (5-LOX) product formation, whereby HNP-COOH and HNP-RGD both exhibited superior uptake, and the HNP-COOH/RGD (2:1) displayed the highest inhibition.

The aim of this study was to retrospectively evaluate the long-term results of lymphatic interventions in adults with abdomino-thoracic lymphatic pathologies. Management of abdomino-thoracic chylous effusions in adults undergoing X-ray-lymphangiography with or without lymph-vessel embolization (LVE) from 2010–2018 was reviewed. Patients underwent lymphangiography alone when imaging showed normal findings or lymphatic obstruction without leakage or reflux; otherwise, LVE was performed (leakage, reflux, obstruction with leakage or reflux, lymphatic masses). Technical and clinical success, complications, and long-term outcomes were assessed. 78 patients (47 male, median age 56.3 years) were treated for chylous effusions (60.3% traumatic, 39.7% non-traumatic). Lymphangiography showed leakage (48.7%), reflux (14.1%), obstruction (28.2%), lymphatic masses (5.1%), and normal findings (3.8%). Embolization was performed in 49/78 (62.8%) cases. Overall, treatment was clinically successful in 74.4% (mean follow-up of 28 months), with significant differences between LVE and lymphangiography (91.8% vs. 44.8%; p < 0.001), traumatic and non-traumatic etiologies (89.4% vs. 51.6%; p < 0.001), and leakage locations (p = 0.003). The clinical success of LVE did not differ between leakage etiologies or locations. Complications occurred in 5 patients (2/5 needed treatment). Patients survived significantly longer after successful treatment (2679 vs. 927 days; p = 0.044) and without malignancy (3214 vs. 1550 days; p = 0.043). Lymphatic interventions are safe and effective. LVE should be attempted whenever feasible, as success is high (>90%). Successful intervention has a positive effect on patient survival.

BackgroundPsoriasis is a chronic disease characterized by inflammation, increased scaling, itching, and other symptoms. Psoriasis is not contagious, but patients have often felt shunned. Therefore, in addition to psoriasis symptoms, stress, anxiety, and depression can also affect quality of life (QoL). Surveys show that only a quarter of patients are satisfied with the success of their therapy. However, in addition to medical therapy, self-management can also make it easier to deal with chronic diseases like psoriasis. ObjectiveThe aim of this project was to develop a smartphone-based self-management tool (SMT) specifically for patients with psoriasis using a community-driven process. The impact of the SMT on QoL as well as its acceptance and usability were evaluated. MethodsIn collaboration with an internet-based self-help community, 2 user surveys were conducted to determine the requirements for a smartphone-based SMT. The surveys consisted of semistructured questionnaires asking for desired features in an SMT for psoriasis. A pilot study was conducted to evaluate QoL, acceptance, and usability. Community users were recruited to use the app for 21 days and complete the Dermatology Life Quality Index (DLQI) questionnaire at the beginning (T0) and end (T1). Afterward, participants were asked to complete another questionnaire on usability and ease of use. ResultsSMT requirements were collected from 97 members of an internet-based community. The SMT was built as a progressive web app that communicates with a server back end and an Angular web app for content management. The app was used by 15 participants who also provided qualitative feedback, and 10 participants answered all questionnaires. The average DLQI score was 7.1 (SD 6.2) at T0 and 6.9 (SD 6.6) at T1. The minimal required sample size of 27 was not reached. ConclusionsThe high degree of community participation in the development process and the responses during the requirement engineering process indicated that there is a general need for an independently developed SMT for patients with psoriasis. However, the feedback received after app use shows that the SMT does not meet the needs of the community. It can be concluded that a more customizable app is needed. The focus and needs of the users were very heterogeneous. Similar developments and research could benefit from the findings of this project.

Colonization of newly ice-free areas by marine benthic organisms intensifies burial of macroalgae detritus in Potter Cove coastal surface sediments (Western Antarctic Peninsula). Thus, fresh and labile macroalgal detritus serves as primary organic matter (OM) source for microbial degradation. Here, we investigated the effects on post-depositional microbial iron reduction in Potter Cove using sediment incubations amended with pulverized macroalgal detritus as OM source, acetate as primary product of OM degradation and lepidocrocite as reactive iron oxide to mimic in situ conditions. Humic substances analogue anthraquinone-2,6-disulfonic acid (AQDS) was also added to some treatments to simulate potential for electron shuttling. Microbial iron reduction was promoted by macroalgae and further enhanced by up to 30-folds with AQDS. Notably, while acetate amendment alone did not stimulate iron reduction, adding macroalgae alone did. Acetate, formate, lactate, butyrate and propionate were detected as fermentation products from macroalgae degradation. By combining 16S rRNA gene sequencing and RNA stable isotope probing, we reconstructed the potential microbial food chain from macroalgae degraders to iron reducers. Psychromonas, Marinifilum, Moritella, and Colwellia were detected as potential fermenters of macroalgae and fermentation products such as lactate. Members of class deltaproteobacteria including Sva1033, Desulfuromonas, and Desulfuromusa together with Arcobacter (former phylum Epsilonbacteraeota, now Campylobacterota) acted as dissimilatory iron reducers. Our findings demonstrate that increasing burial of macroalgal detritus in an Antarctic fjord affected by glacier retreat intensifies early diagenetic processes such as iron reduction. Under scenarios of global warming, the active microbial populations identified above will expand their environmental function, facilitate OM remineralisation, and contribute to an increased release of iron and CO2 from sediments. Such indirect consequences of glacial retreat are often overlooked but might, on a regional scale, be relevant for the assessment of future nutrient and carbon fluxes.

Anaerobic methane oxidizing archaea (ANME) mediate anaerobic oxidation of methane (AOM) in marine sediments and are therefore important for controlling atmospheric methane concentrations in the water column and ultimately the atmosphere. Numerous previous studies have revealed that AOM is coupled to the reduction of different electron acceptors such as sulfate, nitrate/nitrite or Fe(III)/Mn(IV). However, the influence of electron acceptor availability on the in situ ANME community composition in sediments remains largely unknown. Here, we investigated the electron acceptor availability and compared the microbial in situ communities of three methane-rich locations offshore the sub-Antarctic island South Georgia, by Illumina sequencing and qPCR of mcrA genes. The methanic zone (MZ) sediments of Royal Trough and Church Trough comprised high sulfide concentrations of up to 4 and 19 mM, respectively. In contrast, those of the Cumberland Bay fjord accounted for relatively high concentrations of dissolved iron (up to 186 μM). Whereas the ANME community in the sulfidic sites Church Trough and Royal Trough mainly comprised members of the ANME-1 clade, the order-level clade “ANME-1-related” (Lever and Teske, 2015) was most abundant in the iron-rich site in Cumberland Bay fjord, indicating that the availability of electron acceptors has a strong selective effect on the ANME community. This study shows that potential electron acceptors for methane oxidation may serve as environmental filters to select for the ANME community composition and adds to a better understanding of the global importance of AOM.

In this work the use of the solvents 1,1,2,2-tetramethoxyethan (tetramethylglyoxal, TMG) and 1,1,2,2-tetraethoxyethan (tetraethylglyoxal, TEG) in potassium-based systems is reported for the first time. We show that utilizing electrolytes based on these solvents, potassium bis(fluorosulfonyl)imide (KFSI) and the additive vinyl ethylene carbonate (VEC), it is possible to reversibly intercalate and extract potassium-ions into and from graphite electrodes. Graphite electrodes in combination with the electrolyte 1.5 M KFSI in TEG/VEC display an intercalation capacity of 200 mAh g−1, stable for 40 cycles at C/10. This performance is comparable to that achieved with conventional organic electrolytes.

Abstract Objectives Characterisation of the human antibody response to SARS‐CoV‐2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT‐PCR‐positive SARS‐CoV‐2 convalescent adults during the first 250 days after onset of symptoms. Methods We measured antibody responses to the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT‐PCR‐positive SARS‐CoV‐2 convalescent adults. With a median of 5 (range 2–18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed‐effects modelling. Results All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow‐up analysis. Anti‐RBD IgG and anti‐nucleocapsid IgG levels declined with median half‐lives of 62 and 59 days, respectively, 2–5 months after symptom onset, and several‐fold variation in half‐lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow‐up, which points towards long‐term immunological memory. The magnitude of the anti‐RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in‐house developed competitive assay. Conclusion The result of this study gives valuable insight into the long‐term longitudinal response of antibodies to SARS‐CoV‐2.

Ovarian stimulation is an indispensable part of IVF and is employed to produce multiple ovarian follicles. In women who undergo ovarian stimulation with gonadotropins, supraphysiological levels of estradiol, as well as a premature rise in progesterone levels, can be seen on the day of hCG administration. These alterations in hormone levels are associated with reduced embryo implantation and pregnancy rates in IVF cycles with a fresh embryo transfer. This article aims to improve the reader’s understanding of the effects of elevated progesterone levels on human endometrial receptivity and oocyte/embryo quality. Based on current clinical data, it appears that the premature rise in progesterone levels exerts minimal or no effects on oocyte/embryo quality, while advancing the histological development of the secretory endometrium and displacing the window of implantation. These clinical findings strongly suggest that reduced implantation and pregnancy rates are the result of a negatively affected endometrium rather than poor oocyte/embryo quality. Understanding the potential negative impact of elevated progesterone levels on the endometrium is crucial to improving implantation rates following a fresh embryo transfer. Clinical studies conducted over the past three decades, many of which have been reviewed here, have greatly advanced our knowledge in this important area.

Chemical communication via pheromones is considered the oldest and most widespread form of communication in nature. However, the way that the enormous diversity of species-specific pheromones evolved is still of debate. One possible process driving pheromone evolution is the mate-finding and dispersal behavior, as long-distance mate-finding requires highly volatile compounds. In contrast, less volatile compounds might be sufficient attractants in species that search for mates within proximity. In the parasitoid wasp genus Leptopilina, the composition of species-specific sex pheromones ranges from highly volatile iridoid compounds through combinations of iridoids with low volatile cuticular hydrocarbons (CHCs) to only CHCs. To study the selective forces shaping the composition of sex pheromones in Leptopilina, we examined the dispersal behavior, i.e., the proportion of male and female wasps dispersing after emergence, in four species with known sex pheromone compositions. If males and females disperse immediately, long-range mate attraction might become necessary, favoring volatile iridoids over CHCs. If mating occurs directly on the host patch, short-range mate attraction by low volatile CHCs might suffice. Our analyses have revealed that the dispersal behavior of Leptopilina males and females after emergence does indeed differ between species with differently volatile sex pheromones. Specifically, males of species with iridoid sex pheromones start to disperse immediately before their females’ emergence, whereas males of species with CHC sex pheromones delay dispersal until their conspecific females emerge. While the differences in female dispersal behavior turned out to be species-specific, differences in male dispersal correlated with the volatility of female-produced sex pheromones of each species. This study significantly contributes to our understanding of the evolution of sex pheromones by differences in dispersal behavior.

Abstract Background This study aimed to investigate differences in sucking behavior of infants bottle-fed with vented (so-called anticolic) teats (VTs) and nonvented teats (NVTs). Methods Trial design: Prospective, randomized clinical trial. Ninety-six term, healthy infants (aged 1–8 months) were assessed for eligibility. Seventy-three infants remained for intention-to-treat (ITT) and 65 infants (vented group: n = 31; nonvented group: n = 34) for the per-protocol (PP) analysis. During bottle-feeding, sucks/min, pauses/min, amount of formula intake (mL), feeding time (min), heart rate (bpm), respiratory rate (bpm), and oxygen saturation (%) were recorded. In addition, a parental survey was carried out to reveal possible symptoms of infantile colic. Sample-size calculation and confirmatory and exploratory analyses were performed using the Mann-Whitney U test and Fisher’s exact test. Results Except for the parameter sucking pauses per minute (NVTs > VTs, p = .03), no differences between groups were found with the ITT and PP analysis. After excluding infants with a disproportionately complementary diet (subgroup analysis, infants aged 1–6 months, n = 54) the primary outcome (sucks per minute) showed significant differences (NVTs > VTs, p = .01). The amount of formula intake, feeding time, and cardiorespiratory parameters were similar in both groups. The parental survey did not show any relation between types of feeding teats and possible symptoms of infantile colic. Conclusions Compared with an NVT group, infants aged 1–6 months need fewer sucks and pauses when fed with VTs. In both groups, equal amounts of feeding medium and feeding time were observed. With NVT feeding, disruption occurs when the bottle vacuum is released by air from the oral cavity. Therefore, higher sucking frequency is needed to rebuild the oral vacuum for bottle milk flow, which implies higher risk of aerophagia. Overall, we suggest that the VTs provided a more coordinated drinking pattern than did the NVTs, which may have a positive effect on gastric distress. Trial registration Trial Registration: DRKS-Trial Registration No. DRKS00004885. Registered April 16, 2013. Universal Trial No. U1111–1141-5857.

Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10−8). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.

CRISPR/Cas9-mediated forward genetic screens and gene-trap mutagenesis screens in haploid cells are both powerful techniques to examine gene function. Here, the authors show the two approaches have high concordance and identify an uncharacterized gene, TXNDC11, which is involved in endoplasmic reticulum-associated degradation.

Head-down-tilt bed rest (HDT) mimics the changes in hemodynamics and autonomic cardiovascular control induced by weightlessness. However, the time course and reciprocal interplay of these adaptations, and the effective exercise protocol as a countermeasure need further clarification. The overarching aim of this work (as part of a European Space Agency sponsored long-term bed rest study) was therefore to evaluate the time course of cardiovascular hemodynamics and autonomic control during prolonged HDT and to assess whether high-intensity, short-duration exercise could mitigate these effects. A total of n = 23 healthy, young, male participants were randomly allocated to two groups: training (TRAIN, n = 12) and non-training (CTRL, n = 11) before undergoing a 60-day HDT. The TRAIN group underwent a resistance training protocol using reactive jumps (5–6 times per week), whereas the CTRL group did not perform countermeasures. Finger blood pressure (BP), heart rate (HR), and stroke volume were collected beat-by-beat for 10 min in both sitting and supine positions 7 days before HDT (BDC−7) and 10 days after HDT (R+10), as well as on the 2nd (HDT2), 28th (HDT28), and 56th (HDT56) day of HDT. We investigated (1) the isolated effects of long-term HDT by comparing all the supine positions (including BDC−7 and R+10 at 0 degrees), and (2) the reactivity of the autonomic response before and after long-term HDT using a specific postural stimulus (i.e., supine vs. sitting). Two-factorial linear mixed models were used to assess the time course of HDT and the effect of the countermeasure. Starting from HDT28 onwards, HR increased (p < 0.02) and parasympathetic tone decreased exclusively in the CTRL group (p < 0.0001). Moreover, after 60-day HDT, CTRL participants showed significant impairments in increasing cardiac sympathovagal balance and controlling BP levels during postural shift (supine to sitting), whereas TRAIN participants did not. Results show that a 10-day recovery did not compensate for the cardiovascular and autonomic deconditioning following 60-day HDT. This has to be considered when designing rehabilitation programs—not only for astronauts but also in general public healthcare. High-intensity, short-duration exercise training effectively minimized these impairments and should therefore deserve consideration as a cardiovascular deconditioning countermeasure for spaceflight.

Studies on human physical performance in extreme environments have effectively approached the investigation of adaptation mechanisms and their physiological limits. As scientific interest in the interplay between physiological and psychological aspects of performance is growing, we aimed to investigate cardiac autonomic control, by means of heart rate variability, and psychological correlates, in competitors of a subarctic ultramarathon, taking place over a 690 km course (temperatures between +5 and −47°C). At baseline (PRE), after 277 km (D1), 383 km (D2), and post-race (POST, 690 km), heart rate (HR) recordings (supine, 15 min), psychometric measurements (Profile of Mood States/POMS, Borg fatigue, and Karolinska Sleepiness Scale scores both upon arrival and departure) were obtained in 16 competitors (12 men, 4 women, 38.6 ± 9.5 years). As not all participants reached the finish line, comparison of finishers (FIN, n = 10) and non-finishers (NON, n = 6), allowed differential assessment of performance. Resting HR increased overall significantly at D1 (FIN +15.9; NON +14.0 bpm), due to a significant decrease in parasympathetic drive. This decrease was in FIN only partially recovered toward POST. In FIN only, baseline HR was negatively correlated with mean velocity [r −0.63 (P.04)] and parasympathetic drive [pNN50+: r −0.67 (P.03)], a lower HR and a higher vagal tone predicting a better performance. Moreover, in FIN, a persistent increase of the long-term self-similarity coefficient, assessed by detrended fluctuation analysis (DFAα2), was retrieved, possibly due to higher alertness. As for psychometrics, at D1, POMS Vigor decreased (FIN: −7.0; NON: −3.8), while Fatigue augmented (FIN: +6.9; NON: +5.0). Sleepiness increased only in NON, while Borg scales did not exhibit changes. Baseline comparison of mood states with normative data for athletes displayed significantly higher positive mood in our athletes. Results show that: the race conditions induced early decreases in parasympathetic drive; the extent of vagal withdrawal, associated to the timing of its recovery, is crucial for success; pre-competition lower resting HR predicts a better performance; psychological profile is reliably depicted by POMS, but not by Borg fatigue scales. Therefore, assessment of heart rate variability and psychological profile may monitor and partly predict performance in long-duration ultramarathon in extreme cold environment.

Objective. Robotic surgery continues to expand in minimally invasive surgery; however, the literature is insufficient to understand the current training process for general surgery residents. Therefore, the objectives of this study were to identify the current approach to and perspectives on robotic surgery training. Methods. An electronic survey was distributed to general surgery program directors identified by the Accreditation Council for Graduate Medical Education website. Multiple choice and open-ended questions regarding current practices and opinions on robotic surgery training in general surgery residency programs were used. Results. 20 program directors were surveyed, a majority being from medium-sized programs (4–7 graduating residents per year). Most respondents (73.68%) had a formal robotic surgery curriculum at their institution, with 63.16% incorporating simulation training. Approximately half of the respondents believe that more time should be dedicated to robotic surgery training (52.63%), with simulation training prior to console use (84.21%). About two-thirds of the respondents (63.16%) believe that a formal robotic surgery curriculum should be established as a part of general surgery residency, with more than half believing that exposure should occur in postgraduate year one (55%). Conclusion. A formal robotics curriculum with simulation training and early surgical exposure for general surgery residents should be given consideration in surgical residency training.

While humans (like other primates) communicate with facial expressions, the evolution of speech added a new function to the facial muscles (facial expression muscles). The evolution of speech required the development of a coordinated action between visual (movement of the lips) and auditory signals in a rhythmic fashion to produce "visemes" (visual movements of the lips that correspond to specific sounds). Visemes depend upon facial muscles to regulate shape of the lips, which themselves act as speech articulators. This movement necessitates a more controlled, sustained muscle contraction than that produced during spontaneous facial expressions which occur rapidly and last only a short period of time. Recently, it was found that human tongue musculature contains a higher proportion of slow-twitch myosin fibers than in rhesus macaques, which is related to the slower, more controlled movements of the human tongue in the production of speech. Are there similar unique, evolutionary physiologic biases found in human facial musculature related to the evolution of speech?Using myosin immunohistochemistry, we tested the hypothesis that human facial musculature has a higher percentage of slow-twitch myosin fibers relative to chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta). We sampled the orbicularis oris and zygomaticus major muscles from three cadavers of each species and compared proportions of fiber-types. Results confirmed our hypothesis: humans had the highest proportion of slow-twitch myosin fibers while chimpanzees had the highest proportion of fast-twitch fibers.These findings demonstrate that the human face is slower than that of rhesus macaques and our closest living relative, the chimpanzee. They also support the assertion that human facial musculature and speech co-evolved. Further, these results suggest a unique set of evolutionary selective pressures on human facial musculature to slow down while the function of this muscle group diverged from that of other primates.

Background: Depression concomitant with chronic medical conditions is common and burdensome in primary care. Objective: To assess the effectiveness of practice-based interventions for improving depression and chronic medical outcomes. Data Sources: MEDLINE, Embase, the Cochrane Library, CINAHL, and PsycINFO from inception to June 11, 2012. Study Selection, Appraisal, and Synthesis: Two reviewers independently selected, extracted data from, and rated the quality of trials and systematic reviews. Strength of evidence (SOE) was graded using established criteria. Results: Twenty-four published articles reported data from 12 studies, all at least 6 months long. All studies compared a form of collaborative care with usual or enhanced usual care. Studies evaluated adults with arthritis, cancer, diabetes, heart disease, HIV, or multiple medical conditions. Meta-analyses found that intervention recipients achieved greater improvement than controls in depression symptoms, response, remission, and depression-free days (moderate SOE); satisfaction with care (moderate SOE); and quality of life (moderate SOE). Few data were available on outcomes for chronic medical conditions. Meta-analyses revealed that patients with diabetes receiving collaborative care exhibited no difference in diabetes control compared with control groups (change in HbA1c: weighted mean difference 0.13, 95% confidence interval = −0.22 to 0.48 at 6 months; 0.24, 95% confidence interval = −0.14 to 0.62 at 12 months; low SOE). The only study to use HbA1c as a predefined outcome measure and a “treat-to-target” intervention for diabetes as well as depression, TEAMcare, reported significant reductions in HbA1c (7.42 vs 7.87 at 6 months; 7.33 vs 7.81 at 12 months; overall P < .001). Limitations: Few relevant trials reported on medical outcomes. Conclusions: Collaborative care interventions improved outcomes for depression and quality of life in primary care patients with varying medical conditions. Few data were available on medical outcomes. Future studies of concomitant depression and chronic medical conditions should consider measures of medical outcomes as primary outcomes.

Two diary studies investigated the role of social approach and avoidance motivation in important developmental transitions in young and old adulthood. Study 1 comprised a sample of young adults (N = 93, M = 21.5 years) who moved out of their parental homes. The sample of Study 2 consisted of older adults (N = 69, M = 76.95 years) who moved into senior housing. In both studies, participants reported their habitual social approach and avoidance motives as well as their daily social experience and subjective well-being over the course of two weeks. In line with the literature, social approach motives and age were related to higher subjective well-being, whereas social avoidance motives were negatively associated with subjective well-being. Time since the transition was an important moderator of the association between social avoidance motives and negative outcomes. With increasing time from the transition, the negative effects of social avoidance motives decreased. The positive effects of social approach motives remained fairly stable over time. Importantly, age did not moderate any of the associations between social motivation and outcomes. Results are discussed in terms of transition-related instability and age-related stability.

Amyloid-β (Aβ) peptide aggregation is known to play a central role in the etiology of Alzheimer's disease (AD). Among various aggregates, low-molecular weight soluble oligomers of Aβ are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the Aβ aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on Aβ42 aggregation. NEFAs uniquely affected Aβ42 aggregation rates that depended on both the ratio of Aβ:NEFA as well the critical micelle concentration (CMC) of the NEFAs. More importantly, irrespective of the kind of NEFA used, we observed that two distinct oligomers, 12-18 mers and 4-5 mers were formed via different pathway of aggregation under specific experimental conditions: (i) 12-18 mers were generated near the CMC in which NEFAs augment the rate of Aβ42 aggregation towards fibril formation, and, (ii) 4-5 mers were formed above the CMC, where NEFAs inhibit fibril formation. The data indicated that both 12-18 mers and 4-5 mers are formed along an alternate pathway called 'off-pathway' that did not result in fibril formation and yet have subtle structural and morphological differences that distinguish their bulk molecular behavior. These observations, (i) reflect the possible mechanism of Aβ aggregation in physiological lipid-rich environments, and (ii) reiterate the fact that all oligomeric forms of Aβ need not be obligatory intermediates of the fibril formation pathway.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Authors discovered a mass interference in calibration standards analyzed by liquid chromatography-high-resolution mass spectrometry that resulted in underestimation of serum concentrations for perfluoro-3,5,7,9,11- pentaoxadodecanoic acid [PFO5DoA; DTXSID50723994] in the published [...]

This article used data from the GenX Exposure Study reported in Kotlarz et al. 2020. (1) Authors identified an error in the concentration estimates for PFO5DoA that resulted in a [...]

Abstract Background The Northern California county of Marin (MC) has historically had high breast cancer incidence rates. Because of MC's high socioeconomic status (SES) and racial homogeneity (non-Hispanic White), it has been difficult to assess whether these elevated rates result from a combination of established risk factors or other behavioral or environmental factors. This survey was designed to compare potential breast cancer risks and incidence rates for a sample of middle-aged MC women with those of a demographically similar population. Methods A random sample of 1500 middle-aged female members of a large Northern California health plan, half from Marin County (MC) and half from a comparison area in East/Central Contra Costa County (ECCC), were mailed a survey covering family history, reproductive history, use of oral contraceptives (OC) and hormone replacement therapy (HRT), behavioral health risks, recency of breast screening, and demographic characteristics. Weighted data were used to compare prevalence of individual breast cancer risk factors and Gail scores. Age-adjusted cumulative breast cancer incidence rates (2000–2004) were also calculated for female health plan members aged 40–64 residing in the two geographic areas. Results Survey response was 57.1% (n = 427) and 47.9% (n = 359) for MC and ECCC samples, respectively. Women in the two areas were similar in SES, race, obesity, exercise frequency, current smoking, ever use of OCs and HRT, age at onset of menarche, high mammography rates, family history of breast cancer, and Gail scores. However, MC women were significantly more likely than ECCC women to be former smokers (43.6% vs. 31.2%), have Ashkenazi Jewish heritage (12.8% vs. 7.1%), have no live births before age 30 (52.7% vs. 40.8%), and be nulliparous (29.2% vs. 15.4%), and less likely to never or rarely consume alcohol (34.4% vs. 41.9%). MC and ECCC women had comparable 2000–2004 invasive breast cancer incidence rates. Conclusion The effects of reproductive risks factors, Ashkenazi Jewish heritage, smoking history, and alcohol consumption with regard to breast cancer risk in Marin County should be further evaluated. When possible, future comparisons of breast cancer incidence rates between regions should adjust for differences in income and education in addition to age and race/ethnicity, preferably by using a sociodemographically similar comparison group.

Mental health challenges are common during the perinatal period, particularly following pregnancy loss. This longitudinal study investigates the role of self-compassion in the mental health of perinatal women having previously experienced (n = 45) or not having experienced (n = 123) pregnancy loss. Archival data was utilised to compare levels of perinatal depression, psychological distress, and self-compassion for women receiving psychological therapy at session one and session six. Results indicated that both participant groups reported similar levels on all variables at baseline. There were significant increases in self-compassion and decreases in perinatal depression and psychological distress after six sessions of therapy for both groups. A regression showed changes in self-compassion following six sessions of therapy was predictive of psychological distress, particularly for women who reported pregnancy loss. Self-compassion may represent a viable intervention for psychological distress in a perinatal population particularly following pregnancy loss. [ABSTRACT FROM AUTHOR]

PURPOSE: Investigating the impact of social determinants of health (SDOHs) on cancer care in large populations relies on census estimates. Routine clinic SDOH screening provides timely patient-level information which could inform best practices. This study evaluated the correlation between patient-reported SDOH needs and population-level census tract measures. METHODS: This was a retrospective cross-sectional study of a cohort of adult patients with GI malignancy screened for SDOHs such as financial insecurity, transportation, and food insecurity during initial outpatient evaluation at East Carolina University (formerly Vidant) Health Medical Center in Greenville, NC (November 2020-July 2021). Primary outcomes included number and severity of identified SDOH needs and area deprivation index (ADI) and census tract measures for each patient. Spearman rank correlations were calculated among patient-level needs and between patient-level needs and similar census tract measures. RESULTS: Of 112 patients screened, 58.9% self-identified as White (n = 66) and 41.1% as Black (n = 46). A total of 50.5% (n = 54) resided in a rural county. The collective median state ADI rank was 7 (IQR, 5-9). The median household income was $38,125 in US dollars (USD) (IQR, $31,436-$48,934 [USD]). Only 12.5% (n = 14) reported a moderate or severe financial need. Among reported needs, financial need moderately correlated with food insecurity (coefficient, 0.46; P <.001) and transportation (coefficient, 0.45; P <.001). Overall, census tract measures and reported needs poorly correlated. Lack of transportation correlated with percentage of households without a vehicle (coefficient, 0.18; P =.03) and limited access to healthy foods (coefficient, 0.18; P =.04). CONCLUSION: Given the poor correlation between reported and census needs, population-level measures may not accurately predict patient-reported needs. These findings highlight the importance of SDOH screening in the clinical setting to reduce health disparities and identify opportunities to improve care delivery. Individual patient social determinants of health needs do not correlate with geographic region estimates. [ABSTRACT FROM AUTHOR]